Prognostic and predictive significance of CA-125 elimination rate constant K (KELIM) in ovarian cancer patients treated with neoadjuvant chemotherapy in a real-world setting.
Authors: Liontos Michael , Papatheodoridi Alkistis , Kunadis Elena , Svarna Anna , Theofanakis Charalampos , Fiste Oraianthi , Rouvali Angeliki , Goula Kalliroi , Markellos Christos , Andrikopoulou Angeliki , Potiri Eirini , Papanota Aristea-Maria , Kaparelou Maria , Koutsoukos Konstantinos , Thomakos Nikolaos , Haidopoulos Dimitrios , Rodolakis Alexandros , Zagouri Flora , You Benoit , Dimopoulos Meletios A. 
Published: June 2023

e17594

Background: CA-125 ELIMination Rate Constant K (KELIM) is considered a marker of chemosensitivity in ovarian cancer patients and its prognostic and predictive significance in Neo-adjuvant Chemotherapy (NACT) treated patients has been established through prospective trials. Limited data exist regarding the feasibility of its application in the real-world setting. Under this perspective, we undertook a retrospective study of the predictive and prognostic significance of KELIM in ovarian cancer patients treated with NACT in our institution. Methods: Medical records of women with aEOC treated with NACT at Alexandra Hospital from 2010 to 2019 were retrospectively identified. Clinicopathological data, treatment and survival data were analysed. Modeled CA-125 KELIM score was calculated from the available online tool ( https://www.biomarker-kinetics.org/CA-125-neo ). Kaplan-Meier Survival curves were generated using SPSS; survival differences were estimated using the long-rank test. Results: 99 patients treated with 3-4 cycles of NACT with Paclitaxel and Carboplatin with available at least three CA125 measurements within 100 days from the beginning of chemotherapy were included. Median age was 66.6 years (25th-75th percentile was 59.8 and 74.5 years respectively) and median numbers of CA125 measurements were 3. KELIM score < 1 (unfavorable) had 56 patients (56.6%) while score ≥1 had 43 patients (43.4%). All patients had high grade serous histology and 72 patients were treated with debulking surgery (72.8%). BRCA1/2 mutation status was known in 66 patients, among them 18 patients (27.3%) were positive for the presence of BRCA1/2 mutations. Favorable KELIM score was predictive of both increased PFS [mPFS 16.6 months (95% CI 12.6-20.5) in favorable group vs 11.9 months (95% CI 10.6-13.4) in unfavorable, p < 0.001] and OS [mOS 44.7 months (95% CI 40.2-49.1) in favorable group vs 27.2 months (95% CI 18.5-35.9) in unfavorable, p = 0.013]. Predictive and prognostic significance of KELIM was retained in multivariate analysis when other prognostic parameters as age, ECOG-PS, quality of debulking surgery were taken into account. Bevacizumab administration post NACT increased statistical significantly both PFS and OS only in patients with unfavorable KELIM score. There was no statistical correlation between favorable KELIM score and presence of BRCA1/2 mutations, however our analysis is limited by the small number of patients. Conclusions: KELIM score can be easily applied in common clinical practice of ovarian cancer patients treated with NACT and provide valuable prognostic and predictive information. Despite in our analysis no correlation with presence of BRCA1/2 mutations was found further investigation is warranted, since PARP inhibitors constitute the established maintenance treatment in the frontline setting.