*Purpose: Orthotopic Liver Transplantation (OLT) remains a curative option for hepatocellular carcinoma (HCC). Disparity between the supply and demand for OLT necessitates the transplant of only those patients with HCC that have favorable characteristics and comparable outcomes to OLT for benign disease. The Milan criteria have been established with this in mind. However, even in patients within Milan criteria there are some bad actors that lead to early recurrence and inadequate survival. We aim to characterize these patients to allow for identification of their patterns of recurrence, and AFP trends in response to (locoregional therapy) LRT prior to OLT.

*Methods: From a database of over 2000 patients we identified 645 patients that had undergone OLT for cancer. Seventy four patients had recurrences. Among the recurrers we then identified 49 patients with only HCC who had also undergone LRT. Of these 35 patients were within Milan characteristics on pre-LRT imaging & had all needed datapoints. Patient demographics, date of surgery, operative parameters, explant pathology, date of recurrence and death were obtained. Statistical analysis was performed using Chi Square, Student’s T test, Cox-proportional Hazard, Kaplan -Meier curves as needed using SAS software.

*Results: Median age of all patients was 60years and 83% were male. AFP pre LRT was 169+/-314ng/ml. Chemoembolization was the modality of choice in the majority of patients. Seventy-seven percent of the patients underwent more than one LRT- with 31% having 2 LRTs, 23% with 3 LRT, 17% with 4 LRT and 6% with &gt 5 LRTs. Eighty five percent of the patients recurred following the first LRT. The patterns of recurrence were confined to same segment of the liver as the prior tumor in 93% of the cases. AFP demonstrated a substantial decrease after the first LRT- going down on avg to 58+/-89ng/ml. However, subsequent LRT treatments were not associated with a drop- with AFP on avg 62 and 93ng/ml after LRT#2 & LRT#3 respectively. Neutrophil-lymphocyte ratio pre-LRT was 4.4+/-3.6. Explant pathology demonstrated 94% of patients with tumor grade &gt 2 & 86% of patients with moderate to poorly differentiated tumors. Median recurrence free survival was 14 months and overall survival 33 months.

*Conclusions: These data show that patients within Milan criteria who recurred post-OLT underwent multiple rounds of locoregional therapy. Furthermore, after the decrease in the AFP in response to the 1st LRT the AFP does not decrease in response to subsequent LRTs,-staying above normal but within accepted levels for OLT. Additionally, the majority of the tumors recur within the same segment of the liver as the original tumor. Finally, explant pathology suggests a higher incidence of moderate to poorly differentiated tumors in this cohort of patients. Therefore, we conclude that patterns of tumor recurrence & AFP response to LRT could predict bad actors within Milan criteria.

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