Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial.
Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial.
复制标题
DOI：
10.1001/jama.2016.9839
复制
发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Asher AL
中科院分区：
文献类型：
--
作者：
Brown PD;Jaeckle K;Ballman KV;Farace E;Cerhan JH;Anderson SK;Carrero XW;Barker FG 2nd;Deming R;Burri SH;Ménard C;Chung C;Stieber VW;Pollock BE;Galanis E;Buckner JC;Asher AL
全脑放疗（WBRT）可显著改善立体定向放射手术（SRS）后脑肿瘤的控制，但由于其与认知能力下降有关，其在脑转移患者治疗中的作用仍存在争议。确定单独SRS与SRS加WBRT后3个月的认知退化是否更少。在北美的34家机构中，2002年2月至2013年12月期间，1至3例脑转移患者被随机分配接受SRS或SRS + WBRT。WBRT剂量计划为30 Gy，分12次；SRS加WBRT组的SRS剂量为18 ~ 22 Gy，单独SRS组的剂量为20 ~ 24 Gy。主要终点是完成基线和3个月评估的参与者的认知恶化（在3个月时至少进行一次认知测试，比基线下降100个标准差）。次要终点包括颅内衰竭时间、生活质量、功能独立性、长期认知状态和总生存期。213名随机受试者（单独SRS， n = 111； SRS加WBRT， n = 102），平均年龄为60.6岁（SD， 10.5岁）；103例（48%）为女性。单独SRS治疗后3个月的认知功能恶化（40/63例[63.5%]）少于联合WBRT治疗（44/48例[91.7%]），差异为- 28.2%;90% CI, - 41.9%至- 14.4%;P < .001)。单独使用SRS的患者在3个月时的生活质量更高，包括总体生活质量（与基线相比的平均变化，- 0.1 vs - 12.0点；平均差值，11.9;95% CI, 4.8-19.0点；P = .001）。与SRS + WBRT相比，单独SRS组颅内衰竭时间明显缩短（风险比3.6;95% CI, 2.2-5.9; P < 0.001）。治疗组3个月时功能独立性无显著差异（从基线平均变化，单独SRS组为- 1.5点，SRS加WBRT组为- 4.2点；平均差异为2.7点；95% CI, - 2.0至7.4点；P = 0.26）。单独SRS的中位总生存期为10.4个月，SRS加WBRT的中位总生存期为7.4个月（风险比1.02;95% CI, 0.75-1.38; P = 0.92）。对于长期幸存者，单独SRS后3个月（5/11 [45.5%]vs 16/17[94.1%]；差异为- 48.7%;95% CI, - 87.6%至- 9.7%;P = .007）和12个月（6/10 [60%]vs 17/18[94.4%]；差异为- 34.4%;95% CI, - 74.4%至5.5%;P = .04）的认知恶化发生率较低。在1 - 3个脑转移的患者中，与SRS联合WBRT相比，单独使用SRS在3个月时导致的认知衰退更少。在总体生存期没有差异的情况下，这些研究结果表明，对于有1至3个脑转移的患者，放射手术可以接受，单独的SRS可能是首选策略。clinicaltrials.gov标识符：NCT00377156
Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, −28.2%; 90% CI, −41.9% to −14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, −0.1 vs −12.0 points; mean difference, 11.9; 95% CI, 4.8–19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2–5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, −1.5 points for SRS alone vs −4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, −2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75–1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, −48.7%; 95% CI, −87.6% to −9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, −34.4%; 95% CI, −74.4% to 5.5%; P = .04). Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy. clinicaltrials.gov Identifier: NCT00377156