AVAHO

Hepatocellular carcinoma (HCC) is the sixth most common and third most deadly malignancy worldwide, carrying a mean survival rate without treatment of 6 to 20 months depending on stage.¹ Fifty-seven percent of patients with liver cancer are diagnosed with regional or distant metastatic disease that carries 5-year relative survival rates of 10.7% and 3.1%, respectively.² HCC arises most commonly from liver cirrhosis due to chronic hepatocyte injury, which may be mediated by viral hepatitis, alcoholism, and metabolic disease. Other less common causes include autoimmune disease, exposure to environmental hazards, and certain genetic diseases, such as α-1 antitrypsin deficiency and Wilson disease.

Multiple staging systems for HCC exist that incorporate some variation of the following features: size and invasion of the tumor, distant metastases, and liver function. Stage-directed treatments for HCC include ablation, embolization, resection, transplant, and systemic therapy, such as tyrosine kinase inhibitors, immunotherapies, and monoclonal antibodies. In addition to tumor/node/metastasis (TNM) staging, α-fetoprotein (AFP) is a diagnostic marker with prognostic value in HCC with higher levels correlating to higher tumor burden and a worse prognosis. With treatment, the 5-year survival rate for early stage HCC ranges from 60% to 80% but decreases significantly with higher stages.¹ HCC screening in at-risk populations has accounted for > 40% of diagnoses since the practice became widely adopted, and earlier recognition has led to an improvement in survival even when adjusting for lead time bias.³

Systemic therapy for advanced disease continues to improve. Sorafenib remained the standard first-line systemic therapy since it was introduced in 2008.⁴ First-line therapy improved with immunotherapies. The phase 3 IMBrave150 trial comparing atezolizumab plus bevacizumab to sorafenib showed a median overall survival (OS) > 19 months with 7.7% of patients achieving a complete response.⁵ HIMALAYA, another phase 3 trial set for publication later this year, also reported promising results when a priming dose of the CTLA-4 inhibitor tremelimumab followed by durvalumab was compared with sorafenib.⁶

There has been a rise in incidence of HCC in the United States across all races and ethnicities, though Black, Hispanic, and Asian patients remain disproportionately affected. Subsequently, identifying causative biologic, socioeconomic, and cultural factors, as well as implicit bias in health care continues to be a topic of great interest.^7-9 Using Surveillance, Epidemiology, and End Results (SEER) data, a number of large studies have found that Black patients with HCC were more likely to present with an advanced stage, less likely to receive curative intent treatment, and had significantly reduced survival compared with that of White patients.^1,7-9 An analysis of 1117 patients by Rich and colleagues noted a 34% increased risk of death for Black patients with HCC compared with that of White patients, and other studies have shown about a 50% reduction in rate of liver transplantation for Black patients.^10-12 Our study aimed to investigate potential disparities in incidence, etiology, AFP level at diagnosis, and outcomes of HCC in Black and White veterans managed at the Memphis Veterans Affairs Medical Center (VAMC) in Tennessee.

Methods

A single center retrospective chart review was conducted at the Memphis VAMC using the Computerized Patient Record System (CPRS) and the International Statistical Classification of Diseases, Tenth Revision (ICD-10) code C22.0 for HCC. Initial results were manually refined by prespecified criteria. Patients were included if they were diagnosed with HCC and received HCC treatment at the Memphis VAMC. Patients were excluded if HCC was not diagnosed histologically or clinically by imaging characteristics and AFP level, if the patient’s primary treatment was not provided at the Memphis VAMC, if they were lost to follow-up, or if race was not specified as either Black or White.

The following patient variables were examined: age, sex, comorbidities (alcohol or substance use disorder, cirrhosis, HIV), tumor stage, AFP, method of diagnosis, first-line treatments, systemic treatment, surgical options offered, and mortality. Staging was based on the American Joint Committee on Cancer TNM staging for HCC.¹³ Surgical options were recorded as resection or transplant. Patients who were offered treatment but lost to follow-up were excluded from the analysis.

Data Analysis

Our primary endpoint was identifying differences in OS among Memphis VAMC patients with HCC related to race. Kaplan-Meier analysis was used to investigate differences in OS and cumulative hazard ratio (HR) for death. Cox regression multivariate analysis further evaluated discrepancies among investigated patient variables, including age, race, alcohol, tobacco, or illicit drug use, HIV coinfection, and cirrhosis. Treatment factors were further defined by first-line treatment, systemic therapy, surgical resection, and transplant. χ² analysis was used to investigate differences in treatment modalities.

Results

We identified 227 veterans, 95 Black and 132 White, between 2009 and 2021 meeting criteria for primary HCC treated at the Memphis VAMC. This study did not show a significant difference in OS between White and Black veterans (P = .24). Kaplan-Meier assessment showed OS was 1247 days (41 months) for Black veterans compared with 1032 days (34 months) for White veterans (Figure; Table 1).

Additionally, no significant difference was found between veterans for age or stage at diagnosis when stratified by race. The mean age of diagnosis for both groups was 65 years (P = .09). The mean TNM staging was 1.7 for White veterans vs 1.8 for Black veterans (P = .57). There was a significant increase in the AFP level at diagnosis for Black veterans (P = .001) (Table 2).

The most common initial treatment for both groups was transarterial chemoembolization and radiofrequency ablation with 68% of White and 64% of Black veterans receiving this therapy. There was no significant difference between who received systemic therapy.

Discussion

In this retrospective analysis, Black veterans with HCC did not experience a statistically significant decrease in OS compared with that of White veterans despite some differences in therapy offered. Other studies have found that surgery was less frequently recommended to Black patients across multiple cancer types, and in most cases this carried a negative impact on OS.^{8,10,11,14,15} A number of other studies have demonstrated a greater percentage of Black patients receiving no treatment, although these studies are often based on SEER data, which captures only cancer-directed surgery and no other methods of treatment. Inequities in patient factors like insurance and socioeconomic status as well as willingness to receive certain treatments are often cited as major influences in health care disparities, but systemic and clinician factors like hospital volume, clinician expertise, specialist availability, and implicit racial bias all affect outcomes.¹⁶ One benefit of our study was that CPRS provided a centralized recording of all treatments received. Interestingly, the treatment discrepancy in our study was not attributable to a statistically significant difference in tumor stage at presentation. There should be no misconception that US Department of Veterans Affairs patients are less affected by socioeconomic inequities, though still this suggests clinician and systemic factors were significant drivers behind our findings.

This study did not intend to determine differences in incidence of HCC by race, although many studies have shown an age-adjusted incidence of HCC among Black and Hispanic patients up to twice that of White patients.^1,8-10 Notably, the rate of orthotopic liver transplantation in this study was low regardless of race compared with that of other larger studies of patients with HCC.^12,15 Discrepancies in HCC care among White and Black patients have been suggested to stem from a variety of influences, including access to early diagnosis and treatment of hepatitis C virus, comorbid conditions, as well as complex socioeconomic factors. It also has been shown that oncologists’ implicit racial bias has a negative impact on patients’ perceived quality of communication, their confidence in the recommended treatment, and the understood difficulty of the treatment by the patient and should be considered as a contributor to health disparities.^17,18

Studies evaluating survival in HCC using SEER data generally stratify disease by localized, regional, or distant metastasis. For our study, TNM staging provided a more accurate assessment of the disease and reduced the chances that broader staging definitions could obscure differences in treatment choices. Future studies could be improved by stratifying patients by variables impacting treatment choice, such as Child-Pugh score or Barcelona Clinic Liver Cancer staging. Our study demonstrated a statistically significant difference in AFP level between White and Black veterans. This has been observed in prior studies as well, and while no specific cause has been identified, it suggests differences in tumor biologic features across different races. In addition, we found that an elevated AFP level at the time of diagnosis (defined as > 400) correlates with a worsened OS (HR, 1.36; P = .01).

Limitations

This study has several limitations, notably the number of veterans eligible for analysis at a single institution. A larger cohort would be needed to evaluate for statistically significant differences in outcomes by race. Additionally, our study did not account for therapy that was offered to but not pursued by the patient, and this would be useful to determine whether patient or practitioner factors were the more significant influence on the type of therapy received.

Conclusions

This study demonstrated a statistically significant difference in the rate of resection and liver transplantation between White and Black veterans at a single institution, although no difference in OS was observed. This discrepancy was not explained by differences in tumor staging. Additional, larger studies will be useful in clarifying the biologic, cultural, and socioeconomic drivers in HCC treatment and mortality.

Acknowledgments

The authors thank Lorri Reaves, Memphis Veterans Affairs Medical Center, Department of Hepatology.

Hepatocellular carcinoma (HCC) is the sixth most common and third most deadly malignancy worldwide, carrying a mean survival rate without treatment of 6 to 20 months depending on stage.¹ Fifty-seven percent of patients with liver cancer are diagnosed with regional or distant metastatic disease that carries 5-year relative survival rates of 10.7% and 3.1%, respectively.² HCC arises most commonly from liver cirrhosis due to chronic hepatocyte injury, which may be mediated by viral hepatitis, alcoholism, and metabolic disease. Other less common causes include autoimmune disease, exposure to environmental hazards, and certain genetic diseases, such as α-1 antitrypsin deficiency and Wilson disease.

Multiple staging systems for HCC exist that incorporate some variation of the following features: size and invasion of the tumor, distant metastases, and liver function. Stage-directed treatments for HCC include ablation, embolization, resection, transplant, and systemic therapy, such as tyrosine kinase inhibitors, immunotherapies, and monoclonal antibodies. In addition to tumor/node/metastasis (TNM) staging, α-fetoprotein (AFP) is a diagnostic marker with prognostic value in HCC with higher levels correlating to higher tumor burden and a worse prognosis. With treatment, the 5-year survival rate for early stage HCC ranges from 60% to 80% but decreases significantly with higher stages.¹ HCC screening in at-risk populations has accounted for > 40% of diagnoses since the practice became widely adopted, and earlier recognition has led to an improvement in survival even when adjusting for lead time bias.³

Systemic therapy for advanced disease continues to improve. Sorafenib remained the standard first-line systemic therapy since it was introduced in 2008.⁴ First-line therapy improved with immunotherapies. The phase 3 IMBrave150 trial comparing atezolizumab plus bevacizumab to sorafenib showed a median overall survival (OS) > 19 months with 7.7% of patients achieving a complete response.⁵ HIMALAYA, another phase 3 trial set for publication later this year, also reported promising results when a priming dose of the CTLA-4 inhibitor tremelimumab followed by durvalumab was compared with sorafenib.⁶

There has been a rise in incidence of HCC in the United States across all races and ethnicities, though Black, Hispanic, and Asian patients remain disproportionately affected. Subsequently, identifying causative biologic, socioeconomic, and cultural factors, as well as implicit bias in health care continues to be a topic of great interest.^7-9 Using Surveillance, Epidemiology, and End Results (SEER) data, a number of large studies have found that Black patients with HCC were more likely to present with an advanced stage, less likely to receive curative intent treatment, and had significantly reduced survival compared with that of White patients.^1,7-9 An analysis of 1117 patients by Rich and colleagues noted a 34% increased risk of death for Black patients with HCC compared with that of White patients, and other studies have shown about a 50% reduction in rate of liver transplantation for Black patients.^10-12 Our study aimed to investigate potential disparities in incidence, etiology, AFP level at diagnosis, and outcomes of HCC in Black and White veterans managed at the Memphis Veterans Affairs Medical Center (VAMC) in Tennessee.

Methods

A single center retrospective chart review was conducted at the Memphis VAMC using the Computerized Patient Record System (CPRS) and the International Statistical Classification of Diseases, Tenth Revision (ICD-10) code C22.0 for HCC. Initial results were manually refined by prespecified criteria. Patients were included if they were diagnosed with HCC and received HCC treatment at the Memphis VAMC. Patients were excluded if HCC was not diagnosed histologically or clinically by imaging characteristics and AFP level, if the patient’s primary treatment was not provided at the Memphis VAMC, if they were lost to follow-up, or if race was not specified as either Black or White.

The following patient variables were examined: age, sex, comorbidities (alcohol or substance use disorder, cirrhosis, HIV), tumor stage, AFP, method of diagnosis, first-line treatments, systemic treatment, surgical options offered, and mortality. Staging was based on the American Joint Committee on Cancer TNM staging for HCC.¹³ Surgical options were recorded as resection or transplant. Patients who were offered treatment but lost to follow-up were excluded from the analysis.

Data Analysis

Our primary endpoint was identifying differences in OS among Memphis VAMC patients with HCC related to race. Kaplan-Meier analysis was used to investigate differences in OS and cumulative hazard ratio (HR) for death. Cox regression multivariate analysis further evaluated discrepancies among investigated patient variables, including age, race, alcohol, tobacco, or illicit drug use, HIV coinfection, and cirrhosis. Treatment factors were further defined by first-line treatment, systemic therapy, surgical resection, and transplant. χ² analysis was used to investigate differences in treatment modalities.

Results

We identified 227 veterans, 95 Black and 132 White, between 2009 and 2021 meeting criteria for primary HCC treated at the Memphis VAMC. This study did not show a significant difference in OS between White and Black veterans (P = .24). Kaplan-Meier assessment showed OS was 1247 days (41 months) for Black veterans compared with 1032 days (34 months) for White veterans (Figure; Table 1).

Additionally, no significant difference was found between veterans for age or stage at diagnosis when stratified by race. The mean age of diagnosis for both groups was 65 years (P = .09). The mean TNM staging was 1.7 for White veterans vs 1.8 for Black veterans (P = .57). There was a significant increase in the AFP level at diagnosis for Black veterans (P = .001) (Table 2).

The most common initial treatment for both groups was transarterial chemoembolization and radiofrequency ablation with 68% of White and 64% of Black veterans receiving this therapy. There was no significant difference between who received systemic therapy.

Discussion

In this retrospective analysis, Black veterans with HCC did not experience a statistically significant decrease in OS compared with that of White veterans despite some differences in therapy offered. Other studies have found that surgery was less frequently recommended to Black patients across multiple cancer types, and in most cases this carried a negative impact on OS.^{8,10,11,14,15} A number of other studies have demonstrated a greater percentage of Black patients receiving no treatment, although these studies are often based on SEER data, which captures only cancer-directed surgery and no other methods of treatment. Inequities in patient factors like insurance and socioeconomic status as well as willingness to receive certain treatments are often cited as major influences in health care disparities, but systemic and clinician factors like hospital volume, clinician expertise, specialist availability, and implicit racial bias all affect outcomes.¹⁶ One benefit of our study was that CPRS provided a centralized recording of all treatments received. Interestingly, the treatment discrepancy in our study was not attributable to a statistically significant difference in tumor stage at presentation. There should be no misconception that US Department of Veterans Affairs patients are less affected by socioeconomic inequities, though still this suggests clinician and systemic factors were significant drivers behind our findings.

This study did not intend to determine differences in incidence of HCC by race, although many studies have shown an age-adjusted incidence of HCC among Black and Hispanic patients up to twice that of White patients.^1,8-10 Notably, the rate of orthotopic liver transplantation in this study was low regardless of race compared with that of other larger studies of patients with HCC.^12,15 Discrepancies in HCC care among White and Black patients have been suggested to stem from a variety of influences, including access to early diagnosis and treatment of hepatitis C virus, comorbid conditions, as well as complex socioeconomic factors. It also has been shown that oncologists’ implicit racial bias has a negative impact on patients’ perceived quality of communication, their confidence in the recommended treatment, and the understood difficulty of the treatment by the patient and should be considered as a contributor to health disparities.^17,18

Studies evaluating survival in HCC using SEER data generally stratify disease by localized, regional, or distant metastasis. For our study, TNM staging provided a more accurate assessment of the disease and reduced the chances that broader staging definitions could obscure differences in treatment choices. Future studies could be improved by stratifying patients by variables impacting treatment choice, such as Child-Pugh score or Barcelona Clinic Liver Cancer staging. Our study demonstrated a statistically significant difference in AFP level between White and Black veterans. This has been observed in prior studies as well, and while no specific cause has been identified, it suggests differences in tumor biologic features across different races. In addition, we found that an elevated AFP level at the time of diagnosis (defined as > 400) correlates with a worsened OS (HR, 1.36; P = .01).

Limitations

This study has several limitations, notably the number of veterans eligible for analysis at a single institution. A larger cohort would be needed to evaluate for statistically significant differences in outcomes by race. Additionally, our study did not account for therapy that was offered to but not pursued by the patient, and this would be useful to determine whether patient or practitioner factors were the more significant influence on the type of therapy received.

Conclusions

This study demonstrated a statistically significant difference in the rate of resection and liver transplantation between White and Black veterans at a single institution, although no difference in OS was observed. This discrepancy was not explained by differences in tumor staging. Additional, larger studies will be useful in clarifying the biologic, cultural, and socioeconomic drivers in HCC treatment and mortality.

Acknowledgments

The authors thank Lorri Reaves, Memphis Veterans Affairs Medical Center, Department of Hepatology.

Hepatocellular carcinoma (HCC) is the sixth most common and third most deadly malignancy worldwide, carrying a mean survival rate without treatment of 6 to 20 months depending on stage.¹ Fifty-seven percent of patients with liver cancer are diagnosed with regional or distant metastatic disease that carries 5-year relative survival rates of 10.7% and 3.1%, respectively.² HCC arises most commonly from liver cirrhosis due to chronic hepatocyte injury, which may be mediated by viral hepatitis, alcoholism, and metabolic disease. Other less common causes include autoimmune disease, exposure to environmental hazards, and certain genetic diseases, such as α-1 antitrypsin deficiency and Wilson disease.

Multiple staging systems for HCC exist that incorporate some variation of the following features: size and invasion of the tumor, distant metastases, and liver function. Stage-directed treatments for HCC include ablation, embolization, resection, transplant, and systemic therapy, such as tyrosine kinase inhibitors, immunotherapies, and monoclonal antibodies. In addition to tumor/node/metastasis (TNM) staging, α-fetoprotein (AFP) is a diagnostic marker with prognostic value in HCC with higher levels correlating to higher tumor burden and a worse prognosis. With treatment, the 5-year survival rate for early stage HCC ranges from 60% to 80% but decreases significantly with higher stages.¹ HCC screening in at-risk populations has accounted for > 40% of diagnoses since the practice became widely adopted, and earlier recognition has led to an improvement in survival even when adjusting for lead time bias.³

Systemic therapy for advanced disease continues to improve. Sorafenib remained the standard first-line systemic therapy since it was introduced in 2008.⁴ First-line therapy improved with immunotherapies. The phase 3 IMBrave150 trial comparing atezolizumab plus bevacizumab to sorafenib showed a median overall survival (OS) > 19 months with 7.7% of patients achieving a complete response.⁵ HIMALAYA, another phase 3 trial set for publication later this year, also reported promising results when a priming dose of the CTLA-4 inhibitor tremelimumab followed by durvalumab was compared with sorafenib.⁶

There has been a rise in incidence of HCC in the United States across all races and ethnicities, though Black, Hispanic, and Asian patients remain disproportionately affected. Subsequently, identifying causative biologic, socioeconomic, and cultural factors, as well as implicit bias in health care continues to be a topic of great interest.^7-9 Using Surveillance, Epidemiology, and End Results (SEER) data, a number of large studies have found that Black patients with HCC were more likely to present with an advanced stage, less likely to receive curative intent treatment, and had significantly reduced survival compared with that of White patients.^1,7-9 An analysis of 1117 patients by Rich and colleagues noted a 34% increased risk of death for Black patients with HCC compared with that of White patients, and other studies have shown about a 50% reduction in rate of liver transplantation for Black patients.^10-12 Our study aimed to investigate potential disparities in incidence, etiology, AFP level at diagnosis, and outcomes of HCC in Black and White veterans managed at the Memphis Veterans Affairs Medical Center (VAMC) in Tennessee.

Methods

A single center retrospective chart review was conducted at the Memphis VAMC using the Computerized Patient Record System (CPRS) and the International Statistical Classification of Diseases, Tenth Revision (ICD-10) code C22.0 for HCC. Initial results were manually refined by prespecified criteria. Patients were included if they were diagnosed with HCC and received HCC treatment at the Memphis VAMC. Patients were excluded if HCC was not diagnosed histologically or clinically by imaging characteristics and AFP level, if the patient’s primary treatment was not provided at the Memphis VAMC, if they were lost to follow-up, or if race was not specified as either Black or White.

The following patient variables were examined: age, sex, comorbidities (alcohol or substance use disorder, cirrhosis, HIV), tumor stage, AFP, method of diagnosis, first-line treatments, systemic treatment, surgical options offered, and mortality. Staging was based on the American Joint Committee on Cancer TNM staging for HCC.¹³ Surgical options were recorded as resection or transplant. Patients who were offered treatment but lost to follow-up were excluded from the analysis.

Data Analysis

Our primary endpoint was identifying differences in OS among Memphis VAMC patients with HCC related to race. Kaplan-Meier analysis was used to investigate differences in OS and cumulative hazard ratio (HR) for death. Cox regression multivariate analysis further evaluated discrepancies among investigated patient variables, including age, race, alcohol, tobacco, or illicit drug use, HIV coinfection, and cirrhosis. Treatment factors were further defined by first-line treatment, systemic therapy, surgical resection, and transplant. χ² analysis was used to investigate differences in treatment modalities.

Results

We identified 227 veterans, 95 Black and 132 White, between 2009 and 2021 meeting criteria for primary HCC treated at the Memphis VAMC. This study did not show a significant difference in OS between White and Black veterans (P = .24). Kaplan-Meier assessment showed OS was 1247 days (41 months) for Black veterans compared with 1032 days (34 months) for White veterans (Figure; Table 1).

Additionally, no significant difference was found between veterans for age or stage at diagnosis when stratified by race. The mean age of diagnosis for both groups was 65 years (P = .09). The mean TNM staging was 1.7 for White veterans vs 1.8 for Black veterans (P = .57). There was a significant increase in the AFP level at diagnosis for Black veterans (P = .001) (Table 2).

The most common initial treatment for both groups was transarterial chemoembolization and radiofrequency ablation with 68% of White and 64% of Black veterans receiving this therapy. There was no significant difference between who received systemic therapy.

Discussion

In this retrospective analysis, Black veterans with HCC did not experience a statistically significant decrease in OS compared with that of White veterans despite some differences in therapy offered. Other studies have found that surgery was less frequently recommended to Black patients across multiple cancer types, and in most cases this carried a negative impact on OS.^{8,10,11,14,15} A number of other studies have demonstrated a greater percentage of Black patients receiving no treatment, although these studies are often based on SEER data, which captures only cancer-directed surgery and no other methods of treatment. Inequities in patient factors like insurance and socioeconomic status as well as willingness to receive certain treatments are often cited as major influences in health care disparities, but systemic and clinician factors like hospital volume, clinician expertise, specialist availability, and implicit racial bias all affect outcomes.¹⁶ One benefit of our study was that CPRS provided a centralized recording of all treatments received. Interestingly, the treatment discrepancy in our study was not attributable to a statistically significant difference in tumor stage at presentation. There should be no misconception that US Department of Veterans Affairs patients are less affected by socioeconomic inequities, though still this suggests clinician and systemic factors were significant drivers behind our findings.

This study did not intend to determine differences in incidence of HCC by race, although many studies have shown an age-adjusted incidence of HCC among Black and Hispanic patients up to twice that of White patients.^1,8-10 Notably, the rate of orthotopic liver transplantation in this study was low regardless of race compared with that of other larger studies of patients with HCC.^12,15 Discrepancies in HCC care among White and Black patients have been suggested to stem from a variety of influences, including access to early diagnosis and treatment of hepatitis C virus, comorbid conditions, as well as complex socioeconomic factors. It also has been shown that oncologists’ implicit racial bias has a negative impact on patients’ perceived quality of communication, their confidence in the recommended treatment, and the understood difficulty of the treatment by the patient and should be considered as a contributor to health disparities.^17,18

Studies evaluating survival in HCC using SEER data generally stratify disease by localized, regional, or distant metastasis. For our study, TNM staging provided a more accurate assessment of the disease and reduced the chances that broader staging definitions could obscure differences in treatment choices. Future studies could be improved by stratifying patients by variables impacting treatment choice, such as Child-Pugh score or Barcelona Clinic Liver Cancer staging. Our study demonstrated a statistically significant difference in AFP level between White and Black veterans. This has been observed in prior studies as well, and while no specific cause has been identified, it suggests differences in tumor biologic features across different races. In addition, we found that an elevated AFP level at the time of diagnosis (defined as > 400) correlates with a worsened OS (HR, 1.36; P = .01).

Limitations

This study has several limitations, notably the number of veterans eligible for analysis at a single institution. A larger cohort would be needed to evaluate for statistically significant differences in outcomes by race. Additionally, our study did not account for therapy that was offered to but not pursued by the patient, and this would be useful to determine whether patient or practitioner factors were the more significant influence on the type of therapy received.

Conclusions

This study demonstrated a statistically significant difference in the rate of resection and liver transplantation between White and Black veterans at a single institution, although no difference in OS was observed. This discrepancy was not explained by differences in tumor staging. Additional, larger studies will be useful in clarifying the biologic, cultural, and socioeconomic drivers in HCC treatment and mortality.

Acknowledgments

The authors thank Lorri Reaves, Memphis Veterans Affairs Medical Center, Department of Hepatology.

Patients with lung cancer now have another treatment option: If their tumors are found to carry HER2 mutations, they can now be treated with trastuzumab deruxtecan (Enhertu), a drug that specifically targets that defect.

This product is already approved for used in HER2-positive breast cancer and gastric cancer. Now it has become the first product approved by the U.S. Food and Drug Administration for use in HER2-positive lung cancer.

Clinical data welcomed by experts

Clinical data are already available from the DESTINY-Lung 01 trial, and the results were welcomed enthusiastically by experts when they were published in the New England Journal of Medicine earlier this year.

“These results establish the new standard of care for patients with NSCLC harboring HER2 mutations,” Antonio Passaro, MD, PhD, from the European Institute of Oncology IRCCS, Milan, and Solange Peters, MD, PhD, from Lausanne (Switzerland) University Hospital, wrote in an accompanying editorial.

This trial involved 91 patients, all treated with trastuzumab deruxtecan (at 6.4 mg/kg of body weight every 3 weeks). The median duration of treatment was 6.9 months, and the median follow-up was 13.1 months.

The results showed a 55% centrally confirmed objective response, and median duration of response was 9.3 months.

In addition, the investigators reported a median progression-free survival of 8.2 months and a median overall survival of almost 18 months, both of which they described as “encouraging” in this patient population.

However, the results also highlighted a problem with the drug in this patient population. Notably, 26% of patients experienced interstitial lung disease, which resulted in death in two patients. The drug was also withdrawn in 16 patients and interrupted in 8 patients because of this adverse event.

Editorialists Dr. Passaro and Dr. Peters described this finding as “a concern” and note that “the incidence of interstitial lung disease is significantly higher among patients with lung cancer than among those with breast or gastric cancers, which may indicate a role of smoking-related damage.”

They also highlighted the need for an “investigation of the clinical efficacy of a reduced dose of trastuzumab deruxtecan,” and so the dose was reduced for the DESTINY-Lung02 trial.

A version of this article first appeared on Medscape.com.

Patients with lung cancer now have another treatment option: If their tumors are found to carry HER2 mutations, they can now be treated with trastuzumab deruxtecan (Enhertu), a drug that specifically targets that defect.

This product is already approved for used in HER2-positive breast cancer and gastric cancer. Now it has become the first product approved by the U.S. Food and Drug Administration for use in HER2-positive lung cancer.

Clinical data welcomed by experts

Clinical data are already available from the DESTINY-Lung 01 trial, and the results were welcomed enthusiastically by experts when they were published in the New England Journal of Medicine earlier this year.

“These results establish the new standard of care for patients with NSCLC harboring HER2 mutations,” Antonio Passaro, MD, PhD, from the European Institute of Oncology IRCCS, Milan, and Solange Peters, MD, PhD, from Lausanne (Switzerland) University Hospital, wrote in an accompanying editorial.

This trial involved 91 patients, all treated with trastuzumab deruxtecan (at 6.4 mg/kg of body weight every 3 weeks). The median duration of treatment was 6.9 months, and the median follow-up was 13.1 months.

The results showed a 55% centrally confirmed objective response, and median duration of response was 9.3 months.

In addition, the investigators reported a median progression-free survival of 8.2 months and a median overall survival of almost 18 months, both of which they described as “encouraging” in this patient population.

However, the results also highlighted a problem with the drug in this patient population. Notably, 26% of patients experienced interstitial lung disease, which resulted in death in two patients. The drug was also withdrawn in 16 patients and interrupted in 8 patients because of this adverse event.

Editorialists Dr. Passaro and Dr. Peters described this finding as “a concern” and note that “the incidence of interstitial lung disease is significantly higher among patients with lung cancer than among those with breast or gastric cancers, which may indicate a role of smoking-related damage.”

They also highlighted the need for an “investigation of the clinical efficacy of a reduced dose of trastuzumab deruxtecan,” and so the dose was reduced for the DESTINY-Lung02 trial.

A version of this article first appeared on Medscape.com.

Patients with lung cancer now have another treatment option: If their tumors are found to carry HER2 mutations, they can now be treated with trastuzumab deruxtecan (Enhertu), a drug that specifically targets that defect.

This product is already approved for used in HER2-positive breast cancer and gastric cancer. Now it has become the first product approved by the U.S. Food and Drug Administration for use in HER2-positive lung cancer.

Clinical data welcomed by experts

Clinical data are already available from the DESTINY-Lung 01 trial, and the results were welcomed enthusiastically by experts when they were published in the New England Journal of Medicine earlier this year.

“These results establish the new standard of care for patients with NSCLC harboring HER2 mutations,” Antonio Passaro, MD, PhD, from the European Institute of Oncology IRCCS, Milan, and Solange Peters, MD, PhD, from Lausanne (Switzerland) University Hospital, wrote in an accompanying editorial.

This trial involved 91 patients, all treated with trastuzumab deruxtecan (at 6.4 mg/kg of body weight every 3 weeks). The median duration of treatment was 6.9 months, and the median follow-up was 13.1 months.

The results showed a 55% centrally confirmed objective response, and median duration of response was 9.3 months.

In addition, the investigators reported a median progression-free survival of 8.2 months and a median overall survival of almost 18 months, both of which they described as “encouraging” in this patient population.

However, the results also highlighted a problem with the drug in this patient population. Notably, 26% of patients experienced interstitial lung disease, which resulted in death in two patients. The drug was also withdrawn in 16 patients and interrupted in 8 patients because of this adverse event.

Editorialists Dr. Passaro and Dr. Peters described this finding as “a concern” and note that “the incidence of interstitial lung disease is significantly higher among patients with lung cancer than among those with breast or gastric cancers, which may indicate a role of smoking-related damage.”

They also highlighted the need for an “investigation of the clinical efficacy of a reduced dose of trastuzumab deruxtecan,” and so the dose was reduced for the DESTINY-Lung02 trial.

A version of this article first appeared on Medscape.com.

There is a growing body of evidence to show that air pollution is a major risk factor for lung cancer among never-smokers, although there is less certainty about the duration of exposure to fine particulate matter in ambient air as it relates to risk for lung cancer.

But as Canadian researchers now report, even 20 years of data on cumulative exposure to air pollution may underestimate the magnitude of the effect, especially among people diagnosed with lung cancer who have migrated from regions where heavy air pollution is the norm.

In a study of Canadian women with newly diagnosed lung cancer who never smoked, Renelle Myers, MD, FRCPC, from the University of British Columbia in Vancouver and colleagues found that shorter-term assessment of cumulative exposure to ambient air particles smaller than 2.5 microns (PM2.5) may underestimate the health effects of chronic exposure to pollution, especially among those patients who had migrated to Canada after living in areas of high PM2.5 exposure for long periods of time.

“Our study points to the importance of incorporating this long-term cumulative exposure to air pollutants in the assessment of individual lung cancer risk, of course in combination with traditional risk factors, and depending on the country of residence, I think that even a 20-year cumulative exposure may underestimate the effects of PM2.5, as we’re not capturing childhood or adolescent exposure when the lung is developing, and what effect that will have,” she said in an oral abstract presented at the World Conference on Lung Cancer.
 

Satellite data on local pollution

With the objective of comparing cumulative 3-year vs. 20-year exposure to PM2.5 in women who had never smoked and had a new diagnosis of lung cancer, Dr. Myers and colleagues conducted a cross-sectional study.

They recruited a total of 236 women and had them fill out a detailed residential history questionnaire, and demographic details including age, race, country of birth, arrival in Canada for those born out of the country, occupations, family history of lung cancer, and exposure to second-hand smoke.

The investigators linked local addresses or postal to satellite-derived data on local PM2.5 levels, which first became available in 1996.

The median age of participants was 66.1 years. Of the 236 participants, 190 (80.5%) were born outside of Canada, and came to the country at the median age of 45. About half of all participants came from mainland China or Hong Kong, and another one-third came from elsewhere in Asia.

Tumor histologies included adenocarcinomas in 219 patients, squamous cell carcinoma in 1, and other types in 16 patients. Slightly more than half of the patients (55.%) had stage III or IV disease at diagnosis. In all, 106 of 227 evaluable patients had EGFR mutations.

3 years not enough

Among the foreign-born patients, only 4 (2%) had 3-year cumulative PM2.5 exposure greater than 10 mcg/m³, but 38 (20%) had 20-year cumulative exposure greater than 10 mcg/m³ (P < .0001).

All of the patients had cumulative PM2.5 exposures greater than 5 mcg/m³.

Comparing patients with and without EGFR mutations, the investigators found that higher 3-year cumulative PM2.5 exposure was significantly associated with EGFR mutations compared with nonmutated cancers (P = .049), but there was no significant association with higher 20-year cumulative exposures.

“The significance of this study really captures that short term or at least less than 3-year cumulative exposure risk for PM2.5 will probably underestimate the adverse effects that chronic exposure to air pollution has, especially among patients who lived elsewhere that may have had higher exposure throughout their lifetime than where you actually meet them,” Dr. Myers said in a media briefing held prior to her presentation.
 

Lung cancer in female nonsmokers

During the oral abstract session, invited discussant Chang-Chuan Chan, ScD, National Taiwan University, Taipei, said that the study’s focus on female patients with lung cancer is important. He pointed to a 2019 study examining the relationship between air pollution and lung cancer among nonsmokers in Taiwan, in which the authors found that, although smoking levels among women remained low over time (about 5%), the incidence of lung adenocarcinomas among women increased from 7.05 per 100,000 in 1995, to 24.22 per 100,000 in 2015.

The authors of that study also found that changes in PM2.5 levels in Taiwan were predictive of fluctuations in lung cancer prevalence in never-smokers.

“We’re moving from 50-year studies of smoking to these new issues of air pollution, asbestos, and radon, and I think it’s better that these three factors can be combined together,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.

The study was supported by the BC Cancer Foundation, Terry Fox Research Institute, and VGH-UBC Hospital Foundation. Dr. Myers and Dr. Chan reported having no financial conflicts of interest to disclose.

There is a growing body of evidence to show that air pollution is a major risk factor for lung cancer among never-smokers, although there is less certainty about the duration of exposure to fine particulate matter in ambient air as it relates to risk for lung cancer.

But as Canadian researchers now report, even 20 years of data on cumulative exposure to air pollution may underestimate the magnitude of the effect, especially among people diagnosed with lung cancer who have migrated from regions where heavy air pollution is the norm.

In a study of Canadian women with newly diagnosed lung cancer who never smoked, Renelle Myers, MD, FRCPC, from the University of British Columbia in Vancouver and colleagues found that shorter-term assessment of cumulative exposure to ambient air particles smaller than 2.5 microns (PM2.5) may underestimate the health effects of chronic exposure to pollution, especially among those patients who had migrated to Canada after living in areas of high PM2.5 exposure for long periods of time.

“Our study points to the importance of incorporating this long-term cumulative exposure to air pollutants in the assessment of individual lung cancer risk, of course in combination with traditional risk factors, and depending on the country of residence, I think that even a 20-year cumulative exposure may underestimate the effects of PM2.5, as we’re not capturing childhood or adolescent exposure when the lung is developing, and what effect that will have,” she said in an oral abstract presented at the World Conference on Lung Cancer.
 

Satellite data on local pollution

With the objective of comparing cumulative 3-year vs. 20-year exposure to PM2.5 in women who had never smoked and had a new diagnosis of lung cancer, Dr. Myers and colleagues conducted a cross-sectional study.

They recruited a total of 236 women and had them fill out a detailed residential history questionnaire, and demographic details including age, race, country of birth, arrival in Canada for those born out of the country, occupations, family history of lung cancer, and exposure to second-hand smoke.

The investigators linked local addresses or postal to satellite-derived data on local PM2.5 levels, which first became available in 1996.

The median age of participants was 66.1 years. Of the 236 participants, 190 (80.5%) were born outside of Canada, and came to the country at the median age of 45. About half of all participants came from mainland China or Hong Kong, and another one-third came from elsewhere in Asia.

Tumor histologies included adenocarcinomas in 219 patients, squamous cell carcinoma in 1, and other types in 16 patients. Slightly more than half of the patients (55.%) had stage III or IV disease at diagnosis. In all, 106 of 227 evaluable patients had EGFR mutations.

3 years not enough

Among the foreign-born patients, only 4 (2%) had 3-year cumulative PM2.5 exposure greater than 10 mcg/m³, but 38 (20%) had 20-year cumulative exposure greater than 10 mcg/m³ (P < .0001).

All of the patients had cumulative PM2.5 exposures greater than 5 mcg/m³.

Comparing patients with and without EGFR mutations, the investigators found that higher 3-year cumulative PM2.5 exposure was significantly associated with EGFR mutations compared with nonmutated cancers (P = .049), but there was no significant association with higher 20-year cumulative exposures.

“The significance of this study really captures that short term or at least less than 3-year cumulative exposure risk for PM2.5 will probably underestimate the adverse effects that chronic exposure to air pollution has, especially among patients who lived elsewhere that may have had higher exposure throughout their lifetime than where you actually meet them,” Dr. Myers said in a media briefing held prior to her presentation.
 

Lung cancer in female nonsmokers

During the oral abstract session, invited discussant Chang-Chuan Chan, ScD, National Taiwan University, Taipei, said that the study’s focus on female patients with lung cancer is important. He pointed to a 2019 study examining the relationship between air pollution and lung cancer among nonsmokers in Taiwan, in which the authors found that, although smoking levels among women remained low over time (about 5%), the incidence of lung adenocarcinomas among women increased from 7.05 per 100,000 in 1995, to 24.22 per 100,000 in 2015.

The authors of that study also found that changes in PM2.5 levels in Taiwan were predictive of fluctuations in lung cancer prevalence in never-smokers.

“We’re moving from 50-year studies of smoking to these new issues of air pollution, asbestos, and radon, and I think it’s better that these three factors can be combined together,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.

The study was supported by the BC Cancer Foundation, Terry Fox Research Institute, and VGH-UBC Hospital Foundation. Dr. Myers and Dr. Chan reported having no financial conflicts of interest to disclose.

There is a growing body of evidence to show that air pollution is a major risk factor for lung cancer among never-smokers, although there is less certainty about the duration of exposure to fine particulate matter in ambient air as it relates to risk for lung cancer.

But as Canadian researchers now report, even 20 years of data on cumulative exposure to air pollution may underestimate the magnitude of the effect, especially among people diagnosed with lung cancer who have migrated from regions where heavy air pollution is the norm.

In a study of Canadian women with newly diagnosed lung cancer who never smoked, Renelle Myers, MD, FRCPC, from the University of British Columbia in Vancouver and colleagues found that shorter-term assessment of cumulative exposure to ambient air particles smaller than 2.5 microns (PM2.5) may underestimate the health effects of chronic exposure to pollution, especially among those patients who had migrated to Canada after living in areas of high PM2.5 exposure for long periods of time.

“Our study points to the importance of incorporating this long-term cumulative exposure to air pollutants in the assessment of individual lung cancer risk, of course in combination with traditional risk factors, and depending on the country of residence, I think that even a 20-year cumulative exposure may underestimate the effects of PM2.5, as we’re not capturing childhood or adolescent exposure when the lung is developing, and what effect that will have,” she said in an oral abstract presented at the World Conference on Lung Cancer.
 

Satellite data on local pollution

With the objective of comparing cumulative 3-year vs. 20-year exposure to PM2.5 in women who had never smoked and had a new diagnosis of lung cancer, Dr. Myers and colleagues conducted a cross-sectional study.

They recruited a total of 236 women and had them fill out a detailed residential history questionnaire, and demographic details including age, race, country of birth, arrival in Canada for those born out of the country, occupations, family history of lung cancer, and exposure to second-hand smoke.

The investigators linked local addresses or postal to satellite-derived data on local PM2.5 levels, which first became available in 1996.

The median age of participants was 66.1 years. Of the 236 participants, 190 (80.5%) were born outside of Canada, and came to the country at the median age of 45. About half of all participants came from mainland China or Hong Kong, and another one-third came from elsewhere in Asia.

Tumor histologies included adenocarcinomas in 219 patients, squamous cell carcinoma in 1, and other types in 16 patients. Slightly more than half of the patients (55.%) had stage III or IV disease at diagnosis. In all, 106 of 227 evaluable patients had EGFR mutations.

3 years not enough

Among the foreign-born patients, only 4 (2%) had 3-year cumulative PM2.5 exposure greater than 10 mcg/m³, but 38 (20%) had 20-year cumulative exposure greater than 10 mcg/m³ (P < .0001).

All of the patients had cumulative PM2.5 exposures greater than 5 mcg/m³.

Comparing patients with and without EGFR mutations, the investigators found that higher 3-year cumulative PM2.5 exposure was significantly associated with EGFR mutations compared with nonmutated cancers (P = .049), but there was no significant association with higher 20-year cumulative exposures.

“The significance of this study really captures that short term or at least less than 3-year cumulative exposure risk for PM2.5 will probably underestimate the adverse effects that chronic exposure to air pollution has, especially among patients who lived elsewhere that may have had higher exposure throughout their lifetime than where you actually meet them,” Dr. Myers said in a media briefing held prior to her presentation.
 

Lung cancer in female nonsmokers

During the oral abstract session, invited discussant Chang-Chuan Chan, ScD, National Taiwan University, Taipei, said that the study’s focus on female patients with lung cancer is important. He pointed to a 2019 study examining the relationship between air pollution and lung cancer among nonsmokers in Taiwan, in which the authors found that, although smoking levels among women remained low over time (about 5%), the incidence of lung adenocarcinomas among women increased from 7.05 per 100,000 in 1995, to 24.22 per 100,000 in 2015.

The authors of that study also found that changes in PM2.5 levels in Taiwan were predictive of fluctuations in lung cancer prevalence in never-smokers.

“We’re moving from 50-year studies of smoking to these new issues of air pollution, asbestos, and radon, and I think it’s better that these three factors can be combined together,” he said at the meeting sponsored by the International Association for the Study of Lung Cancer.

The study was supported by the BC Cancer Foundation, Terry Fox Research Institute, and VGH-UBC Hospital Foundation. Dr. Myers and Dr. Chan reported having no financial conflicts of interest to disclose.

COVID-19 is far from done in the United States, with more than 111,000 new cases being recorded a day in the second week of August, according to Johns Hopkins University, and 625 deaths being reported every day. And as that toll grows, experts are worried about a second wave of illnesses from long COVID, a condition that already has affected between 7.7 million and 23 million Americans, according to U.S. government estimates.

“It is evident that long COVID is real, that it already impacts a substantial number of people, and that this number may continue to grow as new infections occur,” the U.S. Department of Health and Human Services (HHS) said in a research action plan released Aug. 4.

“We are heading towards a big problem on our hands,” says Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs Hospital in St. Louis. “It’s like if we are falling in a plane, hurtling towards the ground. It doesn’t matter at what speed we are falling; what matters is that we are all falling, and falling fast. It’s a real problem. We needed to bring attention to this, yesterday,” he said.

Bryan Lau, PhD, professor of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and co-lead of a long COVID study there, says whether it’s 5% of the 92 million officially recorded U.S. COVID-19 cases, or 30% – on the higher end of estimates – that means anywhere between 4.5 million and 27 million Americans will have the effects of long COVID.

Other experts put the estimates even higher.

“If we conservatively assume 100 million working-age adults have been infected, that implies 10 to 33 million may have long COVID,” Alice Burns, PhD, associate director for the Kaiser Family Foundation’s Program on Medicaid and the Uninsured, wrote in an analysis.

And even the Centers for Disease Control and Prevention says only a fraction of cases have been recorded.

That, in turn, means tens of millions of people who struggle to work, to get to school, and to take care of their families – and who will be making demands on an already stressed U.S. health care system.

The HHS said in its Aug. 4 report that long COVID could keep 1 million people a day out of work, with a loss of $50 billion in annual pay.

Dr. Lau said health workers and policymakers are woefully unprepared.

“If you have a family unit, and the mom or dad can’t work, or has trouble taking their child to activities, where does the question of support come into play? Where is there potential for food issues, or housing issues?” he asked. “I see the potential for the burden to be extremely large in that capacity.”

Dr. Lau said he has yet to see any strong estimates of how many cases of long COVID might develop. Because a person has to get COVID-19 to ultimately get long COVID, the two are linked. In other words, as COVID-19 cases rise, so will cases of long COVID, and vice versa.

Evidence from the Kaiser Family Foundation analysis suggests a significant impact on employment: Surveys showed more than half of adults with long COVID who worked before becoming infected are either out of work or working fewer hours. Conditions associated with long COVID – such as fatigue, malaise, or problems concentrating – limit people’s ability to work, even if they have jobs that allow for accommodations.

Two surveys of people with long COVID who had worked before becoming infected showed that between 22% and 27% of them were out of work after getting long COVID. In comparison, among all working-age adults in 2019, only 7% were out of work. Given the sheer number of working-age adults with long COVID, the effects on employment may be profound and are likely to involve more people over time. One study estimates that long COVID already accounts for 15% of unfilled jobs.

The most severe symptoms of long COVID include brain fog and heart complications, known to persist for weeks for months after a COVID-19 infection.

A study from the University of Norway published in Open Forum Infectious Diseases found 53% of people tested had at least one symptom of thinking problems 13 months after infection with COVID-19. According to the HHS’ latest report on long COVID, people with thinking problems, heart conditions, mobility issues, and other symptoms are going to need a considerable amount of care. Many will need lengthy periods of rehabilitation.

Dr. Al-Aly worries that long COVID has already severely affected the labor force and the job market, all while burdening the country’s health care system.

“While there are variations in how individuals respond and cope with long COVID, the unifying thread is that with the level of disability it causes, more people will be struggling to keep up with the demands of the workforce and more people will be out on disability than ever before,” he said.

Studies from Johns Hopkins and the University of Washington estimate that 5%-30% of people could get long COVID in the future. Projections beyond that are hazy.

“So far, all the studies we have done on long COVID have been reactionary. Much of the activism around long COVID has been patient led. We are seeing more and more people with lasting symptoms. We need our research to catch up,” Dr. Lau said.

Theo Vos, MD, PhD, professor of health sciences at University of Washington, Seattle, said the main reasons for the huge range of predictions are the variety of methods used, as well as differences in sample size. Also, much long COVID data is self-reported, making it difficult for epidemiologists to track.

“With self-reported data, you can’t plug people into a machine and say this is what they have or this is what they don’t have. At the population level, the only thing you can do is ask questions. There is no systematic way to define long COVID,” he said.

Dr. Vos’s most recent study, which is being peer-reviewed and revised, found that most people with long COVID have symptoms similar to those seen in other autoimmune diseases. But sometimes the immune system can overreact, causing the more severe symptoms, such as brain fog and heart problems, associated with long COVID.

One reason that researchers struggle to come up with numbers, said Dr. Al-Aly, is the rapid rise of new variants. These variants appear to sometimes cause less severe disease than previous ones, but it’s not clear whether that means different risks for long COVID.

“There’s a wide diversity in severity. Someone can have long COVID and be fully functional, while others are not functional at all. We still have a long way to go before we figure out why,” Dr. Lau said.

A version of this article first appeared on WebMD.com.

COVID-19 is far from done in the United States, with more than 111,000 new cases being recorded a day in the second week of August, according to Johns Hopkins University, and 625 deaths being reported every day. And as that toll grows, experts are worried about a second wave of illnesses from long COVID, a condition that already has affected between 7.7 million and 23 million Americans, according to U.S. government estimates.

“It is evident that long COVID is real, that it already impacts a substantial number of people, and that this number may continue to grow as new infections occur,” the U.S. Department of Health and Human Services (HHS) said in a research action plan released Aug. 4.

“We are heading towards a big problem on our hands,” says Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs Hospital in St. Louis. “It’s like if we are falling in a plane, hurtling towards the ground. It doesn’t matter at what speed we are falling; what matters is that we are all falling, and falling fast. It’s a real problem. We needed to bring attention to this, yesterday,” he said.

Bryan Lau, PhD, professor of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and co-lead of a long COVID study there, says whether it’s 5% of the 92 million officially recorded U.S. COVID-19 cases, or 30% – on the higher end of estimates – that means anywhere between 4.5 million and 27 million Americans will have the effects of long COVID.

Other experts put the estimates even higher.

“If we conservatively assume 100 million working-age adults have been infected, that implies 10 to 33 million may have long COVID,” Alice Burns, PhD, associate director for the Kaiser Family Foundation’s Program on Medicaid and the Uninsured, wrote in an analysis.

And even the Centers for Disease Control and Prevention says only a fraction of cases have been recorded.

That, in turn, means tens of millions of people who struggle to work, to get to school, and to take care of their families – and who will be making demands on an already stressed U.S. health care system.

The HHS said in its Aug. 4 report that long COVID could keep 1 million people a day out of work, with a loss of $50 billion in annual pay.

Dr. Lau said health workers and policymakers are woefully unprepared.

“If you have a family unit, and the mom or dad can’t work, or has trouble taking their child to activities, where does the question of support come into play? Where is there potential for food issues, or housing issues?” he asked. “I see the potential for the burden to be extremely large in that capacity.”

Dr. Lau said he has yet to see any strong estimates of how many cases of long COVID might develop. Because a person has to get COVID-19 to ultimately get long COVID, the two are linked. In other words, as COVID-19 cases rise, so will cases of long COVID, and vice versa.

Evidence from the Kaiser Family Foundation analysis suggests a significant impact on employment: Surveys showed more than half of adults with long COVID who worked before becoming infected are either out of work or working fewer hours. Conditions associated with long COVID – such as fatigue, malaise, or problems concentrating – limit people’s ability to work, even if they have jobs that allow for accommodations.

Two surveys of people with long COVID who had worked before becoming infected showed that between 22% and 27% of them were out of work after getting long COVID. In comparison, among all working-age adults in 2019, only 7% were out of work. Given the sheer number of working-age adults with long COVID, the effects on employment may be profound and are likely to involve more people over time. One study estimates that long COVID already accounts for 15% of unfilled jobs.

The most severe symptoms of long COVID include brain fog and heart complications, known to persist for weeks for months after a COVID-19 infection.

A study from the University of Norway published in Open Forum Infectious Diseases found 53% of people tested had at least one symptom of thinking problems 13 months after infection with COVID-19. According to the HHS’ latest report on long COVID, people with thinking problems, heart conditions, mobility issues, and other symptoms are going to need a considerable amount of care. Many will need lengthy periods of rehabilitation.

Dr. Al-Aly worries that long COVID has already severely affected the labor force and the job market, all while burdening the country’s health care system.

“While there are variations in how individuals respond and cope with long COVID, the unifying thread is that with the level of disability it causes, more people will be struggling to keep up with the demands of the workforce and more people will be out on disability than ever before,” he said.

Studies from Johns Hopkins and the University of Washington estimate that 5%-30% of people could get long COVID in the future. Projections beyond that are hazy.

“So far, all the studies we have done on long COVID have been reactionary. Much of the activism around long COVID has been patient led. We are seeing more and more people with lasting symptoms. We need our research to catch up,” Dr. Lau said.

Theo Vos, MD, PhD, professor of health sciences at University of Washington, Seattle, said the main reasons for the huge range of predictions are the variety of methods used, as well as differences in sample size. Also, much long COVID data is self-reported, making it difficult for epidemiologists to track.

“With self-reported data, you can’t plug people into a machine and say this is what they have or this is what they don’t have. At the population level, the only thing you can do is ask questions. There is no systematic way to define long COVID,” he said.

Dr. Vos’s most recent study, which is being peer-reviewed and revised, found that most people with long COVID have symptoms similar to those seen in other autoimmune diseases. But sometimes the immune system can overreact, causing the more severe symptoms, such as brain fog and heart problems, associated with long COVID.

One reason that researchers struggle to come up with numbers, said Dr. Al-Aly, is the rapid rise of new variants. These variants appear to sometimes cause less severe disease than previous ones, but it’s not clear whether that means different risks for long COVID.

“There’s a wide diversity in severity. Someone can have long COVID and be fully functional, while others are not functional at all. We still have a long way to go before we figure out why,” Dr. Lau said.

A version of this article first appeared on WebMD.com.

COVID-19 is far from done in the United States, with more than 111,000 new cases being recorded a day in the second week of August, according to Johns Hopkins University, and 625 deaths being reported every day. And as that toll grows, experts are worried about a second wave of illnesses from long COVID, a condition that already has affected between 7.7 million and 23 million Americans, according to U.S. government estimates.

“It is evident that long COVID is real, that it already impacts a substantial number of people, and that this number may continue to grow as new infections occur,” the U.S. Department of Health and Human Services (HHS) said in a research action plan released Aug. 4.

“We are heading towards a big problem on our hands,” says Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs Hospital in St. Louis. “It’s like if we are falling in a plane, hurtling towards the ground. It doesn’t matter at what speed we are falling; what matters is that we are all falling, and falling fast. It’s a real problem. We needed to bring attention to this, yesterday,” he said.

Bryan Lau, PhD, professor of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, and co-lead of a long COVID study there, says whether it’s 5% of the 92 million officially recorded U.S. COVID-19 cases, or 30% – on the higher end of estimates – that means anywhere between 4.5 million and 27 million Americans will have the effects of long COVID.

Other experts put the estimates even higher.

“If we conservatively assume 100 million working-age adults have been infected, that implies 10 to 33 million may have long COVID,” Alice Burns, PhD, associate director for the Kaiser Family Foundation’s Program on Medicaid and the Uninsured, wrote in an analysis.

And even the Centers for Disease Control and Prevention says only a fraction of cases have been recorded.

That, in turn, means tens of millions of people who struggle to work, to get to school, and to take care of their families – and who will be making demands on an already stressed U.S. health care system.

The HHS said in its Aug. 4 report that long COVID could keep 1 million people a day out of work, with a loss of $50 billion in annual pay.

Dr. Lau said health workers and policymakers are woefully unprepared.

“If you have a family unit, and the mom or dad can’t work, or has trouble taking their child to activities, where does the question of support come into play? Where is there potential for food issues, or housing issues?” he asked. “I see the potential for the burden to be extremely large in that capacity.”

Dr. Lau said he has yet to see any strong estimates of how many cases of long COVID might develop. Because a person has to get COVID-19 to ultimately get long COVID, the two are linked. In other words, as COVID-19 cases rise, so will cases of long COVID, and vice versa.

Evidence from the Kaiser Family Foundation analysis suggests a significant impact on employment: Surveys showed more than half of adults with long COVID who worked before becoming infected are either out of work or working fewer hours. Conditions associated with long COVID – such as fatigue, malaise, or problems concentrating – limit people’s ability to work, even if they have jobs that allow for accommodations.

Two surveys of people with long COVID who had worked before becoming infected showed that between 22% and 27% of them were out of work after getting long COVID. In comparison, among all working-age adults in 2019, only 7% were out of work. Given the sheer number of working-age adults with long COVID, the effects on employment may be profound and are likely to involve more people over time. One study estimates that long COVID already accounts for 15% of unfilled jobs.

The most severe symptoms of long COVID include brain fog and heart complications, known to persist for weeks for months after a COVID-19 infection.

A study from the University of Norway published in Open Forum Infectious Diseases found 53% of people tested had at least one symptom of thinking problems 13 months after infection with COVID-19. According to the HHS’ latest report on long COVID, people with thinking problems, heart conditions, mobility issues, and other symptoms are going to need a considerable amount of care. Many will need lengthy periods of rehabilitation.

Dr. Al-Aly worries that long COVID has already severely affected the labor force and the job market, all while burdening the country’s health care system.

“While there are variations in how individuals respond and cope with long COVID, the unifying thread is that with the level of disability it causes, more people will be struggling to keep up with the demands of the workforce and more people will be out on disability than ever before,” he said.

Studies from Johns Hopkins and the University of Washington estimate that 5%-30% of people could get long COVID in the future. Projections beyond that are hazy.

“So far, all the studies we have done on long COVID have been reactionary. Much of the activism around long COVID has been patient led. We are seeing more and more people with lasting symptoms. We need our research to catch up,” Dr. Lau said.

Theo Vos, MD, PhD, professor of health sciences at University of Washington, Seattle, said the main reasons for the huge range of predictions are the variety of methods used, as well as differences in sample size. Also, much long COVID data is self-reported, making it difficult for epidemiologists to track.

“With self-reported data, you can’t plug people into a machine and say this is what they have or this is what they don’t have. At the population level, the only thing you can do is ask questions. There is no systematic way to define long COVID,” he said.

Dr. Vos’s most recent study, which is being peer-reviewed and revised, found that most people with long COVID have symptoms similar to those seen in other autoimmune diseases. But sometimes the immune system can overreact, causing the more severe symptoms, such as brain fog and heart problems, associated with long COVID.

One reason that researchers struggle to come up with numbers, said Dr. Al-Aly, is the rapid rise of new variants. These variants appear to sometimes cause less severe disease than previous ones, but it’s not clear whether that means different risks for long COVID.

“There’s a wide diversity in severity. Someone can have long COVID and be fully functional, while others are not functional at all. We still have a long way to go before we figure out why,” Dr. Lau said.

A version of this article first appeared on WebMD.com.

Although moderately hypofractionated radiotherapy (MHRT) is an accepted treatment for localized prostate cancer, its adaptation remains limited in the United States.^1,2 MHRT theoretically exploits α/β ratio differences between the prostate (1.5 Gy), bladder (5-10 Gy), and rectum (3 Gy), thereby reducing late treatment-related adverse effects compared with those of conventional fractionation at biologically equivalent doses.^3-8 Multiple randomized noninferiority trials have demonstrated equivalent outcomes between MHRT and conventional fraction with no appreciable increase in patient-reported toxicity.^9-14 Although these studies have led to the acceptance of MHRT as a standard treatment, the majority of these trials involve individuals with low- and intermediate-risk disease.

There are less phase 3 data addressing MHRT for high-risk prostate cancer (HRPC).^10,12,14-17 Only 2 studies examined predominately high-risk populations, accounting for 83 and 292 patients, respectively.^15,16 Additional phase 3 trials with small proportions of high-risk patients (n = 126, 12%; n = 53, 35%) offer limited additional information regarding clinical outcomes and toxicity rates specific to high-risk disease.^10-12 Numerous phase 1 and 2 studies report various field designs and fractionation plans for MHRT in the context of high-risk disease, although the applicability of these data to off-trial populations remains limited.^18-20

Furthermore, African American individuals are underrepresented in the trials establishing the role of MHRT despite higher rates of prostate cancer incidence, more advanced disease stage at diagnosis, and higher rates of prostate cancer–specific survival (PCSS) when compared with White patients.²¹ Racial disparities across patients with prostate cancer and their management are multifactorial across health care literacy, education level, access to care (including transportation issues), and issues of adherence and distrust.^22-25 Correlation of patient race to prostate cancer outcomes varies greatly across health care systems, with the US Department of Veterans Affairs (VA) equal access system providing robust mental health services and transportation services for some patients, while demonstrating similar rates of stage-adjusted PCSS between African American and White patients across a broad range of treatment modalities.^26-28 Given the paucity of data exploring outcomes following MHRT for African American patients with HRPC, the present analysis provides long-term clinical outcomes and toxicity profiles for an off-trial majority African American population with HRPC treated with MHRT within the VA.

Methods

Records were retrospectively reviewed under an institutional review board–approved protocol for all patients with HRPC treated with definitive MHRT at the Durham Veterans Affairs Healthcare System in North Carolina between November 2008 and August 2018. Exclusion criteria included < 12 months of follow-up or elective nodal irradiation. Demographic variables obtained included age at diagnosis, race, clinical T stage, pre-MHRT prostate-specific antigen (PSA), Gleason grade group at diagnosis, favorable vs unfavorable high-risk disease, pre-MHRT international prostate symptom score (IPSS), and pre-MHRT urinary medication usage (yes/no).²⁹

Concurrent androgen deprivation therapy (ADT) was initiated 6 to 8 weeks before MHRT unless medically contraindicated per the discretion of the treating radiation oncologist. Patients generally received 18 to 24 months of ADT, with those with favorable HRPC (ie, T1c disease with either Gleason 4+4 and PSA < 10 mg/mL or Gleason 3+3 and PSA > 20 ng/mL) receiving 6 months after 2015.²⁹ Patients were simulated supine in either standard or custom immobilization with a full bladder and empty rectum. MHRT fractionation plans included 70 Gy at 2.5 Gy per fraction and 60 Gy at 3 Gy per fraction. Radiotherapy targets included the prostate and seminal vesicles without elective nodal coverage per institutional practice. Treatments were delivered following image guidance, either prostate matching with cone beam computed tomography or fiducial matching with kilo voltage imaging. All patients received intensity-modulated radiotherapy. For plans delivering 70 Gy at 2.5 Gy per fraction, constraints included bladder V (volume receiving) 70 < 10 cc, V65 ≤ 15%, V40 ≤ 35%, rectum V70 < 10 cc, V65 ≤ 10%, V40 ≤ 35%, femoral heads maximum point dose ≤ 40 Gy, penile bulb mean dose ≤ 50 Gy, and small bowel V40 ≤ 1%. For plans delivering 60 Gy at 3 Gy per fraction, constraints included rectum V57 ≤ 15%, V46 ≤ 30%, V37 ≤ 50%, bladder V60 ≤ 5%, V46 ≤ 30%, V37 ≤ 50%, and femoral heads V43 ≤ 5%.

Gastrointestinal (GI) and genitourinary (GU) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, with acute toxicity defined as on-treatment < 3 months following completion of MHRT. Late toxicity was defined as ≥ 3 months following completion of MHRT. Individuals were seen in follow-up at 6 weeks and 3 months with PSA and testosterone after MHRT completion, then every 6 to 12 months for 5 years and annually thereafter. Each follow-up visit included history, physical examination, IPSS, and CTCAE grading for GI and GU toxicity.

The Wilcoxon rank sum test and χ² test were used to compare differences in demographic data, dosimetric parameters, and frequency of toxicity events with respect to patient race. Clinical endpoints including biochemical recurrence-free survival (BRFS; defined by Phoenix criteria as 2.0 above PSA nadir), distant metastases-free survival (DMFS), PCSS, and overall survival (OS) were estimated from time of radiotherapy completion by the Kaplan-Meier method and compared between African American and White race by log-rank testing.³⁰ Late GI and GU toxicity-free survival were estimated by Kaplan-Meier plots and compared between African American and White patients by the log-rank test. Statistical analysis was performed using SAS 9.4.

Results

We identified 143 patients with HRPC treated with definitive MHRT between November 2008 and August 2018 (Table 1). Mean age was 65 years (range, 36-80 years); 57% were African American men. Eighty percent of individuals had unfavorable high-risk disease. Median (IQR) PSA was 14.4 (7.8-28.6). Twenty-six percent had grade group 1-3 disease, 47% had grade group 4 disease, and 27% had grade group 5 disease. African American patients had significantly lower pre-MHRT IPSS scores than White patients (mean IPSS, 11 vs 14, respectively; P = .02) despite similar rates of preradiotherapy urinary medication usage (66% and 66%, respectively).

Eighty-six percent received 70 Gy over 28 fractions, with institutional protocol shifting to 60 Gy over 20 fractions (14%) in June 2017. The median (IQR) duration of radiotherapy was 39 (38-42) days, with 97% of individuals undergoing ADT for a median (IQR) duration of 24 (24-36) months. The median follow-up time was 38 months, with 57 (40%) patients followed for at least 60 months.

Grade 3 GI and GU acute toxicity events were observed in 1% and 4% of all individuals, respectively (Table 2). No acute GI or GU grade 4+ events were observed. No significant differences in acute GU or GI toxicity were observed between African American and White patients.

Discussion

In this study, we reported acute and late GI and GU toxicity rates as well as clinical outcomes for a majority African American population with predominately unfavorable HRPC treated with MHRT in an equal access health care environment. We found that MHRT was well tolerated with high rates of biochemical control, PCSS, and OS. Additionally, outcomes were not significantly different across patient race. To our knowledge, this is the first report of MHRT for HRPC in a majority African American population.

We found that MHRT was an effective treatment for patients with HRPC, in particular those with unfavorable high-risk disease. While prior prospective and randomized studies have investigated the use of MHRT, our series was larger than most and had a predominately unfavorable high-risk population.^12,15-17 Our biochemical and PCSS rates compare favorably with those of HRPC trial populations, particularly given the high proportion of unfavorable high-risk disease.^12,15,16 Despite similar rates of biochemical control, OS was lower in the present cohort than in HRPC trial populations, even with a younger median age at diagnosis. The similarly high rates of non–HRPC-related death across race may reflect differences in baseline comorbidities compared with trial populations as well as reported differences between individuals in the VA and the private sector.³¹ This suggests that MHRT can be an effective treatment for patients with unfavorable HRPC.

We did not find any differences in outcomes between African American and White individuals with HRPC treated with MHRT. Furthermore, our study demonstrates long-term rates of BRFS and PCSS in a majority African American population with predominately unfavorable HRPC that are comparable with those of prior randomized MHRT studies in high-risk, predominately White populations.^12,15,16 Prior reports have found that African American men with HRPC may be at increased risk for inferior clinical outcomes due to a number of socioeconomic, biologic, and cultural mediators.^26,27,32 Such individuals may disproportionally benefit from shorter treatment courses that improve access to radiotherapy, a well-documented disparity for African American men with localized prostate cancer.^33-36 The VA is an ideal system for studying racial disparities within prostate cancer, as accessibility of mental health and transportation services, income, and insurance status are not barriers to preventative or acute care.³⁷ Our results are concordant with those previously seen for African American patients with prostate cancer seen in the VA, which similarly demonstrate equal outcomes with those of other races.^28,36 Incorporation of the earlier mentioned VA services into oncologic care across other health care systems could better characterize determinants of racial disparities in prostate cancer, including the prognostic significance of shortening treatment duration and number of patient visits via MHRT.

Limitations

This study has several inherent limitations. While the size of the current HRPC cohort is notably larger than similar populations within the majority of phase 3 MHRT trials, these data derive from a single VA hospital. It is unclear whether these outcomes would be representative in a similar high-risk population receiving care outside of the VA equal access system. Follow-up data beyond 5 years was available for less than half of patients, partially due to nonprostate cancer–related mortality at a higher rate than observed in HRPC trial populations.^12,15,16 Furthermore, all GI toxicity events were exclusively physician reported, and GU toxicity reporting was limited in the off-trial setting with not all patients routinely completing IPSS questionnaires following MHRT completion. However, all patients were treated similarly, and radiation quality was verified over the treatment period with mandated accreditation, frequent standardized output checks, and systematic treatment review.³⁹

Conclusions

Patients with HRPC treated with MHRT in an equal access, off-trial setting demonstrated favorable rates of biochemical control with acceptable rates of acute and late GI and GU toxicities. Clinical outcomes, including biochemical control, were not significantly different between African American and White patients, which may reflect equal access to care within the VA irrespective of income and insurance status. Incorporating VA services, such as access to primary care, mental health services, and transportation across other health care systems may aid in characterizing and mitigating racial and gender disparities in oncologic care.  

Acknowledgments

Portions of this work were presented at the November 2020 ASTRO conference. ⁴⁰

Although moderately hypofractionated radiotherapy (MHRT) is an accepted treatment for localized prostate cancer, its adaptation remains limited in the United States.^1,2 MHRT theoretically exploits α/β ratio differences between the prostate (1.5 Gy), bladder (5-10 Gy), and rectum (3 Gy), thereby reducing late treatment-related adverse effects compared with those of conventional fractionation at biologically equivalent doses.^3-8 Multiple randomized noninferiority trials have demonstrated equivalent outcomes between MHRT and conventional fraction with no appreciable increase in patient-reported toxicity.^9-14 Although these studies have led to the acceptance of MHRT as a standard treatment, the majority of these trials involve individuals with low- and intermediate-risk disease.

There are less phase 3 data addressing MHRT for high-risk prostate cancer (HRPC).^10,12,14-17 Only 2 studies examined predominately high-risk populations, accounting for 83 and 292 patients, respectively.^15,16 Additional phase 3 trials with small proportions of high-risk patients (n = 126, 12%; n = 53, 35%) offer limited additional information regarding clinical outcomes and toxicity rates specific to high-risk disease.^10-12 Numerous phase 1 and 2 studies report various field designs and fractionation plans for MHRT in the context of high-risk disease, although the applicability of these data to off-trial populations remains limited.^18-20

Furthermore, African American individuals are underrepresented in the trials establishing the role of MHRT despite higher rates of prostate cancer incidence, more advanced disease stage at diagnosis, and higher rates of prostate cancer–specific survival (PCSS) when compared with White patients.²¹ Racial disparities across patients with prostate cancer and their management are multifactorial across health care literacy, education level, access to care (including transportation issues), and issues of adherence and distrust.^22-25 Correlation of patient race to prostate cancer outcomes varies greatly across health care systems, with the US Department of Veterans Affairs (VA) equal access system providing robust mental health services and transportation services for some patients, while demonstrating similar rates of stage-adjusted PCSS between African American and White patients across a broad range of treatment modalities.^26-28 Given the paucity of data exploring outcomes following MHRT for African American patients with HRPC, the present analysis provides long-term clinical outcomes and toxicity profiles for an off-trial majority African American population with HRPC treated with MHRT within the VA.

Methods

Records were retrospectively reviewed under an institutional review board–approved protocol for all patients with HRPC treated with definitive MHRT at the Durham Veterans Affairs Healthcare System in North Carolina between November 2008 and August 2018. Exclusion criteria included < 12 months of follow-up or elective nodal irradiation. Demographic variables obtained included age at diagnosis, race, clinical T stage, pre-MHRT prostate-specific antigen (PSA), Gleason grade group at diagnosis, favorable vs unfavorable high-risk disease, pre-MHRT international prostate symptom score (IPSS), and pre-MHRT urinary medication usage (yes/no).²⁹

Concurrent androgen deprivation therapy (ADT) was initiated 6 to 8 weeks before MHRT unless medically contraindicated per the discretion of the treating radiation oncologist. Patients generally received 18 to 24 months of ADT, with those with favorable HRPC (ie, T1c disease with either Gleason 4+4 and PSA < 10 mg/mL or Gleason 3+3 and PSA > 20 ng/mL) receiving 6 months after 2015.²⁹ Patients were simulated supine in either standard or custom immobilization with a full bladder and empty rectum. MHRT fractionation plans included 70 Gy at 2.5 Gy per fraction and 60 Gy at 3 Gy per fraction. Radiotherapy targets included the prostate and seminal vesicles without elective nodal coverage per institutional practice. Treatments were delivered following image guidance, either prostate matching with cone beam computed tomography or fiducial matching with kilo voltage imaging. All patients received intensity-modulated radiotherapy. For plans delivering 70 Gy at 2.5 Gy per fraction, constraints included bladder V (volume receiving) 70 < 10 cc, V65 ≤ 15%, V40 ≤ 35%, rectum V70 < 10 cc, V65 ≤ 10%, V40 ≤ 35%, femoral heads maximum point dose ≤ 40 Gy, penile bulb mean dose ≤ 50 Gy, and small bowel V40 ≤ 1%. For plans delivering 60 Gy at 3 Gy per fraction, constraints included rectum V57 ≤ 15%, V46 ≤ 30%, V37 ≤ 50%, bladder V60 ≤ 5%, V46 ≤ 30%, V37 ≤ 50%, and femoral heads V43 ≤ 5%.

Gastrointestinal (GI) and genitourinary (GU) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, with acute toxicity defined as on-treatment < 3 months following completion of MHRT. Late toxicity was defined as ≥ 3 months following completion of MHRT. Individuals were seen in follow-up at 6 weeks and 3 months with PSA and testosterone after MHRT completion, then every 6 to 12 months for 5 years and annually thereafter. Each follow-up visit included history, physical examination, IPSS, and CTCAE grading for GI and GU toxicity.

The Wilcoxon rank sum test and χ² test were used to compare differences in demographic data, dosimetric parameters, and frequency of toxicity events with respect to patient race. Clinical endpoints including biochemical recurrence-free survival (BRFS; defined by Phoenix criteria as 2.0 above PSA nadir), distant metastases-free survival (DMFS), PCSS, and overall survival (OS) were estimated from time of radiotherapy completion by the Kaplan-Meier method and compared between African American and White race by log-rank testing.³⁰ Late GI and GU toxicity-free survival were estimated by Kaplan-Meier plots and compared between African American and White patients by the log-rank test. Statistical analysis was performed using SAS 9.4.

Results

We identified 143 patients with HRPC treated with definitive MHRT between November 2008 and August 2018 (Table 1). Mean age was 65 years (range, 36-80 years); 57% were African American men. Eighty percent of individuals had unfavorable high-risk disease. Median (IQR) PSA was 14.4 (7.8-28.6). Twenty-six percent had grade group 1-3 disease, 47% had grade group 4 disease, and 27% had grade group 5 disease. African American patients had significantly lower pre-MHRT IPSS scores than White patients (mean IPSS, 11 vs 14, respectively; P = .02) despite similar rates of preradiotherapy urinary medication usage (66% and 66%, respectively).

Eighty-six percent received 70 Gy over 28 fractions, with institutional protocol shifting to 60 Gy over 20 fractions (14%) in June 2017. The median (IQR) duration of radiotherapy was 39 (38-42) days, with 97% of individuals undergoing ADT for a median (IQR) duration of 24 (24-36) months. The median follow-up time was 38 months, with 57 (40%) patients followed for at least 60 months.

Grade 3 GI and GU acute toxicity events were observed in 1% and 4% of all individuals, respectively (Table 2). No acute GI or GU grade 4+ events were observed. No significant differences in acute GU or GI toxicity were observed between African American and White patients.

Discussion

In this study, we reported acute and late GI and GU toxicity rates as well as clinical outcomes for a majority African American population with predominately unfavorable HRPC treated with MHRT in an equal access health care environment. We found that MHRT was well tolerated with high rates of biochemical control, PCSS, and OS. Additionally, outcomes were not significantly different across patient race. To our knowledge, this is the first report of MHRT for HRPC in a majority African American population.

We found that MHRT was an effective treatment for patients with HRPC, in particular those with unfavorable high-risk disease. While prior prospective and randomized studies have investigated the use of MHRT, our series was larger than most and had a predominately unfavorable high-risk population.^12,15-17 Our biochemical and PCSS rates compare favorably with those of HRPC trial populations, particularly given the high proportion of unfavorable high-risk disease.^12,15,16 Despite similar rates of biochemical control, OS was lower in the present cohort than in HRPC trial populations, even with a younger median age at diagnosis. The similarly high rates of non–HRPC-related death across race may reflect differences in baseline comorbidities compared with trial populations as well as reported differences between individuals in the VA and the private sector.³¹ This suggests that MHRT can be an effective treatment for patients with unfavorable HRPC.

We did not find any differences in outcomes between African American and White individuals with HRPC treated with MHRT. Furthermore, our study demonstrates long-term rates of BRFS and PCSS in a majority African American population with predominately unfavorable HRPC that are comparable with those of prior randomized MHRT studies in high-risk, predominately White populations.^12,15,16 Prior reports have found that African American men with HRPC may be at increased risk for inferior clinical outcomes due to a number of socioeconomic, biologic, and cultural mediators.^26,27,32 Such individuals may disproportionally benefit from shorter treatment courses that improve access to radiotherapy, a well-documented disparity for African American men with localized prostate cancer.^33-36 The VA is an ideal system for studying racial disparities within prostate cancer, as accessibility of mental health and transportation services, income, and insurance status are not barriers to preventative or acute care.³⁷ Our results are concordant with those previously seen for African American patients with prostate cancer seen in the VA, which similarly demonstrate equal outcomes with those of other races.^28,36 Incorporation of the earlier mentioned VA services into oncologic care across other health care systems could better characterize determinants of racial disparities in prostate cancer, including the prognostic significance of shortening treatment duration and number of patient visits via MHRT.

Limitations

This study has several inherent limitations. While the size of the current HRPC cohort is notably larger than similar populations within the majority of phase 3 MHRT trials, these data derive from a single VA hospital. It is unclear whether these outcomes would be representative in a similar high-risk population receiving care outside of the VA equal access system. Follow-up data beyond 5 years was available for less than half of patients, partially due to nonprostate cancer–related mortality at a higher rate than observed in HRPC trial populations.^12,15,16 Furthermore, all GI toxicity events were exclusively physician reported, and GU toxicity reporting was limited in the off-trial setting with not all patients routinely completing IPSS questionnaires following MHRT completion. However, all patients were treated similarly, and radiation quality was verified over the treatment period with mandated accreditation, frequent standardized output checks, and systematic treatment review.³⁹

Conclusions

Patients with HRPC treated with MHRT in an equal access, off-trial setting demonstrated favorable rates of biochemical control with acceptable rates of acute and late GI and GU toxicities. Clinical outcomes, including biochemical control, were not significantly different between African American and White patients, which may reflect equal access to care within the VA irrespective of income and insurance status. Incorporating VA services, such as access to primary care, mental health services, and transportation across other health care systems may aid in characterizing and mitigating racial and gender disparities in oncologic care.  

Acknowledgments

Portions of this work were presented at the November 2020 ASTRO conference. ⁴⁰

Although moderately hypofractionated radiotherapy (MHRT) is an accepted treatment for localized prostate cancer, its adaptation remains limited in the United States.^1,2 MHRT theoretically exploits α/β ratio differences between the prostate (1.5 Gy), bladder (5-10 Gy), and rectum (3 Gy), thereby reducing late treatment-related adverse effects compared with those of conventional fractionation at biologically equivalent doses.^3-8 Multiple randomized noninferiority trials have demonstrated equivalent outcomes between MHRT and conventional fraction with no appreciable increase in patient-reported toxicity.^9-14 Although these studies have led to the acceptance of MHRT as a standard treatment, the majority of these trials involve individuals with low- and intermediate-risk disease.

There are less phase 3 data addressing MHRT for high-risk prostate cancer (HRPC).^10,12,14-17 Only 2 studies examined predominately high-risk populations, accounting for 83 and 292 patients, respectively.^15,16 Additional phase 3 trials with small proportions of high-risk patients (n = 126, 12%; n = 53, 35%) offer limited additional information regarding clinical outcomes and toxicity rates specific to high-risk disease.^10-12 Numerous phase 1 and 2 studies report various field designs and fractionation plans for MHRT in the context of high-risk disease, although the applicability of these data to off-trial populations remains limited.^18-20

Furthermore, African American individuals are underrepresented in the trials establishing the role of MHRT despite higher rates of prostate cancer incidence, more advanced disease stage at diagnosis, and higher rates of prostate cancer–specific survival (PCSS) when compared with White patients.²¹ Racial disparities across patients with prostate cancer and their management are multifactorial across health care literacy, education level, access to care (including transportation issues), and issues of adherence and distrust.^22-25 Correlation of patient race to prostate cancer outcomes varies greatly across health care systems, with the US Department of Veterans Affairs (VA) equal access system providing robust mental health services and transportation services for some patients, while demonstrating similar rates of stage-adjusted PCSS between African American and White patients across a broad range of treatment modalities.^26-28 Given the paucity of data exploring outcomes following MHRT for African American patients with HRPC, the present analysis provides long-term clinical outcomes and toxicity profiles for an off-trial majority African American population with HRPC treated with MHRT within the VA.

Methods

Records were retrospectively reviewed under an institutional review board–approved protocol for all patients with HRPC treated with definitive MHRT at the Durham Veterans Affairs Healthcare System in North Carolina between November 2008 and August 2018. Exclusion criteria included < 12 months of follow-up or elective nodal irradiation. Demographic variables obtained included age at diagnosis, race, clinical T stage, pre-MHRT prostate-specific antigen (PSA), Gleason grade group at diagnosis, favorable vs unfavorable high-risk disease, pre-MHRT international prostate symptom score (IPSS), and pre-MHRT urinary medication usage (yes/no).²⁹

Concurrent androgen deprivation therapy (ADT) was initiated 6 to 8 weeks before MHRT unless medically contraindicated per the discretion of the treating radiation oncologist. Patients generally received 18 to 24 months of ADT, with those with favorable HRPC (ie, T1c disease with either Gleason 4+4 and PSA < 10 mg/mL or Gleason 3+3 and PSA > 20 ng/mL) receiving 6 months after 2015.²⁹ Patients were simulated supine in either standard or custom immobilization with a full bladder and empty rectum. MHRT fractionation plans included 70 Gy at 2.5 Gy per fraction and 60 Gy at 3 Gy per fraction. Radiotherapy targets included the prostate and seminal vesicles without elective nodal coverage per institutional practice. Treatments were delivered following image guidance, either prostate matching with cone beam computed tomography or fiducial matching with kilo voltage imaging. All patients received intensity-modulated radiotherapy. For plans delivering 70 Gy at 2.5 Gy per fraction, constraints included bladder V (volume receiving) 70 < 10 cc, V65 ≤ 15%, V40 ≤ 35%, rectum V70 < 10 cc, V65 ≤ 10%, V40 ≤ 35%, femoral heads maximum point dose ≤ 40 Gy, penile bulb mean dose ≤ 50 Gy, and small bowel V40 ≤ 1%. For plans delivering 60 Gy at 3 Gy per fraction, constraints included rectum V57 ≤ 15%, V46 ≤ 30%, V37 ≤ 50%, bladder V60 ≤ 5%, V46 ≤ 30%, V37 ≤ 50%, and femoral heads V43 ≤ 5%.

Gastrointestinal (GI) and genitourinary (GU) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, with acute toxicity defined as on-treatment < 3 months following completion of MHRT. Late toxicity was defined as ≥ 3 months following completion of MHRT. Individuals were seen in follow-up at 6 weeks and 3 months with PSA and testosterone after MHRT completion, then every 6 to 12 months for 5 years and annually thereafter. Each follow-up visit included history, physical examination, IPSS, and CTCAE grading for GI and GU toxicity.

The Wilcoxon rank sum test and χ² test were used to compare differences in demographic data, dosimetric parameters, and frequency of toxicity events with respect to patient race. Clinical endpoints including biochemical recurrence-free survival (BRFS; defined by Phoenix criteria as 2.0 above PSA nadir), distant metastases-free survival (DMFS), PCSS, and overall survival (OS) were estimated from time of radiotherapy completion by the Kaplan-Meier method and compared between African American and White race by log-rank testing.³⁰ Late GI and GU toxicity-free survival were estimated by Kaplan-Meier plots and compared between African American and White patients by the log-rank test. Statistical analysis was performed using SAS 9.4.

Results

We identified 143 patients with HRPC treated with definitive MHRT between November 2008 and August 2018 (Table 1). Mean age was 65 years (range, 36-80 years); 57% were African American men. Eighty percent of individuals had unfavorable high-risk disease. Median (IQR) PSA was 14.4 (7.8-28.6). Twenty-six percent had grade group 1-3 disease, 47% had grade group 4 disease, and 27% had grade group 5 disease. African American patients had significantly lower pre-MHRT IPSS scores than White patients (mean IPSS, 11 vs 14, respectively; P = .02) despite similar rates of preradiotherapy urinary medication usage (66% and 66%, respectively).

Eighty-six percent received 70 Gy over 28 fractions, with institutional protocol shifting to 60 Gy over 20 fractions (14%) in June 2017. The median (IQR) duration of radiotherapy was 39 (38-42) days, with 97% of individuals undergoing ADT for a median (IQR) duration of 24 (24-36) months. The median follow-up time was 38 months, with 57 (40%) patients followed for at least 60 months.

Grade 3 GI and GU acute toxicity events were observed in 1% and 4% of all individuals, respectively (Table 2). No acute GI or GU grade 4+ events were observed. No significant differences in acute GU or GI toxicity were observed between African American and White patients.

Discussion

In this study, we reported acute and late GI and GU toxicity rates as well as clinical outcomes for a majority African American population with predominately unfavorable HRPC treated with MHRT in an equal access health care environment. We found that MHRT was well tolerated with high rates of biochemical control, PCSS, and OS. Additionally, outcomes were not significantly different across patient race. To our knowledge, this is the first report of MHRT for HRPC in a majority African American population.

We found that MHRT was an effective treatment for patients with HRPC, in particular those with unfavorable high-risk disease. While prior prospective and randomized studies have investigated the use of MHRT, our series was larger than most and had a predominately unfavorable high-risk population.^12,15-17 Our biochemical and PCSS rates compare favorably with those of HRPC trial populations, particularly given the high proportion of unfavorable high-risk disease.^12,15,16 Despite similar rates of biochemical control, OS was lower in the present cohort than in HRPC trial populations, even with a younger median age at diagnosis. The similarly high rates of non–HRPC-related death across race may reflect differences in baseline comorbidities compared with trial populations as well as reported differences between individuals in the VA and the private sector.³¹ This suggests that MHRT can be an effective treatment for patients with unfavorable HRPC.

We did not find any differences in outcomes between African American and White individuals with HRPC treated with MHRT. Furthermore, our study demonstrates long-term rates of BRFS and PCSS in a majority African American population with predominately unfavorable HRPC that are comparable with those of prior randomized MHRT studies in high-risk, predominately White populations.^12,15,16 Prior reports have found that African American men with HRPC may be at increased risk for inferior clinical outcomes due to a number of socioeconomic, biologic, and cultural mediators.^26,27,32 Such individuals may disproportionally benefit from shorter treatment courses that improve access to radiotherapy, a well-documented disparity for African American men with localized prostate cancer.^33-36 The VA is an ideal system for studying racial disparities within prostate cancer, as accessibility of mental health and transportation services, income, and insurance status are not barriers to preventative or acute care.³⁷ Our results are concordant with those previously seen for African American patients with prostate cancer seen in the VA, which similarly demonstrate equal outcomes with those of other races.^28,36 Incorporation of the earlier mentioned VA services into oncologic care across other health care systems could better characterize determinants of racial disparities in prostate cancer, including the prognostic significance of shortening treatment duration and number of patient visits via MHRT.

Limitations

This study has several inherent limitations. While the size of the current HRPC cohort is notably larger than similar populations within the majority of phase 3 MHRT trials, these data derive from a single VA hospital. It is unclear whether these outcomes would be representative in a similar high-risk population receiving care outside of the VA equal access system. Follow-up data beyond 5 years was available for less than half of patients, partially due to nonprostate cancer–related mortality at a higher rate than observed in HRPC trial populations.^12,15,16 Furthermore, all GI toxicity events were exclusively physician reported, and GU toxicity reporting was limited in the off-trial setting with not all patients routinely completing IPSS questionnaires following MHRT completion. However, all patients were treated similarly, and radiation quality was verified over the treatment period with mandated accreditation, frequent standardized output checks, and systematic treatment review.³⁹

Conclusions

Patients with HRPC treated with MHRT in an equal access, off-trial setting demonstrated favorable rates of biochemical control with acceptable rates of acute and late GI and GU toxicities. Clinical outcomes, including biochemical control, were not significantly different between African American and White patients, which may reflect equal access to care within the VA irrespective of income and insurance status. Incorporating VA services, such as access to primary care, mental health services, and transportation across other health care systems may aid in characterizing and mitigating racial and gender disparities in oncologic care.  

Acknowledgments

Portions of this work were presented at the November 2020 ASTRO conference. ⁴⁰

Fewer than one-third of cancer patients pay out-of-pocket costs for genetic counseling services.

But even among those who do, the cost is $16 or less, a cohort study shows.

“The findings highlight the relatively low financial costs of genetic counseling, a form of care with potentially substantial implications for cancer treatment,” lead author Mya Roberson, PhD, Vanderbilt University, Nashville, Tenn., and colleagues explained.

The study was published online in JAMA Health Forum.

Genetic counseling is an important feature of cancer care that can affect treatment decisions and surveillance. But coverage of genetic counseling services varies across insurance types.

To understand the costs to patients, the investigators used data from IBM Watson Health MarketScan to create a cohort of privately insured patients with breast, prostate, endometrial, ovarian, colorectal, and pancreatic cancer who had at least one genetic counseling session from 2013 to the end of 2019.

Dr. Roberson and colleagues then calculated out-of-pocket costs – including coinsurance, copayments, and deductibles – and total costs paid on claims for genetic counseling encounters. The cohort included 16,791 patients, the majority of whom had breast cancer.

Although the median insurance payment for genetic counseling encounters was $118 ($58-$211), most patients paid nothing out of pocket for these services. Among the 31% of patients with an out-of-pocket expense, the cost was $16 or less.

Compared with breast cancer patients, men with prostate cancer were 28% more likely to have out-of-pocket costs for genetic counseling, which may “reflect a lack of awareness about the medical necessity of genetic counseling,” the authors suggested.

Overall, the study highlights the value of genetic counseling in cancer care.

“Cancer genetic counseling not only promotes informed decision-making about genetic testing and cancer treatment in the era of precision medicine, but it also is a form of low-cost, high-value care,” the authors wrote.

The study was funded by a grant from the National Cancer Institute. Dr. Roberson disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Fewer than one-third of cancer patients pay out-of-pocket costs for genetic counseling services.

But even among those who do, the cost is $16 or less, a cohort study shows.

“The findings highlight the relatively low financial costs of genetic counseling, a form of care with potentially substantial implications for cancer treatment,” lead author Mya Roberson, PhD, Vanderbilt University, Nashville, Tenn., and colleagues explained.

The study was published online in JAMA Health Forum.

Genetic counseling is an important feature of cancer care that can affect treatment decisions and surveillance. But coverage of genetic counseling services varies across insurance types.

To understand the costs to patients, the investigators used data from IBM Watson Health MarketScan to create a cohort of privately insured patients with breast, prostate, endometrial, ovarian, colorectal, and pancreatic cancer who had at least one genetic counseling session from 2013 to the end of 2019.

Dr. Roberson and colleagues then calculated out-of-pocket costs – including coinsurance, copayments, and deductibles – and total costs paid on claims for genetic counseling encounters. The cohort included 16,791 patients, the majority of whom had breast cancer.

Although the median insurance payment for genetic counseling encounters was $118 ($58-$211), most patients paid nothing out of pocket for these services. Among the 31% of patients with an out-of-pocket expense, the cost was $16 or less.

Compared with breast cancer patients, men with prostate cancer were 28% more likely to have out-of-pocket costs for genetic counseling, which may “reflect a lack of awareness about the medical necessity of genetic counseling,” the authors suggested.

Overall, the study highlights the value of genetic counseling in cancer care.

“Cancer genetic counseling not only promotes informed decision-making about genetic testing and cancer treatment in the era of precision medicine, but it also is a form of low-cost, high-value care,” the authors wrote.

The study was funded by a grant from the National Cancer Institute. Dr. Roberson disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Fewer than one-third of cancer patients pay out-of-pocket costs for genetic counseling services.

But even among those who do, the cost is $16 or less, a cohort study shows.

“The findings highlight the relatively low financial costs of genetic counseling, a form of care with potentially substantial implications for cancer treatment,” lead author Mya Roberson, PhD, Vanderbilt University, Nashville, Tenn., and colleagues explained.

The study was published online in JAMA Health Forum.

Genetic counseling is an important feature of cancer care that can affect treatment decisions and surveillance. But coverage of genetic counseling services varies across insurance types.

To understand the costs to patients, the investigators used data from IBM Watson Health MarketScan to create a cohort of privately insured patients with breast, prostate, endometrial, ovarian, colorectal, and pancreatic cancer who had at least one genetic counseling session from 2013 to the end of 2019.

Dr. Roberson and colleagues then calculated out-of-pocket costs – including coinsurance, copayments, and deductibles – and total costs paid on claims for genetic counseling encounters. The cohort included 16,791 patients, the majority of whom had breast cancer.

Although the median insurance payment for genetic counseling encounters was $118 ($58-$211), most patients paid nothing out of pocket for these services. Among the 31% of patients with an out-of-pocket expense, the cost was $16 or less.

Compared with breast cancer patients, men with prostate cancer were 28% more likely to have out-of-pocket costs for genetic counseling, which may “reflect a lack of awareness about the medical necessity of genetic counseling,” the authors suggested.

Overall, the study highlights the value of genetic counseling in cancer care.

“Cancer genetic counseling not only promotes informed decision-making about genetic testing and cancer treatment in the era of precision medicine, but it also is a form of low-cost, high-value care,” the authors wrote.

The study was funded by a grant from the National Cancer Institute. Dr. Roberson disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

A version of this article first appeared on Medscape.com.

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

A version of this article first appeared on Medscape.com.

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

A version of this article first appeared on Medscape.com.

A novel blood test that can detect up to 50 different cancers from a single blood draw is gaining traction in the United States.

The Galleri blood test is being now offered by a number of United States health networks.

The company marketing the test, GRAIL, has established partnerships with the U.S. Department of Veterans Affairs, Mercy Health, Ochsner Health, Intermountain Healthcare, Community Health Network, Knight Cancer Institute at Oregon Health & Science University, Premier, and Cleveland Clinic, among others.

Cleveland Clinic’s Eric Klein, MD, emeritus chair of the Glickman Urological Kidney Institute, is enthusiastic about the test, describing it as a “game-changer” and emphasizing that it can detect many different cancers and at a very early stage.

“It completely changes the way we think about screening for cancer,” commented Jeff Venstrom, MD, chief medical officer at GRAIL. He joined the company because “there are not many things in life where you can be part of a disruptive paradigm and disruptive technology, and this really is disruptive,” he said in an interview.
 

‘The devil is in the details’

But there is some concern among clinicians that widespread clinical use of the test may be premature.

Having a blood test for multiple cancers is a “very good idea, and the scientific basis for this platform is sound,” commented Timothy R. Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, and Division of Population Sciences, Dana-Farber Cancer Institute, both in Boston.

“But the devil is in the details to ensure the test can accurately detect very early cancers and there is a pathway for subsequent workup (diagnosis, monitoring, treatment, etc.),” Dr. Rebbeck told this news organization.

Galleri is offering the test to individuals who are older than 50 and have a family history of cancer or those who are high risk for cancer or immunocompromised. They suggest that interested individuals get in touch with their health care professional, who then needs to register with GRAIL and order the test.

As well as needing a prescription, interested individuals will have to pay for it out of pocket, around $950. The test is not covered by medical insurance and is not approved by the U.S. Food and Drug Administration.
 

Falls into primary care setting

Dr. Rebbeck commented that Galleri is a screening test for individuals who don’t have cancer, so the test is intended to fall into the primary care setting. But he warned that “clinical pathways are not yet in place (but are being developed) so that primary care providers can effectively use them.”

The test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA in a blood sample.

The methylation turns genes on or off, explains Cleveland Clinic’s Dr. Klein in his post. “It’s like fingerprints and how fingerprints tell the difference between two people,” he wrote. “The methylation patterns are fingerprints that are characteristic of each kind of cancer. They look one way for lung cancer and different for colon cancer.” 

The test returns one of two possible results: either “positive, cancer signal detected” or “negative, no cancer signal detected.”

According to the company, when a cancer signal is detected, the Galleri test predicts the cancer signal origin “with high accuracy, to help guide the next steps to diagnosis.”

However, one problem for clinical practice is all the follow-up tests an individual may undergo if their test comes back positive, said Sameek Roychowdhury, MD, PhD, an oncologist with Ohio State University Comprehensive Cancer Center, Columbus.

“Not everybody will have an actual cancer, but they may undergo many tests, with a lot of stress and cost and still not find anything. I can tell you every time someone undergoes a test looking for cancer, that is not an easy day,” Dr. Roychowdhury said in an interview.

In a large-scale validation study, the Galleri test had a specificity of 99.5% (false-positive rate of 0.5%), meaning in roughly 200 people tested without cancer, only one person received a false-positive result (that is, “cancer signal detected” when cancer is not present).

The overall sensitivity of the test for any stage of cancer was 51.5%, although it was higher for later-stage cancers (77% for stage III and 90.1% for stage IV) and lower for early-stage cancers (16.8% for stage I and 40.4% for stage II).
 

Exacerbate health disparities?

In Dr. Rebbeck’s view, the characteristics of the test are still “relatively poor for detecting very early cancers, so it will need additional tweaking before it really achieves the goal of multi-cancer EARLY detection,” he said.

Dr. Venstrom acknowledges that the test is “not perfect yet” and says the company will continue to update and improve its performance. “We have some new data coming out in September,” he said.

Clinical data are being accumulated in the United Kingdom, where the Galleri test is being investigated in a large trial run by the National Health Service (NHS). The company recently announced that the enrollment of 140,000 healthy cancer-free volunteers aged 50-77 into this trial has now been completed and claimed this the largest-ever study of a multi-cancer early detection test.

Dr. Roychowdhury said he would encourage anyone interested in the test to join a clinical trial.

Another expert approached for comment last year, when GRAIL first started marketing the test, was in agreement. This test should be viewed as one that is still under clinical investigation, commented William Grady, MD, a member of the clinical research division and public health sciences division at the Fred Hutchinson Cancer Research Center, Seattle.

“The Galleri test is still unproven in the clinical care setting and ... I am concerned that many of the results will be false-positives and will cause many unnecessary follow-up tests and imaging studies as well as anxiety in the people getting the test done,” Dr. Grady said.

Dr. Rebbeck said another issue that needs to be addressed is whether all populations will have access to and benefit from these types of blood tests to screen for cancer, given that they are expensive. 

“There is a great danger – as we have seen with many other technological innovations – that the wealthy and connected benefit, but the majority of the population, and particularly those who are underserved, do not,” Dr. Rebbeck said.

“As a result, health disparities are created or exacerbated. This is something that needs to be addressed so that the future use of these tests will provide equitable benefits,” he added.

Dr. Rebbeck and Dr. Roychowdhury have reported no relevant financial relationships. Dr. Venstrom is an employee of GRAIL.

A version of this article first appeared on Medscape.com.

A novel blood test that can detect up to 50 different cancers from a single blood draw is gaining traction in the United States.

The Galleri blood test is being now offered by a number of United States health networks.

The company marketing the test, GRAIL, has established partnerships with the U.S. Department of Veterans Affairs, Mercy Health, Ochsner Health, Intermountain Healthcare, Community Health Network, Knight Cancer Institute at Oregon Health & Science University, Premier, and Cleveland Clinic, among others.

Cleveland Clinic’s Eric Klein, MD, emeritus chair of the Glickman Urological Kidney Institute, is enthusiastic about the test, describing it as a “game-changer” and emphasizing that it can detect many different cancers and at a very early stage.

“It completely changes the way we think about screening for cancer,” commented Jeff Venstrom, MD, chief medical officer at GRAIL. He joined the company because “there are not many things in life where you can be part of a disruptive paradigm and disruptive technology, and this really is disruptive,” he said in an interview.
 

‘The devil is in the details’

But there is some concern among clinicians that widespread clinical use of the test may be premature.

Having a blood test for multiple cancers is a “very good idea, and the scientific basis for this platform is sound,” commented Timothy R. Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, and Division of Population Sciences, Dana-Farber Cancer Institute, both in Boston.

“But the devil is in the details to ensure the test can accurately detect very early cancers and there is a pathway for subsequent workup (diagnosis, monitoring, treatment, etc.),” Dr. Rebbeck told this news organization.

Galleri is offering the test to individuals who are older than 50 and have a family history of cancer or those who are high risk for cancer or immunocompromised. They suggest that interested individuals get in touch with their health care professional, who then needs to register with GRAIL and order the test.

As well as needing a prescription, interested individuals will have to pay for it out of pocket, around $950. The test is not covered by medical insurance and is not approved by the U.S. Food and Drug Administration.
 

Falls into primary care setting

Dr. Rebbeck commented that Galleri is a screening test for individuals who don’t have cancer, so the test is intended to fall into the primary care setting. But he warned that “clinical pathways are not yet in place (but are being developed) so that primary care providers can effectively use them.”

The test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA in a blood sample.

The methylation turns genes on or off, explains Cleveland Clinic’s Dr. Klein in his post. “It’s like fingerprints and how fingerprints tell the difference between two people,” he wrote. “The methylation patterns are fingerprints that are characteristic of each kind of cancer. They look one way for lung cancer and different for colon cancer.” 

The test returns one of two possible results: either “positive, cancer signal detected” or “negative, no cancer signal detected.”

According to the company, when a cancer signal is detected, the Galleri test predicts the cancer signal origin “with high accuracy, to help guide the next steps to diagnosis.”

However, one problem for clinical practice is all the follow-up tests an individual may undergo if their test comes back positive, said Sameek Roychowdhury, MD, PhD, an oncologist with Ohio State University Comprehensive Cancer Center, Columbus.

“Not everybody will have an actual cancer, but they may undergo many tests, with a lot of stress and cost and still not find anything. I can tell you every time someone undergoes a test looking for cancer, that is not an easy day,” Dr. Roychowdhury said in an interview.

In a large-scale validation study, the Galleri test had a specificity of 99.5% (false-positive rate of 0.5%), meaning in roughly 200 people tested without cancer, only one person received a false-positive result (that is, “cancer signal detected” when cancer is not present).

The overall sensitivity of the test for any stage of cancer was 51.5%, although it was higher for later-stage cancers (77% for stage III and 90.1% for stage IV) and lower for early-stage cancers (16.8% for stage I and 40.4% for stage II).
 

Exacerbate health disparities?

In Dr. Rebbeck’s view, the characteristics of the test are still “relatively poor for detecting very early cancers, so it will need additional tweaking before it really achieves the goal of multi-cancer EARLY detection,” he said.

Dr. Venstrom acknowledges that the test is “not perfect yet” and says the company will continue to update and improve its performance. “We have some new data coming out in September,” he said.

Clinical data are being accumulated in the United Kingdom, where the Galleri test is being investigated in a large trial run by the National Health Service (NHS). The company recently announced that the enrollment of 140,000 healthy cancer-free volunteers aged 50-77 into this trial has now been completed and claimed this the largest-ever study of a multi-cancer early detection test.

Dr. Roychowdhury said he would encourage anyone interested in the test to join a clinical trial.

Another expert approached for comment last year, when GRAIL first started marketing the test, was in agreement. This test should be viewed as one that is still under clinical investigation, commented William Grady, MD, a member of the clinical research division and public health sciences division at the Fred Hutchinson Cancer Research Center, Seattle.

“The Galleri test is still unproven in the clinical care setting and ... I am concerned that many of the results will be false-positives and will cause many unnecessary follow-up tests and imaging studies as well as anxiety in the people getting the test done,” Dr. Grady said.

Dr. Rebbeck said another issue that needs to be addressed is whether all populations will have access to and benefit from these types of blood tests to screen for cancer, given that they are expensive. 

“There is a great danger – as we have seen with many other technological innovations – that the wealthy and connected benefit, but the majority of the population, and particularly those who are underserved, do not,” Dr. Rebbeck said.

“As a result, health disparities are created or exacerbated. This is something that needs to be addressed so that the future use of these tests will provide equitable benefits,” he added.

Dr. Rebbeck and Dr. Roychowdhury have reported no relevant financial relationships. Dr. Venstrom is an employee of GRAIL.

A version of this article first appeared on Medscape.com.

A novel blood test that can detect up to 50 different cancers from a single blood draw is gaining traction in the United States.

The Galleri blood test is being now offered by a number of United States health networks.

The company marketing the test, GRAIL, has established partnerships with the U.S. Department of Veterans Affairs, Mercy Health, Ochsner Health, Intermountain Healthcare, Community Health Network, Knight Cancer Institute at Oregon Health & Science University, Premier, and Cleveland Clinic, among others.

Cleveland Clinic’s Eric Klein, MD, emeritus chair of the Glickman Urological Kidney Institute, is enthusiastic about the test, describing it as a “game-changer” and emphasizing that it can detect many different cancers and at a very early stage.

“It completely changes the way we think about screening for cancer,” commented Jeff Venstrom, MD, chief medical officer at GRAIL. He joined the company because “there are not many things in life where you can be part of a disruptive paradigm and disruptive technology, and this really is disruptive,” he said in an interview.
 

‘The devil is in the details’

But there is some concern among clinicians that widespread clinical use of the test may be premature.

Having a blood test for multiple cancers is a “very good idea, and the scientific basis for this platform is sound,” commented Timothy R. Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, and Division of Population Sciences, Dana-Farber Cancer Institute, both in Boston.

“But the devil is in the details to ensure the test can accurately detect very early cancers and there is a pathway for subsequent workup (diagnosis, monitoring, treatment, etc.),” Dr. Rebbeck told this news organization.

Galleri is offering the test to individuals who are older than 50 and have a family history of cancer or those who are high risk for cancer or immunocompromised. They suggest that interested individuals get in touch with their health care professional, who then needs to register with GRAIL and order the test.

As well as needing a prescription, interested individuals will have to pay for it out of pocket, around $950. The test is not covered by medical insurance and is not approved by the U.S. Food and Drug Administration.
 

Falls into primary care setting

Dr. Rebbeck commented that Galleri is a screening test for individuals who don’t have cancer, so the test is intended to fall into the primary care setting. But he warned that “clinical pathways are not yet in place (but are being developed) so that primary care providers can effectively use them.”

The test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA in a blood sample.

The methylation turns genes on or off, explains Cleveland Clinic’s Dr. Klein in his post. “It’s like fingerprints and how fingerprints tell the difference between two people,” he wrote. “The methylation patterns are fingerprints that are characteristic of each kind of cancer. They look one way for lung cancer and different for colon cancer.” 

The test returns one of two possible results: either “positive, cancer signal detected” or “negative, no cancer signal detected.”

According to the company, when a cancer signal is detected, the Galleri test predicts the cancer signal origin “with high accuracy, to help guide the next steps to diagnosis.”

However, one problem for clinical practice is all the follow-up tests an individual may undergo if their test comes back positive, said Sameek Roychowdhury, MD, PhD, an oncologist with Ohio State University Comprehensive Cancer Center, Columbus.

“Not everybody will have an actual cancer, but they may undergo many tests, with a lot of stress and cost and still not find anything. I can tell you every time someone undergoes a test looking for cancer, that is not an easy day,” Dr. Roychowdhury said in an interview.

In a large-scale validation study, the Galleri test had a specificity of 99.5% (false-positive rate of 0.5%), meaning in roughly 200 people tested without cancer, only one person received a false-positive result (that is, “cancer signal detected” when cancer is not present).

The overall sensitivity of the test for any stage of cancer was 51.5%, although it was higher for later-stage cancers (77% for stage III and 90.1% for stage IV) and lower for early-stage cancers (16.8% for stage I and 40.4% for stage II).
 

Exacerbate health disparities?

In Dr. Rebbeck’s view, the characteristics of the test are still “relatively poor for detecting very early cancers, so it will need additional tweaking before it really achieves the goal of multi-cancer EARLY detection,” he said.

Dr. Venstrom acknowledges that the test is “not perfect yet” and says the company will continue to update and improve its performance. “We have some new data coming out in September,” he said.

Clinical data are being accumulated in the United Kingdom, where the Galleri test is being investigated in a large trial run by the National Health Service (NHS). The company recently announced that the enrollment of 140,000 healthy cancer-free volunteers aged 50-77 into this trial has now been completed and claimed this the largest-ever study of a multi-cancer early detection test.

Dr. Roychowdhury said he would encourage anyone interested in the test to join a clinical trial.

Another expert approached for comment last year, when GRAIL first started marketing the test, was in agreement. This test should be viewed as one that is still under clinical investigation, commented William Grady, MD, a member of the clinical research division and public health sciences division at the Fred Hutchinson Cancer Research Center, Seattle.

“The Galleri test is still unproven in the clinical care setting and ... I am concerned that many of the results will be false-positives and will cause many unnecessary follow-up tests and imaging studies as well as anxiety in the people getting the test done,” Dr. Grady said.

Dr. Rebbeck said another issue that needs to be addressed is whether all populations will have access to and benefit from these types of blood tests to screen for cancer, given that they are expensive. 

“There is a great danger – as we have seen with many other technological innovations – that the wealthy and connected benefit, but the majority of the population, and particularly those who are underserved, do not,” Dr. Rebbeck said.

“As a result, health disparities are created or exacerbated. This is something that needs to be addressed so that the future use of these tests will provide equitable benefits,” he added.

Dr. Rebbeck and Dr. Roychowdhury have reported no relevant financial relationships. Dr. Venstrom is an employee of GRAIL.

A version of this article first appeared on Medscape.com.

Although cardiovascular disease (CVD) is known to often strike the mortal blow in patients with cancer, a national analysis puts in stark relief the burden of CV-related hospitalizations in this vulnerable population.

Results show that between 2004 and 2017, CV admissions increased 23.2% among patients with a cancer diagnosis, whereas admissions fell 10.9% among those without cancer.

Admissions increased steadily across all cancer types, except prostate cancer, with heart failure being the most common reason for admission.

“Hospital admissions is really important because we know that the size of this group is increasing, given that they live longer and many of the treatments that we offer cause cardiovascular disease or increase the risk of having cardiovascular events. So, from a health care planning perspective, I think it’s really important to see what the burden is likely to be in the next few years,” senior author Mamas Mamas, MD, Keele University, England, told this news organization.

For physicians and the wider population, he said, the findings underscore the need to shift the conversation from saying that patients with cancer are at increased CVD risk to asking how to mitigate this risk. “Because I would say that this increase in cardiovascular admissions, that’s a failure from a preventative perspective.”

The study was published in the European Heart Journal: Quality of Care & Clinical Outcomes.

Individual cancer types

The researchers, led by Ofer Kobo, MD, also with Keele University, used the National Inpatient Sample to identify 42.5 million weighted cases of CV admissions for acute myocardial infarction (AMI), pulmonary embolism, ischemic stroke, heart failure, atrial fibrillation (AFib) or atrial flutter, and intracranial hemorrhage from January 2004 to December 2017. Of these, 1.9 million had a record of cancer.

Patients with cancer were older; had a higher prevalence of valvular disease, anemia, and coagulopathy; and had a lower prevalence of hypertension, diabetes mellitus, and obesity than did patients without cancer.

The most common cancer type was hematologic cancers (26.1%), followed by lung (18.7%), gastrointestinal (12.4%), prostate (11.6%), breast (6.7%), and other in 24.4%.

The admission rate increased across all six admission causes – between 7% for AMI and ischemic stroke and 46% for AFib.

Heart failure was the chief reason for admission among all patients. Annual rates per 100,000 U.S. population increased in patients with cancer (from 13.6 to 16.6; P for trend = .02) and declined in those without (from 352.2 to 349.8; P for trend < .001).

“In the past, patients would be started on medications, and perhaps the importance of monitoring [left ventricular] LV function wasn’t as widely known, whereas now we’re much more aggressive in looking at it and much more aggressive at trying to prevent it,” Dr. Mamas said. “But even with this greater identification and attempting to modify regimens, we’re still getting quite substantial increases in heart failure admissions in this population. And what really surprised me is that it wasn’t just in the breast cancer population, but it was nearly across the board.”

He noted that patients are at highest risk from CV events within the first 2 years of cancer diagnosis. “So that’s really the time where you’ve got to be really aggressive in looking and working up their cardiovascular profile.”

Patients with hematologic cancers (9.7-13.5), lung (7.4-8.9), and gastrointestinal cancer (4.6-6.3) had the highest crude admission rates of CV hospitalizations per 100,000 U.S. population.

The CV admission rate went up from 2.5 to 3.7 per 100,000 U.S. population for breast cancer, and in prostate cancer, the rate dropped from 5.8 to 4.8 per 100,000 U.S. population.

Of note, patients with hematologic cancers also had the highest rate of heart failure hospitalization across all cancer types, which, coupled with their increasing admission rates, likely reflects their exposure to a “constellation of cardiotoxic therapies” as well as pathologic processes related to the cancers themselves, the authors suggest.

In-hospital mortality rates were higher among patients with cancer than those without, ranging from 5% for patients with breast cancer to 9.6% for patients with lung cancer versus 4.2% for those without cancer.

Among patients with cancer, the odds ratio for mortality was highest in those admitted with AFib (4.43), followed by pulmonary embolism (2.36), AMI (2.31), ischemic stroke (2.29), and heart failure (2.24).

In line with prior work and general population trends, in-hospital deaths in primary CV admissions trended lower among patients with cancer over the study period.

Mitigating risk

Commenting on the study, Joerg Herrmann, MD, director of the cardio-oncology clinic at Mayo Clinic, Rochester, Minn., said that the data are “extremely important” because they reflect admissions during a new era of cancer therapy. “Targeted therapies all came out about the turn of the millennium, so we’re not really looking at cancer patients treated with only old and ancient strategies.”

This may be one reason for the increased admissions, but because the study lacked information on specific cancer treatments and the date of cancer diagnosis, it’s not possible to tease out whether the uptick is related to cardiotoxicity or because the oncology outcomes have improved so much that this is a growing population, he said.

One clear implication, however, is that whoever is working on the hospital service will see more patients with a cancer diagnosis, Dr. Herrmann observed.

“Though some may have tried to maybe not get involved with this topic as much, it really calls for some broader scope to get familiar with this very entity,” he said. “And that plays out, in particular, in those patients with a diagnosis of active cancer.”

Dr. Herrmann and colleagues previously reported that patients with active leukemia or lymphoma who were hospitalized with acute coronary syndrome were less likely to receive guideline-directed therapies, even at the Mayo Clinic.

Similarly, a 2020 report by Dr. Mamas and colleagues found that patients with a variety of active cancers derived similar benefit from primary percutaneous coronary intervention for ST-segment–elevation MI as those without cancer but received the treatment less commonly.

Although there’s a greater appreciation that patients with cancer benefit equally from aggressive treatment, much more can be done to mitigate CV risk, Dr. Mamas noted. Valuable coronary information captured by MRI and CT done as part of the cancer investigation is often overlooked. For example, “we know that breast calcification and vascular calcification in the breast are very strong predictors of cardiovascular outcomes and yet people aren’t using this information.”

There are numerous shared risk factors in the development of cancer and coronary artery disease, and patients with cancer often have much worse CV risk profiles but aren’t routinely risk stratified from a CV perspective, he said.

Dr. Mamas said that his team is also studying whether CVD risk prediction tools like the Framingham Risk Score, which were derived from noncancer populations, work as well in patients with cancer. “Often, when you look at the performance of these tools in populations that weren’t covered, they’re much worse.”

“A lot of cancer survivors worry about the recurrence of their cancer and will religiously go and have repeated scans, religiously check themselves, and have all these investigations but don’t think about the actual risk that is greater for them, which is cardiovascular risk,” he said.

The authors report no study funding or relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although cardiovascular disease (CVD) is known to often strike the mortal blow in patients with cancer, a national analysis puts in stark relief the burden of CV-related hospitalizations in this vulnerable population.

Results show that between 2004 and 2017, CV admissions increased 23.2% among patients with a cancer diagnosis, whereas admissions fell 10.9% among those without cancer.

Admissions increased steadily across all cancer types, except prostate cancer, with heart failure being the most common reason for admission.

“Hospital admissions is really important because we know that the size of this group is increasing, given that they live longer and many of the treatments that we offer cause cardiovascular disease or increase the risk of having cardiovascular events. So, from a health care planning perspective, I think it’s really important to see what the burden is likely to be in the next few years,” senior author Mamas Mamas, MD, Keele University, England, told this news organization.

For physicians and the wider population, he said, the findings underscore the need to shift the conversation from saying that patients with cancer are at increased CVD risk to asking how to mitigate this risk. “Because I would say that this increase in cardiovascular admissions, that’s a failure from a preventative perspective.”

The study was published in the European Heart Journal: Quality of Care & Clinical Outcomes.

Individual cancer types

The researchers, led by Ofer Kobo, MD, also with Keele University, used the National Inpatient Sample to identify 42.5 million weighted cases of CV admissions for acute myocardial infarction (AMI), pulmonary embolism, ischemic stroke, heart failure, atrial fibrillation (AFib) or atrial flutter, and intracranial hemorrhage from January 2004 to December 2017. Of these, 1.9 million had a record of cancer.

Patients with cancer were older; had a higher prevalence of valvular disease, anemia, and coagulopathy; and had a lower prevalence of hypertension, diabetes mellitus, and obesity than did patients without cancer.

The most common cancer type was hematologic cancers (26.1%), followed by lung (18.7%), gastrointestinal (12.4%), prostate (11.6%), breast (6.7%), and other in 24.4%.

The admission rate increased across all six admission causes – between 7% for AMI and ischemic stroke and 46% for AFib.

Heart failure was the chief reason for admission among all patients. Annual rates per 100,000 U.S. population increased in patients with cancer (from 13.6 to 16.6; P for trend = .02) and declined in those without (from 352.2 to 349.8; P for trend < .001).

“In the past, patients would be started on medications, and perhaps the importance of monitoring [left ventricular] LV function wasn’t as widely known, whereas now we’re much more aggressive in looking at it and much more aggressive at trying to prevent it,” Dr. Mamas said. “But even with this greater identification and attempting to modify regimens, we’re still getting quite substantial increases in heart failure admissions in this population. And what really surprised me is that it wasn’t just in the breast cancer population, but it was nearly across the board.”

He noted that patients are at highest risk from CV events within the first 2 years of cancer diagnosis. “So that’s really the time where you’ve got to be really aggressive in looking and working up their cardiovascular profile.”

Patients with hematologic cancers (9.7-13.5), lung (7.4-8.9), and gastrointestinal cancer (4.6-6.3) had the highest crude admission rates of CV hospitalizations per 100,000 U.S. population.

The CV admission rate went up from 2.5 to 3.7 per 100,000 U.S. population for breast cancer, and in prostate cancer, the rate dropped from 5.8 to 4.8 per 100,000 U.S. population.

Of note, patients with hematologic cancers also had the highest rate of heart failure hospitalization across all cancer types, which, coupled with their increasing admission rates, likely reflects their exposure to a “constellation of cardiotoxic therapies” as well as pathologic processes related to the cancers themselves, the authors suggest.

In-hospital mortality rates were higher among patients with cancer than those without, ranging from 5% for patients with breast cancer to 9.6% for patients with lung cancer versus 4.2% for those without cancer.

Among patients with cancer, the odds ratio for mortality was highest in those admitted with AFib (4.43), followed by pulmonary embolism (2.36), AMI (2.31), ischemic stroke (2.29), and heart failure (2.24).

In line with prior work and general population trends, in-hospital deaths in primary CV admissions trended lower among patients with cancer over the study period.

Mitigating risk

Commenting on the study, Joerg Herrmann, MD, director of the cardio-oncology clinic at Mayo Clinic, Rochester, Minn., said that the data are “extremely important” because they reflect admissions during a new era of cancer therapy. “Targeted therapies all came out about the turn of the millennium, so we’re not really looking at cancer patients treated with only old and ancient strategies.”

This may be one reason for the increased admissions, but because the study lacked information on specific cancer treatments and the date of cancer diagnosis, it’s not possible to tease out whether the uptick is related to cardiotoxicity or because the oncology outcomes have improved so much that this is a growing population, he said.

One clear implication, however, is that whoever is working on the hospital service will see more patients with a cancer diagnosis, Dr. Herrmann observed.

“Though some may have tried to maybe not get involved with this topic as much, it really calls for some broader scope to get familiar with this very entity,” he said. “And that plays out, in particular, in those patients with a diagnosis of active cancer.”

Dr. Herrmann and colleagues previously reported that patients with active leukemia or lymphoma who were hospitalized with acute coronary syndrome were less likely to receive guideline-directed therapies, even at the Mayo Clinic.

Similarly, a 2020 report by Dr. Mamas and colleagues found that patients with a variety of active cancers derived similar benefit from primary percutaneous coronary intervention for ST-segment–elevation MI as those without cancer but received the treatment less commonly.

Although there’s a greater appreciation that patients with cancer benefit equally from aggressive treatment, much more can be done to mitigate CV risk, Dr. Mamas noted. Valuable coronary information captured by MRI and CT done as part of the cancer investigation is often overlooked. For example, “we know that breast calcification and vascular calcification in the breast are very strong predictors of cardiovascular outcomes and yet people aren’t using this information.”

There are numerous shared risk factors in the development of cancer and coronary artery disease, and patients with cancer often have much worse CV risk profiles but aren’t routinely risk stratified from a CV perspective, he said.

Dr. Mamas said that his team is also studying whether CVD risk prediction tools like the Framingham Risk Score, which were derived from noncancer populations, work as well in patients with cancer. “Often, when you look at the performance of these tools in populations that weren’t covered, they’re much worse.”

“A lot of cancer survivors worry about the recurrence of their cancer and will religiously go and have repeated scans, religiously check themselves, and have all these investigations but don’t think about the actual risk that is greater for them, which is cardiovascular risk,” he said.

The authors report no study funding or relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although cardiovascular disease (CVD) is known to often strike the mortal blow in patients with cancer, a national analysis puts in stark relief the burden of CV-related hospitalizations in this vulnerable population.

Results show that between 2004 and 2017, CV admissions increased 23.2% among patients with a cancer diagnosis, whereas admissions fell 10.9% among those without cancer.

Admissions increased steadily across all cancer types, except prostate cancer, with heart failure being the most common reason for admission.

“Hospital admissions is really important because we know that the size of this group is increasing, given that they live longer and many of the treatments that we offer cause cardiovascular disease or increase the risk of having cardiovascular events. So, from a health care planning perspective, I think it’s really important to see what the burden is likely to be in the next few years,” senior author Mamas Mamas, MD, Keele University, England, told this news organization.

For physicians and the wider population, he said, the findings underscore the need to shift the conversation from saying that patients with cancer are at increased CVD risk to asking how to mitigate this risk. “Because I would say that this increase in cardiovascular admissions, that’s a failure from a preventative perspective.”

The study was published in the European Heart Journal: Quality of Care & Clinical Outcomes.

Individual cancer types

The researchers, led by Ofer Kobo, MD, also with Keele University, used the National Inpatient Sample to identify 42.5 million weighted cases of CV admissions for acute myocardial infarction (AMI), pulmonary embolism, ischemic stroke, heart failure, atrial fibrillation (AFib) or atrial flutter, and intracranial hemorrhage from January 2004 to December 2017. Of these, 1.9 million had a record of cancer.

Patients with cancer were older; had a higher prevalence of valvular disease, anemia, and coagulopathy; and had a lower prevalence of hypertension, diabetes mellitus, and obesity than did patients without cancer.

The most common cancer type was hematologic cancers (26.1%), followed by lung (18.7%), gastrointestinal (12.4%), prostate (11.6%), breast (6.7%), and other in 24.4%.

The admission rate increased across all six admission causes – between 7% for AMI and ischemic stroke and 46% for AFib.

Heart failure was the chief reason for admission among all patients. Annual rates per 100,000 U.S. population increased in patients with cancer (from 13.6 to 16.6; P for trend = .02) and declined in those without (from 352.2 to 349.8; P for trend < .001).

“In the past, patients would be started on medications, and perhaps the importance of monitoring [left ventricular] LV function wasn’t as widely known, whereas now we’re much more aggressive in looking at it and much more aggressive at trying to prevent it,” Dr. Mamas said. “But even with this greater identification and attempting to modify regimens, we’re still getting quite substantial increases in heart failure admissions in this population. And what really surprised me is that it wasn’t just in the breast cancer population, but it was nearly across the board.”

He noted that patients are at highest risk from CV events within the first 2 years of cancer diagnosis. “So that’s really the time where you’ve got to be really aggressive in looking and working up their cardiovascular profile.”

Patients with hematologic cancers (9.7-13.5), lung (7.4-8.9), and gastrointestinal cancer (4.6-6.3) had the highest crude admission rates of CV hospitalizations per 100,000 U.S. population.

The CV admission rate went up from 2.5 to 3.7 per 100,000 U.S. population for breast cancer, and in prostate cancer, the rate dropped from 5.8 to 4.8 per 100,000 U.S. population.

Of note, patients with hematologic cancers also had the highest rate of heart failure hospitalization across all cancer types, which, coupled with their increasing admission rates, likely reflects their exposure to a “constellation of cardiotoxic therapies” as well as pathologic processes related to the cancers themselves, the authors suggest.

In-hospital mortality rates were higher among patients with cancer than those without, ranging from 5% for patients with breast cancer to 9.6% for patients with lung cancer versus 4.2% for those without cancer.

Among patients with cancer, the odds ratio for mortality was highest in those admitted with AFib (4.43), followed by pulmonary embolism (2.36), AMI (2.31), ischemic stroke (2.29), and heart failure (2.24).

In line with prior work and general population trends, in-hospital deaths in primary CV admissions trended lower among patients with cancer over the study period.

Mitigating risk

Commenting on the study, Joerg Herrmann, MD, director of the cardio-oncology clinic at Mayo Clinic, Rochester, Minn., said that the data are “extremely important” because they reflect admissions during a new era of cancer therapy. “Targeted therapies all came out about the turn of the millennium, so we’re not really looking at cancer patients treated with only old and ancient strategies.”

This may be one reason for the increased admissions, but because the study lacked information on specific cancer treatments and the date of cancer diagnosis, it’s not possible to tease out whether the uptick is related to cardiotoxicity or because the oncology outcomes have improved so much that this is a growing population, he said.

One clear implication, however, is that whoever is working on the hospital service will see more patients with a cancer diagnosis, Dr. Herrmann observed.

“Though some may have tried to maybe not get involved with this topic as much, it really calls for some broader scope to get familiar with this very entity,” he said. “And that plays out, in particular, in those patients with a diagnosis of active cancer.”

Dr. Herrmann and colleagues previously reported that patients with active leukemia or lymphoma who were hospitalized with acute coronary syndrome were less likely to receive guideline-directed therapies, even at the Mayo Clinic.

Similarly, a 2020 report by Dr. Mamas and colleagues found that patients with a variety of active cancers derived similar benefit from primary percutaneous coronary intervention for ST-segment–elevation MI as those without cancer but received the treatment less commonly.

Although there’s a greater appreciation that patients with cancer benefit equally from aggressive treatment, much more can be done to mitigate CV risk, Dr. Mamas noted. Valuable coronary information captured by MRI and CT done as part of the cancer investigation is often overlooked. For example, “we know that breast calcification and vascular calcification in the breast are very strong predictors of cardiovascular outcomes and yet people aren’t using this information.”

There are numerous shared risk factors in the development of cancer and coronary artery disease, and patients with cancer often have much worse CV risk profiles but aren’t routinely risk stratified from a CV perspective, he said.

Dr. Mamas said that his team is also studying whether CVD risk prediction tools like the Framingham Risk Score, which were derived from noncancer populations, work as well in patients with cancer. “Often, when you look at the performance of these tools in populations that weren’t covered, they’re much worse.”

“A lot of cancer survivors worry about the recurrence of their cancer and will religiously go and have repeated scans, religiously check themselves, and have all these investigations but don’t think about the actual risk that is greater for them, which is cardiovascular risk,” he said.

The authors report no study funding or relevant financial relationships.

A version of this article first appeared on Medscape.com.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.

Radiation therapy, along with surgery and systemic therapy, is a primary therapeutic modality for cancer management. At least half of cancer patients receive radiation as part of their treatment regimen.¹ Multiple studies demonstrate that radiotherapy is underutilized worldwide.² One reason for underutilization of radiotherapy globally is poor access to this treatment modality. Factors that contribute to poor access include long wait times for consultation, delays in treatment initiation, distance to a treatment facility, and poor coordination of care.

Taskforce Findings

The presence of onsite radiation oncology and its impact on utilization of radiotherapy is poorly studied. The Veterans Health Administration (VHA) Palliative Radiotherapy Taskforce recently conducted a survey to determine the barriers to referral and timeliness of treatment for palliative radiotherapy within the VHA.³ Key findings of this study comparing centers with onsite radiation departments with centers without onsite radiation departments include:

a. Radiation consults are more likely to be completed within 1 week of consult request at centers with onsite radiation therapy (68% vs 31%, respectively; P = .01).

b. Centers with onsite radiation therapy more frequently deliver emergent treatment within 24 hours for patients with spinal cord compression, an emergency condition in which prompt radiation can prevent or minimize long-term neurologic disability (94% vs 70%, respectively; P = .01).

c. Referring practitioners with onsite radiation departments are less likely to report difficulty contacting a radiation oncologist as a barrier to referral for palliative radiotherapy (0% vs 20%, respectively; P = .006).

d. Referring practitioners with onsite radiotherapy report patient travel as a barrier to referral for palliative radiotherapy less frequently (28% vs 71%, respectively; P < .001).

e. Practitioners with onsite radiation oncology departments are more likely to have multidisciplinary tumor boards (31% vs 3%, respectively; P = .01) and are more likely to be influenced by radiation oncology recommendations at tumor boards (69% vs 44%, respectively; P = .02).

Based on the findings of this study, the VHA Palliative Radiotherapy Taskforce has prepared this consensus statement regarding the importance of onsite radiation oncology departments at VHA medical centers. More information regarding our 5 key findings and their implications for patient care are as follows:

Timeliness of Radiation Oncology Consultation

Delays in radiation oncology consultation, which can also delay treatment initiation, are associated with poor satisfaction among both patients and referring clinicians.⁴ Wait times have been identified as a barrier to utilization of radiotherapy by both patients and clinicians.^5,6 Furthermore, delays in initiation of definitive therapy have been associated with worse outcomes, including worse overall survival.^7,8 Our survey study demonstrates that consults for palliative radiotherapy are occurring in a more timely manner at centers with onsite radiation departments. Radiation oncology consults are more frequently completed within 1 week at centers with onsite radiation oncology departments compared with centers without onsite radiation oncology departments (68% vs 31%, P = .01). This trend would likely be seen for nonpalliative, definitive cases as well. The presence of radiation oncology departments onsite at VHA medical centers is an important component of timely care for veterans to optimize outcomes of cancer treatment.

Timely Delivery of Radiotherapy for Oncologic Emergencies

There are a few scenarios in which emergent radiation treatment, within 24 hours, is indicated. These include malignant spinal cord compression, uncal herniation from brain metastasis, superior vena cava syndrome, and tumor hemorrhage.⁹ Studies on management of metastatic spinal cord compression demonstrate that delays in treatment are associated with reduced ambulation¹⁰ as well as loss of sphincter function and incontinence.¹¹

Our study demonstrates that VHA medical centers with onsite radiotherapy more frequently deliver radiotherapy within 24 hours for patients with metastatic spinal cord compression. This timely delivery of treatment is critical to optimizing functional status and quality of life in patients requiring treatment for oncologic emergencies. Revisiting treatment pathways for such situations at regular intervals is crucial given that residents and staff may rotate and be unfamiliar with emergency protocols.

Communication With Radiation Oncologists

Several studies have demonstrated that the inability to contact a radiation oncologist and poor communication result in decreased referrals for palliative radiotherapy.^12,13 Our study demonstrates that onsite radiation oncology is associated with improved ability to contact a radiation oncologist. About 20% of clinicians at facilities without onsite radiation oncology reported difficulty contacting a radiation oncologist, compared with 0% at facilities with onsite radiation departments (P = .006).

It is possible that increased radiation oncology presence at VHA medical centers, through attenuation of barriers related to contacting a radiation oncologist and improved communication, would lead to increased use of radiotherapy. Increased communication between referring clinicians and radiation oncologists also can help with education of those clinicians making the referral. Since knowledge gaps have been identified in multiple studies as a barrier to referral for radiotherapy, such communication and increased education on the role of radiotherapy could increase use.^12-14

Patient Travel

Patient ability to travel was the most commonly reported barrier (81%) to referral for palliative radiotherapy in our study. Travel time and transportation difficulties have been established in multiple studies as barriers to radiotherapy for both definitive and palliative management.^15-18 Travel for radiotherapy was much less frequently reported as a barrier among respondents with onsite radiation oncology departments compared with those without onsite radiation departments (28% vs 71%, respectively; P < .001).

It is therefore possible that expansion of VHA radiation oncology services, allowing for provision of onsite radiotherapy at more VHA facilities, would reduce travel burden. Increasing travel accommodations for patients and provision of patient lodging on hospital campuses, which is already offered at some VHA medical centers (ie, Fisher House Foundation), could also help attenuate this barrier.

Multidisciplinary Tumor Boards

Our study demonstrates that centers with onsite radiation departments more frequently hold multidisciplinary tumor boards compared with centers without radiation departments (31% vs 3%, respectively; P = .01). Multidisciplinary tumor boards allow subspecialties to meet regularly to communicate about patient care and can help mitigate barriers related to communication and education of the referring health care practitioners.

As cases are discussed in multidisciplinary tumor boards, health care practitioners have the opportunity to make recommendations and provide education on potential benefits and/or downsides of treatments offered by their respective specialties. Several studies have demonstrated that cases discussed at multidisciplinary tumor boards are more likely to be referred for radiation therapy.^19-21 Furthermore, multidisciplinary tumor boards have been associated with improved treatment outcomes.²²

Conclusions

In this consensus statement the VHA Palliative Radiotherapy Taskforce recommends the optimization of use of radiotherapy within the VHA. Radiation oncology services should be maintained where present in the VHA, with consideration for expansion of services to additional facilities. Telehealth should be used to expedite consults and treatment. Hypofractionation should be used, when appropriate, to ease travel burden. Options for transportation services and onsite housing, or hospitalization, should be understood by practitioners and offered to patients to mitigate barriers related to travel.