Normolle Daniel, Pan Charlie, Ben-Josef Edgar, Lawrence Theodore
Biostatistics Facility, University of Pittsburgh Cancer Institute, Suite 325 Sterling Plaza, 201 N Craig St, Pittsburgh, PA 15213, USA, Tel.: +1 412 383 1591, ,
Per Med. 2010;7(2):197-204. doi: 10.2217/pme.10.5.
Primary liver cancer is a major health problem worldwide, with more than 500,000 new cases diagnosed yearly. Preliminary results suggest excellent local control rates of intrahepatic malignancies treated with stereotactic body radiation therapy (SBRT), but some patients have experienced life-threatening toxicity because the current approaches cannot accurately estimate residual liver function after treatment. An early-phase trial of SBRT in hepatocellular carcinoma patients, including those with compromised liver function, is described. Patients are treated with three fractions of SBRT, then treatment is paused for 4 weeks and liver function is evaluated by means of an indocyanine green assay. The size of the final two fractions of SBRT is determined based on the patient's indocyanine green assay after the first three fractions, so that the therapy is personalized to each patient's sensitivity to radiation. The sensitivity to the liver of the final two fractions of SBRT, compared with the first three fractions, is re-estimated using a Bayesian model throughout the trial, so this is an adaptive trial. The operating characteristics of the trial are described by Monte Carlo simulations.
原发性肝癌是全球主要的健康问题，每年有超过50万新发病例被诊断出来。初步结果显示，立体定向体部放射治疗（SBRT）治疗肝内恶性肿瘤的局部控制率极佳，但由于目前的方法无法准确估计治疗后残余肝功能，一些患者经历了危及生命的毒性反应。本文描述了一项针对肝细胞癌患者（包括肝功能受损患者）的SBRT早期试验。患者接受三次分割的SBRT治疗，然后治疗暂停4周，并通过吲哚菁绿试验评估肝功能。SBRT最后两次分割的剂量根据前三分割后患者的吲哚菁绿试验结果确定，从而使治疗针对每个患者对辐射的敏感性进行个性化调整。在整个试验过程中，使用贝叶斯模型重新估计SBRT最后两次分割与前三分割相比对肝脏的敏感性，因此这是一项适应性试验。通过蒙特卡罗模拟描述了该试验的操作特征。
