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Updated: Jun 17, 2025
Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy
Published on: May 8, 2018
Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic
Jennifer Ma1, Luke Del Balzo2, Henry Walch3
1Department of Radiation Oncology and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Background:
Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS).
Objective:
To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort.
Design, Setting, And Participants:
A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021.
Intervention:
SRS for RCC BMs.
Outcome Measurements And Statistical Analysis:
Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death.
Results And Limitations:
Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041).
Conclusions:
To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting.
Patient Summary:
We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.
Insights
This study found stereotactic radiosurgery (SRS) offers durable local control for renal cell carcinoma (RCC) brain metastases (BMs). PI3K pathway alterations were more common in patients with BMs, suggesting a potential therapeutic target.
Area of Science:
- Oncology
- Genetics
- Radiotherapy
Background:
- Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized.
- Systemic therapy advancements have improved overall survival (OS), making locoregional therapies like stereotactic radiosurgery (SRS) critical for effective management.
Purpose of the Study:
- To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort.
- To assess the efficacy of SRS in controlling RCC BMs and identify potential genomic biomarkers associated with brain metastasis.
Main Methods:
- Retrospective analysis of 91 RCC BM patients treated with SRS from 2010-2021.
- Next-generation sequencing to identify prevalent gene alterations in BM patients.
- Clinical factors and gene alterations assessed using Cox models and competing risks regression.
Main Results:
- SRS achieved durable local control in 83% of RCC BMs at 12 months.
- Median intracranial progression-free survival was 7.8 months, and median OS was 21 months.
- Phosphoinositide 3-kinase (PI3K) pathway alterations (including PTEN) were significantly more prevalent in BM+ patients (43%) compared to BM- patients (16%).
Conclusions:
- SRS provides durable in-field local control for RCC BMs.
- Recognizing post-SRS pseudoprogression is crucial for appropriate patient management.
- The higher incidence of PI3K pathway alterations in BM+ patients warrants further investigation as a potential therapeutic target.
