Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial
Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial
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DOI：
10.1186/s12885-019-5977-6
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发表时间：
2019-08-19
期刊：
影响因子：
3.8
通讯作者：
Senan, Suresh
中科院分区：
文献类型：
--
作者：
Palma, David A.;Olson, Robert;Senan, Suresh
背景立体定向消融放射治疗（SABR）已成为一种新的治疗选择，对患者的寡转移性疾病。SABR提供精确、高剂量、低分割放射治疗，并实现了原发性肿瘤或转移瘤的良好局部控制率。最近的一项随机II期试验评估了SABR在一组患有少量转移性疾病（大多数有1-3个转移性病灶）的患者中的作用，发现SABR与无进展生存期和总生存期的获益相关。这项III期试验的目的是评估SABR对4-10个转移性癌症病灶患者的影响。方法将159例患者以1：2的比例随机分配至对照组（由标准护理姑息治疗组成）和SABR组（由标准护理治疗+ SABR组成，用于已知疾病的所有部位）。将根据两个因素对随机化进行分层：组织学（第1组：前列腺、乳腺或肾脏;第2组：所有其他）和预先指定的全身治疗类型（第1组：免疫治疗/靶向;第2组：细胞毒性;第3组：观察）。SABR将在2周内完成，以便快速启动全身治疗。推荐的SABR剂量为20戈伊/1次、30戈伊/3次或35戈伊/5次，选择这些剂量以最大限度地降低毒性风险。主要终点是总生存期，次要终点包括无进展生存期、新转移病灶发生时间、生活质量和毒性。转化终点包括评估循环肿瘤细胞、无细胞DNA和肿瘤组织作为预后和预测标志物，包括评估缓解和长期生存的免疫学预测因子。讨论本研究将评估SABR对临床结局和生活质量的影响，以确定选定的4-10个寡转移性病变患者是否可以实现长期生存。
Background Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4-10 metastatic cancer lesions. Methods One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. Discussion This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4-10 oligometastatic lesions.