Decoding tumor mutation burden and driver mutations in early stage lung adenocarcinoma using CT-based radiomics signature.
BACKGROUND
Tumor mutation burden (TMB) is an important determinant and biomarker for response of targeted therapy and prognosis in patients with lung cancer. The present study aimed to determine whether radiomics signature could non-invasively predict the TMB status and driver mutations in patients with resectable early stage lung adenocarcinoma (LUAD).


METHODS
A total of 61pulmonary nodules (PNs) from 51 patients post-operatively diagnosed LUAD were enrolled for analysis. Two datasets were divided according to two-thirds of patients from different commercial Comprehensive Genomic Profiling (CGP) panels: a training cohort including 41 PNs and a testing cohort including rest 20PNs. We sequenced all tumor specimens and paired blood cells using next generation sequencing (NGS), so as to detect TMB status and somatic mutations. We collected 718 quantitative 3D radiomics features extracted from segmented volumes of each PNs and 78 clinical and pathological features retrieved from medical records as well. Support vector machine methods were performed to establish the predictive model.


RESULTS
We established an efficient fusion-positive tumor prediction model that predicts TMB status and EGFR/TP53 mutations of early stage LUAD. The radiomics signature yielded a median AUC value of 0.606, 0.604, and 0.586 respectively. Combining radiomics with the clinical information can further improve the prediction performance, which the median AUC values are 0.671 for TMB, 0.697 and 0.656 for EGFR/TP53 respectively.


CONCLUSION
It is feasible and effective to facilitate TMB and somatic driver mutations prediction by using the radiomics signature and NGS data in early stage LUAD.
['Wang|Xiaoxiao|X|', 'Kong|Cheng|C|', 'Xu|Weizhang|W|', 'Yang|Sheng|S|', 'Shi|Dan|D|', 'Zhang|Jingyuan|J|', 'Du|Mulong|M|', 'Wang|Siwei|S|', 'Bai|Yongkang|Y|', 'Zhang|Te|T|', 'Chen|Zeng|Z|', 'Ma|Zhifei|Z|', 'Wang|Jie|J|', 'Dong|Gaochao|G|', 'Sun|Mengting|M|', 'Yin|Rong|R|0000-0002-9744-4251', 'Chen|Feng|F|']
D000077192:Adenocarcinoma of Lung D000368:Aged D014408:Biomarkers, Tumor D004252:DNA Mutational Analysis D019468:Disease Management D066246:ErbB Receptors D005260:Female D059014:High-Throughput Nucleotide Sequencing D006801:Humans D007091:Image Processing, Computer-Assisted D007150:Immunohistochemistry D008297:Male D008875:Middle Aged D009154:Mutation D009367:Neoplasm Staging D014057:Tomography, X-Ray Computed D016159:Tumor Suppressor Protein p53
tumor mutation burden radiomics somatic mutations Early stage lung cancer next-generation sequencing