CT derived radiomic score for predicting the added benefit of adjuvant chemotherapy following surgery in stage I, II resectable non-small cell lung cancer: a retrospective multicohort study for outcome prediction

Abstract

Development and validation of a quantitative radiomic risk score (QuRiS) and associated nomogram (QuRNom) for early-stage non-small cell lung cancer (ES-NSCLC) that is prognostic of disease-free survival (DFS) and predictive of the added benefit of adjuvant chemotherapy (ACT) following surgery. QuRiS was developed using radiomic texture features derived from within and outside the primary lung nodule on chest CT scans using a cohort D 1 of 329 patients from the Cleveland Clinic. A LASSO-Cox regularization model was used for data dimension reduction, feature selection, and QuRiS construction. QuRiS was independently validated on D 2 (N=114; University of Pennsylvania) and D 3 (N=82; TCIA). QuRNom was constructed by integrating QuRiS with T-, N-Descriptors, and LVI. The added benefit of ACT using QuRiS and QuRNom was validated by comparing patients who received ACT against patients who underwent surgery alone in D 1 -D 3 . To explore the underlying morphologic basis of the QuRiS, we explored associations with corresponding whole-slide tissue scans (WSIs) and mRNA sequencing data using subsets of D 1 and D 3 . QuRiS consisted three intra- and ten peri-tumoral CT-radiomic features and was found to be significantly associated with DFS (D 1 : HR=1.60 [1.10–2.20];p<·05; D 2 :HR=2.70 [1.40–5.10]; p<·01; D 3 :HR=2.70 [1.20–5.70];p<·01). Patients were partitioned into three risk groups (Q H, Q I, Q L ) based off their corresponding QuRiS score. High QuRiS group, Q H, patients were observed to have significantly prolonged survival with ACT when compared to surgery alone (D 1 : HR=0·27[0.07–0.95],p<0.05; D 2 +D 3 : HR=0·08[0.01–0.42],p<0.01). For developed QuRNom, the actual efficacy of ACT was predictive of nomogram-estimated survival benefit (D 1 : HR= D 1 :0·25 [0·12–0·55], D 3 : HR=0·13 [0·004–0·99]). QuRiS features were found to be associated with the spatial arrangement of TILs and cancer nuclei on corresponding WSIs (D 1 : Rho=0·23,p<0·05, N=70). They were also observed to have an association with biological pathways implicated in chemotaxis (D 3 ,p<0·05, N=86) and other immune specific biological pathways. QuRiS and QuRNom were validated as being prognostic of DFS and predictive of the added benefit of ACT.