Schefter Tracey E, Kavanagh Brian D, Timmerman Robert D, Cardenes Higinia R, Baron Anna, Gaspar Laurie E
Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO 80045-0510, USA.
Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1371-8. doi: 10.1016/j.ijrobp.2005.01.002.
To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) for liver metastases.
A multicenter Phase I clinical trial was conducted. Eligible patients had one to three liver metastases, tumor diameter <6 cm, and adequate liver function. The first cohort received 36 Gy to the planning target volume (PTV) in three fractions (F). Subsequent cohorts received higher doses up to a chosen maximum of 60 Gy/3F. At least 700 mL of normal liver had to receive a total dose <15 Gy. Dose-limiting toxicity (DLT) included acute Grade 3 liver or intestinal toxicity or any acute Grade 4 toxicity. The MTD was exceeded if 2/6 patients in a cohort experienced DLT.
Eighteen patients were enrolled (10 male, 8 female): median age, 55 years (range, 26-83 years); most common primary site, colorectal (6 patients); median aggregate gross tumor volume, 18 ml (range, 3-98 ml). Four patients had multiple tumors. No patient experienced a DLT, and dose was escalated to 60 Gy/3F without reaching MTD.
Biologically potent doses of SBRT are well tolerated in patients with limited liver metastases. Results of this study form the basis for an ongoing Phase II SBRT study of 60 Gy over three fractions for liver metastases.
确定立体定向体部放射治疗（SBRT）用于肝转移瘤的最大耐受剂量（MTD）。
开展了一项多中心I期临床试验。符合条件的患者有1至3个肝转移瘤，肿瘤直径<6 cm，且肝功能良好。第一组患者接受36 Gy的计划靶体积（PTV），分3次分割（F）。后续组接受更高剂量，最高可达选定的60 Gy/3F。至少700 mL正常肝脏接受的总剂量必须<15 Gy。剂量限制毒性（DLT）包括急性3级肝脏或肠道毒性或任何急性4级毒性。如果一组中2/6的患者出现DLT，则超过了MTD。
共纳入18例患者（10例男性，8例女性）：中位年龄55岁（范围26 - 83岁）；最常见的原发部位为结直肠癌（6例）；中位肿瘤总体积18 ml（范围3 - 98 ml）。4例患者有多个肿瘤。无患者出现DLT，剂量逐步递增至60 Gy/3F，未达到MTD。
肝转移瘤局限的患者对生物有效剂量的SBRT耐受性良好。本研究结果为正在进行的肝转移瘤60 Gy分3次分割的II期SBRT研究奠定了基础。
