Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis

Abstract

Background: Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT).

Methods: Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors.

Results: 361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS.

Conclusions: We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.

Conflict of interest statement

Competing Interests: Sources of funding for the various trial data incorporated into this study include: The Mount Sinai study was funded in part by Pfizer (www.pfizer.com) The University of Rochester study was funded in part by Brain-Lab AG (www.brainlab.com) Ludwig Center for Metastasis Research, University of Chicago Research Center. Grant Number: 5-30,073 The Chicago Tumor Institute Center for Radiation Therapy University of Chicago Comprehensive Cancer Center. Grant Number: P30 CA14599. This specific analysis did not have a funding source. The funders of the prospective studies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies. Additionally, Dr. Chmura and Milano disclose royalties from UpToDate which are not related to the current study.

Figures

Fig 1. Overall and progression free survival, treated metastasis control for all 361 oligometastatic patients treated with ablative radiotherapy.

Median survival was 47.1 months and 3-year survival was 56% (A). Median progression-free survival was 10.1 months and 3-year progression-free survival was 24% (B). Median treated metastasis control was not reached and 3-year TMC was 72% (C).

Fig 2. Recursive partitioning models for overall survival and progression-free survival.

For overall survival, recursive partitioning allowed stratification of patients into five prognostic classes (A). Overall survival was well-stratified based on RPA class (B); log-rank p

Fig 3. Overall and progression free survival, treated metastasis control by minimum biologically effective dose (BED).

BED ≥75 Gy was associated with greater overall survival (p