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Cancer patients increasingly being discharged to subacute rehabilitation facilities
As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.
However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.
To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.
Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.
Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.
The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”
Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.
SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.
As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.
However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.
To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.
Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.
Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.
The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”
Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.
SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.
As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.
However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.
To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.
Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.
Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.
The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”
Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.
SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.
FROM THE JOURNAL OF ONCOLOGY PRACTICE
Prior antibiotic use lowers checkpoint inhibitor response and survival
Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.
In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.
A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.
The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.
However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.
The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.
They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.
The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.
“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.
Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.
“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.
The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.
SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.
Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.
In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.
A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.
The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.
However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.
The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.
They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.
The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.
“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.
Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.
“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.
The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.
SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.
Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.
In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.
A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.
The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.
However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.
The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.
They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.
The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.
“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.
Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.
“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.
The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.
SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.
FROM JAMA ONCOLOGY
Key clinical point: People who take antibiotics prior to checkpoint inhibitor therapy have lower treatment response and overall survival.
Major finding: Prior antibiotic use is associated with a nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy.
Study details: A prospective cohort study involving 196 patients receiving checkpoint inhibitor therapy for cancer.
Disclosures: The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.
Source: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.
Chemotherapy may raise CVD risk in pediatric cancer survivors
Pediatric cancer survivors have a higher likelihood of experiencing a cardiac event, developing diabetes, or having hypertension at a median 10-year follow-up, according to results from a recent research letter published in Circulation.
Ashna Khanna of the University of Toronto and colleagues identified 7,289 pediatric patients in the Pediatric Oncology Group of Ontario Networked Information System who were diagnosed with cancer at median age of 7 years old, who were treated between 1987 and 2010, and who were cancer survivors for 5 years. Each patient was matched to five cancer-free control subjects who were a median of 24 years old at the 10-year follow-up (36,205 cancer-free individuals). The researchers studied whether pediatric cancer survivors experienced cardiac events, such as heart failure, arrhythmia, pericardial disease, valvular disease, or coronary artery disease. They also evaluated the incidence of diabetes and hypertension in each group.
Of the children who survived cancer, 2.8% (n = 203) experienced at least one cardiac event versus 0.9% of controls (P less than .001). The cancer survivors experienced 3.2 cardiac events per 1,000 person-years (95% confidence interval, 2.8-3.6), compared with the control group in which there was a rate of 0.9 cardiac events per 1,000 person-years (95% CI, 0.9-1.9).
With regard to cardiovascular disease (CVD) risk, associated factors included cancer relapse or subsequent cancer (hazard ratio, 1.7; 95% CI, 1.1-2.7) and a 250-mg/m2 or greater dose of doxorubicin-equivalent anthracycline chemotherapy, compared with a dose of less than 250 mg/m2 or no anthracycline chemotherapy (HR, 2.0; 95% CI, 1.4-2.9). Patients who developed diabetes mellitus before a CVD diagnosis were also at higher risk of CVD (HR, 3.0; 95% CI, 1.6-5.8).
Heart failure risk was also statistically significant in patients with relapse and subsequent childhood cancer (HR, 2.0; 95% CI, 1.1-3.7), a 250-mg/m2 or greater dose of doxorubicin-equivalent anthracycline chemotherapy (HR, 8.6; 95% CI, 4.5-16.6), diabetes (HR, 4.3; 95% CI, 1.8-10.7), and hypertension (HR, 3.1; 95% CI, 1.3-7.9).
“While anthracycline chemotherapy may induce heart disease, many patients require this cancer treatment to survive,” Paul Nathan, MD, of the Hospital for Sick Children in Canada and a study coauthor said in a statement. “Doctors should address heart disease risk factors – such as diabetes and hypertension – that can be modified.”
This study was funded in part from a grant by the Canadian Institutes for Health Research. Several authors reported support from noncommercial sources. The other authors reported having no relevant conflicts of interest.
SOURCE: Khanna A et al. Circulation. 2019 Aug 26. doi: 10.1161/CIRCULATIONAHA.119.041403.
Pediatric cancer survivors have a higher likelihood of experiencing a cardiac event, developing diabetes, or having hypertension at a median 10-year follow-up, according to results from a recent research letter published in Circulation.
Ashna Khanna of the University of Toronto and colleagues identified 7,289 pediatric patients in the Pediatric Oncology Group of Ontario Networked Information System who were diagnosed with cancer at median age of 7 years old, who were treated between 1987 and 2010, and who were cancer survivors for 5 years. Each patient was matched to five cancer-free control subjects who were a median of 24 years old at the 10-year follow-up (36,205 cancer-free individuals). The researchers studied whether pediatric cancer survivors experienced cardiac events, such as heart failure, arrhythmia, pericardial disease, valvular disease, or coronary artery disease. They also evaluated the incidence of diabetes and hypertension in each group.
Of the children who survived cancer, 2.8% (n = 203) experienced at least one cardiac event versus 0.9% of controls (P less than .001). The cancer survivors experienced 3.2 cardiac events per 1,000 person-years (95% confidence interval, 2.8-3.6), compared with the control group in which there was a rate of 0.9 cardiac events per 1,000 person-years (95% CI, 0.9-1.9).
With regard to cardiovascular disease (CVD) risk, associated factors included cancer relapse or subsequent cancer (hazard ratio, 1.7; 95% CI, 1.1-2.7) and a 250-mg/m2 or greater dose of doxorubicin-equivalent anthracycline chemotherapy, compared with a dose of less than 250 mg/m2 or no anthracycline chemotherapy (HR, 2.0; 95% CI, 1.4-2.9). Patients who developed diabetes mellitus before a CVD diagnosis were also at higher risk of CVD (HR, 3.0; 95% CI, 1.6-5.8).
Heart failure risk was also statistically significant in patients with relapse and subsequent childhood cancer (HR, 2.0; 95% CI, 1.1-3.7), a 250-mg/m2 or greater dose of doxorubicin-equivalent anthracycline chemotherapy (HR, 8.6; 95% CI, 4.5-16.6), diabetes (HR, 4.3; 95% CI, 1.8-10.7), and hypertension (HR, 3.1; 95% CI, 1.3-7.9).
“While anthracycline chemotherapy may induce heart disease, many patients require this cancer treatment to survive,” Paul Nathan, MD, of the Hospital for Sick Children in Canada and a study coauthor said in a statement. “Doctors should address heart disease risk factors – such as diabetes and hypertension – that can be modified.”
This study was funded in part from a grant by the Canadian Institutes for Health Research. Several authors reported support from noncommercial sources. The other authors reported having no relevant conflicts of interest.
SOURCE: Khanna A et al. Circulation. 2019 Aug 26. doi: 10.1161/CIRCULATIONAHA.119.041403.
Pediatric cancer survivors have a higher likelihood of experiencing a cardiac event, developing diabetes, or having hypertension at a median 10-year follow-up, according to results from a recent research letter published in Circulation.
Ashna Khanna of the University of Toronto and colleagues identified 7,289 pediatric patients in the Pediatric Oncology Group of Ontario Networked Information System who were diagnosed with cancer at median age of 7 years old, who were treated between 1987 and 2010, and who were cancer survivors for 5 years. Each patient was matched to five cancer-free control subjects who were a median of 24 years old at the 10-year follow-up (36,205 cancer-free individuals). The researchers studied whether pediatric cancer survivors experienced cardiac events, such as heart failure, arrhythmia, pericardial disease, valvular disease, or coronary artery disease. They also evaluated the incidence of diabetes and hypertension in each group.
Of the children who survived cancer, 2.8% (n = 203) experienced at least one cardiac event versus 0.9% of controls (P less than .001). The cancer survivors experienced 3.2 cardiac events per 1,000 person-years (95% confidence interval, 2.8-3.6), compared with the control group in which there was a rate of 0.9 cardiac events per 1,000 person-years (95% CI, 0.9-1.9).
With regard to cardiovascular disease (CVD) risk, associated factors included cancer relapse or subsequent cancer (hazard ratio, 1.7; 95% CI, 1.1-2.7) and a 250-mg/m2 or greater dose of doxorubicin-equivalent anthracycline chemotherapy, compared with a dose of less than 250 mg/m2 or no anthracycline chemotherapy (HR, 2.0; 95% CI, 1.4-2.9). Patients who developed diabetes mellitus before a CVD diagnosis were also at higher risk of CVD (HR, 3.0; 95% CI, 1.6-5.8).
Heart failure risk was also statistically significant in patients with relapse and subsequent childhood cancer (HR, 2.0; 95% CI, 1.1-3.7), a 250-mg/m2 or greater dose of doxorubicin-equivalent anthracycline chemotherapy (HR, 8.6; 95% CI, 4.5-16.6), diabetes (HR, 4.3; 95% CI, 1.8-10.7), and hypertension (HR, 3.1; 95% CI, 1.3-7.9).
“While anthracycline chemotherapy may induce heart disease, many patients require this cancer treatment to survive,” Paul Nathan, MD, of the Hospital for Sick Children in Canada and a study coauthor said in a statement. “Doctors should address heart disease risk factors – such as diabetes and hypertension – that can be modified.”
This study was funded in part from a grant by the Canadian Institutes for Health Research. Several authors reported support from noncommercial sources. The other authors reported having no relevant conflicts of interest.
SOURCE: Khanna A et al. Circulation. 2019 Aug 26. doi: 10.1161/CIRCULATIONAHA.119.041403.
FROM CIRCULATION
Curative intent and palliative care – compatible goals?
The first signs are always vague. Katie (not her real name) was 33 years old and loved to spend her weekends hiking. First, it was fatigue when doing elevation. Then fatigue even while walking across flat ground. One day she just sat in bed and noticed her heart racing.
One blood test, and her primary care doctor called her at home with the results. Go to the emergency room, she said. Katie’s red blood cells were dangerously low. She would need a blood transfusion.
Something was wrong, but the list of possibilities remained broad. Someone in the emergency room tossed out the word “leukemia.” Katie froze. She liked the resident who tossed out “internal bleeding” better.
This was the start of the ups and downs; the good news and bad news; the branch points that opened and closed her future.
The hematologist-oncologist came by. You need to be admitted to the hospital, and we need to do a bone marrow biopsy, she told Katie. It could be – and then the word was said again – this time by a specialist, making it all the more real: leukemia.
Katie had a few days to sit with this. The bone marrow biopsy was done. Now, what type of leukemia? She read on her computer. She knew there were lots of kinds, some better than others. Now, she was praying for a “good” cancer.
It was one of the bad ones. But.
We sent off additional molecular and genetics testing from your bone marrow, the doctor explained. This type of leukemia can be divided into three groups: high risk, standard risk, and low risk. All the signs so far point to low risk. This is good news, Katie thought.
Six days later. The final cytogenetics came back. Actually, Katie had a rare mutation that automatically put her in the high risk category. It meant she would definitely need a bone marrow transplant to be cured. Bad.
And so she underwent induction chemotherapy. The nurse posted a big calendar on her wall and filled it with her daily blood counts. The counts are dropping, Katie noted. This is good, right? It means the leukemia is responding to chemo? Yes. Good news.
Four days later. The blast count in her blood crept up. It could be anything. It could be reactive. It doesn’t necessarily mean refractory leukemia. But. It’s bad news.
In the interim, some more testing came back. You have one sister, right? Sharon? Yes, Katie confirmed. Looks like Sharon is a perfect match for a bone marrow transplant. Katie cried. Such good news.
Two weeks later the next bone marrow biopsy was done. This shows how you responded to the chemotherapy, the doctors explained. Will it be in remission? Will it be refractory? It’s in remission. Wow, good news.
But the window to transplant is small. In the few weeks to get there, another test came back. Even though the cancer is technically in remission, you have something called minimal residual disease. Meaning there are small amounts of leukemia left over. We should bridge with more chemo before transplant.
Was this good news? Bad news? Who knew anymore?
It’s well known in the hematology and oncology world that – even with advanced disease and poor prognoses – patients with blood cancers are less likely to see palliative care than patients with solid tumors. At conferences and in academic journals, leaders in the field expound on why this may be. One reason is the inability for most hospice agencies to offer blood transfusions. That’s certainly a big piece.
Then there’s Katie. When Katie was diagnosed, she asked me what stage her cancer was. It’s a question I hear a lot. With leukemia, I explained, we don’t think about staging the same way we do for conditions like breast cancer or prostate cancer. Since it’s in the blood, it’s stage 4 by definition, I said, but that doesn’t mean anything about prognosis. Our model of thinking is fundamentally different.
With a solid stage 4 cancer, there is generally no chance for cure. The goal is stabilization: We want to keep the cancer where it is for as long as possible. A stable CT scan, in which the disease burden is identical to 3 months before, is a success. The difference between good news and bad news is in lifespan. Receiving bad news is the difference between projecting 2 years and 6 months to live.
With a stage 4 blood cancer like Katie’s leukemia, there is generally a chance for cure. The goal is to make the cancer disappear completely and have someone live a normal lifespan. The outcomes are binary. The difference between good news and bad news is not a difference in lifespan, but a difference in probability of cure. Receiving bad news is the difference between an 80% chance of cure and a 20% chance.
Whenever I order chemotherapy, the electronic record prompts me for my intent: Is this palliative or curative intent? I always type curative intent. The intent is curative until we choose to stop pursuing cure.
Grappling with uncertainty is an enormous challenge for anyone after a diagnosis of cancer. Not knowing whether cure is even possible makes it that much more complex. The outcomes are as diverse as can be. The next branch point can literally be the difference between no more cancer and no more options.
Which raises the question, at what point – if any – should we have asked palliative care to see Katie? I wish we would have done it sooner, not because patients like Katie won’t be cured, but to help them sit with the toughest of uncertainties; prepare for it; live in it as best as possible.
As I write this, Katie is undergoing a bone marrow transplant from her sister, the match. In a few weeks she will face her next branch point – whether the transplant worked. It will move her closer or further from a cure.
Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz and listen to her each week on the Blood & Cancer podcast.
The first signs are always vague. Katie (not her real name) was 33 years old and loved to spend her weekends hiking. First, it was fatigue when doing elevation. Then fatigue even while walking across flat ground. One day she just sat in bed and noticed her heart racing.
One blood test, and her primary care doctor called her at home with the results. Go to the emergency room, she said. Katie’s red blood cells were dangerously low. She would need a blood transfusion.
Something was wrong, but the list of possibilities remained broad. Someone in the emergency room tossed out the word “leukemia.” Katie froze. She liked the resident who tossed out “internal bleeding” better.
This was the start of the ups and downs; the good news and bad news; the branch points that opened and closed her future.
The hematologist-oncologist came by. You need to be admitted to the hospital, and we need to do a bone marrow biopsy, she told Katie. It could be – and then the word was said again – this time by a specialist, making it all the more real: leukemia.
Katie had a few days to sit with this. The bone marrow biopsy was done. Now, what type of leukemia? She read on her computer. She knew there were lots of kinds, some better than others. Now, she was praying for a “good” cancer.
It was one of the bad ones. But.
We sent off additional molecular and genetics testing from your bone marrow, the doctor explained. This type of leukemia can be divided into three groups: high risk, standard risk, and low risk. All the signs so far point to low risk. This is good news, Katie thought.
Six days later. The final cytogenetics came back. Actually, Katie had a rare mutation that automatically put her in the high risk category. It meant she would definitely need a bone marrow transplant to be cured. Bad.
And so she underwent induction chemotherapy. The nurse posted a big calendar on her wall and filled it with her daily blood counts. The counts are dropping, Katie noted. This is good, right? It means the leukemia is responding to chemo? Yes. Good news.
Four days later. The blast count in her blood crept up. It could be anything. It could be reactive. It doesn’t necessarily mean refractory leukemia. But. It’s bad news.
In the interim, some more testing came back. You have one sister, right? Sharon? Yes, Katie confirmed. Looks like Sharon is a perfect match for a bone marrow transplant. Katie cried. Such good news.
Two weeks later the next bone marrow biopsy was done. This shows how you responded to the chemotherapy, the doctors explained. Will it be in remission? Will it be refractory? It’s in remission. Wow, good news.
But the window to transplant is small. In the few weeks to get there, another test came back. Even though the cancer is technically in remission, you have something called minimal residual disease. Meaning there are small amounts of leukemia left over. We should bridge with more chemo before transplant.
Was this good news? Bad news? Who knew anymore?
It’s well known in the hematology and oncology world that – even with advanced disease and poor prognoses – patients with blood cancers are less likely to see palliative care than patients with solid tumors. At conferences and in academic journals, leaders in the field expound on why this may be. One reason is the inability for most hospice agencies to offer blood transfusions. That’s certainly a big piece.
Then there’s Katie. When Katie was diagnosed, she asked me what stage her cancer was. It’s a question I hear a lot. With leukemia, I explained, we don’t think about staging the same way we do for conditions like breast cancer or prostate cancer. Since it’s in the blood, it’s stage 4 by definition, I said, but that doesn’t mean anything about prognosis. Our model of thinking is fundamentally different.
With a solid stage 4 cancer, there is generally no chance for cure. The goal is stabilization: We want to keep the cancer where it is for as long as possible. A stable CT scan, in which the disease burden is identical to 3 months before, is a success. The difference between good news and bad news is in lifespan. Receiving bad news is the difference between projecting 2 years and 6 months to live.
With a stage 4 blood cancer like Katie’s leukemia, there is generally a chance for cure. The goal is to make the cancer disappear completely and have someone live a normal lifespan. The outcomes are binary. The difference between good news and bad news is not a difference in lifespan, but a difference in probability of cure. Receiving bad news is the difference between an 80% chance of cure and a 20% chance.
Whenever I order chemotherapy, the electronic record prompts me for my intent: Is this palliative or curative intent? I always type curative intent. The intent is curative until we choose to stop pursuing cure.
Grappling with uncertainty is an enormous challenge for anyone after a diagnosis of cancer. Not knowing whether cure is even possible makes it that much more complex. The outcomes are as diverse as can be. The next branch point can literally be the difference between no more cancer and no more options.
Which raises the question, at what point – if any – should we have asked palliative care to see Katie? I wish we would have done it sooner, not because patients like Katie won’t be cured, but to help them sit with the toughest of uncertainties; prepare for it; live in it as best as possible.
As I write this, Katie is undergoing a bone marrow transplant from her sister, the match. In a few weeks she will face her next branch point – whether the transplant worked. It will move her closer or further from a cure.
Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz and listen to her each week on the Blood & Cancer podcast.
The first signs are always vague. Katie (not her real name) was 33 years old and loved to spend her weekends hiking. First, it was fatigue when doing elevation. Then fatigue even while walking across flat ground. One day she just sat in bed and noticed her heart racing.
One blood test, and her primary care doctor called her at home with the results. Go to the emergency room, she said. Katie’s red blood cells were dangerously low. She would need a blood transfusion.
Something was wrong, but the list of possibilities remained broad. Someone in the emergency room tossed out the word “leukemia.” Katie froze. She liked the resident who tossed out “internal bleeding” better.
This was the start of the ups and downs; the good news and bad news; the branch points that opened and closed her future.
The hematologist-oncologist came by. You need to be admitted to the hospital, and we need to do a bone marrow biopsy, she told Katie. It could be – and then the word was said again – this time by a specialist, making it all the more real: leukemia.
Katie had a few days to sit with this. The bone marrow biopsy was done. Now, what type of leukemia? She read on her computer. She knew there were lots of kinds, some better than others. Now, she was praying for a “good” cancer.
It was one of the bad ones. But.
We sent off additional molecular and genetics testing from your bone marrow, the doctor explained. This type of leukemia can be divided into three groups: high risk, standard risk, and low risk. All the signs so far point to low risk. This is good news, Katie thought.
Six days later. The final cytogenetics came back. Actually, Katie had a rare mutation that automatically put her in the high risk category. It meant she would definitely need a bone marrow transplant to be cured. Bad.
And so she underwent induction chemotherapy. The nurse posted a big calendar on her wall and filled it with her daily blood counts. The counts are dropping, Katie noted. This is good, right? It means the leukemia is responding to chemo? Yes. Good news.
Four days later. The blast count in her blood crept up. It could be anything. It could be reactive. It doesn’t necessarily mean refractory leukemia. But. It’s bad news.
In the interim, some more testing came back. You have one sister, right? Sharon? Yes, Katie confirmed. Looks like Sharon is a perfect match for a bone marrow transplant. Katie cried. Such good news.
Two weeks later the next bone marrow biopsy was done. This shows how you responded to the chemotherapy, the doctors explained. Will it be in remission? Will it be refractory? It’s in remission. Wow, good news.
But the window to transplant is small. In the few weeks to get there, another test came back. Even though the cancer is technically in remission, you have something called minimal residual disease. Meaning there are small amounts of leukemia left over. We should bridge with more chemo before transplant.
Was this good news? Bad news? Who knew anymore?
It’s well known in the hematology and oncology world that – even with advanced disease and poor prognoses – patients with blood cancers are less likely to see palliative care than patients with solid tumors. At conferences and in academic journals, leaders in the field expound on why this may be. One reason is the inability for most hospice agencies to offer blood transfusions. That’s certainly a big piece.
Then there’s Katie. When Katie was diagnosed, she asked me what stage her cancer was. It’s a question I hear a lot. With leukemia, I explained, we don’t think about staging the same way we do for conditions like breast cancer or prostate cancer. Since it’s in the blood, it’s stage 4 by definition, I said, but that doesn’t mean anything about prognosis. Our model of thinking is fundamentally different.
With a solid stage 4 cancer, there is generally no chance for cure. The goal is stabilization: We want to keep the cancer where it is for as long as possible. A stable CT scan, in which the disease burden is identical to 3 months before, is a success. The difference between good news and bad news is in lifespan. Receiving bad news is the difference between projecting 2 years and 6 months to live.
With a stage 4 blood cancer like Katie’s leukemia, there is generally a chance for cure. The goal is to make the cancer disappear completely and have someone live a normal lifespan. The outcomes are binary. The difference between good news and bad news is not a difference in lifespan, but a difference in probability of cure. Receiving bad news is the difference between an 80% chance of cure and a 20% chance.
Whenever I order chemotherapy, the electronic record prompts me for my intent: Is this palliative or curative intent? I always type curative intent. The intent is curative until we choose to stop pursuing cure.
Grappling with uncertainty is an enormous challenge for anyone after a diagnosis of cancer. Not knowing whether cure is even possible makes it that much more complex. The outcomes are as diverse as can be. The next branch point can literally be the difference between no more cancer and no more options.
Which raises the question, at what point – if any – should we have asked palliative care to see Katie? I wish we would have done it sooner, not because patients like Katie won’t be cured, but to help them sit with the toughest of uncertainties; prepare for it; live in it as best as possible.
As I write this, Katie is undergoing a bone marrow transplant from her sister, the match. In a few weeks she will face her next branch point – whether the transplant worked. It will move her closer or further from a cure.
Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz and listen to her each week on the Blood & Cancer podcast.
Studies reinforce clinical experience and intuition
In this edition of “How I will treat my next patient,” I examine two recently published efforts to enlighten our sensitivity to the seriousness of immune-related adverse events (IrAEs) in patients on immune checkpoint inhibitors (ICIs) and the effect of delays in initiating systemic adjuvant therapy on the long-term outcomes of patients with resected pancreatic cancer.
IrAEs requiring hospitalization
Investigators led by Aanika Balaji of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, reviewed a 6-month audit of inpatient oncology admissions of solid-tumor patients who had ever received ICIs and ascertained the prevalence of hospitalization for management of IrAEs (J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703). To determine that an IrAE had occurred they required: consensus among two oncologists, clinical improvement with immune-directed therapy, exclusion of alternative diagnoses or pathologic confirmation of an IrAE, or chronic management of an IrAE for more than 6 months.
The bottom line: They found a cumulative incidence of a confirmed IrAEs among hospitalized ICI-treated solid tumor patients of 23%. As expected, the majority (65%) were grade 3-4 in severity. In total, 91% required multidisciplinary management, and 65% improved or resolved. But 87% of patients never received an ICI again.
Patients with preexisting autoimmune disease (25% of patients, although they included hypothyroidism in that group) were not more vulnerable to an IrAE with ICI therapy (odds ratio, 1.0; 95% confidence interval, 0.3-4.0). Not unsurprisingly, the median age was higher for ICI-treated patients who were admitted for IrAEs than for those not admitted (68 years vs. 59 years; OR, 5.4; 95% CI, 1.6-17.8), and more admitted patients had received combination ICIs than single agents (OR, 6.8; 95% CI, 2.0-23.2).
The median time from beginning ICIs to an IrAE-related hospitalization was 64 days, and the median number of ICI doses was one, with a wide range for both days and doses. The authors were quick to comment that this is a small, academic, single-institution survey over a brief period of time and that the generalizability of the results is uncertain.
What this means in practice
This publication changes very little for most practicing oncologists, but it does reinforce that ICI therapy can cause unpredictable, severe IrAEs. Clinical markers for selecting patients at highest risk are imperfect. As with chemotherapy, the patients we worry about the most – older individuals and patients treated with drug combinations – are, in fact, the ones we should be worrying about the most.
In view of the potential severity and impact of IrAEs, research efforts should place equal priority on identifying biomarkers of toxicity, such as tumor mutation burden, and biomarkers of efficacy (JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.3221). The potential financial and societal effects, as well as lost opportunity costs in the form of alternative therapies and early referral to hospice, demand no less, particularly in an era of value-based health care reimbursement.
Timing of adjuvant treatment
Sung Jun Ma, MD, department of radiation medicine at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues analyzed data from the more than 7,500 stage I-II resected pancreatic cancer patients in the National Cancer Database, of whom more than 5,400 ultimately received adjuvant therapy (chemotherapy with or without radiation). The patients were treated during 2004-2015. Appropriately, the investigators focused on correlating survival duration with the interval between surgery and initiation of adjuvant therapy. Other endpoints would be hard to accurately measure and verify without detailed clinical information (JAMA Network Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9126).
They found that the best overall survival was associated with starting adjuvant treatment 28-59 days after surgery – not earlier (17% higher mortality) and not later (9% higher). Patients who did not start adjuvant treatment until more than 90 days post operatively still had an overall survival benefit (hazard ratio, 0.75; 95% confidence interval, 0.66-0.85; P less than .001), a more impressive hazard ratio than that seen for any particular interval between surgery and adjuvant treatment. Overall survival at 2 years was 47.2% versus 38% for the adjuvant therapy and surgery alone cohorts, respectively, with no overlap in the 95% confidence intervals.
As expected, longer delays to receive adjuvant treatment were associated with longer inpatient surgical stays, advanced age, black race, lower income, and a readmission for a postoperative complication within 30 days.
What this means in practice
This is another study that verifies that the patients we worry about most – older patients, those with a complicated recovery from surgery, and those with fewer supportive resources – are exactly the patients we should worry about most. It changes very little for most practicing oncologists. The analysis validates the importance of adjuvant therapy for patients who are able to receive it – whenever that is.
The data collection in this publication precedes recent improvements in adjuvant chemotherapy for resected pancreatic cancer, such as FOLFIRINOX or gemcitabine plus capecitabine. In an era of improved treatment, delays in initiating therapy may be less important since better treatment overcomes many prognostic variables that are significant for less effective therapy.
In my opinion, this large-data analysis is not really hypothesis-generating or practice-changing, but it does compel us to continue research efforts to improve surgical morbidity, identify better adjuvant and advanced disease regimens, and consider neoadjuvant treatment so that more than 72% of patients can receive all components of the multimodality treatment they need.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I examine two recently published efforts to enlighten our sensitivity to the seriousness of immune-related adverse events (IrAEs) in patients on immune checkpoint inhibitors (ICIs) and the effect of delays in initiating systemic adjuvant therapy on the long-term outcomes of patients with resected pancreatic cancer.
IrAEs requiring hospitalization
Investigators led by Aanika Balaji of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, reviewed a 6-month audit of inpatient oncology admissions of solid-tumor patients who had ever received ICIs and ascertained the prevalence of hospitalization for management of IrAEs (J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703). To determine that an IrAE had occurred they required: consensus among two oncologists, clinical improvement with immune-directed therapy, exclusion of alternative diagnoses or pathologic confirmation of an IrAE, or chronic management of an IrAE for more than 6 months.
The bottom line: They found a cumulative incidence of a confirmed IrAEs among hospitalized ICI-treated solid tumor patients of 23%. As expected, the majority (65%) were grade 3-4 in severity. In total, 91% required multidisciplinary management, and 65% improved or resolved. But 87% of patients never received an ICI again.
Patients with preexisting autoimmune disease (25% of patients, although they included hypothyroidism in that group) were not more vulnerable to an IrAE with ICI therapy (odds ratio, 1.0; 95% confidence interval, 0.3-4.0). Not unsurprisingly, the median age was higher for ICI-treated patients who were admitted for IrAEs than for those not admitted (68 years vs. 59 years; OR, 5.4; 95% CI, 1.6-17.8), and more admitted patients had received combination ICIs than single agents (OR, 6.8; 95% CI, 2.0-23.2).
The median time from beginning ICIs to an IrAE-related hospitalization was 64 days, and the median number of ICI doses was one, with a wide range for both days and doses. The authors were quick to comment that this is a small, academic, single-institution survey over a brief period of time and that the generalizability of the results is uncertain.
What this means in practice
This publication changes very little for most practicing oncologists, but it does reinforce that ICI therapy can cause unpredictable, severe IrAEs. Clinical markers for selecting patients at highest risk are imperfect. As with chemotherapy, the patients we worry about the most – older individuals and patients treated with drug combinations – are, in fact, the ones we should be worrying about the most.
In view of the potential severity and impact of IrAEs, research efforts should place equal priority on identifying biomarkers of toxicity, such as tumor mutation burden, and biomarkers of efficacy (JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.3221). The potential financial and societal effects, as well as lost opportunity costs in the form of alternative therapies and early referral to hospice, demand no less, particularly in an era of value-based health care reimbursement.
Timing of adjuvant treatment
Sung Jun Ma, MD, department of radiation medicine at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues analyzed data from the more than 7,500 stage I-II resected pancreatic cancer patients in the National Cancer Database, of whom more than 5,400 ultimately received adjuvant therapy (chemotherapy with or without radiation). The patients were treated during 2004-2015. Appropriately, the investigators focused on correlating survival duration with the interval between surgery and initiation of adjuvant therapy. Other endpoints would be hard to accurately measure and verify without detailed clinical information (JAMA Network Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9126).
They found that the best overall survival was associated with starting adjuvant treatment 28-59 days after surgery – not earlier (17% higher mortality) and not later (9% higher). Patients who did not start adjuvant treatment until more than 90 days post operatively still had an overall survival benefit (hazard ratio, 0.75; 95% confidence interval, 0.66-0.85; P less than .001), a more impressive hazard ratio than that seen for any particular interval between surgery and adjuvant treatment. Overall survival at 2 years was 47.2% versus 38% for the adjuvant therapy and surgery alone cohorts, respectively, with no overlap in the 95% confidence intervals.
As expected, longer delays to receive adjuvant treatment were associated with longer inpatient surgical stays, advanced age, black race, lower income, and a readmission for a postoperative complication within 30 days.
What this means in practice
This is another study that verifies that the patients we worry about most – older patients, those with a complicated recovery from surgery, and those with fewer supportive resources – are exactly the patients we should worry about most. It changes very little for most practicing oncologists. The analysis validates the importance of adjuvant therapy for patients who are able to receive it – whenever that is.
The data collection in this publication precedes recent improvements in adjuvant chemotherapy for resected pancreatic cancer, such as FOLFIRINOX or gemcitabine plus capecitabine. In an era of improved treatment, delays in initiating therapy may be less important since better treatment overcomes many prognostic variables that are significant for less effective therapy.
In my opinion, this large-data analysis is not really hypothesis-generating or practice-changing, but it does compel us to continue research efforts to improve surgical morbidity, identify better adjuvant and advanced disease regimens, and consider neoadjuvant treatment so that more than 72% of patients can receive all components of the multimodality treatment they need.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I examine two recently published efforts to enlighten our sensitivity to the seriousness of immune-related adverse events (IrAEs) in patients on immune checkpoint inhibitors (ICIs) and the effect of delays in initiating systemic adjuvant therapy on the long-term outcomes of patients with resected pancreatic cancer.
IrAEs requiring hospitalization
Investigators led by Aanika Balaji of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, reviewed a 6-month audit of inpatient oncology admissions of solid-tumor patients who had ever received ICIs and ascertained the prevalence of hospitalization for management of IrAEs (J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703). To determine that an IrAE had occurred they required: consensus among two oncologists, clinical improvement with immune-directed therapy, exclusion of alternative diagnoses or pathologic confirmation of an IrAE, or chronic management of an IrAE for more than 6 months.
The bottom line: They found a cumulative incidence of a confirmed IrAEs among hospitalized ICI-treated solid tumor patients of 23%. As expected, the majority (65%) were grade 3-4 in severity. In total, 91% required multidisciplinary management, and 65% improved or resolved. But 87% of patients never received an ICI again.
Patients with preexisting autoimmune disease (25% of patients, although they included hypothyroidism in that group) were not more vulnerable to an IrAE with ICI therapy (odds ratio, 1.0; 95% confidence interval, 0.3-4.0). Not unsurprisingly, the median age was higher for ICI-treated patients who were admitted for IrAEs than for those not admitted (68 years vs. 59 years; OR, 5.4; 95% CI, 1.6-17.8), and more admitted patients had received combination ICIs than single agents (OR, 6.8; 95% CI, 2.0-23.2).
The median time from beginning ICIs to an IrAE-related hospitalization was 64 days, and the median number of ICI doses was one, with a wide range for both days and doses. The authors were quick to comment that this is a small, academic, single-institution survey over a brief period of time and that the generalizability of the results is uncertain.
What this means in practice
This publication changes very little for most practicing oncologists, but it does reinforce that ICI therapy can cause unpredictable, severe IrAEs. Clinical markers for selecting patients at highest risk are imperfect. As with chemotherapy, the patients we worry about the most – older individuals and patients treated with drug combinations – are, in fact, the ones we should be worrying about the most.
In view of the potential severity and impact of IrAEs, research efforts should place equal priority on identifying biomarkers of toxicity, such as tumor mutation burden, and biomarkers of efficacy (JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.3221). The potential financial and societal effects, as well as lost opportunity costs in the form of alternative therapies and early referral to hospice, demand no less, particularly in an era of value-based health care reimbursement.
Timing of adjuvant treatment
Sung Jun Ma, MD, department of radiation medicine at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues analyzed data from the more than 7,500 stage I-II resected pancreatic cancer patients in the National Cancer Database, of whom more than 5,400 ultimately received adjuvant therapy (chemotherapy with or without radiation). The patients were treated during 2004-2015. Appropriately, the investigators focused on correlating survival duration with the interval between surgery and initiation of adjuvant therapy. Other endpoints would be hard to accurately measure and verify without detailed clinical information (JAMA Network Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9126).
They found that the best overall survival was associated with starting adjuvant treatment 28-59 days after surgery – not earlier (17% higher mortality) and not later (9% higher). Patients who did not start adjuvant treatment until more than 90 days post operatively still had an overall survival benefit (hazard ratio, 0.75; 95% confidence interval, 0.66-0.85; P less than .001), a more impressive hazard ratio than that seen for any particular interval between surgery and adjuvant treatment. Overall survival at 2 years was 47.2% versus 38% for the adjuvant therapy and surgery alone cohorts, respectively, with no overlap in the 95% confidence intervals.
As expected, longer delays to receive adjuvant treatment were associated with longer inpatient surgical stays, advanced age, black race, lower income, and a readmission for a postoperative complication within 30 days.
What this means in practice
This is another study that verifies that the patients we worry about most – older patients, those with a complicated recovery from surgery, and those with fewer supportive resources – are exactly the patients we should worry about most. It changes very little for most practicing oncologists. The analysis validates the importance of adjuvant therapy for patients who are able to receive it – whenever that is.
The data collection in this publication precedes recent improvements in adjuvant chemotherapy for resected pancreatic cancer, such as FOLFIRINOX or gemcitabine plus capecitabine. In an era of improved treatment, delays in initiating therapy may be less important since better treatment overcomes many prognostic variables that are significant for less effective therapy.
In my opinion, this large-data analysis is not really hypothesis-generating or practice-changing, but it does compel us to continue research efforts to improve surgical morbidity, identify better adjuvant and advanced disease regimens, and consider neoadjuvant treatment so that more than 72% of patients can receive all components of the multimodality treatment they need.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
Videos help chemo patients better understand their treatments
Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.
Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”
“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.
“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”
Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).
“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.
Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”
SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.
Research conducted by Pentz et al. on how much the core vocabulary is misunderstood is deeply troubling, suggesting that we as oncologists are not meeting the informational needs of patients who are consenting to undergo chemotherapy.
With patients showing better understanding after the videos on the terminology, it revives the notion that informed consent is a process that may require multiple interactions to ensure that patients truly understand what they are getting into with chemotherapy treatment, counter to the current treatment environment where there is a rush to get consent, treat the patient, and move onto the next one.
Whether the results of the study improve informed consent policy is something that remains to be seen.
Kerry Kilbridge, MD , of the Dana-Farber Cancer Institute in Boston made these comments in an Aug. 16 accompanying editorial published in Cancer (doi: 10.1002/cncr.32418).
Research conducted by Pentz et al. on how much the core vocabulary is misunderstood is deeply troubling, suggesting that we as oncologists are not meeting the informational needs of patients who are consenting to undergo chemotherapy.
With patients showing better understanding after the videos on the terminology, it revives the notion that informed consent is a process that may require multiple interactions to ensure that patients truly understand what they are getting into with chemotherapy treatment, counter to the current treatment environment where there is a rush to get consent, treat the patient, and move onto the next one.
Whether the results of the study improve informed consent policy is something that remains to be seen.
Kerry Kilbridge, MD , of the Dana-Farber Cancer Institute in Boston made these comments in an Aug. 16 accompanying editorial published in Cancer (doi: 10.1002/cncr.32418).
Research conducted by Pentz et al. on how much the core vocabulary is misunderstood is deeply troubling, suggesting that we as oncologists are not meeting the informational needs of patients who are consenting to undergo chemotherapy.
With patients showing better understanding after the videos on the terminology, it revives the notion that informed consent is a process that may require multiple interactions to ensure that patients truly understand what they are getting into with chemotherapy treatment, counter to the current treatment environment where there is a rush to get consent, treat the patient, and move onto the next one.
Whether the results of the study improve informed consent policy is something that remains to be seen.
Kerry Kilbridge, MD , of the Dana-Farber Cancer Institute in Boston made these comments in an Aug. 16 accompanying editorial published in Cancer (doi: 10.1002/cncr.32418).
Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.
Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”
“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.
“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”
Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).
“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.
Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”
SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.
Showing cancer patients receiving chemotherapy short videos about their treatments has the potential to improve their understanding about the treatments they are receiving, new research in Cancer has shown.
Researchers showed 50 patients at an underserved hospital six 1-minute videos focused on important terms related to their chemotherapy treatments and found that the videos helped them better understand what those key terms mean. Before viewing the videos, 15 of 20 terms were misunderstood by more than one third of patients, with 98% unable to define “maintenance,” 74% unable to define “cancer,” and 58% unable to define “chemotherapy.” Six pilot educational videos describing a narrowed down list of six terms were created, and patient understanding of all six terms improved by at least 20% after watching the videos. The six terms defined in the videos were “palliative chemotherapy,” “curative,” “cancer,” “blood count,” “risk of infection,” and “chemotherapy.”
“Although a current concern is that precision medicines will not be understood due to genetic illiteracy and misunderstandings about the immune system, it is important to remember that the terminology used to describe chemotherapy, the backbone of many cancer treatments, may also be incomprehensible to some patients,” Rebecca Pentz, PhD, of Emory University, Atlanta, and colleagues wrote.
“Our video pilot suggests that multimedia can help patients understand chemotherapy terminology,” Dr. Pentz and colleagues said. “For each term, there was at least a 20% increase in patient understanding after watching the video. None of the patients could define palliative chemotherapy before watching the video, but 72% were able to provide a definition afterward.”
Researchers noted that the term most understood after the video was curative treatment (patients being able to define the phrase grew from 34% to 88%).
“Our study establishes that basic chemotherapy terminology is widely misunderstood by an underserved population, but that video-based education can significantly increase patient understanding,” the investigators concluded, but noted the research was limited by the small number of videos as well as the single underserved hospital, which may limit the generalizablility of the study.
Dr. Pentz and colleagues added that “education of physicians about the severe patient lack of understanding of basic cancer terminology and methods to improve understanding would be most helpful.”
SOURCE: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.
FROM CANCER
Key clinical point: Short videos on chemotherapy terms improved patient understanding of concepts.
Major finding: Patient understanding of the six terms chosen as part of the study improved by at least 20%.
Study details: 50 patients were asked to define six terms related to cancer treatment before and after seeing a 1-minute video on each term.
Disclosures: The research was sponsored by the Winship Cancer Institute and the National Cancer Institute. Research authors reported no conflicts of interest.
Source: Pentz R et al. Cancer. 2019 Aug 16. doi: 10.1002/cncr.32421.
Cancer survivors face more age-related deficits
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
Long-term survivors of cancer have more age-related functional deficits than do those who have not experienced cancer, and these deficits – as well as their cancer history – are both associated with a higher risk of all-cause mortality, a study has found.
A paper published in Cancer reported the outcomes of a population-based cohort study involving 1,723 female cancer survivors and 11,145 cancer-free women enrolled in the Iowa Women’s Health Study, who were followed for 10 years.
The analysis revealed that women with a history of cancer had significantly more deficits on a geriatric assessment compared with their age-matched controls without a history of cancer. While 66% of women without a cancer history had one or more deficits, 70% of those with a history had at least one age-related deficit, and they were significantly more likely to have two or more deficits.
Cancer survivors were significantly more likely to have two or more physical function limitations than were those without a history of cancer (42.4% vs. 36.9%, P less than .0001), to have two or more comorbidities (41.3% vs. 38.2%, P = .02) and to have poor general health (23.3% vs. 17.4%, P less than .0001). They were also significantly less likely to be underweight.
The study found that both cancer history and age-related functional deficits were predictors of mortality, even after adjustment for confounders such as chronological age, smoking, and physical activity levels. The highest mortality risk was seen in cancer survivors with two or more age-related health deficits, who had a twofold greater mortality risk compared with the noncancer controls with fewer than two health deficits.
Even individuals with a history of cancer but without any health deficits still had a 1.3-1.4-fold increased risk of mortality compared with individuals without a history of cancer and without health deficits.
“These results confirm the increased risk of mortality associated with GA domain deficits and extend the research by demonstrating that a cancer history is associated with an older functional age compared with aged-matched cancer-free individuals,” wrote Cindy K. Blair, PhD, of the department of internal medicine at the University of New Mexico, Albuquerque, and coauthors.
They noted that the study included very long-term cancer survivors who had survived for an average of 11 years before they underwent the geriatric assessment and were then followed for 10 years after that point.
“Further research is needed to identify older cancer survivors who are at risk of accelerated aging,” the authors wrote. “Interventions that target physical function, comorbidity, nutritional status, and general health are greatly needed to improve or maintain the quality of survivorship in older cancer survivors.”
The National Cancer Institute, the University of Minnesota Cancer Center, and the University of New Mexico Comprehensive Cancer Center supported the study. Two authors declared grants from the National Institutes of Health related to the study.
SOURCE: Blair C et al. Cancer 2019, Aug 16. doi: 10.1002/cncr.32449.
FROM CANCER
Diet, exercise don’t improve breast cancer-related lymphedema
Neither weight-loss nor home-based exercise programs improved outcomes for women with breast cancer–related lymphedema, investigators found.
Among 351 overweight breast cancer survivors with breast cancer–related lymphedema (BCRL), there were no significant differences at 1 year of follow-up in the percentage difference between limb volumes from baseline, regardless of whether patients had been randomly assigned to a home-based exercise program, weight-loss program, combined interventions, or to a facility-based lymphedema care–only program, reported Kathryn H. Schmitz, PhD, MPH, from Penn State University, Hershey, and colleagues.
“Our findings are contradictory to our own clinical experience, as we have received reports from patients with BCRL who have noted improvements in their lymphedema symptoms after weight loss. Possible explanations for this mismatch of clinical experience and empirical evidence include alterations in aspects of lymphedema, such as tissue composition, that remain challenging to measure with high reliability and validity,” they wrote in JAMA Oncology.
The findings suggest that breast cancer survivors with lymphedema may benefit more from facility-based exercise than home-based lymphedema care, the investigators wrote.
In the randomized Women in Steady Exercise Research (WISER) Survivor trial, the investigators enrolled 351 overweight breast cancer survivors with lymphedema and randomly assigned them to a 52-week home-based exercise program consisting of strength and resistance training twice per week and 180 minutes per week of walking (87 patients), a weight-loss program consisting of 20 weeks of meal replacement and 1 year of lifestyle-modification counseling (87 patients), a combination of the two programs (87 patients), or a facility-based lymphedema care program only (90 patients, control group).
The primary endpoint was originally intended to be lymphedema clinical events such as incident flare-ups or cellulitis, but was changed to the percentage of interlimb difference (that is, between the affected and unaffected limb) because of a reduction in funding that led to a reduction in the sample size.
There were no significant between-group differences at either baseline or 12 months in either the percentage of interlimb differences or in absolute differences, the investigators found.
Women assigned to the diet and exercise intervention lost significantly more weight than controls (P less than .001), but saw significant improvements in fitness only in the maximum amount of weight they could lift (P = .01).
“Multiple national organizations currently advise overweight women to achieve and maintain a healthy weight to improve the outcomes of previously diagnosed BCRL. The empirical evidence base, including data from the present study, does not support the assertion that weight loss as an intervention improves the hallmark measure of BCRL severity, percentage of interlimb difference,” Dr. Schmitz and colleagues wrote.
They acknowledged that BCRL is a long-term condition and that the 1-year follow-up period may have been too short to observe lymphedema exacerbation or related clinical events; therefore, the results may not apply to women with severe lymphedema, such as those with interlimb differences of greater than 30%.
The study was supported by various National Institutes of Health grants. Compression garments were supplied by BSN Medical. Dr. Schmitz reported receiving grants from the National Cancer Institute and nonfinancial support from BSN Medical during the conduct of the study, personal fees from Klose Training outside the submitted work, and a licensed patent for a Strength After Breast Cancer course.
SOURCE: Schmitz KH et al. JAMA Oncol. 2019 Aug 15. doi: 10.1001/jamaoncol.2019.2109..
Neither weight-loss nor home-based exercise programs improved outcomes for women with breast cancer–related lymphedema, investigators found.
Among 351 overweight breast cancer survivors with breast cancer–related lymphedema (BCRL), there were no significant differences at 1 year of follow-up in the percentage difference between limb volumes from baseline, regardless of whether patients had been randomly assigned to a home-based exercise program, weight-loss program, combined interventions, or to a facility-based lymphedema care–only program, reported Kathryn H. Schmitz, PhD, MPH, from Penn State University, Hershey, and colleagues.
“Our findings are contradictory to our own clinical experience, as we have received reports from patients with BCRL who have noted improvements in their lymphedema symptoms after weight loss. Possible explanations for this mismatch of clinical experience and empirical evidence include alterations in aspects of lymphedema, such as tissue composition, that remain challenging to measure with high reliability and validity,” they wrote in JAMA Oncology.
The findings suggest that breast cancer survivors with lymphedema may benefit more from facility-based exercise than home-based lymphedema care, the investigators wrote.
In the randomized Women in Steady Exercise Research (WISER) Survivor trial, the investigators enrolled 351 overweight breast cancer survivors with lymphedema and randomly assigned them to a 52-week home-based exercise program consisting of strength and resistance training twice per week and 180 minutes per week of walking (87 patients), a weight-loss program consisting of 20 weeks of meal replacement and 1 year of lifestyle-modification counseling (87 patients), a combination of the two programs (87 patients), or a facility-based lymphedema care program only (90 patients, control group).
The primary endpoint was originally intended to be lymphedema clinical events such as incident flare-ups or cellulitis, but was changed to the percentage of interlimb difference (that is, between the affected and unaffected limb) because of a reduction in funding that led to a reduction in the sample size.
There were no significant between-group differences at either baseline or 12 months in either the percentage of interlimb differences or in absolute differences, the investigators found.
Women assigned to the diet and exercise intervention lost significantly more weight than controls (P less than .001), but saw significant improvements in fitness only in the maximum amount of weight they could lift (P = .01).
“Multiple national organizations currently advise overweight women to achieve and maintain a healthy weight to improve the outcomes of previously diagnosed BCRL. The empirical evidence base, including data from the present study, does not support the assertion that weight loss as an intervention improves the hallmark measure of BCRL severity, percentage of interlimb difference,” Dr. Schmitz and colleagues wrote.
They acknowledged that BCRL is a long-term condition and that the 1-year follow-up period may have been too short to observe lymphedema exacerbation or related clinical events; therefore, the results may not apply to women with severe lymphedema, such as those with interlimb differences of greater than 30%.
The study was supported by various National Institutes of Health grants. Compression garments were supplied by BSN Medical. Dr. Schmitz reported receiving grants from the National Cancer Institute and nonfinancial support from BSN Medical during the conduct of the study, personal fees from Klose Training outside the submitted work, and a licensed patent for a Strength After Breast Cancer course.
SOURCE: Schmitz KH et al. JAMA Oncol. 2019 Aug 15. doi: 10.1001/jamaoncol.2019.2109..
Neither weight-loss nor home-based exercise programs improved outcomes for women with breast cancer–related lymphedema, investigators found.
Among 351 overweight breast cancer survivors with breast cancer–related lymphedema (BCRL), there were no significant differences at 1 year of follow-up in the percentage difference between limb volumes from baseline, regardless of whether patients had been randomly assigned to a home-based exercise program, weight-loss program, combined interventions, or to a facility-based lymphedema care–only program, reported Kathryn H. Schmitz, PhD, MPH, from Penn State University, Hershey, and colleagues.
“Our findings are contradictory to our own clinical experience, as we have received reports from patients with BCRL who have noted improvements in their lymphedema symptoms after weight loss. Possible explanations for this mismatch of clinical experience and empirical evidence include alterations in aspects of lymphedema, such as tissue composition, that remain challenging to measure with high reliability and validity,” they wrote in JAMA Oncology.
The findings suggest that breast cancer survivors with lymphedema may benefit more from facility-based exercise than home-based lymphedema care, the investigators wrote.
In the randomized Women in Steady Exercise Research (WISER) Survivor trial, the investigators enrolled 351 overweight breast cancer survivors with lymphedema and randomly assigned them to a 52-week home-based exercise program consisting of strength and resistance training twice per week and 180 minutes per week of walking (87 patients), a weight-loss program consisting of 20 weeks of meal replacement and 1 year of lifestyle-modification counseling (87 patients), a combination of the two programs (87 patients), or a facility-based lymphedema care program only (90 patients, control group).
The primary endpoint was originally intended to be lymphedema clinical events such as incident flare-ups or cellulitis, but was changed to the percentage of interlimb difference (that is, between the affected and unaffected limb) because of a reduction in funding that led to a reduction in the sample size.
There were no significant between-group differences at either baseline or 12 months in either the percentage of interlimb differences or in absolute differences, the investigators found.
Women assigned to the diet and exercise intervention lost significantly more weight than controls (P less than .001), but saw significant improvements in fitness only in the maximum amount of weight they could lift (P = .01).
“Multiple national organizations currently advise overweight women to achieve and maintain a healthy weight to improve the outcomes of previously diagnosed BCRL. The empirical evidence base, including data from the present study, does not support the assertion that weight loss as an intervention improves the hallmark measure of BCRL severity, percentage of interlimb difference,” Dr. Schmitz and colleagues wrote.
They acknowledged that BCRL is a long-term condition and that the 1-year follow-up period may have been too short to observe lymphedema exacerbation or related clinical events; therefore, the results may not apply to women with severe lymphedema, such as those with interlimb differences of greater than 30%.
The study was supported by various National Institutes of Health grants. Compression garments were supplied by BSN Medical. Dr. Schmitz reported receiving grants from the National Cancer Institute and nonfinancial support from BSN Medical during the conduct of the study, personal fees from Klose Training outside the submitted work, and a licensed patent for a Strength After Breast Cancer course.
SOURCE: Schmitz KH et al. JAMA Oncol. 2019 Aug 15. doi: 10.1001/jamaoncol.2019.2109..
FROM JAMA ONCOLOGY
New biomarker model outmatches conventional risk factors for predicting mortality
A new model using 14 biomarkers may be more accurate at predicting longer-term mortality than a model comprising conventional risk factors, based on the largest metabolomics study to date.
The prognostic model was more accurate at predicting 5- and 10-year mortality across all ages, reported Joris Deelen, PhD, of Leiden (the Netherlands) University Medical Center and colleagues.
“These results suggest that metabolic biomarker profiling could potentially be used to guide patient care, if further validated in relevant clinical settings,” the investigators wrote in Nature Communications.
“There is no consensus on the ultimate set of predictors of longer-term [5-10 years] mortality risk, since the predictive power of the currently used risk factors is limited, especially at higher ages,” the investigators wrote. “However, it is especially this age group and follow-up time window for which a robust tool would aid clinicians in assessing whether treatment is still sensible.”
The current study was a survival meta-analysis of 44,168 individuals from 12 cohorts aged between 18 and 109 years at baseline. First, the investigators looked for associations between 226 metabolic biomarkers and all-cause mortality in the 5,512 people who died during follow-up. This revealed associations between mortality and 136 biomarkers, which increased to 159 biomarkers after adjusting for recently reported all-cause mortality associations with albumin, very low-density lipoprotein (VLDL) particle size, citrate, and glycoprotein acetyls. Because of strong correlations between many of the biomarkers evaluated, the investigators pared the field down to 63 biomarkers, then used a forward-backward procedure to ultimately identify 14 biomarkers independently associated with mortality. Of the four recently described biomarkers, citrate was excluded from the final model because of its minimal contribution to mortality estimates.
The 14 biomarkers were total lipids in chylomicrons and extremely large VLDL cholesterol, total lipids in small HDL cholesterol, mean diameter for VLDL cholesterol particles, ratio of polyunsaturated fatty acids to total fatty acids, glucose, lactate, histidine, isoleucine, leucine, valine, phenylalanine, acetoacetate, albumin, and glycoprotein acetyls.
“The 14 identified biomarkers are involved in various processes, such as lipoprotein and fatty acid metabolism, glycolysis, fluid balance, and inflammation. Although the majority of these biomarkers have been associated with mortality before, this is the first study that shows their independent effect when combined into one model,” the researchers wrote.
Implementation of the new biomarker model led to a score that typically ranged from –2 to 3. A 1-point increase was associated with a 173% increased risk of death (hazard ratio, 2.73; P less than 1 x 10–132). Analysis of cause-specific mortality revealed that most biomarkers were predictive of multiple causes of death. Some biomarkers were more focused; glucose, for example, was more predictive of cardiovascular-related death than of death because of cancer or nonlocalized infections. Compared with a model incorporating conventional risk factors, the biomarker model more accurately predicted 5- and 10-year mortality, with respective C-statistics of 0.837 versus 0.772 and 0.830 versus 0.790. This superiority was even more pronounced when only individuals aged older than 60 years were included.
The study was funded by Biobanking and BioMolecular resources Research Initiative–Netherlands. The investigators reported additional relationships with Nightingale Health, Novo Nordisk, and Bayer.
SOURCE: Deelen J et al. Nature Comm. 2019 Aug 20. doi: 10.1038/s41467-019-11311-9.
A new model using 14 biomarkers may be more accurate at predicting longer-term mortality than a model comprising conventional risk factors, based on the largest metabolomics study to date.
The prognostic model was more accurate at predicting 5- and 10-year mortality across all ages, reported Joris Deelen, PhD, of Leiden (the Netherlands) University Medical Center and colleagues.
“These results suggest that metabolic biomarker profiling could potentially be used to guide patient care, if further validated in relevant clinical settings,” the investigators wrote in Nature Communications.
“There is no consensus on the ultimate set of predictors of longer-term [5-10 years] mortality risk, since the predictive power of the currently used risk factors is limited, especially at higher ages,” the investigators wrote. “However, it is especially this age group and follow-up time window for which a robust tool would aid clinicians in assessing whether treatment is still sensible.”
The current study was a survival meta-analysis of 44,168 individuals from 12 cohorts aged between 18 and 109 years at baseline. First, the investigators looked for associations between 226 metabolic biomarkers and all-cause mortality in the 5,512 people who died during follow-up. This revealed associations between mortality and 136 biomarkers, which increased to 159 biomarkers after adjusting for recently reported all-cause mortality associations with albumin, very low-density lipoprotein (VLDL) particle size, citrate, and glycoprotein acetyls. Because of strong correlations between many of the biomarkers evaluated, the investigators pared the field down to 63 biomarkers, then used a forward-backward procedure to ultimately identify 14 biomarkers independently associated with mortality. Of the four recently described biomarkers, citrate was excluded from the final model because of its minimal contribution to mortality estimates.
The 14 biomarkers were total lipids in chylomicrons and extremely large VLDL cholesterol, total lipids in small HDL cholesterol, mean diameter for VLDL cholesterol particles, ratio of polyunsaturated fatty acids to total fatty acids, glucose, lactate, histidine, isoleucine, leucine, valine, phenylalanine, acetoacetate, albumin, and glycoprotein acetyls.
“The 14 identified biomarkers are involved in various processes, such as lipoprotein and fatty acid metabolism, glycolysis, fluid balance, and inflammation. Although the majority of these biomarkers have been associated with mortality before, this is the first study that shows their independent effect when combined into one model,” the researchers wrote.
Implementation of the new biomarker model led to a score that typically ranged from –2 to 3. A 1-point increase was associated with a 173% increased risk of death (hazard ratio, 2.73; P less than 1 x 10–132). Analysis of cause-specific mortality revealed that most biomarkers were predictive of multiple causes of death. Some biomarkers were more focused; glucose, for example, was more predictive of cardiovascular-related death than of death because of cancer or nonlocalized infections. Compared with a model incorporating conventional risk factors, the biomarker model more accurately predicted 5- and 10-year mortality, with respective C-statistics of 0.837 versus 0.772 and 0.830 versus 0.790. This superiority was even more pronounced when only individuals aged older than 60 years were included.
The study was funded by Biobanking and BioMolecular resources Research Initiative–Netherlands. The investigators reported additional relationships with Nightingale Health, Novo Nordisk, and Bayer.
SOURCE: Deelen J et al. Nature Comm. 2019 Aug 20. doi: 10.1038/s41467-019-11311-9.
A new model using 14 biomarkers may be more accurate at predicting longer-term mortality than a model comprising conventional risk factors, based on the largest metabolomics study to date.
The prognostic model was more accurate at predicting 5- and 10-year mortality across all ages, reported Joris Deelen, PhD, of Leiden (the Netherlands) University Medical Center and colleagues.
“These results suggest that metabolic biomarker profiling could potentially be used to guide patient care, if further validated in relevant clinical settings,” the investigators wrote in Nature Communications.
“There is no consensus on the ultimate set of predictors of longer-term [5-10 years] mortality risk, since the predictive power of the currently used risk factors is limited, especially at higher ages,” the investigators wrote. “However, it is especially this age group and follow-up time window for which a robust tool would aid clinicians in assessing whether treatment is still sensible.”
The current study was a survival meta-analysis of 44,168 individuals from 12 cohorts aged between 18 and 109 years at baseline. First, the investigators looked for associations between 226 metabolic biomarkers and all-cause mortality in the 5,512 people who died during follow-up. This revealed associations between mortality and 136 biomarkers, which increased to 159 biomarkers after adjusting for recently reported all-cause mortality associations with albumin, very low-density lipoprotein (VLDL) particle size, citrate, and glycoprotein acetyls. Because of strong correlations between many of the biomarkers evaluated, the investigators pared the field down to 63 biomarkers, then used a forward-backward procedure to ultimately identify 14 biomarkers independently associated with mortality. Of the four recently described biomarkers, citrate was excluded from the final model because of its minimal contribution to mortality estimates.
The 14 biomarkers were total lipids in chylomicrons and extremely large VLDL cholesterol, total lipids in small HDL cholesterol, mean diameter for VLDL cholesterol particles, ratio of polyunsaturated fatty acids to total fatty acids, glucose, lactate, histidine, isoleucine, leucine, valine, phenylalanine, acetoacetate, albumin, and glycoprotein acetyls.
“The 14 identified biomarkers are involved in various processes, such as lipoprotein and fatty acid metabolism, glycolysis, fluid balance, and inflammation. Although the majority of these biomarkers have been associated with mortality before, this is the first study that shows their independent effect when combined into one model,” the researchers wrote.
Implementation of the new biomarker model led to a score that typically ranged from –2 to 3. A 1-point increase was associated with a 173% increased risk of death (hazard ratio, 2.73; P less than 1 x 10–132). Analysis of cause-specific mortality revealed that most biomarkers were predictive of multiple causes of death. Some biomarkers were more focused; glucose, for example, was more predictive of cardiovascular-related death than of death because of cancer or nonlocalized infections. Compared with a model incorporating conventional risk factors, the biomarker model more accurately predicted 5- and 10-year mortality, with respective C-statistics of 0.837 versus 0.772 and 0.830 versus 0.790. This superiority was even more pronounced when only individuals aged older than 60 years were included.
The study was funded by Biobanking and BioMolecular resources Research Initiative–Netherlands. The investigators reported additional relationships with Nightingale Health, Novo Nordisk, and Bayer.
SOURCE: Deelen J et al. Nature Comm. 2019 Aug 20. doi: 10.1038/s41467-019-11311-9.
FROM NATURE COMMUNICATIONS
Key clinical point: A new model using 14 biomarkers may be more accurate at predicting 5- and 10-year mortality than a model comprising conventional risk factors.
Major finding: The biomarker model better predicted 5-year mortality than the conventional model (C-statistic, 0.837 vs. 0.772).
Study details: A retrospective metabolomics study involving 44,168 individuals.
Disclosures: The study was funded by Biobanking and BioMolecular Resources Research Initiative–Netherlands. The investigators reported additional relationships with Nightingale Health, Novo Nordisk, and Bayer.
Source: Deelen J et al. Nature Comm. 2019 Aug 20. doi: 10.1038/s41467-019-11311-9.
USPSTF expands BRCA1/2 testing recommendations
The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.
In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.
The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).
“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.
Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.
By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.
Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.
Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
Important step forward
Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.
“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.
While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.
“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.
Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
More research needed
Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.
Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.
“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.
In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.
“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.
Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.
Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
Treatment implications
While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH
Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.
The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.
“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
Addressing disparities in care
The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.
“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.
Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.
Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.
“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.
The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.
In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.
The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).
“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.
Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.
By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.
Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.
Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
Important step forward
Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.
“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.
While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.
“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.
Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
More research needed
Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.
Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.
“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.
In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.
“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.
Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.
Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
Treatment implications
While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH
Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.
The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.
“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
Addressing disparities in care
The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.
“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.
Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.
Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.
“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.
The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
The U.S. Preventive Services Task Force (USPSTF) has updated its recommendations on assessment of breast cancer susceptibility gene (BRCA)-related cancer, substantially expanding the pool of individuals for whom risk assessment, testing, and counseling would be warranted.
In its 2013 recommendation, the USPSTF said referral for genetic counseling and evaluation for BRCA1/2 testing was warranted for women who had a family history linked to increased risk of potentially harmful BRCA1/2 mutations.
The updated recommendations, just published in JAMA, expand the screening-eligible population to include those with personal cancer history, and more specifically call out ancestry linked to BRCA1/2 mutations as a risk factor (JAMA. 2019;322[7]:652-65. doi: 10.1001/jama.2019.10987).
“The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool,” wrote Douglas K. Owens, MD, of Stanford (Calif.) University, and coauthors of the task force report.
Positive results on the risk assessment tool should prompt genetic counseling, and genetic testing if indicated after counseling, the USPSTF added in its statement.
By contrast, the task force recommends against routine assessment, counseling, and testing in women with no family history, personal history, or ancestry linked to possibly harmful BRCA1/2 gene mutations, consistent with their previous recommendation.
Mutations of BRCA1/2 genes occur in an estimated 1 in 300-500 women in the general population, and account for 15% of ovarian cancer and up to 10% of breast cancer cases, according to the USPSTF.
Breast cancer risk is increased up to 65% by 70 years in those women with clinically significant BRCA1/2 mutations, while risk of ovarian, fallopian tube, or peritoneal cancer are increased by up to 39%, according to studies cited by the USPSTF.
Important step forward
Including women with prior breast and ovarian cancer in the screening-eligible population is an “important step forward,” Susan Domcheck, MD, and Mark Robson, MD, said in a related editorial.
“While further expansion of the USPSTF recommendation should be considered, the importance is clear: Identification of individuals at risk of carrying a BRCA1/2 mutation can be lifesaving and should be a part of routine medical care,” Dr. Domcheck and Dr. Robson said in their editorial, which appears in JAMA.
While the updated recommendations explicitly call out ancestry as a risk factor, they stop short of endorsing testing for unaffected Ashkenazi Jewish women with no family history, the authors said.
“However, the statement may be interpreted as a step toward supporting unselected testing in this group,” they added.
Among unselected individuals of Ashkenazi Jewish descent, 1 in 40 have 1 of 3 specific BRCA1 or BRCA2 founder mutations, according to one study cited by Dr. Domcheck and Dr. Robson.
More research needed
Current research is still “limited or lacking” to address many key questions about the benefits and harms of risk assessment, genetic counseling, and genetic testing in women without BRCA1/2-related cancer, according to authors of a literature review used by the USPSTF.
Notably, the ability of risk assessment, testing, and counseling to reduce cancer incidence and mortality among such women has not been directly evaluated by studies to date, said the review authors, led by Heidi D. Nelson, MD, MPH, of Oregon Health & Science University, Portland.
“Without effectiveness trials of intensive screening, practice standards have preceded supporting evidence,” said Dr. Nelson and coauthors noted in a report on the review findings.
In observational studies, mastectomy and oophorectomy have been associated with substantial reductions in subsequent cancer incidence and mortality; however, they are invasive procedures with potential complications, the authors noted.
“To determine the appropriateness of risk assessment and genetic testing for BRCA1/2 mutations as a preventive service in primary care, more information is needed about mutation prevalence and the effect of testing in the general population,” they added.
Researchers studying BRCA1/2 assessment as preventive service in primary care have generally looked at highly selected patient populations in referral centers, and have reported relatively short-term outcomes, they said.
Research is additionally needed on access to genetic testing and follow-up, effectiveness of risk stratification and multigene panels, and the impact of direct-to-consumer genetic testing, among other key questions, the authors of the review added.
Treatment implications
While the USPSTF recommendations do not mention systemic therapy, finding a BRCA mutation in a cancer patient today has important implications for treatment, said Rachel L. Yung, MD, and Larissa A. Korde, MD, MPH
Specifically, poly (ADP-ribose) polymerase (PARP) inhibitors have proved effective in certain BRCA-related cancers, Dr. Yung and Dr. Korde said in an editorial on the updated recommendations appearing in JAMA Oncology.
The Food and Drug Administration has already approved several PARP inhibitors for treatment of BRCA-linked metastatic breast or ovarian cancers, and studies are underway for other tumor types, including prostate and pancreatic cancers that harbor a BRCA mutation.
“Increasing awareness of BRCA mutation as a target for treatment will likely lead to an increase in the identification of patients with cancer harboring germline BRCA mutations, which in turn will increase the need for cascade testing for relatives of affected probands,” wrote Dr. Yung and Dr. Korde.
Addressing disparities in care
The USPSTF recommendations for BRCA risk assessment do not address disparities in testing referral and variation in breast cancer phenotypes among women of African ancestry, owing to lack of evidence, according to Lisa Newman, MD, MPH, of the Interdisciplinary Breast Program at New York–Presbyterian/Weill Cornell Medical Center, New York.
“Paradoxically, the data-driven basis for the USPSTF recommendation statement may magnify existing genetic testing disparities,” Dr. Newman wrote in an editorial that appears in JAMA Surgery.
Non-Hispanic black women in the United States have a twofold higher incidence of triple-negative breast cancer, which is a well documented risk factor for BRCA1 mutation carrier status, according to Dr. Newman.
Despite this, she added, genetic counseling and testing referrals remain “disproportionately low” among U.S. patients of African ancestry.
“It remains imperative for clinicians to exercise clinical judgment and to be mindful of patient subsets that do not necessarily fit into recommendations designed for the majority or general populations,” Dr. Newman concluded in her editorial.
The USPSTF is funded by the Agency for Healthcare Research and Quality. Members of the task force receive travel reimbursement and honoraria for participating in USPSTF meetings.
FROM JAMA