Department of Radiation Oncology, Klinikum rechts der Isar Hospital, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany.
Department of Radiation Sciences, Institute of Innovative Radiotherapy, 85764, Neuherberg, Germany.
Cancer Commun (Lond). 2019 Nov 9;39(1):73. doi: 10.1186/s40880-019-0416-2.
More than 25% of patients with solid cancers develop intracerebral metastases. Aside of surgery, radiation therapy (RT) is a mainstay in the treatment of intracerebral metastases. Postoperative fractionated stereotactic RT (FSRT) to the resection cavity of intracerebral metastases is a treatment of choice to reduce the risk of local recurrence. However, FSRT has to be delayed until a sufficient wound healing is attained; hence systemic therapy might be postponed. Neoadjuvant stereotactic radiosurgery (SRS) might offer advantages over adjuvant FSRT in terms of better target delineation and an earlier start of systemic chemotherapy. Here, we conducted a study to find the maximum tolerated dose (MTD) of neoadjuvant SRS for intracerebral metastases.
This is a single-center, phase I dose escalation study on neoadjuvant SRS for intracerebral metastases that will be conducted at the Klinikum rechts der Isar Hospital, Technical University of Munich. The rule-based traditional 3 + 3 design for this trial with 3 dose levels and 4 different cohorts depending on lesion size will be applied. The primary endpoint is the MTD for which no dose-limiting toxicities (DLT) occur. The adverse events of each participant will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 continuously during the study until the first follow-up visit (4-6 weeks after surgery). Secondary endpoints include local control rate, survival, immunological tumor characteristics, quality of life (QoL), CTCAE grade of late clinical, neurological, and neurocognitive toxicities. In addition to the intracerebral metastasis which is treated with neoadjuvant SRS and resection up to four additional intracerebral metastases can be treated with definitive SRS. Depending on the occurrence of DLT up to 72 patients will be enrolled. The recruitment phase will last for 24 months.
Neoadjuvant SRS for intracerebral metastases offers potential advantages over postoperative SRS to the resection cavity, such as better target volume definition with subsequent higher efficiency of eliminating tumor cells, and lower damage to surrounding healthy tissue, and much-needed systemic chemotherapy could be initiated more rapidly. Trial registration The local ethical review committee of Technical University of Munich (199/18S) approved this study on September 05, 2018. This trial was registered on German Clinical Trials Register (DRKS00016613; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016613) on January 29, 2019.
超过 25%的实体瘤患者会发生颅内转移。除了手术，放射治疗（RT）也是治疗颅内转移的主要手段。对颅内转移灶切除后的分割立体定向放疗（FSRT）是降低局部复发风险的首选治疗方法。然而，FSRT 必须等到伤口愈合到足够的程度才能进行，因此可能会延迟全身治疗。与辅助 FSRT 相比，新辅助立体定向放疗（SRS）在靶区勾画和更早开始全身化疗方面可能具有优势。在这里，我们进行了一项研究，以确定新辅助 SRS 治疗颅内转移的最大耐受剂量（MTD）。
这是一项在慕尼黑工业大学附属医院开展的单中心、Ⅰ期新辅助 SRS 治疗颅内转移的剂量递增研究。该试验将采用基于规则的传统 3+3 设计，共设 3 个剂量水平和 4 个不同的队列，取决于病变大小。主要终点是无剂量限制性毒性（DLT）的 MTD。根据不良事件通用术语标准（CTCAE）版本 5.0，在研究期间对每个参与者的不良事件进行连续评估，直到第一次随访（术后 4-6 周）。次要终点包括局部控制率、生存率、免疫肿瘤特征、生活质量（QoL）、CTCAE 分级的迟发性临床、神经和神经认知毒性。除了用新辅助 SRS 治疗的颅内转移灶外，还可以用根治性 SRS 治疗多达 4 个额外的颅内转移灶。根据 DLT 的发生情况，将入组 72 名患者。招募阶段将持续 24 个月。
与术后 SRS 相比，新辅助 SRS 治疗颅内转移具有潜在优势，如更好的靶区定义，随后肿瘤细胞清除效率更高，对周围健康组织的损伤更小，并且急需的全身化疗可以更快地开始。
慕尼黑工业大学地方伦理审查委员会（199/18S）于 2018 年 9 月 5 日批准了这项研究。该试验于 2019 年 1 月 29 日在德国临床试验注册处（DRKS00016613；https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016613）注册。
