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 de-escalation 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.
Highlights
Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common cancer worldwide, with 650 000 new cases diagnosed and 330 000 deaths each year [1]
When the cell samples were positioned at the middle of the spread-out Bragg peak (SOBP) (Figure 1), the relative biological effectiveness (RBE) values were found to be higher for protons than for photons in all 6 Head and neck squamous cell carcinomas (HNSCCs) cell lines tested (RBEs all .1.06), and single fractions of 2 Gy each had greater RBE values than did single 4
No enhanced biological effect was observed for protons versus photons when the HNSCC cells were exposed to multiple fractions totaling 8 Gy, when the endpoint was number of viable cells at 96 hours after irradiation [21]. These findings indicate that protons have enhanced biological effects relative to photons in HNSCC
Summary
Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common cancer worldwide, with 650 000 new cases diagnosed and 330 000 deaths each year [1]. The proximity of numerous critical organs and structures in the head and neck region makes IMRT challenging for treating HNSCC, the more precise technique of intensity-modulated proton therapy (IMPT) is a promising alternative because, relative to photons, protons allow highly conformal dose distributions to tumors with a considerable reduction of the integral dose to normal tissue [8], fewer treatment-related side effects [9,10,11], and presumably comparable disease control. This capability for highly conformal doses allows escalation of doses to tumors with simultaneous de-escalation of the dose to normal tissues.
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