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).
To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort.
A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021.
SRS for RCC BMs.
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.
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).
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.
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.
European urology oncology. 2024 Aug 05 [Epub ahead of print]
Jennifer Ma, Luke Del Balzo, Henry Walch, Sari Khaleel, Andrea Knezevic, Jessica Flynn, Zhigang Zhang, Jordan Eichholz, Sahil D Doshi, Martin H Voss, Benjamin Freeman, A Ari Hakimi, Chung-Han Lee, Tejus A Bale, Daniel Kelly, Boris A Mueller, Justin Mann, Yao Yu, Melissa Zinovoy, Linda Chen, John Cuaron, Atif Khan, Yoshiya Yamada, Jacob Y Shin, Kathryn Beal, Nelson S Moss, Maria I Carlo, Robert J Motzer, Brandon S Imber, Ritesh R Kotecha, Luke R G Pike
Department of Radiation Oncology and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Radiation Oncology and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Medical College of Georgia, Augusta, GA, USA., Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Molecular Diagnostics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Technology Division, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Neurosurgery and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Radiation Oncology and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: .