Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
Int J Radiat Oncol Biol Phys. 2018 Feb 1;100(2):335-343. doi: 10.1016/j.ijrobp.2017.10.005.
To develop normal tissue complications (NTCP) models for hepatocellular cancer (HCC) patients who undergo liver radiation therapy (RT) and to evaluate the potential role of functional imaging and measurement of blood-based circulating biological markers before and during RT to improve the performance of these models.
The data from 192 HCC patients who had undergone RT from 2005 to 2014 were evaluated. Of the 192 patients, 146 had received stereotactic body RT (SBRT) and 46 had received conventional RT to a median physical tumor dose of 49.8 Gy and 50.4 Gy, respectively. The physical doses were converted into 2-Gy equivalents for analysis. Two approaches were investigated for modeling NTCP: (1) a generalized Lyman-Kutcher-Burman model; and (2) a generalization of the parallel architecture model. Three clinical endpoints were considered: the change in albumin-bilirubin (ALBI), change in Child-Pugh (C-P) score, and grade ≥3 liver enzymatic changes. Local dynamic contrast-enhanced magnetic resonance imaging portal venous perfusion information was used as an imaging biomarker for local liver function. Four candidate inflammatory cytokines were considered as biological markers. The imaging findings and cytokine levels were incorporated into NTCP modeling, and their role was evaluated using goodness-of-fit metrics.
Using dosimetric information only, the Lyman-Kutcher-Burman model for the ALBI/C-P change had a steeper response curve compared with grade ≥3 enzymatic changes. Incorporating portal venous perfusion imaging information into the parallel architecture model to represent functional reserve resulted in relatively steeper dose-response curves compared with dose-only models. A larger loss of perfusion function was needed for enzymatic changes compared with ALBI/C-P changes. Increased transforming growth factor-β1 and eotaxin expression increased the trend of expected risk in both NTCP modeling approaches but did not reach statistical significance.
The incorporation of imaging findings and biological markers into NTCP modeling of liver toxicity improved the estimates of expected NTCP risk compared with using dose-only models. In addition, such generalized NTCP models should contribute to a better understanding of the normal tissue response in HCC SBRT patients and facilitate personalized treatment.
为接受肝脏放射治疗（RT）的肝细胞癌（HCC）患者开发正常组织并发症（NTCP）模型，并评估在 RT 前后使用功能成像和测量基于血液的循环生物标志物的潜在作用，以提高这些模型的性能。
对 192 例 2005 年至 2014 年间接受 RT 的 HCC 患者的数据进行了评估。192 例患者中，146 例接受立体定向体部 RT（SBRT），46 例接受常规 RT，中位物理肿瘤剂量分别为 49.8 Gy 和 50.4 Gy。为了分析，将物理剂量转换为 2-Gy 等效剂量。研究了两种建模 NTCP 的方法：（1）广义 Lyman-Kutcher-Burman 模型；（2）并行架构模型的推广。考虑了三个临床终点：白蛋白-胆红素（ALBI）变化、Child-Pugh（C-P）评分变化和 3 级以上肝酶变化。局部动态对比增强磁共振成像门静脉灌注信息被用作局部肝功能的成像生物标志物。考虑了四种候选炎症细胞因子作为生物标志物。将成像结果和细胞因子水平纳入 NTCP 建模中，并使用拟合优度指标评估其作用。
仅使用剂量学信息，Lyman-Kutcher-Burman 模型用于 ALBI/C-P 变化的响应曲线比 3 级以上酶变化陡峭。将门静脉灌注成像信息纳入平行架构模型以代表功能储备，与剂量仅模型相比，剂量反应曲线相对陡峭。与 ALBI/C-P 变化相比，酶变化需要更大的灌注功能损失。转化生长因子-β1 和嗜酸性粒细胞趋化因子表达增加增加了两种 NTCP 建模方法中预期风险的趋势，但没有达到统计学意义。
将成像结果和生物标志物纳入肝脏毒性的 NTCP 建模中，与仅使用剂量模型相比，提高了预期 NTCP 风险的估计。此外，这种广义的 NTCP 模型应该有助于更好地了解 HCC SBRT 患者的正常组织反应，并促进个体化治疗。
