Ovarian Cancer Stem Cell Marker Aldh1a2 Is A Candidate Biomarker For Patient Selection For Intraperitoneal Chemotherapy

Objective. To evaluate ovarian cancer stem cells as predictors of survival we analyzed associations of cancer stem cell markers ALDH1, CD117 and CD133 with survival outcomes among patients with high grade serous ovarian cancer (HGS OvCa). Methods. Data from HGS OvCa patients who were surgically staged prior to treatment with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Multivariate Cox proportional-hazards regression tested associations of tumor mRNA expression of 5 cancer stem cell markers with progression free survival (PFS) and overall survival (OS). Expression was analyzed as a continuous variable by restricted mean survival (RMS) analysis. Mean PFS or OS were compared between IP and IV groups by permutation testing stratified by expression. P-values were two-tailed. Results. Increased tumor ALDH1A2 expression was associated with decreased OS among patients treated with IP chemotherapy, HR 2.36 (1.16-4.80), p = 0.017. IP treated patients with upper 20th percentile ALDH1A2 expression had decreased OS compared to bottom 20th percentile expression (30.4 versus 51.1 months, -20.7 months difference, p = 0.017). RMS curves for PFS and OS of IP versus IV treated patients crossed at high ALDH1A2 expression, indicating that IP treated patients had decreased survival compared to IV-only treated patients. Patients with upper 20th percentile ALDH1A2 expression treated with IP versus IV-only chemotherapy had no difference in mean PFS (21.3 versus 21.6 months, -0.3 months difference, p = 0.67) and decreased OS (30.4 versus 35.3 months, -4.9 months difference, p Conclusions. High primary tumor ALDH1A2 expression was independently associated with significantly decreased OS among patients treated with IP chemotherapy. High ALDH1A2 was associated with lack of benefit or decreased survival among patients treated with IP compared to IV-only adjuvant chemotherapy. Citation Format: Brandon-Luke L. Seagle, Monica Dandapani, Chen Hui Luo, Claire Hoppenot, Robert Samuelson, Kevin H. Eng, Kunle Odunsi, Shohreh Shahabi. Ovarian cancer stem cell marker ALDH1A2 is a candidate biomarker for patient selection for intraperitoneal chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4753.