Arriagada R, Le Chevalier T, Borie F, Rivière A, Chomy P, Monnet I, Tardivon A, Viader F, Tarayre M, Benhamou S
Institut Gustave-Roussy, Radiotherapy Department, Villejuif, France.
J Natl Cancer Inst. 1995 Feb 1;87(3):183-90. doi: 10.1093/jnci/87.3.183.
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.
小细胞肺癌患者接受预防性颅脑照射可降低脑转移的总体发生率，但对总生存期无影响。有人认为这种治疗可能会增加神经心理综合征以及计算机断层扫描显示的脑部异常。然而，其他回顾性数据表明，对于完全缓解的患者，预防性颅脑照射对总生存期有有益影响。
我们的目的是评估预防性颅脑照射对完全缓解的小细胞肺癌患者脑转移、总生存期和迟发性毒性作用的影响。
我们对300例完全缓解的小细胞肺癌患者进行了一项前瞻性研究。患者被随机分配接受预防性颅脑照射，在12天内分8次给予24 Gy（治疗组）或不接受预防性颅脑照射（对照组）。在随机分组时进行神经心理学检查和脑部计算机断层扫描，并在6、18、30和48个月时反复评估。根据总事件发生率并使用竞争风险方法，根据孤立的首个复发部位分析失败模式。
对随机分组时没有脑转移的294例患者进行了分析。作为孤立的首个复发部位，对照组2年脑转移累积发生率为45%，治疗组为19%（P < 10⁻⁶）。2年脑转移总发生率分别为67%和40%（相对风险 = 0.35；P < 10⁻¹³）。对照组2年总生存率为21.5%，治疗组为29%（相对风险 = 0.83；P = 0.14）。两组在神经心理功能或脑部计算机断层扫描显示的异常方面无显著差异。
对完全缓解的小细胞肺癌患者进行预防性颅脑照射可将脑转移风险降低三倍，且并发症无显著增加。对总生存期的可能有益影响应以更高的统计效能进行检验。
目前，该试验结果支持对完全缓解的患者进行预防性颅脑照射。需要更长时间的随访和验证性试验来全面评估迟发性毒性作用。对总生存期的可能影响需要在更多完全缓解的患者中进行评估，建议对类似试验进行荟萃分析。
