Volume, Dose, and Fractionation Considerations for IMRT-based Reirradiation in Head and Neck Cancer: A Multi-institution Analysis

Int J Radiat Oncol Biol Phys. 2018 Mar 1;100(3):606-617. doi: 10.1016/j.ijrobp.2017.11.036. Epub 2017 Dec 1.

Abstract

Purpose: Limited data exist to guide the treatment technique for reirradiation of recurrent or second primary squamous carcinoma of the head and neck. We performed a multi-institution retrospective cohort study to investigate the effect of the elective treatment volume, dose, and fractionation on outcomes and toxicity.

Methods and materials: Patients with recurrent or second primary squamous carcinoma originating in a previously irradiated field (≥40 Gy) who had undergone reirradiation with intensity modulated radiation therapy (IMRT); (≥40 Gy re-IMRT) were included. The effect of elective nodal treatment, dose, and fractionation on overall survival (OS), locoregional control, and acute and late toxicity were assessed. The Kaplan-Meier and Gray's competing risks methods were used for actuarial endpoints.

Results: From 8 institutions, 505 patients were included in the present updated analysis. The elective neck was not treated in 56.4% of patients. The median dose of re-IMRT was 60 Gy (range 39.6-79.2). Hyperfractionation was used in 20.2%. Systemic therapy was integrated for 77.4% of patients. Elective nodal radiation therapy did not appear to decrease the risk of locoregional failure (LRF) or improve the OS rate. Doses of ≥66 Gy were associated with improvements in both LRF and OS in the definitive re-IMRT setting. However, dose did not obviously affect LRF or OS in the postoperative re-IMRT setting. Hyperfractionation was not associated with improved LRF or OS. The rate of acute grade ≥3 toxicity was 22.1% overall. On multivariable logistic regression, elective neck irradiation was associated with increased acute toxicity in the postoperative setting. The rate of overall late grade ≥3 toxicity was 16.7%, with patients treated postoperatively with hyperfractionation experiencing the highest rates.

Conclusions: Doses of ≥66 Gy might be associated with improved outcomes in high-performance patients undergoing definitive re-IMRT. Postoperatively, doses of 50 to 66 Gy appear adequate after removal of gross disease. Hyperfractionation and elective neck irradiation were not associated with an obvious benefit and might increase toxicity.

Publication types

  • Multicenter Study

MeSH terms

  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / radiotherapy*
  • Carcinoma, Squamous Cell / virology
  • Dose Fractionation, Radiation*
  • Female
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / radiotherapy*
  • Head and Neck Neoplasms / virology
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Lymphatic Irradiation
  • Male
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / radiotherapy*
  • Neoplasm Recurrence, Local / virology
  • Neoplasms, Second Primary / mortality
  • Neoplasms, Second Primary / radiotherapy*
  • Neoplasms, Second Primary / virology
  • Radiation Dose Hypofractionation
  • Radiation Injuries / etiology
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Radiotherapy, Intensity-Modulated / methods*
  • Re-Irradiation / adverse effects
  • Re-Irradiation / methods*
  • Retrospective Studies
  • Treatment Outcome