In the present investigation, we observed a significant and independent radiographic control benefit with the addition of first-line TKIs to stereotactic radiosurgery.
Jacob A. Miller, BS, Ehsan H. Balagamwala, MD, Lilyana Angelov, MD, John H. Suh, MD, Brian Rini, MD, Jorge Garcia, MD, Manmeet Ahluwalia, MD, Samuel T. Chao, MD; Cleveland Clinic
INTRODUCTION: With the introduction of antiangiogenic tyrosine kinase inhibitors (TKIs), systemic control of metastatic renal cell carcinoma (mRCC) has substantially improved. The second most common site of metastasis in mRCC is the spine. As a radioresistant histology, these metastases require higher doses of radiation for palliation and local control. This may be achieved with spine stereotactic radiosurgery (SRS). In laboratory models, strong evidence exists for a synergistic relationship between TKIs and SRS. However, controlled studies have yet to demonstrate a corresponding clinical benefit. We hypothesized that patients undergoing spine SRS with concurrent first-line TKIs experience superior radiographic control compared with those not receiving concurrent TKI therapy.
METHODS: An institutional retrospectively collected database was queried for patients undergoing spine SRS for mRCC. Patients were divided into one of four cohorts: (A) SRS with concurrent first-line TKIs; (B) chemotherapy-naive patients; (C) patients who had failed first-line chemotherapy undergoing SRS with concurrent TKIs; and (D) patients who had failed first-line chemotherapy undergoing SRS without concurrent TKIs. The primary outcome was actuarial radiographic control. Cox proportional hazards modeling was used to control for confounding differences among cohorts.
RESULTS: A total of 151 consecutive treatments (100 patients) for mRCC were identified. At 12 months, actuarial radiographic failure was lowest (8%) among patients treated with concurrent first-line TKIs, compared with 25% to 31% radiographic failure in cohorts B–D. After adjusting for confounding differences among cohorts, patients treated with concurrent firstline TKIs experienced superior radiographic control (hazard ratio, 0.16; P < .01) compared with patients in other cohorts. No grade ≥ 3 toxicities occurred among patients receiving concurrent therapy.
CONCLUSION: In the present investigation, we observed a significant and independent radiographic control benefit with the addition of first-line TKIs to SRS. These results have significant implications in the oligometastatic and curative settings and support laboratory evidence of an interaction between SRS and TKIs.
Proceedings of the 98th Annual Meeting of the American Radium Society - americanradiumsociety.org