Clinical Implementation and Oncological Relevance of Molecular Profiling in Brain Metastases Patients-A Multicenter
Maria Nikolaeva1, Jacopo Bellomo1, Meltem Gönel1
1Department of Neurosurgery, University Hospital and University of Zurich, Zurich, Switzerland.
Abstract:
Brain metastases (BM) require a multidisciplinary treatment approach combining surgery, radiotherapy, and systemic therapy. While current guidelines recommend the analysis of established cancer driver genes in BM tissue, little is known about its real-life implementation and relevance on oncological treatment strategies. This retrospective multicenter study includes patients with BM from melanoma, lung and breast cancer operated between 2010 and 2022. Clinical records were evaluated for BM molecular analyses of predefined cancer drivers and their discordance to extracranial tumor sites, that is, ALK, BRAF, EGFR, KRAS, NTRK for lung, HER2, estrogen/progesterone receptor, BRCA1/2 for breast cancer and BRAF, KIT, NRAS among others for melanoma. Adjustment of systemic therapies based on BM molecular profiles was analyzed. Among 1431 BMs screened for availability of molecular analysis, molecular profiling was performed at least partially in 723 BMs (51%). In cases with matched extracranial tumor samples (n = 276), discordant alterations were found in 18% of lung, 4.7% of melanoma and 45% of breast cancer BMs. Molecular BM analyses informed systemic therapy adjustments in 13%-27% of patients depending on the primary tumor. Overall survival was significantly better in patients who underwent BM profiling, especially when operated in recensst years (median 19.3 vs. 9.9 months; p < 0.0001) and in patients with breast cancer who had a change in systemic therapies upon BM profiling (p = 0.0085). In conclusion, molecular profiling of BM allows selecting available treatment options for a substantial subset of patients. This study underscores the need for more systematic molecular testing in BM patients to guide systemic treatment decisions.
Insights
Molecular profiling of brain metastases (BM) guides systemic therapy and improves survival. This study highlights the need for systematic BM molecular testing to personalize cancer treatment and optimize patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Brain metastases (BM) necessitate a multidisciplinary treatment strategy.
- Current guidelines advocate for molecular analysis of BM tissue, but real-world implementation and impact on treatment are unclear.
Purpose of the Study:
- To evaluate the real-world implementation of molecular profiling in brain metastases (BM).
- To assess the relevance of BM molecular profiles in guiding oncological treatment strategies.
- To analyze the discordance between BM and extracranial tumor molecular profiles and its impact on survival.
Main Methods:
- Retrospective multicenter study of patients with BM from melanoma, lung, and breast cancer (2010-2022).
- Evaluation of clinical records for BM molecular analyses of predefined cancer drivers.
- Comparison of BM molecular profiles with extracranial tumor sites and analysis of systemic therapy adjustments.
Main Results:
- Molecular profiling was performed in 51% of analyzed BMs.
- Discordant molecular alterations between BM and extracranial tumors were observed in 18% (lung), 4.7% (melanoma), and 45% (breast cancer).
- BM molecular analyses informed systemic therapy adjustments in 13%-27% of patients, leading to significantly better overall survival, particularly in breast cancer patients with treatment changes.
Conclusions:
- Molecular profiling of brain metastases is crucial for identifying targeted treatment options.
- Systematic molecular testing in BM patients is essential for guiding personalized systemic treatment decisions.
- This approach can significantly improve patient outcomes and overall survival.
