Deciphering unclassified tumors of non-small-cell lung cancer through radiomics

Tumors are highly heterogeneous at the phenotypic, physiologic, and genomic levels. They are categorized in terms of a differentiated appearance under a microscope. Non-small-cell lung cancer tumors are categorized into three main subgroups: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. In approximately 20% of pathology reports, they are returned unclassified or classified as not-otherwise-specified (NOS) owing to scant materials or poor tumor differentiation.

We present a radiomic interrogation of molecular spatial variations to decode unclassified NOS tumor architecture quantitatively. Twelve spatial descriptors with various displacements and directions were extracted and profiled with respect to the subgroups. The profiled descriptors were used to decipher the NOS tumor morphologic clues from the imaging phenotype perspective. This profiler was built as an extended version of a conventional support-vector-machine classifier, wherein a genetic algorithm and correlation analysis were embedded to define the molecular signatures of poorly differentiated tumors using well-differentiated-tumor information.

Sixteen multi-class classifier models with an 81% average accuracy and descriptor subset size ranging from 12 to 144 were reported. The average area under the curve was 86.3% at a 95% confidence interval and a 0.03-0.08 standard error. Correlation analysis returned an unclassified NOS membership matrix with respect to the cell-architecture similarity score for the subgroups. The best model demonstrated 53% NOS reduction.

The membership matrix is expected to assist pathologists and oncologists in cases of unresectable tumors or scant biopsy materials for histological subtyping and cancer therapy.