Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Canada.
Department of Medical Physics, Princess Margaret Cancer Centre, Toronto, Canada.
Pract Radiat Oncol. 2017 Sep-Oct;7(5):e331-e337. doi: 10.1016/j.prro.2017.03.004. Epub 2017 Mar 9.
The aim of this study is to describe the incidence and type of liver toxicity seen following liver metastases stereotactic body radiation therapy (SBRT) and the corresponding clinical and dosimetric factors associated with toxicity.
Between 2002 and 2009, 81 evaluable patients with liver metastases were treated on 2 prospective studies assessing SBRT, with prescription doses based on the effective liver volume irradiated evaluated. Toxicity was defined as grade ≥2 classic or nonclassic radiation induced liver disease (RILD). Specific toxicity endpoints evaluated were worsening transaminases and albumin levels within 3 months of SBRT.
Seventy percent of patients had colorectal carcinoma, 55% had extrahepatic disease, 1 patient had hepatitis B, and 54% had received prior chemotherapy. Baseline transaminases were elevated at Common Terminology Criteria for Adverse Effects, V4.0, grade 1, 2, and 3 levels in 33 (41%), 2 (2%), and 0 (0%) patients. The mean prescription dose was 43 Gy (27.7-60 Gy) in 6 fractions. The mean liver (minus gross tumor volume) dose (MLD) was 16 Gy (3-25.6 Gy) in 6 fractions. No classic or nonclassical ≥grade 2 RILD was observed. Within 3 months of SBRT, 49 (61%) patients had worsening of grade of transaminase and 23 (28%) patients had a reduction in albumin, all transient (majority grade ≤2 toxicity) without subsequent clinical toxicity. Seventeen patients exceeded Quantitative Analysis of Normal Tissue Effects in the Clinic MLD guidelines (≤20 Gy), 13 (76%) of whom had worsening of transaminase grade. On multivariate analysis, worsening of liver enzymes was more likely in patients with higher doses to the spared 700 mL of liver (P = .026), and reduction of albumin was more likely with higher effective liver volume (odds ratio, 1.53 [range, 1.08-2.16]) P = .016).
Liver metastases SBRT is safe with a low risk of transient biochemical liver toxicity, more likely in patients with a higher effective liver volume and higher doses to the spared uninvolved liver volume.
本研究旨在描述立体定向体部放射治疗（SBRT）后肝转移瘤发生的肝毒性的发生率和类型，以及与毒性相关的临床和剂量学因素。
在 2002 年至 2009 年期间，81 例可评估的肝转移瘤患者参与了 2 项前瞻性研究，采用基于评估的有效肝脏体积照射的处方剂量进行 SBRT。毒性定义为≥2 级经典或非经典放射性肝损伤（RILD）。评估的具体毒性终点是 SBRT 后 3 个月内转氨酶和白蛋白水平的恶化。
70%的患者患有结直肠癌，55%的患者有肝外疾病，1 例患者患有乙型肝炎，54%的患者接受过化疗。根据不良事件通用术语标准，第 4.0 版，基线时转氨酶升高分别为 33 例（41%）、2 例（2%）和 0 例（0%）患者的 1 级、2 级和 3 级。平均处方剂量为 6 次分割的 43 Gy（27.7-60 Gy）。平均肝脏（减去大体肿瘤体积）剂量（MLD）为 6 次分割的 16 Gy（3-25.6 Gy）。未观察到经典或非经典≥2 级 RILD。在 SBRT 后 3 个月内，49 例（61%）患者的转氨酶水平恶化，23 例（28%）患者的白蛋白水平降低，均为短暂性（多数为 2 级以下毒性），无后续临床毒性。17 例患者超过了临床剂量限制正常组织效应的定量分析（≤20 Gy），其中 13 例（76%）的患者转氨酶水平恶化。多变量分析显示，对于接受较高剂量 spared 700ml 肝脏的患者，肝酶恶化的可能性更大（P=.026），而对于有效肝脏体积较高的患者，白蛋白降低的可能性更大（比值比，1.53[范围，1.08-2.16]），P=.016）。
SBRT 治疗肝转移瘤是安全的，具有低风险的短暂性生化肝毒性，对于有效肝脏体积较高和接受较高剂量 spared 未受累肝脏体积的患者更有可能发生。
