ArticleNeuro-oncology2023
A genomic score to predict local control among patients with brain metastases managed with radiation.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Review
- Genetic and Immunohistochemical Profiling of Malignant Mesothelioma With Brain Metastasis: A Report of Two Cases.Cancer reports (Hoboken, N.J.) · 2026Article
- Impacts of co-mutations in oligometastatic and oligoprogressive non-small cell lung cancer withTranslational lung cancer research · 2025Review
- Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care.Nature reviews. Clinical oncology · 2025Review
- Precision radiotherapy with molecular-profiling of CNS tumours.Journal of neuro-oncology · 2025Review
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundClinical predictors of local recurrence following radiation among patients with brain metastases (BrM) provide limited explanatory power. We developed a DNA-based signature of radiotherapeutic efficacy among patients with BrM to better characterize recurrence risk.
methodsWe identified 570 patients with 1487 BrM managed with whole-brain (WBRT) or stereotactic radiation therapy at Brigham and Women's Hospital/Dana-Farber Cancer Institute (2013-2020) for whom next-generation sequencing panel data (OncoPanel) were available. Fine/Gray's competing risks regression was utilized to compare local recurrence on a per-metastasis level among patients with versus without somatic alterations of likely biological significance across 84 genes. Genes with a q-value ≤ 0.10 were utilized to develop a "Brain-Radiation Prediction Score" ("Brain-RPS").
resultsGenomic alterations in 11 (ATM, MYCL, PALB2, FAS, PRDM1, PAX5, CDKN1B, EZH2, NBN, DIS3, and MDM4) and 2 genes (FBXW7 and AURKA) were associated with decreased or increased risk of local recurrence, respectively (q-value ≤ 0.10). Weighted scores corresponding to the strength of association with local failure for each gene were summed to calculate a patient-level RPS. On multivariable Fine/Gray's competing risks regression, RPS [1.66 (1.44-1.91, P < .001)], metastasis-associated edema [1.60 (1.16-2.21), P = .004], baseline size [1.02 (1.01-1.03), P < .001] and receipt of WBRT without local therapy [4.04 (2.49-6.58), P < .001] were independent predictors of local failure.
conclusionsWe developed a genomic score to quantify local recurrence risk following brain-directed radiation. To the best of our knowledge, this represents the first study to systematically correlate DNA-based alterations with radiotherapeutic outcomes in BrM. If validated, Brain-RPS has potential to facilitate clinical trials aimed at genome-based personalization of radiation in BrM.
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