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

Ian Poon, Darby Erler, Roi Dagan, Kristin J Redmond, Matthew Foote, Serena Badellino, Tithi Biswas, Alexander V Louie, Young Lee, Eshetu G Atenafu, Umberto Ricardi, Arjun Sahgal, Ian Poon, Darby Erler, Roi Dagan, Kristin J Redmond, Matthew Foote, Serena Badellino, Tithi Biswas, Alexander V Louie, Young Lee, Eshetu G Atenafu, Umberto Ricardi, Arjun Sahgal

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.

Conflict of interest statement

Conflict of Interest Disclosures: All authors reported receiving travel support from Elekta AB through the Consortium for Oligometastases Research (CORE). Dr Redmond reported receiving research support, travel expenses, and honoraria for educational seminars from Accuray; participating on a data and safety monitoring board for BioMimetix; and receiving travel expenses from Brainlab. Dr Foote reported receiving research support, travel expenses, and honoraria for educational seminars from Elekta AB. Dr Biswas reported received honoraria from Galera Therapeutics. Dr Louie reported receiving honoraria from Varian Medical Systems, AstraZeneca, and RefleXion. Dr Sahgal reported conducting educational seminars for Medtronic, Elekta AB, Accuray, and Varian Medical Systems; receiving research grants from Elekta AB; and being part of the Elekta MR-Linac Consortium.

Figures

Figure 1.. Kaplan-Meier Estimates
Figure 1.. Kaplan-Meier Estimates
A-C, Data are shown for overall survival and progression-free survival in the entire cohort and for widespread progression among 1015 patients. Shading indicates 95% CIs.
Figure 2.. Overall Survival
Figure 2.. Overall Survival
A-D, Data are shown for the entire cohort. SBRT indicates stereotactic body radiotherapy.

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