Search Results (69)

As survival for cancer patients improves, the incidence of brain metastases has risen. This is likely due to improved systemic disease control, increased diligence in surveillance imaging in high-risk pathologies, improved neuro-imaging techniques and increased systemic screening for clinical trial enrollment. While there are well-established treatments for brain metastases, many patients will experience recurrence after definitive treatment. The management of these recurrent lesions is not well established and often varies on a per-patient basis, owing to the clinical complexity and variety of these patients. Patients with recurrent brain metastases have surgical procedural options to achieve local tumor control, including laser interstitial thermal therapy (LITT) repeat open surgical resection with or without placement of intracavity brachytherapy. Repeat resection can offer rapid improvement in neurological symptoms, performance status, and potentially survival. LITT is less invasive than a standard craniotomy but offers a chance at directed local treatment while still obtaining tissue for diagnostic purposes and achieving acceptable survival outcomes. Further study is needed to determine the role of LITT for recurrent brain metastases, but it is a useful tool, particularly for patients with deep-seated lesions who may not tolerate a large surgery. Intracavitary brachytherapy allows for the immediate delivery of highly conformal radiation to the surgical bed with excellent local control and low rates of radiation necrosis, even in previously irradiated patients. The decision regarding which of the above to employ for recurrent brain metastases will vary on a case-by-case basis, and further studies are needed to standardize their use for this growing problem. Full article

Background: Radiomic analysis enables quantitative characterization of post-radiotherapy brain lesions beyond conventional imaging. However, the longitudinal behavior of radiomic features, particularly across different MRI scanners, remains insufficiently explored. This pilot study aimed to explore the longitudinal evolution of radiomic features in radiation-induced necrosis following radiotherapy for brain metastases by comparing trajectories obtained from MRI follow-up performed on the same scanner with follow-up acquired across different scanners. Methods: This retrospective pilot study included 40 radiation necrosis lesions divided into a same-scanner cohort (20 lesions) and a mixed-scanner cohort (20 lesions). Each lesion underwent three sequential post-contrast T1-weighted MRI examinations, resulting in 120 longitudinal lesion-level observations. Images underwent standardized preprocessing, three-dimensional lesion segmentation, and radiomic feature extraction. Feature robustness to segmentation variability was assessed using the coefficient of variation and intraclass correlation coefficient, and only robust features were retained. Longitudinal coherence was evaluated using the Δ-feature metric quantifying longitudinal variability. Results: Seventy-six of 107 radiomic features (71%) were robust to segmentation perturbations. Substantial longitudinal variability was observed even in the same-scanner cohort. Shape features demonstrated lower longitudinal variability, whereas texture-based features showed descriptively higher variability in the mixed-scanner cohort. However, these differences were not statistically significant after false discovery rate correction. Conclusions: This pilot study highlights the importance of validating longitudinal radiomic feature stability before interpreting temporal radiomic changes as biological phenomena or incorporating radiomic biomarkers into clinical decision-support models. Full article

Headache is a frequent and clinically relevant symptom in patients undergoing cranial radiotherapy, most often reflecting treatment-induced structural and inflammatory changes such as cerebral edema or radiation-related brain injury. Differentiating secondary headache from primary disorders, particularly migraine, is essential for appropriate management. This review aims to examine the pathophysiological mechanisms underlying headache following cranial radiotherapy, evaluate current pharmacological and complementary treatment strategies and highlight key aspects of differential diagnosis with migraine. Unlike existing literature that focuses primarily on radiological findings of radiation injury, this review adopts a symptom-driven approach, reframing headache as a critical clinical gateway for the early detection of structural complications. A structured narrative review of the literature was conducted using PubMed/MEDLINE, Scopus and Google Scholar to identify studies published between 2020 and 2025, focusing on cerebral edema, radiation-related complications, therapeutic approaches and migraine. Relevant clinical trials, systematic reviews and guidelines were included. Cerebral edema consistently emerges as the main mechanism of acute and subacute post-radiotherapy headache, whereas late-onset symptoms are most often linked to radiation necrosis. Corticosteroids remain first-line therapy, while bevacizumab has demonstrated benefit in steroid-refractory cerebral edema and radiation necrosis through inhibition of vascular endothelial growth factor (VEGF), thereby reducing vascular permeability and attenuating peritumoral edema. Its use in the context of cranial radiotherapy requires careful consideration, as the safety of concomitant administration with radiation has not been formally established, and headache itself is among its recognized adverse effects. Evidence for complementary therapies, including Boswellia serrata and plant-based compounds, remains limited. Migraine constitutes a distinct neurovascular disorder requiring careful differentiation from secondary headache in oncological patients. The review emphasizes headache as a clinically relevant indicator of underlying structural complications rather than an isolated symptom. Post-radiotherapy headache should be interpreted as a manifestation of underlying structural pathology. Accurate etiological diagnosis and individualized management are essential. Further research is needed to refine treatment strategies and clarify the role of complementary therapies. Full article

Background: Surgical resection remains the standard treatment for large brain metastases (LBMs), but many patients are not surgical candidates due to poor performance status or uncontrolled systemic disease. Gamma Knife-based hypofractionated stereotactic radiotherapy (GKRS) has emerged as a potential alternative; however, its clinical role in this population remains insufficiently defined. We evaluated whether a uniform daily 5-fraction GKRS provides effective and safe local treatment for surgery-ineligible LBMs. Methods: We retrospectively analyzed 100 patients with LBMs (>14 cm³) who underwent primary hypofractionated GKRS using a uniform daily 5-fraction schedule. Forty-six patients were male; the median age was 60 years. The median Karnofsky Performance Status (KPS) was 70 (60–100); a total of 47 patients (47%) had pre-GKRS neurological deficits. The most common primary sites were lung (41), breast (24), and kidney (14). The median tumor volume was 22.0 cm³ (14–70 cm³), and the marginal dose was 35.2 Gy (50% isodose line) in 5 fractions. The primary endpoints included local tumor control (LTC), intracranial progression-free survival (PFS), and overall survival (OS). Radiation necrosis (RN) was assessed as a key safety outcome. Results: At a median follow-up of 18 months, the overall LTC rate was 74%, with 1-, 2-, and 3-year rates of 73%, 65%, and 60%, respectively. Median PFS and OS were 7.5 and 16.3 months. Higher pre-treatment KPS and absence of neurological deficits were independently associated with improved OS (p = 0.003 and 0.025, respectively). RN occurred in 16% of patients, with 9% developing symptoms; all symptomatic cases were effectively managed with corticosteroids or bevacizumab. Most tumors demonstrated substantial volumetric reduction, with a median decrease of 80% and 30% achieving near-complete response (>95%). Conclusions: A uniform daily 5-fraction hypofractionated GKRS provides effective local control with acceptable toxicity in patients with LBMs. These findings support its role as a feasible local treatment option in selected patients who are not candidates for surgery. Integration with systemic therapies and prospective validation are warranted to refine patient selection and optimize outcomes. Full article

Brain metastases are the third most common metastatic site in melanoma patients, with 40% of melanoma patients developing melanoma brain metastasis (MBM). Symptomology of MBM ranges from headaches, neurological deficits, cognitive changes, and seizures, resulting from MBM embedding in areas of highest blood flow following the breakdown of the blood–brain barrier (BBB) via genetic, cytokine, and molecular processes. The BBB is highly restrictive, making MBM difficult to treat. Challenges in MBM treatment are evident in adverse therapeutic effects, such as neurocognitive decline with whole-brain radiation therapy (WBRT), increased risk of radiation necrosis with stereotactic radiosurgery (SRS), and reduced penetration into the brain, which can lead to drug resistance with prolonged use of MAPK inhibitors. This review investigates current and novel treatments against MBM, including radiotherapy, chemotherapy, targeted therapies such as BRAF/MAPK inhibitors, and immunotherapy. Full article

Background: Radiotherapy is essential for skull base tumor management but carries the risk of radiation-induced brain injury (RIBI). This spectrum ranges from transient radiation-induced contrast enhancement (RICE) to irreversible necrosis. Distinguishing these entities from tumor progression is critical, particularly with the increasing adoption of proton therapy. Methods: A comprehensive narrative review of the peer-reviewed literature was conducted up to October 1, 2025. The search strategy focused on adult patients treated for skull base malignancies, synthesizing data on dose–volume metrics, incidence rates, and modality-specific toxicity profiles. Results: RIBI represents a pathophysiological continuum. (a) Descriptive imaging patterns: In prospective proton therapy series, focal RICE occured in 15% of patients, typically at a median of 12 months, and often resolved spontaneously. (b) Modality comparison: Although proton therapy reduces integral brain dose versus photon therapy, elevated linear energy transfer (LET) at the distal Bragg peak may contribute to focal radiation-associated image changes (RAIC), particularly in the temporal lobes. (c) Risk stratification and diagnosis: Risk increased when >1% of the healthy brain received >57.6 Gy (Relative Biological Energy (RBE)) or when V67Gy exceeded 0.17 cc. Advanced MRI and amino acid positron emission tomography (PET) improved differentiation between radiation effects and tumor recurrence. Conclusions: Post-radiation imaging changes are common and often benign. Distinguishing RICE from progression requires multimodal imaging and adherence to specific dose constraints. Management should prioritize surveillance for asymptomatic lesions. Full article

Background: Brain radiation necrosis is a side effect of radiotherapy that can occur months, or even years, after the end of treatment. From an anatomical–pathological perspective, it is characterized by avascular damage, demyelination, and necrosis. Methods: We present a case of a patient with breast cancer cT2N1M0 and multiple brain metastases occurring at 2 years after diagnosis, who was treated with whole-brain radiotherapy (WBRT) and Stereotactic Radiotherapy (SRT) for tumor progression. Dynamic imaging revealed right parietal post-therapeutic changes in aggravation, requiring differential diagnosis between tumor progression (TP) and brain radionecrosis (BRN). Results: Brain radionecrosis and tumor progression are difficult to differentiate due to their similar radiological and clinical characteristics. MRI perfusion plays an important role in differentiating the two entities. Conclusions: Differentiating radiation necrosis from a recurrent tumor is crucial for appropriate treatment. Medical management includes corticosteroids as first-line treatment, after which bevacizumab is administered as secondary therapy. Full article

Background and Objectives: Cerebral radiation necrosis (CRN) is a delayed complication of radiation therapy (RT), that can appear either as radiological findings without clinical symptoms (i.e., asymptomatic CRN) or symptomatic CRN (sCRN). There is currently a knowledge gap regarding CRN-induced epilepsy, a potentially severe manifestation of sCRN. We aim to give a comprehensive overview of the existing literature on CRN-induced epilepsy, including its prevalence, potential risk factors, and treatment options. Materials and Methods: A scoping analysis was performed according to the PRISMA scoping review guidelines. We searched within PubMed and Embase databases and identified relevant clinical studies for inclusion related to CRN-induced epilepsy, based on predefined criteria. Results: In total, 24 studies were identified. CRN-induced epilepsy was a primary outcome in three studies. In the 21 remaining studies, epilepsy was an exploratory outcome or described as part of a small case series. The studies covered various topics in relation to CRN-induced epilepsy, such as the overall clinical manifestations of CRN, the optimization of RT practices to minimize toxicity and improve outcomes, and the effectiveness of laser interstitial thermal therapy (LITT) and bevacizumab. Considerable heterogeneity was seen across studies, particularly concerning the primary tumor types, used definition of CRN and applied RT practices. Conclusions: Epilepsy is a serious clinical symptom in patients with sCRN. However, the current literature is too limited to draw meaningful conclusions regarding its prevalence, risk factors and management. Future research in patients with sCRN should prioritize the evaluation of clinical response to different treatment strategies with particular attention to seizure control. Full article

Background: Radiation-induced cystic brain necrosis (RCN) can progress rapidly to life-threatening cerebral herniation. This study aimed to develop a predictive model integrating radiomic features and clinical variables to assess the risk of cerebral herniation in RCN patients. Methods: A total of 130 patients diagnosed with RCN following radiotherapy for nasopharyngeal carcinoma were retrospectively enrolled and randomly assigned to training (n = 91) and testing (n = 39) cohorts in a 7:3 ratio. Radiomic features were extracted from baseline T2-weighted magnetic resonance imaging (MRI), and a radiomic signature was constructed using least absolute shrinkage and selection operator regression. A multivariate Cox regression model was then developed by incorporating the radiomic signature and clinical variables to predict cerebral herniation. The model’s discriminative ability, calibration, and clinical utility were evaluated. Results: The radiomic signature based on five selected radiomic features demonstrated good predictive performance. The radiomic model, which integrated the radiomic signature and ratios of perilesional enhancement, exhibited favorable performance in both the training cohort (C-index: 0.841) and testing cohort (C-index: 0.867). The model successfully stratified patients into high- and low-risk groups. The calibration curves showed good agreement and the decision curve confirmed the clinical utility of the model. Conclusions: The MRI-based radiomic model, which integrates radiomic features and clinical variables, demonstrates robust performance in predicting cerebral herniation in RCN patients, offering a practical and user-friendly tool to support clinical decision-making. Full article

Background: Glioblastoma (GBM) is a lethal, highly invasive, and recurrent brain tumor. Standard treatment combines maximal surgical resection, radiation, and chemotherapy; however, such approaches are often infeasible for tumors in eloquent brain regions. Objective: Histotripsy is a noninvasive, nonthermal ultrasound-based mechanical ablation modality that employs focused acoustic energy for targeted tissue destruction. This study aimed to investigate the feasibility, safety, and therapeutic effect of a one-time transcranial histotripsy treatment in a pre-clinical murine GBM model. Methods: GL261 GBM cells were orthotopically implanted into C56BL/6 mouse brains. Transcranial histotripsy was performed using a stereotactically guided 2 MHz transducer targeting either lower (25%) or higher (75%) tumor volume, with 5 or 10 pulses per location (PPL) administered. Tumor growth and cerebral injury were monitored with weekly magnetic resonance imaging (MRI) following treatment. At the study endpoint, hematoxylin and eosin (H&E) histology assessed residual tumor burden and histotripsy-induced tissue changes. Results: Mice receiving 5 PPL high-percent treatment (>30 sites) showed a statistically significant median survival extension of 5 days (18.5%) compared to untreated controls. MRI demonstrated marked tumor volume reduction in the high-percent treatment group at week 4, while H&E confirmed increased tumor necrosis and cellular damage in the treated cohort. Conclusions: Single-session, incisionless transcranial histotripsy was well tolerated and conferred mild yet meaningful survival advantages in this GBM model. These results support ongoing exploration of histotripsy, alone or in combination with existing therapies, for safe and effective treatment of challenging brain tumors. Full article

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and poor survival outcomes. This study evaluated the anticancer potential of seco-duocarmycin SA (seco-DSA), a potent DNA-alkylating agent, alone and in combination with proton radiation in human GBM cell lines. Human glioblastoma cell lines T98G and LN18 were treated with varying concentrations of seco-DSA, proton radiation doses (2, 4, or 8 Gy), or both. Proton irradiation was delivered with a 250-MeV beam. Clonogenic survival, cell proliferation, and cell cycle distribution were analyzed using colony formation and flow cytometry assays. Proteomic analysis of LN18 cells was performed by LC-MS/MS followed by bioinformatic pathway analysis. Statistical significance was determined using a two-tailed unpaired t-test (p ≤ 0.05), and Bliss synergy scores were calculated to assess treatment interactions. Combination therapy produced additive and synergistic inhibition of colony formation and enhanced G2/M phase arrest compared with either treatment alone. Apoptosis and necrosis increased modestly but did not fully account for observed cytotoxicity. Proteomic profiling revealed differential expression of proteins involved in DNA repair, apoptosis, and senescence, indicating that seco-DSA broadened radiation-induced stress responses. Seco-DSA potentiates the cytotoxic effects of proton radiation in GBM cells through enhanced clonogenic inhibition and modulation of cell cycle and DNA repair pathways. These findings support seco-DSA as a promising radiosensitizer for further preclinical evaluation. Full article

Brain metastases have a distinctive vascular ecosystem—shaped by sprouting angiogenesis, vessel co-option, vasculogenic mimicry, and tumor cell transdifferentiation—that governs tumor perfusion, drug exposure, and therapeutic responsiveness. These heterogeneous vascularization patterns exhibit characteristic differences in enhancement morphology, perfusion levels, and metabolic uptake on contrast-enhanced MRI, perfusion imaging, and amino acid PET, providing crucial imaging cues for identifying routes of blood supply, inferring the state of the blood–tumor barrier, and guiding individualized therapeutic strategies. Anti-VEGF therapy is primarily used to alleviate cerebral edema and radiation necrosis, yet it confers limited survival benefit, underscoring the spatiotemporal heterogeneity of the blood–tumor barrier and the persistence of non-classical vascularization pathways. Building on the concept of “vascular normalization,” combinations of anti-angiogenic therapy with immunotherapy, radiotherapy, or targeted agents have shown encouraging intracranial activity in selected settings—most robustly in melanoma brain metastases—but remain insufficiently validated in randomized, brain-metastasis-focused trials. By integrating mechanistic, imaging, and therapeutic perspectives, this review outlines how vascular-ecosystem-based stratification and physics-informed drug-delivery strategies may help transition anti-vascular therapy from symptomatic control toward mechanism-driven precision intervention. Full article

Introduction: Intracranial stereotactic radiosurgery (SRS) is a specialised radiotherapy technique that plays an essential role in achieving local control of brain metastases and therefore optimising quality of life for many cancer patients. It also confers a survival benefit in selected patients. Rural and regional Australians may face significant challenges in accessing this treatment, as it is predominantly delivered at metropolitan institutions. We sought to assess the cost-effectiveness of a brain SRS service implemented using local resources at a North Queensland regional hospital from a societal perspective. Methods: We prospectively collected treatment costs and clinical outcomes for a consecutive cohort of patients who received SRS for intracranial metastatic lesions at a regional cancer centre since the implementation of the brain SRS program in September 2022. We compared the healthcare and non-healthcare costs (e.g., travel and informal care) with the costs that would have otherwise been incurred if patients were referred to metropolitan centres in the state capital. Clinical outcomes incorporated overall survival, intracranial disease control rates, and incidence of radiation necrosis. Clinical outcome data of the metropolitan centres were derived from the published literature. Results: A total of 34 patients received treatment during the study period. Their median age was 65 years (range: 49–78 years). Around 47% received adjuvant SRS following surgical resection, and the remaining 53% were treated for intact brain metastases. The predominant primary malignancy was non-small cell lung cancer. The mean total cost per course of brain SRS at a regional hospital was AUD 6690, including AUD 5754 for healthcare and AUD 1682 for non-healthcare costs, across 34 patients recruited between September 2022 and August 2024. This was AUD 760 less than that of a course of treatment delivered at a metropolitan hospital. Median survival among the cohort was 15.7 months, and eight patients (24%) developed radionecrosis; these were comparable to published data reported by Australian urban and international institutions. Conclusions: The implementation of a brain SRS service at regional cancer centres utilising existing infrastructure and local expertise has the potential to offer cost-effective treatment to rural and regional cancer patients. This approach improves access for patients who might otherwise face logistics barriers and competing life priorities when seeking treatment in metropolitan centres. Full article

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, has a median survival of 14–15 months despite aggressive treatment. Monitoring relies on MRI, but differentiating tumor progression from pseudo-progression or radiation necrosis remains difficult. Plasma extracellular vesicles (EVs) are emerging as promising non-invasive biomarkers due to their molecular cargos and accessibility. This review evaluates studies that specifically isolated plasma EVs for molecular profiling in GBM diagnosis and monitoring. Biomarkers (miRNA, RNA, DNA, proteins), EV characterization methods, and advancements in enriching tumor-derived EV subpopulations and assessing their diagnostic and prognostic potential are highlighted. Plasma EVs carry diverse cargos, including miRNAs (e.g., miR-21, miR-15b-3p), mRNAs (e.g., EGFRvIII), circRNAs, and proteins (e.g., CD44, GFAP). Composite molecular signatures have achieved sensitivities of 87–100% and specificities of 73–100% for GBM diagnosis. Tumor-derived EVs, enriched using techniques like SEC-CD44 immunoprecipitation, microfluidic platforms, or 5-ALA-induced PpIX fluorescence, enhance biomarker detection. Non-tumor-derived EVs may also reflect GBM’s systemic effects. Challenges include EV heterogeneity, non-EV contamination, and variable biomarker expression across studies. Plasma-EV-based liquid biopsies offer significant potential for GBM monitoring, with advanced enrichment methods improving tumor-specific biomarker detection. Standardizing isolation protocols and validating biomarkers in larger cohorts are critical for clinical translation. Full article