To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in metastatic RCC (mRCC) patients concurrently receiving targeted therapy or immunotherapy.
Data on mRCC patients was extracted from a retrospective international multicenter register study (TOaSTT) investigating SRT concurrent (≤30d) to TT/ICI. Overall survival (OS), progression free survival (PFS), local control (LC) and time to systemic therapy switch (TTS) were analyzed using Kaplan-Meier curves and log rank testing. Clinical and treatment factors influencing survival were analyzed using multivariate cox regression. Acute and late SRT-induced toxicity was defined by the CTCAE v4.03 criteria.
Fifty-three patients that underwent 128 SRTs were included, of which 58% of patients presented with oligometastatic disease (OMD). 32% and 68% of patients received ICI and TT, respectively. Twenty (37%) patients paused TT for median of 14 (range 2-21) days, ICI was not paused in any patient. A median of 1 (range 1-5) metastasis was treated per patient, with a median SRT dose of 65Gy BED10 (range 40-129.4Gy). OS, LC and PFS at 1y were 71%, 75% and 25%, respectively. Median OS and PFS was not significantly different among patients receiving TT vs. ICI (p=0.329). New lesions were treated with a repeat-radiotherapy course in 46% of patients. After 1y, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI compared to TT (83% vs. 36%, p=0.035). OMD was an independent factor for OS (p=0.004, 95% CI 0.035-0.528) and PFS (p=0.004, 95% CI 0.165-0.717) in multivariate analysis. ECOG-PS was the other independent factor for OS (p=0.001, 95% CI 0.001-0.351). Acute grade 3 toxicity was observed in 2 patients, late grade 3 toxicity in 1 patient. No grade 4 or 5 toxicity was observed.
Combined modality treatment with targeted therapy or immunotherapy and concurrent SRT was safe without signals of increased severe toxicity. As we observed no signal of excess toxicity, full-dose SRT should be considered to achieve optimal metastasis control in patients receiving targeted-, or immunotherapy. Favorable PFS and OS was observed for oligometastatic RCC patients with a good ECOG-PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.
BJU international. 2020 Oct 28 [Epub ahead of print]
S G C Kroeze, C Fritz, J Schaule, S Siva, K H Kahl, N Sundahl, O Blanck, D Kaul, S Adebahr, J J C Verhoeff, G Skazikis, F Roeder, M Geier, F Eckert, M Guckenberger
Department of Radiation Oncology, University Hospital Zürich, University of Zurich, Zurich, Switzerland., Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Department of Radiation Oncology, University Hospital Augsburg, Augsburg, Germany., Department of Radiation Oncology, University Hospital Ghent, Ghent, Belgium., Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany., Department or Radiation Oncology, Charité-University Hospital Berlin, Berlin, Germany., Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK), Partner Site, Freiburg, Germany., Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands., Department of Radiation Oncology, Schwarzwald-Baar Klinikum, Villingen-Schwenningen, Germany., Department of Radiation Oncology, University Hospital Munich, Munich, Germany., Department of Radiation Oncology, Ordensklinikum Linz, Linz, Austria., Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.