Re-Evaluating Chemotherapy Dosing Strategies for Ovarian Cancer: Impact of Sarcopenia.

We investigated the impact of sarcopenia on adjuvant chemotherapy dosing in advanced epithelial ovarian cancer (EOC). The chemotherapy dosing and toxicity of 173 eligible patients who underwent cytoreductive surgery and adjuvant chemotherapy at a single institution were analyzed. Patients with a skeletal muscle index less than 39 cm2/m2 measured on a CT scan were considered sarcopenic. Sarcopenic and non-sarcopenic patients were compared with regard to relative dose intensity (RDI), completion of scheduled chemotherapy, toxicity, and survival. A total of 62 (35.8%) women were sarcopenic. Sarcopenic women were less likely to complete at least six cycles of chemotherapy (83.9% vs. 95.5%, p = 0.02). The mean RDI for both carboplatin (80.4% vs. 89.4%, p = 0.03) and paclitaxel (91.9% vs. 104.1%, p = 0.03) was lower in sarcopenic patients compared to non-sarcopenic patients. Despite these differences in chemotherapy, there was no difference in neutropenia or median overall survival (3.99 vs. 4.57 years, p = 0.62) between the sarcopenic and non-sarcopenic women, respectively. This study highlights the importance of considering lean body mass instead of body weight or surface area in chemotherapy dosing formulas for sarcopenic women with advanced EOC. Further research is needed to optimize chemotherapy strategies based on individual body composition, potentially leading to improved dosing strategies in this population.

Muscle loss during cancer therapy is associated with poor outcomes in advanced ovarian cancer.

Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)-based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.

Quality is more important than quantity: pre-operative sarcopenia is associated with poor survival in advanced ovarian cancer.

BACKGROUND: Sarcopenia is prevalent among older patients with cancer and is associated with poor outcomes. OBJECTIVE: To explore the relationship between muscle mass, quality, and patient age with overall survival after surgery for advanced ovarian cancer. METHODS: Patients with advanced stage (IIIC/IV) ovarian cancer who underwent primary cytoreductive surgery between January 2006 and July 2016 were included. Body composition measures were calculated from pre-operative CT imaging: skeletal muscle index (skeletal muscle index=skeletal muscle area normalized for height), skeletal muscle density, and skeletal muscle gauge (product of skeletal muscle index and skeletal muscle density). Each measure was transformed to a z-score and evaluated for association with risk of death using Cox proportional hazards models. Recursive partitioning was used to classify patients into homogeneous subgroups considering age and skeletal muscle gauge as predictors of overall survival. RESULTS: The study included 429 patients (mean age 64.2 years). Increased age moderately correlated with decreased skeletal muscle gauge (r=-0.45). Decreasing skeletal muscle density and skeletal muscle gauge were significantly associated with increased risk of death; HR (95% CI) per 1-unit decrease in z-score of 1.24 (1.10 to 1.39) for skeletal muscle density and 1.27 (1.12 to 1.44) for skeletal muscle gauge. Associations were diluted after adjusting for age (1.13 (1.00 to 1.29) skeletal muscle density and 1.14 (0.99 to 1.30) skeletal muscle gauge). Recursive partitioning identified three subgroups: <60 years old, ≥60 years old with skeletal muscle gauge ≥937.3, and ≥60 years old with skeletal muscle gauge <937.3; median overall survival was 5.8, 3.3, and 2.3 years, respectively (p<0.001). CONCLUSIONS: Skeletal muscle gauge, a novel sarcopenia measure incorporating quantity and quality, was associated with poorer survival in patients with advanced ovarian cancer, particularly among patients older than 60. Expanding our knowledge of how sarcopenia relates to solid tumor outcomes among high-risk patients can modify our treatment approach.

Regional and practitioner variations in reporting infant mortality.

OBJECTIVE: Assess regional differences in categorization of preterm delivery outcomes and impact on variation in reported infant mortality rates. STUDY DESIGN: A 27-item questionnaire was distributed to 1072 practitioners associated with U.S. birth hospitals. Five clinical scenarios were created to identify how participants classify delivery outcomes. Statistical analysis included Chi-square analysis and multinomial logistic regression. RESULTS: 234 questionnaires were completed (response rate 22%). While >90% respondents classified a 14-week pregnancy loss with no sign of life as a miscarriage, only 22% would provide a fetal death certificate. Likewise, 37% would provide a certificate of live birth for a loss at 16 weeks with signs of life. There was notable regional variation in classifying these as live births (Northeast: 41%, Midwest: 44%, South: 13%, and West: 18%, p = .003). CONCLUSION: Regional practice variation in recording both live births and stillbirths was noted. Greater standardization in reporting practices may be warranted to improve the accuracy of reported birth outcomes in the U.S.

Advanced ovarian cancer patients identify opportunities for prehabilitation: A qualitative study.

Prehabilitation may modify frailty and increase resilience in a subset of ovarian cancer patients; however there is low adherence to most programs. Our aim was to investigate potential barriers and facilitators of prehabilitation during neoadjuvant chemotherapy (NACT). We identified 15 patients who underwent NACT from 2016 to 2018. Patients underwent a semi-structured one-on-one interview. Transcripts were coded by 4 independent reviewers to identify emerging themes related to patients' experience, functioning and exercise during chemotherapy. Data saturation occurred after 15 interviews. Patients had a mean age of 64 and were triaged to NACT for unresectable disease in 47% of cases. Patients were overall willing to participate in exercise during chemotherapy, including walking (93%), strength training (87%), and yoga or stretching (33%). Patients identified significant factors which would motivate them to exercise during treatment despite the stated barriers, including perceived benefit to overall health and well-being, improving cancer related outcomes and a supportive treatment community. In addition, the majority of patients cited advice from their physician to participate in an exercise program as highly motivating. Cancer and treatment related symptoms such as fatigue, pain, nausea and vomiting, and respiratory distress, as well as access to care, and social and mental barriers were most often identified by patients as barriers to exercise. Patients with advanced ovarian cancer demonstrated high motivation and willingness to exercise during chemotherapy, particularly when recommended by their healthcare team and when they believe there will be a direct benefit on treatment options or cancer cure.

Survival outcomes in patients with cervical cancer treated with open versus robotic radical hysterectomy: Our surgical pathology interrogation.

OBJECTIVE: To compare the survival outcomes and surgical radicality between women who underwent open versus robotic radical hysterectomy (RH) for early cervical cancer. METHODS: In this institutional retrospective study, patients with clinical stage IA2- IIA (FIGO 2009) squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who underwent either open or robotic RH between 2000 and 2017 were identified. Parametrial width and vaginal length were re-measured from pathology slides. An inverse propensity score weighting model was used to adjust selection bias. RESULTS: A total of 333 patients were included (181 open, 152 robotic). The median follow-up time was 130 months for the open group and 53 months for the robotic group. There were 31 (17.1%) recurrences in the open and 21 (13.8%) in the robotic group. The 5-year progression-free survival (PFS) for the robotic and open group were 79.0% and 90.5%, respectively (HR 2.37, 95% CI 1.40-4.02). Five-year overall survival (OS) were 85.8% and 95.3%, respectively (HR 3.17, 95% CI 1.76-5.70). The mean parametrial width was similar between the open and robotic groups (2.5 vs 2.4 cm, p = 0.99). Unique recurrences (38.1%, 8/21) were noted in the robotic group: 2 port-site, 4 peritoneal, and 2 carcinomatosis. The time to vaginal recurrence was shorter in the robotic group than the open group (p = 0.001). CONCLUSION: Patients who underwent robotic RH had inferior PFS and OS compared to open surgery. Surgical radicality according to pathology measurements was similar between the two approaches.

Nationwide salpingectomy rates for an indication of permanent contraception before and after published practice guidelines.

OBJECTIVE: To identify the nationwide rate of salpingectomy for permanent contraception before and after the January 2015 American College of Obstetricians and Gynecologists (ACOG) Committee Opinion, Salpingectomy for Ovarian Cancer Prevention. STUDY DESIGN: Using ICD-9/10 diagnosis and procedure codes within the Vizient database, we identify permanent contraception procedures with and without salpingectomy, among females 18-50 years old between January 2013 and January 2017. Subject, hospital characteristics and costs information were recorded. To determine the changes in salpingectomy rates over time analysis was conducted using the Cochran-Armitage trend test and logistic regression models. RESULTS: A total of 211,312 women across 303 Vizient-member hospitals underwent a permanent contraception procedure over the study period. Of these, 174,930 subjects were selected from 160 hospitals that contributed data over the full 49-month period. Overall, 25,882 (14.8%) subjects underwent a salpingectomy for an indication of permanent contraception. Higher salpingectomy rates were identified among larger (p<.0001), teaching (p<.0001) hospitals versus smaller, non-teaching hospitals and in subjects with commercial/private payers (p<.0001). A lower salpingectomy rate was observed in Northeast hospitals (p<.0001). Median total hospital costs differed by $25 between permanent contraceptions performed with and without salpingectomy. The proportion of salpingectomies was <1% in January 2013 slowly rising to 20.6% in October 2015 and then 61.5% by January 2017 (p<.0001). During the pre-opinion period (Jan 2013-Dec 2014) the monthly increase in the odds of salpingectomy was 6% (OR 1.06, 95% CI 1.05, 1.06) compared to a monthly increase of 18% (OR 1.18, 95% CI 1.18, 1.18) during the post-opinion period (Jan 2015-Jan 2017). CONCLUSIONS: The nationwide rate of salpingectomies for permanent contraception has steadily increased among Vizient-member hospitals since the ACOG committee opinion. IMPLICATIONS: Salpingectomy as an approach to permanent contraception in the United States is increasing since the ACOG Committee Opinion with differing utilization rates by hospital type, region, size, and patient payer types. Physician behavior may be influenced by practice guidelines but other factors mitigate the effect.

Continuous improvement in primary Debulking surgery for advanced ovarian cancer: Do increased complete gross resection rates independently lead to increased progression-free and overall survival?

OBJECTIVES: To assess complete gross resection (CGR) rates and survival outcomes in patients with advanced ovarian cancer who underwent primary debulking surgery (PDS) during a 13-year period in which specific changes to surgical paradigm were implemented. METHODS: We identified all patients with stage IIIB-IV high-grade ovarian carcinoma who underwent PDS at our institution, with the intent of maximal cytoreduction, from 1/2001-12/2013. Patients were categorized by year of PDS based on the implementation of surgical changes to our approach to ovarian cancer debulking (Group 1, 2001-2005; Group 2, 2006-2009; Group 3, 2010-2013). RESULTS: Among 978 patients, 78% had stage IIIC disease and 89% had disease of serous histology. Carcinomatosis was found in 81%, and 60% had bulky upper abdominal disease (UAD). Compared to Group 1, those who underwent PDS during the latter 2 time periods had higher ASA scores (p < 0.001), higher-stage disease (p < 0.001), and more often had carcinomatosis (p = 0.015) and bulky UAD (p = 0.009). CGR rates for Groups 1-3 increased from 29% to 40% to 55%, respectively (p < 0.001). Five-year progression-free survival (PFS) rates increased over time (15%, 16%, and 20%, respectively; p = 0.199), as did 5-year overall survival (OS) rates (40%, 44%, and 56%, respectively; p < 0.001). On multivariable analysis, CGR was independently associated with PFS (p < 0.001) and OS (p < 0.001). CONCLUSIONS: Despite higher-stage disease and greater tumor burden, CGR rates, PFS and OS for patients who underwent PDS increased over a 13-year period. Surgical paradigm shifts implemented specifically to achieve more complete surgical cytoreduction are likely the reason for these improvements.