Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study

Br J Cancer. 2017 Jul 25;117(3):326-331. doi: 10.1038/bjc.2017.198. Epub 2017 Jun 27.


Background: An increasing number and proportion of cancer patients with apparently localised disease are treated with chemotherapy and radiation therapy in contemporary oncology practice. In a pilot study of radiation-induced sarcoma (RIS) patients, we demonstrated that chemotherapy was associated with a reduced time to development of RIS. We now present a multi-centre collaborative study to validate this association.

Methods: This was a retrospective cohort study of RIS cases across five large international sarcoma centres between 1 January 2000 to 31 December 2014. The primary endpoint was time to development of RIS.

Results: We identified 419 patients with RIS. Chemotherapy for the first malignancy was associated with a shorter time to RIS development (HR 1.37; 95% CI: 1.08-1.72; P=0.009). In the multi-variable model, older age (HR 2.11; 95% CI 1.83-2.43; P<0.001) and chemotherapy for the first malignancy (HR 1.61; 95% CI 1.26-2.05; P<0·001) were independently associated with a shorter time to RIS. Anthracyclines and alkylating agents significantly contribute to the effect.

Conclusions: This study confirms an association between chemotherapy given for the first malignancy and a shorter time to development of RIS.

Publication types

  • Multicenter Study
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anthracyclines / adverse effects
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Neoplasms / radiotherapy
  • Neoplasms, Radiation-Induced / etiology*
  • Neoplasms, Second Primary / etiology*
  • Retrospective Studies
  • Sarcoma / etiology*
  • Time Factors
  • Young Adult


  • Anthracyclines
  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating