The biological basis for enhanced effects of proton radiation therapy relative to photon radiation therapy for head and neck squamous cell carcinoma

Li Wang, Piero Fossati, Harald Paganetti, Li Ma, Maura Gillison, Jeffrey N. Myers, Eugen Hug, Steven J. Frank*

*Corresponding author for this work

Research output: Journal article (peer-reviewed)Journal article

13 Citations (Scopus)

Abstract

Head and neck squamous cell carcinomas (HNSCCs) often present as local-regionally advanced disease at diagnosis, for which a current standard of care is x-ray-based radiation therapy, with or without chemotherapy. This approach provides effective local regional tumor control, but at the cost of acute and late toxicity that can worsen quality of life and contribute to mortality. For patients with human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma (SCC) in particular, for whom the prognosis is generally favorable, de-escalation of the radiation dose to surrounding normal tissues without diminishing the radiation dose to tumors is desired to mitigate radiation-related toxic effects. Proton radiation therapy (PRT) may be an excellent deescalation strategy because of its physical properties (that eliminate unnecessary radiation to surrounding tissues) and because of its biological properties (including tumor-specific variations in relative biological effectiveness [RBE] and linear energy transfer [LET]), in combination with concurrent systemic therapy. Early clinical evidence has shown that compared with x-ray-based radiation therapy, PRT offers comparable disease control with fewer and less severe treatment-related toxicities that can worsen the quality of life for patients with HNSCC. Herein, we review aspects of the biological basis of enhanced HNSCC cell response to proton versus x-ray irradiation in terms of radiation-induced gene and protein expression, DNA damage and repair, cell death, tumor immune responses, and radiosensitization of tumors.

Original languageEnglish
Pages (from-to)3-13
Number of pages11
JournalInternational Journal of Particle Therapy
Volume8
Issue number1
DOIs
Publication statusPublished - 01 Jun 2021
Externally publishedYes

Keywords

  • Biological effect
  • Head and neck cancer
  • Proton radiation therapy
  • Radiation sensitization
  • X-ray radiation therapy

ASJC Scopus subject areas

  • Atomic and Molecular Physics, and Optics
  • Radiology, Nuclear Medicine and Imaging

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