Evaluation of chemotherapy response score and lymphocytic infiltration as prognostic markers in ovarian cancer patients treated with neoadjuvant chemotherapy

Abstract

Background: Neoadjuvant Chemotherapy (NACT) followed by Interval Debulking Surgery (IDS) is an alternative frontline treatment in patients with advanced Epithelial Ovarian Cancer (EOC). Histopathologic assessment of tumor post NACT is an ideal mean of response to treatment. The present study aims to characterize the pathological response and to examine its prognostic significance in these patients. Methods: Medical records of women with EOC treated at Alexandra Hospital from 2011 to 2016 were retrospectively identified. Clinicopathological data, treatment and survival data were analyzed. IDS specimens were reviewed by study pathologist and Chemotherapy Response Score (CRS), lymphocytic infiltration, necrosis and mitosis were assessed. Survival differences were estimated using the long-rank test. Results: 55 patients with EOC treated with NACT were identified, 48 had complete clinical and pathological data. Median age was 63 years. All patients had high grade disease and 45 of them had serous carcinoma. At baseline 38 patients had stage IIIc disease and 10 stage IV. All patients received Paclitaxel-Carboplatin combination for 3 cycles. 20 patients had complete debulking (no macroscopic residual disease), 18 had optimal (macroscopic disease <1cm) and 7 suboptimal. 22 patients received also bevacizumab as part of their treatment post IDS. CRS assessed at omentum predicted PFS when adjusted for age, stage, debulking status (complete, optimal, suboptimal) and post IDS bevacizumab administration (mPFS CRS 1vs2vs3: 11.9-14-19.5 months 95% CI [7.4- 18.3], [12.2-20.7], [13.5-31.3]). Lymphocytic invasion was associated with improved OS (log-rank test p=0.022). Presence of necrosis and mitosis per HPF did not predict either PFS or OS. BRCA status was known for 19 patients and presence of BRCA1/2 mutations was strongly correlated with lymphocytic infiltration (P=0.011) but not CRS (p=0.801). Conclusions: Our study confirms the predictive value of CRS in EOC patients treated with NACT and IDS, but also demonstrates the prognostic significance of lymphocytic infiltration in IDS specimens. The later was associated with presence of BRCA mutations with obvious therapeutic implications.