Meeting
2023 ASCO Annual Meeting
Predictive value of tumor-infiltrating lymphocyte (TIL) dynamics in the tumor microenvironment (TME) during preoperative chemoradiotherapy (CRT) on pathologic complete response (pCR) in microsatellite-stable (MSS) locally advanced rectal cancer (LARC).
Authors
Mitsuho Imai
TR supporting office, National Cancer Center Hospital East, Kashiwa-Shi, Japan
Mitsuho Imai , Hideaki Bando , Yuichiro Tsukada , Takeshi Kato , Yoshito Komatsu , Mamoru Uemura , Satoshi Yuki , Akinobu Taketomi , Takao Fujisawa , Yoshiaki Nakamura , Motohiro Kojima , Shohei Koyama , Chiyoon Oum , Seunghwan Shin , Chan-Young Ock , Hiroyoshi Nishikawa , Masaaki Ito , Takayuki Yoshino
Organizations
TR supporting office, National Cancer Center Hospital East, Kashiwa-Shi, Japan, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan, National Cancer Center Hospital East, Japan, Kashiwa-Shi, Japan, Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan, Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan, Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan, Department of Gastroenterological Surgery, Hokkaido University Hospital, Sapporo, Japan, Department of Head and Neck Medical Oncology/Translational Research Support Office, National Cancer Center East Hospital, Chiba, Japan, National Cancer Center Hospital East, Kashiwa, Japan, Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan, Division of Cancer Immunology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba, Japan, Lunit Inc., Seoul, South Korea, Lunit Inc, Gangnam-Gu, Korea, Republic of (South), Lunit Inc., Seoul, Korea, Republic of (South), Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Japan
Research Funding
Other
Lunit Inc
Background : Preoperative CRT followed by consolidation nivolumab before surgery showed a promising pCR rate in MSS LARC; both high PD-L1 expression and an elevated CD8+ T cell/effector regulatory T cell ratio analyzed by pre-CRT samples were independently related to high pCR rate (Bando H, Clin Cancer Res. 2022). Here, we applied AI-powered spatial TIL analysis to the VOLTAGE study to investigate whether dynamic change of TIL in TME may predict pCR in MSS LARC. Methods: The VOLTAGE study is a multicenter phase I/II study to evaluate the efficacy of CRT followed by 5 cycles of nivolumab and surgery in patients (pts) with LARC. In this study, tumor samples were obtained at multiple time points; pre-CRT (B1), post-CRT/pre-nivolumab (B2), post-3 cycles of nivolumab (B3), and surgery. In this analysis, a total of 86 H&E whole-slide images (WSI) harvested at B1 and B2 time points from all the pts enrolled in the VOLTAGE study were included in the analysis. Lunit SCOPE IO (Lunit, Republic of Korea), AI-powered H&E-WSI analyzer developed based on 16,443 WSI with pathologists' annotations, was applied to quantify TIL density in TME. Results: In a total of 43 pts, pCR rate of MSS and microsatellite instability-high (MSI-H) were 28.9% (11/38) and 60% (3/5), respectively. In MSS subgroup (n = 38), which has a higher unmet need for pCR prediction, tumor samples with pCR (n = 11) had increased TIL density in TME (tTIL) in post-CRT (B2, median [IQR] 726 [249-1607] /mm2) compared to pre-CRT (B1, 598 [366-905] /mm2), whereas those without pCR (n = 27) had decreased tTIL in post-CRT (405 [148-748] /mm2), compared to pre-CRT (B1, 748 [460-1153] /mm2). Intratumoral TIL density changes were more prominent than stromal TIL density changes in MSS tumor samples with pCR (mean fold change x17.7 vs. x1.5). MSS Pts with tTIL change from B1 to B2 (during CRT) more than x1.8 times achieved 75% (6/8) pCR rate, whereas those with tTIL change less than x1.8 had 16.7% (5/30) pCR rate (p = 0.0035). Conclusions: Change of TIL density in TME during CRT was significantly correlated with favorable clinical outcome of preoperative CRT and consolidation nivolumab, resulting in high pCR rate in MSS LARC.
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Abstract Details
Session Type
Poster Session
Session Title
Gastrointestinal Cancer—Colorectal and Anal
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Colorectal Cancer–Local-Regional Disease
Citation
J Clin Oncol 41, 2023 (suppl 16; abstr 3608)
DOI
10.1200/JCO.2023.41.16_suppl.3608
Abstract #
3608
Poster Bd #
308
Abstract Disclosures
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