Abstract
Background: Targeted therapy has transformed the outcome for patients with metastatic renal cell carcinoma. Their efficacy and safety have also been demonstrated in brain metastatic RCC. Preclinical evidence suggests synergism of radiation and tyrosine kinase inhibitors. Consequently, several studies have compared their efficacy in the treatment of RCC brain metastases to the era of brain management with surgery/radiation only.Objectives: We seek to systematically review and meta-analyze the results of those studies that involved comparative intervention groups of brain management; TKIs, and never used TKIs.Methods and Materials: Online databases (PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov) were searched for comparative studies. Overall survival as the primary outcome of interest, and local brain control, distant control, and adverse events as secondary outcomes of interest were recorded for meta-analysis. Hazard ratios were pooled together using Review Manager 5.3. Fixed effects or random effects model were adopted according to the level of heterogeneity. Subgroup analysis included studies that involved SRS as the local treatment of management.Results: Overall 7 studies (n = 897) were included for meta-analysis. TKI use was associated with better survival (HR 0.60 [0.52, 0.69], p < 0.00001) and local brain control (HR 0.34 [0.11, 0.98], p = 0.05). SRS subgroup also revealed significantly better survival (HR 0.61 [0.44, 0.83], p = 0.002) and local brain control (HR 0.19 [0.08, 0.45], p = 0.0002). Distant brain control (HR 0.95 [0.67, 1.35], p = 0.79) and brain progression free survival were unaffected (HR 0.94 [0.56, 1.56], p = 0.80). Only one study (n = 376) reported significantly greater 12-months cumulative incidence of radiation necrosis with TKI use within 30 days of SRS (10.9 vs. 6.4%, p = 0.04).Conclusions: TKIs use in combination with SRS is safe and effective for treating RCC brain metastases. Larger randomized controlled trials are warranted to validate the results.
Highlights
Renal cancer is the eighth leading cancer type according to estimated new cancer cases in 2020 [1, 2]
One study included patients managed with observation; numbers were balanced between nonTKI and Tyrosine Kinase Inhibitors (TKIs) groups (n = 37 vs. 38) [44]
TKIs group mainly comprised of VEGFR tyrosine kinase inhibitors, and mammalian target of rapamycin (mTOR) inhibitors
Summary
Renal cancer is the eighth leading cancer type according to estimated new cancer cases in 2020 [1, 2]. A third of RCC patients are diagnosed with evidence of metastatic disease [2, 6]. Management of metastatic RCC has embraced advancements in the shape of immunomodulating, molecularly targeted and immune checkpoint inhibiting agents. These agents have improved the outcome for metastatic RCC as revealed by the 1% decrease per year in death rates from 2008 to 2017 [2, 7]. Targeted therapy has transformed the outcome for patients with metastatic renal cell carcinoma. Their efficacy and safety have been demonstrated in brain metastatic RCC. Several studies have compared their efficacy in the treatment of RCC brain metastases to the era of brain management with surgery/radiation only
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