Carcinoma of the larynx treated with hypofractionated radiation and hyperbaric oxygen: Long-term tumor control and complications

Purpose: To evaluate the long-term outcome with respect to local control, survival, and complications in a cohort of patients with locally advanced laryngeal carcinoma treated with hypofractionated radiation and hyperbaric oxygen at 4 atmosphers of pressure (HBO-4). Methods and Materials: Between January 1970 and August 1982, 45 patients,vith locally advanced carcinoma of the larynx were treated with primary radiation using a unique hypofractionated schedule of 2 fractions of 11 Gy separated by 21 days, with concomitant HBO-4 during each radiotherapy session. To avoid seizures, discomfort and other complications of HBO-4, each session was performed under general anesthesia. All patients had pathologically confirmed squamous cell carcinoma of the glottic (23) or supraglottic larynx (22) and were staged as follows: T2-5, T3-24, T-4-16; N0-26, N1-4, N2-13, N3-1. Patients were treated with opposed lateral wedged fields of 4-6MV photons, with a median field size of 5.5 x 9.75 to a total median dose of 22.5 Gy. Results: As of February 1998, follow-up was complete on all but one patient, who relocated to another country after 8 years. Complete clinical responses were observed in 39 (87%) of the cases. The 10-year local control rate for all 45 patients was 58%, and local control for the complete responders was 69%. Three patients underwent laryngectomy for complications and were found to have no pathological evidence of disease in the laryngectomy specimen. The 10-year survival of the overall population was 27%. The 10-year voice preservation rate for the the 39 complete responders was 55%. Acute mucosal and skin reactions mere modest and acceptable. Significant late complications occurred in 14 patients consisting of severe fibrosis, necrosis, pharyngeal fistula,,vith 3 patients requiring laryngectomy for complications. The actuarial rate of severe complications at 5 years was 42%. Conclusions: The response rate and long-term tumor control rate obtained,vith this treatment program were comparable to more protracted radiation schedules with or without systemic chemotherapy. The complication rate was high resulting in an adverse therapeutic ratio. The radiobiologic interpretation of this clinical data, and implications for hypoxia directed therapy, are discussed. (C) 1999 Elsevier Science Inc.