Role of Stereotactic Body Radiotherapy (SBRT) in the Treatment of Oligo Metastatic Colorectal Cancer: Analysis of a Large Multi-Institutional Database

Abstract

In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective local treatment for oligometastatic cancers. However, it has been suggested that colorectal cancers may represent a more radioresistant histology, even to the high doses used in SBRT. Here, we report local recurrence rates, progression free-survival, and overall survival of patients with oligometastatic CRC treated with SBRT using a large multi-institutional data-base.We collected data retrospectively from six cancer centers with a high volume of SBRT treatments from Jan 1 2008 to December 31, 2016. Our primary outcome was local recurrence while secondary outcomes included overall survival (OS), local recurrence free survival, progression free survival, oligo-progression, and widespread progression. Time-to event outcomes were estimated using the Kaplan-Meier method. Univariable regression analysis was performed to determine the relationship between patient, tumor and treatment variables and outcomes. Variables significant on univariable screen were entered into a multivariable model. All analysis was performed in R (R Foundation for Statistical Computing, version 4.0.2) RESULTS: We identified 235 patients with a total of 381 oligometastatic CRC lesions that were treated with SBRT. The mean age was 70.7 ± 12.2 years, 58% of patients were male with a median follow-up of 25.5 months. The most common site of metastasis was the lung (n = 133, 56.6%) with a total of 239 (62.7%) lesions. The median time to local recurrence was not reached with the 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year probability of 76.1% and 35.9% respectively. On multivariable analysis, a BED10 of ≥100 Gy (HR 0.67, 95% CI 0.45-0.99) and the presence of lung (HR 0.53, 95% CI 0.34-0.82) or lymph node metastasis as opposed to liver metastasis (HR 0.31, 95% CI 0.13-0.74) were associated with improved local control. Larger total PTV size (≥17.5cc) was associated with worse overall survival (HR 2.62, 95% CI 1.45-4.72), progression free survival (HR 2.01, 95% CI 1.39-2.90) and widespread progression (HR = 2.82, 95% CI: 1.63-4.88). Use of prior systemic therapy before SBRT was also adversely associated with widespread progression (HR = 1.90, 95% CI: 1.22-2.95).This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is appreciably lower than what has historically been demonstrated in other cancer primary sites. These results suggest that an increase in BED should be considered if feasible and safe, in order to optimize local control. Increased overall PTV size may also be an indicator for the need for systemic therapy in addition to SBRT.