AVAHO

This article is a based on a video essay. The transcript has been edited for clarity.

I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”

As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.

This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?

This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.

There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.

The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.

By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.

Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.

I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.

Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.

Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.

These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.

Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.

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

This article is a based on a video essay. The transcript has been edited for clarity.

I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”

As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.

This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?

This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.

There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.

The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.

By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.

Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.

I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.

Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.

Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.

These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.

Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.

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

This article is a based on a video essay. The transcript has been edited for clarity.

I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”

As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.

This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?

This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.

There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.

The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.

By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.

Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.

I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.

Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.

Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.

These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.

Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.

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

TOPLINE:

Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.

METHODOLOGY:

• This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
• The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
• More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
• The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.

TAKEAWAY:

• At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
• Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
• KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
• Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.

IN PRACTICE:

“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”

SOURCE:

Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.

DISCLOSURES:

This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.

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:

Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.

METHODOLOGY:

• This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
• The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
• More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
• The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.

TAKEAWAY:

• At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
• Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
• KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
• Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.

IN PRACTICE:

“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”

SOURCE:

Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.

DISCLOSURES:

This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.

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:

Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.

METHODOLOGY:

• This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
• The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
• More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
• The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.

TAKEAWAY:

• At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
• Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
• KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
• Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.

IN PRACTICE:

“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”

SOURCE:

Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.

DISCLOSURES:

This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.

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.

Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.

For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.

Why have CAR T-cell therapies been less effective against solid tumors?

Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.

CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.

“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.

Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.

Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.

A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.

In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.

Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.

Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.

Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.

“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.

Several cell-based agents are in early trials to treat a range of solid tumors.

Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.

Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.

Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.

“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.

Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.

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

Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.

For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.

Why have CAR T-cell therapies been less effective against solid tumors?

Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.

CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.

“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.

Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.

Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.

A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.

In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.

Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.

Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.

Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.

“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.

Several cell-based agents are in early trials to treat a range of solid tumors.

Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.

Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.

Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.

“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.

Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.

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

Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.

For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.

Why have CAR T-cell therapies been less effective against solid tumors?

Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.

CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.

“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.

Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.

Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.

A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.

In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.

Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.

Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.

Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.

“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.

Several cell-based agents are in early trials to treat a range of solid tumors.

Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.

Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.

Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.

“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.

Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.

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

Only about 5% of hereditary prostate cancer (HPC) cases can be explained by known genetic variants, but a groundbreaking US Department of Veterans Affairs (VA) study could revolutionize the diagnosis, prevention, and treatment of HPC in a similar fashion that the discovery of the BRAC2 gene did in breast cancer.

The study, conducted at the VA Tennessee Valley Healthcare System in accordance with Vanderbilt University Medical Center and the VA Million Veteran Program (MVP), linked variants of the WNT9B gene with a greater risk of prostate cancer.

About 15,000 veterans are diagnosed with prostate cancer and treated at the VA annually, and > 200,000 veterans are prostate cancer survivors. According to Bruce Montgomery, MD, an oncologist with VA Puget Sound Health Care System, “Veterans are unique in that those men exposed to Agent Orange during the Vietnam War are at elevated risk for prostate cancer.” Montgomery added that germline pathogenic variants in genes such as BRCA2 and HOXB13 are other risk factors.

This genome-wide study searched for recurrently observed variants that carried the most risk. The study gathered data from a familial case-control population in the Nashville Familial Prostate Cancer Study (NFPCS) and International Consortium for Prostate Cancer Genetics (ICPCG). For evidence of replication, the study turned to 4 biobanks: the MVP, All of Us, the UK Biobank, and FinnGen.

The NFPCS is a case-control study based on family history. Patients included those undergoing treatment for prostate cancer and controls undergoing routine screening at Vanderbilt University Medical Center and the Nashville VA Medical Center between 2003 and 2009. Patients were included in the analysis if they had also had a first- or second-degree relative with prostate cancer. 

The ICPCG dataset encompasses unrelated HPC cases aggregated from 12 study sites across Finland, France, Germany, the UK, and the US. The MVP is the nation’s largest biorepository of veteran data and has one of the world’s most diverse cohorts of any genetic research program. More than 1 million veterans are enrolled, and 800-plus researchers are working on > 100 projects.

Pathogenic variants of only 2 genes met the replication requirement with genome-wide significance: HOXB13 and WNT9B. HOXB13 has been reported on in the literature, but this is the first study to investigate WNT9B.

Researchers identified 2 variants of the WNT9B gene: WNT9B E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing one-half million patients. The association of WNT9B E152K with prostate cancer was supported by the familial study populations and each biobank, with genome-wide significance. Variant WNT9B Q47R reached genome-wide significance in the Finnish study. The Q47R founder haplotype was also carried by familial prostate cancer cases in the US and UK.

Autosomal dominant WNT9B pathogenic variants are already known to cause embryonic developmental sequence defects, leading later to prostatic cysts, enlarged prostate, and seminal vesicle cysts. Seminal vesicle adenocarcinoma (or squamous cell carcinoma) and clear cell carcinoma of the prostate have also been reported. 

The study found that HOXB13 and WNT9B “share an unexpected commonality.” Both genes function in embryonic genitourinary development. WNT9B pathogenic variants cause the autosomal dominant Mayer-Rokitansky-Küster-Hauser syndrome, featuring genitourinary developmental defects. The study concluded: “Collectively, our observations implicate inherited variation in pathways guiding embryonic genitourinary development in the development of prostate cancer.”

“Significant investments” in VA-specific clinical trials recently have been pursued through a joint agreement between the VA and the Prostate Cancer Foundation, Montgomery said: “The Prostate Cancer Foundation is supporting tumor and germline sequencing of prostate cancer for veterans with advanced disease and providing resources to set up research infrastructure at 10 centers nationwide.” 

The VA has also published a prostate cancer clinical pathway and is in the process of creating a national prostate cancer registry. Such a database, as well as the MVP are both unique to the VA and key to research such as the Predicting Metastatic Progression of High Risk Localized Prostate Cancer study, which began in 2023. Five VA medical centers are collaborating on an artificial intelligence algorithm that will detect patterns indicative of aggressive prostate cancer. 

“A digital repository for data will allow for development, testing, and validation of prognostic classifiers that could positively impact clinical management of veterans with high-risk prostate cancer,” said Matthew Rettig, MD, chief of oncology and hematology at the Greater Los Angeles VA Medical Center who was coprincipal investigator for the study. “The infrastructure developed by this research will serve as a valuable hub for future discovery.”

About 12% of men with metastatic prostate cancer carry a pathogenic germline alteration that could warrant the use of PARP (poly [ADP-ribose] polymerase) inhibitors or platinum chemotherapy, neither of which is part of standard care. National Comprehensive Cancer Network guidelines recommend germline testing in men with metastatic prostate cancer. In addition, “the family members of veterans who carry these alterations could benefit from undergoing testing and taking advantage of potentially life-saving interventions and surveillance strategies if they are also carriers,” Montgomery wrote.

The VA is committed to improving access to germline testing for men with metastatic prostate cancer in several ways. Montgomery pointed to the system-wide VA genetic counseling and testing resource, the Genomic Medicine Service, and said somatic testing is available across the VA through the National Precision Oncology Program. Both programs can be extremely important to veterans because they provide access to precision oncology studies, along with off-label use of effective treatments. 

Precision oncology is the most rapidly moving area in prostate cancer, according to Montgomery. “In the VA, this has been embraced as a very specific need to find these therapeutic options for all veterans as quickly as possible. I am most excited by how the enthusiasm for these approaches is supported at all levels, both nationally and locally, because it makes implementing very significant changes to research and treatment possible.”

Only about 5% of hereditary prostate cancer (HPC) cases can be explained by known genetic variants, but a groundbreaking US Department of Veterans Affairs (VA) study could revolutionize the diagnosis, prevention, and treatment of HPC in a similar fashion that the discovery of the BRAC2 gene did in breast cancer.

The study, conducted at the VA Tennessee Valley Healthcare System in accordance with Vanderbilt University Medical Center and the VA Million Veteran Program (MVP), linked variants of the WNT9B gene with a greater risk of prostate cancer.

About 15,000 veterans are diagnosed with prostate cancer and treated at the VA annually, and > 200,000 veterans are prostate cancer survivors. According to Bruce Montgomery, MD, an oncologist with VA Puget Sound Health Care System, “Veterans are unique in that those men exposed to Agent Orange during the Vietnam War are at elevated risk for prostate cancer.” Montgomery added that germline pathogenic variants in genes such as BRCA2 and HOXB13 are other risk factors.

This genome-wide study searched for recurrently observed variants that carried the most risk. The study gathered data from a familial case-control population in the Nashville Familial Prostate Cancer Study (NFPCS) and International Consortium for Prostate Cancer Genetics (ICPCG). For evidence of replication, the study turned to 4 biobanks: the MVP, All of Us, the UK Biobank, and FinnGen.

The NFPCS is a case-control study based on family history. Patients included those undergoing treatment for prostate cancer and controls undergoing routine screening at Vanderbilt University Medical Center and the Nashville VA Medical Center between 2003 and 2009. Patients were included in the analysis if they had also had a first- or second-degree relative with prostate cancer. 

The ICPCG dataset encompasses unrelated HPC cases aggregated from 12 study sites across Finland, France, Germany, the UK, and the US. The MVP is the nation’s largest biorepository of veteran data and has one of the world’s most diverse cohorts of any genetic research program. More than 1 million veterans are enrolled, and 800-plus researchers are working on > 100 projects.

Pathogenic variants of only 2 genes met the replication requirement with genome-wide significance: HOXB13 and WNT9B. HOXB13 has been reported on in the literature, but this is the first study to investigate WNT9B.

Researchers identified 2 variants of the WNT9B gene: WNT9B E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing one-half million patients. The association of WNT9B E152K with prostate cancer was supported by the familial study populations and each biobank, with genome-wide significance. Variant WNT9B Q47R reached genome-wide significance in the Finnish study. The Q47R founder haplotype was also carried by familial prostate cancer cases in the US and UK.

Autosomal dominant WNT9B pathogenic variants are already known to cause embryonic developmental sequence defects, leading later to prostatic cysts, enlarged prostate, and seminal vesicle cysts. Seminal vesicle adenocarcinoma (or squamous cell carcinoma) and clear cell carcinoma of the prostate have also been reported. 

The study found that HOXB13 and WNT9B “share an unexpected commonality.” Both genes function in embryonic genitourinary development. WNT9B pathogenic variants cause the autosomal dominant Mayer-Rokitansky-Küster-Hauser syndrome, featuring genitourinary developmental defects. The study concluded: “Collectively, our observations implicate inherited variation in pathways guiding embryonic genitourinary development in the development of prostate cancer.”

“Significant investments” in VA-specific clinical trials recently have been pursued through a joint agreement between the VA and the Prostate Cancer Foundation, Montgomery said: “The Prostate Cancer Foundation is supporting tumor and germline sequencing of prostate cancer for veterans with advanced disease and providing resources to set up research infrastructure at 10 centers nationwide.” 

The VA has also published a prostate cancer clinical pathway and is in the process of creating a national prostate cancer registry. Such a database, as well as the MVP are both unique to the VA and key to research such as the Predicting Metastatic Progression of High Risk Localized Prostate Cancer study, which began in 2023. Five VA medical centers are collaborating on an artificial intelligence algorithm that will detect patterns indicative of aggressive prostate cancer. 

“A digital repository for data will allow for development, testing, and validation of prognostic classifiers that could positively impact clinical management of veterans with high-risk prostate cancer,” said Matthew Rettig, MD, chief of oncology and hematology at the Greater Los Angeles VA Medical Center who was coprincipal investigator for the study. “The infrastructure developed by this research will serve as a valuable hub for future discovery.”

About 12% of men with metastatic prostate cancer carry a pathogenic germline alteration that could warrant the use of PARP (poly [ADP-ribose] polymerase) inhibitors or platinum chemotherapy, neither of which is part of standard care. National Comprehensive Cancer Network guidelines recommend germline testing in men with metastatic prostate cancer. In addition, “the family members of veterans who carry these alterations could benefit from undergoing testing and taking advantage of potentially life-saving interventions and surveillance strategies if they are also carriers,” Montgomery wrote.

The VA is committed to improving access to germline testing for men with metastatic prostate cancer in several ways. Montgomery pointed to the system-wide VA genetic counseling and testing resource, the Genomic Medicine Service, and said somatic testing is available across the VA through the National Precision Oncology Program. Both programs can be extremely important to veterans because they provide access to precision oncology studies, along with off-label use of effective treatments. 

Precision oncology is the most rapidly moving area in prostate cancer, according to Montgomery. “In the VA, this has been embraced as a very specific need to find these therapeutic options for all veterans as quickly as possible. I am most excited by how the enthusiasm for these approaches is supported at all levels, both nationally and locally, because it makes implementing very significant changes to research and treatment possible.”

Only about 5% of hereditary prostate cancer (HPC) cases can be explained by known genetic variants, but a groundbreaking US Department of Veterans Affairs (VA) study could revolutionize the diagnosis, prevention, and treatment of HPC in a similar fashion that the discovery of the BRAC2 gene did in breast cancer.

The study, conducted at the VA Tennessee Valley Healthcare System in accordance with Vanderbilt University Medical Center and the VA Million Veteran Program (MVP), linked variants of the WNT9B gene with a greater risk of prostate cancer.

About 15,000 veterans are diagnosed with prostate cancer and treated at the VA annually, and > 200,000 veterans are prostate cancer survivors. According to Bruce Montgomery, MD, an oncologist with VA Puget Sound Health Care System, “Veterans are unique in that those men exposed to Agent Orange during the Vietnam War are at elevated risk for prostate cancer.” Montgomery added that germline pathogenic variants in genes such as BRCA2 and HOXB13 are other risk factors.

This genome-wide study searched for recurrently observed variants that carried the most risk. The study gathered data from a familial case-control population in the Nashville Familial Prostate Cancer Study (NFPCS) and International Consortium for Prostate Cancer Genetics (ICPCG). For evidence of replication, the study turned to 4 biobanks: the MVP, All of Us, the UK Biobank, and FinnGen.

The NFPCS is a case-control study based on family history. Patients included those undergoing treatment for prostate cancer and controls undergoing routine screening at Vanderbilt University Medical Center and the Nashville VA Medical Center between 2003 and 2009. Patients were included in the analysis if they had also had a first- or second-degree relative with prostate cancer. 

The ICPCG dataset encompasses unrelated HPC cases aggregated from 12 study sites across Finland, France, Germany, the UK, and the US. The MVP is the nation’s largest biorepository of veteran data and has one of the world’s most diverse cohorts of any genetic research program. More than 1 million veterans are enrolled, and 800-plus researchers are working on > 100 projects.

Pathogenic variants of only 2 genes met the replication requirement with genome-wide significance: HOXB13 and WNT9B. HOXB13 has been reported on in the literature, but this is the first study to investigate WNT9B.

Researchers identified 2 variants of the WNT9B gene: WNT9B E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing one-half million patients. The association of WNT9B E152K with prostate cancer was supported by the familial study populations and each biobank, with genome-wide significance. Variant WNT9B Q47R reached genome-wide significance in the Finnish study. The Q47R founder haplotype was also carried by familial prostate cancer cases in the US and UK.

Autosomal dominant WNT9B pathogenic variants are already known to cause embryonic developmental sequence defects, leading later to prostatic cysts, enlarged prostate, and seminal vesicle cysts. Seminal vesicle adenocarcinoma (or squamous cell carcinoma) and clear cell carcinoma of the prostate have also been reported. 

The study found that HOXB13 and WNT9B “share an unexpected commonality.” Both genes function in embryonic genitourinary development. WNT9B pathogenic variants cause the autosomal dominant Mayer-Rokitansky-Küster-Hauser syndrome, featuring genitourinary developmental defects. The study concluded: “Collectively, our observations implicate inherited variation in pathways guiding embryonic genitourinary development in the development of prostate cancer.”

“Significant investments” in VA-specific clinical trials recently have been pursued through a joint agreement between the VA and the Prostate Cancer Foundation, Montgomery said: “The Prostate Cancer Foundation is supporting tumor and germline sequencing of prostate cancer for veterans with advanced disease and providing resources to set up research infrastructure at 10 centers nationwide.” 

The VA has also published a prostate cancer clinical pathway and is in the process of creating a national prostate cancer registry. Such a database, as well as the MVP are both unique to the VA and key to research such as the Predicting Metastatic Progression of High Risk Localized Prostate Cancer study, which began in 2023. Five VA medical centers are collaborating on an artificial intelligence algorithm that will detect patterns indicative of aggressive prostate cancer. 

“A digital repository for data will allow for development, testing, and validation of prognostic classifiers that could positively impact clinical management of veterans with high-risk prostate cancer,” said Matthew Rettig, MD, chief of oncology and hematology at the Greater Los Angeles VA Medical Center who was coprincipal investigator for the study. “The infrastructure developed by this research will serve as a valuable hub for future discovery.”

About 12% of men with metastatic prostate cancer carry a pathogenic germline alteration that could warrant the use of PARP (poly [ADP-ribose] polymerase) inhibitors or platinum chemotherapy, neither of which is part of standard care. National Comprehensive Cancer Network guidelines recommend germline testing in men with metastatic prostate cancer. In addition, “the family members of veterans who carry these alterations could benefit from undergoing testing and taking advantage of potentially life-saving interventions and surveillance strategies if they are also carriers,” Montgomery wrote.

The VA is committed to improving access to germline testing for men with metastatic prostate cancer in several ways. Montgomery pointed to the system-wide VA genetic counseling and testing resource, the Genomic Medicine Service, and said somatic testing is available across the VA through the National Precision Oncology Program. Both programs can be extremely important to veterans because they provide access to precision oncology studies, along with off-label use of effective treatments. 

Precision oncology is the most rapidly moving area in prostate cancer, according to Montgomery. “In the VA, this has been embraced as a very specific need to find these therapeutic options for all veterans as quickly as possible. I am most excited by how the enthusiasm for these approaches is supported at all levels, both nationally and locally, because it makes implementing very significant changes to research and treatment possible.”

It is the best possible news after an advanced melanoma diagnosis: A clean 10-year scan. This, in all likelihood, means the patient is cured and can leave the office free from their annual ‘scanxiety.’ 

But even in the best-case scenarios, oncologists may dodge the word cure, searching for others such as “remission,” “no evidence of disease,” and “most likely cured” to communicate the good news. Using these more open-ended terms can give patients reassurance without providing false hope that the cancer won’t ever return.

The “risk of future recurrence — even when very small — makes oncologists reluctant to use the word cure, fearing it will be interpreted as a promise, and particularly one that might be broken,” Belinda E. Kiely, MD, and Martin R. Stockler, MD, medical oncologists from the University of Sydney in Australia, wrote in a recent editorial.

Is it ever safe for oncologists to use the word cure? Might doing so backfire? Or does a patient’s underlying fear of recurrence transcend the word?

 

A Word’s Heavy Impact

Part of clinicians’ hesitance to use the word cure may stem from a lack of accepted definition for the term in oncology.

For some experts, a cure means patients will have a normal life expectancy not affected by cancer. Being able to confidently tell a patient that “requires very long-term follow-up,” said James Larkin, PhD, a medical oncologist at The Royal Marsden Hospital, London, England.

The National Cancer Institute (NCI) has a similar definition: “Cure means that there are no traces of your cancer after treatment and the cancer will never come back,” the NCI website says.

The American Society of Clinical Oncology, however, defines cure much more narrowly, as “when a person’s cancer has not returned for at least 5 years after treatment.” 

Not having a standard definition of cure in oncology makes it even more challenging for an oncologist to know how to communicate that a cancer very likely won’t return, without overpromising.

Some of the hesitance in framing good news comes from nuances in prognoses that depend on the type and stage of cancer, explained Marleen Kok, MD, PhD, a breast cancer specialist from the Netherlands Cancer Institute in Amsterdam.

Patients with localized early-stage breast cancer, for instance, have a 5-year survival rate of nearly 100%, and most live 2 decades or longer but, for some, the cancer will return.

“If you talk about early disease, indeed, we cure 80% of breast cancer patients,” Kok said during a press conference at the annual 2024 European Society of Medical Oncology meeting. But sub-dividing breast cancer into tumor type adds complexity. “With triple negative breast cancer, if they relapse, they relapse during the first 2 or 3 years so, at 5 years, the majority are disease free. But that’s different for estrogen receptor positive breast cancer,” in which recurrences can come much later.

In advanced cancers, oncologists may, understandably, be more hesitant to use the word cure. However, ongoing progress in cancer treatments is making the prospect of a cure more likely for some patients.

Take recent findings in melanoma. The landmark CheckMate 067 study in advanced disease revealed that patients receiving the immunotherapy combination of nivolumab plus ipilimumab had a median melanoma-specific survival > 10 years and a median overall survival of about 6 years.

The findings from the trial suggest that “many patients may die from causes unrelated to melanoma — or, in essence, they are cured,” outside expert Elisa Funck-Brentano, MD, PhD, from Ambroise-Paré Hospital in Paris, France, explained to Medscape Medical News.

With CheckMate 067, “what we’re talking about here is potential cure of metastatic solid tumors, which in general is something that’s new,” said senior author Larkin. In fact, late relapses after the 2- to 3-year mark in immunotherapy-treated melanoma are extremely rare.

CheckMate 067 “really made people tempted to use the word cure, and I will say some people in our field do,” said Pauline Funchain, MD, a medical oncologist at Stanford Cancer Institute, and associate professor at Stanford University, Palo Alto, California. “The rest of us really, really want to, but are hesitant because of what we know about melanoma.”

Because the reality is late relapse is still possible.

The cancer can show up decades later and I think, as oncologists, that experience has sort of shaken us,” Funchain told this news organization.

“Oncologists are scarred by those examples,” agreed Evan Hall, MD, a medical oncologist at Fred Hutch Cancer Center and assistant professor at the University of Washington School of Medicine, both in Seattle.

Clinical trials also don’t typically frame patient outcomes in terms of being cured. A recent analysis, which examined the use of “cure” and “hope” in 13,363 oncology articles published between 2000 and 2019 in JAMA Oncology and the Journal of Clinical Oncology, found that both words were used infrequently, especially in primary research articles, and their use decreased significantly over time, even as survival rates in oncology improved. The word cure, for instance, appeared in about 0.1% of sentences in primary research papers published in either journal, though the context of its use was not identified.

Outcomes in cancer clinical trials, which may assess hundreds even thousands of patients, are largely framed in terms of risks and rates of survival — 85% of patients who received treatment X are alive at 5 years or patients receiving treatment Y have a 20% risk for recurrence, for instance.

These risks and rates can’t tell an oncologist whether the patient sitting in front of them can close the cancer chapter of their lives for good.

“I just saw a patient the other day who was 30 years out from their melanoma diagnosis, and they had a recurrence,” Hall recalled. That’s why, “ultimately, it’s a hard thing to tell somebody they’re cured,” he said. “I personally don’t really like using that term.”

While the literature on using the word cure in oncology is limited, one older survey of oncology clinicians supports this view that many feel reluctant to use the term. Of 117 oncology clinicians who responded, 81% said they were “hesitant to tell a patient that they are cured,” and 63% said that they “would never tell a patient that they are cured,” while just 36% said they were comfortable saying the word, with most respondents waiting at least 6-10 years before doing so.

A more recent Italian survey, however, revealed a more favorable view of the word cure in oncology. The survey, which included 224 clinicians and 249 patients, reported that > 90% of cancer physicians, which included surgeons, radiotherapists, and medical oncologists, agreed that it’s possible for a patient to be cured, while about 84% of patients believed this. And > 80% of respondents said using the word cure would be “beneficial” to patients.

Still, even for those hearing the word cure and feeling comforted by an oncologist’s reassurance, it may only provide short-term relief. Fear that the cancer will come slinking, even roaring, back eventually may loom. And this lingering worry can haunt cancer survivors for years.

In a recent cross-sectional study of 229 adults who survived childhood cancer and had lived cancer-free for decades, researchers found that one third reported experiencing clinically significant elevated fear that their primary cancer would recur or a subsequent malignant neoplasm would develop. Similar anxiety has been documented in long-term survivors of adult-onset cancers.

To some degree, every survivor will experience fear and anxiety that their cancer will come back and, at a certain level, that is normal, the study’s senior author Nicole Alberts, PhD, a psychologist, associate professor, and Canada research chair in Behavioural Health Intervention at Concordia University, Montréal, Quebec, Canada, told this news organization.

Although an oncologist’s words do matter and clinicians may wrestle with the right words for patients in the moment, it can take more than words to quell patients’ fear, she said.

“What we know about that kind of anxiety is that there’s this cycle where reassurance doesn’t really help in the long-term,” Alberts said. In other words, hearing the word cure from their oncologist initially makes people feel better, but the anxiety may eventually come back.

Alberts tries to help patients acknowledge and accept uncertainty while also calming residual or lingering anxiety about a cancer recurrence. Ultimately, Alberts’ goal is to help cancer survivors “find the sweet spot to live again.”

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

It is the best possible news after an advanced melanoma diagnosis: A clean 10-year scan. This, in all likelihood, means the patient is cured and can leave the office free from their annual ‘scanxiety.’ 

But even in the best-case scenarios, oncologists may dodge the word cure, searching for others such as “remission,” “no evidence of disease,” and “most likely cured” to communicate the good news. Using these more open-ended terms can give patients reassurance without providing false hope that the cancer won’t ever return.

The “risk of future recurrence — even when very small — makes oncologists reluctant to use the word cure, fearing it will be interpreted as a promise, and particularly one that might be broken,” Belinda E. Kiely, MD, and Martin R. Stockler, MD, medical oncologists from the University of Sydney in Australia, wrote in a recent editorial.

Is it ever safe for oncologists to use the word cure? Might doing so backfire? Or does a patient’s underlying fear of recurrence transcend the word?

 

A Word’s Heavy Impact

Part of clinicians’ hesitance to use the word cure may stem from a lack of accepted definition for the term in oncology.

For some experts, a cure means patients will have a normal life expectancy not affected by cancer. Being able to confidently tell a patient that “requires very long-term follow-up,” said James Larkin, PhD, a medical oncologist at The Royal Marsden Hospital, London, England.

The National Cancer Institute (NCI) has a similar definition: “Cure means that there are no traces of your cancer after treatment and the cancer will never come back,” the NCI website says.

The American Society of Clinical Oncology, however, defines cure much more narrowly, as “when a person’s cancer has not returned for at least 5 years after treatment.” 

Not having a standard definition of cure in oncology makes it even more challenging for an oncologist to know how to communicate that a cancer very likely won’t return, without overpromising.

Some of the hesitance in framing good news comes from nuances in prognoses that depend on the type and stage of cancer, explained Marleen Kok, MD, PhD, a breast cancer specialist from the Netherlands Cancer Institute in Amsterdam.

Patients with localized early-stage breast cancer, for instance, have a 5-year survival rate of nearly 100%, and most live 2 decades or longer but, for some, the cancer will return.

“If you talk about early disease, indeed, we cure 80% of breast cancer patients,” Kok said during a press conference at the annual 2024 European Society of Medical Oncology meeting. But sub-dividing breast cancer into tumor type adds complexity. “With triple negative breast cancer, if they relapse, they relapse during the first 2 or 3 years so, at 5 years, the majority are disease free. But that’s different for estrogen receptor positive breast cancer,” in which recurrences can come much later.

In advanced cancers, oncologists may, understandably, be more hesitant to use the word cure. However, ongoing progress in cancer treatments is making the prospect of a cure more likely for some patients.

Take recent findings in melanoma. The landmark CheckMate 067 study in advanced disease revealed that patients receiving the immunotherapy combination of nivolumab plus ipilimumab had a median melanoma-specific survival > 10 years and a median overall survival of about 6 years.

The findings from the trial suggest that “many patients may die from causes unrelated to melanoma — or, in essence, they are cured,” outside expert Elisa Funck-Brentano, MD, PhD, from Ambroise-Paré Hospital in Paris, France, explained to Medscape Medical News.

With CheckMate 067, “what we’re talking about here is potential cure of metastatic solid tumors, which in general is something that’s new,” said senior author Larkin. In fact, late relapses after the 2- to 3-year mark in immunotherapy-treated melanoma are extremely rare.

CheckMate 067 “really made people tempted to use the word cure, and I will say some people in our field do,” said Pauline Funchain, MD, a medical oncologist at Stanford Cancer Institute, and associate professor at Stanford University, Palo Alto, California. “The rest of us really, really want to, but are hesitant because of what we know about melanoma.”

Because the reality is late relapse is still possible.

The cancer can show up decades later and I think, as oncologists, that experience has sort of shaken us,” Funchain told this news organization.

“Oncologists are scarred by those examples,” agreed Evan Hall, MD, a medical oncologist at Fred Hutch Cancer Center and assistant professor at the University of Washington School of Medicine, both in Seattle.

Clinical trials also don’t typically frame patient outcomes in terms of being cured. A recent analysis, which examined the use of “cure” and “hope” in 13,363 oncology articles published between 2000 and 2019 in JAMA Oncology and the Journal of Clinical Oncology, found that both words were used infrequently, especially in primary research articles, and their use decreased significantly over time, even as survival rates in oncology improved. The word cure, for instance, appeared in about 0.1% of sentences in primary research papers published in either journal, though the context of its use was not identified.

Outcomes in cancer clinical trials, which may assess hundreds even thousands of patients, are largely framed in terms of risks and rates of survival — 85% of patients who received treatment X are alive at 5 years or patients receiving treatment Y have a 20% risk for recurrence, for instance.

These risks and rates can’t tell an oncologist whether the patient sitting in front of them can close the cancer chapter of their lives for good.

“I just saw a patient the other day who was 30 years out from their melanoma diagnosis, and they had a recurrence,” Hall recalled. That’s why, “ultimately, it’s a hard thing to tell somebody they’re cured,” he said. “I personally don’t really like using that term.”

While the literature on using the word cure in oncology is limited, one older survey of oncology clinicians supports this view that many feel reluctant to use the term. Of 117 oncology clinicians who responded, 81% said they were “hesitant to tell a patient that they are cured,” and 63% said that they “would never tell a patient that they are cured,” while just 36% said they were comfortable saying the word, with most respondents waiting at least 6-10 years before doing so.

A more recent Italian survey, however, revealed a more favorable view of the word cure in oncology. The survey, which included 224 clinicians and 249 patients, reported that > 90% of cancer physicians, which included surgeons, radiotherapists, and medical oncologists, agreed that it’s possible for a patient to be cured, while about 84% of patients believed this. And > 80% of respondents said using the word cure would be “beneficial” to patients.

Still, even for those hearing the word cure and feeling comforted by an oncologist’s reassurance, it may only provide short-term relief. Fear that the cancer will come slinking, even roaring, back eventually may loom. And this lingering worry can haunt cancer survivors for years.

In a recent cross-sectional study of 229 adults who survived childhood cancer and had lived cancer-free for decades, researchers found that one third reported experiencing clinically significant elevated fear that their primary cancer would recur or a subsequent malignant neoplasm would develop. Similar anxiety has been documented in long-term survivors of adult-onset cancers.

To some degree, every survivor will experience fear and anxiety that their cancer will come back and, at a certain level, that is normal, the study’s senior author Nicole Alberts, PhD, a psychologist, associate professor, and Canada research chair in Behavioural Health Intervention at Concordia University, Montréal, Quebec, Canada, told this news organization.

Although an oncologist’s words do matter and clinicians may wrestle with the right words for patients in the moment, it can take more than words to quell patients’ fear, she said.

“What we know about that kind of anxiety is that there’s this cycle where reassurance doesn’t really help in the long-term,” Alberts said. In other words, hearing the word cure from their oncologist initially makes people feel better, but the anxiety may eventually come back.

Alberts tries to help patients acknowledge and accept uncertainty while also calming residual or lingering anxiety about a cancer recurrence. Ultimately, Alberts’ goal is to help cancer survivors “find the sweet spot to live again.”

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

It is the best possible news after an advanced melanoma diagnosis: A clean 10-year scan. This, in all likelihood, means the patient is cured and can leave the office free from their annual ‘scanxiety.’ 

But even in the best-case scenarios, oncologists may dodge the word cure, searching for others such as “remission,” “no evidence of disease,” and “most likely cured” to communicate the good news. Using these more open-ended terms can give patients reassurance without providing false hope that the cancer won’t ever return.

The “risk of future recurrence — even when very small — makes oncologists reluctant to use the word cure, fearing it will be interpreted as a promise, and particularly one that might be broken,” Belinda E. Kiely, MD, and Martin R. Stockler, MD, medical oncologists from the University of Sydney in Australia, wrote in a recent editorial.

Is it ever safe for oncologists to use the word cure? Might doing so backfire? Or does a patient’s underlying fear of recurrence transcend the word?

 

A Word’s Heavy Impact

Part of clinicians’ hesitance to use the word cure may stem from a lack of accepted definition for the term in oncology.

For some experts, a cure means patients will have a normal life expectancy not affected by cancer. Being able to confidently tell a patient that “requires very long-term follow-up,” said James Larkin, PhD, a medical oncologist at The Royal Marsden Hospital, London, England.

The National Cancer Institute (NCI) has a similar definition: “Cure means that there are no traces of your cancer after treatment and the cancer will never come back,” the NCI website says.

The American Society of Clinical Oncology, however, defines cure much more narrowly, as “when a person’s cancer has not returned for at least 5 years after treatment.” 

Not having a standard definition of cure in oncology makes it even more challenging for an oncologist to know how to communicate that a cancer very likely won’t return, without overpromising.

Some of the hesitance in framing good news comes from nuances in prognoses that depend on the type and stage of cancer, explained Marleen Kok, MD, PhD, a breast cancer specialist from the Netherlands Cancer Institute in Amsterdam.

Patients with localized early-stage breast cancer, for instance, have a 5-year survival rate of nearly 100%, and most live 2 decades or longer but, for some, the cancer will return.

“If you talk about early disease, indeed, we cure 80% of breast cancer patients,” Kok said during a press conference at the annual 2024 European Society of Medical Oncology meeting. But sub-dividing breast cancer into tumor type adds complexity. “With triple negative breast cancer, if they relapse, they relapse during the first 2 or 3 years so, at 5 years, the majority are disease free. But that’s different for estrogen receptor positive breast cancer,” in which recurrences can come much later.

In advanced cancers, oncologists may, understandably, be more hesitant to use the word cure. However, ongoing progress in cancer treatments is making the prospect of a cure more likely for some patients.

Take recent findings in melanoma. The landmark CheckMate 067 study in advanced disease revealed that patients receiving the immunotherapy combination of nivolumab plus ipilimumab had a median melanoma-specific survival > 10 years and a median overall survival of about 6 years.

The findings from the trial suggest that “many patients may die from causes unrelated to melanoma — or, in essence, they are cured,” outside expert Elisa Funck-Brentano, MD, PhD, from Ambroise-Paré Hospital in Paris, France, explained to Medscape Medical News.

With CheckMate 067, “what we’re talking about here is potential cure of metastatic solid tumors, which in general is something that’s new,” said senior author Larkin. In fact, late relapses after the 2- to 3-year mark in immunotherapy-treated melanoma are extremely rare.

CheckMate 067 “really made people tempted to use the word cure, and I will say some people in our field do,” said Pauline Funchain, MD, a medical oncologist at Stanford Cancer Institute, and associate professor at Stanford University, Palo Alto, California. “The rest of us really, really want to, but are hesitant because of what we know about melanoma.”

Because the reality is late relapse is still possible.

The cancer can show up decades later and I think, as oncologists, that experience has sort of shaken us,” Funchain told this news organization.

“Oncologists are scarred by those examples,” agreed Evan Hall, MD, a medical oncologist at Fred Hutch Cancer Center and assistant professor at the University of Washington School of Medicine, both in Seattle.

Clinical trials also don’t typically frame patient outcomes in terms of being cured. A recent analysis, which examined the use of “cure” and “hope” in 13,363 oncology articles published between 2000 and 2019 in JAMA Oncology and the Journal of Clinical Oncology, found that both words were used infrequently, especially in primary research articles, and their use decreased significantly over time, even as survival rates in oncology improved. The word cure, for instance, appeared in about 0.1% of sentences in primary research papers published in either journal, though the context of its use was not identified.

Outcomes in cancer clinical trials, which may assess hundreds even thousands of patients, are largely framed in terms of risks and rates of survival — 85% of patients who received treatment X are alive at 5 years or patients receiving treatment Y have a 20% risk for recurrence, for instance.

These risks and rates can’t tell an oncologist whether the patient sitting in front of them can close the cancer chapter of their lives for good.

“I just saw a patient the other day who was 30 years out from their melanoma diagnosis, and they had a recurrence,” Hall recalled. That’s why, “ultimately, it’s a hard thing to tell somebody they’re cured,” he said. “I personally don’t really like using that term.”

While the literature on using the word cure in oncology is limited, one older survey of oncology clinicians supports this view that many feel reluctant to use the term. Of 117 oncology clinicians who responded, 81% said they were “hesitant to tell a patient that they are cured,” and 63% said that they “would never tell a patient that they are cured,” while just 36% said they were comfortable saying the word, with most respondents waiting at least 6-10 years before doing so.

A more recent Italian survey, however, revealed a more favorable view of the word cure in oncology. The survey, which included 224 clinicians and 249 patients, reported that > 90% of cancer physicians, which included surgeons, radiotherapists, and medical oncologists, agreed that it’s possible for a patient to be cured, while about 84% of patients believed this. And > 80% of respondents said using the word cure would be “beneficial” to patients.

Still, even for those hearing the word cure and feeling comforted by an oncologist’s reassurance, it may only provide short-term relief. Fear that the cancer will come slinking, even roaring, back eventually may loom. And this lingering worry can haunt cancer survivors for years.

In a recent cross-sectional study of 229 adults who survived childhood cancer and had lived cancer-free for decades, researchers found that one third reported experiencing clinically significant elevated fear that their primary cancer would recur or a subsequent malignant neoplasm would develop. Similar anxiety has been documented in long-term survivors of adult-onset cancers.

To some degree, every survivor will experience fear and anxiety that their cancer will come back and, at a certain level, that is normal, the study’s senior author Nicole Alberts, PhD, a psychologist, associate professor, and Canada research chair in Behavioural Health Intervention at Concordia University, Montréal, Quebec, Canada, told this news organization.

Although an oncologist’s words do matter and clinicians may wrestle with the right words for patients in the moment, it can take more than words to quell patients’ fear, she said.

“What we know about that kind of anxiety is that there’s this cycle where reassurance doesn’t really help in the long-term,” Alberts said. In other words, hearing the word cure from their oncologist initially makes people feel better, but the anxiety may eventually come back.

Alberts tries to help patients acknowledge and accept uncertainty while also calming residual or lingering anxiety about a cancer recurrence. Ultimately, Alberts’ goal is to help cancer survivors “find the sweet spot to live again.”

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

The risk of detecting colorectal cancer (CRC) increases by up to 13-fold in the presence of prior fecal hemoglobin (f-Hb) concentrations in fecal immunochemical tests (FIT), especially negative ones, according to a large international dose-response meta-analysis.

Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”

Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. 

Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.

According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.

 

Study Details

The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.

All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.

With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I² = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.

“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the United States report as a qualitative positive-negative result.”

The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.

Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.

 

Feasibility of Implementation

In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.

“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.

Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.

The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.

This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing. The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.

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

The risk of detecting colorectal cancer (CRC) increases by up to 13-fold in the presence of prior fecal hemoglobin (f-Hb) concentrations in fecal immunochemical tests (FIT), especially negative ones, according to a large international dose-response meta-analysis.

Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”

Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. 

Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.

According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.

 

Study Details

The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.

All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.

With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I² = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.

“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the United States report as a qualitative positive-negative result.”

The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.

Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.

 

Feasibility of Implementation

In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.

“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.

Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.

The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.

This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing. The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.

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

The risk of detecting colorectal cancer (CRC) increases by up to 13-fold in the presence of prior fecal hemoglobin (f-Hb) concentrations in fecal immunochemical tests (FIT), especially negative ones, according to a large international dose-response meta-analysis.

Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”

Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. 

Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.

According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.

 

Study Details

The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.

All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.

With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I² = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.

“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the United States report as a qualitative positive-negative result.”

The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.

Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.

 

Feasibility of Implementation

In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.

“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.

Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.

The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.

This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing. The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.

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

Quitting smoking is challenging, particularly when resources are limited. A recent study in the United States confirmed that an intensive program combining behavioral therapy and medication, linked to a lung cancer screening program, offers the highest success rate. However, its long-term success was similar to that of telephone counseling and drug therapy.

Pulmonologist and experienced smoking cessation specialist from Stuttgart, Germany, Alexander Rupp, MD, emphasized the importance of leveraging routine healthcare interactions to encourage smoking cessation. “Although every doctor-patient contact offers the opportunity to discuss the risks of smoking and the opportunities for smoking cessation, the ‘window of opportunity’ is very wide, especially during lung cancer screening,” he said.

Germany is preparing to launch a lung cancer screening program for high-risk individuals, primarily current smokers and former smokers. Following the establishment of radiation protection regulations for such a program last year, the German Federal Joint Committee is currently working on its design. The initiative could be a game-changer for smoking cessation.

Lung cancer screening has been available for smokers in the United States for some time. Paul M. Cinciripini, PhD, and colleagues from the University of Texas MD Anderson Cancer Center, Houston, examined three smoking cessation strategies with decreasing treatment intensity among screening participants.

 

Unique Opportunity

Previous studies have shown that participation in a lung cancer screening program — typically offered only to high-risk individuals — significantly increases motivation to quit smoking.

“Repeated contact with doctors, repeated CT scans, and especially the findings that require monitoring all contribute to this effect,” explained Rupp, who regularly offers smoking cessation courses.

It has long been known how smoking cessation works best. “The gold standard is a combination of behavioral therapy support and drug treatment — if there is an addiction and withdrawal symptoms occur after quitting, which is the case for the majority of smokers,” Rupp explained.

The US study reinforced what is already well known: More intensive treatment approaches lead to higher quit rates.

“We know that the more intensively we look after smokers, the higher the quit rate. This applies in both areas: The more therapy sessions we do and the more often we prescribe medication, the more likely the patients are to succeed in remaining abstinent,” Rupp said.

However, resources for intensive smoking cessation programs are limited. A database maintained by the German Cancer Research Center and the German Federal Center for Health Education lists only 455 providers of smoking cessation courses in Germany, “not all of which even work on an evidence-based basis,” Rupp emphasized. Given that there are around 16 million smokers in Germany, there is an urgent need for smoking cessation programs that are less resource-intensive.

 

Intensity Variations

The US study compared three smoking cessation strategies of varying intensities, integrating behavioral counseling and medication.

Group 1: An integrated program with eight behavioral therapy sessions and 10-12 weeks of nicotine replacement therapy or medication (bupropion or varenicline).

Group 2: Lighter version of the integrated program. It consisted of four telephone consultations, written materials, online support, and 12 weeks of nicotine replacement therapy or medication prescribed by a radiologist.

Group 3: The least intensive approach, with 12 weeks of nicotine replacement therapy alone.

Each strategy was evaluated in 210 lung cancer screening participants aged 55-64 years who smoked an average of 15-20 cigarettes per day.

After 3 months, significantly more participants in the most intensive program (Group 1, 37.1%) had quit smoking than those in the other two groups (Group 2, 27.1%; Group 3, 25.2%).

But after 6 months, the difference between Groups 1 and 2 was not significant. The quit rates were as follows: Group 1, 32.4%; Group 2, 27.6%; and Group 3, 20.5%.

“It can be concluded from these results that the intensity of smoking cessation can be reduced to a certain extent as long as the combination of behavioral counseling and medication is given,” Rupp concluded.

 

Digital Solutions

Another new possibility, which was not examined in the US study, is digital health applications.

Smoke Free is a digital health application that provides behavioral therapy support for smoking cessation and is available in both German and English. Designed to replicate structured smoking cessation programs and offers an accessible alternative for individuals seeking to quit smoking.

Rupp emphasized the potential of digital tools like Smoke Free to expand access to effective smoking cessation strategies, particularly for those unable to attend in-person programs. While traditional cessation programs are limited in availability, digital apps can increase engagement in and adherence to smoking cessation efforts.

However, the biggest hurdle is smokers’ procrastination: “If you make smokers an offer, they usually do not take action afterward because they are caught in their ambivalence about whether they should quit or not.”

 

Policy Implications

This makes smoking cessation a mandatory component of lung cancer screening in the future. “It’s about cancer, and patients are really afraid of that,” Rupp advocated.

In a position paper, the German Respiratory Society, supported by multiple medical societies, has called for smoking cessation to be integrated into lung cancer screening protocols, with full coverage of counseling and medication by health insurance.

“Smoking cessation must be a mandatory component. If a participant in the lung cancer screening does not want this, then he or she must actively object,” stressed Rupp, lead author of the position paper. Also, the costs of smoking cessation, including those of withdrawal-inhibiting medication, must be fully covered by statutory health insurance, which has not been the case to date.

“That’s the only thing that makes sense. You can’t deny an addict access to proven treatments, especially when we know that a smoker who quits spontaneously without support has a relapse rate of 95%-97%, and the medication per se increases the quit rate by a factor of two or three,” Rupp concluded.

This story was translated and adapted from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Quitting smoking is challenging, particularly when resources are limited. A recent study in the United States confirmed that an intensive program combining behavioral therapy and medication, linked to a lung cancer screening program, offers the highest success rate. However, its long-term success was similar to that of telephone counseling and drug therapy.

Pulmonologist and experienced smoking cessation specialist from Stuttgart, Germany, Alexander Rupp, MD, emphasized the importance of leveraging routine healthcare interactions to encourage smoking cessation. “Although every doctor-patient contact offers the opportunity to discuss the risks of smoking and the opportunities for smoking cessation, the ‘window of opportunity’ is very wide, especially during lung cancer screening,” he said.

Germany is preparing to launch a lung cancer screening program for high-risk individuals, primarily current smokers and former smokers. Following the establishment of radiation protection regulations for such a program last year, the German Federal Joint Committee is currently working on its design. The initiative could be a game-changer for smoking cessation.

Lung cancer screening has been available for smokers in the United States for some time. Paul M. Cinciripini, PhD, and colleagues from the University of Texas MD Anderson Cancer Center, Houston, examined three smoking cessation strategies with decreasing treatment intensity among screening participants.

 

Unique Opportunity

Previous studies have shown that participation in a lung cancer screening program — typically offered only to high-risk individuals — significantly increases motivation to quit smoking.

“Repeated contact with doctors, repeated CT scans, and especially the findings that require monitoring all contribute to this effect,” explained Rupp, who regularly offers smoking cessation courses.

It has long been known how smoking cessation works best. “The gold standard is a combination of behavioral therapy support and drug treatment — if there is an addiction and withdrawal symptoms occur after quitting, which is the case for the majority of smokers,” Rupp explained.

The US study reinforced what is already well known: More intensive treatment approaches lead to higher quit rates.

“We know that the more intensively we look after smokers, the higher the quit rate. This applies in both areas: The more therapy sessions we do and the more often we prescribe medication, the more likely the patients are to succeed in remaining abstinent,” Rupp said.

However, resources for intensive smoking cessation programs are limited. A database maintained by the German Cancer Research Center and the German Federal Center for Health Education lists only 455 providers of smoking cessation courses in Germany, “not all of which even work on an evidence-based basis,” Rupp emphasized. Given that there are around 16 million smokers in Germany, there is an urgent need for smoking cessation programs that are less resource-intensive.

 

Intensity Variations

The US study compared three smoking cessation strategies of varying intensities, integrating behavioral counseling and medication.

Group 1: An integrated program with eight behavioral therapy sessions and 10-12 weeks of nicotine replacement therapy or medication (bupropion or varenicline).

Group 2: Lighter version of the integrated program. It consisted of four telephone consultations, written materials, online support, and 12 weeks of nicotine replacement therapy or medication prescribed by a radiologist.

Group 3: The least intensive approach, with 12 weeks of nicotine replacement therapy alone.

Each strategy was evaluated in 210 lung cancer screening participants aged 55-64 years who smoked an average of 15-20 cigarettes per day.

After 3 months, significantly more participants in the most intensive program (Group 1, 37.1%) had quit smoking than those in the other two groups (Group 2, 27.1%; Group 3, 25.2%).

But after 6 months, the difference between Groups 1 and 2 was not significant. The quit rates were as follows: Group 1, 32.4%; Group 2, 27.6%; and Group 3, 20.5%.

“It can be concluded from these results that the intensity of smoking cessation can be reduced to a certain extent as long as the combination of behavioral counseling and medication is given,” Rupp concluded.

 

Digital Solutions

Another new possibility, which was not examined in the US study, is digital health applications.

Smoke Free is a digital health application that provides behavioral therapy support for smoking cessation and is available in both German and English. Designed to replicate structured smoking cessation programs and offers an accessible alternative for individuals seeking to quit smoking.

Rupp emphasized the potential of digital tools like Smoke Free to expand access to effective smoking cessation strategies, particularly for those unable to attend in-person programs. While traditional cessation programs are limited in availability, digital apps can increase engagement in and adherence to smoking cessation efforts.

However, the biggest hurdle is smokers’ procrastination: “If you make smokers an offer, they usually do not take action afterward because they are caught in their ambivalence about whether they should quit or not.”

 

Policy Implications

This makes smoking cessation a mandatory component of lung cancer screening in the future. “It’s about cancer, and patients are really afraid of that,” Rupp advocated.

In a position paper, the German Respiratory Society, supported by multiple medical societies, has called for smoking cessation to be integrated into lung cancer screening protocols, with full coverage of counseling and medication by health insurance.

“Smoking cessation must be a mandatory component. If a participant in the lung cancer screening does not want this, then he or she must actively object,” stressed Rupp, lead author of the position paper. Also, the costs of smoking cessation, including those of withdrawal-inhibiting medication, must be fully covered by statutory health insurance, which has not been the case to date.

“That’s the only thing that makes sense. You can’t deny an addict access to proven treatments, especially when we know that a smoker who quits spontaneously without support has a relapse rate of 95%-97%, and the medication per se increases the quit rate by a factor of two or three,” Rupp concluded.

This story was translated and adapted from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Quitting smoking is challenging, particularly when resources are limited. A recent study in the United States confirmed that an intensive program combining behavioral therapy and medication, linked to a lung cancer screening program, offers the highest success rate. However, its long-term success was similar to that of telephone counseling and drug therapy.

Pulmonologist and experienced smoking cessation specialist from Stuttgart, Germany, Alexander Rupp, MD, emphasized the importance of leveraging routine healthcare interactions to encourage smoking cessation. “Although every doctor-patient contact offers the opportunity to discuss the risks of smoking and the opportunities for smoking cessation, the ‘window of opportunity’ is very wide, especially during lung cancer screening,” he said.

Germany is preparing to launch a lung cancer screening program for high-risk individuals, primarily current smokers and former smokers. Following the establishment of radiation protection regulations for such a program last year, the German Federal Joint Committee is currently working on its design. The initiative could be a game-changer for smoking cessation.

Lung cancer screening has been available for smokers in the United States for some time. Paul M. Cinciripini, PhD, and colleagues from the University of Texas MD Anderson Cancer Center, Houston, examined three smoking cessation strategies with decreasing treatment intensity among screening participants.

 

Unique Opportunity

Previous studies have shown that participation in a lung cancer screening program — typically offered only to high-risk individuals — significantly increases motivation to quit smoking.

“Repeated contact with doctors, repeated CT scans, and especially the findings that require monitoring all contribute to this effect,” explained Rupp, who regularly offers smoking cessation courses.

It has long been known how smoking cessation works best. “The gold standard is a combination of behavioral therapy support and drug treatment — if there is an addiction and withdrawal symptoms occur after quitting, which is the case for the majority of smokers,” Rupp explained.

The US study reinforced what is already well known: More intensive treatment approaches lead to higher quit rates.

“We know that the more intensively we look after smokers, the higher the quit rate. This applies in both areas: The more therapy sessions we do and the more often we prescribe medication, the more likely the patients are to succeed in remaining abstinent,” Rupp said.

However, resources for intensive smoking cessation programs are limited. A database maintained by the German Cancer Research Center and the German Federal Center for Health Education lists only 455 providers of smoking cessation courses in Germany, “not all of which even work on an evidence-based basis,” Rupp emphasized. Given that there are around 16 million smokers in Germany, there is an urgent need for smoking cessation programs that are less resource-intensive.

 

Intensity Variations

The US study compared three smoking cessation strategies of varying intensities, integrating behavioral counseling and medication.

Group 1: An integrated program with eight behavioral therapy sessions and 10-12 weeks of nicotine replacement therapy or medication (bupropion or varenicline).

Group 2: Lighter version of the integrated program. It consisted of four telephone consultations, written materials, online support, and 12 weeks of nicotine replacement therapy or medication prescribed by a radiologist.

Group 3: The least intensive approach, with 12 weeks of nicotine replacement therapy alone.

Each strategy was evaluated in 210 lung cancer screening participants aged 55-64 years who smoked an average of 15-20 cigarettes per day.

After 3 months, significantly more participants in the most intensive program (Group 1, 37.1%) had quit smoking than those in the other two groups (Group 2, 27.1%; Group 3, 25.2%).

But after 6 months, the difference between Groups 1 and 2 was not significant. The quit rates were as follows: Group 1, 32.4%; Group 2, 27.6%; and Group 3, 20.5%.

“It can be concluded from these results that the intensity of smoking cessation can be reduced to a certain extent as long as the combination of behavioral counseling and medication is given,” Rupp concluded.

 

Digital Solutions

Another new possibility, which was not examined in the US study, is digital health applications.

Smoke Free is a digital health application that provides behavioral therapy support for smoking cessation and is available in both German and English. Designed to replicate structured smoking cessation programs and offers an accessible alternative for individuals seeking to quit smoking.

Rupp emphasized the potential of digital tools like Smoke Free to expand access to effective smoking cessation strategies, particularly for those unable to attend in-person programs. While traditional cessation programs are limited in availability, digital apps can increase engagement in and adherence to smoking cessation efforts.

However, the biggest hurdle is smokers’ procrastination: “If you make smokers an offer, they usually do not take action afterward because they are caught in their ambivalence about whether they should quit or not.”

 

Policy Implications

This makes smoking cessation a mandatory component of lung cancer screening in the future. “It’s about cancer, and patients are really afraid of that,” Rupp advocated.

In a position paper, the German Respiratory Society, supported by multiple medical societies, has called for smoking cessation to be integrated into lung cancer screening protocols, with full coverage of counseling and medication by health insurance.

“Smoking cessation must be a mandatory component. If a participant in the lung cancer screening does not want this, then he or she must actively object,” stressed Rupp, lead author of the position paper. Also, the costs of smoking cessation, including those of withdrawal-inhibiting medication, must be fully covered by statutory health insurance, which has not been the case to date.

“That’s the only thing that makes sense. You can’t deny an addict access to proven treatments, especially when we know that a smoker who quits spontaneously without support has a relapse rate of 95%-97%, and the medication per se increases the quit rate by a factor of two or three,” Rupp concluded.

This story was translated and adapted from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Nearly 96,000 US Department of Veterans Affairs (VA) employees—about 20% of the workforce—will be required to return to in-office work by the end of February. The announcement follows a Jan. 20 presidential memorandum, which states agency heads must “take all necessary steps to terminate remote work arrangements and require employees to return to work in-person at their respective duty stations on a full-time basis.” According to a Jan. 28 email sent from the Office of Personnel Management but without a signature, federal employees who refuse will be offered “dignified, fair departure from the federal government utilizing a deferred resignation program.”

The revised VA work policy states “eligible employees must work full-time at their respective duty stations (agency worksites) unless excused due to a disability, qualifying medical condition or other compelling reason.” All nonbargaining unit employees and supervisors who are within 50 miles of their office have until Feb. 24 to return. The VA stated that further guidance is coming for those who live > 50 miles from a facility. 

“VA’s policy allows exceptions for arrangements approved for employees as a reasonable accommodation due to a disability or a qualifying medical condition. Exceptions may also be allowed for military spouses with permanent change of station orders,” according to a VA press release.

“This is a commonsense step toward treating all VA employees equally,” acting VA Secretary Todd Hunter said. “Most VA clinical staff don’t have the luxury of working remotely, and we believe the performance, collaboration and productivity of the department will improve if all VA employees are held to the same standard.” 

The impact on Veterans Health Administration operations remains difficult to determine. The order appears to include personnel providing telehealth care from remote locations, including those at the Clinical Resource Hub (CRH) program. CRH uses a hub and spoke model for limited time primary care and mental health care staffing to cover local clinician vacancies. CRH clinicians have provided > 500,000 veterans with care, averaging > 25,000 encounters in the program’s first year. Started during fiscal year 2020 amid the COVID-19 pandemic, CRH employed 636 clinicians, but more recent data are not available. The VA provided > 28 million telehealth sessions to veterans across all of its telehealth modalities in 2023. Details on how many CRH clinicians and other telehealth practitioners work remotely are also not available.

On Feb. 3, the Office of Personnel Management issued a memo to federal agency heads arguing that any collective bargaining agreements that include teleworking may “conflict with management rights” and therefore may be “unlawful and cannot be enforced.”

The American Federation of Government Employees (AFGE), which represents 800,000 federal employees, disputed the memo. “Federal employees should know that approved union contracts are enforceable by law, and the President does not have the authority to make unilateral changes to those agreements,” AFGE President Everett Kelley said. “AFGE members will not be intimidated. If our contracts are violated, we will aggressively defend them.”

The VA must decide where to put the more than 47,000 workers who may be coming back. According to the Government Accountability Office, “Federal agencies have long struggled to determine how much office space they needed to fulfill their missions efficiently.” The VA has reduced its office space by > 290,000 ft² over the last few years in the National Capital Region alone. 

In his confirmation hearing last month, VA Secretary nominee Doug Collins told lawmakers that, if confirmed, he would “encourage employees to come back to work,” but he also said he would ensure the department was following the White House’s remote work limits. “We’re going to make sure that we get people in there,” he said, “because at the end of the day, it’s about veterans.”

Nearly 96,000 US Department of Veterans Affairs (VA) employees—about 20% of the workforce—will be required to return to in-office work by the end of February. The announcement follows a Jan. 20 presidential memorandum, which states agency heads must “take all necessary steps to terminate remote work arrangements and require employees to return to work in-person at their respective duty stations on a full-time basis.” According to a Jan. 28 email sent from the Office of Personnel Management but without a signature, federal employees who refuse will be offered “dignified, fair departure from the federal government utilizing a deferred resignation program.”

The revised VA work policy states “eligible employees must work full-time at their respective duty stations (agency worksites) unless excused due to a disability, qualifying medical condition or other compelling reason.” All nonbargaining unit employees and supervisors who are within 50 miles of their office have until Feb. 24 to return. The VA stated that further guidance is coming for those who live > 50 miles from a facility. 

“VA’s policy allows exceptions for arrangements approved for employees as a reasonable accommodation due to a disability or a qualifying medical condition. Exceptions may also be allowed for military spouses with permanent change of station orders,” according to a VA press release.

“This is a commonsense step toward treating all VA employees equally,” acting VA Secretary Todd Hunter said. “Most VA clinical staff don’t have the luxury of working remotely, and we believe the performance, collaboration and productivity of the department will improve if all VA employees are held to the same standard.” 

The impact on Veterans Health Administration operations remains difficult to determine. The order appears to include personnel providing telehealth care from remote locations, including those at the Clinical Resource Hub (CRH) program. CRH uses a hub and spoke model for limited time primary care and mental health care staffing to cover local clinician vacancies. CRH clinicians have provided > 500,000 veterans with care, averaging > 25,000 encounters in the program’s first year. Started during fiscal year 2020 amid the COVID-19 pandemic, CRH employed 636 clinicians, but more recent data are not available. The VA provided > 28 million telehealth sessions to veterans across all of its telehealth modalities in 2023. Details on how many CRH clinicians and other telehealth practitioners work remotely are also not available.

On Feb. 3, the Office of Personnel Management issued a memo to federal agency heads arguing that any collective bargaining agreements that include teleworking may “conflict with management rights” and therefore may be “unlawful and cannot be enforced.”

The American Federation of Government Employees (AFGE), which represents 800,000 federal employees, disputed the memo. “Federal employees should know that approved union contracts are enforceable by law, and the President does not have the authority to make unilateral changes to those agreements,” AFGE President Everett Kelley said. “AFGE members will not be intimidated. If our contracts are violated, we will aggressively defend them.”

The VA must decide where to put the more than 47,000 workers who may be coming back. According to the Government Accountability Office, “Federal agencies have long struggled to determine how much office space they needed to fulfill their missions efficiently.” The VA has reduced its office space by > 290,000 ft² over the last few years in the National Capital Region alone. 

In his confirmation hearing last month, VA Secretary nominee Doug Collins told lawmakers that, if confirmed, he would “encourage employees to come back to work,” but he also said he would ensure the department was following the White House’s remote work limits. “We’re going to make sure that we get people in there,” he said, “because at the end of the day, it’s about veterans.”

Nearly 96,000 US Department of Veterans Affairs (VA) employees—about 20% of the workforce—will be required to return to in-office work by the end of February. The announcement follows a Jan. 20 presidential memorandum, which states agency heads must “take all necessary steps to terminate remote work arrangements and require employees to return to work in-person at their respective duty stations on a full-time basis.” According to a Jan. 28 email sent from the Office of Personnel Management but without a signature, federal employees who refuse will be offered “dignified, fair departure from the federal government utilizing a deferred resignation program.”

The revised VA work policy states “eligible employees must work full-time at their respective duty stations (agency worksites) unless excused due to a disability, qualifying medical condition or other compelling reason.” All nonbargaining unit employees and supervisors who are within 50 miles of their office have until Feb. 24 to return. The VA stated that further guidance is coming for those who live > 50 miles from a facility. 

“VA’s policy allows exceptions for arrangements approved for employees as a reasonable accommodation due to a disability or a qualifying medical condition. Exceptions may also be allowed for military spouses with permanent change of station orders,” according to a VA press release.

“This is a commonsense step toward treating all VA employees equally,” acting VA Secretary Todd Hunter said. “Most VA clinical staff don’t have the luxury of working remotely, and we believe the performance, collaboration and productivity of the department will improve if all VA employees are held to the same standard.” 

The impact on Veterans Health Administration operations remains difficult to determine. The order appears to include personnel providing telehealth care from remote locations, including those at the Clinical Resource Hub (CRH) program. CRH uses a hub and spoke model for limited time primary care and mental health care staffing to cover local clinician vacancies. CRH clinicians have provided > 500,000 veterans with care, averaging > 25,000 encounters in the program’s first year. Started during fiscal year 2020 amid the COVID-19 pandemic, CRH employed 636 clinicians, but more recent data are not available. The VA provided > 28 million telehealth sessions to veterans across all of its telehealth modalities in 2023. Details on how many CRH clinicians and other telehealth practitioners work remotely are also not available.

On Feb. 3, the Office of Personnel Management issued a memo to federal agency heads arguing that any collective bargaining agreements that include teleworking may “conflict with management rights” and therefore may be “unlawful and cannot be enforced.”

The American Federation of Government Employees (AFGE), which represents 800,000 federal employees, disputed the memo. “Federal employees should know that approved union contracts are enforceable by law, and the President does not have the authority to make unilateral changes to those agreements,” AFGE President Everett Kelley said. “AFGE members will not be intimidated. If our contracts are violated, we will aggressively defend them.”

The VA must decide where to put the more than 47,000 workers who may be coming back. According to the Government Accountability Office, “Federal agencies have long struggled to determine how much office space they needed to fulfill their missions efficiently.” The VA has reduced its office space by > 290,000 ft² over the last few years in the National Capital Region alone. 

In his confirmation hearing last month, VA Secretary nominee Doug Collins told lawmakers that, if confirmed, he would “encourage employees to come back to work,” but he also said he would ensure the department was following the White House’s remote work limits. “We’re going to make sure that we get people in there,” he said, “because at the end of the day, it’s about veterans.”

TOPLINE:

Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. 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 cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. 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 cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. 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.