Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX)

Eur J Cancer. 2018 Aug;99:78-85. doi: 10.1016/j.ejca.2018.05.011. Epub 2018 Jun 19.

Abstract

Purpose: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy.

Methods: High-risk STS was defined as high-grade morphology (according to the Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size ≥8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4.

Results: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death.

Conclusions: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.

Trial registration: ClinicalTrials.gov NCT00790244.

Keywords: Adjuvant treatment; Growth pattern; Necrosis; Prognostic factors; Soft tissue sarcoma; Survival; Tumour size; Vascular invasion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant / methods
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Ifosfamide / pharmacology
  • Ifosfamide / therapeutic use
  • Incidence
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control
  • Prospective Studies
  • Radiotherapy, Adjuvant / methods
  • Risk Factors
  • Sarcoma / blood supply
  • Sarcoma / epidemiology*
  • Sarcoma / prevention & control
  • Sarcoma / secondary
  • Soft Tissue Neoplasms / blood supply
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / pathology
  • Soft Tissue Neoplasms / therapy*
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Doxorubicin
  • Ifosfamide

Associated data

  • EudraCT/2007-001152-39
  • ClinicalTrials.gov/NCT00790244