Gynecologic Cancer

Preoperative computerized tomography (CT) demonstrated limited value in the clinical management of patients with early-stage vulvar squamous cell carcinoma (VSCC) analyzed in a single-center study.

The findings suggest preoperative CT imaging could be excluded prior to sentinel inguinal lymph node biopsy or staging surgery in patients with early-stage disease.

“In this study, we aimed to investigate if preoperative CT scan influences the overall course of VSCC management in patients without clinical evidence of groin lymphadenopathy,” wrote Rachel Pounds, MD, of the University of Birmingham (England) and colleagues. The study was published in Gynecologic Oncology.

The researchers prospectively studied a cohort of 225 patients with primary or recurrent VSCC who underwent staging surgery at a single institution in the United Kingdom. The patients’ mean age was 67 years (range, 54-79 years), and most had stage 1B disease (57.8%).

The researchers compared preoperative imaging findings with histological results from sentinel inguinal lymph node biopsy. Other clinical information, including surgery type, evidence of groin node involvement, and age at diagnosis was collected from patient files and included in the analysis.

In all, 51.6% of patients underwent preoperative CT imaging. Among these patients, 37.9% had a positive report of radiological groin lymphatic metastases.

“True groin node metastases, confirmed histologically, were observed in 26 patients (22.4%) with a radiologically positive scan report (true positives) and in 18 patients (15.5%) with a radiological negative scan report (false negatives),” the researchers wrote.

The specificity and sensitivity of preoperative CT to detect groin lymphatic metastasis were 77.8% and 59.1%, respectively. The positive and negative predictive values were 61.9% and 75.7%, respectively.

There was no significant difference in overall survival, disease-specific or disease-free survival, or groin node recurrence between patients who underwent preoperative CT and patients who did not.

Groin node recurrence was observed in 10.3% of patients with preoperative CT and 11.5% of patients without it (P = .7768). Disease-specific death occurred in 16.4% of patients with preoperative CT and 13.5% of patients without it (P = .5451).

“Our results highlight the poor reliability of preoperative CT scans in detecting inguinal lymphatic metastasis,” the researchers wrote. “Preoperative CT scan may be omitted in early stage VSCC prior to surgical staging as it does not affect overall management and surgical outcomes.”

No funding sources were reported for this study. The authors reported having no conflicts of interest.

SOURCE: Pounds R et al. Gynecol Oncol. 2020 Jan 24. doi: 10.1016/j.ygyno.2020.01.031.

Preoperative computerized tomography (CT) demonstrated limited value in the clinical management of patients with early-stage vulvar squamous cell carcinoma (VSCC) analyzed in a single-center study.

The findings suggest preoperative CT imaging could be excluded prior to sentinel inguinal lymph node biopsy or staging surgery in patients with early-stage disease.

“In this study, we aimed to investigate if preoperative CT scan influences the overall course of VSCC management in patients without clinical evidence of groin lymphadenopathy,” wrote Rachel Pounds, MD, of the University of Birmingham (England) and colleagues. The study was published in Gynecologic Oncology.

The researchers prospectively studied a cohort of 225 patients with primary or recurrent VSCC who underwent staging surgery at a single institution in the United Kingdom. The patients’ mean age was 67 years (range, 54-79 years), and most had stage 1B disease (57.8%).

The researchers compared preoperative imaging findings with histological results from sentinel inguinal lymph node biopsy. Other clinical information, including surgery type, evidence of groin node involvement, and age at diagnosis was collected from patient files and included in the analysis.

In all, 51.6% of patients underwent preoperative CT imaging. Among these patients, 37.9% had a positive report of radiological groin lymphatic metastases.

“True groin node metastases, confirmed histologically, were observed in 26 patients (22.4%) with a radiologically positive scan report (true positives) and in 18 patients (15.5%) with a radiological negative scan report (false negatives),” the researchers wrote.

The specificity and sensitivity of preoperative CT to detect groin lymphatic metastasis were 77.8% and 59.1%, respectively. The positive and negative predictive values were 61.9% and 75.7%, respectively.

There was no significant difference in overall survival, disease-specific or disease-free survival, or groin node recurrence between patients who underwent preoperative CT and patients who did not.

Groin node recurrence was observed in 10.3% of patients with preoperative CT and 11.5% of patients without it (P = .7768). Disease-specific death occurred in 16.4% of patients with preoperative CT and 13.5% of patients without it (P = .5451).

“Our results highlight the poor reliability of preoperative CT scans in detecting inguinal lymphatic metastasis,” the researchers wrote. “Preoperative CT scan may be omitted in early stage VSCC prior to surgical staging as it does not affect overall management and surgical outcomes.”

No funding sources were reported for this study. The authors reported having no conflicts of interest.

SOURCE: Pounds R et al. Gynecol Oncol. 2020 Jan 24. doi: 10.1016/j.ygyno.2020.01.031.

Preoperative computerized tomography (CT) demonstrated limited value in the clinical management of patients with early-stage vulvar squamous cell carcinoma (VSCC) analyzed in a single-center study.

The findings suggest preoperative CT imaging could be excluded prior to sentinel inguinal lymph node biopsy or staging surgery in patients with early-stage disease.

“In this study, we aimed to investigate if preoperative CT scan influences the overall course of VSCC management in patients without clinical evidence of groin lymphadenopathy,” wrote Rachel Pounds, MD, of the University of Birmingham (England) and colleagues. The study was published in Gynecologic Oncology.

The researchers prospectively studied a cohort of 225 patients with primary or recurrent VSCC who underwent staging surgery at a single institution in the United Kingdom. The patients’ mean age was 67 years (range, 54-79 years), and most had stage 1B disease (57.8%).

The researchers compared preoperative imaging findings with histological results from sentinel inguinal lymph node biopsy. Other clinical information, including surgery type, evidence of groin node involvement, and age at diagnosis was collected from patient files and included in the analysis.

In all, 51.6% of patients underwent preoperative CT imaging. Among these patients, 37.9% had a positive report of radiological groin lymphatic metastases.

“True groin node metastases, confirmed histologically, were observed in 26 patients (22.4%) with a radiologically positive scan report (true positives) and in 18 patients (15.5%) with a radiological negative scan report (false negatives),” the researchers wrote.

The specificity and sensitivity of preoperative CT to detect groin lymphatic metastasis were 77.8% and 59.1%, respectively. The positive and negative predictive values were 61.9% and 75.7%, respectively.

There was no significant difference in overall survival, disease-specific or disease-free survival, or groin node recurrence between patients who underwent preoperative CT and patients who did not.

Groin node recurrence was observed in 10.3% of patients with preoperative CT and 11.5% of patients without it (P = .7768). Disease-specific death occurred in 16.4% of patients with preoperative CT and 13.5% of patients without it (P = .5451).

“Our results highlight the poor reliability of preoperative CT scans in detecting inguinal lymphatic metastasis,” the researchers wrote. “Preoperative CT scan may be omitted in early stage VSCC prior to surgical staging as it does not affect overall management and surgical outcomes.”

No funding sources were reported for this study. The authors reported having no conflicts of interest.

SOURCE: Pounds R et al. Gynecol Oncol. 2020 Jan 24. doi: 10.1016/j.ygyno.2020.01.031.

Considerable differences in ovarian cancer survival exist between high-income countries, especially for older women with advanced disease, according to a recent study.

The findings suggest additional research is needed to evaluate international differences in both treatment- and patient-specific factors affecting survival.

“This study [evaluated] differences in survival by age and stage at diagnosis within and across seven high-income countries,” wrote Citadel J. Cabasag, PhD, of the International Agency for Research on Cancer in Lyon, France, and colleagues. The results were published in Gynecologic Oncology.

The researchers conducted a retrospective analysis of population-based registry data from 2010 to 2014. Data were collected from 21 cancer registries located in Canada, United Kingdom, New Zealand, Norway, Ireland, Australia, and Denmark.

The cohort included 58,161 women with epithelial and nonepithelial ovarian cancer. The majority of cases were advanced stage, with a median age of 63-67 years at diagnosis, depending on the country.

The researchers compared age- and stage-specific net survival between countries at 1 and 3 years post diagnosis.

The 3-year all-ages net survival was highest for Norway (57%) and Australia (56%), followed by Denmark (54%), Canada (50%), United Kingdom (47%), New Zealand (46%), and Ireland (45%).

Most patients were diagnosed with distant disease (range, 64%-71%), with the greatest proportion of women in the 65- to 74- and 75- to 99-year age categories. The lowest 3-year age-specific survival (range, 20%-34%) was observed in the 75- to 99-year age category.

Marked differences in 3-year net survival between countries were found for women in the 75- to 99-year age group with distant disease (range, 12%-25%).

“International survival differences by age groups were less stark for early-stage disease,” the researchers reported. “Interjurisdictional differences within countries were also observed.”

The researchers acknowledged a key limitation of the analysis was the use of registry data. Variability between, and incomplete data within, registries could have lowered the accuracy of the survival estimates.

“[F]urther research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease [is needed],” the researchers concluded.

The study was supported by funding provided to the International Cancer Benchmarking Partnership. The authors reported having no conflicts of interest.

SOURCE: Cabasag CJ et al. Gynecol Oncol. 2020 Jan 28. doi: 10.1016/j.ygyno.2019.12.047.

Considerable differences in ovarian cancer survival exist between high-income countries, especially for older women with advanced disease, according to a recent study.

The findings suggest additional research is needed to evaluate international differences in both treatment- and patient-specific factors affecting survival.

“This study [evaluated] differences in survival by age and stage at diagnosis within and across seven high-income countries,” wrote Citadel J. Cabasag, PhD, of the International Agency for Research on Cancer in Lyon, France, and colleagues. The results were published in Gynecologic Oncology.

The researchers conducted a retrospective analysis of population-based registry data from 2010 to 2014. Data were collected from 21 cancer registries located in Canada, United Kingdom, New Zealand, Norway, Ireland, Australia, and Denmark.

The cohort included 58,161 women with epithelial and nonepithelial ovarian cancer. The majority of cases were advanced stage, with a median age of 63-67 years at diagnosis, depending on the country.

The researchers compared age- and stage-specific net survival between countries at 1 and 3 years post diagnosis.

The 3-year all-ages net survival was highest for Norway (57%) and Australia (56%), followed by Denmark (54%), Canada (50%), United Kingdom (47%), New Zealand (46%), and Ireland (45%).

Most patients were diagnosed with distant disease (range, 64%-71%), with the greatest proportion of women in the 65- to 74- and 75- to 99-year age categories. The lowest 3-year age-specific survival (range, 20%-34%) was observed in the 75- to 99-year age category.

Marked differences in 3-year net survival between countries were found for women in the 75- to 99-year age group with distant disease (range, 12%-25%).

“International survival differences by age groups were less stark for early-stage disease,” the researchers reported. “Interjurisdictional differences within countries were also observed.”

The researchers acknowledged a key limitation of the analysis was the use of registry data. Variability between, and incomplete data within, registries could have lowered the accuracy of the survival estimates.

“[F]urther research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease [is needed],” the researchers concluded.

The study was supported by funding provided to the International Cancer Benchmarking Partnership. The authors reported having no conflicts of interest.

SOURCE: Cabasag CJ et al. Gynecol Oncol. 2020 Jan 28. doi: 10.1016/j.ygyno.2019.12.047.

Considerable differences in ovarian cancer survival exist between high-income countries, especially for older women with advanced disease, according to a recent study.

The findings suggest additional research is needed to evaluate international differences in both treatment- and patient-specific factors affecting survival.

“This study [evaluated] differences in survival by age and stage at diagnosis within and across seven high-income countries,” wrote Citadel J. Cabasag, PhD, of the International Agency for Research on Cancer in Lyon, France, and colleagues. The results were published in Gynecologic Oncology.

The researchers conducted a retrospective analysis of population-based registry data from 2010 to 2014. Data were collected from 21 cancer registries located in Canada, United Kingdom, New Zealand, Norway, Ireland, Australia, and Denmark.

The cohort included 58,161 women with epithelial and nonepithelial ovarian cancer. The majority of cases were advanced stage, with a median age of 63-67 years at diagnosis, depending on the country.

The researchers compared age- and stage-specific net survival between countries at 1 and 3 years post diagnosis.

The 3-year all-ages net survival was highest for Norway (57%) and Australia (56%), followed by Denmark (54%), Canada (50%), United Kingdom (47%), New Zealand (46%), and Ireland (45%).

Most patients were diagnosed with distant disease (range, 64%-71%), with the greatest proportion of women in the 65- to 74- and 75- to 99-year age categories. The lowest 3-year age-specific survival (range, 20%-34%) was observed in the 75- to 99-year age category.

Marked differences in 3-year net survival between countries were found for women in the 75- to 99-year age group with distant disease (range, 12%-25%).

“International survival differences by age groups were less stark for early-stage disease,” the researchers reported. “Interjurisdictional differences within countries were also observed.”

The researchers acknowledged a key limitation of the analysis was the use of registry data. Variability between, and incomplete data within, registries could have lowered the accuracy of the survival estimates.

“[F]urther research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease [is needed],” the researchers concluded.

The study was supported by funding provided to the International Cancer Benchmarking Partnership. The authors reported having no conflicts of interest.

SOURCE: Cabasag CJ et al. Gynecol Oncol. 2020 Jan 28. doi: 10.1016/j.ygyno.2019.12.047.

A combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and the immune checkpoint inhibitor pembrolizumab (Keytruda) was safe and showed promising activity against advanced renal cell carcinoma and other solid tumors in a phase 1b/2 study.

Overall response rates (ORR) at 24 weeks ranged from 63% for patients with advanced renal cell carcinomas (RCC) to 25% for patients with urothelial cancers, reported Matthew H. Taylor, MD, of Knight Cancer Institute at Oregon Health & Science University in Portland, and colleagues.

The findings from this study sparked additional clinical trials for patients with gastric cancer, gastroesophageal cancer, and differentiated thyroid cancer, and set the stage for larger phase 3 trials in patients with advanced RCC, endometrial cancer, malignant melanoma, and non–small cell lung cancer (NSCLC).

“In the future, we also plan to study lenvatinib plus pembrolizumab in patients with RCC who have had disease progression after treatment with immune checkpoint inhibitors,” they wrote. The report was published in Journal of Clinical Oncology.

Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) with action against vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor (FGF) receptors 1-4, platelet-derived growth factor receptors alpha and the RET and KIT kinases.

“Preclinical and clinical studies suggest that modulation of VEGF-mediated immune suppression via angiogenesis inhibition could potentially augment the immunotherapeutic activity of immune checkpoint inhibitors,” the investigators wrote.

They reported results from the dose finding (1b) phase including 13 patients and initial phase 2 expansion cohorts with a total of 124 patients.

The maximum tolerated dose of lenvatinib in combination with pembrolizumab was established as 20 mg/day.

At 24 weeks of follow-up, the ORR for 30 patients with RCC was 63%; two additional patients had responses after week 24, for a total ORR at study cutoff in this cohort of 70%. The median duration of response for these patients was 20 months, and the median progression-free survival (PFS) was 19.8 months. At the time of data cutoff for this analysis, 9 of the 30 patients with RCC were still on treatment.

For 23 patients with endometrial cancer, the 24-week and overall ORR were 52%, with a median duration of response not reached, and a median PFS of 9.7 months. Seven patients were still on treatment at data cutoff.

For 21 patients with melanoma, the 24-week and overall ORR were 48%, median duration of response was 12.5 months, and median PFS was 5.5 months. Two of the patients were still on treatment at data cutoff.

For the 22 patients with squamous cell cancer of the head and neck, the 24-week ORR was 36%, with two patients having a response after week 24 for a total ORR at data cutoff of 46%. The median duration of response was 8.2 months and the median PFS was 4.7 months. Three patients remained on treatment at data cutoff.

For 21 patients with NSCLC, the 24-week and overall ORR were 33%, the median duration of response was 10.9 months, and median PFS was 5.9 months. Six of the patients were still receiving treatment at data cutoff.

For 20 patients with urothelial cancer, the 24-week and overall ORR were 25%, with a median duration of response not reached, and a median PFS of 5.4 months. Three patients were still receiving the combination at the time of data cutoff.

Treatment related adverse events (TRAEs) occurred in 133 of all 137 patients enrolled in the two study phases. The adverse events were similar across all cohorts, with any grade of events including fatigue in 58%, diarrhea in 52%, hypertension in 47%, hypothyroidism in 42%, and decreased appetite in 39%.

The most frequent grade 3 or 4 TRAEs were hypertension in 20%, fatigue in 12%, diarrhea in 9%, proteinuria in 8%, and increased lipase levels in 7%.

In all, 85% of patients had a TRAE leading to lenvatinib dose reduction and/or interruption, and 13% required lenvatinib discontinuation.

Events leading to pembrolizumab dose interruption occurred in 45% of patients, and pembrolizumab discontinuation in 15%.

The study was sponsored by Eisai with collaboration from Merck Sharp & Dohme. Dr. Taylor disclosed a consulting or advisory role for Bristol-Myers Squibb, Eisai, Array BioPharma, Loxo, Bayer, ArQule, Blueprint Medicines, Novartis, and Sanofi/Genzyme, and speakers bureau activities for BMS and Eisai.

SOURCE: Taylor MH et al. J Clin Oncol. 2020 Jan. 21 doi: 10.1200/JCO.19.01598.

A combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and the immune checkpoint inhibitor pembrolizumab (Keytruda) was safe and showed promising activity against advanced renal cell carcinoma and other solid tumors in a phase 1b/2 study.

Overall response rates (ORR) at 24 weeks ranged from 63% for patients with advanced renal cell carcinomas (RCC) to 25% for patients with urothelial cancers, reported Matthew H. Taylor, MD, of Knight Cancer Institute at Oregon Health & Science University in Portland, and colleagues.

The findings from this study sparked additional clinical trials for patients with gastric cancer, gastroesophageal cancer, and differentiated thyroid cancer, and set the stage for larger phase 3 trials in patients with advanced RCC, endometrial cancer, malignant melanoma, and non–small cell lung cancer (NSCLC).

“In the future, we also plan to study lenvatinib plus pembrolizumab in patients with RCC who have had disease progression after treatment with immune checkpoint inhibitors,” they wrote. The report was published in Journal of Clinical Oncology.

Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) with action against vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor (FGF) receptors 1-4, platelet-derived growth factor receptors alpha and the RET and KIT kinases.

“Preclinical and clinical studies suggest that modulation of VEGF-mediated immune suppression via angiogenesis inhibition could potentially augment the immunotherapeutic activity of immune checkpoint inhibitors,” the investigators wrote.

They reported results from the dose finding (1b) phase including 13 patients and initial phase 2 expansion cohorts with a total of 124 patients.

The maximum tolerated dose of lenvatinib in combination with pembrolizumab was established as 20 mg/day.

At 24 weeks of follow-up, the ORR for 30 patients with RCC was 63%; two additional patients had responses after week 24, for a total ORR at study cutoff in this cohort of 70%. The median duration of response for these patients was 20 months, and the median progression-free survival (PFS) was 19.8 months. At the time of data cutoff for this analysis, 9 of the 30 patients with RCC were still on treatment.

For 23 patients with endometrial cancer, the 24-week and overall ORR were 52%, with a median duration of response not reached, and a median PFS of 9.7 months. Seven patients were still on treatment at data cutoff.

For 21 patients with melanoma, the 24-week and overall ORR were 48%, median duration of response was 12.5 months, and median PFS was 5.5 months. Two of the patients were still on treatment at data cutoff.

For the 22 patients with squamous cell cancer of the head and neck, the 24-week ORR was 36%, with two patients having a response after week 24 for a total ORR at data cutoff of 46%. The median duration of response was 8.2 months and the median PFS was 4.7 months. Three patients remained on treatment at data cutoff.

For 21 patients with NSCLC, the 24-week and overall ORR were 33%, the median duration of response was 10.9 months, and median PFS was 5.9 months. Six of the patients were still receiving treatment at data cutoff.

For 20 patients with urothelial cancer, the 24-week and overall ORR were 25%, with a median duration of response not reached, and a median PFS of 5.4 months. Three patients were still receiving the combination at the time of data cutoff.

Treatment related adverse events (TRAEs) occurred in 133 of all 137 patients enrolled in the two study phases. The adverse events were similar across all cohorts, with any grade of events including fatigue in 58%, diarrhea in 52%, hypertension in 47%, hypothyroidism in 42%, and decreased appetite in 39%.

The most frequent grade 3 or 4 TRAEs were hypertension in 20%, fatigue in 12%, diarrhea in 9%, proteinuria in 8%, and increased lipase levels in 7%.

In all, 85% of patients had a TRAE leading to lenvatinib dose reduction and/or interruption, and 13% required lenvatinib discontinuation.

Events leading to pembrolizumab dose interruption occurred in 45% of patients, and pembrolizumab discontinuation in 15%.

The study was sponsored by Eisai with collaboration from Merck Sharp & Dohme. Dr. Taylor disclosed a consulting or advisory role for Bristol-Myers Squibb, Eisai, Array BioPharma, Loxo, Bayer, ArQule, Blueprint Medicines, Novartis, and Sanofi/Genzyme, and speakers bureau activities for BMS and Eisai.

SOURCE: Taylor MH et al. J Clin Oncol. 2020 Jan. 21 doi: 10.1200/JCO.19.01598.

A combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and the immune checkpoint inhibitor pembrolizumab (Keytruda) was safe and showed promising activity against advanced renal cell carcinoma and other solid tumors in a phase 1b/2 study.

Overall response rates (ORR) at 24 weeks ranged from 63% for patients with advanced renal cell carcinomas (RCC) to 25% for patients with urothelial cancers, reported Matthew H. Taylor, MD, of Knight Cancer Institute at Oregon Health & Science University in Portland, and colleagues.

The findings from this study sparked additional clinical trials for patients with gastric cancer, gastroesophageal cancer, and differentiated thyroid cancer, and set the stage for larger phase 3 trials in patients with advanced RCC, endometrial cancer, malignant melanoma, and non–small cell lung cancer (NSCLC).

“In the future, we also plan to study lenvatinib plus pembrolizumab in patients with RCC who have had disease progression after treatment with immune checkpoint inhibitors,” they wrote. The report was published in Journal of Clinical Oncology.

Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) with action against vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor (FGF) receptors 1-4, platelet-derived growth factor receptors alpha and the RET and KIT kinases.

“Preclinical and clinical studies suggest that modulation of VEGF-mediated immune suppression via angiogenesis inhibition could potentially augment the immunotherapeutic activity of immune checkpoint inhibitors,” the investigators wrote.

They reported results from the dose finding (1b) phase including 13 patients and initial phase 2 expansion cohorts with a total of 124 patients.

The maximum tolerated dose of lenvatinib in combination with pembrolizumab was established as 20 mg/day.

At 24 weeks of follow-up, the ORR for 30 patients with RCC was 63%; two additional patients had responses after week 24, for a total ORR at study cutoff in this cohort of 70%. The median duration of response for these patients was 20 months, and the median progression-free survival (PFS) was 19.8 months. At the time of data cutoff for this analysis, 9 of the 30 patients with RCC were still on treatment.

For 23 patients with endometrial cancer, the 24-week and overall ORR were 52%, with a median duration of response not reached, and a median PFS of 9.7 months. Seven patients were still on treatment at data cutoff.

For 21 patients with melanoma, the 24-week and overall ORR were 48%, median duration of response was 12.5 months, and median PFS was 5.5 months. Two of the patients were still on treatment at data cutoff.

For the 22 patients with squamous cell cancer of the head and neck, the 24-week ORR was 36%, with two patients having a response after week 24 for a total ORR at data cutoff of 46%. The median duration of response was 8.2 months and the median PFS was 4.7 months. Three patients remained on treatment at data cutoff.

For 21 patients with NSCLC, the 24-week and overall ORR were 33%, the median duration of response was 10.9 months, and median PFS was 5.9 months. Six of the patients were still receiving treatment at data cutoff.

For 20 patients with urothelial cancer, the 24-week and overall ORR were 25%, with a median duration of response not reached, and a median PFS of 5.4 months. Three patients were still receiving the combination at the time of data cutoff.

Treatment related adverse events (TRAEs) occurred in 133 of all 137 patients enrolled in the two study phases. The adverse events were similar across all cohorts, with any grade of events including fatigue in 58%, diarrhea in 52%, hypertension in 47%, hypothyroidism in 42%, and decreased appetite in 39%.

The most frequent grade 3 or 4 TRAEs were hypertension in 20%, fatigue in 12%, diarrhea in 9%, proteinuria in 8%, and increased lipase levels in 7%.

In all, 85% of patients had a TRAE leading to lenvatinib dose reduction and/or interruption, and 13% required lenvatinib discontinuation.

Events leading to pembrolizumab dose interruption occurred in 45% of patients, and pembrolizumab discontinuation in 15%.

The study was sponsored by Eisai with collaboration from Merck Sharp & Dohme. Dr. Taylor disclosed a consulting or advisory role for Bristol-Myers Squibb, Eisai, Array BioPharma, Loxo, Bayer, ArQule, Blueprint Medicines, Novartis, and Sanofi/Genzyme, and speakers bureau activities for BMS and Eisai.

SOURCE: Taylor MH et al. J Clin Oncol. 2020 Jan. 21 doi: 10.1200/JCO.19.01598.

In new guidelines, the American Society of Clinical Oncology recommends offering germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes to all women diagnosed with epithelial ovarian cancer, regardless of their clinical features or family history.

Testing should be offered at diagnosis or as soon as possible after that, Panagiotis A. Konstantinopoulos, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and colleagues wrote in the Journal of Clinical Oncology.

For patients who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant, the guidelines recommend offering somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants. This testing can be offered at the time of disease recurrence after up-front therapy.

The guidelines also recommend somatic tumor testing for mismatch repair deficiency in patients diagnosed with clear cell, endometrioid, or mucinous ovarian cancer. This testing may be offered to patients with other histologic types of epithelial ovarian cancer as well.

Genetic testing, as well as genetic risk evaluation and counseling, should be offered to first- or second-degree blood relatives of a patient with ovarian cancer and a known germline pathogenic cancer susceptibility gene variant, according to the guidelines.

According to the guidelines, genetic evaluations should be conducted in cooperation with other health care providers who are “familiar with the diagnosis and management of hereditary cancer syndromes to determine the most appropriate testing strategy and discuss implications of the findings.”

Patients with identified germline or somatic pathogenic or likely pathogenic BRCA1/2 variants should receive treatments approved for them by the Food and Drug Administration, according to the guidelines. The authors note that patients with these variants have responded well to FDA-approved poly (ADP-ribose) polymerase inhibitors, including niraparib (Zejula), olaparib (Lynparza), and rucaparib (Rubraca).

The guidelines also state that mismatch repair deficiency qualifies for FDA-approved treatment, so patients with recurrent epithelial ovarian cancer and mismatch repair deficiency should receive FDA-approved treatments under their labeled indications.

The guidelines note that clinical decisions should not be based on a variant of uncertain significance. When a patient has such a variant, “clinical features and family history should inform clinical decision making,” according to the guidelines.

Dr. Konstantinopoulos and colleagues formulated the guidelines after reviewing data from 19 studies, including 6 meta-analyses; 11 randomized, controlled trials; and 2 observational studies.

The authors reported relationships with a range of pharmaceutical companies, including those that market drugs for epithelial ovarian cancer.

SOURCE: Konstantinopoulos PA et al. J Clin Oncol. 2020 Jan 27. doi: 10.1200/JCO.19.02960.

In new guidelines, the American Society of Clinical Oncology recommends offering germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes to all women diagnosed with epithelial ovarian cancer, regardless of their clinical features or family history.

Testing should be offered at diagnosis or as soon as possible after that, Panagiotis A. Konstantinopoulos, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and colleagues wrote in the Journal of Clinical Oncology.

For patients who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant, the guidelines recommend offering somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants. This testing can be offered at the time of disease recurrence after up-front therapy.

The guidelines also recommend somatic tumor testing for mismatch repair deficiency in patients diagnosed with clear cell, endometrioid, or mucinous ovarian cancer. This testing may be offered to patients with other histologic types of epithelial ovarian cancer as well.

Genetic testing, as well as genetic risk evaluation and counseling, should be offered to first- or second-degree blood relatives of a patient with ovarian cancer and a known germline pathogenic cancer susceptibility gene variant, according to the guidelines.

According to the guidelines, genetic evaluations should be conducted in cooperation with other health care providers who are “familiar with the diagnosis and management of hereditary cancer syndromes to determine the most appropriate testing strategy and discuss implications of the findings.”

Patients with identified germline or somatic pathogenic or likely pathogenic BRCA1/2 variants should receive treatments approved for them by the Food and Drug Administration, according to the guidelines. The authors note that patients with these variants have responded well to FDA-approved poly (ADP-ribose) polymerase inhibitors, including niraparib (Zejula), olaparib (Lynparza), and rucaparib (Rubraca).

The guidelines also state that mismatch repair deficiency qualifies for FDA-approved treatment, so patients with recurrent epithelial ovarian cancer and mismatch repair deficiency should receive FDA-approved treatments under their labeled indications.

The guidelines note that clinical decisions should not be based on a variant of uncertain significance. When a patient has such a variant, “clinical features and family history should inform clinical decision making,” according to the guidelines.

Dr. Konstantinopoulos and colleagues formulated the guidelines after reviewing data from 19 studies, including 6 meta-analyses; 11 randomized, controlled trials; and 2 observational studies.

The authors reported relationships with a range of pharmaceutical companies, including those that market drugs for epithelial ovarian cancer.

SOURCE: Konstantinopoulos PA et al. J Clin Oncol. 2020 Jan 27. doi: 10.1200/JCO.19.02960.

In new guidelines, the American Society of Clinical Oncology recommends offering germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes to all women diagnosed with epithelial ovarian cancer, regardless of their clinical features or family history.

Testing should be offered at diagnosis or as soon as possible after that, Panagiotis A. Konstantinopoulos, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and colleagues wrote in the Journal of Clinical Oncology.

For patients who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant, the guidelines recommend offering somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants. This testing can be offered at the time of disease recurrence after up-front therapy.

The guidelines also recommend somatic tumor testing for mismatch repair deficiency in patients diagnosed with clear cell, endometrioid, or mucinous ovarian cancer. This testing may be offered to patients with other histologic types of epithelial ovarian cancer as well.

Genetic testing, as well as genetic risk evaluation and counseling, should be offered to first- or second-degree blood relatives of a patient with ovarian cancer and a known germline pathogenic cancer susceptibility gene variant, according to the guidelines.

According to the guidelines, genetic evaluations should be conducted in cooperation with other health care providers who are “familiar with the diagnosis and management of hereditary cancer syndromes to determine the most appropriate testing strategy and discuss implications of the findings.”

Patients with identified germline or somatic pathogenic or likely pathogenic BRCA1/2 variants should receive treatments approved for them by the Food and Drug Administration, according to the guidelines. The authors note that patients with these variants have responded well to FDA-approved poly (ADP-ribose) polymerase inhibitors, including niraparib (Zejula), olaparib (Lynparza), and rucaparib (Rubraca).

The guidelines also state that mismatch repair deficiency qualifies for FDA-approved treatment, so patients with recurrent epithelial ovarian cancer and mismatch repair deficiency should receive FDA-approved treatments under their labeled indications.

The guidelines note that clinical decisions should not be based on a variant of uncertain significance. When a patient has such a variant, “clinical features and family history should inform clinical decision making,” according to the guidelines.

Dr. Konstantinopoulos and colleagues formulated the guidelines after reviewing data from 19 studies, including 6 meta-analyses; 11 randomized, controlled trials; and 2 observational studies.

The authors reported relationships with a range of pharmaceutical companies, including those that market drugs for epithelial ovarian cancer.

SOURCE: Konstantinopoulos PA et al. J Clin Oncol. 2020 Jan 27. doi: 10.1200/JCO.19.02960.

Relative to serous borderline ovarian tumors, the proportion of low-grade serous ovarian cancers has decreased in recent years, paralleled by a trend toward decreased survival, results of a large, population-based study suggest.

The number of low-grade serous ovarian cancer (LGSOC) cases declined by almost 26% in the retrospective analysis of registry data from 1998 to 2000, with a relative decrease of survival by nearly 29% over that time period.

Those decreases in LGSOC incidence and survival may be explained by a “diagnosis shift” toward versus serous borderline ovarian tumors (SBOTs) over time, though it could also be due to earlier detection of SBOT, which may be a precursor lesion of LGSOC, said authors of the study, led by oncology researcher Koji Matsuo, MD, PhD, of the University of Southern California, Los Angeles.

Taken together, the findings support the need to distinguish between LGSOC and SBOT, given their “distinctly different” oncologic outcomes and treatment approaches, according to Dr. Matsuo and colleagues.

“Making a proper diagnosis for LGSOC versus SBOT is paramount, as it impacts surgical and postoperative management,” the authors wrote in their report on the study, which appears in Gynecologic Oncology.

The retrospective, population-based, observational study, based on data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, included women with LGSOC or SBOT diagnosed between 1988 and 2000 in the United States. A total of 4,712 cases were analyzed.

The number of LGSOC from 23.2% in 1988 down to 17.2% by 2000, or a relative decrease of 25.9%, Dr. Matsuo and coauthors reported. The decrease was even more pronounced in stage I disease, with a relative decrease of 37.6% versus 21.1% for stage II-IV.

As compared with women with SBOT, women with LGSOC were more likely to be older, more likely to have stage II-IV disease at diagnosis, more likely to have undergone hysterectomy, and less likely to be residents of the western United States, results of a multivariable analysis showed.

There was a downward trend in 15-year overall survival among women with LGSOC, from 53.3% to 38.0% by 2000, representing a relative decrease of 28.7%, according to the investigators. By contrast, overall survival was unchanged in the SBOT cohort, at 76.7% in 1988 and 78.7% by 2000, for a relative increase of about 2.5%.

Gradual changes in diagnostic classification over time may explain these trends, according to the investigators.

That shift would have started with the recognition of borderline ovarian tumors as a separate entity by the World Health Organization until 1971, leading to an increasing number of SBOTs over time as diagnostic practice patterns gradually changed. Later, it would have been fueled by the recognition of LGSOC as a new classification in the mid-1980s, which may have accelerated the shift by enhanced discrimination of SBOT from other serous tumors, the investigators wrote.

On the other hand, since SBOT may be a precursor lesion to LGSOC, the shift in diagnosis over time could be caused at least in part by increasing use of transvaginal ultrasonography, leading to more early detection of SBOT before they could progress to LGGOC. “More study is necessary to identify if SBOT can progress to LGSOC,” Dr. Matsuo and coauthors wrote.

The study was funded by the Ensign Endowment for Gynecologic Cancer Research. Dr. Matsuo reported disclosures related to Chugai, Springer, and VBL Therapeutics. His coauthors provided additional disclosures related to Kiyatec, Merck, Biopath, M-Trap, Quantgene, Tesaro, GlaxoSmithKline, Celgene, Johnson & Johnson, Biogin, Clovis Oncology, Novartis, Elsevier, and UpToDate.

SOURCE: Matsuo K et al. Gynecol Oncol. 2020 Jan 15. doi: 10.1016/j.ygyno.2019.08.030.

Relative to serous borderline ovarian tumors, the proportion of low-grade serous ovarian cancers has decreased in recent years, paralleled by a trend toward decreased survival, results of a large, population-based study suggest.

The number of low-grade serous ovarian cancer (LGSOC) cases declined by almost 26% in the retrospective analysis of registry data from 1998 to 2000, with a relative decrease of survival by nearly 29% over that time period.

Those decreases in LGSOC incidence and survival may be explained by a “diagnosis shift” toward versus serous borderline ovarian tumors (SBOTs) over time, though it could also be due to earlier detection of SBOT, which may be a precursor lesion of LGSOC, said authors of the study, led by oncology researcher Koji Matsuo, MD, PhD, of the University of Southern California, Los Angeles.

Taken together, the findings support the need to distinguish between LGSOC and SBOT, given their “distinctly different” oncologic outcomes and treatment approaches, according to Dr. Matsuo and colleagues.

“Making a proper diagnosis for LGSOC versus SBOT is paramount, as it impacts surgical and postoperative management,” the authors wrote in their report on the study, which appears in Gynecologic Oncology.

The retrospective, population-based, observational study, based on data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, included women with LGSOC or SBOT diagnosed between 1988 and 2000 in the United States. A total of 4,712 cases were analyzed.

The number of LGSOC from 23.2% in 1988 down to 17.2% by 2000, or a relative decrease of 25.9%, Dr. Matsuo and coauthors reported. The decrease was even more pronounced in stage I disease, with a relative decrease of 37.6% versus 21.1% for stage II-IV.

As compared with women with SBOT, women with LGSOC were more likely to be older, more likely to have stage II-IV disease at diagnosis, more likely to have undergone hysterectomy, and less likely to be residents of the western United States, results of a multivariable analysis showed.

There was a downward trend in 15-year overall survival among women with LGSOC, from 53.3% to 38.0% by 2000, representing a relative decrease of 28.7%, according to the investigators. By contrast, overall survival was unchanged in the SBOT cohort, at 76.7% in 1988 and 78.7% by 2000, for a relative increase of about 2.5%.

Gradual changes in diagnostic classification over time may explain these trends, according to the investigators.

That shift would have started with the recognition of borderline ovarian tumors as a separate entity by the World Health Organization until 1971, leading to an increasing number of SBOTs over time as diagnostic practice patterns gradually changed. Later, it would have been fueled by the recognition of LGSOC as a new classification in the mid-1980s, which may have accelerated the shift by enhanced discrimination of SBOT from other serous tumors, the investigators wrote.

On the other hand, since SBOT may be a precursor lesion to LGSOC, the shift in diagnosis over time could be caused at least in part by increasing use of transvaginal ultrasonography, leading to more early detection of SBOT before they could progress to LGGOC. “More study is necessary to identify if SBOT can progress to LGSOC,” Dr. Matsuo and coauthors wrote.

The study was funded by the Ensign Endowment for Gynecologic Cancer Research. Dr. Matsuo reported disclosures related to Chugai, Springer, and VBL Therapeutics. His coauthors provided additional disclosures related to Kiyatec, Merck, Biopath, M-Trap, Quantgene, Tesaro, GlaxoSmithKline, Celgene, Johnson & Johnson, Biogin, Clovis Oncology, Novartis, Elsevier, and UpToDate.

SOURCE: Matsuo K et al. Gynecol Oncol. 2020 Jan 15. doi: 10.1016/j.ygyno.2019.08.030.

Relative to serous borderline ovarian tumors, the proportion of low-grade serous ovarian cancers has decreased in recent years, paralleled by a trend toward decreased survival, results of a large, population-based study suggest.

The number of low-grade serous ovarian cancer (LGSOC) cases declined by almost 26% in the retrospective analysis of registry data from 1998 to 2000, with a relative decrease of survival by nearly 29% over that time period.

Those decreases in LGSOC incidence and survival may be explained by a “diagnosis shift” toward versus serous borderline ovarian tumors (SBOTs) over time, though it could also be due to earlier detection of SBOT, which may be a precursor lesion of LGSOC, said authors of the study, led by oncology researcher Koji Matsuo, MD, PhD, of the University of Southern California, Los Angeles.

Taken together, the findings support the need to distinguish between LGSOC and SBOT, given their “distinctly different” oncologic outcomes and treatment approaches, according to Dr. Matsuo and colleagues.

“Making a proper diagnosis for LGSOC versus SBOT is paramount, as it impacts surgical and postoperative management,” the authors wrote in their report on the study, which appears in Gynecologic Oncology.

The retrospective, population-based, observational study, based on data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, included women with LGSOC or SBOT diagnosed between 1988 and 2000 in the United States. A total of 4,712 cases were analyzed.

The number of LGSOC from 23.2% in 1988 down to 17.2% by 2000, or a relative decrease of 25.9%, Dr. Matsuo and coauthors reported. The decrease was even more pronounced in stage I disease, with a relative decrease of 37.6% versus 21.1% for stage II-IV.

As compared with women with SBOT, women with LGSOC were more likely to be older, more likely to have stage II-IV disease at diagnosis, more likely to have undergone hysterectomy, and less likely to be residents of the western United States, results of a multivariable analysis showed.

There was a downward trend in 15-year overall survival among women with LGSOC, from 53.3% to 38.0% by 2000, representing a relative decrease of 28.7%, according to the investigators. By contrast, overall survival was unchanged in the SBOT cohort, at 76.7% in 1988 and 78.7% by 2000, for a relative increase of about 2.5%.

Gradual changes in diagnostic classification over time may explain these trends, according to the investigators.

That shift would have started with the recognition of borderline ovarian tumors as a separate entity by the World Health Organization until 1971, leading to an increasing number of SBOTs over time as diagnostic practice patterns gradually changed. Later, it would have been fueled by the recognition of LGSOC as a new classification in the mid-1980s, which may have accelerated the shift by enhanced discrimination of SBOT from other serous tumors, the investigators wrote.

On the other hand, since SBOT may be a precursor lesion to LGSOC, the shift in diagnosis over time could be caused at least in part by increasing use of transvaginal ultrasonography, leading to more early detection of SBOT before they could progress to LGGOC. “More study is necessary to identify if SBOT can progress to LGSOC,” Dr. Matsuo and coauthors wrote.

The study was funded by the Ensign Endowment for Gynecologic Cancer Research. Dr. Matsuo reported disclosures related to Chugai, Springer, and VBL Therapeutics. His coauthors provided additional disclosures related to Kiyatec, Merck, Biopath, M-Trap, Quantgene, Tesaro, GlaxoSmithKline, Celgene, Johnson & Johnson, Biogin, Clovis Oncology, Novartis, Elsevier, and UpToDate.

SOURCE: Matsuo K et al. Gynecol Oncol. 2020 Jan 15. doi: 10.1016/j.ygyno.2019.08.030.

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381:1929-1939.

EXPERT COMMENTARY

Ovarian cancer represents the most lethal gynecologic cancer, with an estimated 14,000 deaths in 2019.¹ While the incidence of this disease is low in comparison to uterine cancer, the advanced stage at diagnosis portends poor prognosis. While stage is an independent risk factor for death, it is also a risk for recurrence, with more than 80% of women developing recurrent disease.^2-4 Secondary cytoreduction remains an option for patients in which disease recurs; up until now this management option was driven by retrospective data.⁵

Details of the study

Coleman and colleagues conducted the Gynecologic Oncology Group (GOG) 0213 trial—a phase 3, multicenter, randomized clinical trial that included 485 women with recurrent ovarian cancer. The surgical objective of the trial was to determine whether secondary cytoreduction in operable, platinum-sensitive (PS) patients improved overall survival (OS).

Patients were eligible to participate in the surgical portion of the trial if they had PS measurable disease and had the intention to achieve complete gross resection. Women with ascites, evidence of extraabdominal disease, and “diffuse carcinomatosis” were excluded. The primary and secondary end points were OS and progression-free survival (PFS), respectively.

Results. There were no statistical differences between the surgery and no surgery groups with regard to median OS (50.6 months vs 64.7 months, respectively; hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.97–1.72) or median PFS (18.9 months vs 16.2 months; HR, 0.82; 95% CI, 0.66 to 1.01). When comparing patients in which complete gross resection was achieved (150 patients vs 245 who did not receive surgery), there was only a statistical difference in PFS in favor of the surgical group (22.4 months vs 16.2 months; HR, 0.62; 95% CI, 0.48–0.80).

Of note, 67% of the patients who received surgery (63% intention-to-treat) were debulked to complete gross resection. There were 33% more patients with extraabdominal disease (10% vs 7% of total patients in each group) and 15% more patients with upper abdominal disease (40% vs 33% of total patients in each group) included in the surgical group. Finally, the median time to chemotherapy was 40 days in the surgery group versus 7 days in the no surgery group.

Continue to: Study strengths and weaknesses...

Study strengths and weaknesses

The authors deserve to be commended for this well-designed and laborious trial, which is the first of its kind. The strength of the study is its randomized design producing level I data.

Study weaknesses include lack of reporting of BRCA status and the impact of receiving targeted therapies after the trial was over. It is well established that BRCA-mutated patients have an independent survival advantage, even when taking into account platinum sensitivity.^6-8BRCA status of the study population is not specifically addressed in this paper. The authors noted in the first GOG 0213 trial publication, which assessed bevacizumab in the recurrent setting, that BRCA status has an impact on patient outcomes. Subsequently, they state that they do not report BRCA status because “…its independent effect on response to an anti-angiogenesis agent was unknown,” but it clearly would affect survival analysis if unbalanced between groups.⁹

Similarly, in the introduction to their study, Coleman and colleagues list availability of maintenance therapy, for instance poly ADP (adenosine diphosphate–ribose) polymerase (PARP) inhibitors, as rationale for conducting their trial. They subsequently cite this as a possible reason that the median overall survival was 3 times longer than expected. However, they provide no data on which patients received maintenance therapy, which again could have drastically affected survival outcomes.¹⁰ They do report in the supplementary information that, when stratifying those receiving bevacizumab adjuvantly during the trial, the median OS was comparable between the surgical and nonsurgical groups (58.5 months vs 61.7 months).

The authors discuss the presence of patient selection bias as a weakness in the study. Selection bias is evident in this trial (as in many surgical trials) because patients with a limited volume of disease were selected to participate over those with large-volume disease. It is reasonable to conclude that this study is likely selecting patients with less aggressive tumor biology, not only evident by low-volume disease at recurrence but also by the 20.4-month median platinum-free interval in the surgical group, which certainly affects the trial’s validity. Despite being considered PS, the disease biology in a patient with a platinum-free interval of 20.4 months is surely different from the disease biology in a patient with a 6.4-month platinum-free interval; therefore, it is difficult to generalize these data to all PS recurrent ovarian cancer patients. Similarly, other research has suggested strict selection criteria, which was not apparent in this study’s methodology.¹¹ While the number of metastatic sites were relatively equal between the surgery and no surgery groups, there were more patients in the surgical group with extraabdominal disease, which the authors used as an exclusion criterion.

Lastly, the time to treatment commencement in each arm, which was 40 days for the surgical arm and 7 days in the nonsurgical arm, could represent a flaw in this trial. While we expect a difference in duration to account for recovery time, many centers start chemotherapy as soon as 21 days after surgery, which is almost half of the median interval in the surgical group in this trial. While the authors address this by stating that they completed a landmark analysis, no data or information about what time points they used for the analysis are provided. They simply report an interquartile range of 28 to 51 days. It is hard to know what effect this may have had on the outcome.

Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381:1929-1939.

EXPERT COMMENTARY

Ovarian cancer represents the most lethal gynecologic cancer, with an estimated 14,000 deaths in 2019.¹ While the incidence of this disease is low in comparison to uterine cancer, the advanced stage at diagnosis portends poor prognosis. While stage is an independent risk factor for death, it is also a risk for recurrence, with more than 80% of women developing recurrent disease.^2-4 Secondary cytoreduction remains an option for patients in which disease recurs; up until now this management option was driven by retrospective data.⁵

Details of the study

Coleman and colleagues conducted the Gynecologic Oncology Group (GOG) 0213 trial—a phase 3, multicenter, randomized clinical trial that included 485 women with recurrent ovarian cancer. The surgical objective of the trial was to determine whether secondary cytoreduction in operable, platinum-sensitive (PS) patients improved overall survival (OS).

Patients were eligible to participate in the surgical portion of the trial if they had PS measurable disease and had the intention to achieve complete gross resection. Women with ascites, evidence of extraabdominal disease, and “diffuse carcinomatosis” were excluded. The primary and secondary end points were OS and progression-free survival (PFS), respectively.

Results. There were no statistical differences between the surgery and no surgery groups with regard to median OS (50.6 months vs 64.7 months, respectively; hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.97–1.72) or median PFS (18.9 months vs 16.2 months; HR, 0.82; 95% CI, 0.66 to 1.01). When comparing patients in which complete gross resection was achieved (150 patients vs 245 who did not receive surgery), there was only a statistical difference in PFS in favor of the surgical group (22.4 months vs 16.2 months; HR, 0.62; 95% CI, 0.48–0.80).

Of note, 67% of the patients who received surgery (63% intention-to-treat) were debulked to complete gross resection. There were 33% more patients with extraabdominal disease (10% vs 7% of total patients in each group) and 15% more patients with upper abdominal disease (40% vs 33% of total patients in each group) included in the surgical group. Finally, the median time to chemotherapy was 40 days in the surgery group versus 7 days in the no surgery group.

Continue to: Study strengths and weaknesses...

Study strengths and weaknesses

The authors deserve to be commended for this well-designed and laborious trial, which is the first of its kind. The strength of the study is its randomized design producing level I data.

Study weaknesses include lack of reporting of BRCA status and the impact of receiving targeted therapies after the trial was over. It is well established that BRCA-mutated patients have an independent survival advantage, even when taking into account platinum sensitivity.^6-8BRCA status of the study population is not specifically addressed in this paper. The authors noted in the first GOG 0213 trial publication, which assessed bevacizumab in the recurrent setting, that BRCA status has an impact on patient outcomes. Subsequently, they state that they do not report BRCA status because “…its independent effect on response to an anti-angiogenesis agent was unknown,” but it clearly would affect survival analysis if unbalanced between groups.⁹

Similarly, in the introduction to their study, Coleman and colleagues list availability of maintenance therapy, for instance poly ADP (adenosine diphosphate–ribose) polymerase (PARP) inhibitors, as rationale for conducting their trial. They subsequently cite this as a possible reason that the median overall survival was 3 times longer than expected. However, they provide no data on which patients received maintenance therapy, which again could have drastically affected survival outcomes.¹⁰ They do report in the supplementary information that, when stratifying those receiving bevacizumab adjuvantly during the trial, the median OS was comparable between the surgical and nonsurgical groups (58.5 months vs 61.7 months).

The authors discuss the presence of patient selection bias as a weakness in the study. Selection bias is evident in this trial (as in many surgical trials) because patients with a limited volume of disease were selected to participate over those with large-volume disease. It is reasonable to conclude that this study is likely selecting patients with less aggressive tumor biology, not only evident by low-volume disease at recurrence but also by the 20.4-month median platinum-free interval in the surgical group, which certainly affects the trial’s validity. Despite being considered PS, the disease biology in a patient with a platinum-free interval of 20.4 months is surely different from the disease biology in a patient with a 6.4-month platinum-free interval; therefore, it is difficult to generalize these data to all PS recurrent ovarian cancer patients. Similarly, other research has suggested strict selection criteria, which was not apparent in this study’s methodology.¹¹ While the number of metastatic sites were relatively equal between the surgery and no surgery groups, there were more patients in the surgical group with extraabdominal disease, which the authors used as an exclusion criterion.

Lastly, the time to treatment commencement in each arm, which was 40 days for the surgical arm and 7 days in the nonsurgical arm, could represent a flaw in this trial. While we expect a difference in duration to account for recovery time, many centers start chemotherapy as soon as 21 days after surgery, which is almost half of the median interval in the surgical group in this trial. While the authors address this by stating that they completed a landmark analysis, no data or information about what time points they used for the analysis are provided. They simply report an interquartile range of 28 to 51 days. It is hard to know what effect this may have had on the outcome.

Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381:1929-1939.

EXPERT COMMENTARY

Ovarian cancer represents the most lethal gynecologic cancer, with an estimated 14,000 deaths in 2019.¹ While the incidence of this disease is low in comparison to uterine cancer, the advanced stage at diagnosis portends poor prognosis. While stage is an independent risk factor for death, it is also a risk for recurrence, with more than 80% of women developing recurrent disease.^2-4 Secondary cytoreduction remains an option for patients in which disease recurs; up until now this management option was driven by retrospective data.⁵

Details of the study

Coleman and colleagues conducted the Gynecologic Oncology Group (GOG) 0213 trial—a phase 3, multicenter, randomized clinical trial that included 485 women with recurrent ovarian cancer. The surgical objective of the trial was to determine whether secondary cytoreduction in operable, platinum-sensitive (PS) patients improved overall survival (OS).

Patients were eligible to participate in the surgical portion of the trial if they had PS measurable disease and had the intention to achieve complete gross resection. Women with ascites, evidence of extraabdominal disease, and “diffuse carcinomatosis” were excluded. The primary and secondary end points were OS and progression-free survival (PFS), respectively.

Results. There were no statistical differences between the surgery and no surgery groups with regard to median OS (50.6 months vs 64.7 months, respectively; hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.97–1.72) or median PFS (18.9 months vs 16.2 months; HR, 0.82; 95% CI, 0.66 to 1.01). When comparing patients in which complete gross resection was achieved (150 patients vs 245 who did not receive surgery), there was only a statistical difference in PFS in favor of the surgical group (22.4 months vs 16.2 months; HR, 0.62; 95% CI, 0.48–0.80).

Of note, 67% of the patients who received surgery (63% intention-to-treat) were debulked to complete gross resection. There were 33% more patients with extraabdominal disease (10% vs 7% of total patients in each group) and 15% more patients with upper abdominal disease (40% vs 33% of total patients in each group) included in the surgical group. Finally, the median time to chemotherapy was 40 days in the surgery group versus 7 days in the no surgery group.

Continue to: Study strengths and weaknesses...

Study strengths and weaknesses

The authors deserve to be commended for this well-designed and laborious trial, which is the first of its kind. The strength of the study is its randomized design producing level I data.

Study weaknesses include lack of reporting of BRCA status and the impact of receiving targeted therapies after the trial was over. It is well established that BRCA-mutated patients have an independent survival advantage, even when taking into account platinum sensitivity.^6-8BRCA status of the study population is not specifically addressed in this paper. The authors noted in the first GOG 0213 trial publication, which assessed bevacizumab in the recurrent setting, that BRCA status has an impact on patient outcomes. Subsequently, they state that they do not report BRCA status because “…its independent effect on response to an anti-angiogenesis agent was unknown,” but it clearly would affect survival analysis if unbalanced between groups.⁹

Similarly, in the introduction to their study, Coleman and colleagues list availability of maintenance therapy, for instance poly ADP (adenosine diphosphate–ribose) polymerase (PARP) inhibitors, as rationale for conducting their trial. They subsequently cite this as a possible reason that the median overall survival was 3 times longer than expected. However, they provide no data on which patients received maintenance therapy, which again could have drastically affected survival outcomes.¹⁰ They do report in the supplementary information that, when stratifying those receiving bevacizumab adjuvantly during the trial, the median OS was comparable between the surgical and nonsurgical groups (58.5 months vs 61.7 months).

The authors discuss the presence of patient selection bias as a weakness in the study. Selection bias is evident in this trial (as in many surgical trials) because patients with a limited volume of disease were selected to participate over those with large-volume disease. It is reasonable to conclude that this study is likely selecting patients with less aggressive tumor biology, not only evident by low-volume disease at recurrence but also by the 20.4-month median platinum-free interval in the surgical group, which certainly affects the trial’s validity. Despite being considered PS, the disease biology in a patient with a platinum-free interval of 20.4 months is surely different from the disease biology in a patient with a 6.4-month platinum-free interval; therefore, it is difficult to generalize these data to all PS recurrent ovarian cancer patients. Similarly, other research has suggested strict selection criteria, which was not apparent in this study’s methodology.¹¹ While the number of metastatic sites were relatively equal between the surgery and no surgery groups, there were more patients in the surgical group with extraabdominal disease, which the authors used as an exclusion criterion.

Lastly, the time to treatment commencement in each arm, which was 40 days for the surgical arm and 7 days in the nonsurgical arm, could represent a flaw in this trial. While we expect a difference in duration to account for recovery time, many centers start chemotherapy as soon as 21 days after surgery, which is almost half of the median interval in the surgical group in this trial. While the authors address this by stating that they completed a landmark analysis, no data or information about what time points they used for the analysis are provided. They simply report an interquartile range of 28 to 51 days. It is hard to know what effect this may have had on the outcome.

CHICAGO – Radiation therapy for cervical cancer resulted in pelvic insufficiency fractures more frequently than previously thought, and many fractures were slow to heal, according to research presented at the annual meeting of the Radiological Society of North America.

“Pelvic insufficiency fractures had a prevalence of 38% on MRI follow-up” after chemoradiotherapy for locally advanced cervical cancer, said Alina Dragan, MD. This figure is more than double the previously reported prevalence of about 14%.

Dr. Dragan, a radiology resident at London North West Healthcare, National Health Service Trust, and coinvestigators also tracked the natural history of these fractures over time, to fill a knowledge gap about whether, and at what rate, these pelvic insufficiency fractures healed.

In the single-center retrospective study, the investigators found that just 14% of sacral fractures healed during the period of observation. For acetabular and pubic fractures, roughly one in three fractures had healed by the last MRI scan. About a third of all fractures remained stable across scans, while just over 10% of fractures were either fluctuant or worsened.

The study included 115 women with locally advanced cervical cancer who were treated with radical or adjuvant concurrent chemoradiotherapy over a 5-year period, and had MRI scans performed in-house; the follow-up protocol had patients receiving scans at 3, 12, and 24 months post treatment. From an initial pool of 197 patients, those who had previously had pelvic radiation or were receiving palliative treatment, as well as those with incomplete imaging follow-up and those with metal implants or prostheses that could affect radiation therapy delivery or imaging quality were excluded.

The chemoradiotherapy protocol involved five doses of weekly cisplatin at 400 mg/m² of body surface area, as well as high–dose rate cervix brachytherapy. In practice, all but six participants received these treatments. Patients also received external beam radiotherapy with or without a simultaneous integrated boost to target affected lymph nodes, as clinically indicated.

The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema.

Patients were aged a median of 54 years, and 64 (56%) were postmenopausal. Most patients (n = 84; 73%) had never used tobacco. Participants’ median body mass index was 26 kg/m².

Most patients (n = 73; 64%) were International Federation of Gynecology and Obstetrics stage 2b, and almost half (n = 55; 48%) had pelvic nodal involvement.

Patients were followed for a median of 12 months, with patients receiving a median of two MRIs curing that period. In all, 105 fractures were identified in 44 patients. A median of two fractures were identified among the group of patients who had pelvic insufficiency fractures.

The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema. In this schema, 41% of identified fractures were considered mild, while 32% were moderate and 12% were severe.

Although just over two-thirds of fractures (70%) were identified within 6 months of beginning surveillance, a quarter were not identified until 9-13 months post therapy, and 5% were found after more than 13 months.

Sacral fractures accounted for 72% of those identified, in keeping with previous findings, said Dr. Dragan. Acetabular and pubic fractures made up 16% and 10% of fractures, respectively. One fracture was seen at the ilium and one at the ischium.

Dr. Dragan and colleagues turned to multivariable analysis to look for risk factors for pelvic insufficiency fractures in this cohort of cervical cancer patients. Younger patients had a hazard ratio of 0.30 for fracture, compared with those over the age of 50 years (P less than .01). Similarly, being menopausal carried a hazard ratio of 2.25 for fracture. Higher radiation doses to the sacrum also boosted fracture risk (HR, 2.00; P = .03). Neither sacral volume and slope nor the receipt of simultaneous integrated boost were associated with increased fracture risk.

Dr. Dragan reported that she had no relevant conflicts of interest. She reported no outside sources of funding.
 

SOURCE: Dragan A et al. RSNA 2019, Presentation SSE25-03.

CHICAGO – Radiation therapy for cervical cancer resulted in pelvic insufficiency fractures more frequently than previously thought, and many fractures were slow to heal, according to research presented at the annual meeting of the Radiological Society of North America.

“Pelvic insufficiency fractures had a prevalence of 38% on MRI follow-up” after chemoradiotherapy for locally advanced cervical cancer, said Alina Dragan, MD. This figure is more than double the previously reported prevalence of about 14%.

Dr. Dragan, a radiology resident at London North West Healthcare, National Health Service Trust, and coinvestigators also tracked the natural history of these fractures over time, to fill a knowledge gap about whether, and at what rate, these pelvic insufficiency fractures healed.

In the single-center retrospective study, the investigators found that just 14% of sacral fractures healed during the period of observation. For acetabular and pubic fractures, roughly one in three fractures had healed by the last MRI scan. About a third of all fractures remained stable across scans, while just over 10% of fractures were either fluctuant or worsened.

The study included 115 women with locally advanced cervical cancer who were treated with radical or adjuvant concurrent chemoradiotherapy over a 5-year period, and had MRI scans performed in-house; the follow-up protocol had patients receiving scans at 3, 12, and 24 months post treatment. From an initial pool of 197 patients, those who had previously had pelvic radiation or were receiving palliative treatment, as well as those with incomplete imaging follow-up and those with metal implants or prostheses that could affect radiation therapy delivery or imaging quality were excluded.

The chemoradiotherapy protocol involved five doses of weekly cisplatin at 400 mg/m² of body surface area, as well as high–dose rate cervix brachytherapy. In practice, all but six participants received these treatments. Patients also received external beam radiotherapy with or without a simultaneous integrated boost to target affected lymph nodes, as clinically indicated.

The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema.

Patients were aged a median of 54 years, and 64 (56%) were postmenopausal. Most patients (n = 84; 73%) had never used tobacco. Participants’ median body mass index was 26 kg/m².

Most patients (n = 73; 64%) were International Federation of Gynecology and Obstetrics stage 2b, and almost half (n = 55; 48%) had pelvic nodal involvement.

Patients were followed for a median of 12 months, with patients receiving a median of two MRIs curing that period. In all, 105 fractures were identified in 44 patients. A median of two fractures were identified among the group of patients who had pelvic insufficiency fractures.

The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema. In this schema, 41% of identified fractures were considered mild, while 32% were moderate and 12% were severe.

Although just over two-thirds of fractures (70%) were identified within 6 months of beginning surveillance, a quarter were not identified until 9-13 months post therapy, and 5% were found after more than 13 months.

Sacral fractures accounted for 72% of those identified, in keeping with previous findings, said Dr. Dragan. Acetabular and pubic fractures made up 16% and 10% of fractures, respectively. One fracture was seen at the ilium and one at the ischium.

Dr. Dragan and colleagues turned to multivariable analysis to look for risk factors for pelvic insufficiency fractures in this cohort of cervical cancer patients. Younger patients had a hazard ratio of 0.30 for fracture, compared with those over the age of 50 years (P less than .01). Similarly, being menopausal carried a hazard ratio of 2.25 for fracture. Higher radiation doses to the sacrum also boosted fracture risk (HR, 2.00; P = .03). Neither sacral volume and slope nor the receipt of simultaneous integrated boost were associated with increased fracture risk.

Dr. Dragan reported that she had no relevant conflicts of interest. She reported no outside sources of funding.
 

SOURCE: Dragan A et al. RSNA 2019, Presentation SSE25-03.

CHICAGO – Radiation therapy for cervical cancer resulted in pelvic insufficiency fractures more frequently than previously thought, and many fractures were slow to heal, according to research presented at the annual meeting of the Radiological Society of North America.

“Pelvic insufficiency fractures had a prevalence of 38% on MRI follow-up” after chemoradiotherapy for locally advanced cervical cancer, said Alina Dragan, MD. This figure is more than double the previously reported prevalence of about 14%.

Dr. Dragan, a radiology resident at London North West Healthcare, National Health Service Trust, and coinvestigators also tracked the natural history of these fractures over time, to fill a knowledge gap about whether, and at what rate, these pelvic insufficiency fractures healed.

In the single-center retrospective study, the investigators found that just 14% of sacral fractures healed during the period of observation. For acetabular and pubic fractures, roughly one in three fractures had healed by the last MRI scan. About a third of all fractures remained stable across scans, while just over 10% of fractures were either fluctuant or worsened.

The study included 115 women with locally advanced cervical cancer who were treated with radical or adjuvant concurrent chemoradiotherapy over a 5-year period, and had MRI scans performed in-house; the follow-up protocol had patients receiving scans at 3, 12, and 24 months post treatment. From an initial pool of 197 patients, those who had previously had pelvic radiation or were receiving palliative treatment, as well as those with incomplete imaging follow-up and those with metal implants or prostheses that could affect radiation therapy delivery or imaging quality were excluded.

The chemoradiotherapy protocol involved five doses of weekly cisplatin at 400 mg/m² of body surface area, as well as high–dose rate cervix brachytherapy. In practice, all but six participants received these treatments. Patients also received external beam radiotherapy with or without a simultaneous integrated boost to target affected lymph nodes, as clinically indicated.

The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema.

Patients were aged a median of 54 years, and 64 (56%) were postmenopausal. Most patients (n = 84; 73%) had never used tobacco. Participants’ median body mass index was 26 kg/m².

Most patients (n = 73; 64%) were International Federation of Gynecology and Obstetrics stage 2b, and almost half (n = 55; 48%) had pelvic nodal involvement.

Patients were followed for a median of 12 months, with patients receiving a median of two MRIs curing that period. In all, 105 fractures were identified in 44 patients. A median of two fractures were identified among the group of patients who had pelvic insufficiency fractures.

The fractures were graded as mild, moderate, or severe by the interpreting radiologist according to the course of the fracture line and corresponding bone edema. In this schema, 41% of identified fractures were considered mild, while 32% were moderate and 12% were severe.

Although just over two-thirds of fractures (70%) were identified within 6 months of beginning surveillance, a quarter were not identified until 9-13 months post therapy, and 5% were found after more than 13 months.

Sacral fractures accounted for 72% of those identified, in keeping with previous findings, said Dr. Dragan. Acetabular and pubic fractures made up 16% and 10% of fractures, respectively. One fracture was seen at the ilium and one at the ischium.

Dr. Dragan and colleagues turned to multivariable analysis to look for risk factors for pelvic insufficiency fractures in this cohort of cervical cancer patients. Younger patients had a hazard ratio of 0.30 for fracture, compared with those over the age of 50 years (P less than .01). Similarly, being menopausal carried a hazard ratio of 2.25 for fracture. Higher radiation doses to the sacrum also boosted fracture risk (HR, 2.00; P = .03). Neither sacral volume and slope nor the receipt of simultaneous integrated boost were associated with increased fracture risk.

Dr. Dragan reported that she had no relevant conflicts of interest. She reported no outside sources of funding.
 

SOURCE: Dragan A et al. RSNA 2019, Presentation SSE25-03.

Most young women with epithelial ovarian cancer can undergo surgery preserving the unaffected ovary and uterus – and thus their fertility – without compromising their survival, a cohort study of more than 9,000 women in Cancer suggests.

“Loss of reproductive capability and surgical menopause can negatively affect survivorship and quality of life among young women with ovarian cancer,” noted the investigators, who were led by Sarah M. Crafton, MD, division of gynecologic oncology, Allegheny Health Network in Pittsburgh. “ASCO has published guidelines to address the importance of implementing fertility preservation counseling as standard of care for all patients of reproductive age with cancer. However, the safety of such procedures should be thoroughly assessed in ongoing analyses.”

Dr. Crafton and colleagues used the Surveillance, Epidemiology, and End Results (SEER) program database and the National Cancer Database (NCDB) to retrospectively identify women 44 years old or younger with a primary epithelial ovarian cancer. The women were classified as having undergone surgery that spared fertility (unilateral salpingo-oophorectomy with uterine preservation) or surgery that did not (bilateral salpingo-oophorectomy with hysterectomy).

Study results, reported in Cancer, were based on 9,017 women – 3,932 from the SEER database and 5,085 from the NCDB – with epithelial ovarian cancer diagnosed between the ages of 15 and 44 years. Median follow-up was 6.5 years in SEER and 4.6 years in NCDB.

Overall, 26.1% of the SEER cohort and 24.8% of the NCDB cohort had undergone fertility-sparing surgery. In both cohorts, odds of this surgery were higher among younger women, those with a more recent ovarian cancer diagnosis, and those who did not receive adjuvant chemotherapy.

Among women with stage II-IV serous epithelial ovarian cancer in the SEER cohort, those who underwent fertility-sparing surgery had poorer overall survival (hazard ratio for death, 1.61; P = .0008). However, fertility-sparing surgery was not significantly associated with survival in other SEER subgroups defined by stage and grade or by stage and histology or in any NCDB subgroup defined by these parameters.

“In general, our findings regarding survival support the current National Comprehensive Cancer Network recommendation that fertility-sparing surgery can be considered as an alternative for traditional, comprehensive staging for those patients who desire fertility, for whom ovarian retention is technically feasible, and who have early-stage disease,” Dr. Crafton and coinvestigators wrote.

“Our observation of an increased risk of death associated with fertility-sparing surgery among women with advanced-stage, serous epithelial ovarian cancer in the SEER population supports the clinical recommendation that the decision to pursue fertility-sparing surgery should be individualized on the basis of patient/provider counseling and disease characteristics,” they concluded.

Dr. Crafton did not report any disclosures. The study was supported by the National Cancer Institute.

SOURCE: Crafton SM et al. Cancer. 2019 Nov 27. doi: 10.1002/cncr.32620.

Most young women with epithelial ovarian cancer can undergo surgery preserving the unaffected ovary and uterus – and thus their fertility – without compromising their survival, a cohort study of more than 9,000 women in Cancer suggests.

“Loss of reproductive capability and surgical menopause can negatively affect survivorship and quality of life among young women with ovarian cancer,” noted the investigators, who were led by Sarah M. Crafton, MD, division of gynecologic oncology, Allegheny Health Network in Pittsburgh. “ASCO has published guidelines to address the importance of implementing fertility preservation counseling as standard of care for all patients of reproductive age with cancer. However, the safety of such procedures should be thoroughly assessed in ongoing analyses.”

Dr. Crafton and colleagues used the Surveillance, Epidemiology, and End Results (SEER) program database and the National Cancer Database (NCDB) to retrospectively identify women 44 years old or younger with a primary epithelial ovarian cancer. The women were classified as having undergone surgery that spared fertility (unilateral salpingo-oophorectomy with uterine preservation) or surgery that did not (bilateral salpingo-oophorectomy with hysterectomy).

Study results, reported in Cancer, were based on 9,017 women – 3,932 from the SEER database and 5,085 from the NCDB – with epithelial ovarian cancer diagnosed between the ages of 15 and 44 years. Median follow-up was 6.5 years in SEER and 4.6 years in NCDB.

Overall, 26.1% of the SEER cohort and 24.8% of the NCDB cohort had undergone fertility-sparing surgery. In both cohorts, odds of this surgery were higher among younger women, those with a more recent ovarian cancer diagnosis, and those who did not receive adjuvant chemotherapy.

Among women with stage II-IV serous epithelial ovarian cancer in the SEER cohort, those who underwent fertility-sparing surgery had poorer overall survival (hazard ratio for death, 1.61; P = .0008). However, fertility-sparing surgery was not significantly associated with survival in other SEER subgroups defined by stage and grade or by stage and histology or in any NCDB subgroup defined by these parameters.

“In general, our findings regarding survival support the current National Comprehensive Cancer Network recommendation that fertility-sparing surgery can be considered as an alternative for traditional, comprehensive staging for those patients who desire fertility, for whom ovarian retention is technically feasible, and who have early-stage disease,” Dr. Crafton and coinvestigators wrote.

“Our observation of an increased risk of death associated with fertility-sparing surgery among women with advanced-stage, serous epithelial ovarian cancer in the SEER population supports the clinical recommendation that the decision to pursue fertility-sparing surgery should be individualized on the basis of patient/provider counseling and disease characteristics,” they concluded.

Dr. Crafton did not report any disclosures. The study was supported by the National Cancer Institute.

SOURCE: Crafton SM et al. Cancer. 2019 Nov 27. doi: 10.1002/cncr.32620.

Most young women with epithelial ovarian cancer can undergo surgery preserving the unaffected ovary and uterus – and thus their fertility – without compromising their survival, a cohort study of more than 9,000 women in Cancer suggests.

“Loss of reproductive capability and surgical menopause can negatively affect survivorship and quality of life among young women with ovarian cancer,” noted the investigators, who were led by Sarah M. Crafton, MD, division of gynecologic oncology, Allegheny Health Network in Pittsburgh. “ASCO has published guidelines to address the importance of implementing fertility preservation counseling as standard of care for all patients of reproductive age with cancer. However, the safety of such procedures should be thoroughly assessed in ongoing analyses.”

Dr. Crafton and colleagues used the Surveillance, Epidemiology, and End Results (SEER) program database and the National Cancer Database (NCDB) to retrospectively identify women 44 years old or younger with a primary epithelial ovarian cancer. The women were classified as having undergone surgery that spared fertility (unilateral salpingo-oophorectomy with uterine preservation) or surgery that did not (bilateral salpingo-oophorectomy with hysterectomy).

Study results, reported in Cancer, were based on 9,017 women – 3,932 from the SEER database and 5,085 from the NCDB – with epithelial ovarian cancer diagnosed between the ages of 15 and 44 years. Median follow-up was 6.5 years in SEER and 4.6 years in NCDB.

Overall, 26.1% of the SEER cohort and 24.8% of the NCDB cohort had undergone fertility-sparing surgery. In both cohorts, odds of this surgery were higher among younger women, those with a more recent ovarian cancer diagnosis, and those who did not receive adjuvant chemotherapy.

Among women with stage II-IV serous epithelial ovarian cancer in the SEER cohort, those who underwent fertility-sparing surgery had poorer overall survival (hazard ratio for death, 1.61; P = .0008). However, fertility-sparing surgery was not significantly associated with survival in other SEER subgroups defined by stage and grade or by stage and histology or in any NCDB subgroup defined by these parameters.

“In general, our findings regarding survival support the current National Comprehensive Cancer Network recommendation that fertility-sparing surgery can be considered as an alternative for traditional, comprehensive staging for those patients who desire fertility, for whom ovarian retention is technically feasible, and who have early-stage disease,” Dr. Crafton and coinvestigators wrote.

“Our observation of an increased risk of death associated with fertility-sparing surgery among women with advanced-stage, serous epithelial ovarian cancer in the SEER population supports the clinical recommendation that the decision to pursue fertility-sparing surgery should be individualized on the basis of patient/provider counseling and disease characteristics,” they concluded.

Dr. Crafton did not report any disclosures. The study was supported by the National Cancer Institute.

SOURCE: Crafton SM et al. Cancer. 2019 Nov 27. doi: 10.1002/cncr.32620.

Sequential chemoradiotherapy (CRT) and immunotherapy is safe, well tolerated, and efficacious among patients with locally advanced cervical cancer being treated with curative intent, a multicenter phase 1 trial suggests.

Less than 10% of patients treated with this sequence experienced a grade 3 toxicity. Meanwhile, more than 80% were alive and free of disease progression at 1 year.

“Despite standard CRT, most women with lymph node–positive cervical cancer experience disease recurrence,” note the investigators, led by Jyoti S. Mayadev, MD, associate professor in the department of radiation medicine and applied sciences, University of California, San Diego, in La Jolla. “Our study is potentially transformative in the standard treatment schema of locally advanced cervical cancer, with the prospect for immuno-oncology to add durable survival in patients with node-positive disease, a current unmet oncologic need.”

The investigators enrolled in the trial 32 women from Gynecology Oncology Cooperative Group member institutions who had stage IB2 to IVA cervical cancer with positive pelvic and/or para-aortic lymph nodes. Treatment consisted of six weekly doses of cisplatin, 40 mg/m², concurrent with extended-field, 3-dimensional conformal radiotherapy, followed by the immune checkpoint inhibitor ipilimumab (Yervoy) every 21 days for four cycles.

Results reported in JAMA Oncology showed that all 32 patients completed CRT and 21 patients went on to receive ipilimumab. Among the latter, 86% completed all four planned cycles and the rest completed two cycles.

In the group receiving sequential CRT and ipilimumab, 9.5% experienced grade 3 toxicity (lipase increase in one case and dermatitis in another case). Both toxicities were self-limited.

With a 14.8-month median follow-up, the patients treated with CRT-ipilimumab had a 12-month overall survival rate of 90%, and a 12-month progression-free survival rate of 81% (median durations were not reached). Neither human papillomavirus genotype nor HLA subtype was associated with these outcomes.

Translational analyses showed that patients experienced an increase in peripheral blood T cells expressing programmed cell death 1 (PD-1) after CRT that was then sustained with ipilimumab therapy. “[T]he use of an immune checkpoint inhibitor could stimulate the antitumor activity of tumor-specific cytotoxic T cells and augment radiation-induced neoantigen load,” the investigators proposed.

“To our knowledge, this phase 1 study is the first to show tolerability with a signal of efficacy of an immune check-point inhibitor ... as a part of the definitive treatment of locally advanced cervical cancer,” they concluded. “Our findings show promise for the use of immunotherapy in the definitive setting of locally advanced, node-positive cervical cancer; patients with this cancer historically have a poor prognosis with standard therapy alone.”

Dr. Mayadev disclosed receiving a grant from the National Cancer Institute during the conduct of the study, personal fees from AstraZeneca, grants from NRG Oncology, and personal fees and nonfinancial support from the Gynecology Oncology Group Foundation outside the submitted work; receiving compensation for serving on the advisory board of Varian Medical Systems in 2018; and being a speaker for Samsung Medical Systems in 2017. The study was supported by the National Cancer Institute and by institutional funds.

SOURCE: Mayadev JS et al. JAMA Oncol. 2019 Nov 27. doi: 10.1001/jamaoncol.2019.3857.

Sequential chemoradiotherapy (CRT) and immunotherapy is safe, well tolerated, and efficacious among patients with locally advanced cervical cancer being treated with curative intent, a multicenter phase 1 trial suggests.

Less than 10% of patients treated with this sequence experienced a grade 3 toxicity. Meanwhile, more than 80% were alive and free of disease progression at 1 year.

“Despite standard CRT, most women with lymph node–positive cervical cancer experience disease recurrence,” note the investigators, led by Jyoti S. Mayadev, MD, associate professor in the department of radiation medicine and applied sciences, University of California, San Diego, in La Jolla. “Our study is potentially transformative in the standard treatment schema of locally advanced cervical cancer, with the prospect for immuno-oncology to add durable survival in patients with node-positive disease, a current unmet oncologic need.”

The investigators enrolled in the trial 32 women from Gynecology Oncology Cooperative Group member institutions who had stage IB2 to IVA cervical cancer with positive pelvic and/or para-aortic lymph nodes. Treatment consisted of six weekly doses of cisplatin, 40 mg/m², concurrent with extended-field, 3-dimensional conformal radiotherapy, followed by the immune checkpoint inhibitor ipilimumab (Yervoy) every 21 days for four cycles.

Results reported in JAMA Oncology showed that all 32 patients completed CRT and 21 patients went on to receive ipilimumab. Among the latter, 86% completed all four planned cycles and the rest completed two cycles.

In the group receiving sequential CRT and ipilimumab, 9.5% experienced grade 3 toxicity (lipase increase in one case and dermatitis in another case). Both toxicities were self-limited.

With a 14.8-month median follow-up, the patients treated with CRT-ipilimumab had a 12-month overall survival rate of 90%, and a 12-month progression-free survival rate of 81% (median durations were not reached). Neither human papillomavirus genotype nor HLA subtype was associated with these outcomes.

Translational analyses showed that patients experienced an increase in peripheral blood T cells expressing programmed cell death 1 (PD-1) after CRT that was then sustained with ipilimumab therapy. “[T]he use of an immune checkpoint inhibitor could stimulate the antitumor activity of tumor-specific cytotoxic T cells and augment radiation-induced neoantigen load,” the investigators proposed.

“To our knowledge, this phase 1 study is the first to show tolerability with a signal of efficacy of an immune check-point inhibitor ... as a part of the definitive treatment of locally advanced cervical cancer,” they concluded. “Our findings show promise for the use of immunotherapy in the definitive setting of locally advanced, node-positive cervical cancer; patients with this cancer historically have a poor prognosis with standard therapy alone.”

Dr. Mayadev disclosed receiving a grant from the National Cancer Institute during the conduct of the study, personal fees from AstraZeneca, grants from NRG Oncology, and personal fees and nonfinancial support from the Gynecology Oncology Group Foundation outside the submitted work; receiving compensation for serving on the advisory board of Varian Medical Systems in 2018; and being a speaker for Samsung Medical Systems in 2017. The study was supported by the National Cancer Institute and by institutional funds.

SOURCE: Mayadev JS et al. JAMA Oncol. 2019 Nov 27. doi: 10.1001/jamaoncol.2019.3857.

Sequential chemoradiotherapy (CRT) and immunotherapy is safe, well tolerated, and efficacious among patients with locally advanced cervical cancer being treated with curative intent, a multicenter phase 1 trial suggests.

Less than 10% of patients treated with this sequence experienced a grade 3 toxicity. Meanwhile, more than 80% were alive and free of disease progression at 1 year.

“Despite standard CRT, most women with lymph node–positive cervical cancer experience disease recurrence,” note the investigators, led by Jyoti S. Mayadev, MD, associate professor in the department of radiation medicine and applied sciences, University of California, San Diego, in La Jolla. “Our study is potentially transformative in the standard treatment schema of locally advanced cervical cancer, with the prospect for immuno-oncology to add durable survival in patients with node-positive disease, a current unmet oncologic need.”

The investigators enrolled in the trial 32 women from Gynecology Oncology Cooperative Group member institutions who had stage IB2 to IVA cervical cancer with positive pelvic and/or para-aortic lymph nodes. Treatment consisted of six weekly doses of cisplatin, 40 mg/m², concurrent with extended-field, 3-dimensional conformal radiotherapy, followed by the immune checkpoint inhibitor ipilimumab (Yervoy) every 21 days for four cycles.

Results reported in JAMA Oncology showed that all 32 patients completed CRT and 21 patients went on to receive ipilimumab. Among the latter, 86% completed all four planned cycles and the rest completed two cycles.

In the group receiving sequential CRT and ipilimumab, 9.5% experienced grade 3 toxicity (lipase increase in one case and dermatitis in another case). Both toxicities were self-limited.

With a 14.8-month median follow-up, the patients treated with CRT-ipilimumab had a 12-month overall survival rate of 90%, and a 12-month progression-free survival rate of 81% (median durations were not reached). Neither human papillomavirus genotype nor HLA subtype was associated with these outcomes.

Translational analyses showed that patients experienced an increase in peripheral blood T cells expressing programmed cell death 1 (PD-1) after CRT that was then sustained with ipilimumab therapy. “[T]he use of an immune checkpoint inhibitor could stimulate the antitumor activity of tumor-specific cytotoxic T cells and augment radiation-induced neoantigen load,” the investigators proposed.

“To our knowledge, this phase 1 study is the first to show tolerability with a signal of efficacy of an immune check-point inhibitor ... as a part of the definitive treatment of locally advanced cervical cancer,” they concluded. “Our findings show promise for the use of immunotherapy in the definitive setting of locally advanced, node-positive cervical cancer; patients with this cancer historically have a poor prognosis with standard therapy alone.”

Dr. Mayadev disclosed receiving a grant from the National Cancer Institute during the conduct of the study, personal fees from AstraZeneca, grants from NRG Oncology, and personal fees and nonfinancial support from the Gynecology Oncology Group Foundation outside the submitted work; receiving compensation for serving on the advisory board of Varian Medical Systems in 2018; and being a speaker for Samsung Medical Systems in 2017. The study was supported by the National Cancer Institute and by institutional funds.

SOURCE: Mayadev JS et al. JAMA Oncol. 2019 Nov 27. doi: 10.1001/jamaoncol.2019.3857.