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

BMC Cancer. 2022 Jan 21;22(1):94. doi: 10.1186/s12885-022-09195-y.


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).

Keywords: Chemotherapy; Clinical trial; Doxorubicin; Histological response; Ifosfamide; Neoadjuvant; Prognosis; Soft tissue sarcoma.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Chemotherapy, Adjuvant / statistics & numerical data*
  • Doxorubicin / administration & dosage
  • Drug Monitoring / standards*
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Preoperative Period
  • Prognosis
  • Reference Standards
  • Reference Values
  • Sarcoma / mortality
  • Sarcoma / pathology
  • Sarcoma / therapy*
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / pathology
  • Soft Tissue Neoplasms / therapy*
  • Survival Analysis
  • Treatment Outcome
  • Young Adult


  • Doxorubicin
  • Ifosfamide

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