质子束放疗治疗肝细胞癌的东西方患者放射性肝损伤的预测因子。
Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy.
机构信息
Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; The University of Texas MD Anderson Cancer Center-UT Health Graduate School of Biomedical Sciences, Houston, Texas.
Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
出版信息
Int J Radiat Oncol Biol Phys. 2019 Sep 1;105(1):73-86. doi: 10.1016/j.ijrobp.2019.02.032. Epub 2019 Feb 21.
PURPOSE
To identify predictors of radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) treated with proton beam therapy (PBT).
METHODS
This multicenter study included 136 patients with HCC (eastern, n = 102; western, n = 34) without evidence of intrahepatic tumor progression after PBT. The RILD was defined as ascites with alkaline-phosphatase abnormality, grade ≥3 hepatic toxicity, or Child-Pugh score worsening by ≥2 within 4 months after PBT completion. The proton doses were converted to equivalent doses in 2-GyE fractions. The unirradiated liver volume (ULV) was defined as the absolute liver volume (LV) receiving <1 GyE; the standard liver volume (SLV) was calculated using body surface area. Possible correlations of clinicodosimetric parameters with RILD were examined.
RESULTS
The mean pretreatment LV was 85% of SLV, and patients with a history of hepatectomy (P < .001) or hepatitis B virus infection (P = .035) had significantly smaller LV/SLV. Nineteen (14%) patients developed RILD. Multivariate logistic regression analysis identified ULV/SLV (P = .001), gross tumor volume (P = .001), and Child-Pugh classification (P = .002) as independent RILD predictors, and mean liver dose and target-delivered dose were not associated with RILD occurrence. A "volume-response" relationship between ULV/SLV and RILD was consistently observed in both eastern and western cohorts. In Child-Pugh class-A patients whose ULV/SLV were ≥50%, 49.9%-40%, 39.9%-30% and <30%, the RILD incidences were 0%, 6%, 16%, and 39% (P < .001), respectively. For the Child-Pugh class-B group, the RILD incidences in patients with ≥60%, 59.9%-40%, and <40% of ULV/SLV were 0%, 14%, and 83% (P = .006), respectively.
CONCLUSIONS
The ULV/SLV, not mean liver dose, independently predicts RILD in patients with HCC undergoing PBT. The relative and absolute contraindications for Child-Pugh class-A patient's ULV/SLV are <50% and <30%, and <60% and <40% for Child-Pugh class-B patients, respectively. Our results indicate that the likelihood of hepatic complications for PBT is dictated by similar metrics as that for surgery.
目的
确定质子束治疗（PBT）后肝细胞癌（HCC）患者放射性肝损伤（RILD）的预测因素。
方法
本多中心研究纳入了 136 例 HCC 患者（东部 102 例，西部 34 例），这些患者在 PBT 后无肝内肿瘤进展的证据。RILD 的定义为在 PBT 完成后 4 个月内出现腹水伴碱性磷酸酶异常、≥3 级肝毒性或 Child-Pugh 评分恶化≥2 分。质子剂量被转换为等效 2-GyE 剂量。未受照射的肝体积（ULV）定义为接受<1 GyE 的绝对肝体积（LV）；标准肝体积（SLV）是根据体表面积计算的。检查了临床剂量学参数与 RILD 的可能相关性。
结果
治疗前 LV 平均为 SLV 的 85%，有肝切除术史（P<0.001）或乙型肝炎病毒感染史（P=0.035）的患者 LV/SLV 明显较小。19 例（14%）患者发生 RILD。多变量逻辑回归分析确定 ULV/SLV（P=0.001）、大体肿瘤体积（P=0.001）和 Child-Pugh 分级（P=0.002）是 RILD 的独立预测因素，平均肝剂量和目标剂量与 RILD 发生无关。在东部和西部队列中，均一致观察到 ULV/SLV 与 RILD 之间的“体积反应”关系。在 ULV/SLV≥50%的 Child-Pugh 分级 A 患者中，RILD 发生率分别为 0%、6%、16%和 39%（P<0.001）。对于 Child-Pugh 分级 B 组，ULV/SLV≥60%、59.9%-40%和<40%的患者 RILD 发生率分别为 0%、14%和 83%（P=0.006）。
结论
ULV/SLV 而不是平均肝剂量，独立预测接受 PBT 的 HCC 患者发生 RILD。Child-Pugh 分级 A 患者 ULV/SLV 的相对和绝对禁忌证分别为<50%和<30%，Child-Pugh 分级 B 患者分别为<60%和<40%。我们的结果表明，PBT 的肝并发症发生可能性取决于与手术相似的指标。
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