3483 - KRAS Mutations as Predictor of Radioresistance in Pulmonary Metastases from Colorectal Cancer
Presenter(s)
M. Loi1, M. Aquilano2, M. Valzano3, P. Bonomo4, D. Greto1, G. Simontacchi1, G. Francolini1, V. Salvestrini5, V. Di Cataldo6, M. Mangoni7, E. Olmetto6, P. Garlatti6, I. Desideri1, A. Lastrucci8,9, R. Doro5, L. Masi5, L. Marrazzo10, and L. Livi1; 1Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy, 2Cyberknife Unit, Istituto Fiorentino di Cura ed Assistenza, IFCA, Florence, Italy, 3Radiation Oncology Unit, Careggi University Hospital, University of Florence, Florence, Italy, 4Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy, 5Istituto Fiorentino di Cura e Assistenza (IFCA), CyberKnife Center, Florence, Italy, 6Radiation Oncology, Careggi University Hospital, University of Florence, Florence, Italy, 7Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Firenze, Italy, 8Department of Allied Health Professions, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy, 9Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Firenze, Italy, 10Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy, Florence, Italy
Purpose/Objective(s): Stereotactic Ablative Body Radiotherapy (SABR) has been used to improve disease control in oligo-metastatic (OM) and oligo-progressive (OP) pulmonary metastases (PM) from colorectal cancer (CRC). The aim of this study is to evaluate the impact of KRAS mutations (KRASmt) in risk of local failure following SABR in PM from OM/OP CRC.
Materials/Methods: A consecutive series of OM/OP patients treated at our Institution (2019-2024) with SABR for OM/OP PM from CRC was retrospectively reviewed. Statistical analysis was performed to correlate outcome with clinical (age, KRASmt, OM/OP disease) and treatment-related variables (prior systemic treatment, dose regimen in Biologically Effective Dose assuming an a/ß of 10: BED10).
Results: 103 PM from 62 patients were evaluated. SABR was delivered in the OM and OP setting in respectively 63%(n=65) and 37%(n=38) cases. SABR was performed in previously untreated PM(n=49,5%) or after first (n=31,3%) or further systemic therapy lines (n=23,22%). KRASmt were found in the resected primary tumor in 49% of PM (n=50). SABR was delivered in 3 to 8 fractions (range 48-60 Gy), corresponding to a median BED10 of 115,5 Gy10 (range 76,8-151,2). Median follow-up was 17 (range 2-45) months. Median Local Control (LC) was not reached; 1- and 3 years LC rates were respectively 85% and 67%. At multivariate analysis (MVA), only a BED=100Gy10 (p=0,029; HR 2,99 [CI95% 1,1- 9,5]) and previous administration of >1 systemic therapy lines (p=0,031; HR 3,2 [CI95% 1,1- 8,1]) were independently correlated with poorer LC. In the subset of chemotherapy-naïve and first line treatment patients before SABR, 1- and 3 years LC rates were 92% and 77% respectively (median: NR). At MVA, BED10=100Gy10 (p=0,036;HR 6,96 [CI95% 1,9-25,7] was associated with impaired LC. Conversely, absence of KRASmut (p=0,037;HR 0.26 [CI95% 0,07- 0,9]) was independently correlated with better LC. No grade >2 toxicity was observed. In the overall cohort, median Disease-Free Survival (DFS) and Overall Survival (OS) were 11 and 39 months, respectively. Improved DFS (15 versus 5 months, p=0,0003) and OS (39 versus 21 months, p=0,02) were found in patients receiving no chemotherapy or first-line treatment before SBRT.
Conclusion: SABR in PM from OM/OP CRC results in excellent LC rates, particularly if dose-intensive regimens are used in non-heavily pretreated patients (systemic therapy-naïve or receiving first-line systemic therapy). This subset may draw higher clinical benefit form SABR due to longer DFS and OS. In this setting, an impact of KRASmt in treatment failure was observed, that might be further explored in a dose-escalation perspective. This was not observed after >1 line of systemic therapy, possibly due to occurrence of de novo treatment-induced mutations in PM that may be identified by re-biopsy or liquid biopsy.