Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer in Complete Remission

Institut Gustave-Roussy, Radiotherapy Department, Villejuif, France.
JNCI Journal of the National Cancer Institute (Impact Factor: 15.16). 03/1995; 87(3):183-90. DOI: 10.1093/jnci/87.3.183
Source: PubMed

ABSTRACT Prophylactic cranial irradiation in patients with small-cell lung cancer decreases the overall rate of brain metastases without an effect on overall survival. It has been suggested that this treatment may increase neuropsychological syndromes and brain abnormalities indicated by computed tomography scans. However, other retrospective data suggested a beneficial effect on overall survival for patients in complete remission.
Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis, overall survival, and late-occurring toxic effects in patients with small-cell lung cancer in complete remission.
We conducted a prospective study of 300 patients who had small-cell lung cancer that was in complete remission. The patients were randomly assigned to receive either prophylactic cranial irradiation delivering 24 Gy in eight fractions during 12 days (treatment group) or no prophylactic cranial irradiation (control 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.
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 total 2-year rate of brain metastasis was 67% and 40%, respectively (relative risk = 0.35; P < 10(-13)). The 2-year overall survival rate was 21.5% in the control group and 29% in the treatment group (relative risk = 0.83; P = .14). There were no significant differences between the two groups in terms of neuropsychological function or abnormalities indicated by computed tomography brain scans.
Prophylactic cranial irradiation given to patients with small-cell lung cancer in complete remission decreases the risk of brain metastasis threefold without a significant increase in complications. A possible beneficial effect on overall survival should be tested with a higher statistical power.
The results of the trial favor, at present, the indication of prophylactic cranial irradiation for patients who are in complete remission. A longer follow-up and confirmatory trials are needed to fully assess late-occurring toxic effects. The possible effect on overall survival needs to be evaluated with a larger number of patients in complete remission, and a meta-analysis of similar trials is recommended.

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    • "In the early 1970s, the brain was assumed to be a pharmacologic sanctuary and it was suggested that cranial irradiation might prevent the development of clinically evident brain metastases. These hypotheses led to several clinical trials that evaluated the role of prophylactic cranial irradiation in patients with SCLC: the results of these trials showed a significant decrease in the incidence of brain metastasis, with no increase in neuropsychological complications , but were inconclusive with regard to the benefit in terms of overall survival [21] [22]. A meta-analysis based on individual data of 987 patients with SCLC in complete remission who took part in seven trials evaluated the role of prophylactic cranial irradiation in prolonging survival [23]. "
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    • "The TRT rate in the Sundstrom study was higher in both arms (83 and 88%). Prophylactic cranial irradiation has been shown to be associated with a survival advantage in LD and ED patients responding to chemotherapy (Auperin et al, 1999) (Slotman et al, 2007). In this study, 33% of LD patients receiving PE and 23% of those receiving ACE went on to have PCI. "
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