73.6 Gy and Beyond: Hyperfractionated, Accelerated Radiotherapy for Non–Small-Cell Lung Cancer

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Abstract
PURPOSE: To assess results with twice-daily high-dose radiotherapy (RT) for non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between 1991 and 1998, 94 patients with unresectable NSCLC were prescribed ≥ 73.6 Gy via accelerated fractionation. Fifty were on a phase II protocol (P group); 44 were similarly treated off-protocol (NP group). The clinical target volume received 45 Gy at 1.25 Gy bid (6-hour interval). The gross target volume received 1.6 Gy bid to 73.6 to 80 Gy over 4.5 to 5 weeks using a concurrent boost technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated by the Kaplan-Meier method. Median follow-up durations for surviving P and NP patients were 67 and 16 months, respectively. RESULTS: Total doses received were ≥ 72 Gy in 97% of patients. The median OS by stage was 34, 13, and 12 months for stages I/II, IIIa, and IIIb, respectively. LPFS was significantly longer for patients with T1 lesions (median, 43 months) versus T2-4 (median, 7 to 10 months; P = .01). Results were similar in the P and NP groups. Acute grade ≥ 3 toxicity included esophagus (14 patients; 15%), lung (three patients; 3% [one grade 5]), and skin (four patients; 4%). Grade ≥ 3 late toxicity in 86 assessable patients included esophagus (three patients; 3%), lung (15 patients; 17% [three grade 5]), skin (five patients; 6%), heart (two patients; 2%), and nerve (one patient; 1%). CONCLUSION: This regimen yielded favorable survival results, particularly for T1 lesions. Acute grade ≥ 3 toxicity seems greater than for conventional RT, though most patients recovered. Late grade ≥ 3 pulmonary toxicity occurred in 17%. Because of continued locoregional recurrences, we are currently using doses ≥ 86 Gy.

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