Department of Radiation Oncology, University of Washington School of Medicine, University of Washington, Seattle, Washington.
Department of Radiation Oncology, University of Washington School of Medicine, University of Washington, Seattle, Washington; Department of Radiology, University of Washington School of Medicine, University of Washington, Seattle, Washington.
Int J Radiat Oncol Biol Phys. 2018 Nov 15;102(4):1339-1348. doi: 10.1016/j.ijrobp.2018.08.029. Epub 2018 Aug 28.
Mitigating radiation-induced liver disease (RILD) is an ongoing need in patients with hepatocellular carcinoma. We hypothesize that [Tc]-sulfur colloid (SC) single photon emission computed tomography (SPECT)/computed tomography (CT) scans can provide global functional liver metrics and functional liver dosimetric parameters that are predictive of hepatotoxicity risk in patients with primary liver cancer with cirrhosis.
We retrospectively reviewed 47 patients (n = 26 proton, n = 21 stereotactic body radiation therapy) with Child-Pugh (CP)-A (62%) or CP-B (38%) cirrhosis who underwent SC SPECT/CT scans for radiation therapy planning. SC SPECT scans were mined for image intensity threshold-based functional liver volumes (FLV), mean liver-spleen uptake ratio (L/S), and total liver function (TLF = FLV*L/S). Radiation therapy doses were voxel-wise converted to the biologically equivalent dose (EQD2) and relative biological effectiveness (GyRBE). Normal liver (liver minus gross tumor volume [GTV]) and FLV mean doses, absolute and relative dose-volumes (V[cc], V[%]), and relative dose-function histogram quantiles in 10 GyEQD2 increments were calculated. Logistic regression was performed for correlation to CP score increase of 2 or higher (CP+2). Cox regression was performed for correlation to RILD-specific survival (RILD-SS) and overall survival.
The strongest predictors of RILD-SS were FLV V20 and liver-GTV F20. FLV mean dose, but not CT-derived anatomic mean dose, was predictive of RILD-SS. TLF and L/S were the only parameters that were associated with CP+2 after adjusting for baseline CP score. Optimal cutoffs to mitigate risk RILD-SS were identified: FLV mean dose <23 GyEQD2, liver-GTV V20 <36%, FLV V20 <36%, liver-GTV F20 <36%, FLV <32% (350 cc), L/S >0.75, TLF >0.60, tumor volume <40 cm, and CP score A5-6 versus B7-C10. A narrower therapeutic window was observed in CP-B/C patients. The discriminatory power for RILD-SS within CP-B/C classes was improved with the addition of a functional dosimetric constraint, resulting in low- and high-risk subgroups (P = 3 × 10).
Functional liver metrics and dosimetric parameters derived from pretreatment SC SPECT/CT scans were complementary predictors of hepatotoxicity and may provide useful clinical decision support in the management of cirrhotic patients with primary liver cancer.
减轻放射性肝损伤（RILD）是肝癌患者的一项持续需求。我们假设[Tc]-硫胶体（SC）单光子发射计算机断层扫描（SPECT）/计算机断层扫描（CT）可以提供整体功能肝指标和功能肝剂量学参数，这些指标和参数可以预测肝硬化原发性肝癌患者的肝毒性风险。
我们回顾性分析了 47 名患者（质子治疗 26 例，立体定向体部放射治疗 21 例），这些患者的 Child-Pugh（CP）分级为 A（62%）或 B（38%）级肝硬化，他们接受了 SC SPECT/CT 扫描以进行放射治疗计划。对 SC SPECT 扫描进行基于图像强度阈值的功能性肝体积（FLV）、肝脾摄取比（L/S）和总肝功能（TLF=FLV*L/S）的挖掘。将放射治疗剂量转换为生物等效剂量（EQD2）和相对生物效应（GyRBE）。计算正常肝（肝减去大体肿瘤体积[GTV]）和 FLV 平均剂量、绝对和相对剂量-体积（V[cc]，V[%]）以及 10 GyEQD2 增量的相对剂量功能直方图分位数。进行逻辑回归以分析与 CP 评分增加 2 或更高（CP+2）的相关性。进行 Cox 回归以分析与 RILD 特异性生存（RILD-SS）和总体生存的相关性。
RILD-SS 的最强预测因子是 FLV V20 和肝-GTV F20。FLV 平均剂量，但不是 CT 衍生的解剖平均剂量，与 RILD-SS 相关。在调整基线 CP 评分后，只有 TLF 和 L/S 与 CP+2 相关。确定了减轻 RILD-SS 风险的最佳截止值：FLV 平均剂量<23 GyEQD2，肝-GTV V20<36%，FLV V20<36%，肝-GTV F20<36%，FLV<32%（350 cc），L/S>0.75，TLF>0.60，肿瘤体积<40 cm，CP 评分 A5-6 与 B7-C10。CP-B/C 患者的治疗窗较窄。在 CP-B/C 级内，添加功能剂量学约束可提高 RILD-SS 的鉴别能力，从而形成低风险和高风险亚组（P=3×10）。
预处理 SC SPECT/CT 扫描获得的功能性肝指标和剂量学参数是肝毒性的补充预测因子，可为肝硬化原发性肝癌患者的管理提供有用的临床决策支持。
