Lasley Foster D, Mannina Edward M, Johnson Cynthia S, Perkins Susan M, Althouse Sandra, Maluccio Mary, Kwo Paul, Cárdenes Higinia
Mercy Radiation Oncology, Oklahoma City, Oklahoma.
Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.
Pract Radiat Oncol. 2015 Sep-Oct;5(5):e443-e449. doi: 10.1016/j.prro.2015.02.007. Epub 2015 Apr 18.
An analysis was performed on patients enrolled in a phase 1-2 trial using stereotactic body radiation therapy for hepatocellular carcinoma evaluating variables influencing liver toxicity.
Thirty-eight Child-Pugh class A (CPC-A) (39 lesions) and 21 CPC-B patients (26 lesions) were followed for ≥6 months. Six months local control using modified Response Evaluation Criteria in Solid Tumors criteria, progression-free survival, overall survival, and grade III/IV treatment-related toxicity at 3 months were analyzed.
Median follow-up was 33.3 months (2.8-61.1 months) for CPC-A and 46.3 months (3.7-70.4 months) for CPC-B patients. Local control at 6 months was 92% for CPC-A and 93% for CPC-B. Kaplan-Meier estimated 2- and 3-year local control was 91% for CPC-A and 82% for CPC-B (P = .61). Median overall survival was 44.8 months and 17.0 months for CPC-A and CPC-B. Kaplan-Meier estimated 2- and 3-year overall survival was 72% and 61% for CPC-A and 33% and 26% for CPC-B (P = .03). Four (11%) CPC-A patients and 8 CPC-B patients (38%) experienced grade III/IV liver toxicity. Overall, CPC-A patients with ≥grade III liver toxicity had 4.59 (95% confidence interval, 1.19-17.66) times greater risk of death than those without toxicity (P = .0268). No such correlation was seen for CPC-B patients; however, 3 of these CPC-B patients underwent orthotopic liver transplant. CPC-B patients experiencing grade III/IV liver toxicity had significantly higher mean liver dose, higher dose to one-third normal liver, and larger volumes of liver receiving doses <2.5 to 15 Gy in 2.5-Gy increments. For CPC-A patients, there was no critical liver dose or volume constraint correlated with toxicity.
In our experience, liver stereotactic body radiation therapy is a safe therapy for patients with hepatocellular carcinoma in the context of liver cirrhosis; however, for CPC-B patients, careful attention should be paid to low-dose volumes that could potentially result in increased liver toxicity.
对参加1/2期试验的患者进行分析，该试验采用立体定向体部放射治疗肝细胞癌，评估影响肝脏毒性的变量。
38例Child-Pugh A级（CPC-A）（39个病灶）和21例CPC-B级患者（26个病灶）随访时间≥6个月。采用实体瘤改良疗效评价标准分析6个月时的局部控制率、无进展生存期、总生存期以及3个月时III/IV级治疗相关毒性。
CPC-A级患者的中位随访时间为33.3个月（2.8 - 61.1个月），CPC-B级患者为46.3个月（3.7 - 70.4个月）。CPC-A级患者6个月时的局部控制率为92%，CPC-B级患者为93%。Kaplan-Meier法估计CPC-A级患者2年和3年局部控制率分别为91%和82%，CPC-B级患者分别为82%（P = 0.61）。CPC-A级和CPC-B级患者的中位总生存期分别为44.8个月和17.0个月。Kaplan-Meier法估计CPC-A级患者2年和3年总生存率分别为72%和61%，CPC-B级患者分别为33%和26%（P = 0.03）。4例（11%）CPC-A级患者和8例CPC-B级患者（38%）出现III/IV级肝脏毒性。总体而言，CPC-A级且肝脏毒性≥III级的患者死亡风险是无毒性患者的4.59倍（95%置信区间，1.19 - 17.66）（P = 0.0268）。CPC-B级患者未观察到这种相关性；然而，其中3例CPC-B级患者接受了原位肝移植。出现III/IV级肝脏毒性的CPC-B级患者平均肝脏剂量显著更高，三分之一正常肝脏的剂量更高，且接受2.5 Gy至15 Gy（以2.5 Gy递增）剂量的肝脏体积更大。对于CPC-A级患者，未发现与毒性相关的关键肝脏剂量或体积限制。
根据我们的经验，在肝硬化背景下肝细胞癌患者中，肝脏立体定向体部放射治疗是一种安全的治疗方法；然而，对于CPC-B级患者，应密切关注可能导致肝脏毒性增加的低剂量体积。
