KRAS status in lung oligometastases treated with SBRT.

Abstract

264 Background: Stereotactic Body Radiotherapy (SBRT) to lung metastases (LM) from colorectal cancer (CRC) has been applied to improve disease control in in the oligometastatic (OM) and oligoprogressive (OP) setting. The aim of this study is to assess the impact of KRAS mutational (KRASmut) status in the response to SBRT in LM. Methods: Data from a consecutive cohort of OM/OP CRC patients treated at our Institution with SBRT for LM from May 2019 to March 2024 were retrospectively reviewed. Patients (age, KRASmut in primary tumor, OM/OP disease, chemotherapy lines prior to SBRT) and treatment-related variables (dose regimen and Biologically Effective Dose: BED, toxicity) were collected. Local Control (LC) was defined as time from SBRT to local failure or last radiologic follow-up. Results: Sixty-two patients (median age: 74 years, range 49-85), accounting for 103 LM were included. LM were treated in the OM and OP setting in 65(63%) and 38(37%) cases, respectively. SBRT was delivered before chemotherapy (n=49,48%) or following first (n=31,30%) or further chemotherapy lines (n=23,22%). KRASmut was present ab initio in 49% of cases (n=50). Dose regimens included 48-60 Gy in 3-8 fractions, resulting in a median BED of 115.5 (range 76.8-151.2) Gy 10 : a BED>100Gy 10 was delivered in 92% (n=95) of treatment courses. Median follow-up was 16 (range 2-45) months. Median LC was not reached; 1- and 3 years LC rates were 85% and 67% respectively. At multivariate analysis (MVA), only a BED≤100Gy 10 (p=0.029, HR 2.99, IC95% 1.1- 9.5) and prior second or further chemotherapy line (p=0.031, HR 3.2, IC95% 1.1- 8.1) were independently correlated with impaired LC. No grade >2 toxicity was observed. Focusing on patients receiving no chemotherapy or first-line treatment before SBRT, 1- and 3 years LC rates were 92% and 77% respectively (median: NR). At MVA, while BED≤100Gy 10 (p=0.036, HR 6.96, IC95% 1.9-25.7) was associated with poorer LC, lack of KRASmut (p=0.037, HR 0.26, IC95% 0.07- 0.9) was independently correlated with improved LC. Conclusions: SBRT in LM from OM/OP CRC results in high LC rates, particularly with intensive regimens in non-heavily pretreated patients. No impact of KRASmut was observed. Due to possible occurrence of secondary mutations in the pretreated population, a subset analysis in the chemotherapy-naive/first-line subset suggests an impact of KRASmut in radioresistance that should be further explored in a dose-escalation perspective. Re-biopsy or liquid biopsy may be useful to identify de-novo mutations.