Dawson Laura A, Normolle Daniel, Balter James M, McGinn Cornelius J, Lawrence Theodore S, Ten Haken Randall K
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109-0010, USA.
Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):810-21. doi: 10.1016/s0360-3016(02)02846-8.
To describe the dose-volume tolerance for radiation-induced liver disease (RILD) using the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model.
A total of 203 patients treated with conformal liver radiotherapy and concurrent hepatic arterial chemotherapy were prospectively followed for RILD. Normal liver dose-volume histograms and RILD status for these patients were used as input data for determination of LKB model parameters. A complication was defined as Radiation Therapy Oncology Group Grade 3 or higher RILD < o r =4 months after completion of radiotherapy. A maximal likelihood analysis yielded best estimates for the LKB NTCP model parameters for the liver for the entire patient population. A multivariate analysis of the potential factors associated with RILD was also completed, and refined LKB model parameters were obtained for patient subgroups with different risks of RILD.
Of 203 patients treated with focal liver irradiation, 19 developed RILD. The LKB NTCP model fit the complication data for the entire group. The "n" parameter was larger than previously described, suggesting a strong volume effect for RILD and a correlation of NTCP with the mean liver dose. No cases of RILD were observed when the mean liver dose was <31 Gy. Multivariate analysis demonstrated that in addition to NTCP and the mean liver dose, a primary hepatobiliary cancer diagnosis (vs. liver metastases), bromodeoxyuridine hepatic artery chemotherapy (vs. fluorodeoxyuridine chemotherapy), and male gender were associated with RILD. For 169 patients treated with fluorodeoxyuridine, the refined LKB model parameters were n = 0.97, m = 0.12, tolerance dose for 50% complication risk for whole organ irradiated uniformly [TD50(1)] = 45.8 Gy for patients with liver metastases, and TD50(1) = 39.8 Gy for patients with primary hepatobiliary cancer.
These data demonstrate that the liver exhibits a large volume effect for RILD, suggesting that the mean liver dose may be useful in ranking radiation plans. The inclusion of clinical factors, especially the diagnosis of primary hepatobiliary cancer vs. liver metastases, improves the estimation of NTCP over that obtained solely by the use of dose-volume data. These findings should facilitate the application of focal liver irradiation in future clinical trials.
使用莱曼 - 库彻 - 伯曼（LKB）正常组织并发症概率（NTCP）模型描述放射性肝病（RILD）的剂量 - 体积耐受性。
前瞻性随访了203例接受适形肝脏放疗及同期肝动脉化疗的患者，观察RILD情况。将这些患者的正常肝脏剂量 - 体积直方图和RILD状态作为确定LKB模型参数的输入数据。并发症定义为放疗结束后≤4个月出现放射肿瘤学组3级或更高等级的RILD。通过最大似然分析得出了整个患者群体肝脏的LKB NTCP模型参数的最佳估计值。还完成了与RILD相关潜在因素的多变量分析，并为具有不同RILD风险的患者亚组获得了优化的LKB模型参数。
在203例接受局部肝脏照射的患者中，19例发生了RILD。LKB NTCP模型拟合了整个组的并发症数据。“n”参数大于先前描述的值，表明RILD存在强烈的体积效应，且NTCP与平均肝脏剂量相关。当平均肝脏剂量<31 Gy时，未观察到RILD病例。多变量分析表明，除了NTCP和平均肝脏剂量外，原发性肝胆癌诊断（相对于肝转移）、溴脱氧尿苷肝动脉化疗（相对于氟脱氧尿苷化疗）以及男性性别与RILD相关。对于169例接受氟脱氧尿苷治疗的患者，优化后的LKB模型参数为：n = 0.97，m = 0.12，均匀照射全肝时50%并发症风险的耐受剂量[TD50(1)]，肝转移患者为45.8 Gy，原发性肝胆癌患者为39.8 Gy。
这些数据表明肝脏对RILD表现出较大的体积效应，提示平均肝脏剂量可能有助于对放疗计划进行排序。纳入临床因素，特别是原发性肝胆癌与肝转移的诊断，比仅使用剂量 - 体积数据能更好地估计NTCP。这些发现应有助于在未来的临床试验中应用局部肝脏照射。
