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

Natalia Dengina, Timur Mitin, Sergey Gamayunov, Sufia Safina, Yuliya Kreinina, Ilya Tsimafeyeu, Natalia Dengina, Timur Mitin, Sergey Gamayunov, Sufia Safina, Yuliya Kreinina, Ilya Tsimafeyeu

Abstract

Background: Tyrosine 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.

Methods: Patients 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.

Results: 17 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).

Conclusion: Extracranial SBRT in patients with mRCC treated with TKI or checkpoint inhibitors is well tolerated and could be effective.

Trial registration number: NCT02864615.

Keywords: immunotherapy; metastatic renal cell carcinoma; stereotactic body radiotherapy; targeted therapy.

Conflict of interest statement

Competing interests: None declared.

© Author (s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.

Figures

Figure 1
Figure 1
Response rate in target (A) and control (B) lesions after stereotactic body radiotherapy.
Figure 2
Figure 2
Subject B, before stereotactic body radiotherapy. Metastatic lesion on the right lower lobe.
Figure 3
Figure 3
Subject B, 2.5 months after stereotactic body radiotherapy (50 Gy in 5 fractions). Localised fibrotic changes in the lung tissue. Lesion was not visualised.

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