El Shafie Rami A, Dresel Thorsten, Weber Dorothea, Schmitt Daniela, Lang Kristin, König Laila, Höne Simon, Forster Tobias, von Nettelbladt Bastian, Eichkorn Tanja, Adeberg Sebastian, Debus Jürgen, Rieken Stefan, Bernhardt Denise
Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
Front Oncol. 2020 May 8;10:693. doi: 10.3389/fonc.2020.00693. eCollection 2020.
Following the resection of brain metastases (BM), whole-brain radiotherapy (WBRT) is a long-established standard of care. Its position was recently challenged by the less toxic single-session radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) of the resection cavity, reducing dose exposure of the healthy brain. We analyzed 101 patients treated with either SRS/FSRT ( = 50) or WBRT ( = 51) following BM resection over a 5-year period. Propensity score adjustment was done for age, total number of BM, timepoint of BM diagnosis, controlled primary and extracranial metastases. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS), local control (LC) and distant brain control (DBC). Median patient age was 61 (interquartile range, IQR: 56-67) years and the most common histology was non-small cell lung cancer, followed by breast cancer. 38% of the patients had additional unresected BM. Twenty-four patients received SRS, 26 patients received FSRT and 51 patients received WBRT. Median OS in the SRS/FSRT subgroup was not reached (IQR NA-16.7 months) vs. 12.6 months (IQR 21.3-4.4) in the WBRT subgroup (hazard ratio, HR 3.3, 95%-CI: [1.5; 7.2] < 0.002). Twelve-months LC-probability was 94.9% (95%-CI: [88.3; 100.0]) in the SRS subgroup vs. 81.7% (95%-CI: [66.6; 100.0]) in the WBRT subgroup (HR 0.2, 95%-CI: [0.01; 0.9] = 0.037). Twelve-months DBC-probabilities were 65.0% (95%-CI: [50.8; 83.0]) and 58.8% (95%-CI: [42.9; 80.7]), respectively (HR 1.4, 95%-CI: [0.7; 2.7] = 0.401). In propensity score-adjusted multivariate analysis, incomplete resection negatively impacted OS (HR 3.9, 95%-CI: [2.0;7.4], < 0.001) and LC (HR 5.4, 95%-CI: [1.3; 21.9], = 0.018). Excellent clinical performance (HR 0.4, 95%-CI: [0.2; 0.9], = 0.030) and better graded prognostic assessment (GPA) score (HR 0.4, 95%-CI: [0.2; 1.0], = 0.040) were prognostic of superior OS. A higher number of BM was associated with a greater risk of developing new distant BM (HR 5.6, 95%-CI: [1.0; 30.4], = 0.048). In subgroup analysis, larger cavity volume (HR 1.1, 95%-CI: [1.0; 1.3], = 0.033) and incomplete resection (HR 12.0, 95%-CI: [1.2; 118.3], = 0.033) were associated with inferior LC following SRS/FSRT. This is the first propensity score-adjusted direct comparison of SRS/FSRT and WBRT following the resection of BM. Patients receiving SRS/FSRT showed longer OS and LC compared to WBRT. Future analyses will address the optimal choice of safety margin, dose and fractionation for postoperative stereotactic RT of the resection cavity.
脑转移瘤(BM)切除术后,全脑放疗(WBRT)一直是既定的标准治疗方法。最近,其地位受到了切除腔单次立体定向放射外科治疗(SRS)或分次立体定向放射治疗(FSRT)的挑战,后者毒性较小,可减少健康脑组织的剂量暴露。我们分析了5年间101例BM切除术后接受SRS/FSRT(n = 50)或WBRT(n = 51)治疗的患者。对年龄、BM总数、BM诊断时间点、原发灶及颅外转移灶的控制情况进行了倾向评分调整。采用Cox比例风险模型进行单因素和多因素分析,以评估总生存期(OS)、局部控制率(LC)和远处脑转移控制率(DBC)。患者中位年龄为61岁(四分位间距,IQR:56 - 67岁),最常见的组织学类型为非小细胞肺癌,其次为乳腺癌。38%的患者有额外未切除的BM。24例患者接受SRS治疗,26例患者接受FSRT治疗,51例患者接受WBRT治疗。SRS/FSRT亚组的中位OS未达到(IQR NA - 16.7个月),而WBRT亚组为12.6个月(IQR 21.3 - 4.4)(风险比,HR 3.3,95%置信区间:[1.5;7.2],P < 0.002)。SRS亚组的12个月LC概率为94.9%(95%置信区间:[88.3;100.0]),WBRT亚组为81.7%(95%置信区间:[66.6;100.0])(HR 0.2,95%置信区间:[0.01;0.9],P = 0.037)。12个月的DBC概率分别为65.0%(95%置信区间:[50.8;83.0])和58.8%(95%置信区间:[42.9;80.7])(HR 1.4,95%置信区间:[0.7;2.7],P = 0.401)。在倾向评分调整的多因素分析中,不完全切除对OS(HR 3.9,95%置信区间:[2.0;7.4],P < 0.001)和LC(HR 5.4,95%置信区间:[1.3;21.9],P = 0.018)有负面影响。良好的临床表现(HR 0.4,95%置信区间:[0.2;0.9],P = 0.030)和较好的预后分级评估(GPA)评分(HR 0.4,95%置信区间:[0.2;1.0],P = 0.040)是OS较好的预后因素。较高数量的BM与发生新的远处BM的风险增加相关(HR 5.6,95%置信区间:[1.0;30.4],P = 0.048)。在亚组分析中,较大的腔体积(HR 1.1,95%置信区间:[1.0;1.3],P = 0.033)和不完全切除(HR 12.0,95%置信区间:[1.2;118.3],P = 0.033)与SRS/FSRT后的LC较差相关。这是BM切除术后SRS/FSRT与WBRT的首次倾向评分调整直接比较。与WBRT相比,接受SRS/FSRT的患者OS和LC更长。未来的分析将探讨切除腔术后立体定向放疗安全边缘、剂量和分割的最佳选择。