Walter Alexander

A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the treatment not only reduces fractures long-term, but it may also improve overall survival and increase bone density.

The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.

“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.

Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.

ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.

The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.

The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.

Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).

There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.

Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).

In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.

“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.

A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.

A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the treatment not only reduces fractures long-term, but it may also improve overall survival and increase bone density.

The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.

“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.

Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.

ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.

The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.

The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.

Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).

There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.

Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).

In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.

“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.

A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.

A final long-term analysis of a study designed to evaluate the safety of a common osteoporosis drug used to treat bone loss in women who were treated for breast cancer, finds the treatment not only reduces fractures long-term, but it may also improve overall survival and increase bone density.

The final analysis of “Adjuvant Denosumab in Breast Cancer (ABCSG-18)” was presented at the annual meeting of the American Society of Clinical Oncology.

“Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer on aromatase inhibitors treatment,” said the study’s author Michael Gnant, MD, FACS, director of surgery for the Medical University of Vienna.

Denosumab is currently recommended by ASCO as a treatment option for osteoporosis in patients who were successfully treated for nonmetastatic disease.

ABCSG-18 was a prospective, double-blind, placebo-controlled, phase 3 trial that comprised 3,420 patients (mean age 64.5 years) from 58 treatment centers. It included postmenopausal patients with early HR+ breast cancer who were treated with aromatase inhibitors between 2006 and 2013. Among the patients, 1,711 received denosumab 60 mg and 1,709 received a placebo every 6 months.

The primary endpoint was time to first clinical fracture, and the secondary disease outcome-related endpoints were disease-free survival, bone metastasis–free survival, and overall survival.

The hazard ratio for disease-free survival in the denosumab group was 0.83 (95% confidence interval [CI], 0.71-0.97, P = .02) after a median follow-up of 8 years. Disease-free survival (DFS) was 69.0% in the placebo arm and 74.4% in the denosumab arm, with events occurring in 19.8% of patients overall, including deaths in 8.3%.

Bone metastasis–free survival (BMFS) rates were 81.3% and 85.7% in the placebo and denosumab arms, respectively (HR = 0.81, 95% CI, 0.65-1.00, P = .05). Overall survival was 83.6% and 88.8% in the placebo and denosumab arms, respectively (HR = 0.80; 95% CI, 0.63-1.01, P = .06).

There were no new toxicities, nor was there a single positive case of osteonecrosis of the jaw (ONJ) during the study period, which may be due to the low dosage of denosumab. The bone protection dose of denosumab is much lower than that used for treatment of metastases which can be 12 times higher. In those cases, 4%-6% of patients may develop ONJ. “At these very low doses, even after 30,000 treatment years, we did not observe a single confirmed ONJ case,” he said.

Exploratory observations showed the majority of events to include distant recurrences in bone, liver, and lungs. Analysis revealed a trend toward reduction in contralateral breast cancer in the denosumab arm (24 versus 29 events), with a reduction in second non-breast primary malignancies (101 versus 127 events).

In a much earlier ABCSG-18 study from 2015, the primary endpoint of fracture risk was reduced significantly with denosumab (HR = 0.50, P < .0001), with highly significantly longer time to first clinical fracture, higher percent increase in bone mineral density (P < .0001 for both) and fewer vertebral fractures (P = .009). There is evidence that older generation bisphosphonates have potential beyond bone health, such as reducing metabolism (which benefits bone turnover), and improving breast cancer outcomes. These benefits sparked interest in potential long-term cancer reduction with denosumab, Dr. Gnant said.

“Bone marrow is a putative source of late relapse. Tumor cells can harbor there in a quiescent state for 10-15-20 years, and then for some reason wake up and cause metastases. So, all bone-targeted agents are also evaluated for reductions in cancer which is what we were looking to investigate here in this 15-year data,” he said. Denosumab is more targeted than the bisphosphonates, and directly inhibits the RANK ligand which is an important mediator of osteoclast activation. “This ligand is believed to support metastases in the process of waking up,” Dr. Gnant said.

A limitation of the study is that the outcome endpoints of ABCSG-18 are secondary ones, making the results technically descriptive. The study was sponsored by Amgen.

Results of the KEYNOTE-522 clinical trial highlight the importance of neoadjuvant treatment with pembrolizumab for improving survival in patients with early triple negative breast cancer (TNBC).

The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.

KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.

The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.

A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.

The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.

At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.

Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.

Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.

The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).

“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.

The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.

Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).

“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.

In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.

The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.

Results of the KEYNOTE-522 clinical trial highlight the importance of neoadjuvant treatment with pembrolizumab for improving survival in patients with early triple negative breast cancer (TNBC).

The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.

KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.

The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.

A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.

The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.

At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.

Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.

Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.

The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).

“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.

The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.

Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).

“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.

In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.

The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.

Results of the KEYNOTE-522 clinical trial highlight the importance of neoadjuvant treatment with pembrolizumab for improving survival in patients with early triple negative breast cancer (TNBC).

The findings were presented in Chicago June 4 and 5 at the annual meeting of the American Society of Clinical Oncology by study author Lajos Pusztai, MD, D.Phil, director of Breast Cancer Translational Research at Yale University, New Haven, Conn.

KEYNOTE-522 is the first prospective, randomized, placebo-controlled phase 3 trial of pembrolizumab for early-stage TNBC in the neoadjuvant and adjuvant setting.

The study included 1,174 patients (median age 49 years) with previously untreated stage II or III triple-negative breast cancer. Patients were randomly assigned to receive neoadjuvant therapy with four cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After surgery, patients received pembrolizumab or placebeo for 9 cycles or until recurrence or unacceptable toxicity. The primary end points were pathological complete response and event-free survival.

A total of 784 patients were treated with pembrolizumab and chemotherapy, and the second group of 390 patients received a placebo and chemotherapy. After surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo and chemotherapy for every 3 weeks for up to nine cycles.

The estimated event-free survival at 36 months was 84.5% in the pembrolizumab-chemotherapy group, compared with 76.8% in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% confidence interval, 0.48 to 0.82; P <0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy.

At the first interim analysis, 64.8% achieved pathological complete response in the pembrolizumab group versus 51.2% in the placebo group. At the fourth interim analysis at 36 months, event-free survival was 76.8% in the placebo arm and 84.5% in the pembrolizumab arm. RCB-0 status was achieved by 63.4% and 56.2% of patients in the pembrolizumab and placebo arms, respectively.

Pembrolizumab did contribute immune-related adverse events, mostly grades 1-2, in about 17% of patients with thyroid function abnormalities most common with most occurring 20 weeks prior to surgical treatment.

Treatment with pembrolizumab added to chemotherapy, compared with chemotherapy alone, shifted residual cancer burden to lower categories across the entire spectrum of patients in the trial.

The hazard ratio for event-free survival with RCB-0, which Dr. Pusztai said is equivalent to a pathologic complete response (pCR), was 0.70 (0.38-1.31). For RCB-1 (minimal residual disease) it was 0.92 (0.39-2.20); for RCB-2 (moderate residual disease) it was 0.52 (0.32-0.82); and for RCB-3 (extensive residual disease) it was 1.24 (0.69-2.23).

“The most important finding is that patients in RCB-2, a group with a moderate amount of residual disease, experienced significant improvement with pembrolizumab. This clearly indicates not only that pembrolizumab leads to higher pCR rates but also that the pembrolizumCR/RCB-0 ... extends to patients who do not achieve pCR,” Dr. Pusztai said.

The benefit, he suggested, could be a result of the adjuvant pembrolizumab maintenance phase.

Patients in the RCB-3 category do poorly regardless of treatment (EFS of 34.6 % and 26.2% in the pembrolizumab and placebo arms, respectively).

“The RCB-3 population represents an unmet medical need, and they will need better drugs, and additional postoperative adjuvant therapy,” Dr. Pusztai said. The current standard of care is capecitabine for 6-8 cycles. Emerging new therapies, such as antibody drug conjugates, will be tested, he said.

In terms of limitations, adjuvant capecitabine was not allowed. “It remains uncertain how much better the RCB-2 and -3 patient outcomes would have been if capecitabine were administered,” he said.

The study was funded by Merck Sharp and Dohme, a subsidiary of Merck. Dr. Pusztai has received consulting fees and honoraria from Merck.

A study published in May in The Lancet journal eClinicalMedicine reports that breathomics testing is one step closer to becoming a reality as a lung cancer screening tool.

The tool was successfully used to identify, in 84 patients, 16 lung cancer–related carcinogenic volatile compounds (VOCs), such as aldehydes, hydrocarbons, ketones, carboxylic acids, and furan – some of which are compounds used in the production of common household goods, such as furniture, carpeting, and wood floors.

“The test is anticipated to be highlighted for primary screening of lung cancer but not the final diagnosis,” according to study authors who were led by Peiyu Wang, MD, PhD, chair of social medicine and health at Peking (China) University.

While early diagnosis and treatment are critical for improving lung cancer survival, early detection of lung cancer is challenging because of the lack of clinical manifestations and specific biomarkers. Annual CT scans are costly and include radiation exposure, Dr. Wang and his associates wrote.

Breathomics testing is considered a promising method for detection and screening for lung cancer. It has been under study for years and in 2014, researchers from Belgium published a review in Cancer Epidemiology Biomarkers and Prevention documenting the use of VOCs as early diagnostic or prognostic biomarkers for mesothelioma.

Lung cancer breath biomarkers identified in various studies have been highly heterogeneous because of differing sample collection methods, varying patient conditions, testing environments, and analysis methods. As a result, there currently is no breathomics test for lung cancer screening, Dr. Wang said in an interview.

In terms of its potential as a lung cancer screening tool, “Clinicians may introduce this test for people with high risk for lung cancer, such as elderly smokers, or people with suspected symptoms. It may also be introduced for young populations with subjective or objective needs to screen for lung cancer. As the proportion of lung adenocarcinoma in nonsmoking young women is increasing, the test may be a good method for lung cancer screening in this population,” Dr. Wang said.

After adjusting for age, sex, smoking, and comorbidities, researchers found elevated levels for 16 VOCs in patients with lung cancer. A diagnostic model including the 16 VOCs achieved an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1% in lung cancer diagnosis. A model including the top eight VOCs achieved an area under the curve of 0.931, sensitivity of 86.0%, specificity of 87.2%, and accuracy of 86.9%.

After selecting 28 VOCs as candidates through a literature review, Dr. Wang and associates conducted a prospective discovery study from Sept. 1 to Dec. 31, 2020, using high-pressure photon ionization time-of-flight mass spectrometry to evaluate their performance for lung cancer diagnosis. The validation study included 157 lung cancer patients (mean age 57.0 years; 54.1 percent female) and 368 volunteers (mean age 44.5 years; 31.3% female).

“The external validation confirmed good performance of these biomarkers in lung cancer detection,” the researchers stated. It helped, they added, to solve the heterogeneity among published studies, establishing both 16 VOCs and 8 VOCS for lung cancer screening.

The authors stated that a large gap exists between breathomics research and clinical practices in lung cancer detection and screening. While the validated 16 VOCs, mainly aldehydes and hydrocarbon, showed potential for promoting this lung cancer screening strategy, more scientific studies are warranted to investigate the underlying mechanisms of identified lung cancer VOCs.

Dr. Wang declared no competing interests.

A study published in May in The Lancet journal eClinicalMedicine reports that breathomics testing is one step closer to becoming a reality as a lung cancer screening tool.

The tool was successfully used to identify, in 84 patients, 16 lung cancer–related carcinogenic volatile compounds (VOCs), such as aldehydes, hydrocarbons, ketones, carboxylic acids, and furan – some of which are compounds used in the production of common household goods, such as furniture, carpeting, and wood floors.

“The test is anticipated to be highlighted for primary screening of lung cancer but not the final diagnosis,” according to study authors who were led by Peiyu Wang, MD, PhD, chair of social medicine and health at Peking (China) University.

While early diagnosis and treatment are critical for improving lung cancer survival, early detection of lung cancer is challenging because of the lack of clinical manifestations and specific biomarkers. Annual CT scans are costly and include radiation exposure, Dr. Wang and his associates wrote.

Breathomics testing is considered a promising method for detection and screening for lung cancer. It has been under study for years and in 2014, researchers from Belgium published a review in Cancer Epidemiology Biomarkers and Prevention documenting the use of VOCs as early diagnostic or prognostic biomarkers for mesothelioma.

Lung cancer breath biomarkers identified in various studies have been highly heterogeneous because of differing sample collection methods, varying patient conditions, testing environments, and analysis methods. As a result, there currently is no breathomics test for lung cancer screening, Dr. Wang said in an interview.

In terms of its potential as a lung cancer screening tool, “Clinicians may introduce this test for people with high risk for lung cancer, such as elderly smokers, or people with suspected symptoms. It may also be introduced for young populations with subjective or objective needs to screen for lung cancer. As the proportion of lung adenocarcinoma in nonsmoking young women is increasing, the test may be a good method for lung cancer screening in this population,” Dr. Wang said.

After adjusting for age, sex, smoking, and comorbidities, researchers found elevated levels for 16 VOCs in patients with lung cancer. A diagnostic model including the 16 VOCs achieved an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1% in lung cancer diagnosis. A model including the top eight VOCs achieved an area under the curve of 0.931, sensitivity of 86.0%, specificity of 87.2%, and accuracy of 86.9%.

After selecting 28 VOCs as candidates through a literature review, Dr. Wang and associates conducted a prospective discovery study from Sept. 1 to Dec. 31, 2020, using high-pressure photon ionization time-of-flight mass spectrometry to evaluate their performance for lung cancer diagnosis. The validation study included 157 lung cancer patients (mean age 57.0 years; 54.1 percent female) and 368 volunteers (mean age 44.5 years; 31.3% female).

“The external validation confirmed good performance of these biomarkers in lung cancer detection,” the researchers stated. It helped, they added, to solve the heterogeneity among published studies, establishing both 16 VOCs and 8 VOCS for lung cancer screening.

The authors stated that a large gap exists between breathomics research and clinical practices in lung cancer detection and screening. While the validated 16 VOCs, mainly aldehydes and hydrocarbon, showed potential for promoting this lung cancer screening strategy, more scientific studies are warranted to investigate the underlying mechanisms of identified lung cancer VOCs.

Dr. Wang declared no competing interests.

A study published in May in The Lancet journal eClinicalMedicine reports that breathomics testing is one step closer to becoming a reality as a lung cancer screening tool.

The tool was successfully used to identify, in 84 patients, 16 lung cancer–related carcinogenic volatile compounds (VOCs), such as aldehydes, hydrocarbons, ketones, carboxylic acids, and furan – some of which are compounds used in the production of common household goods, such as furniture, carpeting, and wood floors.

“The test is anticipated to be highlighted for primary screening of lung cancer but not the final diagnosis,” according to study authors who were led by Peiyu Wang, MD, PhD, chair of social medicine and health at Peking (China) University.

While early diagnosis and treatment are critical for improving lung cancer survival, early detection of lung cancer is challenging because of the lack of clinical manifestations and specific biomarkers. Annual CT scans are costly and include radiation exposure, Dr. Wang and his associates wrote.

Breathomics testing is considered a promising method for detection and screening for lung cancer. It has been under study for years and in 2014, researchers from Belgium published a review in Cancer Epidemiology Biomarkers and Prevention documenting the use of VOCs as early diagnostic or prognostic biomarkers for mesothelioma.

Lung cancer breath biomarkers identified in various studies have been highly heterogeneous because of differing sample collection methods, varying patient conditions, testing environments, and analysis methods. As a result, there currently is no breathomics test for lung cancer screening, Dr. Wang said in an interview.

In terms of its potential as a lung cancer screening tool, “Clinicians may introduce this test for people with high risk for lung cancer, such as elderly smokers, or people with suspected symptoms. It may also be introduced for young populations with subjective or objective needs to screen for lung cancer. As the proportion of lung adenocarcinoma in nonsmoking young women is increasing, the test may be a good method for lung cancer screening in this population,” Dr. Wang said.

After adjusting for age, sex, smoking, and comorbidities, researchers found elevated levels for 16 VOCs in patients with lung cancer. A diagnostic model including the 16 VOCs achieved an area under the curve of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1% in lung cancer diagnosis. A model including the top eight VOCs achieved an area under the curve of 0.931, sensitivity of 86.0%, specificity of 87.2%, and accuracy of 86.9%.

After selecting 28 VOCs as candidates through a literature review, Dr. Wang and associates conducted a prospective discovery study from Sept. 1 to Dec. 31, 2020, using high-pressure photon ionization time-of-flight mass spectrometry to evaluate their performance for lung cancer diagnosis. The validation study included 157 lung cancer patients (mean age 57.0 years; 54.1 percent female) and 368 volunteers (mean age 44.5 years; 31.3% female).

“The external validation confirmed good performance of these biomarkers in lung cancer detection,” the researchers stated. It helped, they added, to solve the heterogeneity among published studies, establishing both 16 VOCs and 8 VOCS for lung cancer screening.

The authors stated that a large gap exists between breathomics research and clinical practices in lung cancer detection and screening. While the validated 16 VOCs, mainly aldehydes and hydrocarbon, showed potential for promoting this lung cancer screening strategy, more scientific studies are warranted to investigate the underlying mechanisms of identified lung cancer VOCs.

Dr. Wang declared no competing interests.

In patients with B-cell deficiencies, CoVac-1, a SARS-CoV-2 vaccine currently in clinical trials in Germany, induced T-cell immune responses in a large proportion of patients, according to study results presented at the annual meeting of the American Association for Cancer Research.

The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.

In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).

“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”

B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.

In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.

While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.

CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.

The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.

“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”

Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.

A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.

“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.

“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.

Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.

Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.

In patients with B-cell deficiencies, CoVac-1, a SARS-CoV-2 vaccine currently in clinical trials in Germany, induced T-cell immune responses in a large proportion of patients, according to study results presented at the annual meeting of the American Association for Cancer Research.

The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.

In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).

“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”

B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.

In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.

While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.

CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.

The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.

“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”

Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.

A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.

“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.

“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.

Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.

Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.

In patients with B-cell deficiencies, CoVac-1, a SARS-CoV-2 vaccine currently in clinical trials in Germany, induced T-cell immune responses in a large proportion of patients, according to study results presented at the annual meeting of the American Association for Cancer Research.

The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.

In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).

“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”

B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.

In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.

While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.

CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.

The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.

“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”

Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.

A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.

“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.

“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.

Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.

Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

A ketogenic diet fed to mice with epithelial ovarian cancer led to significantly increased tumor growth and gut microbiome alterations, according to study recently presented at the annual meeting of the Society of Gynecologic Oncology.

“The keto diet is very popular, especially among patients who believe it may treat cancer by starving tumors of the fuel they need to grow, altering the immune system, and other anticancer effects,” said study leader Mariam AlHilli, MD, of the Cleveland Clinic.

The findings are surprising because in other studies the high-fat, zero-carb ketogenic diet has demonstrated tumor-suppressing effects. It has been under study as a possible adjuvant therapy for other cancers, such as glioblastoma, colon cancer, prostate cancer, and pancreatic cancer.

“While we don’t know yet whether these findings extend to patients, the results in animals indicate that instead of being protective, the keto diet appears to promote ovarian cancer growth and progression,” Dr. AlHilli said. In the present study, tumor bearing mice were fed a keto diet consisting of 10% protein, 0% carbohydrates, and 90% fat, while the high-fat diet was 10% protein, 15% carbohydrates, and 75% fat. The control diet consisted of 10% protein, 77% carbohydrates, and 13% fat. Epithelial ovarian cancer tumor growth was monitored weekly.

Over the 6- to 10-week course of study, a 9.1-fold increase from baseline in tumor growth was observed in the keto diet-fed mice (n = 20). Among mice fed a high-fat diet (n = 20) that included some carbohydrates, tumor growth increased 2.0-fold from baseline, and among control group mice (n = 20) fed a low-fat, high carbohydrate diet, tumor growth increased 3.1-fold.

The investigators observed several hallmarks of tumor progression: tumor associated macrophages were enriched significantly, activated lymphoid cells (natural killer cells) were significantly reduced (P < .001), and M2:M1 polarization trended higher. Also, in keto diet–fed mice, gene set enrichment analysis revealed that epithelial ovarian cancer tumors had increased angiogenesis and inflammatory responses, enhanced epithelial-to-mesenchymal transition phenotype, and altered lipid metabolism. Compared with high-fat diet–fed mice, the keto-fed mice had increases in lipid catalytic activity and catabolism, as well as decreases in lipid synthesis.

“The tumor increase could be mediated by the gut microbiome or by gene alterations or by metabolite levels that influence tumor growth. It’s possible that each cancer type is different. The composition of the diet may be a factor, as well as how tumors metabolize fat and ketones,” Dr. AlHilli said.

The results need to be confirmed in preclinical animal studies and in additional models, she added.

The study was funded by a K12 Grant and internal funding from Cleveland Clinic. Dr. AlHilli declared no relevant disclosures.

A ketogenic diet fed to mice with epithelial ovarian cancer led to significantly increased tumor growth and gut microbiome alterations, according to study recently presented at the annual meeting of the Society of Gynecologic Oncology.

“The keto diet is very popular, especially among patients who believe it may treat cancer by starving tumors of the fuel they need to grow, altering the immune system, and other anticancer effects,” said study leader Mariam AlHilli, MD, of the Cleveland Clinic.

The findings are surprising because in other studies the high-fat, zero-carb ketogenic diet has demonstrated tumor-suppressing effects. It has been under study as a possible adjuvant therapy for other cancers, such as glioblastoma, colon cancer, prostate cancer, and pancreatic cancer.

“While we don’t know yet whether these findings extend to patients, the results in animals indicate that instead of being protective, the keto diet appears to promote ovarian cancer growth and progression,” Dr. AlHilli said. In the present study, tumor bearing mice were fed a keto diet consisting of 10% protein, 0% carbohydrates, and 90% fat, while the high-fat diet was 10% protein, 15% carbohydrates, and 75% fat. The control diet consisted of 10% protein, 77% carbohydrates, and 13% fat. Epithelial ovarian cancer tumor growth was monitored weekly.

Over the 6- to 10-week course of study, a 9.1-fold increase from baseline in tumor growth was observed in the keto diet-fed mice (n = 20). Among mice fed a high-fat diet (n = 20) that included some carbohydrates, tumor growth increased 2.0-fold from baseline, and among control group mice (n = 20) fed a low-fat, high carbohydrate diet, tumor growth increased 3.1-fold.

The investigators observed several hallmarks of tumor progression: tumor associated macrophages were enriched significantly, activated lymphoid cells (natural killer cells) were significantly reduced (P < .001), and M2:M1 polarization trended higher. Also, in keto diet–fed mice, gene set enrichment analysis revealed that epithelial ovarian cancer tumors had increased angiogenesis and inflammatory responses, enhanced epithelial-to-mesenchymal transition phenotype, and altered lipid metabolism. Compared with high-fat diet–fed mice, the keto-fed mice had increases in lipid catalytic activity and catabolism, as well as decreases in lipid synthesis.

“The tumor increase could be mediated by the gut microbiome or by gene alterations or by metabolite levels that influence tumor growth. It’s possible that each cancer type is different. The composition of the diet may be a factor, as well as how tumors metabolize fat and ketones,” Dr. AlHilli said.

The results need to be confirmed in preclinical animal studies and in additional models, she added.

The study was funded by a K12 Grant and internal funding from Cleveland Clinic. Dr. AlHilli declared no relevant disclosures.

A ketogenic diet fed to mice with epithelial ovarian cancer led to significantly increased tumor growth and gut microbiome alterations, according to study recently presented at the annual meeting of the Society of Gynecologic Oncology.

“The keto diet is very popular, especially among patients who believe it may treat cancer by starving tumors of the fuel they need to grow, altering the immune system, and other anticancer effects,” said study leader Mariam AlHilli, MD, of the Cleveland Clinic.

The findings are surprising because in other studies the high-fat, zero-carb ketogenic diet has demonstrated tumor-suppressing effects. It has been under study as a possible adjuvant therapy for other cancers, such as glioblastoma, colon cancer, prostate cancer, and pancreatic cancer.

“While we don’t know yet whether these findings extend to patients, the results in animals indicate that instead of being protective, the keto diet appears to promote ovarian cancer growth and progression,” Dr. AlHilli said. In the present study, tumor bearing mice were fed a keto diet consisting of 10% protein, 0% carbohydrates, and 90% fat, while the high-fat diet was 10% protein, 15% carbohydrates, and 75% fat. The control diet consisted of 10% protein, 77% carbohydrates, and 13% fat. Epithelial ovarian cancer tumor growth was monitored weekly.

Over the 6- to 10-week course of study, a 9.1-fold increase from baseline in tumor growth was observed in the keto diet-fed mice (n = 20). Among mice fed a high-fat diet (n = 20) that included some carbohydrates, tumor growth increased 2.0-fold from baseline, and among control group mice (n = 20) fed a low-fat, high carbohydrate diet, tumor growth increased 3.1-fold.

The investigators observed several hallmarks of tumor progression: tumor associated macrophages were enriched significantly, activated lymphoid cells (natural killer cells) were significantly reduced (P < .001), and M2:M1 polarization trended higher. Also, in keto diet–fed mice, gene set enrichment analysis revealed that epithelial ovarian cancer tumors had increased angiogenesis and inflammatory responses, enhanced epithelial-to-mesenchymal transition phenotype, and altered lipid metabolism. Compared with high-fat diet–fed mice, the keto-fed mice had increases in lipid catalytic activity and catabolism, as well as decreases in lipid synthesis.

“The tumor increase could be mediated by the gut microbiome or by gene alterations or by metabolite levels that influence tumor growth. It’s possible that each cancer type is different. The composition of the diet may be a factor, as well as how tumors metabolize fat and ketones,” Dr. AlHilli said.

The results need to be confirmed in preclinical animal studies and in additional models, she added.

The study was funded by a K12 Grant and internal funding from Cleveland Clinic. Dr. AlHilli declared no relevant disclosures.

An artificial intelligence (AI) model successfully predicted which high-grade serous ovarian cancer patients would have excellent responses to laparoscopic surgery. The model, using still-frame images from pretreatment laparoscopic surgical videos, had an overall accuracy rate of 93%, according to the pilot study’s first author, Deanna Glassman, MD, an oncologic fellow at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Glassman described her research in a presentation given at the annual meeting of the Society of Gynecologic Oncology.

While the AI model successfully identified all excellent-response patients, it did classify about a third of patients with poor responses as excellent responses. The smaller number of images in the poor-response category, Dr. Glassman speculated, may explain the misclassification.

Researchers took 435 representative still-frame images from pretreatment laparoscopic surgical videos of 113 patients with pathologically proven high-grade serous ovarian cancer. Using 70% of the images to train the model, they used 10% for validation and 20% for the actual testing. They developed the AI model with images from four anatomical locations (diaphragm, omentum, peritoneum, and pelvis), training it using deep learning and neural networks to extract morphological disease patterns for correlation with either of two outcomes: excellent response or poor response. An excellent response was defined as progression-free survival of 12 months or more, and poor response as PFS of 6 months or less. In the retrospective study of images, after excluding 32 gray-zone patients, 75 patients (66%) had durable responses to therapy and 6 (5%) had poor responses.

The PFS was 19 months in the excellent-response group and 3 months in the poor-response group.

Clinicians have often observed differences in gross morphology within the single histologic diagnosis of high-grade serous ovarian cancer. The research intent was to determine if AI could detect these distinct morphological patterns in the still frame images taken at the time of laparoscopy, and correlate them with the eventual clinical outcomes. Dr. Glassman and colleagues are currently validating the model with a much larger cohort, and will look into clinical testing.

“The big-picture goal,” Dr. Glassman said in an interview, “would be to utilize the model to predict which patients would do well with traditional standard of care treatments and those who wouldn’t do well so that we can personalize the treatment plan for those patients with alternative agents and therapies.”

Once validated, the model could also be employed to identify patterns of disease in other gynecologic cancers or distinguish between viable and necrosed malignant tissue.

The study’s predominant limitation was the small sample size which is being addressed in a larger ongoing study.

Funding was provided by a T32 grant, MD Anderson Cancer Center Support Grant, MD Anderson Ovarian Cancer Moon Shot, SPORE in Ovarian Cancer, the American Cancer Society, and the Ovarian Cancer Research Alliance. Dr. Glassman declared no relevant financial relationships.

An artificial intelligence (AI) model successfully predicted which high-grade serous ovarian cancer patients would have excellent responses to laparoscopic surgery. The model, using still-frame images from pretreatment laparoscopic surgical videos, had an overall accuracy rate of 93%, according to the pilot study’s first author, Deanna Glassman, MD, an oncologic fellow at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Glassman described her research in a presentation given at the annual meeting of the Society of Gynecologic Oncology.

While the AI model successfully identified all excellent-response patients, it did classify about a third of patients with poor responses as excellent responses. The smaller number of images in the poor-response category, Dr. Glassman speculated, may explain the misclassification.

Researchers took 435 representative still-frame images from pretreatment laparoscopic surgical videos of 113 patients with pathologically proven high-grade serous ovarian cancer. Using 70% of the images to train the model, they used 10% for validation and 20% for the actual testing. They developed the AI model with images from four anatomical locations (diaphragm, omentum, peritoneum, and pelvis), training it using deep learning and neural networks to extract morphological disease patterns for correlation with either of two outcomes: excellent response or poor response. An excellent response was defined as progression-free survival of 12 months or more, and poor response as PFS of 6 months or less. In the retrospective study of images, after excluding 32 gray-zone patients, 75 patients (66%) had durable responses to therapy and 6 (5%) had poor responses.

The PFS was 19 months in the excellent-response group and 3 months in the poor-response group.

Clinicians have often observed differences in gross morphology within the single histologic diagnosis of high-grade serous ovarian cancer. The research intent was to determine if AI could detect these distinct morphological patterns in the still frame images taken at the time of laparoscopy, and correlate them with the eventual clinical outcomes. Dr. Glassman and colleagues are currently validating the model with a much larger cohort, and will look into clinical testing.

“The big-picture goal,” Dr. Glassman said in an interview, “would be to utilize the model to predict which patients would do well with traditional standard of care treatments and those who wouldn’t do well so that we can personalize the treatment plan for those patients with alternative agents and therapies.”

Once validated, the model could also be employed to identify patterns of disease in other gynecologic cancers or distinguish between viable and necrosed malignant tissue.

The study’s predominant limitation was the small sample size which is being addressed in a larger ongoing study.

Funding was provided by a T32 grant, MD Anderson Cancer Center Support Grant, MD Anderson Ovarian Cancer Moon Shot, SPORE in Ovarian Cancer, the American Cancer Society, and the Ovarian Cancer Research Alliance. Dr. Glassman declared no relevant financial relationships.

An artificial intelligence (AI) model successfully predicted which high-grade serous ovarian cancer patients would have excellent responses to laparoscopic surgery. The model, using still-frame images from pretreatment laparoscopic surgical videos, had an overall accuracy rate of 93%, according to the pilot study’s first author, Deanna Glassman, MD, an oncologic fellow at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Glassman described her research in a presentation given at the annual meeting of the Society of Gynecologic Oncology.

While the AI model successfully identified all excellent-response patients, it did classify about a third of patients with poor responses as excellent responses. The smaller number of images in the poor-response category, Dr. Glassman speculated, may explain the misclassification.

Researchers took 435 representative still-frame images from pretreatment laparoscopic surgical videos of 113 patients with pathologically proven high-grade serous ovarian cancer. Using 70% of the images to train the model, they used 10% for validation and 20% for the actual testing. They developed the AI model with images from four anatomical locations (diaphragm, omentum, peritoneum, and pelvis), training it using deep learning and neural networks to extract morphological disease patterns for correlation with either of two outcomes: excellent response or poor response. An excellent response was defined as progression-free survival of 12 months or more, and poor response as PFS of 6 months or less. In the retrospective study of images, after excluding 32 gray-zone patients, 75 patients (66%) had durable responses to therapy and 6 (5%) had poor responses.

The PFS was 19 months in the excellent-response group and 3 months in the poor-response group.

Clinicians have often observed differences in gross morphology within the single histologic diagnosis of high-grade serous ovarian cancer. The research intent was to determine if AI could detect these distinct morphological patterns in the still frame images taken at the time of laparoscopy, and correlate them with the eventual clinical outcomes. Dr. Glassman and colleagues are currently validating the model with a much larger cohort, and will look into clinical testing.

“The big-picture goal,” Dr. Glassman said in an interview, “would be to utilize the model to predict which patients would do well with traditional standard of care treatments and those who wouldn’t do well so that we can personalize the treatment plan for those patients with alternative agents and therapies.”

Once validated, the model could also be employed to identify patterns of disease in other gynecologic cancers or distinguish between viable and necrosed malignant tissue.

The study’s predominant limitation was the small sample size which is being addressed in a larger ongoing study.

Funding was provided by a T32 grant, MD Anderson Cancer Center Support Grant, MD Anderson Ovarian Cancer Moon Shot, SPORE in Ovarian Cancer, the American Cancer Society, and the Ovarian Cancer Research Alliance. Dr. Glassman declared no relevant financial relationships.

Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.

The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.

The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.

While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.

“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.

In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.

“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”

Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.

“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.

Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.

Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.

The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.

The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.

While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.

“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.

In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.

“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”

Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.

“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.

Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.

Screening patients for social needs and referring patients to resources should be a routine part of cancer care, said a physician who presented a study on the social needs of patients at the Society of Gynecologic Oncology’s 2022 Annual Meeting on Women’s Cancer held in March.

The study, by Anna L. Beavis, MD, MPH, a gynecologic oncologist with the Johns Hopkins Kelly Gynecologic Oncology Service, Baltimore, identified social needs, such as financial assistance and housing insecurity, among a group of 373 patients who completed a written assessment during regular office visits.

The patients were asked about food and housing insecurities, utility and transportation needs, and financial assistance. For some patients these are such dire issues, they actually affect patient outcomes.

While the results were limited to a single urban population and may not be generalizable to other populations, Dr. Beavis said the findings are noteworthy because for physicians, these are tangible items that can be addressed to improve patient outcomes.

“The greatest obstacle is not asking the questions, it’s in ensuring there are acceptable and effective mechanisms for referrals to resources. It is important to have a plan in place to refer patients to resources before beginning a screening program,” she said.

In an interview, Dr. Beavis said that screening and referring patients to resources should be a routine part of cancer care. In this study, 92% of patients completed the questionnaire in her office and the process doesn’t slow her clinic down, she said.

“Our findings demonstrate that social needs are prevalent, and screening for them should be a routine part of the standard of care for cancer patients,” Dr. Beavis said. “Social needs are also actionable for us as physicians, because we can address tangible, individual-level needs, such as food insecurity and transportation, through the provision of resources. These needs stand in contrast to the social determinants of health, which are community-level and require changes on a much larger scale through policy decisions.”

Of the 373 patients in the study group, 74 patients were identified as having at least one social need. Fifty-seven percent asked for a referral to a partner organization for resource assistance. Fifty-eight percent of the study group were White and 42% identified as patients of color, including Black, Asian, Hispanic, American Indian/Alaska Native, and multiple/other races.

“We’ve begun to assess patient satisfaction and have found that patients feel these questions are important – plus, they’re comfortable answering them,” she said.

Dr. Beavis’ study was funded by a grant from the American Cancer Society and Pfizer Global Medical Grants under the Addressing Racial Disparities in Cancer Care Competitive Grant Program.

Small airway disease with air trapping appears to be a long-lasting sequela of SARS-CoV-2 infection, according to a prospective study that compared 100 COVID-19 survivors who had persistent symptoms and 106 healthy control persons.

“Something is going on in the distal airways related to either inflammation or fibrosis that is giving us a signal of air trapping,” noted senior author Alejandro P. Comellas, MD, in a press release. The study was stimulated by reports from University of Iowa clinicians noting that many patients with initial SARS-CoV-2 infection who were either hospitalized or were treated in the ambulatory setting later reported shortness of breath and other respiratory symptoms indicative of chronic lung disease.

Study results

Investigators classified patients (mean age, 48 years; 66 women) with post-acute sequelae of COVID-19 according to whether they were ambulatory (67%), hospitalized (17%), or required treatment in the intensive care unit (16%). They then compared CT findings of patients who had COVID-19 and persistent symptoms with those of a healthy control group.

COVID-19 severity did not affect the percentage of cases of lung with air trapping among these patients. Air trapping occurred at rates of 25.4% among ambulatory patients, 34.6% in hospitalized patients, and in 27.3% of those requiring intensive care (P = .10). The percentage of lungs affected by air trapping in ambulatory participants was sharply and significantly higher than in healthy controls (25.4% vs. 7.2%; P < .001). Also, air trapping persisted; it was still present in 8 of 9 participants who underwent imaging more than 200 days post diagnosis.

Qualitative analysis of chest CT images showed that the most common imaging abnormality was air trapping (58%); ground glass opacities (GGOs) were found in 51% (46/91), note Dr. Comellas and coauthors. This suggests ongoing lung inflammation, edema, or fibrosis. These symptoms are often observed during acute COVID-19, frequently in an organizing pneumonia pattern, and have been shown to persist for months after infection in survivors of severe disease. The mean percentage of total lung classified as having regional GGOs on chest CT scans was 13.2% and 28.7%, respectively, in the hospitalized and ICU groups, both very much higher than in the ambulatory group, at 3.7% (P < .001 for both). Among healthy controls, the GGO rate on chest CT was only 0.06% (P < .001).

In addition, air trapping correlated with the ratio of residual volume to total lung capacity (r = 0.6; P < .001) but not with spirometry results. In fact, the investigators did not observe airflow obstruction by spirometry in any group, suggesting that air trapping in these patients involves only small rather than large airways and that these small airways contribute little to total airway resistance. Only when a large percentage, perhaps 75% or more, of all small airways are obstructed will spirometry pick up small airways disease, the authors observe.

Continuing disease

The findings taken together suggest that functional small airways disease and air trapping are a consequence of SARS-CoV-2 infection, according to Dr. Comellas. “If a portion of patients continues to have small airways disease, then we need to think about the mechanisms behind it,” he said. “It could be something related to inflammation that’s reversible, or it may be something related to a scar that is irreversible, and then we need to look at ways to prevent further progression of the disease.” Furthermore, “studies aimed at determining the natural history of functional small airways disease in patients with post-acute sequelae of COVID-19 and the biological mechanisms that underlie these findings are urgently needed to identify therapeutic and preventative interventions,” Dr. Comellas, professor of internal medicine at Carver College of Medicine, University of Iowa, Iowa City, concluded.

The study limitations, the authors state, include the fact that theirs was a single-center study that enrolled participants infected early during the COVID-19 pandemic and did not include patients with Delta or Omicron variants, thus limiting the generalizability of the findings.

The study was published in Radiology.

The reported findings “indicate a long-term impact on bronchiolar obstruction,” states Brett M. Elicker, MD, professor of clinical radiology, University of California, San Francisco, in an accompanying editorial . Because collagen may be absorbed for months after an acute insult, it is not entirely clear whether the abnormalities seen in the current study will be permanent. He said further, “the presence of ground glass opacity and/or fibrosis on CT were most common in the patients admitted to the ICU and likely correspond to post-organizing pneumonia and/or post-diffuse alveolar damage fibrosis.”

Dr. Elicker also pointed out that organizing pneumonia is especially common among patients with COVID-19 and is usually highly steroid-responsive. The opacities improve or resolve with treatment, but sometimes residual fibrosis occurs. “Longer-term studies assessing the clinical and imaging manifestations 1-2 years after the initial infection are needed to fully ascertain the permanent manifestations of post-COVID fibrosis.”

The study was supported by grants from the National Institutes of Health. The authors and Dr. Elicker have disclosed no relevant financial relationships.

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

Small airway disease with air trapping appears to be a long-lasting sequela of SARS-CoV-2 infection, according to a prospective study that compared 100 COVID-19 survivors who had persistent symptoms and 106 healthy control persons.

“Something is going on in the distal airways related to either inflammation or fibrosis that is giving us a signal of air trapping,” noted senior author Alejandro P. Comellas, MD, in a press release. The study was stimulated by reports from University of Iowa clinicians noting that many patients with initial SARS-CoV-2 infection who were either hospitalized or were treated in the ambulatory setting later reported shortness of breath and other respiratory symptoms indicative of chronic lung disease.

Study results

Investigators classified patients (mean age, 48 years; 66 women) with post-acute sequelae of COVID-19 according to whether they were ambulatory (67%), hospitalized (17%), or required treatment in the intensive care unit (16%). They then compared CT findings of patients who had COVID-19 and persistent symptoms with those of a healthy control group.

COVID-19 severity did not affect the percentage of cases of lung with air trapping among these patients. Air trapping occurred at rates of 25.4% among ambulatory patients, 34.6% in hospitalized patients, and in 27.3% of those requiring intensive care (P = .10). The percentage of lungs affected by air trapping in ambulatory participants was sharply and significantly higher than in healthy controls (25.4% vs. 7.2%; P < .001). Also, air trapping persisted; it was still present in 8 of 9 participants who underwent imaging more than 200 days post diagnosis.

Qualitative analysis of chest CT images showed that the most common imaging abnormality was air trapping (58%); ground glass opacities (GGOs) were found in 51% (46/91), note Dr. Comellas and coauthors. This suggests ongoing lung inflammation, edema, or fibrosis. These symptoms are often observed during acute COVID-19, frequently in an organizing pneumonia pattern, and have been shown to persist for months after infection in survivors of severe disease. The mean percentage of total lung classified as having regional GGOs on chest CT scans was 13.2% and 28.7%, respectively, in the hospitalized and ICU groups, both very much higher than in the ambulatory group, at 3.7% (P < .001 for both). Among healthy controls, the GGO rate on chest CT was only 0.06% (P < .001).

In addition, air trapping correlated with the ratio of residual volume to total lung capacity (r = 0.6; P < .001) but not with spirometry results. In fact, the investigators did not observe airflow obstruction by spirometry in any group, suggesting that air trapping in these patients involves only small rather than large airways and that these small airways contribute little to total airway resistance. Only when a large percentage, perhaps 75% or more, of all small airways are obstructed will spirometry pick up small airways disease, the authors observe.

Continuing disease

The findings taken together suggest that functional small airways disease and air trapping are a consequence of SARS-CoV-2 infection, according to Dr. Comellas. “If a portion of patients continues to have small airways disease, then we need to think about the mechanisms behind it,” he said. “It could be something related to inflammation that’s reversible, or it may be something related to a scar that is irreversible, and then we need to look at ways to prevent further progression of the disease.” Furthermore, “studies aimed at determining the natural history of functional small airways disease in patients with post-acute sequelae of COVID-19 and the biological mechanisms that underlie these findings are urgently needed to identify therapeutic and preventative interventions,” Dr. Comellas, professor of internal medicine at Carver College of Medicine, University of Iowa, Iowa City, concluded.

The study limitations, the authors state, include the fact that theirs was a single-center study that enrolled participants infected early during the COVID-19 pandemic and did not include patients with Delta or Omicron variants, thus limiting the generalizability of the findings.

The study was published in Radiology.

The reported findings “indicate a long-term impact on bronchiolar obstruction,” states Brett M. Elicker, MD, professor of clinical radiology, University of California, San Francisco, in an accompanying editorial . Because collagen may be absorbed for months after an acute insult, it is not entirely clear whether the abnormalities seen in the current study will be permanent. He said further, “the presence of ground glass opacity and/or fibrosis on CT were most common in the patients admitted to the ICU and likely correspond to post-organizing pneumonia and/or post-diffuse alveolar damage fibrosis.”

Dr. Elicker also pointed out that organizing pneumonia is especially common among patients with COVID-19 and is usually highly steroid-responsive. The opacities improve or resolve with treatment, but sometimes residual fibrosis occurs. “Longer-term studies assessing the clinical and imaging manifestations 1-2 years after the initial infection are needed to fully ascertain the permanent manifestations of post-COVID fibrosis.”

The study was supported by grants from the National Institutes of Health. The authors and Dr. Elicker have disclosed no relevant financial relationships.

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

Small airway disease with air trapping appears to be a long-lasting sequela of SARS-CoV-2 infection, according to a prospective study that compared 100 COVID-19 survivors who had persistent symptoms and 106 healthy control persons.

“Something is going on in the distal airways related to either inflammation or fibrosis that is giving us a signal of air trapping,” noted senior author Alejandro P. Comellas, MD, in a press release. The study was stimulated by reports from University of Iowa clinicians noting that many patients with initial SARS-CoV-2 infection who were either hospitalized or were treated in the ambulatory setting later reported shortness of breath and other respiratory symptoms indicative of chronic lung disease.

Study results

Investigators classified patients (mean age, 48 years; 66 women) with post-acute sequelae of COVID-19 according to whether they were ambulatory (67%), hospitalized (17%), or required treatment in the intensive care unit (16%). They then compared CT findings of patients who had COVID-19 and persistent symptoms with those of a healthy control group.

COVID-19 severity did not affect the percentage of cases of lung with air trapping among these patients. Air trapping occurred at rates of 25.4% among ambulatory patients, 34.6% in hospitalized patients, and in 27.3% of those requiring intensive care (P = .10). The percentage of lungs affected by air trapping in ambulatory participants was sharply and significantly higher than in healthy controls (25.4% vs. 7.2%; P < .001). Also, air trapping persisted; it was still present in 8 of 9 participants who underwent imaging more than 200 days post diagnosis.

Qualitative analysis of chest CT images showed that the most common imaging abnormality was air trapping (58%); ground glass opacities (GGOs) were found in 51% (46/91), note Dr. Comellas and coauthors. This suggests ongoing lung inflammation, edema, or fibrosis. These symptoms are often observed during acute COVID-19, frequently in an organizing pneumonia pattern, and have been shown to persist for months after infection in survivors of severe disease. The mean percentage of total lung classified as having regional GGOs on chest CT scans was 13.2% and 28.7%, respectively, in the hospitalized and ICU groups, both very much higher than in the ambulatory group, at 3.7% (P < .001 for both). Among healthy controls, the GGO rate on chest CT was only 0.06% (P < .001).

In addition, air trapping correlated with the ratio of residual volume to total lung capacity (r = 0.6; P < .001) but not with spirometry results. In fact, the investigators did not observe airflow obstruction by spirometry in any group, suggesting that air trapping in these patients involves only small rather than large airways and that these small airways contribute little to total airway resistance. Only when a large percentage, perhaps 75% or more, of all small airways are obstructed will spirometry pick up small airways disease, the authors observe.

Continuing disease

The findings taken together suggest that functional small airways disease and air trapping are a consequence of SARS-CoV-2 infection, according to Dr. Comellas. “If a portion of patients continues to have small airways disease, then we need to think about the mechanisms behind it,” he said. “It could be something related to inflammation that’s reversible, or it may be something related to a scar that is irreversible, and then we need to look at ways to prevent further progression of the disease.” Furthermore, “studies aimed at determining the natural history of functional small airways disease in patients with post-acute sequelae of COVID-19 and the biological mechanisms that underlie these findings are urgently needed to identify therapeutic and preventative interventions,” Dr. Comellas, professor of internal medicine at Carver College of Medicine, University of Iowa, Iowa City, concluded.

The study limitations, the authors state, include the fact that theirs was a single-center study that enrolled participants infected early during the COVID-19 pandemic and did not include patients with Delta or Omicron variants, thus limiting the generalizability of the findings.

The study was published in Radiology.

The reported findings “indicate a long-term impact on bronchiolar obstruction,” states Brett M. Elicker, MD, professor of clinical radiology, University of California, San Francisco, in an accompanying editorial . Because collagen may be absorbed for months after an acute insult, it is not entirely clear whether the abnormalities seen in the current study will be permanent. He said further, “the presence of ground glass opacity and/or fibrosis on CT were most common in the patients admitted to the ICU and likely correspond to post-organizing pneumonia and/or post-diffuse alveolar damage fibrosis.”

Dr. Elicker also pointed out that organizing pneumonia is especially common among patients with COVID-19 and is usually highly steroid-responsive. The opacities improve or resolve with treatment, but sometimes residual fibrosis occurs. “Longer-term studies assessing the clinical and imaging manifestations 1-2 years after the initial infection are needed to fully ascertain the permanent manifestations of post-COVID fibrosis.”

The study was supported by grants from the National Institutes of Health. The authors and Dr. Elicker have disclosed no relevant financial relationships.

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

A new analysis of KEYNOTE-564 demonstrates that pembrolizumab continues to show consistent and clinically meaningful improvement in disease-free survival for patients at high risk of a renal cell carcinoma recurrence.

The updated analysis was presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The study, which was led by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, Boston, found no increase in high-grade, or other, adverse events with 30 months of follow-up.

Pembrolizumab (Keytruda, Merck) is approved by the Food and Drug Administration in combination with axitinib, as a first-line treatment for patients with advanced renal cell carcinoma (RCC). The combination is also recommended by the European Society for Medical Oncology for advanced RCC.

KEYNOTE-564 is a phase 3, double-blind, multicenter trial of pembrolizumab versus placebo after surgery in participants with renal cell carcinoma. In previously presented interim KEYNOTE-564 results, the primary endpoint of disease-free survival for adjuvant pembrolizumab versus placebo was met in the intent-to-treat population (hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = .001).

KEYNOTE-564 includes 994 patients (mean age, 60 years; 71% male) with confirmed clear cell RCC who were either intermediate to high risk, high risk, or M1 with no evidence of disease after surgery. All patients had surgery 12 or fewer weeks prior to randomization.

At 30.1 months, the disease-free survival difference in the intent-to-treat population between pembrolizumab and placebo at 78.3% versus 67.3% had a HR of 0.63 (95% CI, 0.50-0.80; nominal P < .0001), greater than the 77.3% versus 68.1% difference at 24.1 months (hazard ratio, 0.68, 95% CI, 0.53-0.87; P = .001).

Analysis of disease-free survival by recurrence risk subgroups showed an increasing benefit with increasing risk. In the intermediate- to high-risk group, the 24-month rates were 81.1% and 72.0% for pembrolizumab and placebo, respectively (HR, 0.68; 95% CI, 0.52-0.89). In the high-risk group, the 24-month rates were 48.7% and 35.4%, respectively (HR, 0.60; 95% CI, 0.33-1.10). In the M1 NED group, the rates were 78.4% and 37.9% for pembrolizumab and placebo, respectively (HR, 0.28; 95% CI, 0.12-0.66).

During a discussion about the presentation, Daniel M Geynisman, MD, of Fox Chase Cancer Center, Philadelphia, pointed to the respective absolute differences between pembrolizumab and placebo of 9% in the intermediate- to high-risk group, 13% in the high-risk group, and a “whopping difference of 41% in the M1 NED group,” but underscored that the M1 NED population represents only a small part of the trial population (5.8%). The same relationship was evident among sarcomatoid status subgroups, with 24-month absolute differences of 10.1% favoring pembrolizumab (HR, 0.63) with sarcomatoid features absent and 19.8% (HR, 0.54) when they were present.

Overall survival estimates showed an increasing benefit for pembrolizumab versus placebo (96.6% vs. 93.5%; HR, 0.54) at 24.1 months (96.2% vs. 93.8%, HR, 0.52), but this wasn’t statistically significance because the data collection was incomplete.

Between 24.1 months and 30.1 months, rates of treatment-related adverse events remained the same at 79.1% for pembrolizumab and 53.4% for placebo, with a treatment-related discontinuations in the pembrolizumab group at 17.6% and 18.6% at 24.1 and 30.1 months, respectively.

The study was funded by Merck Sharp & Dohme.

A new analysis of KEYNOTE-564 demonstrates that pembrolizumab continues to show consistent and clinically meaningful improvement in disease-free survival for patients at high risk of a renal cell carcinoma recurrence.

The updated analysis was presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The study, which was led by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, Boston, found no increase in high-grade, or other, adverse events with 30 months of follow-up.

Pembrolizumab (Keytruda, Merck) is approved by the Food and Drug Administration in combination with axitinib, as a first-line treatment for patients with advanced renal cell carcinoma (RCC). The combination is also recommended by the European Society for Medical Oncology for advanced RCC.

KEYNOTE-564 is a phase 3, double-blind, multicenter trial of pembrolizumab versus placebo after surgery in participants with renal cell carcinoma. In previously presented interim KEYNOTE-564 results, the primary endpoint of disease-free survival for adjuvant pembrolizumab versus placebo was met in the intent-to-treat population (hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = .001).

KEYNOTE-564 includes 994 patients (mean age, 60 years; 71% male) with confirmed clear cell RCC who were either intermediate to high risk, high risk, or M1 with no evidence of disease after surgery. All patients had surgery 12 or fewer weeks prior to randomization.

At 30.1 months, the disease-free survival difference in the intent-to-treat population between pembrolizumab and placebo at 78.3% versus 67.3% had a HR of 0.63 (95% CI, 0.50-0.80; nominal P < .0001), greater than the 77.3% versus 68.1% difference at 24.1 months (hazard ratio, 0.68, 95% CI, 0.53-0.87; P = .001).

Analysis of disease-free survival by recurrence risk subgroups showed an increasing benefit with increasing risk. In the intermediate- to high-risk group, the 24-month rates were 81.1% and 72.0% for pembrolizumab and placebo, respectively (HR, 0.68; 95% CI, 0.52-0.89). In the high-risk group, the 24-month rates were 48.7% and 35.4%, respectively (HR, 0.60; 95% CI, 0.33-1.10). In the M1 NED group, the rates were 78.4% and 37.9% for pembrolizumab and placebo, respectively (HR, 0.28; 95% CI, 0.12-0.66).

During a discussion about the presentation, Daniel M Geynisman, MD, of Fox Chase Cancer Center, Philadelphia, pointed to the respective absolute differences between pembrolizumab and placebo of 9% in the intermediate- to high-risk group, 13% in the high-risk group, and a “whopping difference of 41% in the M1 NED group,” but underscored that the M1 NED population represents only a small part of the trial population (5.8%). The same relationship was evident among sarcomatoid status subgroups, with 24-month absolute differences of 10.1% favoring pembrolizumab (HR, 0.63) with sarcomatoid features absent and 19.8% (HR, 0.54) when they were present.

Overall survival estimates showed an increasing benefit for pembrolizumab versus placebo (96.6% vs. 93.5%; HR, 0.54) at 24.1 months (96.2% vs. 93.8%, HR, 0.52), but this wasn’t statistically significance because the data collection was incomplete.

Between 24.1 months and 30.1 months, rates of treatment-related adverse events remained the same at 79.1% for pembrolizumab and 53.4% for placebo, with a treatment-related discontinuations in the pembrolizumab group at 17.6% and 18.6% at 24.1 and 30.1 months, respectively.

The study was funded by Merck Sharp & Dohme.

A new analysis of KEYNOTE-564 demonstrates that pembrolizumab continues to show consistent and clinically meaningful improvement in disease-free survival for patients at high risk of a renal cell carcinoma recurrence.

The updated analysis was presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The study, which was led by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, Boston, found no increase in high-grade, or other, adverse events with 30 months of follow-up.

Pembrolizumab (Keytruda, Merck) is approved by the Food and Drug Administration in combination with axitinib, as a first-line treatment for patients with advanced renal cell carcinoma (RCC). The combination is also recommended by the European Society for Medical Oncology for advanced RCC.

KEYNOTE-564 is a phase 3, double-blind, multicenter trial of pembrolizumab versus placebo after surgery in participants with renal cell carcinoma. In previously presented interim KEYNOTE-564 results, the primary endpoint of disease-free survival for adjuvant pembrolizumab versus placebo was met in the intent-to-treat population (hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = .001).

KEYNOTE-564 includes 994 patients (mean age, 60 years; 71% male) with confirmed clear cell RCC who were either intermediate to high risk, high risk, or M1 with no evidence of disease after surgery. All patients had surgery 12 or fewer weeks prior to randomization.

At 30.1 months, the disease-free survival difference in the intent-to-treat population between pembrolizumab and placebo at 78.3% versus 67.3% had a HR of 0.63 (95% CI, 0.50-0.80; nominal P < .0001), greater than the 77.3% versus 68.1% difference at 24.1 months (hazard ratio, 0.68, 95% CI, 0.53-0.87; P = .001).

Analysis of disease-free survival by recurrence risk subgroups showed an increasing benefit with increasing risk. In the intermediate- to high-risk group, the 24-month rates were 81.1% and 72.0% for pembrolizumab and placebo, respectively (HR, 0.68; 95% CI, 0.52-0.89). In the high-risk group, the 24-month rates were 48.7% and 35.4%, respectively (HR, 0.60; 95% CI, 0.33-1.10). In the M1 NED group, the rates were 78.4% and 37.9% for pembrolizumab and placebo, respectively (HR, 0.28; 95% CI, 0.12-0.66).

During a discussion about the presentation, Daniel M Geynisman, MD, of Fox Chase Cancer Center, Philadelphia, pointed to the respective absolute differences between pembrolizumab and placebo of 9% in the intermediate- to high-risk group, 13% in the high-risk group, and a “whopping difference of 41% in the M1 NED group,” but underscored that the M1 NED population represents only a small part of the trial population (5.8%). The same relationship was evident among sarcomatoid status subgroups, with 24-month absolute differences of 10.1% favoring pembrolizumab (HR, 0.63) with sarcomatoid features absent and 19.8% (HR, 0.54) when they were present.

Overall survival estimates showed an increasing benefit for pembrolizumab versus placebo (96.6% vs. 93.5%; HR, 0.54) at 24.1 months (96.2% vs. 93.8%, HR, 0.52), but this wasn’t statistically significance because the data collection was incomplete.

Between 24.1 months and 30.1 months, rates of treatment-related adverse events remained the same at 79.1% for pembrolizumab and 53.4% for placebo, with a treatment-related discontinuations in the pembrolizumab group at 17.6% and 18.6% at 24.1 and 30.1 months, respectively.

The study was funded by Merck Sharp & Dohme.