Comparative analysis of circulating tumor cell distribution with PD-L1 expression in baseline and follow up patients across cancer types.

Abstract

e14540 Background: India presents diverse genetic pool and varying cancer incidence patterns. Common cancers in the Indian population include head and neck, lung, breast, colorectal, prostate, ovary, and gastrointestinal cancers. Understanding circulating tumor cells (CTC) distribution across these cancers could account cellular / minimal residual disease, and early recurrence in solid cancers. Surgery with curative intent could be assessed for residual disease using CtDNA and CTC dual biomarkers. Methods: In retrospective analysis of 5935 patient’s peripheral blood from various cancer types viz. Head and neck, lung, breast, colorectal, prostate, ovary, and gastrointestinal cancers was analyzed for the presence of CTCs with and without the over-expression of PD-L1 and CTC clusters. CTCs were detected using OncoDiscover platform approved by CDSCO in 1.5 ml peripheral blood. The platform contains multifunctional magnetonanosystem mediated by anti-epithelial cellular adhesion molecule (EpCAM) antibody. CTCs were confirmed, EpCAM+ve, CK18+ve, DAPI+ve, and CD45-ve. PD-L1 expression on the CTCs was analyzed based on the linear intensity gradients of the fluorescence signals using image acquisition on an automated Zeiss Microscope. In addition computational model was developed to evaluate the CTC frequency, mean distribution, regression analysis, and normal probability plots with predictability of CTC number across cancer types, age, stage, and genders. Results: The study was conducted on 5935 patients’ blood samples (Baseline 90.07% and Follow-up 09.92%). The CTC distribution ranged from 1-10 CTCs with mean value of 1.12. Among these patients, 69.87% (n = 2,854) showed PD-L1 expression on their CTCs, with a mean value of 0.99. The age group 51–60 exhibited the highest proportion of both CTCs (19.16%, n = 1,137) and PD-L1-positive CTCs (19.71%, n = 805). Most CTC clusters were identified in cases of breast, colorectal, and endometrial cancers. Surprisingly, pancreatic cancer patients exhibited the highest mean CTC count (1.4), while laryngeal cancer samples had the lowest mean count (0.78). Using model, the age grp- 51-60 showed highest impact of cancer prevalence and mean CTC distribution. The model also showed good co-relation of blood based outcome versus normal probability scores. Conclusions: Higher CTC counts were strongly correlated with advanced disease stages, particularly in cancers with an inclination for hematogenous spread, such as breast, lung, and prostate cancers. Tailored diagnostics and surveillance strategies that incorporate CTC profiling from baseline could improve personalized cancer management. The CTC occurrence in DFS, suggests that poor therapy response, disease progression, and the presence of minimal residual disease.