Response to preoperative chemotherapy: impact of change in total burden score and mutational tumor status on prognosis of patients undergoing resection for colorectal liver metastases. HPB : the official journal of the International Hepato Pancreato Biliary Association Ruzzenente, A., Bagante, F., Ratti, F., Beal, E. W., Alexandrescu, S., Merath, K., Makris, E. A., Poultsides, G. A., Margonis, G. A., Weiss, M. J., Popescu, I., Aldrighetti, L., Guglielmi, A., Pawlik, T. M. 2019


BACKGROUND: Progression of colorectal liver metastasis (CRLM) on preoperative chemotherapy has been associated with a worse prognosis compared with patients who have responsive disease. Defining response can be challenging as traditional criteria largely assess only tumor size.METHODS: Patients who underwent hepatectomy between 2010 and 2017 were identified using a multi-centric database. This study aimed to define the impact of preoperative chemotherapy response relative to initial tumor burden score (TBS) and determine impact of clinico-pathological variables on overall survival (OS).RESULTS: Among 784 patients who received preoperative chemotherapy, the regimen was oxaliplatin- (66%) or irinotecan-based (34%). Among patients with a TBS<6at diagnosis, genetic status was the most important prognostic variable. Patients with a TBS<6, 5-year OS was 55%, 35%, and 0% for patients with KRAS/NRAS/BRAF wild-type, KRAS/NRAS, and BRAF mutations, respectively. Among patients who presented with CRLM with a TBS=6, only Delta-TBS was prognostically important and patients with a Delta-TBS=-10% had a 5-year OS of 27% compared with 49% for patients with a Delta-TBS<-10%.CONCLUSIONS: Prognostic stratification of patients with CRLM receiving preoperative chemotherapy should be multi-faceted and include consideration of initial tumor burden, change in tumor burden due to chemotherapy, and tumor genetic status.

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