III.

While high-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants [by DNA next-generation sequencing (NGS) using a 50 gene Ion Torrent panel] and gene expression (using the NanoString PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n ¼ 14) to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted, whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways.Implications: Gene expression profiles at the time of interval debulking provide additional genetic information that could help impact treatment decisions after NACT; although, continued collection and analysis of matched tumor and cfDNA from multiple time points are needed to determine the role of cfDNA in the management of HGSOC. Mol Cancer Res; 16(5); 813-24. Ó2018 AACR.

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BACKGROUND. Current chemotherapy in platinum‐resistant ovarian cancer patients has demonstrated minimal to no improvements in survival. Despite the lack of benefit, significant resources are utilized with such therapies. Therefore, the objective in the current study was to assess the cost‐effectiveness of salvage chemotherapy for patients with platinum‐resistant epithelial ovarian cancer (EOC). METHODS. A decision analysis model evaluated a hypothetical cohort of 4000 platinum‐resistant patients with recurrent EOC. Several chemotherapy strategies were analyzed: 1) best supportive care (BSC); 2) second‐line chemotherapy‐monotherapy; 3) second‐line chemotherapy‐combination therapy; 4) third‐line chemotherapy after disease progression on second‐line monotherapy; and 5) third‐line chemotherapy after disease progression on second‐line combination therapy. Sensitivity analyses were performed on all pertinent uncertainties. RESULTS. Using costs alone, BSC was the only definitive cost‐effective treatment for platinum‐resistant recurrent ovarian cancer patients, and second‐line monotherapy was a reasonable cost‐effective strategy with an incremental cost‐effectiveness ratio (ICER) of $64,104. The cost‐effectiveness ranged from $4,065 per month of overall survival (OS) for BSC to $12,927 for third‐line previous combination therapy. Compared with BSC, second‐line monotherapy gained an additional 3 months of OS, with a cost‐effectiveness of $4,703 per month of OS. Second‐line combination therapy and third‐line therapies exhibited unfavorable ICER. CONCLUSIONS. The current decision analysis was intended to be thought‐provoking and bring awareness to the high costs of subsequent chemotherapy with limited effectiveness in patients with recurrent platinum‐resistant EOC. Although actual patients may receive multiple lines of chemotherapy, from the perspective of costs alone this model using a hypothetical cohort demonstrated that best supportive care was the only cost‐effective strategy, with second‐line monotherapy appearing to be a reasonable cost‐effective strategy given current chemotherapeutic options. Cancer 2006. © 2006 American Cancer Society.

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