Radiosurgical Treatments for Brain Metastases

Brain metastases complicate the course of many solid tumours and pose a formidable clinical challenge due to the delicate nature of cerebral tissue and the blood–brain barrier. Radiosurgery has emerged as a precision modality that delivers high doses of radiation to discrete targets in the brain, sparing surrounding healthy parenchyma. Techniques such as frame-based stereotactic radiosurgery, linac-based volumetric modulated arc therapy and image-guided robotic platforms enable single-fraction or hypofractionated regimens tailored to lesion size, location and patient performance status. These approaches achieve local control rates exceeding 80 per cent while minimising cognitive sequelae associated with whole-brain irradiation. Contemporary practice emphasises the integration of advanced imaging for target delineation, dose-painting strategies to account for radioresistant tumour subregions and adaptive protocols that respond to intracranial tumour dynamics. Ongoing efforts address the risks of radiation necrosis, optimise fractionation schedules for larger or eloquent lesions and explore synergistic combinations with systemic therapies, including immunotherapy and targeted agents. The global uptake of radiosurgical platforms reflects their role in extending survival, preserving neurological function and improving quality of life for patients with intracranial metastatic disease.

Research from Nature Portfolio

Recent studies have refined the intracranial efficacy of antibody–drug conjugates in patients with metastatic breast cancer. A large prospective trial demonstrated that a novel HER2-targeted conjugate achieved durable central nervous system progression-free survival of over 58 per cent at 12 months, with manageable toxicity. Parallel reports from early-phase cohorts confirmed high rates of complete and partial intracranial responses in heavily pretreated cohorts, reinforcing this agent as a systemic option with meaningful blood–brain barrier penetration. In a complementary preclinical advance, engineered nanobiological particles that home to HER3 receptors on both tumour and endothelial cells were shown to cross an intact barrier, accumulate within intracranial lesions and deliver cytotoxic payloads, resulting in significant growth inhibition in models of breast cancer metastasis to the brain. Such findings pave the way for precision radiosurgical regimens augmented by targeted delivery systems.

Radiosurgical Treatments for Brain Metastases publication trend

The graph below shows the total number of articles in radiosurgical treatments for brain metastases across all publications each year (not limited to Nature Index journals).

Technical terms

Stereotactic radiosurgery (SRS): A non-invasive radiation technique that delivers a high dose to a precise intracranial target in one or a few fractions.

Volumetric modulated arc therapy (VMAT): A linac-based method of delivering conformal radiation by continuously varying beam shape and dose rate during gantry rotation.

Hypofractionated stereotactic radiotherapy: Fractionated delivery of radiosurgical doses over two to five sessions to balance tumour control with normal tissue tolerance.

Blood–brain barrier (BBB): A selective endothelial interface that restricts systemic agents from entering the central nervous system.

Radiation necrosis: Tissue injury resulting from vascular and cellular damage after high-dose irradiation, manifesting as contrast-enhancing lesions that may mimic tumour recurrence.

References

1. Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial. Nature Medicine (2024).
2. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nature Medicine (2022).
3. Systemic HER3 ligand-mimicking nanobioparticles enter the brain and reduce intracranial tumour growth. Nature Nanotechnology (2025).
4. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiation Oncology (2011).
5. Linac-based VMAT radiosurgery for multiple brain lesions: comparison between a conventional multi-isocenter approach and a new dedicated mono-isocenter technique. Radiation Oncology (2018).