PROPHYLACTIC CRANIAL IRRADIATION FOR PATIENTS WITH SMALL-CELL LUNG-CANCER IN COMPLETE REMISSION

Background: Prophylactic cranial irradiation in patients with small-ce ll lung cancer decreases the overall rate of brain metastases without an effect on overall survival, It has been suggested that this treatme nt may increase neuropsychological syndromes and brain abnormalities i ndicated by computed tomography scans, However, other retrospective da ta suggested a beneficial effect on overall survival for patients in c omplete remission, Purpose: Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis, overall surviva l, and late-occurring toxic effects in patients with small-cell lung c ancer in complete remission. Methods: We conducted a prospective study of 300 patients who had small-cell lung cancer that was in complete r emission, The patients were randomly assigned to receive either prophy lactic cranial irradiation delivering 24 Gy in eight fractions during 12 days (treatment group) or no prophylactic cranial irradiation (cont rol group), A neuropsychological examination and a computed tomography scan of the brain were performed at the time of random assignment and repeatedly assessed at 6, 18, 30, and 48 months, Patterns of failure were analyzed according to total event rates and also according to an isolated first site of relapse, using a competing-risk approach, Resul ts: Two hundred ninety-four patients who did not have brain metastases at the time of random assignment were analyzed, The 2-year cumulative rate of brain metastasis as an isolated first site of relapse was 45% in the control group and 19% in the treatment group (P<10(-6)), The t otal 2-year rate of brain metastasis was 67% and 40%, respectively (re lative risk = 0.35; p<10(-13)). The 2-year overall survival rate was 2 1.5% in the control group and 29% in the treatment group (relative ris k = 0.83; P = .14), There were no significant differences between the two groups in terms of neuropsychological function or abnormalities in dicated by computed tomography brain scans, Conclusions: Prophylactic cranial irradiation given to patients with small-cell lung cancer in c omplete remission decreases the risk of brain metastasis threefold wit hout a significant increase in complications, A possible beneficial ef fect on overall survival should be tested with a higher statistical po wer, Implications: The results of the trial favor, at present, the ind ication of prophylactic cranial irradiation for patients who are in co mplete remission. A longer follow-up and confirmatory trials are neede d to fully assess late-occurring toxic effects. The possible effect on overall survival needs to be evaluated with a larger number of patien ts in complete remission, and a meta-analysis of similar trials is rec ommended.