BRAF 突变转移性黑色素瘤患者早期 18F-FDG PET/CT 对 BRAF 和 MEK 抑制的反应与生存之间的相关性
Correlation between early 18F-FDG PET/CT response to BRAF and MEK inhibition and survival in patients with BRAF-mutant metastatic melanoma.
作者信息
Schmitt Ronald J, Kreidler Sarah M, Glueck Deborah H, Amaria Rodabe N, Gonzalez Rene, Lewis Karl, Bagrosky Brian M, Kwak Jennifer J, Koo Phillip J
机构信息
aDepartment of Radiology bDepartment of Medicine, Division of Medical Oncology, University of Colorado School of Medicine cDepartment of Biostatistics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado dThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
出版信息
Nucl Med Commun. 2016 Feb;37(2):122-8. doi: 10.1097/MNM.0000000000000406.
PURPOSE
Metabolic response to treatment measured by fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on (18)F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy.
MATERIALS AND METHODS
Overall, 24 patients with advanced BRAF-mutant melanoma were included. Patients were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK inhibitor (cobimetinib or trametinib), and were imaged at baseline and shortly thereafter with (18)F-FDG PET/CT. Each scan yielded two values of maximum standardized uptake value (SUVmax): one for the most metabolically active focus and one for the least responsive focus. Short-term treatment response was assessed by evaluating the target lesions using the EROTC criteria. A Cox proportional hazards model was used to examine associations between overall survival (OS) and progression-free survival (PFS) and changes in SUVmax.
RESULTS
The mean time to follow-up (18)F-FDG PET/CT was 26 days. At follow-up, two patients achieved a complete response. For the most metabolically active focus, 22 patients showed a partial response. For the least responsive focus, 18 patients showed a partial response, two had stable disease, and two had progressive disease.A total of 16 patients were alive at the end of the study. For the most metabolically active tumor, no association was observed between changes in SUVmax and OS (P=0.73) or PFS (P=0.17). For the least responsive tumor, change in SUVmax was associated with PFS [hazard ratio (HR)=1.34, 95% confidence interval (CI): 1.06-1.71, P=0.01], but not OS (P=0.52). The ECOG score was associated with OS (HR=11.81, 95% CI: 1.42-97.60, P=0.02) and PFS (HR=24.72, 95% CI: 3.23-189.42, P=0.002).
CONCLUSION
Change in SUVmax for the least responsive tumor and baseline functional performance may be useful prognostic indicators for PFS in patients with BRAF-mutant melanoma.
目的
通过氟-18氟脱氧葡萄糖（(18)F-FDG）PET测量的治疗代谢反应在许多癌症中具有预后意义。本研究调查了接受BRAF和MEK联合抑制治疗的BRAF突变型黑色素瘤患者的生存情况与(18)F-FDG PET/计算机断层扫描（CT）早期变化之间的关联。
材料与方法
总共纳入了24例晚期BRAF突变型黑色素瘤患者。患者接受BRAF抑制剂（维莫非尼或达拉非尼）和MEK抑制剂（考比替尼或曲美替尼）治疗，并在基线期及此后不久进行(18)F-FDG PET/CT成像。每次扫描产生两个最大标准化摄取值（SUVmax）：一个用于代谢最活跃的病灶，另一个用于反应最差的病灶。通过使用欧洲肿瘤内科学会（EROTC）标准评估靶病灶来评估短期治疗反应。采用Cox比例风险模型来研究总生存期（OS）和无进展生存期（PFS）与SUVmax变化之间的关联。
结果
(18)F-FDG PET/CT的平均随访时间为26天。随访时，2例患者达到完全缓解。对于代谢最活跃的病灶，22例患者显示部分缓解。对于反应最差的病灶，18例患者显示部分缓解，2例病情稳定，2例病情进展。在研究结束时共有16例患者存活。对于代谢最活跃的肿瘤，未观察到SUVmax变化与OS（P=0.73）或PFS（P=0.17）之间存在关联。对于反应最差的肿瘤，SUVmax变化与PFS相关[风险比（HR）=1.34，95%置信区间（CI）：1.06-1.71，P=0.01]，但与OS无关（P=0.52）。东部肿瘤协作组（ECOG）评分与OS（HR=11.81，95%CI：1.42-97.60，P=0.02）和PFS（HR=24.72，95%CI：3.23-189.42，P=0.002）相关。
结论
反应最差肿瘤的SUVmax变化和基线功能状态可能是BRAF突变型黑色素瘤患者PFS的有用预后指标。
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