Rationale for integrating high-dose rate intraoperative radiation (HDR-IORT) and postoperative external beam radiation with subcutaneous amifostine for the management of stage III/IV head and neck cancer.

Locoregional recurrence remains a major obstacle to achieving cure of locally advanced head and neck cancers despite maximal resection and postoperative external beam radiation therapy (EBRT). Locoregional failure occurs in 30% to 40% of high-risk resected head and neck cancer patients after standard postoperative EBRT. In an effort to overcome this problem, a number of strategies have been designed to enhance the effectiveness of radiation including concurrent postoperative chemoradiation, accelerated radiation schedules, incorporation of targeted biologic therapies, and improved radiation delivery techniques such as intensity modulated radiation and high-dose rate (HDR) intraoperative radiation therapy. Intraoperative radiation therapy (IORT) represents an important approach to improve outcome in head and neck cancer patients treated with definitive surgery. High-dose rate IORT is defined as the delivery of a single, large dose of radiation at the time of surgery when the tumor bed is exposed. In conjunction with EBRT, HDR-IORT offers several advantages including: (1) conformal delivery of a large dose of radiation while the tumor bed is precisely defined, minimizing the risk of a geographic miss; (2) potential for subsequent dose reduction of EBRT; (3) shortening overall treatment time; and (4) dose-escalation. Because mucositis represents the dose-limiting acute toxicity and xerostomia ranks as the most common long-term quality-of-life complaint, a reduction of the EBRT dose may provide an important benefit in reducing toxicity, especially when combined with the radioprotectant amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD). The purpose of this article is to review the rationale for integrating HDR-IORT with a reduced dose of postoperative EBRT combined with amifostine to improve locoregional control and quality of life outcomes in advanced-stage resected head and neck cancer patients.