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Abstract
Introduction/Background Ovarian cancer (OC) is conventionally treated with debulking surgery and platinum-based chemotherapy. However, the majority of OC cases experience relapse, often developing resistance to platinum or PARP inhibitors. Recent preclinical data suggests a crucial role for tumor-induced senescence (TIS) programs in platinum resistance. This study aims to evaluate whether neoadjuvant chemotherapy (NACT) induces TIS and if TIS holds prognostic significance in OC.
Methodology A retrospective cohort study was conducted on high-grade serous ovarian cancer (HGSOC) specimens fixed in formalin and embedded in paraffin (FFPE). Specimens were collected during interval debulking (group 1) and primary cytoreductive surgery (group 2) at Careggi University between May 2019 and January 2020. Lipofuscin staining within stromal cells on FFPE samples served as immunohistochemistry (IHC) biomarkers of TIS. Results were correlated with progression-free survival (PFS) using Cox proportional hazard regression. Univariate and multivariate analyses on clinical data of the two groups were performed.
Results Ten patients were enrolled in group 1, and nine in group 2. Lipofuscin staining was significantly more pronounced in group 1 (37% vs. 8%). Univariate analysis revealed a significantly higher CA125 serum level at diagnosis in group 1 (p=0.0112), while PFS was longer in group 2 (p = 0.0012). Multivariate analysis demonstrated a statistically significant correlation of positive lipofuscin IHC with CA125 at diagnosis (p = 0.041), PFS (p = 0.035), and relapse (p = 0.039).
Conclusion Our preliminary ex-vivo data suggests the development of TIS in HGSOC cells exposed to NACT. Additionally, TIS appears to be associated with higher CA125 at diagnosis, prolonged progression-free survival, and increased risk of relapse. Further research on TIS in OC is imperative to enhance our understanding of disease progression and identify new biomarkers for personalized patient managemen
Disclosures We declare no conflicts of interest and no financial relationship with commercial interests.
