Kang Joseph I, Sufficool Daniel C, Hsueh Chung-Tsen, Wroe Andrew J, Patyal Baldev, Reeves Mark E, Slater Jerry D, Yang Gary Y
Department of Radiation Oncology Loma Linda University Medical Center, Loma Linda, CA, USA.
Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA.
J Gastrointest Oncol. 2019 Feb;10(1):112-117. doi: 10.21037/jgo.2018.08.17.
A phase I trial to determine the maximum tolerated dose (MTD) of Proton stereotactic body radiation therapy (SBRT) for liver metastases in anticipation of a subsequent phase II study.
An institutional IRB approved phase I clinical trial was conducted. Eligible patients had 1-3 liver metastases measuring less than 5 cm, and no metastases location within 2 cm of the GI tract. Dose escalation was conducted with three dose cohorts. The low, intermediate, and high dose cohorts were planned to receive 36, 48, and 60 respectively to the internal target volume (ITV) in 3 fractions. At least 700 mL of normal liver had to receive <15. Dose-limiting toxicity (DLT) included acute grade 3 liver, intestinal or spinal cord toxicity or any grade 4 toxicity. The MTD is defined as the dose level below that which results in DLT in 2 or more of the 6 patients in the highest dose level cohort.
Nine patients were enrolled (6 male, 3 female): median age 64 years (range, 33-77 years); median gross tumor volume (GTV) 11.1 mL (range, 2.14-89.3 mL); most common primary site, colorectal (5 patients). Four patients had multiple tumors. No patient experienced a DLT and dose was escalated to 60 in 3 fractions without reaching MTD. The only toxicity within 90 days of completion of treatment was one patient with a grade 1 skin hyperpigmentation without tenderness or desquamation. Two patients in the low dose cohort had local recurrence and repeat SBRT was done to previously treated lesions without any toxicities.
Biologically ablative Proton SBRT doses are well tolerated in patients with limited liver metastases with no patients experiencing any grade 2+ acute toxicity. Results from this trial provide the grounds for an ongoing phase II Proton SBRT study of 60 over 3 fractions for liver metastases.
开展一项I期试验，以确定质子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），为后续的II期研究做准备。
进行了一项经机构审查委员会（IRB）批准的I期临床试验。符合条件的患者有1 - 3个直径小于5 cm的肝转移瘤，且转移瘤距胃肠道的距离在2 cm以内。采用三个剂量组进行剂量递增。低、中、高剂量组计划分别以3次分割给予内部靶区（ITV）36、48和60的剂量。至少700 mL的正常肝脏接受的剂量必须<15。剂量限制毒性（DLT）包括急性3级肝脏、肠道或脊髓毒性或任何4级毒性。MTD定义为在最高剂量组的6名患者中，导致2名或更多患者出现DLT的剂量水平以下的剂量。
9名患者入组（6名男性，3名女性）；中位年龄64岁（范围33 - 77岁）；中位肿瘤总体积（GTV）11.1 mL（范围2.14 - 89.3 mL）；最常见的原发部位为结直肠癌（5例患者）。4例患者有多个肿瘤。没有患者出现DLT，且在未达到MTD的情况下，剂量递增至3次分割给予60的剂量。治疗完成后90天内唯一的毒性反应是1例患者出现1级皮肤色素沉着，无压痛或脱屑。低剂量组的2例患者出现局部复发，对先前治疗的病灶进行了再次SBRT，未出现任何毒性反应。
对于肝转移瘤局限的患者，生物消融性质子SBRT剂量耐受性良好，没有患者出现任何2级以上的急性毒性反应。该试验结果为正在进行的II期质子SBRT治疗肝转移瘤的研究提供了依据，该研究采用3次分割给予60的剂量。
