Assessment of Medical Students' Knowledge of Lynch Syndrome Cancers, Screening, and Prevention
Background: Lynch syndrome accounts for 3% of newly diagnosed endometrial cancers and colon cancers. Identifying patients with Lynch syndrome is fundamental to enable proper screening and prevention of at-risk malignancies, along with encouraging cascade testing of family members. We aimed to assess medical students' knowledge of Lynch syndrome-associated cancers and screening and prevention measures to decrease malignancy risk in patients with Lynch syn-drome.
Method(s): An anonymous, voluntary, multiple-choice survey was emailed to 14 medical schools throughout the US to evaluate medical students' knowledge of Lynch syndrome.
Result(s): We surveyed 342 medical students, and 65% were third or fourth-year medical students. Ninety-three percent knew that colon cancer is one of two most commonly diagnosed cancers in Lynch syndrome; however, only 37% knew endometrial cancer was the other most common malignancy in Lynch syndrome patients. Fifty-nine percent of students recognized that 2-5% of all newly diagnosed endometrial and colon cancers are due to Lynch syndrome. Ninety-one percent recognized a family history that would indicate evaluation for Lynch syndrome, but only 49% knew that all patients diagnosed with endometrial cancer prior to age 50 should be evaluated for Lynch syndrome as per the National Comprehensive Cancer Network guidelines regardless of other risk fac-tors.
Conclusion(s): Almost two-thirds of medical students did not recognize endometrial cancer as a common Lynch syndrome malignancy and less than 50% were aware of when to evaluate patients with endometrial cancer for Lynch syndrome; comparatively almost all students recognized the link between colon cancer and Lynch syndrome. Curriculum change with targeted education regarding en-dometrial cancer and Lynch syndrome during medical school obstetrics and gynecology clinical ro-tations should be implemented. This call to action is critical in improving the diagnosis of Lynch syndrome, evaluation, screening, and prevention of cancers in both patients and family members to reduce mortality.
Impact of disease progression on health-related quality of life of advanced ovarian cancer patients - Pooled analysis from the PRIMA trial
OBJECTIVE:Progression-free survival (PFS) is an important early efficacy endpoint in ovarian cancer (OC) and its relevance to patients should be assessed. PRIMA, a phase III trial, assessed niraparib in patients with OC; this post hoc analysis examined the relationship between disease progression in OC and health-related quality of life (HRQoL). METHODS:The PRIMA trial randomized patients with advanced OC responsive to first-line platinum-based chemotherapy to once daily maintenance oral niraparib or placebo. This post hoc analysis evaluated the impact of disease progression on HRQoL by comparing HRQoL at the last visit pre-progression to end of treatment (EoT), and after 4, 8, 12, and 24 weeks. Assessments included the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), the European Quality of Life Five Dimension Five Level questionnaire (EQ-5D-5L) and EQ Visual Analogue Scale (EQ-VAS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC-QLQ-C30), and the EORTC Quality of Life Questionnaire Ovarian Cancer module (EORTC-QLQ-OV28). RESULTS:This post hoc analysis included 733 patients. Mean FOSI, EQ-5D-5L, and EQ-VAS scores deteriorated from last visit pre-progression to EoT and remained low up to 24-week follow-up. Least squares mean changes from last visit pre-progression to EoT were -2.1 (95% confidence interval -2.4, -1.7) for FOSI, -4.6 (-5.6, -3.5) for the EQ-5D-5L index, and -7.9 (-9.6, -6.3) for EQ-VAS. CONCLUSIONS:Disease progression negatively impacted HRQoL in patients with OC. PFS is clinically relevant, and prolonging PFS may preserve HRQoL.
Immunotherapy toxicities: An SGO clinical practice statement
Practice changing cervical cancer clinical trials [Editorial]
Appropriate Selection of PARP Inhibitors in Ovarian Cancer
OPINION STATEMENT/UNASSIGNED:Poly-ADP-ribose polymerase inhibitors (PARPi) are a class of anti-cancer drugs that target DNA repair pathways and have shown promising efficacy in patients with ovarian cancer in recent clinical trials. To date, there have been 9 FDA PARPi approvals/indications in ovarian cancer since 2014, highlighting the importance of this class of agents in the treatment of ovarian cancer. BRCA1/2-mutated tumors or other forms of homologous recombination deficient (HRD) tumors are particularly susceptible to PARP inhibition and have seen the greatest benefits of improvement in response rate and progression-free survival (PFS) in clinical trials. Patients with homologous recombination-proficient tumors also receive benefit, especially when a nice response to paltinum is noted, but to a lesser extent. PARP inhibitors now have FDA approval and indications in first-line and recurrent maintenance, and treatment. PARP inhibitor use as maintenance therapy in the front-line setting is now considered the standard of care in patients with BRCA1/2 mutations based on the SOLO-1/GOG-3004/ENGOT study. PARP inhibitors are also recommended per ASCO guidelines in all patients with ovarian cancer as front-line maintenance therapy based on the PRIMA/ENGOT-OV26/GOG-3012 trial. The combination of PARP inhibitor, olaparib, and the anti-angiogenesis inhibitor bevacizumab is also approved as maintenance therapy after front-line chemotherapy treatment in patients with HRD tumors and is an option for patients who have initiated bevacizumab with their chemotherapy treatment. PARPi are also FDA approved and can be utilized as a treatment in third-line and beyond in recurrent ovarian cancer patients with BRCA1/2 mutations and HRD tumors. In this review, we will cover in detail when PARP inhibitor use is appropriate in ovarian cancer, as well as the various clinical factors to take into consideration when selecting a PARP inhibitor regimen.
Utility of germline multi-gene panel testing in patients with endometrial cancer
OBJECTIVES/OBJECTIVE:Patients with germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) associated with Lynch syndrome (LS) have an increased lifetime risk of endometrial cancer (EC). Multi-gene panel testing (MGPT) is a recent hereditary cancer risk tool enabling next-generation sequencing of numerous genes in parallel. We determined the prevalence of actionable cancer predisposition gene mutations identified through MGPT in an EC patient cohort. METHODS:A single center retrospective cohort study was conducted of patients with EC who had a clinical indication for genetic testing and who underwent MGPT as part of standard of care treatment between 2012 and 2021. Pathogenic mutations were identified and actionable mutations were defined as those with clinical management implications. Additionally, the number of individuals identified with LS was compared between MGPT and tumor-based screening. RESULTS:The study included a total of 224 patients. Thirty-three patients [14.7%, 95% confidence interval (CI) = 10.4-20.1] had actionable mutations. Twenty-one patients (9.4%, 95% CI = 5.9-14.0) had mutations in LS genes (4 MLH1, 5 MSH2, 7 MSH6, 4 PMS2, 1 Epcam-MSH2). MGPT revealed two patients with LS (9.5% of LS cases) not identified through routine tumor-based screening. Thirteen patients (5.8%, 95% CI = 3.1-9.7) had at least one actionable mutation in a non-Lynch syndrome gene (6 CHEK2, 2 BRCA2, 2 ATM, 2 APC, 1 RAD51C, 1 BRCA1). CONCLUSIONS:Germline MGPT is both feasible and informative as it identifies LS cases not found on tumor testing as well as additional actionable mutations in patients with EC.
In memoriam: Franco M Muggia [Letter]
COVID-19 outcomes of patients with gynecologic cancer in New York City: An updated analysis from the initial surge of the pandemic
BACKGROUND:Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS:Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS:Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0Â years (interquartile range (IQR), 53.0-73.0Â years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an ageÂ â‰¥Â 65Â years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status â‰¥2 (OR 3.67, CI 1.25, 13.55) andÂ â‰¥Â 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90Â days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS:The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.
Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study
BACKGROUND:Dostarlimab is a humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. We report interim data from patients with endometrial cancer (EC) participating in a phase I trial of single-agent dostarlimab. METHODS:GARNET, an ongoing, single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumors, is being undertaken at 123 sites. Two cohorts of patients with EC were recruited: those with dMMR/MSI-H disease (cohort A1) and those with proficient/stable (MMRp/MSS) disease (cohort A2). Patients received dostarlimab 500â€‰mg every 3 weeks for 4 cycles, then dostarlimab 1000â€‰mg every 6 weeks until disease progression. The primary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST V.1.1, as assessed by blinded independent central review. RESULTS:Screening began on April 10, 2017, and 129 and 161 patients with advanced EC were enrolled in cohorts A1 and A2, respectively. The median follow-up duration was 16.3 months (IQR 9.5-22.1) for cohort A1 and 11.5 months (IQR 11.0-25.1) for cohort A2. In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses. In cohort A2, ORR was 14.1% (95% CI 9.1% to 20.6%) with three complete responses and 19 partial responses. Median DOR was not reached in either cohort. In the combined cohorts, the majority of treatment-related adverse events (TRAEs) were grade 1-2 (75.5%), most commonly fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%). Gradeâ‰¥3 TRAEs occurred in 16.6% of patients, and 5.5% discontinued dostarlimab because of TRAEs. No deaths were attributable to dostarlimab. CONCLUSION:Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile. TRIAL REGISTRATION NUMBER:NCT02715284.
Optimizing Robotic Hysterectomy for the Morbidly Obese Patient with a Surgical Safety Pathway
STUDY OBJECTIVE/OBJECTIVE:Obesity is a growing worldwide epidemic, and obese patients undergoing gynecologic robotic surgery are at increased risk for surgical complications. This study aimed to evaluate the feasibility and outcomes of a surgical safety protocol known as the High BMI pathway (HBP) for patients with a body mass index (BMI) of 40 or greater undergoing planned robotic hysterectomy. Our primary outcome was rate of all-cause perioperative complications in patients undergoing surgery with the utilization of the HBP. DESIGN/METHODS:A retrospective cohort study. SETTING/METHODS:An academic teaching hospital. PATIENTS/METHODS:) undergoing robotic hysterectomy. INTERVENTIONS/METHODS:The HBP was developed by a multidisciplinary team and was instituted January 1, 2016 as a quality improvement project. Morbidly obese patients undergoing robotic hysterectomy after this date were compared to consecutive historic controls. MEASUREMENTS AND MAIN RESULTS/RESULTS:Seventy-two patients underwent robotic hysterectomies on the HBP and were compared to 66 controls. There were no differences in age, BMI, blood loss, number of comorbidities, or cancer diagnosis. Since the implementation of HBP, there has been a decrease in anesthesia time (-57.0 min; p=.001), total operating room time (-47.0 min; p=.020), lower estimated blood loss (median 150 cc [IQR 100-200] vs 200 cc [IQR 100-300]; p=.002), and overnight hospital admissions (33.3% vs 63.6%; p < 0.001). There were fewer all-cause complications seen in HBP (19.4% vs 37.9%; p=.023) and infectious complications (8.3% vs 33.3%; p=.001) and no increase in readmission rates (p=.400). In multivariable analysis, the HBP reduced all-cause complications (odds ratio [OR] 0.353; p=.010) after controlling for covariate (total time in OR). CONCLUSION/CONCLUSIONS:HBP is a feasible method of optimizing outcome for morbidly obese patients undergoing major gynecologic surgery. Initiation of HBP can lead to decreased all-cause complications and overnight hospital admissions without increasing readmission rates.