Absence of progression, not extent of tumour shrinkage, defines prognosis in soft-tissue sarcoma - An analysis of the EORTC 62012 study of the EORTC STBSG

Viktor Grünwald, Saskia Litière, Robin Young, Christina Messiou, Michela Lia, Eva Wardelmann, Winette Van Der Graaf, Alessandro Gronchi, Ian Judson

Research output: Contribution to journalArticlepeer-review

Abstract

Background Anthracycline-based chemotherapy remains the mainstay of first-line treatment in metastatic or advanced soft-tissue sarcoma (STS). Age, performance status, tumour histology and tumour grade are recognised prognostic factors; however, the prognostic value of tumour response and tumour shrinkage is ill-defined. Methods Patients recruited to the European Organisation for Research and Treatment of Cancer 62012 trial with advanced intermediate or high-grade STS, who received at least one cycle of chemotherapy and one tumour assessment of response, were eligible for this study. Kaplan-Meier estimates of overall survival (OS) by tumour response were computed using a landmark approach after two, four, and six cycles of chemotherapy. The prognostic role of the kinetics of tumour response was analysed by Cox proportional hazards. Results Three hundred eighty-nine patients were included in this study. Compared to stable or responding patients, patients with progressive disease (PD) after two, four and six cycles of chemotherapy achieved a worse OS: hazard ratio [HR] 2.62 (95% confidence interval [CI] 1.72-4.00), p <0.001; HR 2.23 (95% CI 1.4-3.56), p = 0.0001; and HR 3.16 (95% CI 1.96-5.08), p = 0.0001, respectively. However, patients with stable or responding disease achieved similar OS outcomes. Correspondingly, patients with an increase in tumour size by 10% or more correlated with a worse OS in Cox proportional hazard analysis. Conclusions No association between prognosis and amount of tumour shrinkage was detected. Interestingly, an increase in tumour size by at least 10% correlated with a worse OS, but re-defining PD as a ≥10% increase in tumour size did not translate into a better discrimination of survival outcomes for responders versus stable disease. Disease control rather than tumour response is a valuable end-point in advanced or metastatic STS receiving palliative anthracycline-based chemotherapy, supporting the use of time-to-event end-points in future STS trials.

Original languageEnglish
Pages (from-to)44-51
Number of pages8
JournalEuropean Journal of Cancer
Volume64
DOIs
Publication statusPublished - Sep 1 2016

Keywords

  • Chemotherapy
  • Prognosis
  • Soft-tissue sarcoma
  • Tumour shrinkage

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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