Stereotactic body radiation therapy in combination with systemic therapy for metastatic renal cell carcinoma: a prospective multicentre study

Abstract

BackgroundTyrosine kinase inhibitors (TKIs) and checkpoint inhibitors have been established as effective treatment for metastatic renal cell carcinoma (mRCC), but only a minority of patients achieve complete response. Additional strategies are necessary to improve these agents’ efficacy.MethodsPatients with stable disease for at least 4 months on TKI or checkpoint inhibitors were included. Stereotactic body radiotherapy (SBRT) was delivered to an organ with comparable lesions, where one lesion was in the treatment target and the other one was intentionally left untreated (control lesion). Response in both lesions was scored using the Response Evaluation Criteria in Solid Tumors V.1.1 criteria 2 months after completion of SBRT. The primary endpoint was the rate of SBRT adverse events, and the secondary endpoints included the rate of reduction in target lesion size.Results17 patients were enrolled (14 men and 3 women, median age: 54.5 years old). SBRT was delivered to the lungs (n=5), bones (n=4), lymph nodes (n=4), liver (n=1), primary renal cell carcinoma (RCC) (n=1) and locally recurrent RCC (n=2). The equivalent dose in 2 Gy with an alpha to beta ratio of 2.6 was 114 Gy. With a median follow-up of 8 months, the cumulative rate of SBRT-related toxicity (grade 1) was 12% (n=2), consisting of oesophagitis and skin erythema. No grade 2 or higher toxicity was detected. Radiographic response in the target lesion was seen in 13 patients (76%), with complete response in 5 (29%) patients and partial response in 8 (47%), including abscopal effect in 1 patient. Control lesions remained stable in 16 patients. The difference between response in the target and control lesions as judged by the mean sizes of these lesions before and at 2 months after SBRT was statistically significant (p<0.01). Fraction size of 10 Gy or greater was associated with complete response (p<0.01).ConclusionExtracranial SBRT in patients with mRCC treated with TKI or checkpoint inhibitors is well tolerated and could be effective.Trial registration number NCT02864615

Oligometastasis and local ablation in the era of systemic targeted and immunotherapy

“…In a recent phase I/II study including 13 patients treated with Pazopanib and SBRT local control and response rates outside the radiation field were good but seemed not to be superior when compared to SBRT or Pazopanib in monotherapy [52]. Contrarily, Dengina et al [53] observed in a small phase 1b Volga Study (VEGFR inhibitor or mTOR inhibitor or checkpoint inhibitors and SRT) that the difference in response in the target and control metastases evaluated by a mean size of the lesions before and at 2 months after SBRT was statistically significant (p < 0.01). Miller et al [54] demonstrated in the multivariate competing risks regression that concurrent first-line TKI treatment was independently associated with a local control benefit (HR 0.21, p = 0.04), while patients treated with TKIs alone experienced an increased rate of local failure (HR 2.43, p = 0.03).…”

Radiation induces dynamic changes to the T cell repertoire in renal cell carcinoma patients

“…These findings have sparked further interest in the use of available tumor-modulating agents, including radiation, to sensitize patients to immunotherapy. With mounting questions surrounding the synergy between immune therapies and SBRT (6,17), there is an urgent need to understand how radiation impacts the tumor immune landscape in patients.…”

“…Several studies have demonstrated the ability of high-dose radiation delivered with SBRT to control RCC growth ( 12 – 16 ). In addition, clinical trials that combined SBRT with IL-2, immune checkpoint blockade (ICB), or tyrosine kinase inhibition have shown promise in treating RCC ( 6 , 7 , 17 ).…”

Possible abscopal effect after discontinuation of nivolumab in metastatic renal cell carcinoma

“…In another prospective study, patients were treated with SRT in combination with tyrosine kinase inhibitor or ICI. Thirteen of 17 patients (76%) achieved partial response (47%) or complete response (29%) 10 . These results suggest that radiotherapy could enhance the efficacy of systemic therapy.…”