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Oxidative stress linked to cytogenetic abnormalities in CLL
Oxidative stress may play a role in pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL), according to the results of a biochemical and cytogenetic study of patients published online in Experimental and Molecular Pathology.
The study evaluated the serum levels of oxidative stress biomarkers [conjugated dienes (CD), malondialdehyde (MDA), and nitrite levels] and the levels of antioxidant biomarkers [ceruloplasmin (CP) and glutathione peroxidase (GPx)] in 64 B-CLL patients. The relationship between these biomarkers and the presence of cytogenetic abnormalities was examined, according to Tatiana Zhevak, MD, of Sechenov First Moscow (Russia) State Medical University, and colleagues.
Cytogenetic abnormalities have previously been determined to be linked to a poorer prognosis in CLL patients, and factors that increase the frequency of CA have been shown to increase the risk of rapid tumor progression, Dr. Zhevak and her colleagues stated.
Oxidative stress connection
Enhanced oxidative stress was detected in B-CLL patients as shown by their increased levels of serum CD, MDA, and nitrite, as well as a demonstrated imbalance in the antioxidant defense system as shown by an increased serum CP level and decreased serum GPx activity, according to the researchers.
In addition, these metabolic changes were found to be greater in those patients whose lymphocytes harbored specific cytogenetic abnormalities, and could be predicted by the serum levels of CD. Specifically, the odds of harboring a cytogenetic abnormality increased by a factor of 1.88 (P = .004) for every one-unit increase in serum CD level (mcmol/L), according to the authors.
“Collectively, the results support our hypothesis that oxidative stress and resulting lipid peroxidation play a role in pathogenesis of B-CLL and provide a rational basis for the use of agents regulating the pro-oxidant and antioxidant activity in the treatment of B-CLL patients,” the researchers concluded.
The research was unsponsored and the authors reported having no conflicts.
SOURCE: Zhevak T et al. Exp Mol Patholo. 2020 Oct;16:104524 doi: 10.1016/j.yexmp.2020.104524.
Oxidative stress may play a role in pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL), according to the results of a biochemical and cytogenetic study of patients published online in Experimental and Molecular Pathology.
The study evaluated the serum levels of oxidative stress biomarkers [conjugated dienes (CD), malondialdehyde (MDA), and nitrite levels] and the levels of antioxidant biomarkers [ceruloplasmin (CP) and glutathione peroxidase (GPx)] in 64 B-CLL patients. The relationship between these biomarkers and the presence of cytogenetic abnormalities was examined, according to Tatiana Zhevak, MD, of Sechenov First Moscow (Russia) State Medical University, and colleagues.
Cytogenetic abnormalities have previously been determined to be linked to a poorer prognosis in CLL patients, and factors that increase the frequency of CA have been shown to increase the risk of rapid tumor progression, Dr. Zhevak and her colleagues stated.
Oxidative stress connection
Enhanced oxidative stress was detected in B-CLL patients as shown by their increased levels of serum CD, MDA, and nitrite, as well as a demonstrated imbalance in the antioxidant defense system as shown by an increased serum CP level and decreased serum GPx activity, according to the researchers.
In addition, these metabolic changes were found to be greater in those patients whose lymphocytes harbored specific cytogenetic abnormalities, and could be predicted by the serum levels of CD. Specifically, the odds of harboring a cytogenetic abnormality increased by a factor of 1.88 (P = .004) for every one-unit increase in serum CD level (mcmol/L), according to the authors.
“Collectively, the results support our hypothesis that oxidative stress and resulting lipid peroxidation play a role in pathogenesis of B-CLL and provide a rational basis for the use of agents regulating the pro-oxidant and antioxidant activity in the treatment of B-CLL patients,” the researchers concluded.
The research was unsponsored and the authors reported having no conflicts.
SOURCE: Zhevak T et al. Exp Mol Patholo. 2020 Oct;16:104524 doi: 10.1016/j.yexmp.2020.104524.
Oxidative stress may play a role in pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL), according to the results of a biochemical and cytogenetic study of patients published online in Experimental and Molecular Pathology.
The study evaluated the serum levels of oxidative stress biomarkers [conjugated dienes (CD), malondialdehyde (MDA), and nitrite levels] and the levels of antioxidant biomarkers [ceruloplasmin (CP) and glutathione peroxidase (GPx)] in 64 B-CLL patients. The relationship between these biomarkers and the presence of cytogenetic abnormalities was examined, according to Tatiana Zhevak, MD, of Sechenov First Moscow (Russia) State Medical University, and colleagues.
Cytogenetic abnormalities have previously been determined to be linked to a poorer prognosis in CLL patients, and factors that increase the frequency of CA have been shown to increase the risk of rapid tumor progression, Dr. Zhevak and her colleagues stated.
Oxidative stress connection
Enhanced oxidative stress was detected in B-CLL patients as shown by their increased levels of serum CD, MDA, and nitrite, as well as a demonstrated imbalance in the antioxidant defense system as shown by an increased serum CP level and decreased serum GPx activity, according to the researchers.
In addition, these metabolic changes were found to be greater in those patients whose lymphocytes harbored specific cytogenetic abnormalities, and could be predicted by the serum levels of CD. Specifically, the odds of harboring a cytogenetic abnormality increased by a factor of 1.88 (P = .004) for every one-unit increase in serum CD level (mcmol/L), according to the authors.
“Collectively, the results support our hypothesis that oxidative stress and resulting lipid peroxidation play a role in pathogenesis of B-CLL and provide a rational basis for the use of agents regulating the pro-oxidant and antioxidant activity in the treatment of B-CLL patients,” the researchers concluded.
The research was unsponsored and the authors reported having no conflicts.
SOURCE: Zhevak T et al. Exp Mol Patholo. 2020 Oct;16:104524 doi: 10.1016/j.yexmp.2020.104524.
FROM Experimental and Molecular Pathology
First drug for MET+ NSCLC shows high response rates
conclude investigators of the pivotal trial that led to the drug’s approval.
Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.
Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.
These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.
“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.
“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.
Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.
“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”
That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.
It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.
Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.
“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”
The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.
In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.
Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.
The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.
Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”
He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
The future is bright
Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”
Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.
“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”
The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
conclude investigators of the pivotal trial that led to the drug’s approval.
Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.
Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.
These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.
“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.
“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.
Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.
“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”
That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.
It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.
Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.
“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”
The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.
In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.
Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.
The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.
Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”
He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
The future is bright
Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”
Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.
“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”
The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
conclude investigators of the pivotal trial that led to the drug’s approval.
Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.
Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.
These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.
“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.
“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.
Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.
“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”
That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.
It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.
Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.
“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”
The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.
In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.
Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.
The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.
Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”
He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
The future is bright
Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”
Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.
“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”
The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Durable response 5 years after adjuvant combo in melanoma
Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.
New data show that the benefit is maintained over the longer term.
At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.
The combination of the investigators concluded.
These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.
“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”
Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”
“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”
In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”
As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.
“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.
“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”
“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.
Study details
The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.
Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.
Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.
Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.
At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).
The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).
The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.
Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
A viable option
Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”
He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.
The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.
A version of this article originally appeared on Medscape.com.
Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.
New data show that the benefit is maintained over the longer term.
At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.
The combination of the investigators concluded.
These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.
“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”
Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”
“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”
In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”
As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.
“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.
“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”
“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.
Study details
The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.
Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.
Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.
Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.
At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).
The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).
The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.
Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
A viable option
Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”
He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.
The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.
A version of this article originally appeared on Medscape.com.
Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.
New data show that the benefit is maintained over the longer term.
At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.
The combination of the investigators concluded.
These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.
“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”
Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”
“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”
In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”
As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.
“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.
“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”
“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.
Study details
The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.
Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.
Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.
Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.
At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).
The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).
The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.
Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
A viable option
Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”
He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.
The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.
A version of this article originally appeared on Medscape.com.
VA-Radiation Oncology Quality Surveillance Program: Enhancing Quality Measure Data Capture, Measuring Quality Benchmarks and Ensuring Long Term Sustainability of Quality Improvements in Community Care
INTRODUCTION: Delivery of high-quality cancer care improves oncologic outcomes, including survival and quality of life. The VA National Radiation Oncology (NROP) established the VA Radiation Oncology Quality Surveillance Program (VAROQS) which has developed clinical quality measures (QM) as a measure of quality indices in radiation oncology. We sought to measure quality in community care, assess barriers to data capture, and develop solutions to ensure long term sustainability of continuous quality improvement for veterans that receive dual care, both within the VA and in non-VA community care (NVCC).
METHODS: From 2016-2018, the VA-ROQS project randomly selected three Veterans Integrated Service Networks (VISNs) for quality analysis using established QM for prostate cancer, specifically, 6, 16, and 22. NROP manually abstracted data for QM treated in NVCC QMs, which was compared to the performance of the VA QM in the same VISN as well as for all VISNs in the VA.
RESULTS: Out of the 723 NVCC cases that were examined, none were fully evaluable for all 25 Prostate quality metrics. QM was able to be assessed in only 28% of NVCC patients (n=208) reviewed. Only 12/25 (48%) of all Prostate QM were able to be compared between VA and NVCC. Out of the 12 available Prostate QM, 9 were performance, 2 were surveillance, while 1 was an aspirational measure. The overall > 75% pass rate of all the expected performance QM measures for the VA was 13/14 (92%). For NVCC, of the available expected QM for comparison, 8 of which were high potential impact, only 1/9 (11%) QM received a >75% pass rate in all three NVCC VISNs. When examining the 8 high potential impact QM, the VA had a 100% pass rate.
CONCLUSIONS: There are challenges to obtaining data to perform QM assessment from community care. For cases where QM performance could be assessed, VA care outperformed non-VA care. VA-ROQS program is an ongoing quality improvement initiative and in order to ensure that quality is comprehensively collected for NVCC, we propose a web-based portal that will enable providers to directly upload anonymized treatment information and the DICOM treatment plan.
INTRODUCTION: Delivery of high-quality cancer care improves oncologic outcomes, including survival and quality of life. The VA National Radiation Oncology (NROP) established the VA Radiation Oncology Quality Surveillance Program (VAROQS) which has developed clinical quality measures (QM) as a measure of quality indices in radiation oncology. We sought to measure quality in community care, assess barriers to data capture, and develop solutions to ensure long term sustainability of continuous quality improvement for veterans that receive dual care, both within the VA and in non-VA community care (NVCC).
METHODS: From 2016-2018, the VA-ROQS project randomly selected three Veterans Integrated Service Networks (VISNs) for quality analysis using established QM for prostate cancer, specifically, 6, 16, and 22. NROP manually abstracted data for QM treated in NVCC QMs, which was compared to the performance of the VA QM in the same VISN as well as for all VISNs in the VA.
RESULTS: Out of the 723 NVCC cases that were examined, none were fully evaluable for all 25 Prostate quality metrics. QM was able to be assessed in only 28% of NVCC patients (n=208) reviewed. Only 12/25 (48%) of all Prostate QM were able to be compared between VA and NVCC. Out of the 12 available Prostate QM, 9 were performance, 2 were surveillance, while 1 was an aspirational measure. The overall > 75% pass rate of all the expected performance QM measures for the VA was 13/14 (92%). For NVCC, of the available expected QM for comparison, 8 of which were high potential impact, only 1/9 (11%) QM received a >75% pass rate in all three NVCC VISNs. When examining the 8 high potential impact QM, the VA had a 100% pass rate.
CONCLUSIONS: There are challenges to obtaining data to perform QM assessment from community care. For cases where QM performance could be assessed, VA care outperformed non-VA care. VA-ROQS program is an ongoing quality improvement initiative and in order to ensure that quality is comprehensively collected for NVCC, we propose a web-based portal that will enable providers to directly upload anonymized treatment information and the DICOM treatment plan.
INTRODUCTION: Delivery of high-quality cancer care improves oncologic outcomes, including survival and quality of life. The VA National Radiation Oncology (NROP) established the VA Radiation Oncology Quality Surveillance Program (VAROQS) which has developed clinical quality measures (QM) as a measure of quality indices in radiation oncology. We sought to measure quality in community care, assess barriers to data capture, and develop solutions to ensure long term sustainability of continuous quality improvement for veterans that receive dual care, both within the VA and in non-VA community care (NVCC).
METHODS: From 2016-2018, the VA-ROQS project randomly selected three Veterans Integrated Service Networks (VISNs) for quality analysis using established QM for prostate cancer, specifically, 6, 16, and 22. NROP manually abstracted data for QM treated in NVCC QMs, which was compared to the performance of the VA QM in the same VISN as well as for all VISNs in the VA.
RESULTS: Out of the 723 NVCC cases that were examined, none were fully evaluable for all 25 Prostate quality metrics. QM was able to be assessed in only 28% of NVCC patients (n=208) reviewed. Only 12/25 (48%) of all Prostate QM were able to be compared between VA and NVCC. Out of the 12 available Prostate QM, 9 were performance, 2 were surveillance, while 1 was an aspirational measure. The overall > 75% pass rate of all the expected performance QM measures for the VA was 13/14 (92%). For NVCC, of the available expected QM for comparison, 8 of which were high potential impact, only 1/9 (11%) QM received a >75% pass rate in all three NVCC VISNs. When examining the 8 high potential impact QM, the VA had a 100% pass rate.
CONCLUSIONS: There are challenges to obtaining data to perform QM assessment from community care. For cases where QM performance could be assessed, VA care outperformed non-VA care. VA-ROQS program is an ongoing quality improvement initiative and in order to ensure that quality is comprehensively collected for NVCC, we propose a web-based portal that will enable providers to directly upload anonymized treatment information and the DICOM treatment plan.
VA Connecticut Friendly Phone Call Program (FPCP): A Collaborative, Team-based Approach to Alleviating Loneliness related to Social Isolation in Veterans with Cancer During the Covid-19 Pandemic
BACKGROUND: At VACHS, we identified oncology patients at risk for loneliness subsequent to COVID-19 social distancing recommendations. Cancer patients are older, more physically frail and immune compromised, making them high-risk for complications related to covid-19 infection. Given this risk, social isolation might extend significantly beyond the initial period of lockdown for oncology patients. To protect this vulnerable population, we shifted from face-to-face visits to telemedicine. A workgroup formed to develop an intervention to support Veterans at-risk for prolonged isolation. Social isolation is a well-established risk factor for poor health and mortality (Caccioppo & Hawkley, 2003). For individuals with cancer, social isolation has been linked to poorer survival (Reynolds & Kaplan, 1990; Hislop, Waxler, Coldman, Elwood, and Kan, 1987). Research in woman with ovarian cancer suggests that limited social support is associated with higher angiogenic cytokine levels (Costanzo et al., 2005). Thus, bolstering social support for individuals with cancer is important for both psychological wellbeing as well as possibly for cancer outcomes.
METHODS: A Friendly Phone Call Program (FPCP) was developed in collaboration by the Cancer Coordinator, Health Psychologist, Recreation Therapist and Social Worker to support Veterans who live alone, are elderly, or are physically frail throughout the COVID- 19 pandemic. Oncology providers were educated to identify socially isolated Veterans at-risk for distress during their phone appointments. The FPCP was notified of referrals by alert in CPRS. Charts were reviewed and triaged to the appropriate team member (i.e., psychology, recreation therapy, or social work). Follow-up phone calls were made utilizing a script to introduce FPCP and educate patients on available psychosocial services. In concert with FPCP, recreation therapy groups were offered by phone.
RESULTS: From 4/1/20 to 6/30/20, oncology providers identified 45 patients with psychosocial needs related to social isolation. 23 received outreach from Recreation Therapy, 9 by mental health, 8 by Social Work and 3 get weekly check-in calls from the Cancer Coordinator. 2 patients have since passed away.
CONCLUSIONS: VACHS developed a collaborative, multidisciplinary intervention that identifies patients at risk for psychosocial distress related to loneliness and provides ongoing, individualized, emotional support using existing staff and technology that is replicable in any VA setting.
BACKGROUND: At VACHS, we identified oncology patients at risk for loneliness subsequent to COVID-19 social distancing recommendations. Cancer patients are older, more physically frail and immune compromised, making them high-risk for complications related to covid-19 infection. Given this risk, social isolation might extend significantly beyond the initial period of lockdown for oncology patients. To protect this vulnerable population, we shifted from face-to-face visits to telemedicine. A workgroup formed to develop an intervention to support Veterans at-risk for prolonged isolation. Social isolation is a well-established risk factor for poor health and mortality (Caccioppo & Hawkley, 2003). For individuals with cancer, social isolation has been linked to poorer survival (Reynolds & Kaplan, 1990; Hislop, Waxler, Coldman, Elwood, and Kan, 1987). Research in woman with ovarian cancer suggests that limited social support is associated with higher angiogenic cytokine levels (Costanzo et al., 2005). Thus, bolstering social support for individuals with cancer is important for both psychological wellbeing as well as possibly for cancer outcomes.
METHODS: A Friendly Phone Call Program (FPCP) was developed in collaboration by the Cancer Coordinator, Health Psychologist, Recreation Therapist and Social Worker to support Veterans who live alone, are elderly, or are physically frail throughout the COVID- 19 pandemic. Oncology providers were educated to identify socially isolated Veterans at-risk for distress during their phone appointments. The FPCP was notified of referrals by alert in CPRS. Charts were reviewed and triaged to the appropriate team member (i.e., psychology, recreation therapy, or social work). Follow-up phone calls were made utilizing a script to introduce FPCP and educate patients on available psychosocial services. In concert with FPCP, recreation therapy groups were offered by phone.
RESULTS: From 4/1/20 to 6/30/20, oncology providers identified 45 patients with psychosocial needs related to social isolation. 23 received outreach from Recreation Therapy, 9 by mental health, 8 by Social Work and 3 get weekly check-in calls from the Cancer Coordinator. 2 patients have since passed away.
CONCLUSIONS: VACHS developed a collaborative, multidisciplinary intervention that identifies patients at risk for psychosocial distress related to loneliness and provides ongoing, individualized, emotional support using existing staff and technology that is replicable in any VA setting.
BACKGROUND: At VACHS, we identified oncology patients at risk for loneliness subsequent to COVID-19 social distancing recommendations. Cancer patients are older, more physically frail and immune compromised, making them high-risk for complications related to covid-19 infection. Given this risk, social isolation might extend significantly beyond the initial period of lockdown for oncology patients. To protect this vulnerable population, we shifted from face-to-face visits to telemedicine. A workgroup formed to develop an intervention to support Veterans at-risk for prolonged isolation. Social isolation is a well-established risk factor for poor health and mortality (Caccioppo & Hawkley, 2003). For individuals with cancer, social isolation has been linked to poorer survival (Reynolds & Kaplan, 1990; Hislop, Waxler, Coldman, Elwood, and Kan, 1987). Research in woman with ovarian cancer suggests that limited social support is associated with higher angiogenic cytokine levels (Costanzo et al., 2005). Thus, bolstering social support for individuals with cancer is important for both psychological wellbeing as well as possibly for cancer outcomes.
METHODS: A Friendly Phone Call Program (FPCP) was developed in collaboration by the Cancer Coordinator, Health Psychologist, Recreation Therapist and Social Worker to support Veterans who live alone, are elderly, or are physically frail throughout the COVID- 19 pandemic. Oncology providers were educated to identify socially isolated Veterans at-risk for distress during their phone appointments. The FPCP was notified of referrals by alert in CPRS. Charts were reviewed and triaged to the appropriate team member (i.e., psychology, recreation therapy, or social work). Follow-up phone calls were made utilizing a script to introduce FPCP and educate patients on available psychosocial services. In concert with FPCP, recreation therapy groups were offered by phone.
RESULTS: From 4/1/20 to 6/30/20, oncology providers identified 45 patients with psychosocial needs related to social isolation. 23 received outreach from Recreation Therapy, 9 by mental health, 8 by Social Work and 3 get weekly check-in calls from the Cancer Coordinator. 2 patients have since passed away.
CONCLUSIONS: VACHS developed a collaborative, multidisciplinary intervention that identifies patients at risk for psychosocial distress related to loneliness and provides ongoing, individualized, emotional support using existing staff and technology that is replicable in any VA setting.
Understanding De-Implementation of Low Value Castration for Men With Prostate Cancer
RESEARCH OBJECTIVE: Men with prostate cancer are often treated with androgen deprivation therapy (ADT). While ADT monotherapy is not appropriate treatment for most localized prostate cancer, it continues to be used raising questions of low-value care. Guided by the Theoretical Domains Framework (TDF) and the Behavior Change Wheel’s Capability, Opportunity, Motivation Model (COM-B), we conducted a qualitative study to identify determinants of low value ADT use and opportunities for de-implementation strategy development.
STUDY DESIGN: We used VA national cancer registry and administrative data from 2016-2017 to select facilities with the highest and lowest rates of ADT monotherapy as localized prostate cancer treatment. We used purposive sampling to select high and low performing sites and complete and code 20 provider interviews from 14 facilities across the nation (17 high and 3 low ADT use sites). Next, we mapped TDF domains to the COM-B Model to generate a conceptual framework of provider approaches to low value ADT.
PRINCIPAL FINDINGS: Based on emerging behavioral themes, our conceptual model characterized 3 groups of providers based on low value ADT use: (1) never prescribe; (2) willing, under some circumstances, to prescribe; and (3) routinely prescribe as an acceptable treatment option. Providers in all groups demonstrated strengths in the Capability domain, such as knowledge of appropriate localized prostate cancer treatment options (knowledge), coupled with interpersonal skills to engage patients in educational discussion (skills). Motivation to prescribe low value ADT depended on goals of care, including patient preferences (goals), view of their role (beliefs in capabilities/professional role and identity), and beliefs about benefits and harms ADT would afford patients (beliefs about consequences). In the Opportunity domain, access to resources, such as guidelines and interdisciplinary colleagues (environmental resources) and advice of peers (social influences) were influential factors in providers’ decision- making about low value ADT prescribing.
CONCLUSIONS: Behavioral theory-based characterization of provider practices helps clarify determinants implicated in provider decisions to prescribe low value ADT.
IMPLICATIONS: Identifying behavioral determinants impacting provider decisions to prescribe low value ADT informs theory-based de-implementation strategy development, and serves as a model to decrease low-value care more broadly.
RESEARCH OBJECTIVE: Men with prostate cancer are often treated with androgen deprivation therapy (ADT). While ADT monotherapy is not appropriate treatment for most localized prostate cancer, it continues to be used raising questions of low-value care. Guided by the Theoretical Domains Framework (TDF) and the Behavior Change Wheel’s Capability, Opportunity, Motivation Model (COM-B), we conducted a qualitative study to identify determinants of low value ADT use and opportunities for de-implementation strategy development.
STUDY DESIGN: We used VA national cancer registry and administrative data from 2016-2017 to select facilities with the highest and lowest rates of ADT monotherapy as localized prostate cancer treatment. We used purposive sampling to select high and low performing sites and complete and code 20 provider interviews from 14 facilities across the nation (17 high and 3 low ADT use sites). Next, we mapped TDF domains to the COM-B Model to generate a conceptual framework of provider approaches to low value ADT.
PRINCIPAL FINDINGS: Based on emerging behavioral themes, our conceptual model characterized 3 groups of providers based on low value ADT use: (1) never prescribe; (2) willing, under some circumstances, to prescribe; and (3) routinely prescribe as an acceptable treatment option. Providers in all groups demonstrated strengths in the Capability domain, such as knowledge of appropriate localized prostate cancer treatment options (knowledge), coupled with interpersonal skills to engage patients in educational discussion (skills). Motivation to prescribe low value ADT depended on goals of care, including patient preferences (goals), view of their role (beliefs in capabilities/professional role and identity), and beliefs about benefits and harms ADT would afford patients (beliefs about consequences). In the Opportunity domain, access to resources, such as guidelines and interdisciplinary colleagues (environmental resources) and advice of peers (social influences) were influential factors in providers’ decision- making about low value ADT prescribing.
CONCLUSIONS: Behavioral theory-based characterization of provider practices helps clarify determinants implicated in provider decisions to prescribe low value ADT.
IMPLICATIONS: Identifying behavioral determinants impacting provider decisions to prescribe low value ADT informs theory-based de-implementation strategy development, and serves as a model to decrease low-value care more broadly.
RESEARCH OBJECTIVE: Men with prostate cancer are often treated with androgen deprivation therapy (ADT). While ADT monotherapy is not appropriate treatment for most localized prostate cancer, it continues to be used raising questions of low-value care. Guided by the Theoretical Domains Framework (TDF) and the Behavior Change Wheel’s Capability, Opportunity, Motivation Model (COM-B), we conducted a qualitative study to identify determinants of low value ADT use and opportunities for de-implementation strategy development.
STUDY DESIGN: We used VA national cancer registry and administrative data from 2016-2017 to select facilities with the highest and lowest rates of ADT monotherapy as localized prostate cancer treatment. We used purposive sampling to select high and low performing sites and complete and code 20 provider interviews from 14 facilities across the nation (17 high and 3 low ADT use sites). Next, we mapped TDF domains to the COM-B Model to generate a conceptual framework of provider approaches to low value ADT.
PRINCIPAL FINDINGS: Based on emerging behavioral themes, our conceptual model characterized 3 groups of providers based on low value ADT use: (1) never prescribe; (2) willing, under some circumstances, to prescribe; and (3) routinely prescribe as an acceptable treatment option. Providers in all groups demonstrated strengths in the Capability domain, such as knowledge of appropriate localized prostate cancer treatment options (knowledge), coupled with interpersonal skills to engage patients in educational discussion (skills). Motivation to prescribe low value ADT depended on goals of care, including patient preferences (goals), view of their role (beliefs in capabilities/professional role and identity), and beliefs about benefits and harms ADT would afford patients (beliefs about consequences). In the Opportunity domain, access to resources, such as guidelines and interdisciplinary colleagues (environmental resources) and advice of peers (social influences) were influential factors in providers’ decision- making about low value ADT prescribing.
CONCLUSIONS: Behavioral theory-based characterization of provider practices helps clarify determinants implicated in provider decisions to prescribe low value ADT.
IMPLICATIONS: Identifying behavioral determinants impacting provider decisions to prescribe low value ADT informs theory-based de-implementation strategy development, and serves as a model to decrease low-value care more broadly.
Trends in Colorectal Cancer Survival by Sidedness and Age in the Veterans Health Administration 2000 – 2017
BACKGROUND: Colorectal cancer (CRC) accounts for about 10% of all cancers in the VA. Three-year survival is associated with both age at diagnosis and CRC stage. Yet, the minority of cases are detected at an early stage and the overall incidence of cancer in the VA patient population is forecast to rise. CRC survival and pathogenesis differ by tumor location Increases in CRC cases in individuals younger than fifty-years-of age and at more advanced stages have been reported in large, U.S. population-based cohorts (Meester et al., 2019). Here, we present a preliminary investigation of these trends amongst CRC patients in the VA.
METHODS: Briefly, a cohort of veteran patients (n = 40,951) was identified from 2000 – 2017 using the VA Central Cancer Registry (VACCR). We required all included patients to have a histologically-confirmed case of CRC as consistent with previous studies (Zullig et al., 2016) and only one registry entry. We constructed Kaplan- Meier curves and created a Cox-Proportional Hazards model to examine survival. Additional filtering by age at the date of diagnosis was used to identify patients between ages 40 and 49 and tumor location as abstracted in the VACCR. Regression analysis was used to examine trends in stage at diagnosis and in those between aged 40 and 49.
RESULTS: Our findings indicate that proximal (rightsided) colon cancer is associated with poorer survival than distal (left-sided), consistent with previous findings. During this time period, 3% of the cohort or 1,249 cases were diagnosed amongst individuals of ages 40 – 49. Regression analysis indicated differences in trends amongst VHA patients younger than fifty years of age and in stage at diagnosis. Though, the time period of this study was shorter than those previously published.
CONCLUSION: Further work is underway to identify the sources of these differences in survivorship in VHA patients, including the analysis of therapeutic regimens. This work was performed under R&D and IRB protocols reviewed approved by the VA Boston Healthcare System.
BACKGROUND: Colorectal cancer (CRC) accounts for about 10% of all cancers in the VA. Three-year survival is associated with both age at diagnosis and CRC stage. Yet, the minority of cases are detected at an early stage and the overall incidence of cancer in the VA patient population is forecast to rise. CRC survival and pathogenesis differ by tumor location Increases in CRC cases in individuals younger than fifty-years-of age and at more advanced stages have been reported in large, U.S. population-based cohorts (Meester et al., 2019). Here, we present a preliminary investigation of these trends amongst CRC patients in the VA.
METHODS: Briefly, a cohort of veteran patients (n = 40,951) was identified from 2000 – 2017 using the VA Central Cancer Registry (VACCR). We required all included patients to have a histologically-confirmed case of CRC as consistent with previous studies (Zullig et al., 2016) and only one registry entry. We constructed Kaplan- Meier curves and created a Cox-Proportional Hazards model to examine survival. Additional filtering by age at the date of diagnosis was used to identify patients between ages 40 and 49 and tumor location as abstracted in the VACCR. Regression analysis was used to examine trends in stage at diagnosis and in those between aged 40 and 49.
RESULTS: Our findings indicate that proximal (rightsided) colon cancer is associated with poorer survival than distal (left-sided), consistent with previous findings. During this time period, 3% of the cohort or 1,249 cases were diagnosed amongst individuals of ages 40 – 49. Regression analysis indicated differences in trends amongst VHA patients younger than fifty years of age and in stage at diagnosis. Though, the time period of this study was shorter than those previously published.
CONCLUSION: Further work is underway to identify the sources of these differences in survivorship in VHA patients, including the analysis of therapeutic regimens. This work was performed under R&D and IRB protocols reviewed approved by the VA Boston Healthcare System.
BACKGROUND: Colorectal cancer (CRC) accounts for about 10% of all cancers in the VA. Three-year survival is associated with both age at diagnosis and CRC stage. Yet, the minority of cases are detected at an early stage and the overall incidence of cancer in the VA patient population is forecast to rise. CRC survival and pathogenesis differ by tumor location Increases in CRC cases in individuals younger than fifty-years-of age and at more advanced stages have been reported in large, U.S. population-based cohorts (Meester et al., 2019). Here, we present a preliminary investigation of these trends amongst CRC patients in the VA.
METHODS: Briefly, a cohort of veteran patients (n = 40,951) was identified from 2000 – 2017 using the VA Central Cancer Registry (VACCR). We required all included patients to have a histologically-confirmed case of CRC as consistent with previous studies (Zullig et al., 2016) and only one registry entry. We constructed Kaplan- Meier curves and created a Cox-Proportional Hazards model to examine survival. Additional filtering by age at the date of diagnosis was used to identify patients between ages 40 and 49 and tumor location as abstracted in the VACCR. Regression analysis was used to examine trends in stage at diagnosis and in those between aged 40 and 49.
RESULTS: Our findings indicate that proximal (rightsided) colon cancer is associated with poorer survival than distal (left-sided), consistent with previous findings. During this time period, 3% of the cohort or 1,249 cases were diagnosed amongst individuals of ages 40 – 49. Regression analysis indicated differences in trends amongst VHA patients younger than fifty years of age and in stage at diagnosis. Though, the time period of this study was shorter than those previously published.
CONCLUSION: Further work is underway to identify the sources of these differences in survivorship in VHA patients, including the analysis of therapeutic regimens. This work was performed under R&D and IRB protocols reviewed approved by the VA Boston Healthcare System.
Transportation as a Barrier to Colorectal Cancer Care
PURPOSE: To describe the frequency of Veterans reporting and the factors associated with transportation barriers to or from colorectal cancer (CRC) care visits.
BACKGROUND: Transportation barriers limit access to healthcare services and contribute to suboptimal clinical outcomes across the cancer care continuum. The relationship between patient-level characteristics, travel-related factors (e.g., mode of transportation), and transportation barriers among Veterans with CRC has been poorly described.
METHODS: Between November 2015 and September 2016, Veterans with incident stage I, II, or III CRC completed the Colorectal Cancer Patient Adherence to Survivorship Treatment survey to assess their perceived barriers to, and adherence with, recommended care. The survey measured: (1) demographics; (2) travel-related factors, including distance traveled to and convenience of care; and (3) perceived chaotic lifestyle (e.g., ability to organize, predictability of schedules) using the Confusion, Hubbub, and Order Scale. Veterans who reported “Always”, “Often”, or “Sometimes” experiencing difficulty with transportation to or from CRC care appointments were categorized as having transportation barriers.
DATA ANALYSIS: We assessed pairwise correlations between transportation barriers, travel-related factors, and chaotic lifestyle and used logistic regression to evaluate the association between the reporting of transportation barriers, distance traveled to care, and chaotic lifestyle.
RESULTS: Of the 115 Veterans included in this analysis, 21 (18%) reported transportation barriers to or from CRC care visits. A majority of Veterans who reported transportation barriers were previously married (62%), traveled more than 20 miles for care (81%), and had a chaotic lifestyle (57%). Distance to care was not strongly correlated with reporting transportation barriers (Spearman’s ρ=0.12, p=0.19), whereas a chaotic lifestyle was both positively and significantly correlated with experiencing transportation barriers (Spearman’s ρ=0.22, p=0.02). Results from the logistic regression model modestly supported the findings from the pairwise correlations, but were not statistically significant.
IMPLICATIONS: Transportation is an important barrier to or from CRC care visits, especially among Veterans who experience chaotic lifestyles. Identifying Veterans with chaotic lifestyles would allow for timely intervention (e.g., patient navigation, organizational skills training), which could result in the potential modification of observed risk factors and thus, support access to healthcare services and treatment across the cancer care continuum.
PURPOSE: To describe the frequency of Veterans reporting and the factors associated with transportation barriers to or from colorectal cancer (CRC) care visits.
BACKGROUND: Transportation barriers limit access to healthcare services and contribute to suboptimal clinical outcomes across the cancer care continuum. The relationship between patient-level characteristics, travel-related factors (e.g., mode of transportation), and transportation barriers among Veterans with CRC has been poorly described.
METHODS: Between November 2015 and September 2016, Veterans with incident stage I, II, or III CRC completed the Colorectal Cancer Patient Adherence to Survivorship Treatment survey to assess their perceived barriers to, and adherence with, recommended care. The survey measured: (1) demographics; (2) travel-related factors, including distance traveled to and convenience of care; and (3) perceived chaotic lifestyle (e.g., ability to organize, predictability of schedules) using the Confusion, Hubbub, and Order Scale. Veterans who reported “Always”, “Often”, or “Sometimes” experiencing difficulty with transportation to or from CRC care appointments were categorized as having transportation barriers.
DATA ANALYSIS: We assessed pairwise correlations between transportation barriers, travel-related factors, and chaotic lifestyle and used logistic regression to evaluate the association between the reporting of transportation barriers, distance traveled to care, and chaotic lifestyle.
RESULTS: Of the 115 Veterans included in this analysis, 21 (18%) reported transportation barriers to or from CRC care visits. A majority of Veterans who reported transportation barriers were previously married (62%), traveled more than 20 miles for care (81%), and had a chaotic lifestyle (57%). Distance to care was not strongly correlated with reporting transportation barriers (Spearman’s ρ=0.12, p=0.19), whereas a chaotic lifestyle was both positively and significantly correlated with experiencing transportation barriers (Spearman’s ρ=0.22, p=0.02). Results from the logistic regression model modestly supported the findings from the pairwise correlations, but were not statistically significant.
IMPLICATIONS: Transportation is an important barrier to or from CRC care visits, especially among Veterans who experience chaotic lifestyles. Identifying Veterans with chaotic lifestyles would allow for timely intervention (e.g., patient navigation, organizational skills training), which could result in the potential modification of observed risk factors and thus, support access to healthcare services and treatment across the cancer care continuum.
PURPOSE: To describe the frequency of Veterans reporting and the factors associated with transportation barriers to or from colorectal cancer (CRC) care visits.
BACKGROUND: Transportation barriers limit access to healthcare services and contribute to suboptimal clinical outcomes across the cancer care continuum. The relationship between patient-level characteristics, travel-related factors (e.g., mode of transportation), and transportation barriers among Veterans with CRC has been poorly described.
METHODS: Between November 2015 and September 2016, Veterans with incident stage I, II, or III CRC completed the Colorectal Cancer Patient Adherence to Survivorship Treatment survey to assess their perceived barriers to, and adherence with, recommended care. The survey measured: (1) demographics; (2) travel-related factors, including distance traveled to and convenience of care; and (3) perceived chaotic lifestyle (e.g., ability to organize, predictability of schedules) using the Confusion, Hubbub, and Order Scale. Veterans who reported “Always”, “Often”, or “Sometimes” experiencing difficulty with transportation to or from CRC care appointments were categorized as having transportation barriers.
DATA ANALYSIS: We assessed pairwise correlations between transportation barriers, travel-related factors, and chaotic lifestyle and used logistic regression to evaluate the association between the reporting of transportation barriers, distance traveled to care, and chaotic lifestyle.
RESULTS: Of the 115 Veterans included in this analysis, 21 (18%) reported transportation barriers to or from CRC care visits. A majority of Veterans who reported transportation barriers were previously married (62%), traveled more than 20 miles for care (81%), and had a chaotic lifestyle (57%). Distance to care was not strongly correlated with reporting transportation barriers (Spearman’s ρ=0.12, p=0.19), whereas a chaotic lifestyle was both positively and significantly correlated with experiencing transportation barriers (Spearman’s ρ=0.22, p=0.02). Results from the logistic regression model modestly supported the findings from the pairwise correlations, but were not statistically significant.
IMPLICATIONS: Transportation is an important barrier to or from CRC care visits, especially among Veterans who experience chaotic lifestyles. Identifying Veterans with chaotic lifestyles would allow for timely intervention (e.g., patient navigation, organizational skills training), which could result in the potential modification of observed risk factors and thus, support access to healthcare services and treatment across the cancer care continuum.
Thromboembolic Events in Lung Cancer Patients Treated With Conventional Chemotherapy Alone Compared With Immunotherapy
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
The Vaping Epidemic: Implications for Cancer Care
BACKGROUND: There has been an unprecedented increase in vaping by young people. In 2019, an outbreak of acute lung injuries linked to vaping was later recognized as a disease entity known as e-cigarette or vaping product-use associated lung injury (EVALI). A number of cancer therapeutics have been associated with pulmonary toxicity, and the incidence and severity of immune- and chemotherapy-related pneumonitis may be additionally compounded by EVALI. Here we present the case of a 42-year-old male with good-risk advanced seminoma treated with three cycles of bleomycin, etoposide, and cisplatin for curative intent.
CASE REPORT: The patient developed febrile neutropenia after the third cycle of treatment, and upon count recovery, he rapidly deteriorated into acute hypoxic respiratory failure that was ultimately fatal and most consistent with bleomycin-induced lung toxicity. It was later revealed that the patient had been an avid user of tetrahydrocannabinol-containing vaping products, and whether this contributed to a more progressive injurious picture is unknown.
DISCUSION: We have also encountered several cases of non-infectious hypoxic respiratory failure in patients who reported a history of vaping while receiving checkpoint inhibitor immunotherapy for advanced lung cancer. While the incidence of EVALI has declined following its highly publicized notoriety, vaping remains quite popular despite known hazards and represents a significant public health challenge. The risks posed by the use of vaping products may be higher for individuals with cancer who are often older and more frequently suffer from comorbidities that may increase susceptibility to drug-induced lung injury. Consequently, additional efforts should be made to increase awareness of the harmful effects of vaping, especially in the era of COVID-19. To minimize oncology-related pulmonary complications for which vaping may be a risk factor, we updated our infusion nursing evaluation to include questions on vaping activities and implemented provider notification before administering cancer-directed therapy. We have also educated our oncology team about the importance of obtaining a vaping history.
CONCLUSION: As oncology providers for the Veteran population, we should be mindful to counsel our cancer patients about the health risks of vaping and encourage alternative nicotine replacement therapy for those who use nicotine-based vaping products for smoking cessation.
BACKGROUND: There has been an unprecedented increase in vaping by young people. In 2019, an outbreak of acute lung injuries linked to vaping was later recognized as a disease entity known as e-cigarette or vaping product-use associated lung injury (EVALI). A number of cancer therapeutics have been associated with pulmonary toxicity, and the incidence and severity of immune- and chemotherapy-related pneumonitis may be additionally compounded by EVALI. Here we present the case of a 42-year-old male with good-risk advanced seminoma treated with three cycles of bleomycin, etoposide, and cisplatin for curative intent.
CASE REPORT: The patient developed febrile neutropenia after the third cycle of treatment, and upon count recovery, he rapidly deteriorated into acute hypoxic respiratory failure that was ultimately fatal and most consistent with bleomycin-induced lung toxicity. It was later revealed that the patient had been an avid user of tetrahydrocannabinol-containing vaping products, and whether this contributed to a more progressive injurious picture is unknown.
DISCUSION: We have also encountered several cases of non-infectious hypoxic respiratory failure in patients who reported a history of vaping while receiving checkpoint inhibitor immunotherapy for advanced lung cancer. While the incidence of EVALI has declined following its highly publicized notoriety, vaping remains quite popular despite known hazards and represents a significant public health challenge. The risks posed by the use of vaping products may be higher for individuals with cancer who are often older and more frequently suffer from comorbidities that may increase susceptibility to drug-induced lung injury. Consequently, additional efforts should be made to increase awareness of the harmful effects of vaping, especially in the era of COVID-19. To minimize oncology-related pulmonary complications for which vaping may be a risk factor, we updated our infusion nursing evaluation to include questions on vaping activities and implemented provider notification before administering cancer-directed therapy. We have also educated our oncology team about the importance of obtaining a vaping history.
CONCLUSION: As oncology providers for the Veteran population, we should be mindful to counsel our cancer patients about the health risks of vaping and encourage alternative nicotine replacement therapy for those who use nicotine-based vaping products for smoking cessation.
BACKGROUND: There has been an unprecedented increase in vaping by young people. In 2019, an outbreak of acute lung injuries linked to vaping was later recognized as a disease entity known as e-cigarette or vaping product-use associated lung injury (EVALI). A number of cancer therapeutics have been associated with pulmonary toxicity, and the incidence and severity of immune- and chemotherapy-related pneumonitis may be additionally compounded by EVALI. Here we present the case of a 42-year-old male with good-risk advanced seminoma treated with three cycles of bleomycin, etoposide, and cisplatin for curative intent.
CASE REPORT: The patient developed febrile neutropenia after the third cycle of treatment, and upon count recovery, he rapidly deteriorated into acute hypoxic respiratory failure that was ultimately fatal and most consistent with bleomycin-induced lung toxicity. It was later revealed that the patient had been an avid user of tetrahydrocannabinol-containing vaping products, and whether this contributed to a more progressive injurious picture is unknown.
DISCUSION: We have also encountered several cases of non-infectious hypoxic respiratory failure in patients who reported a history of vaping while receiving checkpoint inhibitor immunotherapy for advanced lung cancer. While the incidence of EVALI has declined following its highly publicized notoriety, vaping remains quite popular despite known hazards and represents a significant public health challenge. The risks posed by the use of vaping products may be higher for individuals with cancer who are often older and more frequently suffer from comorbidities that may increase susceptibility to drug-induced lung injury. Consequently, additional efforts should be made to increase awareness of the harmful effects of vaping, especially in the era of COVID-19. To minimize oncology-related pulmonary complications for which vaping may be a risk factor, we updated our infusion nursing evaluation to include questions on vaping activities and implemented provider notification before administering cancer-directed therapy. We have also educated our oncology team about the importance of obtaining a vaping history.
CONCLUSION: As oncology providers for the Veteran population, we should be mindful to counsel our cancer patients about the health risks of vaping and encourage alternative nicotine replacement therapy for those who use nicotine-based vaping products for smoking cessation.