Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Moffitt Cancer Center, Tampa, Florida, USA.
Med Phys. 2023 Sep;50(9):5597-5608. doi: 10.1002/mp.16386. Epub 2023 Apr 6.
Stereotactic body radiation therapy (SBRT) produces excellent local control for patients with hepatocellular carcinoma (HCC). However, the risk of toxicity for normal liver tissue is still a limiting factor. Normal tissue complication probability (NTCP) models have been proposed to estimate the toxicity with the assumption of uniform liver function distribution, which is not optimal. With more accurate regional liver functional imaging available for individual patient, we can improve the estimation and be more patient-specific.
To develop normal tissue complication probability (NTCP) models using pre-/during-treatment (RT) dynamic Gadoxetic Acid-enhanced (DGAE) MRI for adaptation of RT in a patient-specific manner in hepatocellular cancer (HCC) patients who receive SBRT.
24 of 146 HCC patients who received SBRT underwent DGAE MRI. Physical doses were converted into EQD2 for analysis. Voxel-by-voxel quantification of the contrast uptake rate (k1) from DGAE-MRI was used to quantify liver function. A logistic dose-response model was used to estimate the fraction of liver functional loss, and NTCP was estimated using the cumulative functional reserve model for changes in Child-Pugh (C-P) scores. Model parameters were calculated using maximum-likelihood estimations. During-RT liver functional maps were predicted from dose distributions and pre-RT k1 maps with a conditional Wasserstein generative adversarial network (cWGAN). Imaging prediction quality was assessed using root-mean-square error (RMSE) and structural similarity (SSIM) metrics. The dose-response and NTCP were fit on both original and cWGAN predicted images and compared using a Wilcoxon signed-rank test.
Logistic dose response models for changes in k1 yielded D50 of 35.2 (95% CI: 26.7-47.5) Gy and k of 0.62 (0.49-0.75) for the whole population. The high baseline ALBI (poor liver function) subgroup showed a significantly smaller D50 of 11.7 (CI: 9.06-15.4) Gy and larger k of 0.96 (CI: 0.74-1.22) compared to a low baseline ALBI (good liver function) subgroup of 54.8 (CI: 38.3-79.1) Gy and 0.59 (CI: 0.48-0.74), with p-values of < 0.001 and = 0.008, respectively, which indicates higher radiosensitivity for the worse baseline liver function cohort. Subset analyses were also performed for high/low baseline CP subgroups. The corresponding NTCP models showed good agreement for the fit parameters between cWGAN predicted and the ground-truth during-RT images with no statistical differences for low ALBI subgroup.
NTCP models which incorporate voxel-wise functional information from DGAE-MRI k1 maps were successfully developed and feasibility was demonstrated in a small patient cohort. cWGAN predicted functional maps show promise for estimating localized patient-specific response to RT and warrant further validation in a larger patient cohort.
立体定向体部放射治疗（SBRT）可使肝细胞癌（HCC）患者获得优异的局部控制效果。然而，正常肝脏组织的毒性风险仍然是一个限制因素。已经提出了正常组织并发症概率（NTCP）模型来估计毒性，假设肝脏功能分布均匀，但这种假设并不理想。随着更精确的区域肝脏功能成像在个体患者中得到应用，我们可以提高对肝脏功能的估计，实现更个体化的治疗。
使用治疗前/期间（RT）的钆塞酸增强（DGAE）MRI 开发正常组织并发症概率（NTCP）模型，以便对接受 SBRT 的 HCC 患者进行个体化的 RT 适应性调整。
146 例接受 SBRT 的 HCC 患者中有 24 例接受了 DGAE MRI 检查。将物理剂量转换为 EQD2 进行分析。通过 DGAE-MRI 中的对比摄取率（k1）的体素定量来定量肝脏功能。使用逻辑剂量反应模型来估计肝脏功能丧失的分数，使用累积功能储备模型来估计 Child-Pugh（C-P）评分变化的 NTCP。模型参数通过最大似然估计计算。使用条件 Wasserstein 生成对抗网络（cWGAN）从剂量分布和治疗前 k1 图预测治疗期间的肝脏功能图。使用均方根误差（RMSE）和结构相似性（SSIM）指标评估图像预测质量。使用 Wilcoxon 符号秩检验比较原始图像和 cWGAN 预测图像的剂量反应和 NTCP 拟合结果。
用于 k1 变化的逻辑剂量反应模型得出了整个队列的 D50 为 35.2（95%CI：26.7-47.5）Gy 和 k 为 0.62（0.49-0.75）。基线 ALBI 较高（肝功能较差）亚组的 D50 明显较小，为 11.7（CI：9.06-15.4）Gy，k 较大，为 0.96（CI：0.74-1.22），而基线 ALBI 较低（肝功能较好）亚组的 D50 为 54.8（CI：38.3-79.1）Gy，k 为 0.59（CI：0.48-0.74），p 值均<0.001 和=0.008，这表明基线肝功能较差的队列对放射治疗的敏感性更高。还对高/低基线 CP 亚组进行了亚组分析。cWGAN 预测的功能图与治疗期间的真实功能图之间的拟合参数具有良好的一致性，低 ALBI 亚组之间没有统计学差异。
成功开发了纳入 DGAE-MRI k1 图的体素级功能信息的 NTCP 模型，并在小患者队列中证明了其可行性。cWGAN 预测的功能图有望估计局部患者对 RT 的特异性反应，值得在更大的患者队列中进一步验证。
