Washington, DC (UroToday.com) During the kidney cancer session at the 20th Annual Meeting of the Society of Urologic Oncology, Dr. Vitaly Margulis from UT Southwestern provided an update of stereotactic radiation for the treatment of renal cell carcinoma (RCC). Historically, Dr. Margulis notes that RCC has been thought of as a radio-resistant tumor. However, what we have found in mouse model studies is that the tumor was resistant at conventional dosing, but not at higher levels.
In the localized setting, there are several studies that have assessed outcomes of stereotactic radiation. A multi-institutional study included all patients with renal masses who underwent SBRT during a 5-year period.1 Forty patients underwent SBRT for the treatment of 41 renal tumors, and the mean maximum tumor diameter before treatment was 3.9 cm (range, 1.6-8.3 cm). The mean pretreatment tumor growth rate of 0.68 cm/year decreased to -0.37 cm/year post-treatment (p < 0.0001), and the mean tumor volume growth rate of 21.2 cm3/year before treatment decreased to -5.35 cm3/year after treatment (p = 0.002). Local control-defined as less than 5 mm of growth-was achieved in 92.7% tumors. No statistically significant change in tumor enhancement was shown (mean follow-up, 142 days; range, 7-581 days).
A recent systematic review and meta-analysis has also assessed the emerging role of stereotactic ablative radiotherapy for primary RCC.2 From 2,386 PubMed entries and 924 meeting abstracts, Correa et al. identified 26 studies (11 prospective trials), including 383 tumors in 372 patients, most of whom were deemed inoperable. The median follow-up was 28.0 (5.8-79.2) months, the median age was 70.4 (62-83) years, and mean tumor size was 4.6 (2.3-9.5) cm. Dose fractionation varied, but 26 Gy in one fraction and 40 Gy in five fractions were the most common. The random-effect estimates for local control was 97.2% (95% CI 93.9-99.5%, I2=20%), grade 3-4 toxicity was 1.5% (95% CI 0-4.3%, I2=0%), and post-SABR eGFR change was -7.7ml/min (95% CI -12.5 to -2.8, I2=2%). Currently UT Southwestern has a phase II SBRT trial ongoing for primary RCC, with a primary endpoint of local control (n=16).
SBRT has also been reported for locally advanced disease by the UT Southwestern group,3 providing symptomatic relief and survival of 24 and 18 months (n=2) for two inoperable patients with IVC tumor thrombus. At UT Southwestern, they are currently running a phase II trial of neoadjuvant SBRT for patients planned for surgery with IVC tumor thrombus. Currently, they have enrolled 7 patients, hoping to increase 1-year RFS by 30%.
SBRT has also recently been described in the treatment of oligometastatic disease. The UT Southwestern team recently reviewed their patients with metastatic RCC treated with front-line SBRT with curative intent from 2007 to 2017.4 There were 47 patients with oligometastatic RCC treated with SBRT to 88 metastases. The local control rate was 91.5% at 2 years with no reported grade ≥3 toxicity. With a median follow-up of 30 months (IQR 13.7-40.9), median freedom from systemic therapy from the first SBRT was 15.2 months (95% CI 8.8-40.1). Improved freedom from systemic therapy was also observed in patients with metachronous disease (HR 2.67, p = 0.02), solitary metastasis (HR 2.26, p = 0.05), and non-bone metastasis (HR 2.21, p = 0.04).
Dr. Margulis notes that the most exciting field with SBRT and RCC is in radiation priming the immune response for systemic therapy – a concept he terms in situ vaccination with SBRT. The Abscopal Effect is well described in that radiation stimulates the systemic immune response. Currently, UT Southwestern is running the RadVax RCC Trial, which opened in March 2017, enrolling 25 of 25 patients. An induction phase of 5 x 10 Gy QOD SBRT is followed by nivolumab monotherapy. This data has been submitted to GU ASCO 2020.
Dr. Margulis concluded with several take-home messages:
- RCC is radiosensitive and SBRT can be used to stabilize or palliate primary tumors.
- SBRT may be useful as an adjunct for the management of locally advanced disease, such as IVC tumor thrombus.
- SBRT to metastatic sites may stabilize disease and delay or obviate the need for additional systematic therapy.
- SBRT is a palliative option and may be used to enhance the response to immunotherapy.
Presented by: Vitaly Margulis, MD, Professor, Department of Urology, UT Southwestern Medical Center, Dallas, Texas, USA.
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC
References:
- Sun MR, Brook A, Powell MF, et al. Effect of Stereotactic Body Radiotherapy on Growth Kinetics and Enhancement Pattern of Primary Renal Tumors. AJR Am J Roentgenol. 2016;206(3):544-553.
- Correa RJM, Louie AV, Zaorsky NG, et al. The Emerging role of stereotactic ablative radiotherapy for primary renal cell carcinoma: A Systematic review and meta-analysis. Eur Urol Focus 2018;5(6):958-969.
- Hannan R, Margulis V, Chun SG, et al. Stereotactic radiation therapy of renal cancer inferior vena cava tumor thrombus. Cancer Biol Ther 2015;16(5):657-661.
- Zhang Y, Schoenhals J, Christie A, et al. Stereotactic Ablative Radiation Therapy (SAbR) Used to Defer Systemic Therapy in Oligometastatic Renal Cancer. Int J Radiat Oncol Biol Phys 2019;105(2):367-375.