Hanouneh I A, Macaron C, Lopez R, Aucejo F, Zein N N
Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Transplant Proc. 2011 Dec;43(10):3813-8. doi: 10.1016/j.transproceed.2011.09.043.
It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC).
We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr3, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed.
Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7-30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P=.001), poorly differentiated tumors (HR 13; P=.039), the presence of microvascular invasion (HR 7.9; P=.001), higher TTV (HR 1.03; P<.001), and faster tumor growth (HR 1.09; P<.001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm3/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth<1.61 cm3/mo experienced less recurrence (11% vs 58%; P=.023) than those beyond the Milan criteria with tumor growth>1.61 cm3/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria.
Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.
一些肿瘤负荷超过当前移植标准的患者可能具有良好的肿瘤生物学特性，并且这些患者肝移植（LT）后肿瘤复发风险较低。为评估肿瘤生长速度作为肝细胞癌（HCC）患者LT选择标准的情况。
我们确定了2002年至2008年在本机构接受LT治疗HCC的所有患者。计算总肿瘤体积（TTV），即移植前影像学上所有肿瘤体积之和[（4/3）πr³，其中r为每个HCC的最大半径]。肿瘤生长速度按在任何局部区域治疗前连续移植前影像学上TTV的每月变化计算。构建Kaplan-Meier曲线并进行Cox回归分析。
92例患者纳入研究。中位随访时间为19.5（范围10.7 - 30.7）个月，期间12例患者（13%）发生HCC复发。24例患者（26%）的HCC超出米兰标准，整个组的总生存率为72%。移植前甲胎蛋白水平较高（风险比[HR] 1.01；P = 0.001）、肿瘤分化差（HR 13；P = 0.039）、存在微血管侵犯（HR 7.9；P = 0.001）、TTV较高（HR 1.03；P < 0.001）以及肿瘤生长较快（HR 1.09；P < 0.001）与复发风险显著相关。根据复发风险利用受试者工作特征曲线选择肿瘤生长的临界值为1.61 cm³/月。肿瘤生长<1.61 cm³/月且超出米兰标准的患者比肿瘤生长>1.61 cm³/月且超出米兰标准的患者复发率更低（11%对58%；P = 0.023）。同样，肿瘤生长速度可预测超出加利福尼亚大学旧金山分校（UCSF）标准患者的HCC复发情况。
目前因肿瘤负荷超过传统米兰和UCSF标准而被排除在LT之外的肿瘤生长缓慢的患者，移植后可能有良好的预后。
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