Research

Brain metastases affect more than 200,000 people in the United States each year and remain the most common type of intracranial tumor. Yet for much of the history of oncology, this patient population was systematically underserved and excluded from clinical trials. The UVA Brain Metastases Research Collaborative is committed to changing that. Our investigators work across the full spectrum of discovery, from molecular biology to clinical trials to population-level outcomes, with the goal of developing treatments that extend life, preserve function, and honor what patients care about most. We believe that a brain metastases diagnosis will no longer be the end of the road.

Understanding why cancer spreads to the brain and what makes that process possible is foundational to developing treatments capable of preventing or reversing it. Basic and translational research in brain metastases seeks to characterize the molecular and cellular mechanisms that allow cancer cells to penetrate the blood-brain barrier, adapt to the brain microenvironment, and establish secondary tumors. Uncovering these mechanisms reveals potential therapeutic targets that could be exploited before metastatic disease becomes refractory to existing treatments, and points toward the next generation of systemic therapies capable of reaching the central nervous system directly.

Clinical trials are the mechanism by which scientific advances become available to patients, and this pipeline has historically been inaccessible to patients with brain metastases. Patients with active brain involvement were routinely excluded from oncology trials, limiting the evidence base and perpetuating empirical, one-size-fits-all treatment. Our clinical research spans the full range of treatment modalities with an increasing emphasis on biomarker-driven trial design that can generate personalized, actionable guidance rather than population-level averages.

Even the most effective treatments fail to reach their potential when the systems delivering them are inconsistent or insufficiently attentive to what patient’s value. UVA investigators have led international efforts to address that gap and establish consensus performance standards for brain metastases care. Alongside that work, research on patient-reported outcomes and caregiver perspectives asks the questions clinical metrics alone cannot answer: how patients weigh survival against cognitive function, what quality of life means in the context of active brain metastases, and how well goals-of-care conversations align the treatment being delivered with what patients actually want.

• McLoughlin EM, Fadul CE, Patel SH, Hall RD, Gentzler RD. Clinical and Radiographic Response of Leptomeningeal and Brain Metastases to Encorafenib and Binimetinib in a Patient With BRAF V600E-Mutated Lung Adenocarcinoma. J Thorac Oncol. 2019;14(12):e269-e71. doi: 10.1016/j.jtho.2019.07.019. PubMed PMID: 31757377.
• Dutta SW, Mack ML, Aliotta E, Ward KA, Muller DA, Larner JM, Fadul CE, Hall RD, Gentzler RD, Sheehan JP. Intracranial disease control for EGFR-mutant and ALK-rearranged lung cancer with large volume or symptomatic brain metastases. J Neurooncol. 2020;149(2):357-66. Epub 20200909. doi: 10.1007/s11060-020-03615-4. PubMed PMID: 32902767.
• Bovi JA, Fadul CE. A window into the care needs of patients with brain metastases. Neurooncol Pract. 2021;8(6):625-6. Epub 20211110. doi: 10.1093/nop/npab057. PubMed PMID: 34777831; PMCID: PMC8579085.
• Silvestre J, Gosse T, Read P, Gentzler R, Purow B, Asthagiri A, Gaughan E, Dillon PM, Larner JM, Anderson RT, Sheehan JP, Fadul CE. Genesis of Quality Measurements to Improve the Care Delivered to Patients With Brain Metastases. JCO Oncol Pract. 2021;17(3):e397-e405. Epub 20200811. doi: 10.1200/OP.20.00233. PubMed PMID: 32780641.
• Fadul CE, Sarai G, Bovi JA, Thomas AA, Novicoff W, Anderson R, Amidon RF, Schuetz S, Singh R, Chang A, Gentzler RD, Gaughan EM, Sheehan JP. Relevance of the Updated Recursive Partitioning Analysis (U-RPA) Classification in the Contemporary Care of Patients with Brain Metastases. Cancers (Basel). 2023;15(12). Epub 20230620. doi: 10.3390/cancers15123255. PubMed PMID: 37370865; PMCID: PMC10297002.
• Jusino S, Fadul CE, Dillon P. Systematic review of the management of brain metastases from hormone receptor-positive breast cancer. J Neurooncol. 2023;162(1):45-57. Epub 20230308. doi: 10.1007/s11060-023-04276-9. PubMed PMID: 36884200; PMCID: PMC10049940.
• Fadul CE, Sheehan JP, Silvestre J, Bonilla G, Bovi JA, Ahluwalia M, Soffietti R, Hui D, Anderson RT. Defining the quality of interdisciplinary care for patients with brain metastases: modified Delphi panel recommendations. Lancet Oncol. 2024;25(9):e432-e40. doi: 10.1016/S1470-2045(24)00198-0. PubMed PMID: 39214114.
• Lehrer EJ, Trifiletti DM, Fadul CE, Brown PD, Sheehan JP. Chemoimmunotherapy for Untreated Lung Cancer Brain Metastases: A Reason for Optimism While Avoiding Overreaching Interpretations. J Clin Oncol. 2024;42(7):857-8. Epub 20231211. doi: 10.1200/JCO.23.01876. PubMed PMID: 38079583.
• Mondia MWL, Batchala PP, Dreicer R, Devitt ME, McCord MR, Mut M, Sheehan JP, Schiff D, Fadul CE. Incidental Brain Metastases From Prostate Cancer Diagnosed With PSMA PET/CT and MRI: A Case Series and Literature Review. Prostate. 2025;85(9):841-9. Epub 20250313. doi: 10.1002/pros.24890. PubMed PMID: 40079497; PMCID: PMC12068031.
• Petrosian D, Fadul CE, Reilley M, Dillon P. Oesophageal adenocarcinoma presenting with synchronous brain metastases. BMJ Case Rep. 2025;18(1). Epub 20250131. doi: 10.1136/bcr-2024-263641. PubMed PMID: 39890418; PMCID: PMC11791889.
• Soto DJ, Lundberg CW, D’Agostino E, Wirth S, Wendel S, Amidon RF, Catalino MP, Lobo JM, Anderson RT, Brady W, Nguyen L, Schneider B, Guterman I, Sheehan JP, Bovi JA, Thomas AA, Fadul CE. Hospital Admission and Survival of Patients With Brain Metastases Diagnosed in the Emergency Care Setting. JCO Oncol Pract. 2025:OP2500508. Epub 20251114. doi: 10.1200/OP-25-00508. PubMed PMID: 41237362.
• Young S, Dougherty SC, DeRidder AM, Fadul CE, Gentzler RD. Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naive HER2-Mutated Non-Small-Cell Lung Cancer. Case Rep Oncol Med. 2025;2025:9936011. Epub 20250423. doi: 10.1155/crom/9936011. PubMed PMID: 40313527; PMCID: PMC12043382.
• Chung JH, Tos SM, Mantziaris G, Shinya Y, Hajikarimloo B, Guiry J, Kareddy A, Vegiraju T, Llinas E, Penberthy D, Xu Z, Gentzler R, Fadul C, Sheehan JP. Stereotactic Radiosurgery Dose Reduction for Patients With Brain Metastases From Non-Small Cell Lung Primary on Immunotherapy or Targeted Therapy. Neurosurgery. 2026. Epub 20260212. doi: 10.1227/neu.0000000000003961. PubMed PMID: 41677281.
• Singh R, Fadul CE, Kopp E, Sarai G, Anderson R, Amidon RF, Schuetz S, Chang A, Iqbal AN, Bovi JA, Thomas AA. Palliative Care and Quality Outcomes in Patients With Brain Metastases and Poor Prognosis: A Multi-Institutional Analysis. JCO Oncol Pract. 2026:OP2500882. Epub 20260223. doi: 10.1200/OP-25-00882. PubMed PMID: 41730153.