Department of Radiation Oncology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Department of Medical Physics, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Radiother Oncol. 2019 Jun;135:100-106. doi: 10.1016/j.radonc.2019.03.003. Epub 2019 Mar 19.
To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancer patients.
Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/β ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method.
Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-A patients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision.
Patients with CP-A and viral hepatitis infection or CP-B/C cirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach.
预测放射性肝毒性（RILT）的概率，并实施基于正常组织并发症概率（NTCP）模型的方法，考虑置信区间（CI），以选择接受新治疗技术（如质子束治疗）的患者，这些新治疗技术基于原发性肝癌患者的特定 NTCP 降低（ΔNTCP）阈值。
对不良事件通用毒性标准（CTCAE）等级≥2 的 RILT 进行评分。使用参考分割大小 2 Gy/分割和α/β比 2 Gy，使用最大似然法拟合预测 CTCAE 等级≥2 RILT 概率作为分割大小调整平均肝剂量（MLD）函数的 Lyman NTCP 模型。在特定的 MLD 组合下，通过差值法评估具有 CI 的 ΔNTCP。
在 239 名患者中，CTCAE 等级≥2 的 RILT 发生率为 55%（CP-A 为 46%，CP-B/C 为 81%，p<0.001）。在 180 名 CP-A 患者中，40%的病毒性肝炎感染者出现毒性反应，而非肝炎亚组为 32%。毒性组的 MLD 为 18 Gy，非毒性组为 16.1 Gy（p=0.002）。针对患者亚组的特定 MLD 估计 NTCP 模型参数和具有特定 CP 分类和病毒性肝炎感染状态的 CI 假设的 ΔNTCP 差异较大，这可能改变治疗决策。
CP-A 且有病毒性肝炎感染或 CP-B/C 肝硬化的患者对 CTCAE 等级≥2 的 RILT 更敏感。针对个体患者的估计 NTCP 和 ΔNTCP 以及对不确定性的考虑，提高了基于 NTCP 模型的方法的可靠性。
