Gastrointestinal Cancer

TOPLINE:

A novel method combining genetic variants, symptoms, and patient characteristics is moderately successful at predicting which primary care patients are at high risk of developing colorectal cancer (CRC) within the next 2 years — without the benefit of a faecal immunochemical test (FIT). Up to 16% of primary care patients are non-compliant with FIT, which is the gold standard for predicting CRC.

METHODOLOGY:

• This study was retrospective cohort of 50,387 UK Biobank participants reporting a CRC symptom in primary care at age ≥ 40 years.
• The novel method, called an integrated risk model, used a combination of a polygenic risk score from genetic testing, symptoms, and patient characteristics to identify patients likely to develop CRC in the next 2 years.
• The primary outcome was the risk model’s performance in classifying a CRC case according to a statistical metric, the receiver operating characteristic area under the curve. Values range from 0 to 1, where 1 indicates perfect discriminative power and 0.5 indicates no discriminative power.

TAKEAWAY:

• The cohort of 50,387 participants was found to have 438 cases of CRC and 49,949 controls without CRC within 2 years of symptom reporting. CRC cases were diagnosed by hospital records, cancer registries, or death records.
• Increased risk of a CRC diagnosis was identified by a combination of six variables: older age at index date of symptom, higher polygenic risk score, which included 201 variants, male sex, previous smoking, rectal bleeding, and change in bowel habit.
• The polygenic risk score alone had good ability to distinguish cases from controls because 1.45% of participants in the highest quintile and 0.42% in the lowest quintile were later diagnosed with CRC.
• The variables were used to calculate an integrated risk model, which estimated the cross-sectional risk (in 80% of the final cohort) of a subsequent CRC diagnosis within 2 years. The highest scoring integrated risk model in this study was found to have a receiver operating characteristic area under the curve value of 0.76 with a 95% CI of 0.71-0.81. (A value of this magnitude indicates moderate discriminative ability to distinguish cases from controls because it falls between 0.7 and 0.8. A higher value [above 0.8] is considered strong and a lower value [< 0.7] is considered weak.)

IN PRACTICE:

The authors concluded, “The [integrated risk model] developed in this study predicts, with good accuracy, which patients presenting with CRC symptoms in a primary care setting are likely to be diagnosed with CRC within the next 2 years.”

The integrated risk model has “potential to be immediately actionable in the clinical setting … [by] inform[ing] patient triage, improving early diagnostic rates and health outcomes and reducing pressure on diagnostic secondary care services.”

SOURCE:

The corresponding author is Harry D. Green of the University of Exeter, England. The study (2024 Aug 1. doi: 10.1038/s41431-024-01654-3) appeared in the European Journal of Human Genetics.

LIMITATIONS:

Limitations included an observational design and the inability of the integrated risk model to outperform FIT, which has a receiver operating characteristic area under the curve of 0.95.

DISCLOSURES:

None of the authors reported competing interests. The funding sources included the National Institute for Health and Care Research and others.

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

TOPLINE:

A novel method combining genetic variants, symptoms, and patient characteristics is moderately successful at predicting which primary care patients are at high risk of developing colorectal cancer (CRC) within the next 2 years — without the benefit of a faecal immunochemical test (FIT). Up to 16% of primary care patients are non-compliant with FIT, which is the gold standard for predicting CRC.

METHODOLOGY:

• This study was retrospective cohort of 50,387 UK Biobank participants reporting a CRC symptom in primary care at age ≥ 40 years.
• The novel method, called an integrated risk model, used a combination of a polygenic risk score from genetic testing, symptoms, and patient characteristics to identify patients likely to develop CRC in the next 2 years.
• The primary outcome was the risk model’s performance in classifying a CRC case according to a statistical metric, the receiver operating characteristic area under the curve. Values range from 0 to 1, where 1 indicates perfect discriminative power and 0.5 indicates no discriminative power.

TAKEAWAY:

• The cohort of 50,387 participants was found to have 438 cases of CRC and 49,949 controls without CRC within 2 years of symptom reporting. CRC cases were diagnosed by hospital records, cancer registries, or death records.
• Increased risk of a CRC diagnosis was identified by a combination of six variables: older age at index date of symptom, higher polygenic risk score, which included 201 variants, male sex, previous smoking, rectal bleeding, and change in bowel habit.
• The polygenic risk score alone had good ability to distinguish cases from controls because 1.45% of participants in the highest quintile and 0.42% in the lowest quintile were later diagnosed with CRC.
• The variables were used to calculate an integrated risk model, which estimated the cross-sectional risk (in 80% of the final cohort) of a subsequent CRC diagnosis within 2 years. The highest scoring integrated risk model in this study was found to have a receiver operating characteristic area under the curve value of 0.76 with a 95% CI of 0.71-0.81. (A value of this magnitude indicates moderate discriminative ability to distinguish cases from controls because it falls between 0.7 and 0.8. A higher value [above 0.8] is considered strong and a lower value [< 0.7] is considered weak.)

IN PRACTICE:

The authors concluded, “The [integrated risk model] developed in this study predicts, with good accuracy, which patients presenting with CRC symptoms in a primary care setting are likely to be diagnosed with CRC within the next 2 years.”

The integrated risk model has “potential to be immediately actionable in the clinical setting … [by] inform[ing] patient triage, improving early diagnostic rates and health outcomes and reducing pressure on diagnostic secondary care services.”

SOURCE:

The corresponding author is Harry D. Green of the University of Exeter, England. The study (2024 Aug 1. doi: 10.1038/s41431-024-01654-3) appeared in the European Journal of Human Genetics.

LIMITATIONS:

Limitations included an observational design and the inability of the integrated risk model to outperform FIT, which has a receiver operating characteristic area under the curve of 0.95.

DISCLOSURES:

None of the authors reported competing interests. The funding sources included the National Institute for Health and Care Research and others.

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

TOPLINE:

A novel method combining genetic variants, symptoms, and patient characteristics is moderately successful at predicting which primary care patients are at high risk of developing colorectal cancer (CRC) within the next 2 years — without the benefit of a faecal immunochemical test (FIT). Up to 16% of primary care patients are non-compliant with FIT, which is the gold standard for predicting CRC.

METHODOLOGY:

• This study was retrospective cohort of 50,387 UK Biobank participants reporting a CRC symptom in primary care at age ≥ 40 years.
• The novel method, called an integrated risk model, used a combination of a polygenic risk score from genetic testing, symptoms, and patient characteristics to identify patients likely to develop CRC in the next 2 years.
• The primary outcome was the risk model’s performance in classifying a CRC case according to a statistical metric, the receiver operating characteristic area under the curve. Values range from 0 to 1, where 1 indicates perfect discriminative power and 0.5 indicates no discriminative power.

TAKEAWAY:

• The cohort of 50,387 participants was found to have 438 cases of CRC and 49,949 controls without CRC within 2 years of symptom reporting. CRC cases were diagnosed by hospital records, cancer registries, or death records.
• Increased risk of a CRC diagnosis was identified by a combination of six variables: older age at index date of symptom, higher polygenic risk score, which included 201 variants, male sex, previous smoking, rectal bleeding, and change in bowel habit.
• The polygenic risk score alone had good ability to distinguish cases from controls because 1.45% of participants in the highest quintile and 0.42% in the lowest quintile were later diagnosed with CRC.
• The variables were used to calculate an integrated risk model, which estimated the cross-sectional risk (in 80% of the final cohort) of a subsequent CRC diagnosis within 2 years. The highest scoring integrated risk model in this study was found to have a receiver operating characteristic area under the curve value of 0.76 with a 95% CI of 0.71-0.81. (A value of this magnitude indicates moderate discriminative ability to distinguish cases from controls because it falls between 0.7 and 0.8. A higher value [above 0.8] is considered strong and a lower value [< 0.7] is considered weak.)

IN PRACTICE:

The authors concluded, “The [integrated risk model] developed in this study predicts, with good accuracy, which patients presenting with CRC symptoms in a primary care setting are likely to be diagnosed with CRC within the next 2 years.”

The integrated risk model has “potential to be immediately actionable in the clinical setting … [by] inform[ing] patient triage, improving early diagnostic rates and health outcomes and reducing pressure on diagnostic secondary care services.”

SOURCE:

The corresponding author is Harry D. Green of the University of Exeter, England. The study (2024 Aug 1. doi: 10.1038/s41431-024-01654-3) appeared in the European Journal of Human Genetics.

LIMITATIONS:

Limitations included an observational design and the inability of the integrated risk model to outperform FIT, which has a receiver operating characteristic area under the curve of 0.95.

DISCLOSURES:

None of the authors reported competing interests. The funding sources included the National Institute for Health and Care Research and others.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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

TOPLINE:

Adding metastasis-directed therapy (MDT) to systemic therapy improves progression-free survival (PFS) to 10.3 months vs 2.5 months with systemic therapy alone in patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).

METHODOLOGY:

• Researchers conducted a phase 2 multicenter, randomized basket trial involving 41 patients with oligometastatic PDAC in the EXTEND trial.
• Participants were randomly assigned 1:1 to receive MDT plus systemic therapy or systemic therapy alone.
• MDT included definitive local therapy, with stereotactic ablative radiotherapy recommended when feasible. Members of the control group were allowed to receive MDT if their disease progressed.
• The primary endpoint was PFS, measured from random assignment to radiologic progression, clinical progression, or death.
• “Secondary endpoints included overall survival, time to next-line systemic therapy, time to local failure, time to new lesion formation, toxicity, and quality of life,” the authors said.

TAKEAWAY:

• According to the authors, adding MDT to systemic therapy significantly improved PFS to 10.3 months vs 2.5 months with systemic therapy alone (P = .030).
• The hazard ratio for PFS was 0.43 (95% CI, 0.20-0.94), indicating a substantial reduction in the risk for disease progression or death with MDT.
• No grade 4 or 5 treatment-emergent adverse events were observed, suggesting that MDT is a safe addition to systemic therapy.
• Longer PFS and overall survival were associated with activated systemic immunity after MDT, suggesting that “an activated systemic immune profile, supported by a diverse T-cell receptor repertoire, might promote immunosurveillance of distant microscopic disease.”

IN PRACTICE:

“No other PDAC-specific trials have been reported, and tumor-agnostic studies, such as SABR-COMET or the National Health Service single-arm registry study, have not published PDAC-specific outcomes. Thus, the EXTEND trial provides the strongest evidence to date in favor of the existence of an oligometastatic state in PDAC.”

SOURCE:

The study was led by Ethan B. Ludmir, MD, and Alexander D. Sherry, MD, both of the University of Texas MD Anderson Cancer Center, Houston. It was published online on August 5 in The Journal of Clinical Oncology.

LIMITATIONS:

The study’s broad enrollment criteria may have introduced heterogeneity in the patient population, potentially affecting the generalizability of the findings. The study was not powered to evaluate overall survival, and the small sample size may have limited the robustness of the results. Crossover and non–cancer-related deaths could have influenced the comparisons, and quality-of-life data were limited because of the COVID-19 pandemic. The definition of oligometastasis used in the trial may have oversimplified the complex spectrum of the disease.

DISCLOSURES:

Dr. Ludmir disclosed employment with Alaunos Therapeutics and consulting for Xerient. Dr. Sherry reported employment with MD Anderson Cancer Center and honoraria from Sermo. One coauthor has an uncompensated relationship with Polaris Consulting. Another coauthor has stock ownership in BriaCell and a consulting or an advisory role with Regeneron. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Adding metastasis-directed therapy (MDT) to systemic therapy improves progression-free survival (PFS) to 10.3 months vs 2.5 months with systemic therapy alone in patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).

METHODOLOGY:

• Researchers conducted a phase 2 multicenter, randomized basket trial involving 41 patients with oligometastatic PDAC in the EXTEND trial.
• Participants were randomly assigned 1:1 to receive MDT plus systemic therapy or systemic therapy alone.
• MDT included definitive local therapy, with stereotactic ablative radiotherapy recommended when feasible. Members of the control group were allowed to receive MDT if their disease progressed.
• The primary endpoint was PFS, measured from random assignment to radiologic progression, clinical progression, or death.
• “Secondary endpoints included overall survival, time to next-line systemic therapy, time to local failure, time to new lesion formation, toxicity, and quality of life,” the authors said.

TAKEAWAY:

• According to the authors, adding MDT to systemic therapy significantly improved PFS to 10.3 months vs 2.5 months with systemic therapy alone (P = .030).
• The hazard ratio for PFS was 0.43 (95% CI, 0.20-0.94), indicating a substantial reduction in the risk for disease progression or death with MDT.
• No grade 4 or 5 treatment-emergent adverse events were observed, suggesting that MDT is a safe addition to systemic therapy.
• Longer PFS and overall survival were associated with activated systemic immunity after MDT, suggesting that “an activated systemic immune profile, supported by a diverse T-cell receptor repertoire, might promote immunosurveillance of distant microscopic disease.”

IN PRACTICE:

“No other PDAC-specific trials have been reported, and tumor-agnostic studies, such as SABR-COMET or the National Health Service single-arm registry study, have not published PDAC-specific outcomes. Thus, the EXTEND trial provides the strongest evidence to date in favor of the existence of an oligometastatic state in PDAC.”

SOURCE:

The study was led by Ethan B. Ludmir, MD, and Alexander D. Sherry, MD, both of the University of Texas MD Anderson Cancer Center, Houston. It was published online on August 5 in The Journal of Clinical Oncology.

LIMITATIONS:

The study’s broad enrollment criteria may have introduced heterogeneity in the patient population, potentially affecting the generalizability of the findings. The study was not powered to evaluate overall survival, and the small sample size may have limited the robustness of the results. Crossover and non–cancer-related deaths could have influenced the comparisons, and quality-of-life data were limited because of the COVID-19 pandemic. The definition of oligometastasis used in the trial may have oversimplified the complex spectrum of the disease.

DISCLOSURES:

Dr. Ludmir disclosed employment with Alaunos Therapeutics and consulting for Xerient. Dr. Sherry reported employment with MD Anderson Cancer Center and honoraria from Sermo. One coauthor has an uncompensated relationship with Polaris Consulting. Another coauthor has stock ownership in BriaCell and a consulting or an advisory role with Regeneron. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Adding metastasis-directed therapy (MDT) to systemic therapy improves progression-free survival (PFS) to 10.3 months vs 2.5 months with systemic therapy alone in patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).

METHODOLOGY:

• Researchers conducted a phase 2 multicenter, randomized basket trial involving 41 patients with oligometastatic PDAC in the EXTEND trial.
• Participants were randomly assigned 1:1 to receive MDT plus systemic therapy or systemic therapy alone.
• MDT included definitive local therapy, with stereotactic ablative radiotherapy recommended when feasible. Members of the control group were allowed to receive MDT if their disease progressed.
• The primary endpoint was PFS, measured from random assignment to radiologic progression, clinical progression, or death.
• “Secondary endpoints included overall survival, time to next-line systemic therapy, time to local failure, time to new lesion formation, toxicity, and quality of life,” the authors said.

TAKEAWAY:

• According to the authors, adding MDT to systemic therapy significantly improved PFS to 10.3 months vs 2.5 months with systemic therapy alone (P = .030).
• The hazard ratio for PFS was 0.43 (95% CI, 0.20-0.94), indicating a substantial reduction in the risk for disease progression or death with MDT.
• No grade 4 or 5 treatment-emergent adverse events were observed, suggesting that MDT is a safe addition to systemic therapy.
• Longer PFS and overall survival were associated with activated systemic immunity after MDT, suggesting that “an activated systemic immune profile, supported by a diverse T-cell receptor repertoire, might promote immunosurveillance of distant microscopic disease.”

IN PRACTICE:

“No other PDAC-specific trials have been reported, and tumor-agnostic studies, such as SABR-COMET or the National Health Service single-arm registry study, have not published PDAC-specific outcomes. Thus, the EXTEND trial provides the strongest evidence to date in favor of the existence of an oligometastatic state in PDAC.”

SOURCE:

The study was led by Ethan B. Ludmir, MD, and Alexander D. Sherry, MD, both of the University of Texas MD Anderson Cancer Center, Houston. It was published online on August 5 in The Journal of Clinical Oncology.

LIMITATIONS:

The study’s broad enrollment criteria may have introduced heterogeneity in the patient population, potentially affecting the generalizability of the findings. The study was not powered to evaluate overall survival, and the small sample size may have limited the robustness of the results. Crossover and non–cancer-related deaths could have influenced the comparisons, and quality-of-life data were limited because of the COVID-19 pandemic. The definition of oligometastasis used in the trial may have oversimplified the complex spectrum of the disease.

DISCLOSURES:

Dr. Ludmir disclosed employment with Alaunos Therapeutics and consulting for Xerient. Dr. Sherry reported employment with MD Anderson Cancer Center and honoraria from Sermo. One coauthor has an uncompensated relationship with Polaris Consulting. Another coauthor has stock ownership in BriaCell and a consulting or an advisory role with Regeneron. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

A breakthrough in medical testing now allows for colorectal cancer screening with just a simple blood test, promising a more accessible and less invasive way to catch the disease early. 

The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.

Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.

The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.

While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.

In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.

If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.

“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
 

A version of this article appeared on WebMD.com.

WASHINGTON — A risk-stratified upper age limit may be beneficial for colorectal cancer (CRC) screening among patients who are ages 75 and older, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.

“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.

In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.

FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.

Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.

Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.

However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).

In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.

About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.

In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.

For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.

“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”

The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.

“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.

At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.

“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”

Ms. van Stigt and Dr. Saini reported no relevant disclosures.

WASHINGTON — A risk-stratified upper age limit may be beneficial for colorectal cancer (CRC) screening among patients who are ages 75 and older, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.

“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.

In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.

FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.

Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.

Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.

However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).

In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.

About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.

In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.

For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.

“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”

The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.

“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.

At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.

“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”

Ms. van Stigt and Dr. Saini reported no relevant disclosures.

WASHINGTON — A risk-stratified upper age limit may be beneficial for colorectal cancer (CRC) screening among patients who are ages 75 and older, according to a study presented at the annual Digestive Disease Week^® (DDW).

In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.

“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.

In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.

FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.

Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.

Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.

However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).

In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.

About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.

In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.

For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.

“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”

The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.

“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.

At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.

“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”

Ms. van Stigt and Dr. Saini reported no relevant disclosures.