*Purpose: Loco-Regional therapy (LRT) for hepatocellular carcinoma (HCC) patients is an established bridge to Orthotopic Liver Transplantation (OLT). However, no large cohort data exist correlating patterns of spatial recurrence within the liver Post-LRT and HCC recurrence post-transplant. Recurrences in segments away from the original tumor would represent de-novo HCC or intra-hepatic spread. Intuitively, this pattern of recurrence would represent a higher oncologic risk than patients that recur in the same or adjacent areas of the liver. Patients with solitary tumors represent an ideal group to evaluate this response. Therefore, we hypothesized that patients with solitary tumors undergoing LRT that have recurrences of HCC away from the original segment of the tumor carry a higher oncologic risk & increased recurrence post-OLT.

*Methods: From a database of 645 patients who had OLT for HCC we identified 508 patients who had LRT pre-OLT. 74 had cancer recurrence post-OLT. Of these 20 cases had a single tumors within Milan criteria pre-first LRT. We matched them with patients who did not have a recurrence post-OLT based on etiology, MELD, AFP and tumor size pre-first LRT. Tumor data was recorded after reviewing imaging pre-and post- each LRT as well as pre-transplant. Demographics, etiology, AFP and NLR (at each LRT), and explant tumor pathology post-OLT was recorded.

*Results: Median age of all patients was 59years and 74% were male. Neutrophil-Lymphocyte ratio (NLR) was no different prior to 1^st LRT between groups (2 +/- 1 vs. 2 +/- 1) but was significantly higher pre-OLT in recurrers (5+/-6 vs 2+/-1; p=0.05). Median AFP levels of both groups was 25 pre-LRT and stayed unchanged pre-OLT. No differences existed in mean number of LRTs between groups (2 +/- 1 vs. 2 +/- 1) . Percent patients with >=3 LRTs was 36% vs 39% in Recurrers and Controls respectively. However, location of recurrence was distant from tumor in a greater proportion of recurrers (50%vs 12,5%, p=0.07). Explant pathology showed higher grade (82% vs 28%, p<0.05) and larger tumor size (5+/-2 vs 3+/-2; p<0.05) in recurrers. Interestingly, on explant only 50% of recurrers and 59% of non-recurrers had single tumors.

*Conclusions: These data show that HCC patients with solitary lesions within Milan criteria need multiple LRTs and the number of LRTs do not predict who recurs. However, a pattern of recurrence distant from the original tumor bearing segment of the liver is present in patients that recur. Patients with these patterns of recurrence have higher tumor grade on final pathology. Finally, while an altered immune response, represented by NLR, was not present pre-LRT -patients that develop distant liver segment recurrences generate an elevated NLR. Therefore, we conclude that patients with solitary tumors undergoing LRT that have recurrences away from the original segment of involved tumor carry a higher oncologic risk & increased recurrence post-OLT.

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