Sperduto Paul W, Jiang Wen, Brown Paul D, Braunstein Steve, Sneed Penny, Wattson Daniel A, Shih Helen A, Bangdiwala Ananta, Shanley Ryan, Lockney Natalie A, Beal Kathryn, Lou Emil, Amatruda Thomas, Sperduto William A, Kirkpatrick John P, Yeh Norman, Gaspar Laurie E, Molitoris Jason K, Masucci Laura, Roberge David, Yu James, Chiang Veronica, Mehta Minesh
Minneapolis Radiation Oncology, Minneapolis, Minnesota.
MD Anderson Cancer Center, Houston, Texas.
Int J Radiat Oncol Biol Phys. 2017 Aug 1;98(5):1069-1077. doi: 10.1016/j.ijrobp.2017.03.030. Epub 2017 Mar 29.
Brain metastases are a common problem in patients with melanoma, but little is known about the effect of gene mutations on survival in these patients.
We created a retrospective multi-institutional database of 823 patients with melanoma and brain metastases diagnosed between 2006 and 2015. Clinical parameters, gene mutation status (BRAF, C-KIT, NRAS), and treatment were correlated with survival. Treatment patterns and outcomes were compared with a prior era (1985-2005).
BRAF status was known in 584 of 823 patients (71%). BRAF, NRAS, and C-KIT mutations were present in 51%, 22%, and 11% of tested patients, respectively. The median time from primary diagnosis to brain metastasis was 32 months, and overall median survival (MS) from the time of initial treatment of brain metastases was 10 months. MS for BRAF-positive and BRAF-negative patients was 13 months and 9 months, respectively (P=.02). There was no significant difference in MS in patients with or without NRAS or C-KIT mutations. The time from primary diagnosis to brain metastasis did not vary by mutation and was not associated with survival after the diagnosis of brain metastases. MS for the 1985 to 2005 and 2006 to 2015 cohorts was 6.7 months and 10.0 months, respectively (P<.01). Reflecting treatment-trend changes, use of whole-brain radiation therapy decreased from 48% to 26% during this period. Among BRAF-positive patients, 71% received targeted BRAF and/or MEK inhibitors and 57% received some combination of targeted therapy, chemotherapy, and/or immunotherapy.
For melanoma patients with brain metastases, BRAF-positive patients survive longer than BRAF-negative patients and overall survival has improved from 1985-2005 to 2006-2015.
脑转移是黑色素瘤患者的常见问题，但关于基因突变对这些患者生存的影响知之甚少。
我们建立了一个回顾性多机构数据库，纳入了2006年至2015年间诊断的823例黑色素瘤合并脑转移患者。将临床参数、基因突变状态（BRAF、C-KIT、NRAS）和治疗与生存情况进行关联分析。将治疗模式和结果与之前的时期（1985 - 2005年）进行比较。
823例患者中有584例（71%）的BRAF状态已知。BRAF、NRAS和C-KIT突变分别出现在51%、22%和11%的检测患者中。从原发诊断到脑转移的中位时间为32个月，从脑转移初始治疗时间起的总体中位生存期（MS）为10个月。BRAF阳性和BRAF阴性患者的MS分别为13个月和9个月（P = 0.02）。NRAS或C-KIT突变患者与未突变患者的MS无显著差异。从原发诊断到脑转移的时间不因突变而异，且与脑转移诊断后的生存无关。1985年至2005年队列和2006年至2015年队列的MS分别为6.7个月和10.0个月（P < 0.01）。反映治疗趋势变化，在此期间全脑放疗的使用从48%降至26%。在BRAF阳性患者中，71%接受了靶向BRAF和/或MEK抑制剂治疗，57%接受了靶向治疗、化疗和/或免疫治疗的某种联合治疗。
对于黑色素瘤脑转移患者，BRAF阳性患者的生存期长于BRAF阴性患者，且从1985 - 2005年到2006 - 2015年总体生存率有所提高。
