AVAHO

ORLANDO – Patients with hepatocellular carcinoma (HCC) who undergo surgery or thermal ablation with curative intent are at high risk for recurrence, but currently, no adjuvant therapy standard of care exists for these patients.

New findings signal a promising option for these patients. The combination of the immune checkpoint inhibitor atezolizumab (Tecentriq) and the angiogenesis inhibitor bevacizumab (Avastin) was associated with a significant improvement in recurrence-free survival, compared with active surveillance, and represents the first option to show efficacy in the adjuvant setting following surgical resection of HCCs for patients at high risk for recurrence.

The recurrence-free survival benefit corresponded to a 28% reduced risk of recurrence or death among patients who received the combination therapy in comparison with active surveillance. However, the overall survival data remain immature.

The data come from an interim analysis of the IMbrave050 trial, which was presented at the annual meeting of the American Association for Cancer Research.

“Atezolizumab plus bevacizumab may be a practice-changing adjuvant treatment options for patients with high-risk HCC,” said lead investigator Pierce Chow, MBBS, PhD, codirector of the National Cancer Centre Singapore Comprehensive Liver Cancer Clinic. He presented the results in an oral abstract session at the meeting. The combination “may also change clinical indications for surgical resection” because clinicians may be more likely to consider resection for patients at extremely high risk for recurrence if the risk of recurrence can be reduced with this combination.

In the previous IMbrave150 trial, the combination of atezolizumab and bevacizumab significantly improved outcomes for patients with high-risk and non–high-risk unresectable HCC, compared with the standard of care sorafenib (Nexavar).

In that trial, the median overall survival in the intention-to-treat population was 19.2 months for patients who received atezolizumab-bevacizumab versus 13.4 months for patients who received sorafenib (P = .0009).

The combination was also associated with improvements in progression-free survival and objective response rates, compared with sorafenib.

On the basis of these results, the IMbrave050 investigators explored whether the same benefits would occur for patients with resectable disease considered to be at high risk for recurrence owing to tumor size, vascular invasion, or poor tumor differentiation. The trial compared the combination for 334 patients with active surveillance, also for 334 patients, in the adjuvant setting.

Patients were considered good candidates for thermal ablation if they had a single tumor greater than 2 cm, but not larger than 5 cm in its longest dimension, or if they had four or fewer tumors, all of which were no larger than 5 cm. For all other patients, surgical resection was recommended.

The median age of the patients was 60. For about half of patients in each arm, the expression level of programmed death–ligand-1 (PD-L1) was 1% or higher.

After a median follow-up of 17.4 months, the 12-month recurrence-free survival rate, as assessed by independent review, was 78% for patients in the treatment arm, compared with 65% for patients who were assigned to active surveillance (hazard ratio, 0.72; P = .012). This finding was generally consistent across clinical subgroups, including groups based on age, sex, race/ethnicity, performance status, PD-L1 expression, number of high-risk features, Barcelona Clinic Liver Cancer stage, cancer etiology, procedure type, microvascular invasion, or tumor numbers and size.

Of 133 patients on active surveillance who experienced a protocol-defined recurrence event, 81 (61%) crossed over to the atezolizumab/bevacizumab arm.

The overall survival benefit of the combination therapy was less clear. Dr. Chow called the overall survival data “highly immature” at the time of data cutoff.

Overall, 47 patients died – 7 more in the combination arm (27 vs. 20). More specifically, 17 patients in the combination arm and 16 on active surveillance died from progressive disease; 6 patients in the treatment arm versus 1 on surveillance died from adverse events. The remaining deaths were attributed to other causes. Two deaths in the combination arm were considered treatment related, one from esophageal varices hemorrhage, and the other from ischemic stroke.

Dr. Chow said a number of deaths attributed to HCC recurrence was similar between the groups. There were three COVID-19–related deaths within 1 year of randomization, all in the combination arm.

As for adverse events, the safety of the combination was largely consistent with that reported in the IMbrave150 trial. Nearly all patients experienced at least one adverse event. Treatment-related grade 3 or 4 adverse events occurred in 34.9% of patients in the combination group, and serious treatment-related events occurred in 13.3%.

The most common adverse events of any grade were proteinuria, hypertension, decreased platelet count, increases in liver enzyme level, hypothyroidism, arthralgia, pruritus, rash, increase in serum bilirubin level, and fever.

Invited discussant Stephen L. Chan, MD, from the Chinese University of Hong Kong, said the study was “definitely” relevant to clinicians and addresses “a very important unmet need.”

Dr. Chan noted that he thinks this combination will “likely” be practice changing, given the improvement in recurrence-free survival, but “certainly we need more data to guide us in patient selection.”

The study was funded by F. Hoffman–La Roche. Dr. Chow has consulting for and has received honoraria and grant/research support from Roche and others. Dr. Chan has received honoraria from Roche and consulting fees and grant/research support from others.

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

ORLANDO – Patients with hepatocellular carcinoma (HCC) who undergo surgery or thermal ablation with curative intent are at high risk for recurrence, but currently, no adjuvant therapy standard of care exists for these patients.

New findings signal a promising option for these patients. The combination of the immune checkpoint inhibitor atezolizumab (Tecentriq) and the angiogenesis inhibitor bevacizumab (Avastin) was associated with a significant improvement in recurrence-free survival, compared with active surveillance, and represents the first option to show efficacy in the adjuvant setting following surgical resection of HCCs for patients at high risk for recurrence.

The recurrence-free survival benefit corresponded to a 28% reduced risk of recurrence or death among patients who received the combination therapy in comparison with active surveillance. However, the overall survival data remain immature.

The data come from an interim analysis of the IMbrave050 trial, which was presented at the annual meeting of the American Association for Cancer Research.

“Atezolizumab plus bevacizumab may be a practice-changing adjuvant treatment options for patients with high-risk HCC,” said lead investigator Pierce Chow, MBBS, PhD, codirector of the National Cancer Centre Singapore Comprehensive Liver Cancer Clinic. He presented the results in an oral abstract session at the meeting. The combination “may also change clinical indications for surgical resection” because clinicians may be more likely to consider resection for patients at extremely high risk for recurrence if the risk of recurrence can be reduced with this combination.

In the previous IMbrave150 trial, the combination of atezolizumab and bevacizumab significantly improved outcomes for patients with high-risk and non–high-risk unresectable HCC, compared with the standard of care sorafenib (Nexavar).

In that trial, the median overall survival in the intention-to-treat population was 19.2 months for patients who received atezolizumab-bevacizumab versus 13.4 months for patients who received sorafenib (P = .0009).

The combination was also associated with improvements in progression-free survival and objective response rates, compared with sorafenib.

On the basis of these results, the IMbrave050 investigators explored whether the same benefits would occur for patients with resectable disease considered to be at high risk for recurrence owing to tumor size, vascular invasion, or poor tumor differentiation. The trial compared the combination for 334 patients with active surveillance, also for 334 patients, in the adjuvant setting.

Patients were considered good candidates for thermal ablation if they had a single tumor greater than 2 cm, but not larger than 5 cm in its longest dimension, or if they had four or fewer tumors, all of which were no larger than 5 cm. For all other patients, surgical resection was recommended.

The median age of the patients was 60. For about half of patients in each arm, the expression level of programmed death–ligand-1 (PD-L1) was 1% or higher.

After a median follow-up of 17.4 months, the 12-month recurrence-free survival rate, as assessed by independent review, was 78% for patients in the treatment arm, compared with 65% for patients who were assigned to active surveillance (hazard ratio, 0.72; P = .012). This finding was generally consistent across clinical subgroups, including groups based on age, sex, race/ethnicity, performance status, PD-L1 expression, number of high-risk features, Barcelona Clinic Liver Cancer stage, cancer etiology, procedure type, microvascular invasion, or tumor numbers and size.

Of 133 patients on active surveillance who experienced a protocol-defined recurrence event, 81 (61%) crossed over to the atezolizumab/bevacizumab arm.

The overall survival benefit of the combination therapy was less clear. Dr. Chow called the overall survival data “highly immature” at the time of data cutoff.

Overall, 47 patients died – 7 more in the combination arm (27 vs. 20). More specifically, 17 patients in the combination arm and 16 on active surveillance died from progressive disease; 6 patients in the treatment arm versus 1 on surveillance died from adverse events. The remaining deaths were attributed to other causes. Two deaths in the combination arm were considered treatment related, one from esophageal varices hemorrhage, and the other from ischemic stroke.

Dr. Chow said a number of deaths attributed to HCC recurrence was similar between the groups. There were three COVID-19–related deaths within 1 year of randomization, all in the combination arm.

As for adverse events, the safety of the combination was largely consistent with that reported in the IMbrave150 trial. Nearly all patients experienced at least one adverse event. Treatment-related grade 3 or 4 adverse events occurred in 34.9% of patients in the combination group, and serious treatment-related events occurred in 13.3%.

The most common adverse events of any grade were proteinuria, hypertension, decreased platelet count, increases in liver enzyme level, hypothyroidism, arthralgia, pruritus, rash, increase in serum bilirubin level, and fever.

Invited discussant Stephen L. Chan, MD, from the Chinese University of Hong Kong, said the study was “definitely” relevant to clinicians and addresses “a very important unmet need.”

Dr. Chan noted that he thinks this combination will “likely” be practice changing, given the improvement in recurrence-free survival, but “certainly we need more data to guide us in patient selection.”

The study was funded by F. Hoffman–La Roche. Dr. Chow has consulting for and has received honoraria and grant/research support from Roche and others. Dr. Chan has received honoraria from Roche and consulting fees and grant/research support from others.

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

ORLANDO – Patients with hepatocellular carcinoma (HCC) who undergo surgery or thermal ablation with curative intent are at high risk for recurrence, but currently, no adjuvant therapy standard of care exists for these patients.

New findings signal a promising option for these patients. The combination of the immune checkpoint inhibitor atezolizumab (Tecentriq) and the angiogenesis inhibitor bevacizumab (Avastin) was associated with a significant improvement in recurrence-free survival, compared with active surveillance, and represents the first option to show efficacy in the adjuvant setting following surgical resection of HCCs for patients at high risk for recurrence.

The recurrence-free survival benefit corresponded to a 28% reduced risk of recurrence or death among patients who received the combination therapy in comparison with active surveillance. However, the overall survival data remain immature.

The data come from an interim analysis of the IMbrave050 trial, which was presented at the annual meeting of the American Association for Cancer Research.

“Atezolizumab plus bevacizumab may be a practice-changing adjuvant treatment options for patients with high-risk HCC,” said lead investigator Pierce Chow, MBBS, PhD, codirector of the National Cancer Centre Singapore Comprehensive Liver Cancer Clinic. He presented the results in an oral abstract session at the meeting. The combination “may also change clinical indications for surgical resection” because clinicians may be more likely to consider resection for patients at extremely high risk for recurrence if the risk of recurrence can be reduced with this combination.

In the previous IMbrave150 trial, the combination of atezolizumab and bevacizumab significantly improved outcomes for patients with high-risk and non–high-risk unresectable HCC, compared with the standard of care sorafenib (Nexavar).

In that trial, the median overall survival in the intention-to-treat population was 19.2 months for patients who received atezolizumab-bevacizumab versus 13.4 months for patients who received sorafenib (P = .0009).

The combination was also associated with improvements in progression-free survival and objective response rates, compared with sorafenib.

On the basis of these results, the IMbrave050 investigators explored whether the same benefits would occur for patients with resectable disease considered to be at high risk for recurrence owing to tumor size, vascular invasion, or poor tumor differentiation. The trial compared the combination for 334 patients with active surveillance, also for 334 patients, in the adjuvant setting.

Patients were considered good candidates for thermal ablation if they had a single tumor greater than 2 cm, but not larger than 5 cm in its longest dimension, or if they had four or fewer tumors, all of which were no larger than 5 cm. For all other patients, surgical resection was recommended.

The median age of the patients was 60. For about half of patients in each arm, the expression level of programmed death–ligand-1 (PD-L1) was 1% or higher.

After a median follow-up of 17.4 months, the 12-month recurrence-free survival rate, as assessed by independent review, was 78% for patients in the treatment arm, compared with 65% for patients who were assigned to active surveillance (hazard ratio, 0.72; P = .012). This finding was generally consistent across clinical subgroups, including groups based on age, sex, race/ethnicity, performance status, PD-L1 expression, number of high-risk features, Barcelona Clinic Liver Cancer stage, cancer etiology, procedure type, microvascular invasion, or tumor numbers and size.

Of 133 patients on active surveillance who experienced a protocol-defined recurrence event, 81 (61%) crossed over to the atezolizumab/bevacizumab arm.

The overall survival benefit of the combination therapy was less clear. Dr. Chow called the overall survival data “highly immature” at the time of data cutoff.

Overall, 47 patients died – 7 more in the combination arm (27 vs. 20). More specifically, 17 patients in the combination arm and 16 on active surveillance died from progressive disease; 6 patients in the treatment arm versus 1 on surveillance died from adverse events. The remaining deaths were attributed to other causes. Two deaths in the combination arm were considered treatment related, one from esophageal varices hemorrhage, and the other from ischemic stroke.

Dr. Chow said a number of deaths attributed to HCC recurrence was similar between the groups. There were three COVID-19–related deaths within 1 year of randomization, all in the combination arm.

As for adverse events, the safety of the combination was largely consistent with that reported in the IMbrave150 trial. Nearly all patients experienced at least one adverse event. Treatment-related grade 3 or 4 adverse events occurred in 34.9% of patients in the combination group, and serious treatment-related events occurred in 13.3%.

The most common adverse events of any grade were proteinuria, hypertension, decreased platelet count, increases in liver enzyme level, hypothyroidism, arthralgia, pruritus, rash, increase in serum bilirubin level, and fever.

Invited discussant Stephen L. Chan, MD, from the Chinese University of Hong Kong, said the study was “definitely” relevant to clinicians and addresses “a very important unmet need.”

Dr. Chan noted that he thinks this combination will “likely” be practice changing, given the improvement in recurrence-free survival, but “certainly we need more data to guide us in patient selection.”

The study was funded by F. Hoffman–La Roche. Dr. Chow has consulting for and has received honoraria and grant/research support from Roche and others. Dr. Chan has received honoraria from Roche and consulting fees and grant/research support from others.

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

Exposure to four or more CT scans before age 18 years is associated with more than double the risk for certain cancers into early adulthood, data indicate.
 

In a population-based case-control study that included more than 85,000 participants, researchers found a ninefold increased risk of intracranial tumors among children who received four or more CT scans.

The results “indicate that judicious CT usage and radiation-reducing techniques should be advocated,” Yu-Hsuan Joni Shao, PhD, professor of biomedical informatics at Taipei (Taiwan) Medical University, and colleagues wrote.

The study was published in the Canadian Medical Association Journal.
 

Dose-response relationship

The investigators used the National Health Insurance Research Database in Taiwan to identify 7,807 patients under age 25 years with intracranial tumors (grades I-IV), leukemia, non-Hodgkin lymphomas, or Hodgkin lymphomas that had been diagnosed in a 14-year span between the years 2000 and 2013. They matched each case with 10 control participants without cancer by sex, date of birth, and date of entry into the cohort.

Radiation exposure was calculated for each patient according to number and type of CT scans received and an estimated organ-specific cumulative dose based on previously published models. The investigators excluded patients from the analysis if they had a diagnosis of any malignant disease before the study period or if they had any cancer-predisposing conditions, such as Down syndrome (which entails an increased risk of leukemia) or immunodeficiency (which may require multiple CT scans).

Compared with no exposure, exposure to a single pediatric CT scan was not associated with increased cancer risk. Exposure to two to three CT scans, however, was associated with an increased risk for intracranial tumour (adjusted odds ratio, 2.36), but not for leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma.  Exposure to four or more CT scans was associated with increased risk for intracranial tumor (aOR, 9.01), leukemia (aOR, 4.80), and non-Hodgkin lymphoma (aOR, 6.76), but not for Hodgkin lymphoma.

The researchers also found a dose-response relationship. Participants in the top quintile of cumulative brain radiation dose had a significantly higher risk for intracranial tumor, compared with nonexposed participants (aOR, 3.61), although this relationship was not seen with the other cancers.

Age at exposure was also a significant factor. Children exposed to four or more CT scans at or before age 6 years had the highest risk for cancer (aOR, 22.95), followed by the same number of scans in those aged 7-12 years (aOR, 5.69) and those aged 13-18 years (aOR, 3.20).

The authors noted that, although these cancers are uncommon in children, “our work reinforces the importance of radiation protection strategies, addressed by the International Atomic Energy Agency. Unnecessary CT scans should be avoided, and special attention should be paid to patients who require repeated CT scans. Parents and pediatric patients should be well informed on risks and benefits before radiological procedures and encouraged to participate in decision-making around imaging.”
 

True risks underestimated?  

Commenting on the findings, Rebecca Smith-Bindman, MD, a radiologist at the University of California, San Francisco, and an expert on the impact of CT scans on patient outcomes, said that she trusts the authors’ overall findings. But “because of the direction of their biases,” the study design “doesn’t let me accept their conclusion that one CT does not elevate the risk.

“It’s an interesting study that found the risk of brain cancer is more than doubled in children who undergo two or more CT scans, but in many ways, their assumptions will underestimate the true risk,” said Dr. Smith-Bindman, who is a professor of epidemiology and biostatistics at UCSF. She said reasons for this include the fact that the investigators used estimated, rather than actual radiation doses; that their estimates “reflect doses far lower than we have found actually occur in clinical practice”; that they do not differentiate between a low-dose or a high-dose CT; and that that they include a long, 3-year lag during which leukemia can develop after a CT scan.

“They did a lot of really well-done adjustments to ensure that they were not overestimating risk,” said Dr. Smith-Bindman. “They made sure to delete children who had cancer susceptibility syndrome, they included a lag of 3 years, assuming that there could be hidden cancers for up to 3 years after the first imaging study when they might have had a preexisting cancer. These are decisions that ensure that any cancer risk they find is real, but it also means that the risks that are estimated are almost certainly an underestimate of the true risks.”

The study was conducted without external funding. The authors declared no relevant financial relationships. Dr. Smith-Bindman is a cofounder of Alara Imaging, a company focused on collecting and reporting radiation dose information associated with CT.

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

Exposure to four or more CT scans before age 18 years is associated with more than double the risk for certain cancers into early adulthood, data indicate.
 

In a population-based case-control study that included more than 85,000 participants, researchers found a ninefold increased risk of intracranial tumors among children who received four or more CT scans.

The results “indicate that judicious CT usage and radiation-reducing techniques should be advocated,” Yu-Hsuan Joni Shao, PhD, professor of biomedical informatics at Taipei (Taiwan) Medical University, and colleagues wrote.

The study was published in the Canadian Medical Association Journal.
 

Dose-response relationship

The investigators used the National Health Insurance Research Database in Taiwan to identify 7,807 patients under age 25 years with intracranial tumors (grades I-IV), leukemia, non-Hodgkin lymphomas, or Hodgkin lymphomas that had been diagnosed in a 14-year span between the years 2000 and 2013. They matched each case with 10 control participants without cancer by sex, date of birth, and date of entry into the cohort.

Radiation exposure was calculated for each patient according to number and type of CT scans received and an estimated organ-specific cumulative dose based on previously published models. The investigators excluded patients from the analysis if they had a diagnosis of any malignant disease before the study period or if they had any cancer-predisposing conditions, such as Down syndrome (which entails an increased risk of leukemia) or immunodeficiency (which may require multiple CT scans).

Compared with no exposure, exposure to a single pediatric CT scan was not associated with increased cancer risk. Exposure to two to three CT scans, however, was associated with an increased risk for intracranial tumour (adjusted odds ratio, 2.36), but not for leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma.  Exposure to four or more CT scans was associated with increased risk for intracranial tumor (aOR, 9.01), leukemia (aOR, 4.80), and non-Hodgkin lymphoma (aOR, 6.76), but not for Hodgkin lymphoma.

The researchers also found a dose-response relationship. Participants in the top quintile of cumulative brain radiation dose had a significantly higher risk for intracranial tumor, compared with nonexposed participants (aOR, 3.61), although this relationship was not seen with the other cancers.

Age at exposure was also a significant factor. Children exposed to four or more CT scans at or before age 6 years had the highest risk for cancer (aOR, 22.95), followed by the same number of scans in those aged 7-12 years (aOR, 5.69) and those aged 13-18 years (aOR, 3.20).

The authors noted that, although these cancers are uncommon in children, “our work reinforces the importance of radiation protection strategies, addressed by the International Atomic Energy Agency. Unnecessary CT scans should be avoided, and special attention should be paid to patients who require repeated CT scans. Parents and pediatric patients should be well informed on risks and benefits before radiological procedures and encouraged to participate in decision-making around imaging.”
 

True risks underestimated?  

Commenting on the findings, Rebecca Smith-Bindman, MD, a radiologist at the University of California, San Francisco, and an expert on the impact of CT scans on patient outcomes, said that she trusts the authors’ overall findings. But “because of the direction of their biases,” the study design “doesn’t let me accept their conclusion that one CT does not elevate the risk.

“It’s an interesting study that found the risk of brain cancer is more than doubled in children who undergo two or more CT scans, but in many ways, their assumptions will underestimate the true risk,” said Dr. Smith-Bindman, who is a professor of epidemiology and biostatistics at UCSF. She said reasons for this include the fact that the investigators used estimated, rather than actual radiation doses; that their estimates “reflect doses far lower than we have found actually occur in clinical practice”; that they do not differentiate between a low-dose or a high-dose CT; and that that they include a long, 3-year lag during which leukemia can develop after a CT scan.

“They did a lot of really well-done adjustments to ensure that they were not overestimating risk,” said Dr. Smith-Bindman. “They made sure to delete children who had cancer susceptibility syndrome, they included a lag of 3 years, assuming that there could be hidden cancers for up to 3 years after the first imaging study when they might have had a preexisting cancer. These are decisions that ensure that any cancer risk they find is real, but it also means that the risks that are estimated are almost certainly an underestimate of the true risks.”

The study was conducted without external funding. The authors declared no relevant financial relationships. Dr. Smith-Bindman is a cofounder of Alara Imaging, a company focused on collecting and reporting radiation dose information associated with CT.

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

Exposure to four or more CT scans before age 18 years is associated with more than double the risk for certain cancers into early adulthood, data indicate.
 

In a population-based case-control study that included more than 85,000 participants, researchers found a ninefold increased risk of intracranial tumors among children who received four or more CT scans.

The results “indicate that judicious CT usage and radiation-reducing techniques should be advocated,” Yu-Hsuan Joni Shao, PhD, professor of biomedical informatics at Taipei (Taiwan) Medical University, and colleagues wrote.

The study was published in the Canadian Medical Association Journal.
 

Dose-response relationship

The investigators used the National Health Insurance Research Database in Taiwan to identify 7,807 patients under age 25 years with intracranial tumors (grades I-IV), leukemia, non-Hodgkin lymphomas, or Hodgkin lymphomas that had been diagnosed in a 14-year span between the years 2000 and 2013. They matched each case with 10 control participants without cancer by sex, date of birth, and date of entry into the cohort.

Radiation exposure was calculated for each patient according to number and type of CT scans received and an estimated organ-specific cumulative dose based on previously published models. The investigators excluded patients from the analysis if they had a diagnosis of any malignant disease before the study period or if they had any cancer-predisposing conditions, such as Down syndrome (which entails an increased risk of leukemia) or immunodeficiency (which may require multiple CT scans).

Compared with no exposure, exposure to a single pediatric CT scan was not associated with increased cancer risk. Exposure to two to three CT scans, however, was associated with an increased risk for intracranial tumour (adjusted odds ratio, 2.36), but not for leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma.  Exposure to four or more CT scans was associated with increased risk for intracranial tumor (aOR, 9.01), leukemia (aOR, 4.80), and non-Hodgkin lymphoma (aOR, 6.76), but not for Hodgkin lymphoma.

The researchers also found a dose-response relationship. Participants in the top quintile of cumulative brain radiation dose had a significantly higher risk for intracranial tumor, compared with nonexposed participants (aOR, 3.61), although this relationship was not seen with the other cancers.

Age at exposure was also a significant factor. Children exposed to four or more CT scans at or before age 6 years had the highest risk for cancer (aOR, 22.95), followed by the same number of scans in those aged 7-12 years (aOR, 5.69) and those aged 13-18 years (aOR, 3.20).

The authors noted that, although these cancers are uncommon in children, “our work reinforces the importance of radiation protection strategies, addressed by the International Atomic Energy Agency. Unnecessary CT scans should be avoided, and special attention should be paid to patients who require repeated CT scans. Parents and pediatric patients should be well informed on risks and benefits before radiological procedures and encouraged to participate in decision-making around imaging.”
 

True risks underestimated?  

Commenting on the findings, Rebecca Smith-Bindman, MD, a radiologist at the University of California, San Francisco, and an expert on the impact of CT scans on patient outcomes, said that she trusts the authors’ overall findings. But “because of the direction of their biases,” the study design “doesn’t let me accept their conclusion that one CT does not elevate the risk.

“It’s an interesting study that found the risk of brain cancer is more than doubled in children who undergo two or more CT scans, but in many ways, their assumptions will underestimate the true risk,” said Dr. Smith-Bindman, who is a professor of epidemiology and biostatistics at UCSF. She said reasons for this include the fact that the investigators used estimated, rather than actual radiation doses; that their estimates “reflect doses far lower than we have found actually occur in clinical practice”; that they do not differentiate between a low-dose or a high-dose CT; and that that they include a long, 3-year lag during which leukemia can develop after a CT scan.

“They did a lot of really well-done adjustments to ensure that they were not overestimating risk,” said Dr. Smith-Bindman. “They made sure to delete children who had cancer susceptibility syndrome, they included a lag of 3 years, assuming that there could be hidden cancers for up to 3 years after the first imaging study when they might have had a preexisting cancer. These are decisions that ensure that any cancer risk they find is real, but it also means that the risks that are estimated are almost certainly an underestimate of the true risks.”

The study was conducted without external funding. The authors declared no relevant financial relationships. Dr. Smith-Bindman is a cofounder of Alara Imaging, a company focused on collecting and reporting radiation dose information associated with CT.

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

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

The investigational drug motixafortide shows promise for improving the stem cell transplantation process in patients with multiple myeloma (MM), according to research led by investigators at Washington University in St. Louis.

Motixafortide, a   novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity , appears to increase the number of stem cells that can be harvested from transplant candidates, thereby increasing the likelihood of successful transplant, the authors reported.

An application for a new drug approval is currently under review by the Food and Drug Administration.

In the prospective, international, phase 3 GENESIS clinical trial , motixafortide plus granulocyte colony-stimulating factor (G-CSF) – the standard therapy for mobilizing stem cells – significantly increased the number stem cells harvested, when compared with standard therapy plus placebo. After one collection procedure, the combination approach allowed for harvesting of an optimal number of cells in 88% versus 9% of patients who received G-CSF plus placebo. After two collections, optimal collection occurred in 92% versus 26% of patients in the groups, respectively, first author Zachary D. Crees, MD, and colleagues found.

Motixafortide plus G-CSF was also associated with a tenfold increase in the number of primitive stem cells that could be collected. These stem cells are particularly effective for reconstituting red blood cells, white blood cells, and platelets, which all are important for patients’ recovery, they noted.

Stem cells mobilized by motixafortide were also associated with increased expression of genes and genetic pathways involved in self-renewal and regeneration, which are also of benefit for increasing the effectiveness of stem cell transplantation.

The findings were published in Nature Medicine.

“Stem cell transplantation is central to the treatment of multiple myeloma, but some patients don’t see as much benefit because standard therapies can’t harvest enough stem cells for the transplant to be effective, senior author John F. DiPersio, MD, PhD, stated in a news release . “This study suggests motixafortide works extremely well in combination with [G-CSF] in mobilizing stem cells in patients with multiple myeloma.

“The study also found that the combination worked rapidly and was generally well tolerated by patients,” added Dr. DiPersio, the Virginia E. & Sam J. Goldman Professor of Medicine at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University.

Dr. DiPersio is the lead author of another study investigating therapies beyond stem cell transplants. He and his colleagues recently reported the first comprehensive genomic and protein-based analysis of bone marrow samples from patients with multiple myeloma in an effort to identify targets for immunotherapies.

That study, published online in Cancer Research, identified 53 genes that could be targets, including 38 that are responsible for creating abnormal proteins on the surface of multiple myeloma cells; 11 of the 38 had not been previously identified as potential targets.

Dr. DiPersio and Dr. Crees, an assistant professor of medicine and the assistant clinical director of the Washington University Center for Gene and Cellular Immunotherapy, are also evaluating motixafortide’s potential for mobilizing stem cells to support “the genetic correction of the inherited disease sickle cell anemia.”

“This work is of particular importance because patients with sickle cell disease can’t be treated with G-CSF … due to dangerous side effects,” the news release stated. “The hope is that development of a novel, effective, and well-tolerated stem cell mobilizing regimen for a viral-based gene therapy approach using CRISPR-based gene editing will lead to improved outcomes for patients with sickle cell disease.”

The study published in Nature Medicine was supported by the National Institutes of Health and BioLineRx, which makes motixafortide. The study published in Cancer Research was supported by the Paula C. And Rodger O. Riney Blood Cancer Research Fund and the National Cancer Institute.

Dr. Crees reported research funding from BioLineRx. Dr. DiPersio reported relationships with Magenta Therapeutics, WUGEN, Incyte, RiverVest Venture Partners, Cellworks Group, Amphivena Therapeutics, NeoImmune Tech, Macrogenics, and BioLineRx.

Correction, 4/26/23: The headline on an earlier version of this article mischaracterized the study findings.

The investigational drug motixafortide shows promise for improving the stem cell transplantation process in patients with multiple myeloma (MM), according to research led by investigators at Washington University in St. Louis.

Motixafortide, a   novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity , appears to increase the number of stem cells that can be harvested from transplant candidates, thereby increasing the likelihood of successful transplant, the authors reported.

An application for a new drug approval is currently under review by the Food and Drug Administration.

In the prospective, international, phase 3 GENESIS clinical trial , motixafortide plus granulocyte colony-stimulating factor (G-CSF) – the standard therapy for mobilizing stem cells – significantly increased the number stem cells harvested, when compared with standard therapy plus placebo. After one collection procedure, the combination approach allowed for harvesting of an optimal number of cells in 88% versus 9% of patients who received G-CSF plus placebo. After two collections, optimal collection occurred in 92% versus 26% of patients in the groups, respectively, first author Zachary D. Crees, MD, and colleagues found.

Motixafortide plus G-CSF was also associated with a tenfold increase in the number of primitive stem cells that could be collected. These stem cells are particularly effective for reconstituting red blood cells, white blood cells, and platelets, which all are important for patients’ recovery, they noted.

Stem cells mobilized by motixafortide were also associated with increased expression of genes and genetic pathways involved in self-renewal and regeneration, which are also of benefit for increasing the effectiveness of stem cell transplantation.

The findings were published in Nature Medicine.

“Stem cell transplantation is central to the treatment of multiple myeloma, but some patients don’t see as much benefit because standard therapies can’t harvest enough stem cells for the transplant to be effective, senior author John F. DiPersio, MD, PhD, stated in a news release . “This study suggests motixafortide works extremely well in combination with [G-CSF] in mobilizing stem cells in patients with multiple myeloma.

“The study also found that the combination worked rapidly and was generally well tolerated by patients,” added Dr. DiPersio, the Virginia E. & Sam J. Goldman Professor of Medicine at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University.

Dr. DiPersio is the lead author of another study investigating therapies beyond stem cell transplants. He and his colleagues recently reported the first comprehensive genomic and protein-based analysis of bone marrow samples from patients with multiple myeloma in an effort to identify targets for immunotherapies.

That study, published online in Cancer Research, identified 53 genes that could be targets, including 38 that are responsible for creating abnormal proteins on the surface of multiple myeloma cells; 11 of the 38 had not been previously identified as potential targets.

Dr. DiPersio and Dr. Crees, an assistant professor of medicine and the assistant clinical director of the Washington University Center for Gene and Cellular Immunotherapy, are also evaluating motixafortide’s potential for mobilizing stem cells to support “the genetic correction of the inherited disease sickle cell anemia.”

“This work is of particular importance because patients with sickle cell disease can’t be treated with G-CSF … due to dangerous side effects,” the news release stated. “The hope is that development of a novel, effective, and well-tolerated stem cell mobilizing regimen for a viral-based gene therapy approach using CRISPR-based gene editing will lead to improved outcomes for patients with sickle cell disease.”

The study published in Nature Medicine was supported by the National Institutes of Health and BioLineRx, which makes motixafortide. The study published in Cancer Research was supported by the Paula C. And Rodger O. Riney Blood Cancer Research Fund and the National Cancer Institute.

Dr. Crees reported research funding from BioLineRx. Dr. DiPersio reported relationships with Magenta Therapeutics, WUGEN, Incyte, RiverVest Venture Partners, Cellworks Group, Amphivena Therapeutics, NeoImmune Tech, Macrogenics, and BioLineRx.

Correction, 4/26/23: The headline on an earlier version of this article mischaracterized the study findings.

The investigational drug motixafortide shows promise for improving the stem cell transplantation process in patients with multiple myeloma (MM), according to research led by investigators at Washington University in St. Louis.

Motixafortide, a   novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity , appears to increase the number of stem cells that can be harvested from transplant candidates, thereby increasing the likelihood of successful transplant, the authors reported.

An application for a new drug approval is currently under review by the Food and Drug Administration.

In the prospective, international, phase 3 GENESIS clinical trial , motixafortide plus granulocyte colony-stimulating factor (G-CSF) – the standard therapy for mobilizing stem cells – significantly increased the number stem cells harvested, when compared with standard therapy plus placebo. After one collection procedure, the combination approach allowed for harvesting of an optimal number of cells in 88% versus 9% of patients who received G-CSF plus placebo. After two collections, optimal collection occurred in 92% versus 26% of patients in the groups, respectively, first author Zachary D. Crees, MD, and colleagues found.

Motixafortide plus G-CSF was also associated with a tenfold increase in the number of primitive stem cells that could be collected. These stem cells are particularly effective for reconstituting red blood cells, white blood cells, and platelets, which all are important for patients’ recovery, they noted.

Stem cells mobilized by motixafortide were also associated with increased expression of genes and genetic pathways involved in self-renewal and regeneration, which are also of benefit for increasing the effectiveness of stem cell transplantation.

The findings were published in Nature Medicine.

“Stem cell transplantation is central to the treatment of multiple myeloma, but some patients don’t see as much benefit because standard therapies can’t harvest enough stem cells for the transplant to be effective, senior author John F. DiPersio, MD, PhD, stated in a news release . “This study suggests motixafortide works extremely well in combination with [G-CSF] in mobilizing stem cells in patients with multiple myeloma.

“The study also found that the combination worked rapidly and was generally well tolerated by patients,” added Dr. DiPersio, the Virginia E. & Sam J. Goldman Professor of Medicine at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University.

Dr. DiPersio is the lead author of another study investigating therapies beyond stem cell transplants. He and his colleagues recently reported the first comprehensive genomic and protein-based analysis of bone marrow samples from patients with multiple myeloma in an effort to identify targets for immunotherapies.

That study, published online in Cancer Research, identified 53 genes that could be targets, including 38 that are responsible for creating abnormal proteins on the surface of multiple myeloma cells; 11 of the 38 had not been previously identified as potential targets.

Dr. DiPersio and Dr. Crees, an assistant professor of medicine and the assistant clinical director of the Washington University Center for Gene and Cellular Immunotherapy, are also evaluating motixafortide’s potential for mobilizing stem cells to support “the genetic correction of the inherited disease sickle cell anemia.”

“This work is of particular importance because patients with sickle cell disease can’t be treated with G-CSF … due to dangerous side effects,” the news release stated. “The hope is that development of a novel, effective, and well-tolerated stem cell mobilizing regimen for a viral-based gene therapy approach using CRISPR-based gene editing will lead to improved outcomes for patients with sickle cell disease.”

The study published in Nature Medicine was supported by the National Institutes of Health and BioLineRx, which makes motixafortide. The study published in Cancer Research was supported by the Paula C. And Rodger O. Riney Blood Cancer Research Fund and the National Cancer Institute.

Dr. Crees reported research funding from BioLineRx. Dr. DiPersio reported relationships with Magenta Therapeutics, WUGEN, Incyte, RiverVest Venture Partners, Cellworks Group, Amphivena Therapeutics, NeoImmune Tech, Macrogenics, and BioLineRx.

Correction, 4/26/23: The headline on an earlier version of this article mischaracterized the study findings.

The painful paused and repaused rollout of the new Cerner electronic health record (EHR) system at the US Department of Veterans Affairs (VA) is now halted as the VA announces a “reset.” The decision applies to all planned deployments. An exception is the Captain James A. Lovell Federal Health Care Center in Chicago, the only fully integrated VA and US Department of Defense (DoD) health care system, which is expected go live in March 2024 as planned. The DoD rollout of its Cerner EHR is further along and expected to be completed in 2024.

The new plan is to redirect resources and “prioritize improvements” at the 5 sites currently using the new EHR: Spokane VA Health Care System, VA Walla Walla Health Care, Roseburg VA Health Care System, VA Southern Oregon Health Care, and VA Central Ohio Health Care System. Additional deployments will not be scheduled, the VA says, until it is confident that the new EHR is highly functioning at the current sites and ready to deliver at future sites, as demonstrated by “clear improvements” in the clinician and veteran experience, sustained high performance and high reliability.

“For the past few years, we’ve tried to fix this plane while flying it—and that hasn’t delivered the results that veterans or our staff deserve,” said Neil Evans, MD, acting program executive director at the Electronic Health Record Modernization Integration Office. “This reset changes that. We are going to take the time necessary to get this right for veterans and VA clinicians alike, and that means focusing our resources solely on improving the EHR at the sites where it is currently in use, and improving its fit for VA more broadly. In doing so, we will enhance the EHR for both current and future users, paving the way for successful future deployments.”  

The various EHR rollouts around the country have been bumpy from the beginning, operating by fits and starts as new problems surfaced and were addressed. To be fair, the whole implementation process only started in 2020 (and deployed at the first VA hospital during the COVID-19 pandemic), but in that time, the VA has had to, in its own words, “revise the timeline” again and again. The Boise VA Medical Center, for instance, was originally scheduled to go live June 25, 2022, then a month later—then 2023.

The VA Office of the Inspector General published 3 reports last year that found significant issues, including improperly routed clinical orders. VA Secretary Denis McDonough announced last July that the VA would delay EHR deployments until January 2023 to ensure that the system’s issues had been resolved. “During VA’s subsequent investigation at our current sites,” he said, “several additional technical and system issues were identified—including challenges with performance, such as latency and slowness, problems with patient scheduling, referrals, medication management, and other types of medical orders.”

In February, Ken Glueck, executive vice president of Oracle, wrote a blog post that was both apologia and explanation. Modernization, he said, “doesn’t come with a magic wand and there’s no easy button.”

After the DoD moved to Cerner for a new EHR system, the VA decided to follow suit. The goal was to create a “seamless, longitudinal record”—and that was the beginning of the largest health IT modernization project in history, Glueck said. And, although he didn’t mention it, the beginning of one of the VA’s biggest headaches. The problem, Glueck wrote, was that the new project involved “standardizing procedures and workflows that may have been different across 130 VistA implementations at largely autonomous VA medical centers.”

In June 2022—a significant month in the whole rollout process—Cerner was acquired by Oracle. By Glueck’s lights, that meant the VA “now has essentially 2 vendors for the price of one—one with extensive clinical expertise and one with extensive engineering expertise.”

Oracle, he said, “is hard at work to stabilize and improve performance; make fixes to functionality and design issues; improve training and build a better user experience.” He noted that significant improvements to the system’s capacity and performance have included reducing the most severe outage incidents by 67%.

In a recent statement, House VA Committee Chairman Mike Bost (R-IL) and Technology Modernization Subcommittee Chairman Matt Rosendale (R-MT) said, “We support Secretary McDonough’s decision in the strongest possible terms. The best way to get out of a hole is to stop digging, and we’re encouraged that VA and Oracle Cerner have finally realized that.”

VA and Oracle Cerner are currently working toward an amended contract that will "increase Oracle Cerner’s accountability to deliver a high-functioning, high-reliability, world-class EHR system,” the VA says. As part of the re-set, the VA also will work with Congress on resource requirements. The VA estimates FY 2023 costs will be reduced by $400 million. 

The painful paused and repaused rollout of the new Cerner electronic health record (EHR) system at the US Department of Veterans Affairs (VA) is now halted as the VA announces a “reset.” The decision applies to all planned deployments. An exception is the Captain James A. Lovell Federal Health Care Center in Chicago, the only fully integrated VA and US Department of Defense (DoD) health care system, which is expected go live in March 2024 as planned. The DoD rollout of its Cerner EHR is further along and expected to be completed in 2024.

The new plan is to redirect resources and “prioritize improvements” at the 5 sites currently using the new EHR: Spokane VA Health Care System, VA Walla Walla Health Care, Roseburg VA Health Care System, VA Southern Oregon Health Care, and VA Central Ohio Health Care System. Additional deployments will not be scheduled, the VA says, until it is confident that the new EHR is highly functioning at the current sites and ready to deliver at future sites, as demonstrated by “clear improvements” in the clinician and veteran experience, sustained high performance and high reliability.

“For the past few years, we’ve tried to fix this plane while flying it—and that hasn’t delivered the results that veterans or our staff deserve,” said Neil Evans, MD, acting program executive director at the Electronic Health Record Modernization Integration Office. “This reset changes that. We are going to take the time necessary to get this right for veterans and VA clinicians alike, and that means focusing our resources solely on improving the EHR at the sites where it is currently in use, and improving its fit for VA more broadly. In doing so, we will enhance the EHR for both current and future users, paving the way for successful future deployments.”  

The various EHR rollouts around the country have been bumpy from the beginning, operating by fits and starts as new problems surfaced and were addressed. To be fair, the whole implementation process only started in 2020 (and deployed at the first VA hospital during the COVID-19 pandemic), but in that time, the VA has had to, in its own words, “revise the timeline” again and again. The Boise VA Medical Center, for instance, was originally scheduled to go live June 25, 2022, then a month later—then 2023.

The VA Office of the Inspector General published 3 reports last year that found significant issues, including improperly routed clinical orders. VA Secretary Denis McDonough announced last July that the VA would delay EHR deployments until January 2023 to ensure that the system’s issues had been resolved. “During VA’s subsequent investigation at our current sites,” he said, “several additional technical and system issues were identified—including challenges with performance, such as latency and slowness, problems with patient scheduling, referrals, medication management, and other types of medical orders.”

In February, Ken Glueck, executive vice president of Oracle, wrote a blog post that was both apologia and explanation. Modernization, he said, “doesn’t come with a magic wand and there’s no easy button.”

After the DoD moved to Cerner for a new EHR system, the VA decided to follow suit. The goal was to create a “seamless, longitudinal record”—and that was the beginning of the largest health IT modernization project in history, Glueck said. And, although he didn’t mention it, the beginning of one of the VA’s biggest headaches. The problem, Glueck wrote, was that the new project involved “standardizing procedures and workflows that may have been different across 130 VistA implementations at largely autonomous VA medical centers.”

In June 2022—a significant month in the whole rollout process—Cerner was acquired by Oracle. By Glueck’s lights, that meant the VA “now has essentially 2 vendors for the price of one—one with extensive clinical expertise and one with extensive engineering expertise.”

Oracle, he said, “is hard at work to stabilize and improve performance; make fixes to functionality and design issues; improve training and build a better user experience.” He noted that significant improvements to the system’s capacity and performance have included reducing the most severe outage incidents by 67%.

In a recent statement, House VA Committee Chairman Mike Bost (R-IL) and Technology Modernization Subcommittee Chairman Matt Rosendale (R-MT) said, “We support Secretary McDonough’s decision in the strongest possible terms. The best way to get out of a hole is to stop digging, and we’re encouraged that VA and Oracle Cerner have finally realized that.”

VA and Oracle Cerner are currently working toward an amended contract that will "increase Oracle Cerner’s accountability to deliver a high-functioning, high-reliability, world-class EHR system,” the VA says. As part of the re-set, the VA also will work with Congress on resource requirements. The VA estimates FY 2023 costs will be reduced by $400 million. 

The painful paused and repaused rollout of the new Cerner electronic health record (EHR) system at the US Department of Veterans Affairs (VA) is now halted as the VA announces a “reset.” The decision applies to all planned deployments. An exception is the Captain James A. Lovell Federal Health Care Center in Chicago, the only fully integrated VA and US Department of Defense (DoD) health care system, which is expected go live in March 2024 as planned. The DoD rollout of its Cerner EHR is further along and expected to be completed in 2024.

The new plan is to redirect resources and “prioritize improvements” at the 5 sites currently using the new EHR: Spokane VA Health Care System, VA Walla Walla Health Care, Roseburg VA Health Care System, VA Southern Oregon Health Care, and VA Central Ohio Health Care System. Additional deployments will not be scheduled, the VA says, until it is confident that the new EHR is highly functioning at the current sites and ready to deliver at future sites, as demonstrated by “clear improvements” in the clinician and veteran experience, sustained high performance and high reliability.

“For the past few years, we’ve tried to fix this plane while flying it—and that hasn’t delivered the results that veterans or our staff deserve,” said Neil Evans, MD, acting program executive director at the Electronic Health Record Modernization Integration Office. “This reset changes that. We are going to take the time necessary to get this right for veterans and VA clinicians alike, and that means focusing our resources solely on improving the EHR at the sites where it is currently in use, and improving its fit for VA more broadly. In doing so, we will enhance the EHR for both current and future users, paving the way for successful future deployments.”  

The various EHR rollouts around the country have been bumpy from the beginning, operating by fits and starts as new problems surfaced and were addressed. To be fair, the whole implementation process only started in 2020 (and deployed at the first VA hospital during the COVID-19 pandemic), but in that time, the VA has had to, in its own words, “revise the timeline” again and again. The Boise VA Medical Center, for instance, was originally scheduled to go live June 25, 2022, then a month later—then 2023.

The VA Office of the Inspector General published 3 reports last year that found significant issues, including improperly routed clinical orders. VA Secretary Denis McDonough announced last July that the VA would delay EHR deployments until January 2023 to ensure that the system’s issues had been resolved. “During VA’s subsequent investigation at our current sites,” he said, “several additional technical and system issues were identified—including challenges with performance, such as latency and slowness, problems with patient scheduling, referrals, medication management, and other types of medical orders.”

In February, Ken Glueck, executive vice president of Oracle, wrote a blog post that was both apologia and explanation. Modernization, he said, “doesn’t come with a magic wand and there’s no easy button.”

After the DoD moved to Cerner for a new EHR system, the VA decided to follow suit. The goal was to create a “seamless, longitudinal record”—and that was the beginning of the largest health IT modernization project in history, Glueck said. And, although he didn’t mention it, the beginning of one of the VA’s biggest headaches. The problem, Glueck wrote, was that the new project involved “standardizing procedures and workflows that may have been different across 130 VistA implementations at largely autonomous VA medical centers.”

In June 2022—a significant month in the whole rollout process—Cerner was acquired by Oracle. By Glueck’s lights, that meant the VA “now has essentially 2 vendors for the price of one—one with extensive clinical expertise and one with extensive engineering expertise.”

Oracle, he said, “is hard at work to stabilize and improve performance; make fixes to functionality and design issues; improve training and build a better user experience.” He noted that significant improvements to the system’s capacity and performance have included reducing the most severe outage incidents by 67%.

In a recent statement, House VA Committee Chairman Mike Bost (R-IL) and Technology Modernization Subcommittee Chairman Matt Rosendale (R-MT) said, “We support Secretary McDonough’s decision in the strongest possible terms. The best way to get out of a hole is to stop digging, and we’re encouraged that VA and Oracle Cerner have finally realized that.”

VA and Oracle Cerner are currently working toward an amended contract that will "increase Oracle Cerner’s accountability to deliver a high-functioning, high-reliability, world-class EHR system,” the VA says. As part of the re-set, the VA also will work with Congress on resource requirements. The VA estimates FY 2023 costs will be reduced by $400 million. 

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

The combination of a patient-specific mRNA-based cancer vaccine (mRNA-4157/V940, Moderna and Merck) and the immune checkpoint inhibitor pembrolizumab significantly improved recurrence-free survival for patients with high-risk melanoma compared with pembrolizumab alone, according to the latest data from the KEYNOTE-942 trial.

This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.

The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.

“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.

“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.

Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
 

A promising personalized vaccine

The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.

Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”

The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.

The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.

“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.

In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.

Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).

Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.

In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.

The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.

Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).

The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).

The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.

Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.

The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”

Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.

KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
 

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

The combination of a patient-specific mRNA-based cancer vaccine (mRNA-4157/V940, Moderna and Merck) and the immune checkpoint inhibitor pembrolizumab significantly improved recurrence-free survival for patients with high-risk melanoma compared with pembrolizumab alone, according to the latest data from the KEYNOTE-942 trial.

This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.

The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.

“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.

“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.

Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
 

A promising personalized vaccine

The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.

Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”

The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.

The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.

“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.

In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.

Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).

Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.

In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.

The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.

Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).

The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).

The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.

Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.

The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”

Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.

KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
 

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

The combination of a patient-specific mRNA-based cancer vaccine (mRNA-4157/V940, Moderna and Merck) and the immune checkpoint inhibitor pembrolizumab significantly improved recurrence-free survival for patients with high-risk melanoma compared with pembrolizumab alone, according to the latest data from the KEYNOTE-942 trial.

This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.

The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.

“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.

“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.

Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
 

A promising personalized vaccine

The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.

Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”

The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.

The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.

“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.

In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.

Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).

Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.

In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.

The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.

Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).

The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).

The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.

Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.

The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”

Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.

KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
 

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

Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.

But a new analysis of breast cancer deaths supports a “race and ethnicity-adapted” approach to breast screening, with Black women starting screening 8 years sooner – at age 42.

The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.

The study was published online in JAMA Network Open.

Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.

Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.

“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”

The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.

Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.

The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.

For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).

If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.

If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.

If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.

Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.

“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.

Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.

“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”

The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
 

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

The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.

But a new analysis of breast cancer deaths supports a “race and ethnicity-adapted” approach to breast screening, with Black women starting screening 8 years sooner – at age 42.

The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.

The study was published online in JAMA Network Open.

Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.

Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.

“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”

The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.

Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.

The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.

For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).

If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.

If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.

If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.

Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.

“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.

Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.

“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”

The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
 

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

The U.S. Preventive Services Task Force currently recommends that breast cancer screening start at age 50 years, regardless of race or ethnicity.

But a new analysis of breast cancer deaths supports a “race and ethnicity-adapted” approach to breast screening, with Black women starting screening 8 years sooner – at age 42.

The current “one-size-fits-all” policy to screen the entire female population from a certain age may be “neither fair and equitable nor optimal,” noted the authors, led by Tianhui Chen, PhD, with Zhejiang Cancer Hospital, Hangzhou, China.

The study was published online in JAMA Network Open.

Laurie R. Margolies, MD, chief of breast imaging at the Dubin Breast Center of the Mount Sinai Tisch Cancer Center in New York City, agreed.

Black women get breast cancer at a much younger age, are less likely to be diagnosed with early breast cancer, and are more likely to die of breast cancer, explained Dr. Margolies, who was not involved in the study.

“That’s why the guidelines that say begin at age 50 are flawed and so dangerous,” she said in an interview with this news organization. “This study is really important to highlight that we’re missing an opportunity to detect and treat breast cancer early in the Black population.”

The current study explored the optimal race- and ethnicity-specific ages to initiate breast cancer screening to address racial disparities in breast cancer mortality.

Using a nationwide population-based cross-sectional study design, the team analyzed data on 415,277 women who died of breast cancer in the United States from 2011 to 2020.

The cohort was 75% White, 15% Black, 7% Hispanic, 3% Asian or Pacific Islander, and < 1% Native American or Alaska Native. A total of 115,214 women (28%) died before age 60. The team calculated the 10-year cumulative risk of breast cancer–specific death by age and by race and ethnicity.

For those aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years), followed by White women (15 deaths per 100,000 person-years) and American Indian/Alaska Native, Hispanic, and Asian/Pacific Islander women (11 deaths per 100,000 person-years).

If breast screening started at age 50 for the entire population, the mean 10-year cumulative risk of dying from breast cancer would be 0.329%. Black women reached this risk threshold level at age 42, whereas non-Hispanic White women reached the threshold at age 51, American Indian/Alaska Native and Hispanic women at age 57, and Asian/Pacific Islander women at age 61.

If screening started at age 45 for all women, the mean 10-year cumulative risk of breast cancer death would be 0.235%. Black women reached this risk threshold level at age 38, non-Hispanic White women at age 46, Hispanic women at age 49, Asian/Pacific Islander women at age 50, and American Indian/Alaska Native women at age 51.

If screening started at age 40 for all women, with a mean 10-year cumulative risk of 0.154%, Black women would reach this risk threshold at age 34, White women at age 41, Hispanic women at age 43, and American Indian/Alaska Native and Asian/Pacific Islander women at age 43.

Dr. Chen and colleagues concluded that failure to consider race and ethnicity in breast cancer screening guidelines “may pose a significant risk for greater harm to a group already at increased risk.

“Changing guidelines based on readily available risk factors, such as race and ethnicity, is possible and may be the first, yet important step toward a personalized and fair screening program,” the team explained.

Dr. Margolies said she believes individualized screening recommendations will likely come, but first, all women should start screening at age 40 instead of age 50.

“Most American women are starting in their 40s, or starting at 40, because we know what the current guidelines are,” she said. “The question that this study doesn’t answer is, is age 40 young enough for the Black population? Maybe it should be 35.”

The study was supported by grants from the National Key Research-Development Program of China and from the Ten-Thousand Talents Plan of Zhejiang Province and by Start-Up Funds for Recruited Talents in Zhejiang Cancer Hospital. Dr. Chen and Dr. Margolies have disclosed no relevant financial relationships.
 

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