Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Oncologist. 2020 Aug;25(8):e1195-e1201. doi: 10.1634/theoncologist.2019-0693. Epub 2020 Jun 16.
Local treatment of metastases is frequently performed in patients with multiorgan metastatic colorectal carcinoma (mCRC) analogous to selected patients with oligometastatic disease for whom this is standard of care. The ORCHESTRA trial (NCT01792934) was designed to prospectively evaluate overall survival benefit from tumor debulking in addition to chemotherapy in patients with multiorgan mCRC. Here, we report the preplanned safety and feasibility evaluation after inclusion of the first 100 patients.
Patients were eligible if at least 80% tumor debulking was deemed feasible by resection, radiotherapy and/or thermal ablative therapy. In case of clinical benefit after three or four cycles of respectively 5-fluorouracil/leucovorin or capecitabine and oxaliplatin ± bevacizumab patients were randomized to tumor debulking followed by chemotherapy in the intervention arm, or standard treatment with chemotherapy.
Twelve patients dropped out prior to randomization for various reasons. Eighty-eight patients were randomized to the standard (n = 43) or intervention arm (n = 45). No patients withdrew after randomization. Debulking was performed in 82% (n = 37). Two patients had no lesions left to treat, five had progressive disease, and one patient died prior to local treatment. In 15 patients (40%) 21 serious adverse events related to debulking were reported. Postoperative mortality was 2.7% (n = 1). After debulking chemotherapy was resumed in 89% of patients.
Tumor debulking is feasible and does not prohibit administration of palliative chemotherapy in the majority of patients with multiorgan mCRC, despite the occurrence of serious adverse events related to local treatment.
This first prospective randomized trial on tumor debulking in addition to chemotherapy shows that local treatment of metastases is feasible in patients with multiorgan metastatic colorectal cancer and does not prohibit administration of palliative systemic therapy, despite the occurrence of serious adverse events related to local treatment. The trial continues accrual, and overall survival (OS) data and quality of life assessment are collected to determine whether the primary aim of >6 months OS benefit with preserved quality of life will be met. This will support evidence-based decision making in multidisciplinary colorectal cancer care and can be readily implemented in daily practice.
局部治疗转移性疾病经常用于患有多器官转移性结直肠癌（mCRC）的患者，类似于寡转移疾病的选定患者，后者是标准治疗方法。ORCHESTRA 试验（NCT01792934）旨在前瞻性评估在多器官 mCRC 患者中，除化疗外，肿瘤减瘤术是否具有总体生存获益。在此，我们报告了纳入前 100 例患者后的预先计划的安全性和可行性评估。
如果通过手术、放疗和/或热消融治疗认为至少 80%的肿瘤可以减瘤，则患者符合条件。如果在前三个或四个周期的 5-氟尿嘧啶/亚叶酸或卡培他滨和奥沙利铂±贝伐珠单抗后有临床获益，患者将被随机分配至干预组的肿瘤减瘤术加化疗，或标准治疗加化疗。
由于各种原因，有 12 名患者在随机分组前退出。88 名患者被随机分配至标准治疗组（n=43）或干预组（n=45）。随机分组后无患者退出。82%（n=37）的患者进行了减瘤术。2 名患者没有可治疗的病变，5 名患者发生疾病进展，1 名患者在局部治疗前死亡。15 名患者（40%）报告了 21 例与减瘤术相关的严重不良事件。术后死亡率为 2.7%（n=1）。减瘤术后，89%的患者恢复了化疗。
尽管与局部治疗相关的严重不良事件发生，但多器官 mCRC 患者的大多数患者可行肿瘤减瘤术，并且不会阻碍姑息性化疗的应用。
这项关于化疗加局部治疗转移性疾病的首个前瞻性随机试验表明，多器官转移性结直肠癌患者的局部治疗是可行的，并且不会阻碍姑息性全身治疗的应用，尽管与局部治疗相关的严重不良事件发生。该试验正在继续入组，正在收集总生存（OS）数据和生活质量评估，以确定是否会达到 OS 获益超过 6 个月且生活质量得以保留的主要目标。这将支持多学科结直肠癌治疗的循证决策，并可在日常实践中得到快速实施。
