Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2019; 25(35): 5334-5343
Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5334
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
Abstract
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. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown.

AIM

To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice.

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, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders; we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria.

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 prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and N-classification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively).

CONCLUSION

The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.

Keywords: Stomach neoplasm, Neoadjuvant therapy, Drug therapy, Pathology, Prognostic factor

Core tips: Although pathological response is commonly evaluated to assess the efficacy of neoadjuvant chemotherapy for gastric cancer in clinical practice, the results evaluated by pathologists are sometimes discordant. A previous study suggested that pathological evaluation using digital virtual microscopic slides might be useful. However, the application of this approach to clinical practice was not investigated. We thus assessed the utility of this method in clinical practice and the concordance rate between evaluators, and compared the usefulness of this method with conventional histological evaluation using Japanese Classification of Gastric Carcinoma criteria.