Published April 12, 2018 | Version v1
Journal article Open

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

  • 1. Duke University
  • 2. Vanderbilt University
  • 3. Memorial & St. Elizabeth's Cancer Treatment Center
  • 4. Wake Forest University
  • 5. University of Florida
  • 6. Mount Sinai
  • 7. University of Chicago
  • 8. Good Samaritan Hospital Medical Center
  • 9. University of California San Diego
  • 10. University of Rochester Medical Center

Description

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.

Data availability

Data are not publicly available because they contain sensitive patient information. The approved project and corresponding data use agreement between the Veteran’s Health Administration and the University of Chicago institutional review boards did not authorize further data sharing and data are to be destroyed following this study. Please direct data access requests to Jeffrey “Scott” Gardiner, Information Security Officer at the Durham VA Medical Center, using the following email address: Jeffrey.gardiner@va.gov. While individual patient data are not available, the source code is available through GitHub at the following URL: https://github.com/julianhong/oligometastasis.

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Additional details

Identifiers

DOI
10.1371/journal.pone.0195149
Other
oai:uchicago.tind.io:6580

Funding

Pfizer
Brain-Lab AG
University of Chicago
5-30,073
University of Chicago
P30 CA14599

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Radiation and Cellular Oncology