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评价立体定向体部放射治疗成人颅外寡转移的疗效和结局。

Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis.

机构信息

Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Department of Radiation Oncology, University of Florida, Jacksonville.

出版信息

JAMA Netw Open. 2020 Nov 2;3(11):e2026312. doi: 10.1001/jamanetworkopen.2020.26312.

Abstract

IMPORTANCE

The outcomes and factors that influence survival in patients with oligometastasis (OM) are not well understood and have not been well described in large-scale studies.

OBJECTIVE

To evaluate overall progression-free survival (PFS), widespread progression (WSP) outcomes, and survival factors from a pooled data set of 1033 patients with OM treated with stereotactic body radiotherapy (SBRT).

DESIGN, SETTING, AND PARTICIPANTS: Case series from January 1, 2008, to December 31, 2016. The dates of analysis were April 2019 to May 2020. The setting was multi-institutional tertiary care hospitals. Participants were consecutive patients with 5 or fewer extracranial OMs whose primary tumor was treated curatively.

EXPOSURE

Definitive SBRT.

MAIN OUTCOMES AND MEASURES

Overall survival (OS), progression-free survival, rate of WSP, patterns of failure, and factors altering OS.

RESULTS

In the largest international OM case series to date (1033 participants) (mean age, 68.0 years [range, 18.0-94.3 years]; 601 [58.2%] men), 1416 SBRT courses were delivered to patients with 1 OM (596 [57.7%]), 2 OMs (245 [23.7%]), 3 OMs (105 [10.2%]), 4 OMs (55 [5.3%]), and 5 OMs (32 [3.1%]). The median follow-up was 24.1 months (range, 0.3-104.7 months), and the median OS was 44.2 months (95% CI, 39.2-48.8 months). The median PFS was 12.9 months (95% CI, 11.6-14.2 months), and the median time to WSP was 42.5 months (95% CI, 36.8-53.5 months). The OS rates were 84.1% (95% CI, 81.7%-86.2%) at 1 year, 56.7% (95% CI, 53.0%-60.2%) at 3 years, and 35.2% (95% CI, 30.1%-40.3%) at 5 years. The 3-year OS, PFS, and WSP rates were 56.7% (95% CI, 53.0%-60.2%), 23.0% (95% CI, 20.2%-25.9%), and 45.2% (95% CI, 41.4%-48.9%), respectively. The 5-year OS, PFS, and WSP rates were 35.2% (95% CI, 30.1%-40.3%), 14.8% (95% CI, 11.9%-17.9%), and 54.5% (95% CI, 49.8%-59.2%), respectively. At the time of first progression, 342 patients (33.1%) had recurrence of OM disease, and 230 patients (22.3%) underwent subsequent ablative therapies to all known metastatic sites. Multivariable analyses identified primary tumor type (hazard ratio [HR], 3.73; 95% CI, 1.75-7.94; P < .001 for breast; 5.75; 95% CI, 2.88-11.46; P < .001 for colorectal; 4.67; 95% CI, 2.12-10.31; P < .001 for kidney; 10.61; 95% CI, 5.36-20.99; P < .001 for lung; and 12.00; 95% CI, 6.06-23.76; P < .001 for other [with prostate being the reference group]), metachronous OM presentation more than 24 months since initial diagnosis (HR, 0.63; 95% CI, 0.49-0.80; P < .001), metastases confined to the lung only (HR, 0.58; 95% CI, 0.48-0.72; P < .001), and nodal or soft-tissue metastases only (HR, 0.49; 95% CI, 0.26-0.90; P = .02) as survival factors. Sixty-six (6.4%) grade 3 or higher toxic effects were observed, including 1 (0.1%) grade 5 event.

CONCLUSIONS AND RELEVANCE

This study found favorable long-term OS and WSP rates associated with extracranial OM ablated with SBRT; however, modest PFS rates were observed. A substantial proportion of patients with OM developed progressive disease and were treated with local ablation. Factors that can inform clinical decision-making and clinical trial design include primary tumor type, a metachronous presentation more than 24 months since diagnosis, and the site of OM presentation.

摘要

重要性

寡转移(OM)患者的生存结果和影响因素尚不清楚,也没有在大规模研究中得到很好的描述。

目的

评估 1033 例接受立体定向体部放疗(SBRT)治疗的 OM 患者的总无进展生存期(PFS)、广泛进展(WSP)结局和生存因素。

设计、地点和参与者:2008 年 1 月 1 日至 2016 年 12 月 31 日的病例系列。分析日期为 2019 年 4 月至 2020 年 5 月。地点为多机构三级保健医院。参与者为连续的 5 个或 5 个以下颅外 OM 患者,其原发肿瘤经根治性治疗。

暴露

确定性 SBRT。

主要结局和测量

总生存(OS)、PFS、WSP 率、失败模式和改变 OS 的因素。

结果

在迄今为止最大的国际 OM 病例系列中(1033 例参与者)(平均年龄,68.0 岁[范围,18.0-94.3 岁];601 例[58.2%]为男性),1416 次 SBRT 疗程用于治疗 1 个 OM(596 例[57.7%])、2 个 OM(245 例[23.7%])、3 个 OM(105 例[10.2%])、4 个 OM(55 例[5.3%])和 5 个 OM(32 例[3.1%])。中位随访时间为 24.1 个月(范围,0.3-104.7 个月),中位 OS 为 44.2 个月(95%CI,39.2-48.8 个月)。中位 PFS 为 12.9 个月(95%CI,11.6-14.2 个月),中位 WSP 时间为 42.5 个月(95%CI,36.8-53.5 个月)。OS 率在 1 年时为 84.1%(95%CI,81.7%-86.2%),3 年时为 56.7%(95%CI,53.0%-60.2%),5 年时为 35.2%(95%CI,30.1%-40.3%)。3 年 OS、PFS 和 WSP 率分别为 56.7%(95%CI,53.0%-60.2%)、23.0%(95%CI,20.2%-25.9%)和 45.2%(95%CI,41.4%-48.9%)。5 年 OS、PFS 和 WSP 率分别为 35.2%(95%CI,30.1%-40.3%)、14.8%(95%CI,11.9%-17.9%)和 54.5%(95%CI,49.8%-59.2%)。在首次进展时,342 例(33.1%)患者出现 OM 疾病复发,230 例(22.3%)患者随后对所有已知转移性部位进行了消融治疗。多变量分析确定了原发性肿瘤类型(HR,3.73;95%CI,1.75-7.94;P<0.001 为乳腺癌;5.75;95%CI,2.88-11.46;P<0.001 为结直肠癌;4.67;95%CI,2.12-10.31;P<0.001 为肾癌;10.61;95%CI,5.36-20.99;P<0.001 为肺癌;12.00;95%CI,6.06-23.76;P<0.001 为其他肿瘤[以前列腺为参照组])、OM 呈现有 24 个月以上的时间间隔(HR,0.63;95%CI,0.49-0.80;P<0.001)、转移局限于肺(HR,0.58;95%CI,0.48-0.72;P<0.001)和仅淋巴结或软组织转移(HR,0.49;95%CI,0.26-0.90;P=0.02)是生存因素。观察到 66 例(6.4%)3 级或更高的毒性反应,包括 1 例(0.1%)5 级事件。

结论和相关性

本研究发现,SBRT 消融治疗颅外 OM 患者的 OS 和 WSP 率较高,但 PFS 率较低。相当一部分 OM 患者发生进展性疾病并接受局部消融治疗。可用于指导临床决策和临床试验设计的因素包括原发肿瘤类型、诊断后 24 个月以上的同步表现以及 OM 表现部位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5709/7670310/db1ff80321dc/jamanetwopen-e2026312-g001.jpg

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