利用 SEER-Medicare 和国家癌症数据库评估辅助治疗起始时间对老年胶质母细胞瘤患者生存的影响。

Impact of timing to initiate adjuvant therapy on survival of elderly glioblastoma patients using the SEER-Medicare and national cancer databases.

机构信息

The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA.

Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA.

出版信息

Sci Rep. 2023 Feb 25;13(1):3266. doi: 10.1038/s41598-023-30017-z.

Abstract

The optimal time to initiate adjuvant therapy (AT) in elderly patients with glioblastoma (GBM) remains unclear. We investigated the impact of timing to start AT on overall survival (OS) using two national-scale datasets covering elderly GBM populations in the United States. A total of 3159 and 8161 eligible elderly GBM patients were derived from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked dataset (2004-2013) and the National Cancer Database (NCDB) (2004-2014), respectively. The intervals in days from the diagnosis to the initiation of AT were categorized based on two scenarios: Scenario I (quartiles), ≤ 15, 16-26, 27-37, and ≥ 38 days; Scenario II (median), < 27, and ≥ 27 days. The primary outcome was OS. We performed the Kaplan-Meier and Cox proportional hazards regression methods for survival analysis. A sensitivity analysis was performed using Propensity Score Matching (PSM) method to achieve well-balanced characteristics between early-timing and delayed-timing in Scenario II. Improved OS was observed among patients who underwent resection and initiated AT with either a modest delay (27-37 days) or a longer delay (≥ 38 days) compared to those who received AT immediately (≤ 15 days) from both the SEER-Medicare dataset [adjusted hazard ratio (aHR) 0.74, 95% CI 0.64-0.84, P < 0.001; and aHR 0.81, 95% CI 0.71-0.92, P = 0.002] and the NCDB (aHR 0.83, 95% CI 0.74-0.93, P = 0.001; and aHR 0.87, 95% CI 0.77-0.98, P = 0.017). The survival advantage is observed in delayed-timing group as well in Scenario II. For elderly patients who had biopsy only, improved OS was only detected in a longer delay (Scenario I: ≥ 38 days vs. ≤ 15 days) or the delayed-timing group (Scenario II: ≥ 27 days vs. < 27 days) in the NCDB while no survival difference was seen in SEER-Medicare population. For the best timing to start AT in elderly GBM patients, superior survivals were observed among those who had craniotomy and initiated AT with a modest (27-37 days) or longer delays (≥ 38 days) following diagnosis using both the SEER-Medicare and NCDB datasets (Scenario I). Such survival advantage was confirmed when categorizing delayed-timing vs. early-timing with the cut-off at 27 day in both datasets (Scenario II). The increased likelihood of receiving delayed AT (≥ 27 days) was significantly associated with tumor resection (STR/GTR), years of diagnosis after 2006, African American and Hispanics races, treatments at academic facilities, and being referred. There is no difference in timing of AT on survival among elderly GBM patients who had biopsy in the SEER-Medicare dataset. In conclusion, initiating AT with a modest delay (27-37 days) or a longer delay (≥ 38 days) after craniotomy may be the preferred timing in the elderly GBM population.

摘要

在老年胶质母细胞瘤(GBM)患者中启动辅助治疗(AT)的最佳时机仍不清楚。我们使用涵盖美国老年 GBM 人群的两个国家规模数据集,研究了开始 AT 的时间对总生存期(OS)的影响。从监测、流行病学和最终结果(SEER)-医疗保险链接数据集(2004-2013 年)和国家癌症数据库(NCDB)(2004-2014 年)中分别获得了 3159 名和 8161 名符合条件的老年 GBM 患者。根据两种情况将 AT 开始时间的天数间隔分类:方案 I(四分位数),≤15、16-26、27-37 和≥38 天;方案 II(中位数),<27 和≥27 天。主要结果是 OS。我们使用 Kaplan-Meier 和 Cox 比例风险回归方法进行生存分析。在方案 II 中,使用倾向评分匹配(PSM)方法进行敏感性分析,以实现早期和延迟时间之间的特征良好平衡。与立即接受 AT(≤15 天)的患者相比,接受切除术并在适度延迟(27-37 天)或更长延迟(≥38 天)后开始 AT 的患者的 OS 得到改善,从 SEER-医疗保险数据集[调整后的危险比(aHR)0.74,95%置信区间(CI)0.64-0.84,P<0.001;和 aHR 0.81,95%CI 0.71-0.92,P=0.002]和 NCDB[aHR 0.83,95%CI 0.74-0.93,P=0.001;和 aHR 0.87,95%CI 0.77-0.98,P=0.017]。在方案 II 中,也观察到延迟时间组的生存优势。对于仅接受活检的老年患者,仅在较长的延迟(方案 I:≥38 天与≤15 天)或延迟时间组(方案 II:≥27 天与<27 天)中观察到 OS 改善,而在 SEER-医疗保险人群中则未观察到生存差异。对于老年 GBM 患者开始 AT 的最佳时机,在 SEER-医疗保险和 NCDB 数据集(方案 I)中,接受开颅术并在诊断后适度(27-37 天)或更长时间(≥38 天)延迟开始 AT 的患者,观察到更好的生存。当在两个数据集(方案 II)中将截止时间定义为 27 天时,对延迟时间与早期时间进行分类,确认了这种生存优势。与早期相比,接受延迟 AT(≥27 天)的可能性显著增加与肿瘤切除术(STR/GTR)、诊断后 2006 年的年份、非裔美国人、西班牙裔种族、在学术机构接受治疗以及转诊有关。在 SEER-医疗保险数据集中,接受活检的老年 GBM 患者的 AT 时机对生存没有影响。总之,在接受开颅手术后,适度延迟(27-37 天)或较长延迟(≥38 天)开始 AT 可能是老年 GBM 人群的首选时机。

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