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Open research questions in Brain Metastases and Treatment

131 gap statements mined from Brain Metastases and Treatment papers in our 4.5M-paper local library, which holds 572 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Future trials must include CNS-specific endpoints, incorporate liquid biopsy and imaging biomarkers, and emphasize preservation of neurocognitive function alongside survival.

    Breast cancer brain metastasis: from molecular insights to therapeutic innovation · 2026 · DOI

  • There is a need for a predictive model to identify high-risk patients. Current models lack interpretability, making it challenging to understand the decision-making process.

    An interpretable machine learning model for predicting brain metastasis in breast cancer · 2026 · DOI

  • The underlying mechanisms of brain metastasis in ER+BC are poorly understood. Specific drivers of brain metastasis from ER+BC remain poorly characterized.

    RET signaling as a mediator of estrogen receptor positive breast cancer brain metastasis · 2026 · DOI

  • These findings support further investigation of WBRT-SIB, preferably in a randomized setting and in patients with BM originating from SCLC, for patients who are not candidates for stereotactic radiosurgery.

    Whole-brain radiotherapy with simultaneous integrated boost in treatment of patients with brain metastases: a systematic review and meta-analysis · 2026 · DOI

  • It highlights the need for caution in treatment planning to avoid exceeding brain dose constraints. The paper also notes the challenge of managing the risk of brain radionecrosis when irradiating skull bone metastases.

    Cerebral Radionecrosis Following Stereotactic Irradiation of Skull Bone Metastases: A Diagnostic Pitfall to Be Aware of · 2026 · DOI

  • It highlights the need for further research on this topic to improve treatment planning and imaging interpretation.

    Cerebral Radionecrosis Following Stereotactic Irradiation of Skull Bone Metastases: A Diagnostic Pitfall to Be Aware of · 2026 · DOI

  • Cesium-131 collagen tile has gained traction as an intraoperative brachytherapy platform for recurrent intracranial tumors, but outcome data in newly diagnosed brain metastases (nBM) remain sparse, with fewer than ten cases reported.

    Intraoperative, Interstitial Brachytherapy in Newly Diagnosed Brain Metastases Through Cesium-131 Collagen Tile Implant: A Multi-Institutional Case Series · 2026 · DOI

  • The role of FGFR1 in estrogen receptor-positive breast cancer brain metastases is not well understood. The effectiveness of FGFR inhibitors in preventing brain metastases is not well established.

    Brain FGF2 and NCAM1 contribute to FGFR1-dependent progression of estrogen receptor-positive breast cancer brain metastases · 2026 · DOI

  • The lack of standardized prognostic indices for patients with brain metastases treated with cranial radiotherapy. The need for accurate prediction of overall survival to guide treatment decisions.

    Comparative validation of prognostic indices in brain metastases receiving cranial radiotherapy · 2026 · DOI

  • There is a need for external validation of prognostic indices in patients with brain metastases treated with cranial radiotherapy. There is a need to evaluate the combined prognostic impact of clinical variables and treatment-related factors on overall survival.

    Comparative validation of prognostic indices in brain metastases receiving cranial radiotherapy · 2026 · DOI

  • 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.

    Clinical Implementation and Oncological Relevance of Molecular Profiling in Brain Metastases Patients—A Multicenter Retrospective Cohort Study · 2026 · DOI

  • The case presents a single patient's experience and may not be generalizable. The role of COVID-19 vaccination in the development of radiation necrosis is unclear.

    Late radiation necrosis following stereotactic radiosurgery after COVID-19 vaccination: a case report and hypothesis of immune-mediated inflammatory activation · 2026 · DOI

  • Late radiation necrosis occurring several years after SRS remains uncommon and incompletely characterized. The role of COVID-19 vaccination in the development of radiation necrosis is unclear.

    Late radiation necrosis following stereotactic radiosurgery after COVID-19 vaccination: a case report and hypothesis of immune-mediated inflammatory activation · 2026 · DOI

  • Future studies should investigate the long-term cognitive function and quality of life outcomes of SRT+ICIs and HA-WBRT+ICIs. Future studies should explore the efficacy of SRT+ICIs in other patient populations, such as those with breast cancer or melanoma. Future studies should investigate the potential prognostic factors associated with overall survival and intracranial progression-free survival.

    Stereotactic versus hippocampal avoidance whole-brain radiotherapy combined with immune checkpoint inhibitors for multiple brain metastases in non-small cell lung cancer: a multi-center retrospective study · 2026 · DOI

  • There is a lack of research on whether chemotherapy improves survival in elderly LUAD patients with brain metastases. The efficacy of chemotherapy in elderly LUAD patients has been controversial.

    The persistent benefit of chemotherapy in elderly lung adenocarcinoma patients with brain metastases in the immunotherapy era · 2026 · DOI

  • Further studies are needed to confirm the efficacy of 22 Gy SRS in achieving local control of brain metastases. Studies should investigate the long-term outcomes of SRS for brain metastases. Research should focus on optimizing SRS dosing strategies to minimize the risk of radiation necrosis.

    Impact of stereotactic radiosurgery dose on local control and radiation necrosis in metastatic brain lesions: a comparative study · 2026 · DOI

  • The optimal dosing strategies for SRS in the treatment of brain metastases remain unclear. The balance between achieving adequate local control and minimizing the risk of radiation necrosis is complex.

    Impact of stereotactic radiosurgery dose on local control and radiation necrosis in metastatic brain lesions: a comparative study · 2026 · DOI

  • Therapeutic strategies for brain metastases in non-small cell lung cancer are limited and often ineffective.

    The Tumor Microenvironment in Non-Small Cell Lung Cancer Brain Metastases: Composition, Dynamics, and Therapeutic Implications · 2026 · DOI

  • The presentation of neuroendocrine carcinoma as a breast abscess has not previously been reported. Management guidelines for LCNEC remain limited due to the rarity of the disease.

    Metastatic neuroendocrine carcinoma mimicking a breast abscess: a case report · 2026 · DOI

  • The study also notes the difficulty in assessing FEQ status and the need for independent review of images by multiple reviewers.

    Contributions of previous whole-brain radiation therapy, cumulative intracranial tumor volume, and repeat radiosurgery to adverse radiation effects following stereotactic radiosurgery for brain metastasis · 2026 · DOI

  • The study aims to address this gap by investigating these factors and their impact on adverse radiation effects.

    Contributions of previous whole-brain radiation therapy, cumulative intracranial tumor volume, and repeat radiosurgery to adverse radiation effects following stereotactic radiosurgery for brain metastasis · 2026 · DOI

  • Lack of a reliable imaging marker for differentiating tumor recurrence from radiation necrosis. Prior imaging biomarkers have demonstrated poor reproducibility and sensitivity.

    Pathology-validated structural and physiologic habitat imaging for differentiating radiation necrosis from tumor recurrence in brain metastases · 2026 · DOI

  • The previously observed NCF benefit of SRT over WBRT (+/- HA) is better characterized as a delay in NCF decline—both modalities lead to deterioration from baseline over time. Emerging evidence indicates that NCF depends not only on the hippocampus but also on the integrity of key white matter tracts (WMT) that subserve memory, language, executive function, and other cognitive domains.

    Stereotactic radiotherapy for brain metastases: indications, dose fractionation, technological innovations, and evolving combination strategies – a comprehensive review · 2026 · DOI

  • There is a limited regional literature on the MRI characteristics of brain metastases in Iraqi patients. The study aims to provide valuable information regarding the MRI characteristics of brain metastases in this population.

    MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF BRAIN METASTASES IN PATIENTS WITH MALIGNANCY AT AL-THAQALAYN ONCOLOGY HOSPITAL, BASRA, IRAQ · 2026 · DOI

  • Despite these advances, clinical trial eligibility criteria frequently restrict enrolment to patients with “stable”, “treated”, or “asymptomatic” BrM, often without standardised definitions.

    Exclusion of patients with brain metastases from early-phase systemic therapy trials: a cross-sectional analysis of eligibility criteria · 2026 · DOI

Most-cited papers in Brain Metastases and Treatment

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Open questions raised by papers listed on this page include: (1) Future trials must include CNS-specific endpoints, incorporate liquid biopsy and imaging biomarkers, and emphasize preservation of neurocognitive function alongside survival (“Breast cancer brain metastasis: from molecular insights to therapeutic…”, 2026); (2) There is a need for a predictive model to identify high-risk patients (“An interpretable machine learning model for predicting brain metastasis in…”, 2026); (3) The role of FGFR1 in estrogen receptor-positive breast cancer brain metastases is not well understood (“Brain FGF2 and NCAM1 contribute to FGFR1-dependent progression of estrogen…”, 2026); (4) The lack of standardized prognostic indices for patients with brain metastases treated with cranial radiotherapy (“Comparative validation of prognostic indices in brain metastases receiving…”, 2026); (5) 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 (“Clinical Implementation and Oncological Relevance of Molecular Profiling in…”, 2026). 131 gap statements have been mined from Brain Metastases and Treatment papers in our 4.5M-paper local library, which holds 572 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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