Abstract

ObjectiveThe objectives of our study were to assess the association of radiomic and genomic data with histology and patient outcome in non-small cell lung cancer (NSCLC).MethodsIn this retrospective single-centre observational study, we selected 151 surgically treated patients with adenocarcinoma or squamous cell carcinoma who performed baseline [18F] FDG PET/CT. A subgroup of patients with cancer tissue samples at the Institutional Biobank (n = 74/151) was included in the genomic analysis. Features were extracted from both PET and CT images using an in-house tool. The genomic analysis included detection of genetic variants, fusion transcripts, and gene expression. Generalised linear model (GLM) and machine learning (ML) algorithms were used to predict histology and tumour recurrence.ResultsStandardised uptake value (SUV) and kurtosis (among the PET and CT radiomic features, respectively), and the expression of TP63, EPHA10, FBN2, and IL1RAP were associated with the histotype. No correlation was found between radiomic features/genomic data and relapse using GLM. The ML approach identified several radiomic/genomic rules to predict the histotype successfully. The ML approach showed a modest ability of PET radiomic features to predict relapse, while it identified a robust gene expression signature able to predict patient relapse correctly. The best-performing ML radiogenomic rule predicting the outcome resulted in an area under the curve (AUC) of 0.87.ConclusionsRadiogenomic data may provide clinically relevant information in NSCLC patients regarding the histotype, aggressiveness, and progression. Gene expression analysis showed potential new biomarkers and targets valuable for patient management and treatment. The application of ML allows to increase the efficacy of radiogenomic analysis and provides novel insights into cancer biology.

Highlights

  • Lung cancer is a leading global cause of cancer-related deaths, with more than 2.2 million people diagnosed and 1.9 million deaths documented worldwide in 2017 [1]

  • We observed a weak correlation between the histotype and the relapse status, with AC cases more prone to relapse than squamous cell carcinoma (SQC) patients (P = 0.032; the significance was retained after correction for age, sex, and smoking status, P = 0.026) (Supplementary Figure 1)

  • Our study explored the ability of radiomics, genomics, and radiogenomics to provide clinically relevant information in lung cancer patients using explainable models

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Summary

Introduction

Lung cancer is a leading global cause of cancer-related deaths, with more than 2.2 million people diagnosed and 1.9 million deaths documented worldwide in 2017 [1]. The survival rate rises above 50% if the disease is diagnosed early when local treatment is feasible [2]. Genetic information may be used to predict survival, as a prognostic biomarker or response to treatment, as a predictive biomarker to support clinical decisions [7]. In lung cancer, genetic mutations in ALK, BRAF, EGFR, and ROS1 guide treatment decisions in patients affected by advanced disease and recurrence [3, 4]. Beyond these alterations, other oncogenic driver mutations— even if currently not targetable—include RET, HER2, KRAS, and MET [8]. Molecular data are not routinely used in earlystage lung cancer

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