Characterization of early recurrences following liver resection by ALPPS and two stage hepatectomy (TSH) in patients with colorectal liver-metastases and small future liver remnants (FLR)

Abstract

Background: Surgical resection is the only curative treatment option for patients with CRLM. Novel therapeutic strategies therefore aim at offering surgery to patients outside traditional resection criteria. In patients with small FLR, ALPPS is described as an alternative to TSH but initial reports suggested higher rates of early recurrences. This study aims at identifying clinical and biological factors associated with early recurrences following liver resection by ALPPS and TSH in patients with colorectal liver-metastases (CRLM). Materials and methods: All patients included at one site participating in the LIGRO study* were included (n = 43). Twenty-three patients were randomized to PVE and 20 to ALPPS. Cross-over to rescue surgery by ALPPS was allowed (n = 4). Three patients were excluded for inoperability. Thus, 16 liver resections were completed by TSH and 24 by ALPPS. Tumor samples were analyzed for KRAS, BRAF, NRAS, PIK3CA and TP53 gene mutations. Results: A similar fraction (25%) in each group developed recurrent liver metastases within one year after resection. Rapid recurrences were not associated with primary tumor location or liver resection margin. The mutation status of RAS/RAF/PIK3CA genes were comparable in patients with and without recurrences. All coding sequences of TP53 were investigated for 6 samples with recurrence; the 4 with mutation were all found in the ALPPS group. Conclusion: ALPPS was not associated with a higher rate of early recurrences than TSH in this randomized setting. Early recurrences were not conclusively associated with specific mutational patterns. Long term survival analysis for the entire cohort is ongoing.