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, s urvival, and complications in a cohort of patients with locally advanced la ryngeal carcinoma treated with hypofractionated radiation and hyperbaric ox ygen at 4 atmosphers of pressure (HBO-4). Methods and Materials: Between January 1970 and August 1982, 45 patients,vi th locally advanced carcinoma of the larynx were treated with primary radia tion using a unique hypofractionated schedule of 2 fractions of 11 Gy separ ated by 21 days, with concomitant HBO-4 during each radiotherapy session. T o avoid seizures, discomfort and other complications of HBO-4, each session was performed under general anesthesia. All patients had pathologically co nfirmed 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, N 3-1. Patients were treated with opposed lateral wedged fields of 4-6MV phot ons, 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 respons es were observed in 39 (87%) of the cases. The 10-year local control rate f or all 45 patients was 58%, and local control for the complete responders w as 69%. Three patients underwent laryngectomy for complications and were fo und to have no pathological evidence of disease in the laryngectomy specime n. The 10-year survival of the overall population was 27%. The 10-year voic e preservation rate for the the 39 complete responders was 55%. Acute mucos al and skin reactions mere modest and acceptable. Significant late complica tions occurred in 14 patients consisting of severe fibrosis, necrosis, phar yngeal fistula,,vith 3 patients requiring laryngectomy for complications. T he actuarial rate of severe complications at 5 years was 42%. Conclusions: The response rate and long-term tumor control rate obtained,vi th this treatment program were comparable to more protracted radiation sche dules with or without systemic chemotherapy. The complication rate was high resulting in an adverse therapeutic ratio. The radiobiologic interpretatio n of this clinical data, and implications for hypoxia directed therapy, are discussed. (C) 1999 Elsevier Science Inc.