Standardization of evaluation method and prognostic significance of histological response to preoperative chemotherapy in high-grade non-round cell soft tissue sarcomas
Yoshinao Oda,
Kazuhiro Tanaka,
Takanori Hirose,
Tadashi Hasegawa,
Nobuyuki Hiruta,
Masanori Hisaoka,
Masato Yoshimoto,
Hiroshi Otsuka,
Hirofumi Bekki,
Takeaki Ishii,
Makoto Endo,
Toshiyuki Kunisada,
Toru Hiruma,
Hiroyuki Tsuchiya,
Hirohisa Katagiri,
Yoshihiro Matsumoto,
Akira Kawai,
Robert Nakayama,
Hiroyuki Kawashima,
Satoshi Takenaka,
Makoto Emori,
Munenori Watanuki,
Yukihiro Yoshida,
Takeshi Okamoto,
Junki Mizusawa,
Haruhiko Fukuda,
Toshifumi Ozaki,
Yukihide Iwamoto,
Takayuki Nojima
Affiliations
Yoshinao Oda
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University
Kazuhiro Tanaka
Department of Orthopaedic Surgery, Faculty of Medicine, Oita University
Takanori Hirose
Department of Diagnostic Pathology, Hyogo Cancer Center
Tadashi Hasegawa
Department of Surgical Pathology, School of Medicine, Sapporo Medical University
Nobuyuki Hiruta
Department of Surgical Pathology, Toho University Sakura Medical Center
Masanori Hisaoka
Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health
Masato Yoshimoto
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University
Hiroshi Otsuka
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University
Hirofumi Bekki
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University
Takeaki Ishii
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University
Makoto Endo
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University
Toshiyuki Kunisada
Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Toru Hiruma
Department of Musculoskeletal Tumor Surgery, Kanagawa Cancer Center
Hiroyuki Tsuchiya
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University
Hirohisa Katagiri
Division of Orthopaedic Oncology, Shizuoka Cancer Center Hospital
Yoshihiro Matsumoto
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University
Akira Kawai
Department of Musculoskeletal Oncology, National Cancer Center Hospital
Robert Nakayama
Department of Orthopaedic Surgery, Keio University School of Medicine
Hiroyuki Kawashima
Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences
Satoshi Takenaka
Department of Orthopaedic Surgery, Osaka International Cancer Institute
Makoto Emori
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine
Munenori Watanuki
Department of Orthopaedic Surgery, Tohoku University School of Medicine
Yukihiro Yoshida
Department of Orthopaedic Surgery, Nihon University Itabashi Hospital
Takeshi Okamoto
Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine
Junki Mizusawa
JCOG Data Center, National Cancer Center Hospital
Haruhiko Fukuda
JCOG Data Center, National Cancer Center Hospital
Toshifumi Ozaki
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Yukihide Iwamoto
Department of Orthopaedic Surgery, Kyushu Rosai Hospital
Takayuki Nojima
Department of Pathology, Graduate School of Medical Sciences, Kanazawa University
Abstract Background Preoperative 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. Methods Using 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. Results A 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). Conclusion The 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 registration UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).
