BACKGROUND Stereotactic ablative radiotherapy (SABR) is an emerging therapy for primary renal cell carcinoma. The authors assessed safety, efficacy, and survival in a multi-institutional setting. Outcomes between single-fraction and multifraction SABR were compared. METHODS Individual patient data sets from 9 International Radiosurgery Oncology Consortium for Kidney institutions across Germany, Australia, the United States, Canada, and Japan were pooled. Toxicities were recorded using Common Terminology Criteria for Adverse Events, version 4.0. Patient, tumor, and treatment characteristics were stratified according to the number of radiotherapy fractions (single vs multiple). Survival outcomes were examined using Kaplan-Meier estimates and Cox proportional-hazards regression. RESULTS Of 223 patients, 118 received single-fraction SABR, and 105 received multifraction SABR. The mean patient age was 72 years, and 69.5% of patients were men. There were 83 patients with grade 1 and 2 toxicity (35.6%) and 3 with grade 3 and 4 toxicities (1.3%). The rates of local control, cancer-specific survival, and progression-free survival were 97.8%, 95.7%, and 77.4%, respectively, at 2 years; and they were 97.8%, 91.9%, and 65.4%, respectively, at 4 years. On multivariable analysis, tumors with a larger maximum dimension and the receipt of multifraction SABR were associated with poorer progression-free survival (hazard ratio, 1.16 [P < .01] and 1.13 [P = .02], respectively) and poorer cancer-specific survival (hazard ratio, 1.28 [P < .01] and 1.33 [P = .01], respectively). There were no differences in local failure between the single-fraction cohort (n = 1) and the multifraction cohort (n = 2; P = .60). The mean ( ± standard deviation) estimated glomerular filtration rate at baseline was 59.9 ± 21.9 mL per minute, and it decreased by 5.5 ± 13.3 mL per minute (P < .01). CONCLUSIONS SABR is well tolerated and locally effective for treating patients who have primary renal cell carcinoma and has an acceptable impact on renal function. An interesting observation is that patients who receive single-fraction SABR appear to be less likely to progress distantly or to die of cancer. Cancer 2018;124:934-42. © 2017 American Cancer Society.

Pooled analysis of stereotactic ablative radiotherapy for primary renal cell carcinoma: A report from the International Radiosurgery Oncology Consortium for Kidney (IROCK)

The Role of Stereotactic Ablative Body Radiotherapy in Renal Cell Carcinoma.

Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0-100), 5-year progression-free survival was 80·5% (95% CI 72-92), and 5-year overall survival was 77·2% (95% CI 65-89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25-26 Gy in one fraction, or 42-48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice. 

Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS).

Stereotactic body radiation therapy (SBRT) has become a new therapeutic option for primary renal cell carcinoma. However, treatment doses lack consistency in the literature. The primary objective of this study was to determine the maximum tolerated dose for renal cancer SBRT.This phase 1 multicentric dose-escalation study assessed 4 dose levels: 8 Gy × 4, 8 Gy × 5, 10 Gy × 4, and 12 Gy × 4. The primary objective of this study was to determine the maximal tolerated dose, defined by the occurrence of dose-limiting toxicity was defined as any acute side effect of grade ≥4 based on the Common Terminology Criteria for Averse Events, version 4.0.From October 2010 to September 2017, 13 patients were enrolled. The median follow-up was 23 months. There was no dose-limiting toxicity in our study, and the highest dose was reached successfully. No acute or late toxic effects above grade 2 were seen. There was no significant alteration of renal function after treatment. At 24 months, 2 patients had partial response and the others had stable disease.After 24 months of follow-up, no dose-limiting toxicity was seen at any of the prescribed dose levels in our study. The findings suggest that our last dose level of 48 Gy in 4 12-Gy fractions can be considered safe and can be used in further studies. 

Safety and efficacy of stereotactic ablative radiotherapy for renal cell cancer: 24-months results of the RSR1 phase I dose escalation study.

Stereotactic body radiotherapy (SBRT) allows high doses of radiation to be administered in a limited number of fractions. The high doses per session might allow the theoretical radioresistance of renal carcinoma to be overcome. SBRT may be a therapeutic alternative in inoperable patients with localized renal carcinoma. This review studied the available literature on the use of SBRT in inoperable localized renal carcinoma. The review including data from English-language studies was conducted in PubMed and MEDLINE between January 2010 and December 2020. Articles were included with data from patients with renal carcinoma treated with SBRT, their indications, simulation, dose and fractionation, local control, survival and side effects, comparison with other treatments, response assessment and radioimmunotherapy. The articles included were evaluated for content and validation. The immobilization systems were variable between studies. Doses and fractions were variable from 25-26 Gy in single fractions to 21-48 Gy in 3-5 fractions, with local control being around 90% with a low rate of side-effects. We review the state of the art in SBRT for renal cell carcinoma. More research is needed to determine optimal doses and fractionation, and to develop a reliable response assessment tool. The role of radioimmunotherapy in renal carcinoma is being studied.

/pdf/sbrt-in-localized-renal-carcinoma-a-review-of-the-literature-eyhe4ky3.pdf

SBRT in Localized Renal Carcinoma: A Review of the Literature

Robotic stereotactic ablative radiotherapy (SABR) is currently under investigation as a noninvasive treatment option for patients with renal cell carcinoma (RCC). For radiation therapy of RCC, tumor motion and the need for high ablative doses while preserving the remaining renal parenchyma is a challenge. We aimed to analyze the safety and efficacy of robotic radiosurgery in RCC in a specific difficult subgroup of patients with impaired renal function. We retrospectively identified all patients with RCC, treated with robotic SABR and motion compensation in our institution between 2012 and 2017. Either single fraction SABR of 24 or 25 Gy or 3 fractions of 12 Gy prescribed to the 70% isodose line was applied. Local control, overall survival, radiation side effects were evaluated together with renal function and tumor motion. We analyzed data of 13 lesions treated in 10 patients with clear cell RCC and a mean age of 70.5 ± 13.6 years (range: 48–87). Prior to SABR, 8 patients underwent previous complete and/or partial nephrectomy, 7 patients presented with chronic kidney disease ≥ stage 3. The median of minimum, mean and maximum planning target volume doses were 23.2, 29.5 and 35.0 Gy for single fraction and 24.4, 42.5 and 51.4 Gy for the three fractions regime. Persistent local control by robotic SABR was achieved in 9 out of 10 patients (92.3% of all lesions) within a median follow-up period of 27 month (range: 15–54). One patient underwent nephrectomy due to progressive disease and sufficient renal function of the contralateral kidney. Renal function remained stable with a mean estimated glomerular filtration rate (eGFR) of 51.3 ± 19.7 ml/min at baseline and 51.6 ± 25.8 ml/min at follow-up. The largest respiratory-induced tumor motion was seen in superior-inferior direction, compensated by the CyberKnife with mean targeting errors of maximal 2.2 mm. Robotic SABR is technically feasible for the treatment of RCC in preexisting kidney disease with good local tumor control at about 2 years follow-up. Robotic SABR with motion tracking offers a valid treatment option for patients, who are at increased risk for progression to end-stage renal disease due to partial nephrectomy or ablative techniques.

/pdf/robotic-stereotactic-ablative-radiotherapy-for-renal-cell-1jpkcm47lm.pdf

Robotic stereotactic ablative radiotherapy for renal cell carcinoma in patients with impaired renal function.

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Robotic stereotactic ablative radiotherapy for renal cell carcinoma in patients with impaired renal function.