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Reframing the approach to patients with hepatocellular carcinoma: Longitudinal assessment with hazard associated with liver transplantation for HCC (HALTHCC) improves ablate and wait strategy
Author(s) -
Firl Daniel J.,
Kimura Shoko,
McVey John,
Hashimoto Koji,
Yeh Heidi,
Miller Charles M.,
Markmann James F.,
Sasaki Kazunari,
Aucejo Federico N.
Publication year - 2018
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.29907
Subject(s) - hepatocellular carcinoma , medicine , liver transplantation , hazard ratio , proportional hazards model , oncology , retrospective cohort study , cohort , transplantation , gastroenterology , confidence interval
Patients with hepatocellular carcinoma (HCC) are screened at presentation for appropriateness of liver transplantation (LT) using morphometric criteria, which poorly specifies risk. Morphology is the crux of measuring tumor response to locoregional therapy (LRT) using modified Response Evaluation Criteria in Solid Tumors (mRECIST). This study investigated the utility of following a continuous risk score (hazard associated with liver transplantation in hepatocellular carcinoma; HALTHCC) to longitudinally assess risk. This multicenter, retrospective study from 2002 to 2014 enrolled 419 patients listed for LT for HCC. One cohort had LRT while waiting (n = 351), compared to the control group (n = 68) without LRT. Imaging studies (n = 2,085) were collated to laboratory data to calculate HALTHCC, MORAL, Metroticket 2.0, and alpha fetoprotein (AFP) score longitudinally. Cox proportional hazards evaluated associations of HALTHCC and peri‐LRT changes with intention‐to‐treat (ITT) survival (considering dropout or post‐LT mortality), and utility was assessed with Harrell's C‐index. HALTHCC better predicted ITT outcome (LT = 309; dropout = 110) when assessed closer to delisting ( P < 0.0001), maximally just before delisting (C‐index, 0.742 [0.643‐0.790]). Delta‐HALTHCC post‐LRT was more sensitive to changes in risk than mRECIST. HALTHCC score and peri‐LRT percentage change were independently associated with ITT mortality (hazard ratio = 1.105 [1.045‐1.169] per point and 1.014 [1.004‐1.024] per percent, respectively). Conclusions: HALTHCC is superior in assessing tumor risk in candidates awaiting LT, and its utility increases over time. Peri‐LRT relative change in HALTHCC outperforms mRECIST in stratifying risk of dropout, mortality, and recurrence post‐LT. With improving estimates of post‐LT outcomes, it is reasonable to consider allocation using HALTHCC and not just waiting time. Furthermore, this study supports a shift in perspective, from listing to allocation, to better utilize precious donor organs. (H epatology 2018).