The Impact of KRAS Mutation and PD-L1 Status on Outcomes of Definitive Stereotactic Body Radiation (SBRT) for Stage I Non-Small Cell Lung Cancer (NSCLC)

Abstract

<h3>Purpose/Objective(s)</h3> Mutational and PD-L1 status of non-small cell lung cancer (NSCLC) correlate with response to systemic therapy. KRAS mutations have been implicated in radio-resistance of both colorectal liver metastasis as well as NSCLC after stereotactic body radiation (SBRT), while the effect of PD-L1 status on outcomes after SBRT is unknown. Here we examine the relationship of these molecular markers on outcomes after SBRT for stage I NSCLC. <h3>Materials/Methods</h3> Reflexive testing for mutations associated w NSCLC (EGFR, ALK, KRAS, ROS1, BRAF, RET, HER2, MET) was gradually implemented at our institution beginning in 2016, followed by PD-L1 testing in 2018, provided biopsy samples were obtained internally and adequate tissue for molecular testing was available. We cross-referenced an institutional database of all patients treated with definitive intent SBRT for stage I NSCLC from 1/2015-12/2020 in order to correlate mutational/PD-L1 testing along with other patient, tumor and treatment factors on local recurrence (LR), disease recurrence (AR) and overall survival (OS) after SBRT. Gray's test was used to compare cumulative incidence rates of LR and AR, and OS rates were compared using the log rank test. No patients received adjuvant systemic therapy of any kind. <h3>Results</h3> 148 patients with known mutational status were identified, of which 62 (41.9%) had known KRAS mutations. Other mutations (EGFR 16, ALK 3, BRAF 9, MET 4, ROS1 1, RET 1, and HER2 0) were identified too infrequently for analysis. PD-L1 status was known for 161 patients and was analyzed in the following groups (0% in 58, 1-49% in 60, and 50-100% in 43 patients) as well as a continuous variable. SBRT regimen was at physician discretion; 34 Gy/1 fx in 30.6%, 48-50 Gy/4-5 fx in 30.6%, 54-60 Gy/ 3 fx in 37.1%, and 60 Gy/8fx in 1.6% of patients. KRAS and PD-L1 groups were balanced for known prognostic factors, except KRAS mutated was a/w higher SBRT dose. At median follow-up of 25.7 months 55% of patients were living. By Gray's test KRAS mutation status was not associated with a difference in LR (2-year cumulative incidence of 1.3% versus 1.6%, p=0.25), AR (2-year cumulative incidence of 27.2% v 24.8%, p=0.70) or OS (5-year survival 44.9% v 49.1%, p=0.34) for wild-type versus mutant status respectively. There was a trend towards higher LR in the PD-L1 0% group with 2y LR of 10.2%, 5.2%, and 2.9% and 5y LR of 19.5, 10.9 and 9.2% in the three PD-L1 groups respectively (P=0.085), however PD-L1 did not correlate with LR as a continuous variable (p=0.15). The PD-L1 1-49% group experienced the lowest risk of 2y AR (28% v 20% v 36%, p=0.11) and greatest 5y OS (37% v 44.% v 28%, p=0.06) however PD-L1 was not correlated to AR (p=0.79) or OS (p=0.25) as a continuous variable. <h3>Conclusion</h3> Unlike prior series suggesting increased LF after SBRT in KRAS mutated adenocarcinoma, KRAS status was not correlated with LF in this series of patients of whom 70% received BED 149 or higher dose SBRT. Whether PD-L1 status is correlated with LR, AR or OS after SBRT for stage I NSCLC requires a larger sample for study.