Effect of total dose and fraction size on survival of patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a phase 2, single-center, randomized controlled trial

Cancer. 2014 Nov 15;120(22):3502-9. doi: 10.1002/cncr.28934. Epub 2014 Jul 23.

Abstract

Background: The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model.

Methods: Between January 2003 and December 2007, a total of 117 patients with locally recurrent nonmetastatic nasopharyngeal carcinoma were randomized to 2 different models of total dose and fraction size: group A (59 patients) received 60 gray in 27 fractions and group B (58 patients) received 68 gray in 34 fractions. Both groups received 5 daily fractions per week. All patients received IMRT alone.

Results: The median follow-up was 25.0 months. The 5-year overall survival in group A was higher than that in group B (44.2% vs 30.3%; P =.06), and the local failure-free survival in group A was slightly lower than that in group B (63.7% vs 71.0%; P =.41). Severe late complications were the main cause of death. The incidences of mucosal necrosis and massive hemorrhage in patients in group B were significantly higher than those among patients in group A at 50.8% versus 28.8% (P =.02) and 31.0% versus 18.6% (P =.12), respectively. Tumor volume (P<.01) and model of total dose and fraction size (P =.03) were found to be significant factors for mucosal necrosis and massive hemorrhage.

Conclusions: Appropriately decreasing the total dose and increasing the fraction size can achieve local control similar to that achieved with a higher dose after IMRT; furthermore, it can improve overall survival by significantly reducing the incidence of severe late complications including mucosal necrosis and massive hemorrhage.

Keywords: fraction size; intensity-modulated radiotherapy (IMRT); late complications; local recurrence; nasopharyngeal carcinoma; total dose.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Carcinoma
  • Cause of Death
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / radiotherapy*
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Treatment Failure
  • Tumor Burden