Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy.
J Nucl Med. 2010 Sep;51(9):1377-85. doi: 10.2967/jnumed.110.075861. Epub 2010 Aug 18.
Radioactive (90)Y-selective internal radiation (SIR) sphere therapy is increasingly used for the treatment of nonresectable hepatocellular carcinoma (HCC). However, the maximum delivered dose is limited by severe injury to the nontarget tissue, including liver parenchyma. Our study aimed to implement radiobiologic models for both tumor control probability (TCP) and normal-tissue complication probability (NTCP) to describe more effectively local response and the liver toxicity rate, respectively.
Patients with documented HCC, adequate bone marrow parameters, and regular hepatic and pulmonary function were eligible for the study. Patients who had pulmonary shunt greater than 20% of (99m)Tc-labeled macroaggregated albumin or any uncorrectable delivery to the gastrointestinal tract, reverse blood flow out of the liver, or complete portal vein thrombosis were excluded. Patients received a planned activity of the (90)Y-SIR spheres, determined using the empiric body surface area method. The dose distribution was determined using posttreatment (3-dimensional) activity distribution and Monte Carlo dose voxel kernel calculations, and the mean doses to healthy liver and tumor were calculated for each patient. Response was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) and recommendations of the European Association for the Study of the Liver (EASL). Criteria were used to assess possible liver toxicities. The parameters of TCP and NTCP models were established by direct maximization of the likelihood.
Seventy-three patients were treated. With an average dose of 110 Gy to the tumor, complete or partial response was observed in 74% and 55% of patients according to the EASL guideline and RECIST, respectively, and the predicted TCPs were 73% and 55%, respectively. With a median liver dose of 36 Gy (range, 6-78 Gy), the >or=grade 2 (G2), >or=grade 3 (G3), and >or=grade 4 (G4) liver toxicities were observed in 32% (23/73), 21% (15/73), and 11% (8/73) of patients, respectively. The parameters describing the >or=G2 liver toxicity data using the NTCP model were a tolerance dose of the whole organ leading to a 50% complication probability of 52 Gy (95% confidence interval, 44-61 Gy) and a slope of NTCP versus dose of 0.28 (95% confidence interval, 0.18-0.60), assuming n = 1.
The radiobiologic approach, based on patient-specific dosimetry, could improve the (90)Y-microsphere therapeutic approach of HCC, maintaining an acceptable liver toxicity.
描述肿瘤控制概率（TCP）和正常组织并发症概率（NTCP）的放射生物模型，以分别更有效地描述局部反应和肝脏毒性发生率。
纳入有记录的 HCC、足够的骨髓参数、正常肝和肺功能的患者。排除肺分流>20%（99m）Tc 标记的大聚合白蛋白或任何不可纠正的胃肠道输送、肝外血流、或完全门静脉血栓形成的患者。患者接受计划的（90）Y-SIR 球体活性，使用经验体表面积法确定。使用治疗后（三维）活性分布和蒙特卡罗剂量体素核计算来确定剂量分布，并为每位患者计算健康肝脏和肿瘤的平均剂量。根据实体瘤反应评价标准（RECIST）和欧洲肝脏研究协会（EASL）的建议定义反应。使用标准评估可能的肝毒性。通过直接最大化似然度来建立 TCP 和 NTCP 模型的参数。
共 73 例患者接受治疗。根据 EASL 指南和 RECIST，肿瘤平均剂量为 110 Gy 时，74%和 55%的患者完全或部分缓解，预测 TCP 分别为 73%和 55%。肝脏中位剂量为 36 Gy（范围 6-78 Gy），32%（23/73）、21%（15/73）和 11%（8/73）的患者分别出现>或=2 级（G2）、>或=3 级（G3）和>或=4 级（G4）肝脏毒性。使用 NTCP 模型描述>或=G2 肝脏毒性数据的参数是导致 50%并发症概率为 52 Gy（95%置信区间，44-61 Gy）的全器官耐受剂量，以及 NTCP 与剂量的斜率为 0.28（95%置信区间，0.18-0.60），假设 n = 1。
基于患者特定剂量学的放射生物学方法可以改善 HCC 的（90）Y 微球体治疗方法，同时保持可接受的肝脏毒性。
