{'fraction_non_alphanumeric': 0.018433179723502304, 'fraction_numerical': 0.008378718056137411, 'mean_word_length': 5.524590163934426, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Response to Comment on "Deleterious Effect of RAS and Evolutionary High Risk TP53 Double Mutation in Colorectal Liver Metastases".

To the Editor: We read with great interest the article ‘‘Deleterious effect of RAS and evolutionary high-risk TP53 double mutation in colorectal liver metastases’’ by Chun et al. They found concomitant RAS and TP53 mutations are associated with decreased survival after colorectal liver metastasis resection. In this study, 401 patients were involved, including 99 with the tumor in the right colon and 299 in the left colon. Compared with patients lacking double mutations, those with mutated RAS and TP53 were more likely to have primary tumors in the right colon. This result was similar to those of some other studies. But in the following survival analysis, they did not stratify the patients according to the tumor location. The current view is that metastatic colorectal cancer is a heterogeneous disease; primary tumors arising from different part of the colon are distinct clinically and molecularly. Left colon derives from the embryonic hindgut; right colon derives from the embryonic midgut. In addition, left colon and right colon tumors have unique gene expression profiles. In particular, right colon tumors are more frequently with a host of adverse prognostic factors, including BRAF mutation positivity, microsatellite instability, serrated pathway signature positivity, hypermutation and mucinous histology; conversely, left colon tumors are more frequently with gene expression profiles characteristic of an EGFR inhibitor–sensitive phenotype. These molecular differences represent different clinical behavior, and the right colon tumors usually have poor prognosis. According to the latest NCCN guidelines, the inclusion of primary tumor sites into the selection criteria of targeted drugs for firstline treatment of metastatic colorectal cancer was recommended, which would surely be a milestone update. Now that the authors had come to a similar conclusion, which indicated different primary tumor sites were associated with different types of mutations in RAS/TP53, maybe it could make the data more accurate and convincing by stratifying the patients according to the tumor location and estimating the association between RAS/TP53 mutations and decreased survival after colorectal liver metastasis resection in different subgroup.