Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases

Margonis, Georgios Antonios; Kim, Yuhree; Sasaki, Kazunari; Samaha, Mario; Buettner, Stefan; Amini, Neda; Pawlik, Timothy M.

doi:10.1002/jso.24319

Cited by 14 publications

(6 citation statements)

References 37 publications

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“…Only three previous prediction models included RAS and BRAF mutation status 13–15 , potentially owing to the low prevalence of BRAF mutations in patients with local treatment of CRLMs (approximately 2 per cent) 13 . In contrast to previous studies 28 , 43 , there was no interaction between neoadjuvant treatment status and RAS mutational status here.…”

Section: Discussioncontrasting

confidence: 99%

Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases

Wensink

Bolhuis

Elferink

et al. 2023

British Journal of Surgery

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Background Patients who develop early extrahepatic recurrence (EHR) may not benefit from local treatment of colorectal liver metastases (CRLMs). This study aimed to develop a prediction model for early EHR after local treatment of CRLMs using a national data set. Methods A Cox regression prediction model for EHR was developed and validated internally using data on patients who had local treatment for CRLMs with curative intent. Performance assessment included calibration, discrimination, net benefit, and generalizability by internal–external cross-validation. The prognostic relevance of early EHR (within 6 months) was evaluated by landmark analysis. Results During a median follow-up of 35 months, 557 of the 1077 patients had EHR and 249 died. Median overall survival was 19.5 (95 per cent c.i. 15.6 to 23.0) months in patients with early EHR after CRLM treatment, compared with not reached (45.3 months to not reached) in patients without an early EHR. The EHR prediction model included side and stage of the primary tumour, RAS/BRAFV600E mutational status, and number and size of CRLMs. The range of 6-month EHR predictions was 5.9–56.0 (i.q.r. 12.9–22.0) per cent. The model demonstrated good calibration and discrimination. The C-index through 6 and 12 months was 0.663 (95 per cent c.i. 0.624 to 0.702) and 0.661 (0.632 to 0.689) respectively. The observed 6-month EHR risk was 6.5 per cent for patients in the lowest quartile of predicted risk compared with 32.0 per cent in the highest quartile. Conclusion Early EHR after local treatment of CRLMs can be predicted.

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Section: Discussioncontrasting

confidence: 99%

Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases

Wensink

Bolhuis

Elferink

et al. 2023

British Journal of Surgery

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“…As such, the practical clinical implications of BRAF mutational status should be further explored. For example, it has been demonstrated that the presence of BRAF mutations in metastatic CRC predicts lack of response to anti-EGFR agent treatment similarly to what occurs in the presence of KRAS pathway mutations (35)(36)(37). Nonetheless, no specific therapy for this patient subgroup is currently in widespread use.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of BRAF Mutations in Colorectal Cancer Liver Metastases

Pikoulis

Margonis

Andreatos

et al. 2016

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“…35 KRAS was reported to be informative for prognosis only among patients who received preoperative chemotherapy and not for patients undergone upfront surgery. 36 Thus this is the first report of a significant correlation between KRAS mutant status, CXCR4 and prognosis in CRLM.…”

Section: Discussionmentioning

confidence: 64%

CXCR4–CXCL12–CXCR7, TLR2–TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients

et al. 2016

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A neoadjuvant clinical trial was previously conducted in patients with resectable colorectal cancer liver metastases (CRLM). At a median follow up of 28 months, 20/33 patients were dead of disease, 8 were alive with disease and 5 were alive with no evidence of disease. To shed further insight into biological features accounting for different outcomes, the expression of CXCR4-CXCL12-CXCR7, TLR2-TLR4, and the programmed death receptor-1 (PD-1)/programmed death-1 ligand (PD-L1) was evaluated in excised liver metastases. Expression profiles were assessed through qPCR in metastatic and unaffected liver tissue of 33 CRLM neoadjuvant-treated patients. CXCR4 and CXCR7, TLR2/TLR4, and PD-1/PD-L1 mRNA were significantly overexpressed in metastatic compared to unaffected liver tissues.

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Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases

Cited by 14 publications

References 37 publications

Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases

Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases

Prognostic Role of BRAF Mutations in Colorectal Cancer Liver Metastases

CXCR4–CXCL12–CXCR7, TLR2–TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients

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