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The Importance of Adjuvant Treatment and Primary Anatomical Site in Head and Neck Basaloid Squamous Cell Carcinoma Survival: An Analysis of the National Cancer Database
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that account for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within basaloid squamous cell carcinoma subtype and its impact on survival.
METHODS: A cohort of 1,999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy.
RESULTS: In this cohort, 82% were male with a median age of 59 years. The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The majority of the cohort had stage IV disease, while 3.9% had metastases. The presence of metastasis increased probability of mortality (HR=2.14; 95% CI: 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR=2.45; 95% CI: 1.83-3.29), hypopharynx (HR=2.58; 95% CI: 1.64-4.05), and larynx (HR=2.89; 95% CI: 2.25-3.73). Adjuvant chemoradiation (HR=0.36; 95% CI: 0.23-0.58) and adjuvant radiation (HR=0.38; 95% CI: 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy alone. Patients with microscopic tumor margins had better survival outcomes when compared to no surgery (HR=0.38, 98% Cl: 0.23-0.64) while there was no better survival outcomes of patients with macroscopic margins compared to no surgery.
CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, microscopic margins or residual tumor were associated with greater survival. This study demonstrates the importance of these factors as independent prognostic factors when considering survival of patients diagnosed with BSCC of the head and neck.
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that account for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within basaloid squamous cell carcinoma subtype and its impact on survival.
METHODS: A cohort of 1,999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy.
RESULTS: In this cohort, 82% were male with a median age of 59 years. The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The majority of the cohort had stage IV disease, while 3.9% had metastases. The presence of metastasis increased probability of mortality (HR=2.14; 95% CI: 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR=2.45; 95% CI: 1.83-3.29), hypopharynx (HR=2.58; 95% CI: 1.64-4.05), and larynx (HR=2.89; 95% CI: 2.25-3.73). Adjuvant chemoradiation (HR=0.36; 95% CI: 0.23-0.58) and adjuvant radiation (HR=0.38; 95% CI: 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy alone. Patients with microscopic tumor margins had better survival outcomes when compared to no surgery (HR=0.38, 98% Cl: 0.23-0.64) while there was no better survival outcomes of patients with macroscopic margins compared to no surgery.
CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, microscopic margins or residual tumor were associated with greater survival. This study demonstrates the importance of these factors as independent prognostic factors when considering survival of patients diagnosed with BSCC of the head and neck.
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that account for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within basaloid squamous cell carcinoma subtype and its impact on survival.
METHODS: A cohort of 1,999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy.
RESULTS: In this cohort, 82% were male with a median age of 59 years. The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The majority of the cohort had stage IV disease, while 3.9% had metastases. The presence of metastasis increased probability of mortality (HR=2.14; 95% CI: 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR=2.45; 95% CI: 1.83-3.29), hypopharynx (HR=2.58; 95% CI: 1.64-4.05), and larynx (HR=2.89; 95% CI: 2.25-3.73). Adjuvant chemoradiation (HR=0.36; 95% CI: 0.23-0.58) and adjuvant radiation (HR=0.38; 95% CI: 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy alone. Patients with microscopic tumor margins had better survival outcomes when compared to no surgery (HR=0.38, 98% Cl: 0.23-0.64) while there was no better survival outcomes of patients with macroscopic margins compared to no surgery.
CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, microscopic margins or residual tumor were associated with greater survival. This study demonstrates the importance of these factors as independent prognostic factors when considering survival of patients diagnosed with BSCC of the head and neck.
Delaying RT for higher-risk prostate cancer found safe
A study of more than 60,000 prostate cancer patients suggests it is safe to delay radiation therapy (RT) for at least 6 months for localized higher-risk disease being treated with androgen deprivation therapy.
These findings are relevant to oncology care in the COVID-19 era, as the pandemic has complicated delivery of radiation therapy (RT) in several ways, the study authors wrote in JAMA Oncology.
“Daily hospital trips for RT create many possible points of COVID-19 transmission, and patients with cancer are at high risk of COVID-19 mortality,” Edward Christopher Dee, a research fellow at Dana-Farber Cancer Institute in Boston, and colleagues wrote.
To assess the safety of delaying RT, the investigators analyzed National Cancer Database data for 63,858 men with localized but unfavorable intermediate-risk, high-risk, or very-high-risk prostate cancer diagnosed during 2004-2014 and managed with external beam RT and androgen deprivation therapy (ADT).
Only 5.6% of patients (n = 3,572) initiated their RT 0-60 days before starting ADT. Another 36.3% (n = 23,207) initiated RT 1-60 days after starting ADT, 47.4% (n = 30,285) initiated RT 61-120 days after starting ADT, and 10.6% (n = 6,794) initiated RT 121-180 days after starting ADT.
The investigators found that 10-year overall survival rates were similar regardless of when patients started RT.
Multivariate analysis in the unfavorable intermediate-risk group showed that, relative to peers who started RT before ADT, men initiating RT later did not have significantly poorer overall survival, regardless of whether RT was initiated 1-60 days after starting ADT (hazard ratio for death, 1.03; P = .64), 61-120 days after (HR, 0.95; P = .42), or 121-180 days after (HR, 0.99; P = .90).
Findings were similar in the combined high-risk and very-high-risk group, with no significant elevation of mortality risk for patients initiating RT 1-60 days after starting ADT (HR, 1.07; P = .12), 61-120 days after (HR, 1.04; P = .36), or 121-180 days after (HR, 1.07; P = .17).
“These results validate the findings of two prior randomized trials and possibly justify the delay of prostate RT for patients currently receiving ADT until COVID-19 infection rates in the community and hospitals are lower,” the authors wrote.
Despite the fairly short follow-up period and other study limitations, “if COVID-19 outbreaks continue to occur sporadically during the coming months to years, these data could allow future flexibility about the timing of RT initiation,” the authors concluded.
Experts weigh in
“Overall, this study is asking a good question given the COVID situation and the fact that many providers are delaying RT due to COVID concerns of patients and providers,” Colleen A. Lawton, MD, of the Medical College of Wisconsin, Milwaukee, commented in an interview.
At the same time, Dr. Lawton cautioned about oversimplifying the issue, noting that results of the Radiation Therapy Oncology Group (RTOG) 9413 trial suggest important interactions between the anatomic extent of RT and the timing of ADT on outcomes (Int J Radiat Oncol Biol Phys. 2007 Nov 1;69[3]:646-55).
“I have certainly delayed some of my own patients with ADT during the COVID pandemic,” she reported. “No one knows what the maximum acceptable delay should be. A few months is likely not a problem, and a year is probably too much, but scientifically, we just don’t know.”
The interplay of volume irradiated and ADT timing is relevant here, agreed Mack Roach III, MD, of University of California, San Francisco.
In addition, the study did not address why ADT was given when it was, the duration of this therapy, and endpoints other than overall survival (such as prostate-specific antigen failure rate) that may better reflect the effectiveness of cancer treatment.
“Yes, delays are safe for patients on ADT, but not for the reasons stated. A more appropriate source of data is RTOG 9910, which compared 28 versus 8 weeks of ADT prior to RT for mostly intermediate-risk prostate cancer patients with comparable results,” Dr. Roach noted (J Clin Oncol. 2015 Feb 1;33[4]:332-9).
“Delay duration should be based on the risk of disease, but 6 months is probably safe, especially if on ADT,” he said.
Michael J. Zelefsky, MD, of Memorial Sloan Kettering Cancer Center in New York, said he agreed with the investigators’ main conclusions. “Once ADT suppression is achieved, maintaining patients on this regimen for 6 months would not likely lead to the development of a castrate-resistant state where radiotherapy would be less effective,” he elaborated.
However, limitations of the database used preclude conclusions about the safety of longer delays or the impact on other outcomes, he cautioned.
“This study provides further support to the accepted notion that delays of up to 6 months prior to initiation of planned prostate radiation would be safe and appropriate, especially where concerns of COVID outbreaks may present significant logistic challenges and concerns for the patient, who needs to commit to a course of daily radiation treatments, which could span for 5-8 weeks,” Dr. Zelefsky said.
“We have, in fact, adopted this approach in our clinics during the COVID outbreaks in New York,” he reported. “Most of our patients with unfavorable intermediate- or high-risk disease were initiated on ADT planned for at least 4-6 months before the radiotherapy was initiated. In addition, for these reasons, our preference has been to also offer such patients, if feasible, an ultrahypofractionated treatment course where the radiotherapy course is completed in five fractions over 1-2 weeks.”
This research was funded by the National Institutes of Health. The authors disclosed various grants and personal fees outside the submitted work. Dr. Lawton disclosed that she was a coauthor on RTOG 9413. Dr. Roach and Dr. Zelefsky disclosed no relevant conflicts of interest.
SOURCE: Dee EC et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.3545.
A study of more than 60,000 prostate cancer patients suggests it is safe to delay radiation therapy (RT) for at least 6 months for localized higher-risk disease being treated with androgen deprivation therapy.
These findings are relevant to oncology care in the COVID-19 era, as the pandemic has complicated delivery of radiation therapy (RT) in several ways, the study authors wrote in JAMA Oncology.
“Daily hospital trips for RT create many possible points of COVID-19 transmission, and patients with cancer are at high risk of COVID-19 mortality,” Edward Christopher Dee, a research fellow at Dana-Farber Cancer Institute in Boston, and colleagues wrote.
To assess the safety of delaying RT, the investigators analyzed National Cancer Database data for 63,858 men with localized but unfavorable intermediate-risk, high-risk, or very-high-risk prostate cancer diagnosed during 2004-2014 and managed with external beam RT and androgen deprivation therapy (ADT).
Only 5.6% of patients (n = 3,572) initiated their RT 0-60 days before starting ADT. Another 36.3% (n = 23,207) initiated RT 1-60 days after starting ADT, 47.4% (n = 30,285) initiated RT 61-120 days after starting ADT, and 10.6% (n = 6,794) initiated RT 121-180 days after starting ADT.
The investigators found that 10-year overall survival rates were similar regardless of when patients started RT.
Multivariate analysis in the unfavorable intermediate-risk group showed that, relative to peers who started RT before ADT, men initiating RT later did not have significantly poorer overall survival, regardless of whether RT was initiated 1-60 days after starting ADT (hazard ratio for death, 1.03; P = .64), 61-120 days after (HR, 0.95; P = .42), or 121-180 days after (HR, 0.99; P = .90).
Findings were similar in the combined high-risk and very-high-risk group, with no significant elevation of mortality risk for patients initiating RT 1-60 days after starting ADT (HR, 1.07; P = .12), 61-120 days after (HR, 1.04; P = .36), or 121-180 days after (HR, 1.07; P = .17).
“These results validate the findings of two prior randomized trials and possibly justify the delay of prostate RT for patients currently receiving ADT until COVID-19 infection rates in the community and hospitals are lower,” the authors wrote.
Despite the fairly short follow-up period and other study limitations, “if COVID-19 outbreaks continue to occur sporadically during the coming months to years, these data could allow future flexibility about the timing of RT initiation,” the authors concluded.
Experts weigh in
“Overall, this study is asking a good question given the COVID situation and the fact that many providers are delaying RT due to COVID concerns of patients and providers,” Colleen A. Lawton, MD, of the Medical College of Wisconsin, Milwaukee, commented in an interview.
At the same time, Dr. Lawton cautioned about oversimplifying the issue, noting that results of the Radiation Therapy Oncology Group (RTOG) 9413 trial suggest important interactions between the anatomic extent of RT and the timing of ADT on outcomes (Int J Radiat Oncol Biol Phys. 2007 Nov 1;69[3]:646-55).
“I have certainly delayed some of my own patients with ADT during the COVID pandemic,” she reported. “No one knows what the maximum acceptable delay should be. A few months is likely not a problem, and a year is probably too much, but scientifically, we just don’t know.”
The interplay of volume irradiated and ADT timing is relevant here, agreed Mack Roach III, MD, of University of California, San Francisco.
In addition, the study did not address why ADT was given when it was, the duration of this therapy, and endpoints other than overall survival (such as prostate-specific antigen failure rate) that may better reflect the effectiveness of cancer treatment.
“Yes, delays are safe for patients on ADT, but not for the reasons stated. A more appropriate source of data is RTOG 9910, which compared 28 versus 8 weeks of ADT prior to RT for mostly intermediate-risk prostate cancer patients with comparable results,” Dr. Roach noted (J Clin Oncol. 2015 Feb 1;33[4]:332-9).
“Delay duration should be based on the risk of disease, but 6 months is probably safe, especially if on ADT,” he said.
Michael J. Zelefsky, MD, of Memorial Sloan Kettering Cancer Center in New York, said he agreed with the investigators’ main conclusions. “Once ADT suppression is achieved, maintaining patients on this regimen for 6 months would not likely lead to the development of a castrate-resistant state where radiotherapy would be less effective,” he elaborated.
However, limitations of the database used preclude conclusions about the safety of longer delays or the impact on other outcomes, he cautioned.
“This study provides further support to the accepted notion that delays of up to 6 months prior to initiation of planned prostate radiation would be safe and appropriate, especially where concerns of COVID outbreaks may present significant logistic challenges and concerns for the patient, who needs to commit to a course of daily radiation treatments, which could span for 5-8 weeks,” Dr. Zelefsky said.
“We have, in fact, adopted this approach in our clinics during the COVID outbreaks in New York,” he reported. “Most of our patients with unfavorable intermediate- or high-risk disease were initiated on ADT planned for at least 4-6 months before the radiotherapy was initiated. In addition, for these reasons, our preference has been to also offer such patients, if feasible, an ultrahypofractionated treatment course where the radiotherapy course is completed in five fractions over 1-2 weeks.”
This research was funded by the National Institutes of Health. The authors disclosed various grants and personal fees outside the submitted work. Dr. Lawton disclosed that she was a coauthor on RTOG 9413. Dr. Roach and Dr. Zelefsky disclosed no relevant conflicts of interest.
SOURCE: Dee EC et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.3545.
A study of more than 60,000 prostate cancer patients suggests it is safe to delay radiation therapy (RT) for at least 6 months for localized higher-risk disease being treated with androgen deprivation therapy.
These findings are relevant to oncology care in the COVID-19 era, as the pandemic has complicated delivery of radiation therapy (RT) in several ways, the study authors wrote in JAMA Oncology.
“Daily hospital trips for RT create many possible points of COVID-19 transmission, and patients with cancer are at high risk of COVID-19 mortality,” Edward Christopher Dee, a research fellow at Dana-Farber Cancer Institute in Boston, and colleagues wrote.
To assess the safety of delaying RT, the investigators analyzed National Cancer Database data for 63,858 men with localized but unfavorable intermediate-risk, high-risk, or very-high-risk prostate cancer diagnosed during 2004-2014 and managed with external beam RT and androgen deprivation therapy (ADT).
Only 5.6% of patients (n = 3,572) initiated their RT 0-60 days before starting ADT. Another 36.3% (n = 23,207) initiated RT 1-60 days after starting ADT, 47.4% (n = 30,285) initiated RT 61-120 days after starting ADT, and 10.6% (n = 6,794) initiated RT 121-180 days after starting ADT.
The investigators found that 10-year overall survival rates were similar regardless of when patients started RT.
Multivariate analysis in the unfavorable intermediate-risk group showed that, relative to peers who started RT before ADT, men initiating RT later did not have significantly poorer overall survival, regardless of whether RT was initiated 1-60 days after starting ADT (hazard ratio for death, 1.03; P = .64), 61-120 days after (HR, 0.95; P = .42), or 121-180 days after (HR, 0.99; P = .90).
Findings were similar in the combined high-risk and very-high-risk group, with no significant elevation of mortality risk for patients initiating RT 1-60 days after starting ADT (HR, 1.07; P = .12), 61-120 days after (HR, 1.04; P = .36), or 121-180 days after (HR, 1.07; P = .17).
“These results validate the findings of two prior randomized trials and possibly justify the delay of prostate RT for patients currently receiving ADT until COVID-19 infection rates in the community and hospitals are lower,” the authors wrote.
Despite the fairly short follow-up period and other study limitations, “if COVID-19 outbreaks continue to occur sporadically during the coming months to years, these data could allow future flexibility about the timing of RT initiation,” the authors concluded.
Experts weigh in
“Overall, this study is asking a good question given the COVID situation and the fact that many providers are delaying RT due to COVID concerns of patients and providers,” Colleen A. Lawton, MD, of the Medical College of Wisconsin, Milwaukee, commented in an interview.
At the same time, Dr. Lawton cautioned about oversimplifying the issue, noting that results of the Radiation Therapy Oncology Group (RTOG) 9413 trial suggest important interactions between the anatomic extent of RT and the timing of ADT on outcomes (Int J Radiat Oncol Biol Phys. 2007 Nov 1;69[3]:646-55).
“I have certainly delayed some of my own patients with ADT during the COVID pandemic,” she reported. “No one knows what the maximum acceptable delay should be. A few months is likely not a problem, and a year is probably too much, but scientifically, we just don’t know.”
The interplay of volume irradiated and ADT timing is relevant here, agreed Mack Roach III, MD, of University of California, San Francisco.
In addition, the study did not address why ADT was given when it was, the duration of this therapy, and endpoints other than overall survival (such as prostate-specific antigen failure rate) that may better reflect the effectiveness of cancer treatment.
“Yes, delays are safe for patients on ADT, but not for the reasons stated. A more appropriate source of data is RTOG 9910, which compared 28 versus 8 weeks of ADT prior to RT for mostly intermediate-risk prostate cancer patients with comparable results,” Dr. Roach noted (J Clin Oncol. 2015 Feb 1;33[4]:332-9).
“Delay duration should be based on the risk of disease, but 6 months is probably safe, especially if on ADT,” he said.
Michael J. Zelefsky, MD, of Memorial Sloan Kettering Cancer Center in New York, said he agreed with the investigators’ main conclusions. “Once ADT suppression is achieved, maintaining patients on this regimen for 6 months would not likely lead to the development of a castrate-resistant state where radiotherapy would be less effective,” he elaborated.
However, limitations of the database used preclude conclusions about the safety of longer delays or the impact on other outcomes, he cautioned.
“This study provides further support to the accepted notion that delays of up to 6 months prior to initiation of planned prostate radiation would be safe and appropriate, especially where concerns of COVID outbreaks may present significant logistic challenges and concerns for the patient, who needs to commit to a course of daily radiation treatments, which could span for 5-8 weeks,” Dr. Zelefsky said.
“We have, in fact, adopted this approach in our clinics during the COVID outbreaks in New York,” he reported. “Most of our patients with unfavorable intermediate- or high-risk disease were initiated on ADT planned for at least 4-6 months before the radiotherapy was initiated. In addition, for these reasons, our preference has been to also offer such patients, if feasible, an ultrahypofractionated treatment course where the radiotherapy course is completed in five fractions over 1-2 weeks.”
This research was funded by the National Institutes of Health. The authors disclosed various grants and personal fees outside the submitted work. Dr. Lawton disclosed that she was a coauthor on RTOG 9413. Dr. Roach and Dr. Zelefsky disclosed no relevant conflicts of interest.
SOURCE: Dee EC et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.3545.
FROM JAMA ONCOLOGY
The Impact of Sequencing of Abiraterone and Enzalutamide in Veterans With Metastatic Castration- Resistant Prostate Cancer
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC). BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC). BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC). BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
The Impact of Sequencing of Abiraterone and Enzalutamide in Veterans With Metastatic Castration- Resistant Prostate Cancer
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC).
BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC).
BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
PURPOSE: To evaluate outcomes of disease progression based on the sequence of abiraterone and enzalutamide in veterans diagnosed with metastatic castration-resistant prostate cancer (mCRPC).
BACKGROUND: Two of the current options for mCRPC treatment are the novel oral hormonal agents abiraterone and enzalutamide. After progression on one of these agents, one option is to switch to the other agent not previously used. Previously published retrospective studies and one prospective study have shown a difference in outcomes favoring abiraterone followed by enzalutamide, while others have shown no difference based on sequence. The optimal sequence of abiraterone and enzalutamide is still unclear.
METHODS: This was a retrospective chart review of patients who received abiraterone and enzalutamide in sequence for the treatment of mCRPC within our healthcare system from April 28, 2011 through October 31, 2019. Baseline demographic information such as age, race, Gleason score, and prior treatments were collected. The primary outcome was combined prostate-specific antigen progression-free survival (cPSA-PFS). Secondary outcomes included radiographic PFS (rPFS), overall survival (OS), adverse events causing treatment discontinuation, and medication adherence. Between-group survival differences were estimated by the Kaplan-Meier method and an unadjusted Cox regression model.
RESULTS: A total of 77 patients met criteria for study inclusion, with 51 in the abiraterone-to-enzalutamide group (ABI-ENZ) and 26 in the enzalutamide-to-abiraterone group (ENZ-ABI). For the primary outcome of cPSA-PFS, the median survival of the ABI-ENZ and ENZ-ABI groups was 17.3 months (95% CI, 10.3-24.3 months) and 10.2 months (95% CI, 8.5-11.8 months), respectively, which was significantly different (log-rank P=0.009) in favor of the ABI-ENZ sequence (HR 0.46; 95% CI, 0.26-0.83). Secondary outcomes of rPFS and OS were not significantly different between groups.
CONCLUSION: This study adds to the evidence supporting the sequence of abiraterone before enzalutamide for improving PSA-PFS. It is thought this might be related to differences in mechanisms of resistance between the two drugs. This benefit has not yet translated to an improvement in rPFS and OS. Based on the results of this study in conjunction with previously published studies, use of abiraterone before enzalutamide should be considered over the alternate sequence.
The Effect of Treatment Facility and Race on Survival for Signet Ring Cell Carcinoma of the Esophagus: An Analysis of the National Cancer Database
BACKGROUND: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this study is to assess differences in survival based on the type of treatment facility.
METHODS: There were 1,442 patients with SRCCE identified using the histology 8490 and topography codes C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a multivariable Cox hazard regression analysis were all utilized to determine the significance and impact of treatment facility type, race, age, sex, tumor stage, use of adjuvant or neoadjuvant radiation, and surgical margins on survival.
RESULTS: The cohort was mostly male (86.6%) and Non-Hispanic Caucasian (96.3%) with 52.7% receiving treatment at academic centers followed by 35.9% at community programs and 11.4% at integrated cancer programs. As age increased, mortality also increased (HR = 1.02; 95% CI: 1.01-1.02, p < 0.001). Both Hispanic Caucasians (HR = 2.09; 95% CI: 1.21-3.62, = 0.009) and Africans Americans (HR = 1.69; 95% CI: 1.04-2.75, = 0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at academic facilities demonstrated a decreased risk of mortality when compared to community programs (HR = 0.73; 95% CI: 0.63-0.86, p < 0.001) and integrated cancer programs (HR = 0.74; 95% CI: 0.60- 0.93, = 0.008).
CONCLUSION: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better survival probabilities compared to nonacademic facilities. Older patients, African Americans and Hispanic Caucasians, increasing tumor stage, positive surgical margins, and comorbidities with Charlson- Deyo scores of 1 and 2+ were all associated with an increased risk of mortality from SRCCE.
BACKGROUND: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this study is to assess differences in survival based on the type of treatment facility.
METHODS: There were 1,442 patients with SRCCE identified using the histology 8490 and topography codes C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a multivariable Cox hazard regression analysis were all utilized to determine the significance and impact of treatment facility type, race, age, sex, tumor stage, use of adjuvant or neoadjuvant radiation, and surgical margins on survival.
RESULTS: The cohort was mostly male (86.6%) and Non-Hispanic Caucasian (96.3%) with 52.7% receiving treatment at academic centers followed by 35.9% at community programs and 11.4% at integrated cancer programs. As age increased, mortality also increased (HR = 1.02; 95% CI: 1.01-1.02, p < 0.001). Both Hispanic Caucasians (HR = 2.09; 95% CI: 1.21-3.62, = 0.009) and Africans Americans (HR = 1.69; 95% CI: 1.04-2.75, = 0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at academic facilities demonstrated a decreased risk of mortality when compared to community programs (HR = 0.73; 95% CI: 0.63-0.86, p < 0.001) and integrated cancer programs (HR = 0.74; 95% CI: 0.60- 0.93, = 0.008).
CONCLUSION: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better survival probabilities compared to nonacademic facilities. Older patients, African Americans and Hispanic Caucasians, increasing tumor stage, positive surgical margins, and comorbidities with Charlson- Deyo scores of 1 and 2+ were all associated with an increased risk of mortality from SRCCE.
BACKGROUND: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this study is to assess differences in survival based on the type of treatment facility.
METHODS: There were 1,442 patients with SRCCE identified using the histology 8490 and topography codes C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a multivariable Cox hazard regression analysis were all utilized to determine the significance and impact of treatment facility type, race, age, sex, tumor stage, use of adjuvant or neoadjuvant radiation, and surgical margins on survival.
RESULTS: The cohort was mostly male (86.6%) and Non-Hispanic Caucasian (96.3%) with 52.7% receiving treatment at academic centers followed by 35.9% at community programs and 11.4% at integrated cancer programs. As age increased, mortality also increased (HR = 1.02; 95% CI: 1.01-1.02, p < 0.001). Both Hispanic Caucasians (HR = 2.09; 95% CI: 1.21-3.62, = 0.009) and Africans Americans (HR = 1.69; 95% CI: 1.04-2.75, = 0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at academic facilities demonstrated a decreased risk of mortality when compared to community programs (HR = 0.73; 95% CI: 0.63-0.86, p < 0.001) and integrated cancer programs (HR = 0.74; 95% CI: 0.60- 0.93, = 0.008).
CONCLUSION: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better survival probabilities compared to nonacademic facilities. Older patients, African Americans and Hispanic Caucasians, increasing tumor stage, positive surgical margins, and comorbidities with Charlson- Deyo scores of 1 and 2+ were all associated with an increased risk of mortality from SRCCE.
The Association of Modifiable Baseline Risk Factors with a Diagnosis of Advanced Neoplasia Among an Asymptomatic Veteran Population
BACKGROUND: Colorectal cancer (CRC) screening guidelines generally recommend healthy lifestyle choices for cancer prevention. However, studies have shown inconsistent associations between various risk factors and advanced neoplasia (AN) development. AIM: To identify potentially modifiable baseline dietary and lifestyle risk factors associated with AN among an asymptomatic Veteran population, while accounting for prior colonoscopic findings and varying surveillance intensity.
METHODS: We used data from a prospective colonoscopy screening study collected by the VA Cooperative Studies Program. From 1994 to 1997, 3,121 asymptomatic Veterans aged 50-75 received a baseline colonoscopy screening, at which time they selfreported dietary and lifestyle information. Veterans were subsequently assigned to colonoscopy surveillance regimens and followed for 10 years. AN was defined as invasive CRC or any adenoma ≥1 cm, or with villous histology, or high-grade dysplasia. To detect associations with AN diagnosis, we utilized a longitudinal joint model with two sub-models. A multivariate logistic regression modeled the longitudinal probability of AN, while a time-to-event process adjusted for survival. Here we focus on the multivariate logistic regression, representing associations of dietary and lifestyle risk factors with the odds of being diagnosed with AN.
RESULTS: Of the 3,121 Veterans, 1,915 received at least one colonoscopy following baseline screening. Among the 1,915, we detected a significant positive association with AN for current daily smokers (odds ratio (OR) 1.43, 95% CI: 1.02-2.01) compared to those with prior or no history. We found a protective effect for each 100 IU of dietary vitamin D consumed (OR 0.95, 95% CI: 0.95-0.99). We did not detect any significant associations with BMI, red meat consumption, or physical activity. We found that African American race had a lower odds of AN compared to Caucasian race (OR 0.57, 95% CI: 0.32-0.97).
CONCLUSIONS: We identified smoking status and vitamin D consumption as potentially modifiable baseline risk factors associated with AN development. While these results suggest possible points of intervention and targeted screening, more evidence is required across more diverse populations. Future efforts should focus on understanding changes in such risk factors on associations with AN for patients over time. Finally, racial differences in AN incidence merit further investigation.
BACKGROUND: Colorectal cancer (CRC) screening guidelines generally recommend healthy lifestyle choices for cancer prevention. However, studies have shown inconsistent associations between various risk factors and advanced neoplasia (AN) development. AIM: To identify potentially modifiable baseline dietary and lifestyle risk factors associated with AN among an asymptomatic Veteran population, while accounting for prior colonoscopic findings and varying surveillance intensity.
METHODS: We used data from a prospective colonoscopy screening study collected by the VA Cooperative Studies Program. From 1994 to 1997, 3,121 asymptomatic Veterans aged 50-75 received a baseline colonoscopy screening, at which time they selfreported dietary and lifestyle information. Veterans were subsequently assigned to colonoscopy surveillance regimens and followed for 10 years. AN was defined as invasive CRC or any adenoma ≥1 cm, or with villous histology, or high-grade dysplasia. To detect associations with AN diagnosis, we utilized a longitudinal joint model with two sub-models. A multivariate logistic regression modeled the longitudinal probability of AN, while a time-to-event process adjusted for survival. Here we focus on the multivariate logistic regression, representing associations of dietary and lifestyle risk factors with the odds of being diagnosed with AN.
RESULTS: Of the 3,121 Veterans, 1,915 received at least one colonoscopy following baseline screening. Among the 1,915, we detected a significant positive association with AN for current daily smokers (odds ratio (OR) 1.43, 95% CI: 1.02-2.01) compared to those with prior or no history. We found a protective effect for each 100 IU of dietary vitamin D consumed (OR 0.95, 95% CI: 0.95-0.99). We did not detect any significant associations with BMI, red meat consumption, or physical activity. We found that African American race had a lower odds of AN compared to Caucasian race (OR 0.57, 95% CI: 0.32-0.97).
CONCLUSIONS: We identified smoking status and vitamin D consumption as potentially modifiable baseline risk factors associated with AN development. While these results suggest possible points of intervention and targeted screening, more evidence is required across more diverse populations. Future efforts should focus on understanding changes in such risk factors on associations with AN for patients over time. Finally, racial differences in AN incidence merit further investigation.
BACKGROUND: Colorectal cancer (CRC) screening guidelines generally recommend healthy lifestyle choices for cancer prevention. However, studies have shown inconsistent associations between various risk factors and advanced neoplasia (AN) development. AIM: To identify potentially modifiable baseline dietary and lifestyle risk factors associated with AN among an asymptomatic Veteran population, while accounting for prior colonoscopic findings and varying surveillance intensity.
METHODS: We used data from a prospective colonoscopy screening study collected by the VA Cooperative Studies Program. From 1994 to 1997, 3,121 asymptomatic Veterans aged 50-75 received a baseline colonoscopy screening, at which time they selfreported dietary and lifestyle information. Veterans were subsequently assigned to colonoscopy surveillance regimens and followed for 10 years. AN was defined as invasive CRC or any adenoma ≥1 cm, or with villous histology, or high-grade dysplasia. To detect associations with AN diagnosis, we utilized a longitudinal joint model with two sub-models. A multivariate logistic regression modeled the longitudinal probability of AN, while a time-to-event process adjusted for survival. Here we focus on the multivariate logistic regression, representing associations of dietary and lifestyle risk factors with the odds of being diagnosed with AN.
RESULTS: Of the 3,121 Veterans, 1,915 received at least one colonoscopy following baseline screening. Among the 1,915, we detected a significant positive association with AN for current daily smokers (odds ratio (OR) 1.43, 95% CI: 1.02-2.01) compared to those with prior or no history. We found a protective effect for each 100 IU of dietary vitamin D consumed (OR 0.95, 95% CI: 0.95-0.99). We did not detect any significant associations with BMI, red meat consumption, or physical activity. We found that African American race had a lower odds of AN compared to Caucasian race (OR 0.57, 95% CI: 0.32-0.97).
CONCLUSIONS: We identified smoking status and vitamin D consumption as potentially modifiable baseline risk factors associated with AN development. While these results suggest possible points of intervention and targeted screening, more evidence is required across more diverse populations. Future efforts should focus on understanding changes in such risk factors on associations with AN for patients over time. Finally, racial differences in AN incidence merit further investigation.
Short Story Clubs to Decrease Burnout
Burnout is common in hematology/oncology practice where work pressure is high, patients are complex, and outcomes are variable. We hypothesized that a short story club could be helpful to improve community, humanism, and transcendence; and thereby to decrease burnout. Most of the potential participants indicated little time for preparation and we, therefore, chose short stories rather than books as reading material. The meetings began in April 2019 and continued until April 2020 when they were suspended for the COVID-19 epidemic. Participants included oncologists (6), oncology fellows (2), psychologist (1), social workers (2), research writer (1) and, student (1). Of these, 7 were females and 6 were males; 4 in senior and 9 in junior positions. Country of origin of participants was USA (6), India (3), Syria (2), Pakistan (1) and, Poland (1). Meetings were held every two months, each time with different stories, focus, themes, and points of view. Readings included classical stories, modern stories, and personal essays, from the eyes of other oncologists, country doctor, patients, nurses, or students. Stories included “The Doctor” by Chekhov, “The Country Doctor” by Kafka, “Three Questions” by Tolstoy, “Elephant Hills” and “Indian Camp” each by Hemingway, “Interpreter of Maladies” by Lahiri, “Get your Own Fatal Disease” by Yalom, “Caves of Lascaux” by Karmel, “The Plagiarist” by Seamon and three essays on “undying,” end-of-life and love. Themes included falling in love with a patient, empathy, loneliness, burnout, communication, helplessness, and end-of-life issues. Discussions lasted two hours and promoted a sense of belonging and community; sharing of feelings and concerns; and transcendence of everyday burdens. Attendance was more than 80% at each meeting and all participants indicated an interest in continuing the club for the foreseeable future. Short story clubs may be one way to overcome or prevent burnout in oncology. Further quantitative and qualitative studies are needed.
Burnout is common in hematology/oncology practice where work pressure is high, patients are complex, and outcomes are variable. We hypothesized that a short story club could be helpful to improve community, humanism, and transcendence; and thereby to decrease burnout. Most of the potential participants indicated little time for preparation and we, therefore, chose short stories rather than books as reading material. The meetings began in April 2019 and continued until April 2020 when they were suspended for the COVID-19 epidemic. Participants included oncologists (6), oncology fellows (2), psychologist (1), social workers (2), research writer (1) and, student (1). Of these, 7 were females and 6 were males; 4 in senior and 9 in junior positions. Country of origin of participants was USA (6), India (3), Syria (2), Pakistan (1) and, Poland (1). Meetings were held every two months, each time with different stories, focus, themes, and points of view. Readings included classical stories, modern stories, and personal essays, from the eyes of other oncologists, country doctor, patients, nurses, or students. Stories included “The Doctor” by Chekhov, “The Country Doctor” by Kafka, “Three Questions” by Tolstoy, “Elephant Hills” and “Indian Camp” each by Hemingway, “Interpreter of Maladies” by Lahiri, “Get your Own Fatal Disease” by Yalom, “Caves of Lascaux” by Karmel, “The Plagiarist” by Seamon and three essays on “undying,” end-of-life and love. Themes included falling in love with a patient, empathy, loneliness, burnout, communication, helplessness, and end-of-life issues. Discussions lasted two hours and promoted a sense of belonging and community; sharing of feelings and concerns; and transcendence of everyday burdens. Attendance was more than 80% at each meeting and all participants indicated an interest in continuing the club for the foreseeable future. Short story clubs may be one way to overcome or prevent burnout in oncology. Further quantitative and qualitative studies are needed.
Burnout is common in hematology/oncology practice where work pressure is high, patients are complex, and outcomes are variable. We hypothesized that a short story club could be helpful to improve community, humanism, and transcendence; and thereby to decrease burnout. Most of the potential participants indicated little time for preparation and we, therefore, chose short stories rather than books as reading material. The meetings began in April 2019 and continued until April 2020 when they were suspended for the COVID-19 epidemic. Participants included oncologists (6), oncology fellows (2), psychologist (1), social workers (2), research writer (1) and, student (1). Of these, 7 were females and 6 were males; 4 in senior and 9 in junior positions. Country of origin of participants was USA (6), India (3), Syria (2), Pakistan (1) and, Poland (1). Meetings were held every two months, each time with different stories, focus, themes, and points of view. Readings included classical stories, modern stories, and personal essays, from the eyes of other oncologists, country doctor, patients, nurses, or students. Stories included “The Doctor” by Chekhov, “The Country Doctor” by Kafka, “Three Questions” by Tolstoy, “Elephant Hills” and “Indian Camp” each by Hemingway, “Interpreter of Maladies” by Lahiri, “Get your Own Fatal Disease” by Yalom, “Caves of Lascaux” by Karmel, “The Plagiarist” by Seamon and three essays on “undying,” end-of-life and love. Themes included falling in love with a patient, empathy, loneliness, burnout, communication, helplessness, and end-of-life issues. Discussions lasted two hours and promoted a sense of belonging and community; sharing of feelings and concerns; and transcendence of everyday burdens. Attendance was more than 80% at each meeting and all participants indicated an interest in continuing the club for the foreseeable future. Short story clubs may be one way to overcome or prevent burnout in oncology. Further quantitative and qualitative studies are needed.
Sequential Targeted Treatment of an Elderly Patient With Acute Myeloid Leukemia Harboring Concurrent FLT3-TKD and IDH1 Mutations: A Case Report
INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.
CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.
CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.
INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.
CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.
CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.
INTRODUCTION: With the increasing availability of novel targeted therapies and next-generation sequencing (NGS) hematology panels, the treatment paradigm for patients with acute myeloid leukemia (AML) has recently been altered. Specifically, patients who bear mutations within the FMS-like tyrosine kinase (FLT3) gene or the isocitrate dehydrogenase (IDH) 1 or IDH2 genes may now be candidates for targeted treatments either in the frontline or relapsed or refractory (R/R) settings. The sequential targeted approach to AML patients who harbor mutations within both FLT3 and IDH genes has yet to be elucidated.
CASE PRESENTATION: Herein, we report a case of an elderly patient with FLT3 and IDH1 mutations who underwent induction chemotherapy in combination with midostaurin, and subsequently, ivosidenib in the R/R setting. Clonal evaluation was demonstrated with repeated cytogenetic analysis and NGS of blood and bone marrow specimens. At diagnosis, the patient’s AML harbored several pathogenic gene variants, including FLT3 and IDH1 mutations. Following induction chemotherapy with midostaurin, the patient’s FLT3 mutation was no longer detected. Upon relapse, the FLT3 mutation was still undetectable, however the IDH1 mutation remained. Unfortunately, the patient’s AML did not respond to ivosidenib, and expansion of a leukemic clone with a BCOR mutation was observed.
CONCLUSION: This case conveys the use of multiple targeted therapies in a sequential fashion for an AML patient with frequent completion of NGS panels to monitor clonal evolution. Given that a considerable minority of patients harbor both FLT3 and IDH mutations, further investigations evaluating optimal sequencing or combinations of targeted therapies are required.
Screening Colonoscopy Findings Are Associated With Non-Colorectal Cancer Mortality
PURPOSE: Examine whether baseline colonoscopy findings are associated with non-Colorectal Cancer (CRC) mortality in a Veteran screening population.
BACKGROUND: Although screening colonoscopy findings are associated with future risk of CRC mortality, whether these findings are also associated with non- CRC mortality remains unknown.
METHODS: The Cooperative Studies Program (CSP) #380 cohort is comprised of 3,121 Veterans age 50-75 who underwent screening colonoscopy from 1994-97. Veterans were followed for 10 years or death, as verified in electronic medical records. Those who died from CRC-specific causes were excluded from this analysis (n=18, 0.6%). Hazard ratios (HR) for risk factors on non-CRC mortality were calculated by Cox Proportional Hazard model, adjusting for demographics, baseline comorbidities, and lifestyle factors. Information on comorbidities, family history, diet, physical activity, and medications were obtained from self-reported questionnaires at baseline.
RESULTS: Of the included 3,103 Veterans, most were male (n=3,021, 96.8%), white (n=2,609, 83.6%), with a mean age of 62.9. During the 10-year follow-up period, 837 (27.0%) Veterans died from non-CRC causes. The risk of non-CRC mortality was higher in Veterans with ≥3 small adenomas (HR 1.45, p=0.02), advanced adenomas (HR 1.34, p=0.04), or CRC (HR 3.00, =0.05) on baseline colonoscopy when compared to Veterans without neoplasia. Additionally, increasing age (HR 1.07, <0.001), modified Charlson score (HR 1.57 for 3-4 points, <0.001, compared to 0-2 points) and current smoking (HR 2.09, <0.001, compared to former and non-smokers) were associated with higher non-CRC mortality. On the other hand, increasing physical activity (HR 0.88, <0.001), family history of CRC (HR 0.75, =0.02), and increased BMI (HR 0.73-0.75, <0.01) were associated with reduced non-CRC mortality. Neither race, NSAID use (including aspirin), or dietary factors impacted non-CRC mortality.
CONCLUSIONS: In a Veteran CRC screening population, we found that high-risk adenomas or CRC on baseline colonoscopy were independently associated with increased non-CRC mortality within 10 years. Future work will examine the cause-specific factors associated with non-CRC mortality in these groups to 1) identify potential high-yield strategies for tailored non-CRC mortality risk reduction during CRC screening, and 2) better determine when competing risks of non-CRC mortality outweigh the benefit of follow up colonoscopy.
PURPOSE: Examine whether baseline colonoscopy findings are associated with non-Colorectal Cancer (CRC) mortality in a Veteran screening population.
BACKGROUND: Although screening colonoscopy findings are associated with future risk of CRC mortality, whether these findings are also associated with non- CRC mortality remains unknown.
METHODS: The Cooperative Studies Program (CSP) #380 cohort is comprised of 3,121 Veterans age 50-75 who underwent screening colonoscopy from 1994-97. Veterans were followed for 10 years or death, as verified in electronic medical records. Those who died from CRC-specific causes were excluded from this analysis (n=18, 0.6%). Hazard ratios (HR) for risk factors on non-CRC mortality were calculated by Cox Proportional Hazard model, adjusting for demographics, baseline comorbidities, and lifestyle factors. Information on comorbidities, family history, diet, physical activity, and medications were obtained from self-reported questionnaires at baseline.
RESULTS: Of the included 3,103 Veterans, most were male (n=3,021, 96.8%), white (n=2,609, 83.6%), with a mean age of 62.9. During the 10-year follow-up period, 837 (27.0%) Veterans died from non-CRC causes. The risk of non-CRC mortality was higher in Veterans with ≥3 small adenomas (HR 1.45, p=0.02), advanced adenomas (HR 1.34, p=0.04), or CRC (HR 3.00, =0.05) on baseline colonoscopy when compared to Veterans without neoplasia. Additionally, increasing age (HR 1.07, <0.001), modified Charlson score (HR 1.57 for 3-4 points, <0.001, compared to 0-2 points) and current smoking (HR 2.09, <0.001, compared to former and non-smokers) were associated with higher non-CRC mortality. On the other hand, increasing physical activity (HR 0.88, <0.001), family history of CRC (HR 0.75, =0.02), and increased BMI (HR 0.73-0.75, <0.01) were associated with reduced non-CRC mortality. Neither race, NSAID use (including aspirin), or dietary factors impacted non-CRC mortality.
CONCLUSIONS: In a Veteran CRC screening population, we found that high-risk adenomas or CRC on baseline colonoscopy were independently associated with increased non-CRC mortality within 10 years. Future work will examine the cause-specific factors associated with non-CRC mortality in these groups to 1) identify potential high-yield strategies for tailored non-CRC mortality risk reduction during CRC screening, and 2) better determine when competing risks of non-CRC mortality outweigh the benefit of follow up colonoscopy.
PURPOSE: Examine whether baseline colonoscopy findings are associated with non-Colorectal Cancer (CRC) mortality in a Veteran screening population.
BACKGROUND: Although screening colonoscopy findings are associated with future risk of CRC mortality, whether these findings are also associated with non- CRC mortality remains unknown.
METHODS: The Cooperative Studies Program (CSP) #380 cohort is comprised of 3,121 Veterans age 50-75 who underwent screening colonoscopy from 1994-97. Veterans were followed for 10 years or death, as verified in electronic medical records. Those who died from CRC-specific causes were excluded from this analysis (n=18, 0.6%). Hazard ratios (HR) for risk factors on non-CRC mortality were calculated by Cox Proportional Hazard model, adjusting for demographics, baseline comorbidities, and lifestyle factors. Information on comorbidities, family history, diet, physical activity, and medications were obtained from self-reported questionnaires at baseline.
RESULTS: Of the included 3,103 Veterans, most were male (n=3,021, 96.8%), white (n=2,609, 83.6%), with a mean age of 62.9. During the 10-year follow-up period, 837 (27.0%) Veterans died from non-CRC causes. The risk of non-CRC mortality was higher in Veterans with ≥3 small adenomas (HR 1.45, p=0.02), advanced adenomas (HR 1.34, p=0.04), or CRC (HR 3.00, =0.05) on baseline colonoscopy when compared to Veterans without neoplasia. Additionally, increasing age (HR 1.07, <0.001), modified Charlson score (HR 1.57 for 3-4 points, <0.001, compared to 0-2 points) and current smoking (HR 2.09, <0.001, compared to former and non-smokers) were associated with higher non-CRC mortality. On the other hand, increasing physical activity (HR 0.88, <0.001), family history of CRC (HR 0.75, =0.02), and increased BMI (HR 0.73-0.75, <0.01) were associated with reduced non-CRC mortality. Neither race, NSAID use (including aspirin), or dietary factors impacted non-CRC mortality.
CONCLUSIONS: In a Veteran CRC screening population, we found that high-risk adenomas or CRC on baseline colonoscopy were independently associated with increased non-CRC mortality within 10 years. Future work will examine the cause-specific factors associated with non-CRC mortality in these groups to 1) identify potential high-yield strategies for tailored non-CRC mortality risk reduction during CRC screening, and 2) better determine when competing risks of non-CRC mortality outweigh the benefit of follow up colonoscopy.
Review of Efficacy and Safety Outcomes of Ibrutinib in a Veteran Population with Chronic Lymphocytic Leukemia
BACKGROUND/RATIONALE: Chronic lymphocytic leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are indolent hematologic malignancies that account for one-quarter of all lymphomas primarily affecting older patients. Survival has improved due to the development of novel oral drugs with 85.1% 5-year survival in 2019. Ibrutinib is an oral Bruton’s tyrosine kinase inhibitor that interferes with malignant B-cell proliferation and survival. The National Comprehensive Cancer Network recommends ibrutinib as a category one treatment recommendation in all settings of CLL including relapsed/refractory disease and adverse cytogenetics. This study aims to improve clinical knowledge of ibrutinib’s efficacy and safety in a Veteran population.
OBJECTIVES: The primary objective was to determine the efficacy of ibrutinib in the Veteran population as defined by progression-free survival. Secondary objectives included overall survival, overall response, duration of therapy, and prevalence of adverse drug reactions.
METHODS: This was a single center, retrospective study conducted at the Southern Arizona VA Health Care System. A retrospective chart review of patients age 18-89 with CLL or SLL treated with ibrutinib between November 1st, 2013 to August 1st, 2019 was conducted. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Descriptive statistics was used for all other endpoints. RESULTS: Twenty-three patients were included in this study. Progression free survival and overall survival at 63 months (5.25 years) was 68.2% and 72.7%, respectively. The average duration of therapy was 20.3 months with 65.2% achieving partial response, 17.3% with stable disease, and 17.3% with progression of disease. The most common adverse events were gastrointestinal (21.7%) and cardiac (17.4%) including 3 patients who developed atrial fibrillation; 34.7% of patients required a dose reduction due to toxicity.
CONCLUSION: Use of ibrutinib in the Veteran population had similar progression-free survival as the clinical trials that led to its approval; however, slightly lower overall survival was noted compared to the clinical trials. The rate of atrial fibrillation was higher in the Veteran population compared to clinical trials, whereas the prevalence of gastrointestinal, dermatologic, neurologic, and musculoskeletal adverse events was consistent with published data.
BACKGROUND/RATIONALE: Chronic lymphocytic leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are indolent hematologic malignancies that account for one-quarter of all lymphomas primarily affecting older patients. Survival has improved due to the development of novel oral drugs with 85.1% 5-year survival in 2019. Ibrutinib is an oral Bruton’s tyrosine kinase inhibitor that interferes with malignant B-cell proliferation and survival. The National Comprehensive Cancer Network recommends ibrutinib as a category one treatment recommendation in all settings of CLL including relapsed/refractory disease and adverse cytogenetics. This study aims to improve clinical knowledge of ibrutinib’s efficacy and safety in a Veteran population.
OBJECTIVES: The primary objective was to determine the efficacy of ibrutinib in the Veteran population as defined by progression-free survival. Secondary objectives included overall survival, overall response, duration of therapy, and prevalence of adverse drug reactions.
METHODS: This was a single center, retrospective study conducted at the Southern Arizona VA Health Care System. A retrospective chart review of patients age 18-89 with CLL or SLL treated with ibrutinib between November 1st, 2013 to August 1st, 2019 was conducted. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Descriptive statistics was used for all other endpoints. RESULTS: Twenty-three patients were included in this study. Progression free survival and overall survival at 63 months (5.25 years) was 68.2% and 72.7%, respectively. The average duration of therapy was 20.3 months with 65.2% achieving partial response, 17.3% with stable disease, and 17.3% with progression of disease. The most common adverse events were gastrointestinal (21.7%) and cardiac (17.4%) including 3 patients who developed atrial fibrillation; 34.7% of patients required a dose reduction due to toxicity.
CONCLUSION: Use of ibrutinib in the Veteran population had similar progression-free survival as the clinical trials that led to its approval; however, slightly lower overall survival was noted compared to the clinical trials. The rate of atrial fibrillation was higher in the Veteran population compared to clinical trials, whereas the prevalence of gastrointestinal, dermatologic, neurologic, and musculoskeletal adverse events was consistent with published data.
BACKGROUND/RATIONALE: Chronic lymphocytic leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are indolent hematologic malignancies that account for one-quarter of all lymphomas primarily affecting older patients. Survival has improved due to the development of novel oral drugs with 85.1% 5-year survival in 2019. Ibrutinib is an oral Bruton’s tyrosine kinase inhibitor that interferes with malignant B-cell proliferation and survival. The National Comprehensive Cancer Network recommends ibrutinib as a category one treatment recommendation in all settings of CLL including relapsed/refractory disease and adverse cytogenetics. This study aims to improve clinical knowledge of ibrutinib’s efficacy and safety in a Veteran population.
OBJECTIVES: The primary objective was to determine the efficacy of ibrutinib in the Veteran population as defined by progression-free survival. Secondary objectives included overall survival, overall response, duration of therapy, and prevalence of adverse drug reactions.
METHODS: This was a single center, retrospective study conducted at the Southern Arizona VA Health Care System. A retrospective chart review of patients age 18-89 with CLL or SLL treated with ibrutinib between November 1st, 2013 to August 1st, 2019 was conducted. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Descriptive statistics was used for all other endpoints. RESULTS: Twenty-three patients were included in this study. Progression free survival and overall survival at 63 months (5.25 years) was 68.2% and 72.7%, respectively. The average duration of therapy was 20.3 months with 65.2% achieving partial response, 17.3% with stable disease, and 17.3% with progression of disease. The most common adverse events were gastrointestinal (21.7%) and cardiac (17.4%) including 3 patients who developed atrial fibrillation; 34.7% of patients required a dose reduction due to toxicity.
CONCLUSION: Use of ibrutinib in the Veteran population had similar progression-free survival as the clinical trials that led to its approval; however, slightly lower overall survival was noted compared to the clinical trials. The rate of atrial fibrillation was higher in the Veteran population compared to clinical trials, whereas the prevalence of gastrointestinal, dermatologic, neurologic, and musculoskeletal adverse events was consistent with published data.