246. SPATIAL HETEROGENEITY OF PD-L1 EXPRESSION INFLUENCE ITS ASSESSMENT IN ESOPHAGEAL SQUAMOUS CARCINOMA (ESCC)

Abstract Background Anti-PD-1/PD-L1 immunotherapy is a promising treatment for ESCC. High PD-L1 expression is a theoretical predictive biomarker, but the poor response is also observed in some patients with high PD-L1 expression. Biopsies assessment of PD-L1 expression always focuses on a single region which may be influenced by spatial heterogeneity of tumor microenvironment. This study investigates whether the PD-L1 expression by biopsy assessment in the different spatial regions is related to its paradoxical predictive value. Methods We prospectively included 30 consecutive patients with treatment-naïve, stage II-III ESCC who underwent upfront esophagectomy. Multi-region sampling was taken with endoscopic biopsy forceps (Fig. A) from four regions (A/B/C/D) from the proximal, distal, midpoint of tumor surface, and internal center, respectively. Each region was spaced ≥1 cm apart and avoided areas of severe necrosis. We compared the PD-L1 expression at different endoscopic-biopsy regions and the overall surgical-resected tumor specimen. PD-L1 expression was evaluated by immunohistochemistry using combined positive score (CPS). PD-L1 expression positive and negative is defined as CPS ≥ 1 and CPS < 1, respectively. Results Based on surgical-resected tumor, PD-L1 positive and high were 66.7% and 10% of 30 patients, respectively. PD-L1 positive/negative discordance rate of four sampling regions was 66.7% with poor concordance (kappa = 0.206) (Fig. B). Correlations between four biopsy regions of PD-L1 expression (Fig. C) revealed high in B and D (r = 0.77) but relatively low in others. Combining multi-region sampling for evaluation improved the correlation consistency of PD-L1 expression assessment (Fig. D). Comparing PD-L1 expression based on the endoscopic-biopsy region with the gold standard surgical-resected specimen, the sensitivity was increased by 12.5% for multi-region versus single-region assessment. Conclusion PD-L1 expression was spatially heterogeneous in ESCC, and a single region cannot reflect the PD-L1 status of the tumor, consistent with the observation of suboptimal prediction of PD-L1 expression for ESCC immunotherapy. Multi-region biopsy could help improve the assessment bias of PD-L1 expression related to spatial heterogeneity, and may help to improve the identification of the candidate for immunotherapy.