Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases

Abstract

Purpose Renal cell carcinoma is refractory to conventional radiation therapy but responds to higher doses per fraction. However, the dosimetric data and clinical factors affecting local control (LC) are largely unknown. We aimed to evaluate the safety and efficacy of stereotactic ablative radiation therapy (SAbR) for extracranial renal cell carcinoma metastases. Methods and Materials We reviewed 175 metastatic lesions from 84 patients treated with SAbR between 2005 and 2015. LC and toxicity after SAbR were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Predictors of local failure were analyzed with χ2, Kaplan-Meier, and log-rank tests. Results In most cases (74%), SAbR was delivered with total doses of 40 to 60 Gy, 30 to 54 Gy, and 20 to 40 Gy in 5 fractions, 3 fractions, and a single fraction, respectively. The median biologically effective dose (BED) using the universal survival model was 134.5 Gy. The 1-year LC rate after SAbR was 91.2% (95% confidence interval, 84.9%–95.0%; median follow-up, 16.7 months). Local failures were associated with prior radiation therapy (hazard ratio [HR], 10.49; P<.0001), palliative-intent radiation therapy (HR, 4.63; P=.0189), spinal location (HR, 5.36; P=.0041), previous systemic therapy status (0–1 vs >1; HR, 3.52; P=.0217), and BED <115 Gy (HR, 3.45; P=.0254). Dose received by 99% of the target volume was the strongest dosimetric predictor for LC. Upon multivariate analysis, dose received by 99% of the target volume greater than BED of 98.7 Gy and systemic therapy status remained significant (HR, 0.12 and 3.64, with P=.0014 and P=.0472, respectively). Acute and late grade 3 toxicities attributed to SAbR were observed in 3 patients (1.7%) and 5 patients (2.9%), respectively. Conclusions SAbR demonstrated excellent LC of metastatic renal cell carcinoma with a favorable safety profile when an adequate dose and coverage were applied. Multimodality treatment with surgery should be considered for reirradiation or vertebral metastasis. A higher radiation dose may be required in patients who received previous systemic therapies.

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma—a multicenter analysis of the German working group “Stereotactic Radiotherapy”

“…In the clinical setting, dose escalation has also been shown to overcome radioresistance in RCC tumors: Zelefsky and colleagues reported 3-year LC of 88% following SBRT with high fractional doses for extracranial RCC metastases, while LC dropped to only about 20% when lower doses were used (30). A few other reports have also revealed LC rates of about 80-90% for extracranial SBRT in RCC patients (5,6,28,29,31,33). However, due to the limited number of RCC patients treated with SBRT, these reports combined data form different metastatic sites of including lung, bone, liver, lymph nodes or even primary RCC tumors (5,6,28,29,31,33).…”

“…However, some RCC patients are medically inoperable due to reduced performance status or comorbidities and some pulmonary metastases are technically not accessible or resectable. For these patients, stereotactic body radiotherapy (SBRT) which utilizes highly conformal ablative local doses to the tumor while sparing surrounding organs, has shown encouraging results (5,(28)(29)(30). However, available reports concerning SBRT for RCC metastases have pooled heterogeneous data from various tumor locations (lung, bone, lymph node, brain, liver, etc.)…”

“…However, available reports concerning SBRT for RCC metastases have pooled heterogeneous data from various tumor locations (lung, bone, lymph node, brain, liver, etc.) with different sensitivities to high-dose radiation (5,6,(28)(29)(30)(31)(32)(33). This multi-institutional study reports the feasibility, safety, and efficacy of SBRT for pulmonary RCC metastases.…”

Non-Surgical Ablative Treatment of Distant Extracranial Metastases for Renal Cell Carcinoma: A Systematic Review

“…Non-comparative retrospective series on SBRT for RCC-bone metastases report local control rates of 70-90% at one or two years, using different fractionation regimens [40][41][42][43][44][45]. Other series including non-bone metastases find similar LCRs [34,35,[46][47][48][49][50]. In a recent systematic review of mainly non-comparative series, the weighted LCR for extracranial RCC-metastases was 89% [22].…”

“…After two years their LCR was 100%, but 64% had progressed at other sites [34]. Another large study reported significantly better local control in patients treated with curative versus palliative intent, but the numerical difference was not large (95% versus 88%) and overall survival data were not provided [35]. There are no comparative studies on SBRT versus metastasectomy, the latter being considered standard therapy though without a proven survival advantage [6].…”