Combined assessment of KRAS mutational status and tumor size has no impact on prognosis in early-stage non-small cell lung cancer

Background KRAS mutation status, stage and tumor size at the time of diagnosis are well-established independent prognostic factors in non-small cell lung cancer (NSCLC). Here, we investigate the prognostic value of combining survival data on KRAS mutation status and tumor size in early-stage NSCLC. Methods We studied the combined impact of KRAS mutational status and tumor size on overall survival (OS) and risk of death in patients with stage I-II NSCLC. We performed a retrospective study including 310 consecutively diagnosed patients with early (stage I-II) NSCLCs. All consecutive patients molecularly assessed and diagnosed between 2016-2018 with stage I-II NSCLC in the Västra Götaland region of western Sweden were included in this multi-center retrospective study. The primary study outcome was OS and risk of death (hazard ratio). Results Out of 310 patients with stage I-II NSCLC, 37% harbored an activating mutation in the KRAS gene. Our study confirmed staging and tumor size as prognostic factors. However, KRAS mutational status was not found to impact OS and there was no difference in the risk of death when combining KRAS mutational status and primary tumor size. Conclusions In our patient cohort, KRAS mutations in combination with primary tumor size are not associated with a worse prognosis in stage I-II NSCLC. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Swedish Research Council (2018-02318 and 2022-00971 to VIS, 2021-03138 to CW), the Swedish Cancer Society (20-1278 to VIS and 22-0612FE to CW), the Gothenburg Society of Medicine (2019; 19/889991 to EAE), Assar Gabrielsson Research Foundation (to EAE, CW and VIS), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (to HF), Department of Oncology, Sahlgrenska University Hospital (to EAE and AH), the Swedish Society for Medical Research (2018; S18-034 to VIS) and the Knut and Alice Wallenberg Foundation and the Wallenberg Centre for Molecular and Translational Medicine (to VIS). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board Statement Ethics committee of the Swedish Ethical Review Authority gave approval for this work (Dnr 2019-04771 and 2021-04987) prior to the commencement of the study. Informed Consent Statement: Patient statement was not required due to the retrospective nature of this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. * CT : Computed Tomography ECOG : Eastern Cooperative Oncology Group HR : Hazard Ratio NSCLC : Non-Small Cell Lung Cancer NGS : Next Generation Sequencing PS : Performance Status OS : Overall Survival