Department of Radiation Oncology, University of Texas Southwestern, Dallas, TX, USA; Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Radiation Oncology, University of Texas Southwestern, Dallas, TX, USA.
Eur Urol. 2023 Sep;84(3):275-286. doi: 10.1016/j.eururo.2023.02.016. Epub 2023 Mar 8.
Most renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited.
To investigate whether SAbR is effective in the management of primary RCCs.
DESIGN, SETTING, AND PARTICIPANTS: Patients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions.
The primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 mm/yr on active surveillance) and pathologic evidence of tumor response at 1 yr. Secondary endpoints included LC by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), safety, and preservation of kidney function. Exploratory tumor cell-enriched spatial protein and gene expression analysis were conducted on pre- and post-treatment biopsy samples.
Target accrual was reached with the enrollment of 16 ethnically diverse patients. Radiographic LC at 1 yr was observed in 94% of patients (15/16; 95% confidence interval: 70, 100), and this was accompanied by pathologic evidence of tumor response (hyalinization, necrosis, and reduced tumor cellularity) in all patients. By RECIST, 100% of the sites remained without progression at 1 yr. The median pretreatment growth rate was 0.8 cm/yr (interquartile range [IQR]: 0.3, 1.4), and the median post-treatment growth rate was 0.0 cm/yr (IQR: -0.4, 0.1, p < 0.002). Tumor cell viability decreased from 4.6% to 0.7% at 1 yr (p = 0.004). With a median follow-up of 36 mo for censored patients, the disease control rate was 94%. SAbR was well tolerated with no grade ≥2 (acute or late) toxicities. The average glomerular filtration rate declined from a baseline of 65.6 to 55.4 ml/min at 1 yr (p = 0.003). Spatial protein and gene expression analyses were consistent with the induction of cellular senescence by radiation.
This clinical trial adds to the growing body of evidence suggesting that SAbR is effective for primary RCC supporting its evaluation in comparative phase 3 clinical trials.
In this clinical trial, we investigated a noninvasive treatment option of stereotactic radiation therapy for the treatment of primary kidney cancer and found that it was safe and effective.
大多数肾细胞癌（RCC）是局限性的，可通过主动监测、手术或微创技术进行治疗。立体定向消融放疗（SAbR）可能提供一种创新的非侵入性替代方法，尽管前瞻性数据有限。
研究 SAbR 在治疗原发性 RCC 中的有效性。
设计、地点和参与者：入组经活检证实影像学上肿瘤增大的原发性 RCC（≤5cm）患者。SAbR 分 3 次（12Gy）或 5 次（8Gy）给予。
主要终点是局部控制（LC），定义为肿瘤生长速度降低（与主动监测的 4mm/yr 基准相比）和 1 年时肿瘤反应的病理证据。次要终点包括实体瘤反应评价标准（RECIST 1.1）的 LC、安全性和肾功能的保留。在治疗前后的活检样本上进行了肿瘤细胞富集的空间蛋白和基因表达分析。
通过招募 16 名不同种族的患者，达到了目标入组人数。16 名患者中有 94%（15/16；95%置信区间：70，100）在 1 年内实现了影像学 LC，所有患者均伴有肿瘤反应的病理证据（玻璃样变、坏死和肿瘤细胞减少）。根据 RECIST，100%的病灶在 1 年内无进展。中位预处理生长率为 0.8cm/yr（四分位距[IQR]：0.3，1.4），中位治疗后生长率为 0.0cm/yr（IQR：-0.4，0.1，p<0.002）。肿瘤细胞活力从 1 年时的 4.6%下降到 0.7%（p=0.004）。对接受censored 的患者进行中位 36 个月的随访，疾病控制率为 94%。SAbR 耐受性良好，无≥2 级（急性或迟发性）毒性。肾小球滤过率从基线的 65.6ml/min 下降到 1 年时的 55.4ml/min（p=0.003）。空间蛋白和基因表达分析与辐射诱导的细胞衰老一致。
这项临床试验增加了越来越多的证据表明，SAbR 对原发性 RCC 有效，支持其在比较性 3 期临床试验中的评估。
在这项临床试验中，我们研究了一种非侵入性的立体定向放射治疗方法治疗原发性肾癌，发现该方法安全有效。
