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Published in: Gastric Cancer 5/2020

01-09-2020 | Gastric Cancer | Original Article

Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer

Authors: Akinori Sasaki, Yoshiaki Nakamura, Yosuke Togashi, Hirofumi Kuno, Hidehiro Hojo, Shunichiro Kageyama, Naoki Nakamura, Kenji Takashima, Tomohiro Kadota, Yusuke Yoda, Saori Mishima, Kentaro Sawada, Daisuke Kotani, Akihito Kawazoe, Yasutoshi Kuboki, Hiroya Taniguchi, Takashi Kojima, Toshihiko Doi, Takayuki Yoshino, Tomonori Yano, Tatsushi Kobayashi, Tetsuo Akimoto, Hiroyoshi Nishikawa, Kohei Shitara

Published in: Gastric Cancer | Issue 5/2020

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Abstract

Background

Immune checkpoint inhibitors may enhance the efficacy of radiotherapy (RT) in cancer treatment but the effect remains unknown in metastatic gastric cancer (mGC). This study aimed to compare the tumor shrinkage by palliative RT for mGC patients with or without previous exposure to anti-PD-1 therapy.

Methods

Data of 36 mGC patients who had received palliative RT from April 2013 to May 2019 were analyzed. Primary tumor responses were evaluated through a volumetric measurement-based method using computed tomography (CT) and endoscopic responses were evaluated in patients who underwent endoscopy before and after RT. Tumor microenvironment (TME) immune status was investigated by analyzing tumor-infiltrating lymphocytes by flow cytometry.

Results

Among 36 patients, 18 had previous exposure to anti-PD-1 before RT showing no significant differences in baseline characteristics with the other 18 patients without exposure to anti-PD-1 treatment. Tumor responses were observed in 28% (5/18) and none (0/18) in the anti-PD-1-exposed vs. naïve group, respectively (P = 0.045). Five out of eight patients in the anti-PD-1-exposed group, who underwent endoscopy after RT showed partial response, but none in the anti-PD-1-naïve patients showed response (P = 0.026). Increase in the CD8+ T cell/effector regulatory T cell ratio in TILs after anti-PD-1 therapy was noted in three responders to RT, but not in the other three non-responders.

Conclusions

Prior exposure to anti-PD-1 therapy increases tumor response to RT. Immune profiling suggests that anti-PD-1 therapy may enhance the efficacy of RT by immunoactivation in the TME.
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Metadata
Title
Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer
Authors
Akinori Sasaki
Yoshiaki Nakamura
Yosuke Togashi
Hirofumi Kuno
Hidehiro Hojo
Shunichiro Kageyama
Naoki Nakamura
Kenji Takashima
Tomohiro Kadota
Yusuke Yoda
Saori Mishima
Kentaro Sawada
Daisuke Kotani
Akihito Kawazoe
Yasutoshi Kuboki
Hiroya Taniguchi
Takashi Kojima
Toshihiko Doi
Takayuki Yoshino
Tomonori Yano
Tatsushi Kobayashi
Tetsuo Akimoto
Hiroyoshi Nishikawa
Kohei Shitara
Publication date
01-09-2020
Publisher
Springer Singapore
Published in
Gastric Cancer / Issue 5/2020
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-020-01058-4

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