Abstract

<b>Objectives:</b> To assess treatment response and disease outcomes in frail patients with advanced-stage ovarian cancer who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). <b>Methods:</b> This is a retrospective cohort study of women with advanced-stage ovarian cancer treated from April 2012 to June 2020 across three medical centers. Patients underwent either primary or interval cytoreduction followed by HIPEC administered with closed technique. A frailty score modified from the Johns Hopkins Frailty Assessment Calculator was assigned to each patient. Its components included age, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) status, number of comorbid conditions, and albumin. Points were assigned on a sliding scale using information, including age older than 60, underweight, overweight, or obese, ECOG greater than or equal to one, the number of comorbid conditions, and albumin less than 4. A frailty score greater than 2.7 (average score) indicated frail, and below 2.7 indicated non-frail. Perioperative outcomes were compared between frail and non-frail patients via univariate and multivariate analysis. Statistical analysis was completed with Chi-square and Fisher's exact test for categorical outcomes, Wilcoxon rank-sum test for continuous variables, and Kaplan-Meier method using the log-rank test for disease-free survival (DFS) and overall survival (OS). <b>Results:</b> A total of 43 patients were included in our study cohort. The median age was 61 years (range: 34-81), and most patients were non-Hispanic White (23; 53.5%). Twenty-seven (63%) patients had stage III disease, while 16 (37%) patients had stage IV disease. Thirty-eight (88%) patients underwent interval CRS with HIPEC, and five (12%) patients underwent primary CRS with HIPEC. Patients received a median of three cycles (range: 0-4) of neoadjuvant and four cycles (range: 0-10) of postoperative platinum-based chemotherapy. Of the available records, six patients (14%) had germline or somatic <i>BRCA</i> mutation, and 28 were known <i>BRCA</i> wild-type (65%). Ethnicity (<i>p</i>=0.08), tumor histology (<i>p</i>=1), duration of surgery (<i>p</i>=0.90), use of neoadjuvant chemotherapy (<i>p</i>=0.95), maintenance therapy (<i>p</i>=0.36), recurrence (<i>p</i>=0.40), and adverse events were all non-significant between frail and non-frail patients. Although not significant, 100% of non-frail patients achieved R0 cytoreduction versus only 88% of frail patients. Frail patients were more likely to have a longer length of stay in the intensive care unit (ICU) (1.6 vs 4.5, <i>p</i>= 0.02). Frail patients had a longer hospital length of stay in general, although this was not significant in this cohort (9.0 vs 11.7, <i>p</i>=0.12). With a median follow-up of 29 months, the median DFS was 11.1 months versus 18.4 months (p=0.20) for frail and non-frail patients, respectively. <b>Conclusions:</b> While data exists for the use of HIPEC in the initial management of advanced-stage ovarian cancer, frail patients are at higher risk of longer ICU stays. Frail patients were less likely to have R0 cytoreduction. Immediate postoperative outcomes appear overall similar in frail versus non-frail patients who undergo HIPEC. Further prospective studies are needed in frail patients to better quantify the risk-benefit discussion for the use of HIPEC.

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