Evaluating Heterogeneity of Primary Lung Tumor Using Clinical Routine Magnetic Resonance Imaging and a Tumor Heterogeneity Index.

Nan Hu,Bo Qiu,Qiwen Li,Shaohan Yin,Linchang Zhong,Haoqiang He,Hui Liu,Nan-Jie Gong,Chuanmiao Xie,Jinyu Guo,Peiqiang Cai

doi:10.3389/fonc.2020.591485

Abstract

ObjectiveTo improve the assessment of primary tumor heterogeneity in magnetic resonance imaging (MRI) of non-small cell lung cancer (NSCLC), we proposed a method using basic measurements from T1- and T2-weighted MRI.MethodsOne hundred and four NSCLC patients with different T stages were studied. Fifty-two patients were analyzed as training group and another 52 as testing group. The ratios of standard deviation (SD)/mean signal value of primary tumor from T1-weighted (T1WI), T1-enhanced (T1C), T2-weighted (T2WI), and T2 fat suppression (T2fs) images were calculated. In the training group, correlation analyses were performed between the ratios and T stages. Then an ordinal regression model was built to generate the tumor heterogeneous index (THI) for evaluating the heterogeneity of tumor. The model was validated in the testing group.ResultsThere were 11, 32, 40, and 21 patients with T1, T2, T3, and T4 disease, respectively. In the training group, the median SD/mean on T1WI, T1C, T2WI, and T2fs sequences was 0.11, 0.19, 0.16, and 0.15 respectively. The SD/mean on T1C (p=0.003), T2WI (p=0.000), and T2fs sequences (p=0.002) correlated significantly with T stages. Patients with more advanced T stage showed higher SD/mean on T2-weighted, T2fs, and T1C sequences. The median THI in the training group was 2.15. THI correlated with T stage significantly (p=0.000). In the testing group, THI was also significantly related to T stages (p=0.001). Higher THI had relevance to more advanced T stage.ConclusionsThe proposed ratio measurements and THI based on MRI can serve as functional radiomic markers that correlated with T stages for evaluating heterogeneity of lung tumors.

Highlights

Malignant tumors usually consist of sub-clonal cells with different gene mutations, histology and morphology in a single lesion, which is termed as intratumoral heterogeneity [1,2,3]
tumor heterogeneity index (THI) correlated with T stage significantly (p=0.000)
The proposed ratio measurements and THI based on magnetic resonance imaging (MRI) can serve as functional radiomic markers that correlated with T stages for evaluating heterogeneity of lung tumors

Summary

Introduction

Malignant tumors usually consist of sub-clonal cells with different gene mutations, histology and morphology in a single lesion, which is termed as intratumoral heterogeneity [1,2,3]. High level of heterogeneity has been reported to be associated with adverse survival outcomes in multiple cancer types [4, 5]. Non-small cell lung cancer (NSCLC) is a highly heterogeneous disease regarding the genetic and phenotypic features [2, 3]. The assessment of intratumoral heterogeneity helps in treatment decision and survival prediction. In patients with inoperable NSCLC, the diagnosis and treatment usually rely on a small amount of tissue by biopsy, which could not represent the chunk of tumor. It’s important to develop a noninvasive method to evaluate the full spectrum of heterogeneity for primary lesions in NSCLC

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Discussion

Conclusion