3364 - Gastrointestinal and Renal Adverse Events following Kidney SBRT for Renal Cell Carcinoma: Impact of Recent Systemic Therapy Use
Presenter(s)
K. A. Rummel1, M. Borras-Osorio1, F. Mastroleo1,2, A. Attia3, H. Mohammadi3, B. J. Davis1, T. D. Malouff1, R. Phillips1, A. W. Rajkumar1, J. C. M. Rwigema4, R. S. Smith1, B. J. Traughber Jr1, J. M. Wilson1, N. Y. Yu4, B. J. Stish1, and M. R. Waddle1; 1Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 2Division of Radiation Oncology, IEO, European Institute of Oncology, IRCCS, Milan, Italy, 3Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, 4Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ
Purpose/Objective(s): Gastrointestinal (GI) and renal adverse events (AEs) can occur after kidney stereotactic body radiation therapy (SBRT) for renal cell carcinoma (RCC). Bowel perforation (BP) is a severe AE associated with SBRT, with reports suggesting increased risk when combined with systemic therapy. We characterized BP and other renal and GI AEs in RCC patients treated with kidney SBRT and hypothesized that recent systemic therapy would increase severe AEs.
Materials/Methods: We retrospectively reviewed our institutional database to identify RCC patients treated with SBRT to the kidney or nephrectomy bed. Exclusion criteria included non-kidney/nephrectomy bed targets, palliative treatment (<5 Gy/fraction or clinical documentation of palliative intent), spatially fractionated regimens, or <3 months of follow-up. Collected AEs were CTCAE >grade 2 events. Recent systemic therapy was defined as RCC-directed agent within 6 months pre- or 12 months post-SBRT, classified as multitarget tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), or other (everolimus, belzutifan, bevacizumab). Exploratory bivariate analysis was performed for BP.
Results: 106 patients met inclusion criteria. Median follow-up was 13 months (IQR 7-24). Median age was 72 years (IQR 65-81); 76 (71.7%) were male. Most frequent RCC subtype was clear cell (n=66, 62.3%); 30 had radiologic RCC diagnosis (no biopsy). Median tumor size was 5.1 cm. T stage was T1 in 60 patients, T2 in 3, T3 in 60, and T4 in 4; 12 patients were N1, and 35 were M1. Most patients received photon radiation (n=99, 93.4%); the most frequent regimen was 42 Gy/3 fx (n=64, 60.4%). Median small and large bowel D0.03cc biologically effective dose (BED) was 62.2 Gy3 (IQR 31.7-88.6) and 93.9 Gy3 (IQR 53.1-114.2), respectively. Recent systemic therapy included TKI monotherapy (n=6, 5.7%), ICI monotherapy (n=8, 7.5%), TKI+ICI (n=23, 21.7%), belzutifan (n=4, 3.8%), everolimus (n=1, 0.9%), and bevacizumab (n=1, 0.9%). TKIs included cabozantinib (n=11), axitinib (n=9), lenvatinib (n=8), and tivozanib (n=1).
GI AEs included intestinal hemorrhage (n=12), ulceration (n=4), obstruction (n=3), and BP (n=8); renal failure requiring dialysis occurred in 4 patients. All BP occurred in photon treated patients, mean time to event 8.9 months (range 5.1 - 17.7) post-SBRT; most were in large intestine (n=7). CTCAE severity was grade 3 (n=4), grade 4 (n=3), and grade 5 (n=1). Bivariate analysis identified large bowel D0.03cc BED (p=0.029) and recent systemic therapy (p=0.041) as significant factors associated with BP. T-stage (p=0.578) and tumor size (p=0.203) were not found to be significantly associated with BP. Six of eight BP events (75%) occurred in patients who received recent systemic therapy, all of whom received combination TKI+ICI therapy.Conclusion: BP rates were higher among kidney SBRT patients treated with recent combination TKI+ICI therapy. Given the retrospective design and limited sample size, results should be interpreted cautiously.