A phase II trial of accelerated hypofractionated three-dimensional conformal radiation therapy in locally advanced non-small cell lung cancer.
ABSTRACT The aim of this study is to evaluate the safety and efficacy of accelerated hypofractionated radiotherapy (HypoRT) combined with sequential chemotherapy in locally advanced non-small cell lung cancer (NSCLC).
A total of 34 patients with stage III NSCLC were enrolled. All patients received accelerated HypoRT (initially 50Gy/20 fractions, then a fraction dose of 3Gy) using three-dimensional conformal radiation therapy (3D-CRT), omitting elective nodal irradiation (ENI), to a total dose of 65-68Gy. All patients received two cycles of induction chemotherapy; 1-2 cycles of consolidation chemotherapy were given to 31 patients. The primary outcome measure was a profile of radiation toxicity. The secondary endpoints included overall survival (OS), progression-free survival (PFS), locoregional PFS (LR-PFS) and the pattern of initial failure.
Radiation toxicity was minimal. The median and 3-year OS, PFS were 19.0 months, 32.1%; 10.0 months, 29.8%, respectively. The 1-, 2-, and 3-year LR-PFS were 69.6%, 60.9% and 60.9%, respectively. No patient experienced isolated elective nodal failure as the first site of failure.
This study suggests that accelerated HypoRT using 3D-CRT omitting ENI can be used in combination with sequential chemotherapy in locally advanced NSCLC.
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ABSTRACT: For many years, high dose radiation therapy was the standard treatment for patients with locally or regionally advanced non-small-cell lung cancer (NSCLC), despite a 5-year survival rate of only 3%-10% following such therapy. From May 1984 through May 1987, the Cancer and Leukemia Group B (CALGB) conducted a randomized trial that showed that induction chemotherapy before radiation therapy improved survival during the first 3 years of follow-up. This report provides data for 7 years of follow-up of patients enrolled in the CALGB trial. The patient population consisted of individuals who had clinical or surgical stage III, histologically documented NSCLC; a CALGB performance status of 0-1; less than 5% loss of body weight in the 3 months preceding diagnosis; and radiographically visible disease. Patients were randomly assigned to receive either 1) cisplatin (100 mg/m2 body surface area intravenously on days 1 and 29) and vinblastine (5 mg/m2 body surface area intravenously weekly on days 1, 8, 15, 22, and 29) followed by radiation therapy with 6000 cGy given in 30 fractions beginning on day 50 (CT-RT group) or 2) radiation therapy with 6000 cGy alone beginning on day 1 (RT group) for a maximum duration of 6-7 weeks. Patients were evaluated for tumor regression if they had measurable or evaluable disease and were monitored for toxic effects, disease progression, and date of death. There were 78 eligible patients randomly assigned to the CT-RT group and 77 randomly assigned to the RT group. Both groups were similar in terms of sex, age, histologic cell type, performance status, substage of disease, and whether staging had been clinical or surgical. All patients had measurable or evaluable disease at the time of random assignment to treatment groups. Both groups received a similar quantity and quality of radiation therapy. As previously reported, the rate of tumor response, as determined radiographically, was 56% for the CT-RT group and 43% for the RT group (P = .092). After more than 7 years of follow-up, the median survival remains greater for the CT-RT group (13.7 months) than for the RT group (9.6 months) (P = .012) as ascertained by the logrank test (two-sided). The percentages of patients surviving after years 1 through 7 were 54, 26, 24, 19, 17, 13, and 13 for the CT-RT group and 40, 13, 10, 7, 6, 6, and 6 for the RT group. Long-term follow-up confirms that patients with stage III NSCLC who receive 5 weeks of chemotherapy with cisplatin and vinblastine before radiation therapy have a 4.1-month increase in median survival. The use of sequential chemotherapy-radiotherapy increases the projected proportion of 5-year survivors by a factor of 2.8 compared with that of radiotherapy alone. However, inasmuch as 80%-85% of such patients still die within 5 years and because treatment failure occurs both in the irradiated field and at distant sites in patients receiving either sequential chemotherapy-radiotherapy or radiotherapy alone, the need for further improvements in both the local and systemic treatment of this disease persists.JNCI Journal of the National Cancer Institute 10/1996; 88(17):1210-5. · 14.34 Impact Factor
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ABSTRACT: Clinical observations often reveal individual differences in the severity of lung fibrosis after definitive radiation therapy for lung cancer. Recent experimental studies suggest that the risk of developing lung fibrosis may be genetically controlled. The present study was undertaken to examine the magnitude of individual variation in the incidence and severity of lung fibrosis in a well-defined patient population treated by concurrent chemoradiation for limited small-cell lung carcinomas (LSCLC). Between 1989 and 1994, 56 patients with LSCLC were enrolled in one of two controlled prospective studies of concurrent chemotherapy and concomitant conventional (45 Gy in 25 fractions q.d. over 5 weeks) or accelerated (45 Gy in 30 fractions b.i.d. over 3 weeks) radiotherapy. Chemotherapy consisted of cisplatin and etoposide (PE) or PE plus ifosfamide and mesna (PIE). Of the 56, a group of 25 patients who had serial computerized tomography (CT) examinations of the chest and were deemed to have unequivocal radiographic complete responses were selected for this study. The severity of lung fibrosis was recorded for each patient from the CT images using an arbitrary scale (0 to 3) at 1 year after treatment. Radiographic fibrosis scores were recorded on 1-3 CT slices in 3 different dose-areas (20-30 Gy; 30-40 Gy; and >40 Gy) that were defined using the corresponding CT slices from the patient's CT treatment plan. Of these patients, 23 (92%) had at least 2 slices scored; 11 patients had all 3 slices scored. Among the clinical and treatment parameters investigated (including type of chemotherapy), only total dose and fractionation schedule were identified as significant and independent determinants of lung fibrosis. Radiographic fibrosis scores were higher in high-dose areas and among patients treated with the accelerated schedule. Using a fit of the proportional odds (PO) model based on the total dose and fractionation schedule, fibrosis score residuals were calculated for each patient. The residual for each score is defined as the difference between the observed and expected score based on the dose and treatment schedule received. Average residuals varied significantly among patients (p = 0.005, Kruskal-Willis test). Using a modified version of the PO model, the coefficient of variation in patient heterogeneity was estimated to be 10.1% (95% confidence interval: 6.2-14.9%). Inclusion of the heterogeneity factor, in addition to total dose and fractionation schedule, improved the fit of the PO model to an extremely high level of significance (p < 10(-7)). Our data indicate that the risk and severity of lung fibrosis analyzed radiographically on CT images increases with total dose and with the use of an accelerated radiation schedule, for patients treated with chemoradiation for small-cell lung cancer. There was also demonstrable patient-to-patient heterogeneity, suggesting that the risk of lung fibrosis is strongly affected by inherent factors that vary among individuals.International Journal of Radiation OncologyBiologyPhysics 06/1998; 41(2):279-86. · 4.52 Impact Factor
- International Journal of Radiation OncologyBiologyPhysics 02/2000; 46(2):516-7. · 4.52 Impact Factor