264 - Ultra-Hypofractionated Stereotactic Ablative Body Radiotherapy (SABR) for Primary Renal Cell Carcinoma: Pooled Outcomes from the FASTRACK and FASTRACK II Clinical Trials
Presenter(s)
S. Siva1, M. Ali2, D. Moon3, N. Hardcastle4,5, T. Kron4, B. G. Higgs6, F. Foroudi7, J. Ruben8, J. M. Martin9, S. Sridharan10, R. Montgomery11, R. Davey12, C. Lin13, M. Shaw4, M. Sidhom14, B. Vanneste15, D. Murphy16, N. Lawrentschuk4, S. Wood17, and D. I. Pryor17; 1Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia, 2Peter MacCallum Cancer Centre, Melbourne, Australia, 3Peter MacCallum Cancer Centre, Parkville, Australia, 4Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, 5Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia, 6Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia, 7Olivia Newton John Cancer Wellness and Research Centre, Austin Hospital, Melbourne, VIC, Australia, 8The William Buckland Radiotherapy Centre, Alfred Health, Melbourne, VIC, Australia, 9University of Newcastle, Newcastle, Australia, 10Calvary Mater Newcastle Hospital, Waratah, NSW, Australia, 11TROG Cancer Research, Sydney, Australia, 12TROG Cancer Research, Waratah, NSW, Australia, 13Dept of Radiation Oncology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia, 14Liverpool Hospital Cancer Therapy Centre, University of New South Wales, School of Medicine, Sydney, NSW, Australia, 15Maastro, Maastricht, Netherlands, 16Department of Surgery, Peter MacCallum Cancer Center, Melbourne, VIC, Australia, 17Princess Alexandra Hospital, Brisbane, QLD, Australia
Purpose/Objective(s):
Stereotactic ablative body radiotherapy (SABR) is an emerging non-invasive therapy for inoperable renal cell carcinoma (RCC). Schedules using 5-fractions are common in North America. We hypothesize that pooled data from two clinical trials (FASTRACK [ID NCT01676428] and FASTRACK II [ID NCT02613819]) will confirm the efficacy and safety of high-dose single and three fraction SABR schedules.Materials/Methods:
Data across two consecutive prospective trials were pooled and analyzed, recruited from 28/06/2012 until 17/10/2014, and from 28/07/2016 and 27/02/2020. The treatment protocol, inclusion/exclusion criteria and dose constraints were shared in both trials. Patients had biopsy-confirmed RCC and were deemed medically inoperable or high-risk for surgery. Tumors =4 cm received a single fraction of 26 Gy, while tumors >4 cm received 42 Gy in three fractions. Local control (freedom from local progression) was the primary endpoint, assessed using RECIST 1.1 criteria. Secondary endpoints included overall survival (OS), freedom from distant progression (FFDP), toxicity (graded per CTCAE v4.0), and changes in estimated glomerular filtration rate (eGFR).Results:
Of 107 patients (median age: 77 years), five did not receive treatment (opted for surgery [n=1], did not meet dose constraints and withdrawn [n=3], deceased before treatment [n=1]). The mean RCC size was 4.7cm (SD +/- 1.1cm). The estimated median follow-up was 38 months. One patient had bilateral RCC treated with SABR. There was 100% histological confirmation of malignant disease, with 72 (69.2%) kidneys having clear cell RCC. Local control at 1 and 2 years was 100%, and at 5 years was 99% (95% CI: 93-99%). FFDP at 1-year was 97% (95% CI: 93.7%–100%), 2-years 94.5% (95% CI:88.1%–98.1%) and 5-years 83.9% (95% CI:76.4% – 91.4%). OS at 1-year was 98% (95% CI: 94.4% –100%), 2-years was 87.5% (95%CI: 81.9%–93.1%) and 5-years was 73.6% (95%CI: 65.1%–82.1%). Mean baseline eGFR was 59mL/min. The decline in eGFR at 1-year was ~9.4 mL/min, 2-years ~13.4 mL/min and 5-years ~15.8 mL/min. One patient (1%) underwent dialysis. Eight patients (7.8%) experienced grade 3 (fatigue, vomiting, chest wall or flank pain and colonic obstruction) adverse events; no grade 4 or 5 events were reported.Conclusion:
To our knowledge, this is the largest prospective trial cohort of a non-surgical curative treatment for primary RCC. Pooled results indicate that SABR using high-dose single fraction and three fraction approaches is highly effective and nephron sparing, with low rates of severe adverse events. These findings support the use of ultra-hypofractionated SABR schedules for primary RCC.