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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Pathological response measured using virtual microscopic slides for gastric cancer patients who underwent neoadjuvant chemotherapy
Sadayuki Kawai, Tadakazu Shimoda, Takashi Nakajima, Masanori Terashima, Katsuhiro Omae, Nozomu Machida, Hirofumi Yasui
Sadayuki Kawai, Hirofumi Yasui, Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun 411-8777, Shizuoka, Japan
Tadakazu Shimoda, Takashi Nakajima, Division of Pathology, Shizuoka Cancer Center, Sunto-gun 411-8777, Shizuoka, Japan
Masanori Terashima, Division of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi 411-0932, Shizuoka, Japan
Katsuhiro Omae, Clinical Research Center, Shizuoka Cancer Center, Sunto-gun 411-8777, Shizuoka, Japan
Nozomu Machida, Department of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun 411-8777, Shizuoka, Japan
Author contributions: All authors helped to perform the research: Kawai S manuscript writing, performing procedures, experiments, and data analysis; Shimoda T manuscript writing, drafting the conception and design of this work, and performing experiments; Nakajima T performing experiments; Terashima M contributing to writing the manuscript; Omae K data analysis and statistical review; Machida N and Yasui H contributing to writing the manuscript, and drafting the conception and design of this work.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Committee of Shizuoka Cancer Center.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that had been obtained after each patient had agreed to treatment by providing written informed consent.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sadayuki Kawai, MD, PhD, Doctor, Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Sunto-gun 411-8777, Shizuoka, Japan. sadayuki-kawai@i.shizuoka-pho.jp
Telephone: +81-55-9895222 Fax: +81-55-9895634
Received: May 8, 2019
Peer-review started: May 8, 2019
First decision: July 22, 2019
Revised: August 8, 2019
Accepted: August 19, 2019
Article in press: August 19, 2019
Published online: September 21, 2019
ARTICLE HIGHLIGHTS
Research background
Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation.
Research motivation
Pathological response is commonly used for a surrogate marker for progression-free survival and overall survival (OS) after surgery. However, no globally accepted consensus has been reached regarding the optimal cut-off, and the reproducibility between pathologists was limited.
Research objectives
To examine the clinical utility of 10% cut-off for pathological response evaluated using virtual microscopic slides as a prognostic marker.
Research methods
We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders; we then compared OS and relapse-free survival (RFS) between these two groups.
Research results
Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR) = 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated).
Research conclusions
The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice because of its objectivity and its high concordance rate. We consider that this approach is more applicable for evaluating pathological response.
Research perspectives
Out results indicated that the measurement of pathological response using digitally captured virtual microscopic slides might be as useful as conventional criteria. However, further studies is needed to evaluate the utility of the method especially for patients who have undergone R1 or R2 resection, and type 4 tumor.
