Department of Radiation Oncology, Fondazione di Ricerca e Cura Giovanni Paolo II, Università Cattolica del S. Cuore, and Department of Oncology, A. Cardarelli Hospital, Campobasso, Italy.
Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e463-8. doi: 10.1016/j.ijrobp.2012.06.023. Epub 2012 Aug 18.
To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases.
A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded.
Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%).
Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.
确定短疗程加速全脑放射治疗（SHARON）治疗多发脑转移患者的最大耐受剂量（MTD）。
设计了 4 个剂量递增阶段的 1 期试验：12 Gy（3 Gy/次）、14 Gy（3.5 Gy/次）、16 Gy（4 Gy/次）和 18 Gy（4.5 Gy/次）。入选标准包括递归分区分析（RPA）分级>或=2，至少有 3 个脑转移灶或 3 个以上器官系统有转移病灶，东部肿瘤协作组（ECOG）表现状态≤3。治疗采用每日 2 次分割，2 天内完成。每 6-12 例患者为 1 组，以确定 MTD。根据放射治疗肿瘤学组的标准，剂量限制性毒性（DLT）定义为任何急性毒性≥3 级。记录主要神经症状和生活质量的状态信息。
49 例入组患者的特征如下：男/女，30/19；中位年龄 66 岁（范围，23-83 岁）。ECOG 表现状态<3 的患者有 46 例（94%）。14 例（29%）患者被认为处于递归分区分析（RPA）3 级。记录到 1 级-2 级急性神经（26.4%）和皮肤（18.3%）毒性。仅有 1 例患者出现 DLT（神经学 3 级急性毒性）。中位随访时间为 5 个月（范围，1-23 个月），未观察到迟发性毒性。治疗后 3 周，21 例有症状患者中有 16 例症状改善或缓解（总症状缓解率为 76.2%；置信区间 0.95：60.3-95.9%）。
每日 2 次分割，连续 2 天共 18 Gy 的短疗程加速放疗可耐受。已计划开展 2 期研究，以评估总生存期、症状控制和生活质量指标的疗效。
