Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lancet Oncol. 2021 Dec;22(12):1732-1739. doi: 10.1016/S1470-2045(21)00528-3. Epub 2021 Oct 28.
The role of radiotherapy in metastatic renal cell carcinoma is controversial. We prospectively tested the feasibility and efficacy of radiotherapy to defer systemic therapy for patients with oligometastatic renal cell carcinoma.
This single-arm, phase 2, feasibility trial was done at one centre in the USA (The MD Anderson Cancer Center, Houston, TX, USA). Patients (aged ≥18 years) with five or fewer metastatic lesions, an Eastern Cooperative Oncology Group status of 0-2, and no more than one previous systemic therapy (if this therapy was stopped at least 1 month before enrolment) without limitations on renal cell carcinoma histology were eligible for inclusion. Patients were treated with stereotactic body radiotherapy (defined as ≤5 fractions with ≥7 Gy per fraction) to all lesions and maintained off systemic therapy. When lesion location precluded safe stereotactic body radiotherapy, patients were treated with hypofractionated intensity-modulated radiotherapy regimes consisting of 60-70 Gy in ten fractions or 52·5-67·5 Gy in 15 fractions. Additional rounds of radiotherapy were allowed to treat subsequent sites of progression. Co-primary endpoints were feasibility (defined as all planned radiotherapy completed with <7 days unplanned breaks) and progression-free survival. All efficacy analyses were intention-to-treat. Safety was analysed in the as-treated population. A second cohort, with the aim of assessing the feasibility of sequential stereotactic body radiotherapy alone in patients with low-volume metastatic disease, was initiated and will be reported separately. This study is registered with ClinicalTrials.gov, NCT03575611.
30 patients (six [20%] women) were enrolled from July 13, 2018, to Sept 18, 2020. All patients had clear cell histology and had a nephrectomy before enrolment. All patients completed at least one round of radiotherapy with less than 7 days of unplanned breaks. At a median follow-up of 17·5 months (IQR 13·2-24·6), median progression-free survival was 22·7 months (95% CI 10·4-not reached; 1-year progression-free survival 64% [95% CI 48-85]). Three (10%) patients had severe adverse events: two grade 3 (back pain and muscle weakness) and one grade 4 (hyperglycaemia) adverse events were observed. There were no treatment-related deaths.
Sequential radiotherapy might facilitate deferral of systemic therapy initiation and could allow sustained systemic therapy breaks for select patients with oligometastatic renal cell carcinoma.
Anna Fuller Foundation, the Cancer Prevention and Research Institute of Texas (CPRIT), and the National Cancer Institute.
放疗在转移性肾细胞癌中的作用存在争议。我们前瞻性地测试了放疗对寡转移性肾细胞癌患者延迟全身治疗的可行性和疗效。
这是一项在美国一家中心（美国德克萨斯州休斯顿的 MD 安德森癌症中心）进行的单臂、2 期可行性试验。符合条件的患者（年龄≥18 岁）具有五个或更少的转移性病变，东部合作肿瘤学组（ECOG）状态为 0-2，且无超过一次的全身治疗（如果该治疗在入组前至少停止 1 个月），且无肾细胞癌组织学限制。所有病变均采用立体定向体部放疗（定义为≤5 次分割，每次分割≥7 Gy）进行治疗，并维持全身治疗停药。当病变部位不适合安全的立体定向体部放疗时，患者采用分割强度调制放疗方案治疗，包括 60-70 Gy 共 10 次分割或 52.5-67.5 Gy 共 15 次分割。允许额外的放疗回合治疗后续进展部位。主要终点是可行性（定义为所有计划的放疗均完成，无计划中断超过 7 天）和无进展生存期。所有疗效分析均为意向治疗。安全性在治疗人群中进行分析。为评估低肿瘤负荷转移性疾病患者单独序贯立体定向体部放疗的可行性，启动了第二个队列，将单独报告。本研究在 ClinicalTrials.gov 注册，编号为 NCT03575611。
从 2018 年 7 月 13 日至 2020 年 9 月 18 日，共有 30 名患者（6 名[20%]女性）入组。所有患者均为透明细胞癌，且在入组前接受了肾切除术。所有患者均至少完成一轮放疗，且无计划中断超过 7 天。中位随访 17.5 个月（IQR 13.2-24.6）时，中位无进展生存期为 22.7 个月（95%CI 10.4-未达到；1 年无进展生存率为 64%[95%CI 48-85]）。有 3 名（10%）患者发生严重不良事件：2 级（背痛和肌肉无力）和 1 级（高血糖）各 1 例不良事件。无治疗相关死亡。
序贯放疗可能有助于延迟全身治疗的开始，并可能为选择的寡转移性肾细胞癌患者提供持续的全身治疗暂停。
安娜·富勒基金会、德克萨斯州癌症预防与研究所（CPRIT）和美国国家癌症研究所。
