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 multi-cohort study for outcome prediction.

Background: 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.

Methods: QuRiS was developed using radiomic texture features derived from within and outside the primary lung nodule on chest CT scans using a cohort D 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(N=114; University of Pennsylvania) and D(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-D. 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 and D.

Findings: QuRiS consisted three intra- and ten peri-tumoral CT-radiomic features and was found to be significantly associated with DFS (D: HR=1.60 [1.10-2.20];p<·05; D:HR=2.70 [1.40-5.10]; p<·01; D:HR=2.70 [1.20-5.70];p<·01). Patients were partitioned into three risk groups (Q Q Q) based off their corresponding QuRiS score. High QuRiS group, Q patients were observed to have significantly prolonged survival with ACT when compared to surgery alone (D: HR=0·27[0.07-0.95],p<0.05; D+D: 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: HR= D:0·25 [0·12-0·55], D: 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: Rho=0·23,p<0·05, N=70). They were also observed to have an association with biological pathways implicated in chemotaxis (D,p<0·05, N=86) and other immune specific biological pathways.

Interpretation: QuRiS and QuRNom were validated as being prognostic of DFS and predictive of the added benefit of ACT.