1 Predictive and Prognostic Value of Hepatic Steatosis 2 in Conversion Therapy for Colorectal Liver-limited 3 Metastases 4

This study is aimed to assess the role of hepatic steatosis (HS) on outcome of conversion 15 therapy for patients with initially unresectable synchronous colorectal liver-limited metastases 16 (CLLMs). We identified 346 patients with initially unresectable CLLMs received conversion therapy 17 under the guidance of multidisciplinary team (MDT) in Zhongshan hospital (2013 to 2016). HS 18 status of all patients was evaluated before the first circle of conversion therapy. The objective 19 response rate (ORR), hepatectomy rate, predictor of conversion hepatectomy, and overall survival 20 (OS) were compared using propensity-score matching (PSM). Predictive value of HS in conversion 21 hepatectomy was validated with a separate cohort of 60 patients initially unresectable CLLMs who 22 received conversion therapy (2017 to 2018). Before conversion therapy start, 108 (31.2%) patients 23 were detected with HS status. In study set after PSM, compared with non-HS group, HS group 24 supplied improved ORR (36.7% vs 23.9%, P=0.020), hepatectomy rate from MDT (27.7% vs. 16.9%, 25 P<0.001) following conversion therapy. Multivariate analysis confirmed that HS (OR, 5.234; 95%CI, 26 2.398-11.423, P<0.001), targeted therapy and transarterial chemoembolization treatment were 27 independent predictors of hepatectomy rate. In the validation cohort, patients with HS had an 28 improved conversion hepatectomy rate (43.7% vs. 15.9%, P=0.038) following conversion therapy. 29 Hepatic steatosis status could be a predictor of conversion hepatectomy in patients with 30 synchronous colorectal liver-limited metastases. This effect appears to be independent of use of 31 targeted therapy. 32