Introduction/Background*As stated by ESGO-ESMO, there is a need for indicators of chemotherapy efficacy in ovarian carcinoma patients treated in first-line setting (Colombo et al, IGCS, 2020). The pathological chemotherapy response score (CRS) and the modeled CA-125 KELIM during neo-adjuvant chemotherapy were reported as potential markers. Moreover, changes in tumor infiltrating lymphocytes (TILs) after neo-adjuvant chemotherapy were reported as a prognostic factor (Leary et al, Cancer Immunol Immunother, 2021). We studied the relationships between changes in TILs, the pathological response (pR) and KELIM in patients treated with neo-adjuvant chemotherapy +/- interval debulking surgery (IDS) from CHIVA phase II trial.
Methodology The patients were enrolled in the randomized phase II trial CHIVA (NCT01583322, neo-adjuvant carboplatin-paclitaxel +/- nintedanib, +/- IDS, n=188 patients). KELIM were previously calculated (You et al CCR 2020). The 30 patients with the highest KELIM (very chemosensitive) or the lowest KELIM (poorly chemosensitive) were selected. HE-stained sections from available tissue blocks at baseline and after chemotherapy were analyzed for stromal TILs (sTILs, surface of the tumor stroma occupied by lymphocytes) and intra-epithelial TILs (ieTILs, brisk or non-brisk). The pathological response (pR) was assessed on the most tumoral available tissue block obtained after chemotherapy (good response if extensive fibrous changes with no or isolated tumor cells, or <2 mm cell clusters). Descriptive statistics assessed the relationships between KELIM, TIL changes, and pR.
Result(s)*No relationships between KELIM and TILs infiltrates on baseline tumor samples were found. However, strong associations were found between KELIM and TIL infiltrates after neo-adjuvant chemotherapy for sTILs (median KELIM for sTILs 0-5% vs >5%: 0.28 versus 1.32, P < 0.001) and for ieTILs (median KELIM for ieTILs non-brisk versus brisk: 0.31 versus 1.31, P = 0.04). Similarly, an association was found between KELIM and the quality of pR (median KELIM for patients with poor vs good pR: 0.31 versus 1.32, P = 0.05).
Conclusion*High consistency was found between the modeled CA125 KELIM calculated during the first 100 days of neo-adjuvant chemotherapy and the pathological response, consistent with their values as indicators of the tumor chemosensitivity in first-line setting. Moreover, TILs changes were strongly associated with chemosensitivity, opening hypotheses about the mechanisms of chemosensitivity, and immunotherapy opportunity.
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