Radiotherapy Research - Cancer treatment, Side effects

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Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): predictors for radiation pneumonitis and fibrosis.

Kong FM, Hayman JA, Griffith KA, Kalemkerian GP, Arenberg D, Lyons S, Turrisi A, Lichter A, Fraass B, Eisbruch A, Lawrence TS, Ten Haken RK

Department of Radiation Oncology, University of Michigan, and Radiation Oncology, Veterans Administration Medical Center, Ann Arbor, MI 48109, USA. Fengkong@med.umich.edu

PURPOSE: We aimed to report the final toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non-small-cell lung cancer (NSCLC) by quantifying the dose-volume toxicity relationship of the lung. METHODS AND MATERIALS: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. RESULTS: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly (p<0.001) associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. If cutoffs are 30% for V20, 20 Gy for MLD, and 10% for NTCP, these factors have positive predictive values of 50% to 71% and negative predictive value of 85% to 89%. CONCLUSIONS: With long-term follow-up for toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative lung dose-volume toxicity-based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients.

Published 26 June 2006 in Int J Radiat Oncol Biol Phys, 65(4): 1075-86.
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