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Adverse skin effects of cancer immunotherapy reviewed
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Untargeted CT scans leads to overdiagnoses in lung cancer
Such overdiagnosis was illustrated in a recent study from JAMA Internal Medicine of women in Taiwan who were screened for lung cancer using low-dose CT (LDCT).
The study, and the accompanying editorial, pointed out the potential for large databases of routine clinical data to track long-term outcomes, and potentially identify patient subgroups that could benefit from early diagnosis using digital technologies.
The Taiwanese findings echo a similar trend identified in a 2018 post hoc analysis of the Danish Lung Cancer Screening Trial, which estimated that 67.2% of cancers found during that CT screening program for current or former smokers were overdiagnosed. The authors recommended that researchers report rates of overdiagnosis in future screening studies.
The authors of the Taiwan study noted that LDCT is low cost and is frequently offered to individuals who are not considered at high risk of lung cancer, and advertisements in Taiwan often target women, who rarely smoke. The researchers examined data from the Taiwan National Cancer Registry. They looked for evidence of an increased incidence of early-stage detection and reduced incidence of late-stage diagnosis. They found that, from 2004 to 2018, there was an increase of lung cancer incidence from 2.3 to 14.4 per 100,000 (difference, 12.1; 95% confidence interval, 11.3-12.8), but no significant difference in the incidence of late-stage disease (from 18.7 to 19.3 per 100,000; difference, 0.6; 95% CI, –0.5 to 1.7).
“This combination of findings, an additional 12.1 early-stage cancers per 100,000 population and no reduction in late-stage cancers, is strongly suggestive of overdiagnosis,” the authors wrote.
It can be difficult to convince people of the potential harms of overdiagnosis, especially when patients have a nodule removed and remain healthy years later. “It’s very counterintuitive, but it’s a reality, and I think this paper paints the reality very, very clearly,” said Daniel Capurro, MD, PhD, deputy director of the Centre for the Digital Transformation of Health at University of Melbourne, and an author of the editorial.
The issue is that some lung cancers progress so slowly that they may never cause a problem clinically, and their removal can lead to unnecessary cost and risk. And it’s not just cancer. “There are a bunch of other conditions that are defined by specific criteria, but we don’t add the prognosis to that definition. At the individual patient level, we don’t know the prognosis,” Dr. Capurro said.
Dr. Capurro discussed the increasing use of digital technologies like smartphone apps. Machine learning can potentially use such data to diagnose conditions like sleep or mood disorders before they become clinically significant, allowing earlier intervention, but they could also lead to overdiagnosis. Dr. Capurro proposed using longitudinal databases to track patient outcomes, which could be applied to digital screening technologies.
“You might be able to find unknown patterns that help discriminate between these pathological definitions. You should be able to train (digital screens) with the pathological definition plus the disease trajectory as a way to improve that label,” he said.
The study was funded by the Taiwan Ministry of Health and Welfare Clinical Trial Center.
Such overdiagnosis was illustrated in a recent study from JAMA Internal Medicine of women in Taiwan who were screened for lung cancer using low-dose CT (LDCT).
The study, and the accompanying editorial, pointed out the potential for large databases of routine clinical data to track long-term outcomes, and potentially identify patient subgroups that could benefit from early diagnosis using digital technologies.
The Taiwanese findings echo a similar trend identified in a 2018 post hoc analysis of the Danish Lung Cancer Screening Trial, which estimated that 67.2% of cancers found during that CT screening program for current or former smokers were overdiagnosed. The authors recommended that researchers report rates of overdiagnosis in future screening studies.
The authors of the Taiwan study noted that LDCT is low cost and is frequently offered to individuals who are not considered at high risk of lung cancer, and advertisements in Taiwan often target women, who rarely smoke. The researchers examined data from the Taiwan National Cancer Registry. They looked for evidence of an increased incidence of early-stage detection and reduced incidence of late-stage diagnosis. They found that, from 2004 to 2018, there was an increase of lung cancer incidence from 2.3 to 14.4 per 100,000 (difference, 12.1; 95% confidence interval, 11.3-12.8), but no significant difference in the incidence of late-stage disease (from 18.7 to 19.3 per 100,000; difference, 0.6; 95% CI, –0.5 to 1.7).
“This combination of findings, an additional 12.1 early-stage cancers per 100,000 population and no reduction in late-stage cancers, is strongly suggestive of overdiagnosis,” the authors wrote.
It can be difficult to convince people of the potential harms of overdiagnosis, especially when patients have a nodule removed and remain healthy years later. “It’s very counterintuitive, but it’s a reality, and I think this paper paints the reality very, very clearly,” said Daniel Capurro, MD, PhD, deputy director of the Centre for the Digital Transformation of Health at University of Melbourne, and an author of the editorial.
The issue is that some lung cancers progress so slowly that they may never cause a problem clinically, and their removal can lead to unnecessary cost and risk. And it’s not just cancer. “There are a bunch of other conditions that are defined by specific criteria, but we don’t add the prognosis to that definition. At the individual patient level, we don’t know the prognosis,” Dr. Capurro said.
Dr. Capurro discussed the increasing use of digital technologies like smartphone apps. Machine learning can potentially use such data to diagnose conditions like sleep or mood disorders before they become clinically significant, allowing earlier intervention, but they could also lead to overdiagnosis. Dr. Capurro proposed using longitudinal databases to track patient outcomes, which could be applied to digital screening technologies.
“You might be able to find unknown patterns that help discriminate between these pathological definitions. You should be able to train (digital screens) with the pathological definition plus the disease trajectory as a way to improve that label,” he said.
The study was funded by the Taiwan Ministry of Health and Welfare Clinical Trial Center.
Such overdiagnosis was illustrated in a recent study from JAMA Internal Medicine of women in Taiwan who were screened for lung cancer using low-dose CT (LDCT).
The study, and the accompanying editorial, pointed out the potential for large databases of routine clinical data to track long-term outcomes, and potentially identify patient subgroups that could benefit from early diagnosis using digital technologies.
The Taiwanese findings echo a similar trend identified in a 2018 post hoc analysis of the Danish Lung Cancer Screening Trial, which estimated that 67.2% of cancers found during that CT screening program for current or former smokers were overdiagnosed. The authors recommended that researchers report rates of overdiagnosis in future screening studies.
The authors of the Taiwan study noted that LDCT is low cost and is frequently offered to individuals who are not considered at high risk of lung cancer, and advertisements in Taiwan often target women, who rarely smoke. The researchers examined data from the Taiwan National Cancer Registry. They looked for evidence of an increased incidence of early-stage detection and reduced incidence of late-stage diagnosis. They found that, from 2004 to 2018, there was an increase of lung cancer incidence from 2.3 to 14.4 per 100,000 (difference, 12.1; 95% confidence interval, 11.3-12.8), but no significant difference in the incidence of late-stage disease (from 18.7 to 19.3 per 100,000; difference, 0.6; 95% CI, –0.5 to 1.7).
“This combination of findings, an additional 12.1 early-stage cancers per 100,000 population and no reduction in late-stage cancers, is strongly suggestive of overdiagnosis,” the authors wrote.
It can be difficult to convince people of the potential harms of overdiagnosis, especially when patients have a nodule removed and remain healthy years later. “It’s very counterintuitive, but it’s a reality, and I think this paper paints the reality very, very clearly,” said Daniel Capurro, MD, PhD, deputy director of the Centre for the Digital Transformation of Health at University of Melbourne, and an author of the editorial.
The issue is that some lung cancers progress so slowly that they may never cause a problem clinically, and their removal can lead to unnecessary cost and risk. And it’s not just cancer. “There are a bunch of other conditions that are defined by specific criteria, but we don’t add the prognosis to that definition. At the individual patient level, we don’t know the prognosis,” Dr. Capurro said.
Dr. Capurro discussed the increasing use of digital technologies like smartphone apps. Machine learning can potentially use such data to diagnose conditions like sleep or mood disorders before they become clinically significant, allowing earlier intervention, but they could also lead to overdiagnosis. Dr. Capurro proposed using longitudinal databases to track patient outcomes, which could be applied to digital screening technologies.
“You might be able to find unknown patterns that help discriminate between these pathological definitions. You should be able to train (digital screens) with the pathological definition plus the disease trajectory as a way to improve that label,” he said.
The study was funded by the Taiwan Ministry of Health and Welfare Clinical Trial Center.
FROM JAMA INTERNAL MEDICINE
Ways to lessen toxic effects of chemo in older adults
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
FDA approves first PARP inhibitor for early BRCA+ breast cancer
BRCA+ breast cancer
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
BRCA+ breast cancer
BRCA+ breast cancer
Registry data support lowering CRC screening age to 45
Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.
According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.
Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.
The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.
Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.
A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).
The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.
Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.
The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.
“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.
Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.
Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.
According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.
Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.
The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.
Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.
A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).
The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.
Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.
The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.
“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.
Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.
Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.
According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.
Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.
The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.
Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.
A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).
The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.
Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.
The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.
“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.
Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.
FROM GASTROENTEROLOGY
New 3D printable stent holds promise for tracheal tumors
Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.
The research was published online Jan. 29 in Materials Today Chemistry.
The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.
“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.
All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.
The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.
Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.
“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
In vivo evaluation
Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.
The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.
Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.
“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
Pediatric airway obstruction
Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.
“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).
When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.
In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.
The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.
A version of this article first appeared on Medscape.com.
Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.
The research was published online Jan. 29 in Materials Today Chemistry.
The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.
“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.
All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.
The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.
Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.
“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
In vivo evaluation
Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.
The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.
Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.
“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
Pediatric airway obstruction
Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.
“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).
When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.
In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.
The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.
A version of this article first appeared on Medscape.com.
Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.
The research was published online Jan. 29 in Materials Today Chemistry.
The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.
“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.
All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.
The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.
Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.
“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
In vivo evaluation
Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.
The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.
Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.
“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
Pediatric airway obstruction
Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.
“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).
When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.
In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.
The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.
A version of this article first appeared on Medscape.com.
RFA has long-lasting protective effects in esophageal cancer
Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.
Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.
Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.
Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.
“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”
Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.
They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.
One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.
At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.
“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.
Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
Researchers look for minimally invasive solutions
Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.
This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.
Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”
She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.
Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”
She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”
That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.
“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”
Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.
“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.
Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.
Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.
Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.
Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.
Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.
“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”
Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.
They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.
One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.
At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.
“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.
Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
Researchers look for minimally invasive solutions
Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.
This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.
Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”
She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.
Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”
She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”
That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.
“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”
Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.
“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.
Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.
Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.
Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.
Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.
Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.
“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”
Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.
They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.
One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.
At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.
“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.
Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
Researchers look for minimally invasive solutions
Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.
This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.
Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”
She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.
Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”
She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”
That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.
“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”
Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.
“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.
Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.
FROM GASTROINTESTINAL ENDOSCOPY
Heavy drinking in your 20s has lasting impact on cancer risk
according to a new study from Australia.
Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”
The study, published online Feb. 19 in the International Journal of Cancer, assessed lifetime drinking trajectories and risk for alcohol-related cancer using data from 22,756 women and 15,701 men recruited to the prospective Melbourne Collaborative Cohort Study from 1990-1994. Heavy drinking was considered an average alcohol intake of at least 60 g/day, which is equivalent to the alcohol content in 6 standard drinks.
During 485,525 person-years of follow-up among women, 2,303 incident alcohol-related cancers were diagnosed, most commonly breast (64%) and colorectal cancer (31%).
During 303,218 person-years of follow-up among men, 789 alcohol-related cancers were found, most commonly colorectal cancer (83%).
The researchers identified three distinct lifetime alcohol intake trajectories for women – lifetime abstainer (39%), stable light (54%), and increasing moderate (7%) – and six for men – lifetime abstainer (14.3%), stable light (51.5%), stable moderate (20.4%), increasing heavy (6.6%), early decreasing heavy (5.1%), and late decreasing heavy (2.2%).
Almost three times more, women were lifetime abstainers (39% vs. 14% of men). And approximately the same percentage of men and women increased their alcohol consumption over time. About 7% of men were classified as increasing heavy drinkers, consuming a moderate amount of alcohol (30-59 g/day) at age 20-39 and increasing their intake markedly from age 40-49 (over 60 g/day) before reducing it by age 60-69. Among women, 7% were classified as increasing moderate, tending to consume around 20 g/day at age 20-29 and gradually increasing their alcohol intake over time to consume close to 40 g/day at age 50-59.
Among men, the early decreasing heavy group started as heavy drinkers at age 20-39 (greater than or equal to 60 g/day) and continued to cut down their intake over time until developing stable light drinking habits by age 60-69, whereas late decreasing heavy drinks continued to drink a lot until age 60-69 before cutting their intake in their 70s.
Impact on cancer risk
For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.
The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).
The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.
Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.
For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.
Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).
The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
‘Striking’ findings
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.
“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.
Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”
Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”
“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”
The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new study from Australia.
Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”
The study, published online Feb. 19 in the International Journal of Cancer, assessed lifetime drinking trajectories and risk for alcohol-related cancer using data from 22,756 women and 15,701 men recruited to the prospective Melbourne Collaborative Cohort Study from 1990-1994. Heavy drinking was considered an average alcohol intake of at least 60 g/day, which is equivalent to the alcohol content in 6 standard drinks.
During 485,525 person-years of follow-up among women, 2,303 incident alcohol-related cancers were diagnosed, most commonly breast (64%) and colorectal cancer (31%).
During 303,218 person-years of follow-up among men, 789 alcohol-related cancers were found, most commonly colorectal cancer (83%).
The researchers identified three distinct lifetime alcohol intake trajectories for women – lifetime abstainer (39%), stable light (54%), and increasing moderate (7%) – and six for men – lifetime abstainer (14.3%), stable light (51.5%), stable moderate (20.4%), increasing heavy (6.6%), early decreasing heavy (5.1%), and late decreasing heavy (2.2%).
Almost three times more, women were lifetime abstainers (39% vs. 14% of men). And approximately the same percentage of men and women increased their alcohol consumption over time. About 7% of men were classified as increasing heavy drinkers, consuming a moderate amount of alcohol (30-59 g/day) at age 20-39 and increasing their intake markedly from age 40-49 (over 60 g/day) before reducing it by age 60-69. Among women, 7% were classified as increasing moderate, tending to consume around 20 g/day at age 20-29 and gradually increasing their alcohol intake over time to consume close to 40 g/day at age 50-59.
Among men, the early decreasing heavy group started as heavy drinkers at age 20-39 (greater than or equal to 60 g/day) and continued to cut down their intake over time until developing stable light drinking habits by age 60-69, whereas late decreasing heavy drinks continued to drink a lot until age 60-69 before cutting their intake in their 70s.
Impact on cancer risk
For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.
The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).
The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.
Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.
For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.
Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).
The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
‘Striking’ findings
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.
“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.
Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”
Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”
“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”
The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new study from Australia.
Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”
The study, published online Feb. 19 in the International Journal of Cancer, assessed lifetime drinking trajectories and risk for alcohol-related cancer using data from 22,756 women and 15,701 men recruited to the prospective Melbourne Collaborative Cohort Study from 1990-1994. Heavy drinking was considered an average alcohol intake of at least 60 g/day, which is equivalent to the alcohol content in 6 standard drinks.
During 485,525 person-years of follow-up among women, 2,303 incident alcohol-related cancers were diagnosed, most commonly breast (64%) and colorectal cancer (31%).
During 303,218 person-years of follow-up among men, 789 alcohol-related cancers were found, most commonly colorectal cancer (83%).
The researchers identified three distinct lifetime alcohol intake trajectories for women – lifetime abstainer (39%), stable light (54%), and increasing moderate (7%) – and six for men – lifetime abstainer (14.3%), stable light (51.5%), stable moderate (20.4%), increasing heavy (6.6%), early decreasing heavy (5.1%), and late decreasing heavy (2.2%).
Almost three times more, women were lifetime abstainers (39% vs. 14% of men). And approximately the same percentage of men and women increased their alcohol consumption over time. About 7% of men were classified as increasing heavy drinkers, consuming a moderate amount of alcohol (30-59 g/day) at age 20-39 and increasing their intake markedly from age 40-49 (over 60 g/day) before reducing it by age 60-69. Among women, 7% were classified as increasing moderate, tending to consume around 20 g/day at age 20-29 and gradually increasing their alcohol intake over time to consume close to 40 g/day at age 50-59.
Among men, the early decreasing heavy group started as heavy drinkers at age 20-39 (greater than or equal to 60 g/day) and continued to cut down their intake over time until developing stable light drinking habits by age 60-69, whereas late decreasing heavy drinks continued to drink a lot until age 60-69 before cutting their intake in their 70s.
Impact on cancer risk
For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.
The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).
The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.
Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.
For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.
Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).
The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
‘Striking’ findings
Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.
“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.
Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”
Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”
“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”
The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE INTERNATIONAL JOURNAL OF CANCER
Radioactive iodine shows no benefit in low-risk thyroid cancer
, suggesting these patients can be spared the previously common treatment.
The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.
The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.
While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”
However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.
Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.
The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
ESTIMABL2 trial
The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.
Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).
Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.
Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.
After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.
Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).
Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.
There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.
Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.
The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted.
“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.
“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
Patients spared costs, work losses
Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.
For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.
“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.
A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.
“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.
Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
Some continue radioiodine use, but lobectomies add to decline
Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.
“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”
In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.
“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.
The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, suggesting these patients can be spared the previously common treatment.
The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.
The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.
While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”
However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.
Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.
The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
ESTIMABL2 trial
The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.
Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).
Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.
Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.
After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.
Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).
Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.
There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.
Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.
The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted.
“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.
“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
Patients spared costs, work losses
Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.
For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.
“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.
A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.
“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.
Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
Some continue radioiodine use, but lobectomies add to decline
Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.
“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”
In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.
“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.
The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, suggesting these patients can be spared the previously common treatment.
The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.
The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.
While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”
However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.
Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.
The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
ESTIMABL2 trial
The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.
Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).
Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.
Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.
After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.
Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).
Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.
There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.
Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.
The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted.
“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.
“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
Patients spared costs, work losses
Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.
For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.
“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.
A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.
“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.
Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
Some continue radioiodine use, but lobectomies add to decline
Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.
“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”
In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.
“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.
The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Why is there an increased risk of cancer in depressed patients?
LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?
According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.
“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”
Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”
Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”
Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.
In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”
Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.
In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.
A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).
Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”
He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.
A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.
According to Dr. Nemeroff, For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”
Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.
LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?
According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.
“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”
Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”
Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”
Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.
In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”
Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.
In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.
A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).
Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”
He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.
A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.
According to Dr. Nemeroff, For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”
Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.
LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?
According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.
“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”
Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”
Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”
Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.
In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”
Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.
In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.
A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).
Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”
He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.
A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.
According to Dr. Nemeroff, For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”
Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.
FROM NPA 2022