Standardization of evaluation method and prognostic significance of histological response to preoperative chemotherapy in high-grade non-round cell soft tissue sarcomas

Yoshinao Oda,Toshifumi Ozaki,Toshiyuki Kunisada,Makoto Endo,Munenori Watanuki,Masami Yoshimoto ,Yukihiro Yoshida,Satoshi Takenaka,Hirofumi Bekki,Takeshi Okamoto,Robert Nakayama,Hiroyuki Tsuchiya,Toru Hiruma,Takanori Hirose,Yoshihiro Matsumoto,Takeaki Ishii,Junki Mizusawa,Masanori Hisaoka,Nobuyuki Hiruta,Tadashi Hasegawa,Hiroyuki Kawashima,Akira Kawai,Yukihide Iwamoto,Haruhiko Fukuda,Hiroshi Otsuka,Hirohisa Katagiri,Makoto Emori,Kazuhiro Tanaka,Takayuki Nojima

doi:10.1186/s12885-022-09195-y

Abstract

BackgroundPreoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis.MethodsUsing data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board.ResultsA total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (κ) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the p-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor < 25%, to the responder was 4.029 (95% confidence interval 0.893–18.188, p = 0.070).ConclusionThe standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted κ score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO.Trial registrationUMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Highlights

Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); the prognostic significance of histological response to chemotherapy remains controversial
This study protocol was approved by the Protocol Review Committee of the Japan Clinical Oncology Group (JCOG) and by the Institutional Review Boards in each of the 20 participating institutes
All patient data and specimens used in this study were obtained from the patients who had registered in JCOG0304

Summary

Introduction

Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis. Soft tissue sarcomas (STS) are a heterogenous group of rare malignant tumors with a wide spectrum in terms of histological findings, which comprise less than 1% of all malignant tumors [1]. Preoperative chemotherapy has been reported to be effective for localized high-risk STS [3]. The prognostic significance of histological response to preoperative chemotherapy in high-grade STS has not been established yet. There is a growing interest in the evaluation of histological effects in an attempt to assess prognosis after chemotherapy

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