Faculty Bibliography

OBJECTIVES:The aim of this study was to investigate the impact of body mass index (BMI) on completion, complications, and clinical outcomes of intraperitoneal (IP) chemotherapy in patients with advanced-stage ovarian cancer. METHODS:Patients with optimally cytoreduced International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer treated with IP chemotherapy were retrospectively identified using an institutional review board-approved database. Clinical data were abstracted from the longitudinal medical record. Survival estimates were calculated using the Kaplan-Meier method. RESULTS:Ninety-two patients (35.5%) completed at least one cycle of IP chemotherapy. For these patients, there was no difference in histology, surgical complexity, or degree of cytoreduction based on BMI. Sixty-five percent of normal weight, 70% of overweight, and 59.1% of obese women completed 6 cycles (P = 0.697). There was also no significant difference in IP chemotherapy complications (P = 0.303). Body mass index had no impact on disease-free survival (P = 0.44) or overall survival, with a median overall survival of 68.5 months for normal weight, 65.9 months for overweight, and 61.7 months for obese women (P = 0.25). However, on multivariate analysis, obesity had an odds ratio of 2.92 (P = 0.02) for mortality. There was a trend toward treatment with intravenous chemotherapy (84.2%) over IP (15.8%) in patients with class II obesity (P = 0.06). DISCUSSION:There was no difference in completion of IP chemotherapy or complications with respect to BMI; however, there was a trend away from treatment with IP therapy in extreme obesity. These data suggest that IP chemotherapy is feasible in obese patients without incurring increased morbidity.

IMPORTANCE/OBJECTIVE:Patients with squamous cell carcinoma (SCC) of the cervix or vulva have limited therapeutic options, and the potential for immunotherapy for this population has not been evaluated. Recent trials suggest that tumors with a genetic basis for PD-1 (programmed cell death protein 1) ligand expression are highly sensitive to therapeutic antibodies targeting PD-1. OBJECTIVE:To determine the genetic status of CD274 (encoding PD-L1 [programmed cell death 1 ligand 1]) and PDCD1LG2 (encoding PD-L2 [programmed cell death 1 ligand 2]) in SCCs of the cervix and vulva and to correlate the findings with PD-L1 protein expression. DESIGN, SETTING, AND PARTICIPANTS/METHODS:We performed fluorescence in situ hybridization (FISH) using probes targeting CD274, PDCD1LG2, and the centromeric portion of chromosome 9, and immunohistochemistry (IHC) using an antibody recognizing PD-L1 on formalin-fixed, paraffin-embedded (FFPE) biopsy specimens from 48 cervical SCCs and 23 vulvar SCCs. MAIN OUTCOMES AND MEASURES/METHODS:Tumors were categorized according to the genetic abnormality in CD274 and PDCD1LG2 (coamplification > cogain > polysomy > disomy) as detected by FISH, and evaluated on a semiquantitative scale (modified H score, the product of the percentage of tumor cells with positive staining and the maximum intensity of positive staining) for PD-L1 protein expression as detected by IHC. RESULTS:Overall, 71 samples of FFPE tissue from cases of cervical SCCs (n = 48) and vulvar SCCs (n = 23) were retrieved from the archives of Brigham and Women's Hospital and included in this study. We observed cogain or coamplification of CD274 and PDCD1LG2 in 32 of 48 cervical SCCs (67%) and 10 of 23 vulvar SCCs (43%). Median PD-L1 protein expression was highest among tumors with CD274 and PDCD1LG2 coamplification and lowest among tumors with disomy. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Recurrent copy number gain of the genes encoding the PD-1 ligands provides a genetic basis for PD-L1 expression in a subset of cervical and vulvar SCCs and identifies a class of patients that are rational candidates for therapies targeting PD-1.