Introduction & Objectives
Selective Internal Radiation Therapy (SIRT) is an interventional procedure used for unresectable liver tumours, and has properties that make it potentially useful for primary Renal Cell Carcinoma (RCC) that is unsuitable for nephrectomy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.
Material & Methods
Patients (pts) not amenable for or who declined conventional therapy were eligible. A single transfemoral microcatheter administration of Yttrium-90 (Y-90) resin microspheres (SIR-Spheres; Sirtex, Australia) was delivered super-selectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gray and a final cohort with a procedural endpoint of imminent stasis, in a dose-escalation design. Post-SIRT follow-up was 12 months. The primary endpoint was safety and toxicity 30 days post-SIRT. Secondary endpoints included tumour response (RECIST v1.1).
The study enrolled 21 pts with RCC (33% left and 67% right kidney), mean age 75.0 years (SD: 9.3; range 48–86) and WHO performance status of 0 (81%) or 1 (19%); gender was 6 (29%) female and 15 (71%) male. Eight pts (38%) had metastatic RCC. Seven pts (33%) had previously undergone total nephrectomy of the contralateral kidney, 1 (5%) received prior chemotherapy and 1 (5%) progressed after cryotherapy to the target organ. Three patients were re-treated within the RESIRT study at a higher Y-90 dose, after at least a 12-month interval from their previous SIRT treatment. Median follow-up was 12.0 months (95% CI 11.9–12.1). Sum of longest diameters for the target lesion was median 45 mm (range 23‒123 mm). The intended Y-90 doses were delivered without any dose-limiting toxicity. Imminent stasis was reached in 11 (52%) pts. 18 (86%) pts experienced 70 adverse events (AEs) at any time to 12 months, with 8 (38%) pts experiencing 18 SAEs; 4 (19%) pts experienced 5 SAEs within 30 days post-SIRT, all determined as not related to SIRT. Ten (48%) pts had 24 AEs grade ≥3 at any time point to 12 months and all were considered unrelated to SIRT; 9 pts (43%) had 16 AEs that were related to SIRT (all grade 1–2, no SAEs), of which 2 occurred pre SIRT. Treatment-related AEs were fatigue/tiredness/lethargy, pain, hypertension, lack of appetite, nausea, ‘heaviness’, bruised groin andhypomagnesemia. Best overall tumour responses were Partial Response [PR] 1/18 (6%), stable disease [SD] 16/18 (89%) and progressive disease 1/18 (6%), with SD in 2 further patients with on-going follow-up.
This pilot study demonstrates good tolerability of SIRT at all dose levels including imminent stasis in treating primary tumours in RCC pts otherwise unsuitable for conventional therapy.