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

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).

Feasibility of indocyanine green‐guided localization of pulmonary nodules in children with solid tumors

“…Adult studies have shown the feasibility of ICG-guided localization of high-grade sarcomas. 17,[34][35][36][37][38] Similarly, our trial suggests that IGCguided localization of pediatric high-grade sarcomas should be further investigated.…”

“…Different tumor histologies may have variable vascular permeability and interstitial fluid pressure, which in turn would result in variable EPRs 31,32 . In addition, the variable rate of tumor neoangiogenesis after chemotherapy of different nonhepatic tumor‐related metastases suggests the failure of ICG guidance is a histology‐related event in our study or the effectiveness for some nonhepatic tumor metastases, including high‐grade sarcomas 33,34 …”

“…31,32 In addition, the variable rate of tumor neoangiogenesis after chemotherapy of different nonhepatic tumor-related metastases suggests the failure of ICG guidance is a histology-related event in our study or the effectiveness for some nonhepatic tumor metastases, including high-grade sarcomas. 33,34 Multiple retrospective studies have shown a high success rate of localizing pulmonary metastases of hepatic primary tumors in pediatric populations. Those studies reported increased ICG uptake and impaired excretion of the fluorophore due to the tumor's biliary characteristics.…”

Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306

“…Those displaying any evidence of pyknosis, karyorrhexis, karyolysis, severe vacuolation, or loss of nuclear staining were defined as non-viable. The results demonstrated a substantial agreement in the weighted κ score of 0.71 among six pathologists who specialise in STS [ 30 ]. We are currently carrying out a validation study of this method using the resected specimens from JCOG1306.…”

Kappa statistic considerations in evaluating inter-rater reliability between two raters: which, when and context matters

“…In cases where there is a need to evaluate the level of agreement between two raters regarding ordered categorical variables that consist of three or more categories, the weighted Kappa is frequently utilized as a measure [ 9 ]. Weighted Kappa comes in two forms: linear weighted Kappa (LWK) [ 10 ] and quadratic weighted Kappa (QWK) [ 11 ].…”