Discussion
KRAS, colorectal cancer, thymoma, tumour
MUTANT, COLORECTAL CANCER, LUNG, METASTASIS, LUNG METASTASIS, DISEASE, THYMOMA, MUTANT, TUMOUR, EVENTS, METASTASES
In this study, we developed and validated a radiomic model based on pretreatment MRI scans for predicting KRAS status that had AUCs of 0.983 and 0.814 in the training cohort and testing cohort, respectively. The prediction stratification showed a significant association with lung metastasis.KRAS is a proto-oncogene involving several tumour-related molecular pathways. Mutant KRAS may lead to constitutive activation of downstream pathways, for example mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene pathways (PI3K/AKT) [Lung is one of the most common metastatic sites in colorectal cancer [Currently, KRAS mutation detection still meets difficulties in clinical practice. Sufficient tissue sample is needed to conduct next-generation sequencing which is the gold standard approach to detect KRAS mutation status. In the circumstances, postoperative specimens are preferred compared with preoperative tissue sampling biopsy. However, in LARC patients, with the rapid development of neoadjuvant treatment in recent years, more and more patients reached complete or near complete response, leading to less TME surgery to obtain macrodissected sample [The advantages of the present radiomic model lie in three aspects. First, this is a multicentre study, indicating the robustness and practicality of the model. Second, to the best of our knowledge, this is the first exploratory study to associate pretreatment MRI scans to KRAS status and further analyse its association with distant metastasis. We preliminarily investigated the prognostic value of KRAS status for lung metastasis. The model is not only a noninvasive prediction tool for KRAS status but could also be used as a stratification tool for lung metastasis risk. In the future, we would like to further investigate the association of pretreatment MRI radiomic features and lung metastasis in a larger cohort. Third, it is well established that KRAS status indicates the response to anti-EGFR treatment. However, since anti-EGFR treatment is not recommended for LARC patients as neoadjuvant treatment, KRAS status detection is not commonly performed in these patients. In the present study, we offered a noninvasive method to identify KRAS status in LARC patients before neoadjuvant therapy. With increasing evidence of the prognostic value of KRAS status, we hope this study offers a way to obtain some prognostic information in a relatively early stage.This study also has several limitations. First, the sample size is small. Despite its multicentre natures, LARC patients were not routinely tested for KRAS status. KRAS detection was recommended for patients with simultaneous distant metastasis or those with late stage locally advanced disease and several clinical risk factors. Consequently, a small number of LARC patients were included in the present study, indicating the necessity for further validation in larger, prospective cohorts. Second, we investigated the clinical value of KRAS mutation in risk stratification for lung metastasis. This exploratory study indicated that KRAS may play a role in tumour invasion and metastases and that KRAS status could be a prognostic factor for such events. However, the small sample size and short follow-up duration were two limitations. This association needs to be tested in the future. Third, the two classes of KRAS status were imbalanced. Only 36 patients were KRAS mutant, while in the testing cohort the number is 9. We believe techniques for example Synthetic Minority Over-sampling TEchnique (SMOTE) or stratified cross validation may help overcome this limitation.