Increased Efficacy of Stereotactic Ablative Radiation Therapy in Combination with Bevacizumab in Lung Oligopersistent/Oligoprogressive Metastases from Colon Cancer

Abstract

Metastases from colorectal cancer are poor responsive to Stereotactic Ablative Radiation Therapy (SABR) probably due to intra-tumor hypoxia. Intratumoral oxygenation is improved by angiogenesis inhibitors administration. Thus, a possible clinical synergistic efficacy of SABR with Bevacizumab could exists in metastases from colorectal cancer. Aim of the analysis is to evaluate the feasibility and efficacy of SABR in combination with Bevacizumab in the setting of lung oligopersistent/oligoprogressive metastases from colon cancer. Dataset of lung metastases from colon cancer underwent to SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤ 3; oligopersistent and oligoprogressive disease underwent to SABR; patients underwent to previous chemotherapy alone or in combination with Bevacizumab; Karnofsky performance status > 80; life-expectancy > 6 months; at least 6 months of follow up after SABR; a mutational K-RAS status. Findings were compared with a similar cohort of irradiated lung lesions from colorectal cancer in which Bevacizumab was not previously administered. Forty lung metastases for a total of twenty-three patients were object of analysis. The median follow-up was 24 months (range, 9 - 35 months). All lesions were treated with a BED ≥ 100 Gy. Prior to SABR, Bevacizumab was administered in combination with standard chemotherapy in 17/40 lesions (42.5%). One-year LC (defined as lack of in field recurrence) in Bevacizumab-group was 93% versus 86% in No-Bevacizumab group. The rate of complete response after SABR was higher in the cohort of lesions previously underwent to Bevacizumab, comparing to the remaining (p 0.04). Additionally, in the Bevacizumab group, higher rate of complete response post-SABR was observed in case of oligopersistent versus oligorecurrent metastases (p 0.001). During SABR, in the Bevacizumab arm 1 patient (4%) experienced a grade-2 pulmonary toxicity while two patients (6%) in the other cohort of patients experienced acute grade-1 toxicity. At the time of the analysis, no late toxicity superior or equal G3 was recorded in both groups of patients. Late toxic adverse events included: chest wall pain (2 patients with peripheral metastases, 6%) and asymptomatic pneumonitis (2 patients, 6%) without differences between the two groups of patients. In the setting of lung oligopersistent/oligoprogressive metastases from colon cancer present study attested the feasibility/efficacy of SABR in combination with Bevacizumab. Further studies in this field of research are strongly advocated.