Draw on advantages and avoid disadvantages: CT-derived individualized radiomic signature for predicting chemo-radiotherapy sensitivity in unresectable advanced non-small cell lung cancer.

Abstract

Background: Presently, the options of concurrent chemo-radiotherapy (CCR) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) are controversial and there is no reliable prediction tool to stratify poor- and good-responders. Although radiomic analysis has provided new opportunities for personalized medicine in oncological practice, the repeatability and reproducibility of radiomic features are critical challenges that hinder their widespread clinical adoption. This study aimed to develop a qualitative radiomic signature based on the within-sample rank of radiomics features, and to use this novel method to predict CCR sensitivity in LA-NSCLC, avoiding the variability of quantitative signatures to multicenter effect.

Methods: We retrospectively analyzed 125 patients with stage III NSCLC who received treatment from our hospital. Radiomic features were extracted from pretreatment plain CT scans and constructed as feature pairs based on their within-sample rank. Fisher and univariate Cox analyses were performed to select feature pairs significantly associated with patients' overall survival (OS). NSCLC-Radiomic (R422) cohort including 104 NSCLC patients was used as an independent testing cohort. NSCLC-Radiogenomic (RG211) cohort with matched RNA sequencing profiles, was used for functional enrichment analysis to reveal the underlying biological mechanism reflected by the signature.

Results: A qualitative signature, consisting of 15 radiomic feature pairs (termed as 15-R_iFPS), was developed based on the Genetic Algorithm, which could optimally distinguish responder from non-responder with significantly improved OS if they received CCR treatment (log-rank P = 0.0009, HR = 13.79, 95% CIs 1.83-104.1). The performance of 15-R_iFPS was validated in an independent public cohort (log-rank P = 0.0037, HR = 2.40, 95% CIs 1.30-4.40). Furthermore, the transcriptomic analyses provided biological pathways ('glutathione metabolic process', 'cellular oxidant detoxification') underlying the signature.

Conclusions: We developed a CT-derived 15-R_iFPS, which could potentially help predict individualized therapeutic benefit of CCR in patients with LA-NSCLC. Additionally, we investigated the underlying intra-tumoral biological characteristics behind 15-R_iFPS which would accelerate its clinical application. This approach could be applied to a wider range of treatments and cancer types.