73.6 Gy and beyond: hyperfractionated, accelerated radiotherapy for non-small-cell lung cancer.

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 > or = 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 > or = 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 > or = 3 toxicity included esophagus (14 patients; 15%), lung (three patients; 3% [one grade 5]), and skin (four patients; 4%). Grade > or = 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 > or = 3 toxicity seems greater than for conventional RT, though most patients recovered. Late grade > or = 3 pulmonary toxicity occurred in 17%. Because of continued locoregional recurrences, we are currently using doses > or = 86 Gy.

Clinical and dosimetric predictors of radiation-induced esophageal toxicity.

PURPOSE: To evaluate the incidence, severity, and clinical/dosimetric predictors of acute and chronic esophageal toxicities in patients with non-small cell lung cancer (NSCLC) treated with high-dose conformal thoracic radiation. METHODS AND MATERIALS: Ninety-one patients with localized NSCLC treated definitively with high-dose conformal radiation therapy (RT) at Duke University Medical Center (DUMC) were reviewed. Patient characteristics were as follows: 53 males and 38 females; median age 64 yr (range 46-82); stage I--16, II--3, IIIa--40, IIIb--30, X--2; dysphagia pre-RT--6 (7%). Treatment parameters included: median corrected dose-78.8 Gy (range 64.2-85.6); BID fractionation-58 (64%); chemotherapy-43 (47%). Acute and late esophageal toxicities were graded by RTOG criteria. Using 3D treatment planning tools, the esophagus was contoured in a uniform fashion, the 3D dose distribution calculated (with lung density correction), and the dose-volume (DVH) and dose-surface histograms (DSH) generated. At each axial level, the percentage of the esophageal circumference at each dose level was calculated. The length of circumferential esophagus and the maximum circumference treated to doses >50 Gy were assessed. Patient and treatment factors were correlated with acute and chronic esophageal dysfunction using univariate and multivariate logistic regression analyses. RESULTS: There were no acute or late grade 4 or 5 esophageal toxicities. Ten of 91 patients (11%) developed grade 3 acute toxicity. On univariate analysis of clinical parameters, both dysphagia pre-RT (p = 0.10) and BID fractionation (p = 0.11) tended toward significantly predicting grade 3 acute esophagitis. None of the dosimetric parameters analyzed significantly predicted for grade 3 acute esophagitis. Twelve of 66 assessable patients (18%) developed late esophageal toxicity. Of the clinical parameters analyzed, only dysphagia pre-RT (p = 0.06) tended toward significantly predicting late esophageal toxicity. On univariate analyses, the effects of percent organ volume treated >50 Gy (p = 0.05), percent surface area treated >50 Gy (p = 0.05), length of 100% circumference treated >50 Gy (p = 0.04), and maximum percent of circumference treated >80 Gy (p = 0.01) significantly predicted for late toxicity of all grades. On multivariate analysis, percent organ volume treated >50 Gy (p = 0.02) and maximum percent of circumference treated >80 Gy (p = 0.02) predicted for late toxicity. CONCLUSIONS: Late esophageal toxicity following aggressive, high-dose conformal radiotherapy is common but rarely severe. Dosimetric variables addressing the longitudinal and circumferential character of the esophagus have biologic rationale and are predictive of late toxicity. Further studies are needed to assess whether these parameters are better predictors than those derived from traditional DVHs.