Abstract：
BACKGROUND: Single session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2cm) to determine the safety of preoperative SRS at escalating doses.
METHODS: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity.
RESULTS: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%.
CONCLUSIONS: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.
METHODS: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity.
RESULTS: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%.
CONCLUSIONS: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.
摘要：
背景：对于大于2cm的脑转移瘤，单次立体定向放射外科（SRS）或单独手术切除导致局部控制不令人满意。我们进行了一项脑转移（>2cm）的I期试验，以确定术前SRS在递增剂量下的安全性。
方法：根据最大肿瘤尺寸从18Gy开始，>2-3cm，以3Gy增量递增放射手术剂量。15Gy对于>3-4厘米，和12Gy>4-6厘米。剂量限制性毒性(DLT)定义为III级或更大的急性毒性。
结果：共纳入35例患者/36个病灶。对于肿瘤大小>2-3厘米，患者被纳入第二剂量水平（21Gy）；对于>3-4cm和>4-6cm的队列，第三剂量水平（21Gy和18Gy，分别)达成。在21Gy处>3-4cm臂中存在2个DLT。未达到>2-3cm的SRS的最大耐受剂量（MTD）；对于>3-4cm的手臂和>4-6cm的手臂均为18Gy。中位随访时间为64.0个月，6个月和12个月的局部控制率分别为85.9%和76.6%，分别。一名患者在5个月时出现3级放射性坏死。软脑膜疾病（LMD）的2年发生率为0％。
结论：对于大小大于2厘米的脑转移瘤，术前增加SRS剂量，然后进行手术切除，显示出可接受的急性毒性。试验的II期部分将在最大耐受SRS剂量下进行。
方法：根据最大肿瘤尺寸从18Gy开始，>2-3cm，以3Gy增量递增放射手术剂量。15Gy对于>3-4厘米，和12Gy>4-6厘米。剂量限制性毒性(DLT)定义为III级或更大的急性毒性。
结果：共纳入35例患者/36个病灶。对于肿瘤大小>2-3厘米，患者被纳入第二剂量水平（21Gy）；对于>3-4cm和>4-6cm的队列，第三剂量水平（21Gy和18Gy，分别)达成。在21Gy处>3-4cm臂中存在2个DLT。未达到>2-3cm的SRS的最大耐受剂量（MTD）；对于>3-4cm的手臂和>4-6cm的手臂均为18Gy。中位随访时间为64.0个月，6个月和12个月的局部控制率分别为85.9%和76.6%，分别。一名患者在5个月时出现3级放射性坏死。软脑膜疾病（LMD）的2年发生率为0％。
结论：对于大小大于2厘米的脑转移瘤，术前增加SRS剂量，然后进行手术切除，显示出可接受的急性毒性。试验的II期部分将在最大耐受SRS剂量下进行。
