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Combined chemotherapy and radiotherapy versus surgery and postoperative radiotherapy for advanced hypopharyngeal cancer.

BACKGROUND: Although the standard therapy for locally advanced hypopharyngeal cancer remains surgery and postoperative radiotherapy (RT), alternative treatment approaches include induction chemotherapy and RT. The purpose of this retrospective study was to compare the long-term outcome of these treatments performed in a single institution. METHODS: Twenty-six patients with advanced, resectable, squamous cell carcinoma of the hypopharynx were treated with induction chemotherapy and definitive RT (group I), reserving laryngectomy for salvage. The induction phase of therapy consisted of 2-3 cycles of cisplatin-based chemotherapy followed by conventional fractionated RT to doses of 66-70 Gy. The outcomes of this group of patients were compared with the outcomes of 30 patients with hypopharyngeal cancer who were treated at our institution with surgery and postoperative RT (group II). The median follow-up times of the surviving patients in groups I and II were 5 and 9 years, respectively. RESULTS: The local recurrence-free survival at 5 years from the completion of therapy for group I was 50%, compared with 69% for group II (p = .41). Among patients with T3-T4 primary tumors, the 5-year local control rates were 58% and 59% for groups I and II, respectively (p = .78). The likelihood of larynx preservation, free of local disease at 5 years for group I, was 52%. The 5-year neck recurrence-free survival for groups I and II were 47% and 69%, respectively (p = .66). Among patients with N2-N3 stage disease, the 5-year incidence of neck failure for groups I and II were 73% and 68%, respectively (p = .74). The 5-year distant metastases-free survival for groups I and II were 67% and 57%, respectively (p = .19). The 5-year disease-free survival rates for groups I and II were 30% and 42%, respectively (p = .9). The 5-year overall survival rates for groups I and II were 15% and 22%, respectively (p = .65). CONCLUSIONS: Nonsurgical therapy for advanced stage hypopharyngeal cancer provides survivorship comparable with that achieved with standard approaches of surgery and postoperative RT. However, despite the therapy, the outcome is poor. Future studies will need to explore new treatment strategies in an effort to improve upon the outcome for this group of patients.

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Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer.

PURPOSE AND OBJECTIVE: Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precision radiotherapy designed to increase the tumor dose and decrease the dose to normal tissues. This study reports the final results of the first two dose levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D-CRT for the treatment of non-small cell lung cancer. PATIENTS AND METHODS: Fifty-two patients were treated with 3D-CRT without chemotherapy. The median age was 67 years (range, 39-82 years). The majority of patients had locally advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week. A radiation dose level was considered complete when 10 patients received the intended dose without unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme. RESULTS: Twenty patients were initially assigned to the 70.2-Gy level; 14 of them received the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 (fatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxicity, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible for dose escalation. Patients who had a normal tissue complication probability (NTCP) of greater than 25% received a lower dose of radiation. An additional 18 patients were entered on the modified study; 11 of them received 70.2 Gy. One patient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients developed grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75.6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity, and one patient refused treatment. The 2-year local control, disease-free survival, and overall survival rates were 37%, 12%, and 24%, respectively. The median survival time was 11 months. DISCUSSION: Treatment to 70.2 Gy and 75.6 Gy using 3D-CRT was delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouraging in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gy level of the study.

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