Effectiveness of immune checkpoint inhibitors in combination with stereotactic radiosurgery for patients with brain metastases from renal cell carcinoma: inverse probability of treatment weighting using propensity scores

Abstract

OBJECTIVE Stereotactic radiosurgery (SRS) is the mainstay for treating brain metastases (BMs) from renal cell carcinoma (RCC). In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic RCC and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for RCC BM prolongs overall survival (OS) and improves intracranial disease control and whether there are any safety concerns. METHODS Patients who underwent SRS for RCC BMs at the authors’ institution between January 2010 and January 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The time-to-event analysis of OS and intracranial progression-free survival (IC-PFS) between the groups with and without ICIs (ICI+SRS and SRS, respectively) was performed using inverse probability of treatment weighting (IPTW) based on propensity scores (PSs) to control for selection bias. Four baseline covariates (Karnofsky Performance Scale score, extracranial metastases, hemoglobin, and number of BMs) were selected to calculate PSs. RESULTS In total, 57 patients with 147 RCC BMs were eligible. The median OS for all patients was 9.1 months (95% CI 6.0–18.9 months), and the median IC-PFS was 4.4 months (95% CI 3.1–6.8 months). Twelve patients (21%) received concurrent ICIs. The IPTW-adjusted 1-year OS rates in the ICI+SRS and SRS groups were 66% and 38%, respectively (HR 0.30, 95% C 0.13–0.69; p = 0.005), and the IPTW-adjusted 1-year IC-PFS rates were 52% and 16%, respectively (HR 0.30, 95% CI 0.14–0.62; p = 0.001). Severe tumor hemorrhage (Common Terminology Criteria for Adverse Events [CTCAE] grade 4 or 5) occurred immediately after SRS in 2 patients in the SRS group. CTCAE grade 2 or 3 toxicity was observed in 2 patients in the ICI+SRS group and 5 patients in the SRS group. CONCLUSIONS Although the patient number was small and the analysis preliminary, the present study found that SRS with concurrent ICIs for RCC BM patients prolonged survival and provided durable intracranial disease control, with no apparent increase in treatment-related adverse events.

Gradual and Remarkable Tumor Shrinkage Following Seven-Fraction Stereotactic Radiosurgery Alone With a Marginal Dose of 48.3 Gy for Large Lobar Possibly Intra-sulcal Brain Metastasis From Renal Cell Carcinoma

“…However, the BED for 30 Gy in 3 fr is considerably low compared to that for 48.3 Gy in 7 fr, irrespective of the alpha/beta ratio. Sequential administration of tyrosine kinase inhibitors (TKIs) and ICI would contribute to enhanced tumor responses [ 5 , 19 ].…”

“…Therefore, long-term steroid administration was required. To further enhance efficacy, and especially earlier and more superior tumor response, dose escalation of the GTV marginal dose and combined administration of anti-cancer medications including TKI and/or ICI concurrently and/or sequentially were considered [ 5 , 19 ]. If the alpha/beta ratio of RCC is assumed to be ≤6-8, the single dose equivalent to 48.3 Gy in 7 fr is ≤22.1-23.1 Gy as shown in Table 3 .…”

“…The GTV D 98% ≥50.5-53.1 Gy in 7 fr with BED 6-8 ≥96-120 Gy, equivalent to 24 Gy in 1 fr, may provide better tumor response in the present case, while the risk of ARE inevitably increases. TKI and ICI can provide efficacy for existing BMs, and therefore continued administration following SRS may enhance tumor response [ 1 , 5 , 19 ]. These regimens are also anticipated to enhance intra- and extra-cranial overall disease control for metastatic RCC [ 1 , 5 , 19 ].…”

“…TKI and ICI can provide efficacy for existing BMs, and therefore continued administration following SRS may enhance tumor response [ 1 , 5 , 19 ]. These regimens are also anticipated to enhance intra- and extra-cranial overall disease control for metastatic RCC [ 1 , 5 , 19 ]. Furthermore, vascular endothelial growth factor receptor (VEGFR) TKI can mitigate AREs relevant to high-dose SRS [ 20 ].…”

Combination of radiosurgery and immunotherapy in brain metastases: balance between efficacy and toxicities

“…]. Yomo et al [19] published a propensity score matched analysis on 178 NSCLC patients divided into two groups of 89 patients each (ICI-RS group and SRS group). The 1-year survival rates of the ICI þ SRS and SRS groups after the initial SRS were 65 and 50% and the median OS was 16.9 and 12.0 months, respectively (hazard ratio 0.62, 95% CI 0.44-0.87, P ¼ 0.006).…”