Reirradiation of Recurrent and Second Primary Head and Neck Cancer With Proton Therapy

Int J Radiat Oncol Biol Phys. 2016 Nov 15;96(4):808-819. doi: 10.1016/j.ijrobp.2016.07.037. Epub 2016 Aug 3.


Purpose: To report the clinical outcomes of head and neck reirradiation with proton therapy.

Methods and materials: From 2004 to 2014, 61 patients received curative-intent proton reirradiation, primarily for disease involving skull base structures, at a median of 23 months from the most recent previous course of radiation. Most had squamous cell (52.5%) or adenoid cystic (16.4%) carcinoma. Salvage surgery before reirradiation was undertaken in 47.5%. Gross residual disease was present in 70.5%. For patients with microscopic residual disease, the median dose of reirradiation was 66 Gy (relative biological effectiveness), and for gross disease was 70.2 Gy (relative biological effectiveness). Concurrent chemotherapy was given in 27.9%.

Results: The median follow-up time was 15.2 months and was 28.7 months for patients remaining alive. The 2-year overall survival estimate was 32.7%, and the median overall survival was 16.5 months. The 2-year cumulative incidence of local failure with death as a competing risk was 19.7%; regional nodal failure, 3.3%; and distant metastases, 38.3%. On multivariable analysis, Karnofsky performance status ≤70%, the presence of a gastrostomy tube before reirradiation, and an increasing number of previous courses of radiation therapy were associated with a greater hazard ratio for death. A cutaneous primary tumor, gross residual disease, increasing gross tumor volume, and a lower radiation dose were associated with a greater hazard ratio for local failure. Grade ≥3 toxicities were seen in 14.7% acutely and 24.6% in the late setting, including 3 treatment-related deaths.

Conclusions: Reirradiation with proton therapy, with or without chemotherapy, provided reasonable locoregional disease control, toxicity profiles, and survival outcomes for an advanced-stage and heavily pretreated population. Additional data are needed to identify which patients are most likely to benefit from aggressive efforts to achieve local disease control and to evaluate the potential benefit of proton therapy relative to other modalities of reirradiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Adenoid Cystic / mortality
  • Carcinoma, Adenoid Cystic / pathology
  • Carcinoma, Adenoid Cystic / radiotherapy*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / radiotherapy*
  • Neoplasm, Residual
  • Neoplasms, Second Primary / mortality
  • Neoplasms, Second Primary / radiotherapy*
  • Proton Therapy*
  • Radiotherapy Dosage
  • Re-Irradiation* / adverse effects
  • Relative Biological Effectiveness
  • Salvage Therapy
  • Skin Neoplasms / radiotherapy
  • Time Factors
  • Treatment Outcome