Ultra-hypofractionated stereotactic ablative body radiotherapy for primary renal cell carcinoma: 5-year outcomes from a pooled analysis of the FASTRACK trials - 17/05/26

Doi : 10.1016/S1470-2045(26)00170-1

Shankar Siva, ProfMBBS PhD ^a,^d,⁎ , Muhammad Ali, MBBS ^a,^d, Nicholas Hardcastle, PhD ^a,^d,^e, Tomas Kron, ProfPhD ^a,^d,^e, Braden Higgs, MBBS ^f, Farshad Foroudi, ProfMBBS DMedSc ^g,^h, Jeremy Ruben, MbBCh MMed ⁱ, Sree Appu, MBBS ^j, Jarad Martin, ProfMBChB PhD ^k, Swetha Sridharan, MBBS ^k, Rebecca Montgomery, BBiomedSc ^l, Ryan Davey, PhD ^l, Charles Lin, MBBS ^m,ⁿ, Mark Shaw, MBChB ^a,^d, Sarat Chander, MBBS ^a,^d, Mark Sidhom, MBBS ^o,^p, Ben G L Vanneste, MD PhD ^q,^r, Declan G Murphy, ProfMbBCh BAO ^b,^d, Nathan Lawrentschuk, ProfMBBS PhD ^b,^s, David Pryor, MBBS ^t, Simon Wood, MBBS ^t, Daniel Moon, MBBS ^u,^v, Mathias Bressel, MSc ^c,^d

^a Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

^b Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

^c Centre of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

^d Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia

^e Centre of Medical Radiation Physics, University of Wollongong, Wollongong, NSW, Australia

^f Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia

^g Department of Radiation Oncology, Olivia Newton-John Cancer Centre, Heidelberg, VIC, Australia

^h Medical Imaging and Radiation Sciences, School of Primary and Allied Health Care, Monash University, Melbourne, VIC, Australia

ⁱ Department of Radiation Oncology, Alfred Health, Melbourne, VIC, Australia

^j Cabrini Clinical School, Monash University, Melbourne, VIC, Australia

^k Department of Radiation Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia

^l TransTasman Radiation Oncology Group Cancer Research, Research Development, Newcastle, NSW, Australia

^m Department of Radiation Oncology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia

ⁿ School of Medicine, University of Queensland, Brisbane, QLD, Australia

^o South West Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia

^p Department of Radiation Oncology, Liverpool Cancer Therapy Centre, Sydney, NSW, Australia

^q Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium

^r Department of Radiation Oncology, MAASTRO-Clinic, Maastricht, Netherlands

^s Department of Surgery, University of Melbourne, Melbourne, VIC, Australia

^t Department of Urology and Radiation Oncology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia

^u Department of Surgery, University of Melbourne, Melbourne, VIC, Australia

^v Royal Melbourne Clinical School, University of Melbourne, Melbourne, VIC, Australia

^* Correspondence to: Prof Shankar Siva, Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia Department of Radiation Oncology Peter MacCallum Cancer Centre Melbourne VIC 3000 Australia

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Summary

Background

Stereotactic ablative body radiotherapy (SABR) is a non-invasive therapy for inoperable primary renal cell carcinoma. However, long-term prospective clinical trial data are scarce. We aimed to use pooled data from two clinical trials (FASTRACK and FASTRACK II) to evaluate activity and safety of SABR in the long term.

Methods

In this pooled analysis, we used data from FASTRACK, a single-institutional, phase 1, prospective clinical trial conducted at the Peter MacCallum Cancer Centre (Melbourne, VIC, Australia), and FASTRACK II, an international, non-randomised, phase 2 clinical trial conducted in seven academic hospitals in Australia and one in the Netherlands. The treatment protocol, inclusion and exclusion criteria, and dose constraints were the same in both trials. Patients had primary renal cell carcinoma and were deemed medically inoperable or high-risk for surgery, were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 2 or less, tumours of 10 cm or less in maximal dimension, and N0–N1 disease. Tumours 4 cm or smaller in FASTRACK II and smaller than 5 cm in FASTRACK received a single fraction of 26 Gy and larger tumours received 42 Gy in three fractions 48 h apart. Local control (freedom from local progression) was the primary endpoint, assessed using Response Evaluation Criteria in Solid Tumours (version 1.1) criteria. The analyses were conducted only in patients who commenced protocol treatment. Safety was evaluated with the Common Terminology Criteria for Adverse Events in participants who started protocol treatment. A patient representative was involved in the study design and conduct of FASTRACK II. Both trials were registered with ClinicalTrials.gov (FASTRACK: NCT01676428 ; FASTRACK II: NCT02613819 ) and are both completed.

Findings

108 patients were enrolled between June 28, 2012, and Oct 17, 2014 (FASTRACK), and between July 28, 2016, and Feb 27, 2020 (FASTRACK II). Five patients did not receive treatment (one opted for surgery, three did not meet dose constraints and were withdrawn, and one died before treatment). Median age was 76·9 years (IQR 70·0–81·9). 74 (72%) of 103 patients analysed were male and 29 (28%) were female. Race and ethnicity data were not collected. The median follow-up was 5·0 years (IQR 2·3–6·0). Local control at 1 year was 100%, at 3 years was 98% (89–100), and at 5 years was 98% (89–100), with local progression occurring in only one patient who had both local and distant progression at 28 months. Eight (8%) patients had grade 3 adverse events: abdominal or flank pain (four [4%] patients), nausea or vomiting (two [2%]), colonic obstruction (two [2%]), fatigue (one [1%]), and colitis or diarrhoea (one [1%]). All grade 3 or worse adverse events occurred within 2 years of SABR delivery. No grade 4 adverse events or treatment-related deaths were reported.

Interpretation

This pooled analysis from two clinical trials of SABR in patients with larger primary kidney tumours unsuitable for surgery supports evidence of long-term local control and low rate of severe adverse events. These results support further investigation through a randomised trial comparing SABR with surgery in select operable patients.