Survival After Combining Stereotactic Body Radiation Therapy and Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma

Abstract

BackgroundStereotactic body radiation therapy (SBRT) and tyrosine kinase inhibitors (TKIs) are effective treatments for metastatic renal cell carcinoma, but data on combining these two modalities are scarce. We aimed to investigate the survival outcomes of SBRT plus TKIs.MethodsData of patients treated with TKIs from December 2007 to June 2019 were collected. Patients received SBRT plus TKIs (TKI + SBRT group) or TKIs alone (TKI alone group). Local control (LC), time to change of systemic therapy (TTS), and overall survival (OS) were assessed.ResultsA total of 190 patients were included, and 85 patients received TKI + SBRT. The 2-year LC rate was 92.8%. The median OS in the TKI + SBRT group was significantly longer than that of the TKI alone group (63.2 vs 29.8 months; P < 0.001). In multivariate analysis, IMDC intermediate (HR 1.96; 95% CI 1.10–3.48; P = 0.022) and poor risk (HR 2.43; 95% CI 1.25–4.75; P = 0.009), oligometastasis (HR 0.41; 95% CI 0.26–0.65; P < 0.001), and the addition of SBRT (HR 0.48; 95% CI 0.31–0.75; P = 0.001) were prognostic factors for OS. Patients with oligometastasis (P = 0.009) and those with IMDC favorable (P = 0.044) or intermediate (P = 0.002) risk had significantly longer OS with TKI + SBRT. The median TTS were 21.5, 6.4, and 9.0 months in patients receiving SBRT before first-line TKI failure, SBRT after first-line TKI failure, and first-line TKI alone (P < 0.001). Five patients (5.9%) experienced SBRT-related grade 3 toxicities.ConclusionsCombining SBRT with TKIs is tolerable and associated with longer OS in selected patients, such as those with oligometastasis and favorable or intermediate risk.

Incorporating Stereotactic Ablative Radiotherapy into the Multidisciplinary Management of Renal Cell Carcinoma

“…Several other retrospective studies have evaluated safety and outcomes with a combination of first-line targeted therapy and SABR, the largest of which (reported by Liu et al) included 190 mRCC patients treated with either a tyrosine kinase inhibitor (TKI) + SABR (45%) or a TKI alone and revealed significantly longer survival in the TKI + SABR group than that of the TKI alone. Importantly, SABR was also found to be safe in this study, with no grade 4 or 5 toxicities and a SABR-related grade 3 toxicity of 5.9% [67].…”

“…Newer systemic therapies in the form of targeted therapy or ICIs, either alone or in combination, have improved oncologic outcomes in mRCC. Unfortunately, eventual resistance to systemic therapy remains unavoidable [67]. In the context of this inevitable failure of systemic therapy, there remains a role for SABR as a local metastasis-directed therapy in selected mRCC patients.…”

“…Despite these encouraging data, the blood-brain barrier poses a considerable challenge in the management of BMs with systemic therapies, and local therapy with surgery, SRS, and/or whole-brain radiotherapy (WBRT) remains the mainstay of management for these patients. SRS has recently gained favor over WBRT for patients with limited BMs, as stereotactic techniques not only permit a higher dose per fraction to overcome radioresistance, but also spare these patients from neurocognitive toxicities [81], while maintaining excellent LC rates and comparable survival outcomes [60,[67][68][69]82]. Similarly, SABR for the treatment of RCC spinal metastases has shown LC rates of 70-90% with minimal grade 3 toxicity (nausea) [83].…”

Stereotactic body radiation therapy for kidney cancer. Where do we stand?

“…Traditionally, SBRT has been employed in oligoprogressive and oligometastatic patients. The aim of this strategy was double: firstly, to achieve better LC of the irradiated lesion and secondly, to improve PFS in oligometastatic patients and delay the change to a different line of systemic therapy by eliminating resistant tumor subclones in oligoprogressive patients 44–52 . However, most of the evidence on this combination is based on retrospective studies, and clinical trials are limited to early phase, nonrandomized studies with small sample sizes (Table 3).…”

Identification of a Somatic Mutation-Derived Long Non-Coding RNA Signatures of Genomic Instability in Renal Cell Carcinoma

“…RCC has a poor sensitivity to radiotherapy and chemotherapy. Targeted therapy and immunotherapy are the other treatment options (5)(6)(7). Currently, there is no biomarker in clinical practice that can well predict the prognosis of RCC patients.…”