Search Results (43)

We report an unusual case of brain radionecrosis following fractionated stereotactic radiotherapy (FSRT) delivered to a calvarial metastasis in a patient with metastatic luminal A breast cancer. A 40-year-old woman developed three subcentimetric brain lesions during follow-up, initially interpreted as new metastases and treated with FSRT. Subsequent radiological progression and advanced imaging suggested radionecrosis, which was confirmed histologically after surgical resection. Retrospective dosimetric analysis revealed that all lesions arose within the high-dose isodose region of the previously irradiated skull metastasis, despite compliance with established brain dose constraints. This case highlights a previously unreported risk of brain radionecrosis after stereotactic irradiation of skull bone metastases and underscores the need for caution in treatment planning and imaging interpretation. Full article

Background: Brain tumors represent a major cause of neurological morbidity and mortality, often requiring radiotherapy as a central component of treatment. While advances in radiation techniques have improved tumor control, increasing attention has been directed toward radiation-induced effects on healthy brain tissue, particularly regarding neuronal function and cognitive outcomes. Objective: This review aims to provide a structured synthesis of current evidence on radiation-induced neuronal dysfunction, integrating dose–volume parameters, neuroimaging biomarkers, and clinical neurological manifestations. Methods: A structured literature review was conducted using electronic databases including PubMed, Scopus, and Web of Science. Relevant studies evaluating dose–volume effects, neuroimaging findings, and clinical outcomes following cranial radiotherapy were included. Results: Dose–volume histogram (DVH) parameters, including mean brain dose and intermediate-dose volumes (V10–V30), as well as hippocampal dose, were identified as key factors associated with cognitive decline and neuronal dysfunction. Conventional MRI detects structural changes such as white matter injury and radionecrosis, while advanced techniques including diffusion tensor imaging (DTI) and functional MRI (fMRI) reveal microstructural damage and network disruption. These imaging findings correlate with a spectrum of clinical manifestations ranging from subtle cognitive impairment to significant neurological deficits. Conclusions: Radiation-induced neuronal dysfunction represents a complex and multifactorial process that extends beyond localized tissue injury. Integrating dose–volume considerations with advanced imaging biomarkers may improve risk stratification and support the development of neuroprotective strategies in patients undergoing cranial radiotherapy. 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

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

Background/Objectives: Despite multimodal therapeutic concepts, treatment of recurrent malignant gliomas remains challenging. Stereotactic radiosurgery (SRS) may be a possible safe and effective non-invasive salvage treatment. In this study, we aim to investigate the SRS treatment outcomes using partly 18F-Fluorethylthyrosine (FET)-PET-imaging sequences for SRS treatment planning focusing on overall survival, event-free survival, and the incidence and factors influencing radiation necrosis (RN) occurrence. Additionally, we evaluated the potential application of AI-based tumor segmentation. Methods: We conducted a retrospective analysis of patients with recurrent malignant glioma treated with single-fraction or hypofractionated SRS at our institution. The outcomes assessed included local control, overall survival (OS), and local event-free survival (LEFS, defined as the interval until tumor recurrence or the onset of RN). We also performed a simulation analysis to assess the potential of AI-based tumor segmentation. Results: The study included 27 patients with a median age of 57 years and 41 lesions. The median OS post-SRS was 9.6 months and an LEFS of 5.2 months. Factors positively influencing OS and LEFS included the gross tumor volume (GTV) of the lesions before SRS therapy, presence of an IDH mutation, and lomustine treatment post-SRS. The incidence of RN post-SRS was 31.7%. RN was confirmed histopathologically in 15.4%, based on MRI in 46.2% and by FET-PET in 38.5% of lesions. In a simulation analysis, AI-based tumor segmentation reliably delineated all lesions, requiring only minimal manual adjustments to define target volumes. Conclusions: High-dose SRS is a feasible salvage treatment for small-volume recurrent high-grade gliomas, achieving local control and survival outcomes comparable to other re-irradiation strategies. IDH mutation, smaller tumor volume, and lomustine therapy were associated with improved survival. RN occurred frequently, particularly in periventricular lesions. AI-based tumor segmentation showed promise in well-defined satellite recurrences, but remains limited in cavity-adjacent lesions, underlining the need for expert review and ¹⁸FET-PET imaging. Full article

Background: Radiation therapy is a key treatment modality for brain metastases. While providing a treatment alternative, post-treatment imaging often presents diagnostic challenges, particularly in distinguishing tumor recurrence from radiation-induced changes such as necrosis. Advanced imaging techniques and artificial intelligence (AI)-based radiomic analyses emerge as alternatives to help lesion characterization. The objective of this study was to assess the capacity of machine learning algorithms to distinguish between brain metastases recurrence and radiation necrosis. Methods: The research was conducted in two phases and used publicly available MRI data from patients treated with Gamma Knife radiosurgery. In the first phase, 30 cases of local recurrence of brain metastases and 30 cases of radiation-induced necrosis were considered. Image segmentation and radiomic feature extraction were performed on these data using MatRadiomics_1_5_3, a MATLAB-based framework integrating PyRadiomics. Features were then selected using point-biserial correlation. In the second phase, a classification was performed using a Support Vector Machine model with repeated stratified cross-validation settings. Results: The results achieved an accuracy on the test set of 83% for distinguishing metastases from necrosis. Conclusions: The results of this feasibility study demonstrate the potential of radiomics and AI to improve diagnostic accuracy and personalized care in neuro-oncology. Full article

To evaluate the factors influencing the outcomes of patients who underwent surgical resection of brain metastasis followed by either surveillance or post-operative stereotactic radiosurgery/fractionated radiotherapy (SRS/SFRT), a retrospective multi-center chart review was performed on all patients who underwent brain metastases resection in British Columbia between 2018 and 2020. Patients with prior whole-brain radiotherapy were excluded from the study. The primary study endpoints included local recurrence, distant intracranial control, radionecrosis (RN), leptomeningeal disease (LMD), and overall survival (OS). The Kaplan–Meier method was used to analyze survival. The Cox proportional hazards model was used to perform univariable (UVA) and multivariable (MVA) analyses to identify predictors of local control. A total of 113 patients met the inclusion criteria. A total of 31 patients received adjuvant SRS/SFRT to the surgical cavity, while 82 went on observation. The 12-month local control was 69% (50–88%) for the SRS/SFRT cohort and 31% (18–45%) for the observation cohort (p < 0.001). The 12-month distant intracranial control was 44% (26–63%) for the SRS/SFRT cohort and 46% (30–62%) for the observation cohort (p = 0.9). Sensitivity analysis did not show a difference in overall survival (p = 0.6). En bloc resection (p < 0.05), resection without residual disease (p < 0.05), and SRS/SFRT (p < 0.001) were predictive of local control on MVA. Three SRS/SFRT patients (10%) and two observation patients (2%) developed LMD. Four SRS/SFRT patients experienced RN (13%), with no grade 3 or higher toxicities observed. Post-operative SRT outcomes based on real-world population data are consistent with the data from clinical trials and support the established guidelines. For patients requiring surgical resection of brain metastasis, en bloc gross total resection should be encouraged when feasible to reduce local recurrence. Full article

Background and Objectives: Brain radionecrosis is an under-recognized but potentially life-altering late complication of radiotherapy in patients with locally advanced nasopharyngeal cancer. Temporal lobe radionecrosis and high-dose exposure to the hippocampus are strongly associated with cognitive decline and radiation-induced dementia, negatively impacting patients’ long-term quality of life (QoL). This study aimed to evaluate and compare radiation dose distributions to critical brain structures across three radiotherapy techniques—3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT)—in order to assess potential neurocognitive risks and support hippocampal-sparing protocols. Materials and Methods: Ten patients previously treated with 3D-CRT were retrospectively replanned using IMRT and VMAT techniques on the Eclipse v13.3 (VARIAN) planning system. Bilateral hippocampi and temporal lobes were delineated as organs at risk (OARs) according to the RTOG atlas, and dosimetric parameters including D_max, D_mean, and D_min were recorded. V7.3 values were evaluated for hippocampal avoidance regions. Results: While IMRT and VMAT provided improved target volume coverage and reduced high-dose exposure to many standard OARs, both techniques were associated with increased D_mean and D_min to the hippocampus and temporal lobes compared to 3D-CRT. The highest D_max values to the temporal lobes were observed in 3D-CRT plans, indicating a potential risk of radionecrosis. VMAT plans showed hippocampal mean doses exceeding 10 Gy in some cases, with V7.3 > 40%, breaching established neurocognitive risk thresholds. Conclusions: These findings support the routine delineation of the hippocampus and temporal lobes as OARs in radiotherapy planning for nasopharyngeal cancer. The implementation of hippocampal-sparing strategies, particularly in IMRT and VMAT, is recommended to reduce the risk of radiation-induced cognitive toxicity and preserve long-term QoL in survivors. Full article

Differentiating tumor progression from radionecrosis in patients with treated brain glioma represents a significant clinical challenge due to overlapping imaging features. This study aimed to develop and evaluate a machine learning model that integrates radiomics features and T2*-weighted Dynamic Susceptibility Contrast MRI perfusion (DSC MRI) parameters to improve diagnostic accuracy in distinguishing these entities. A retrospective cohort of 46 patients (25 with confirmed radionecrosis, 21 with glioma progression) was analyzed. From lesion segmentation on DSC MRI, 851 radiomics features were extracted using PyRadiomics, alongside seven perfusion parameters (e.g., relative cerebral blood volume, time to peak) obtained from time–intensity curves (TICs). These features were combined into a single dataset and 14 classification algorithms were evaluated with GroupKFold cross-validation (k = 4). The top-performing model was selected based on predictive area under the curve (AUC) yield. The Logistic Regression classifier achieved the highest performance, with an AUC of 0.88, followed by multilayer perceptron and AdaBoost with AUC values of 0.85 and 0.79, respectively. The precision values were 72%, 74%, and 78% for the three models, respectively, while the accuracy was 63%, 70%, and 71%. Key predictive variables included radiomics features like wavelet-HHH_firstorder_Mean and mean normalized TIC values. Our combined approach integrating radiomics and DSC MRI parameters shows strong potential for distinguishing radionecrosis from glioma progression. However, further validation with larger cohorts is essential to confirm the generalizability of this approach. Full article

Background: Differentiating brain radionecrosis (RN) from tumor progression (TP) is a persistent clinical difficulty. Here, we compared the diagnostic accuracy of leakage-corrected relative cerebral blood volume (rCBV) and fluid-suppressed amide proton transfer-weighted (APTw) imaging in distinguishing between RN and TP in metastases. Methods: Subjects with enlarging lesions after stereotactic radiosurgery were prospectively examined at 3T. APTw data were acquired with a 3D snapshot-gradient echo sequence. B0 and B1 inhomogeneities were corrected using the WASAB1 protocol. rCBV was calculated according to established guidelines. Image analysis was performed using Olea Sphere 3.0 software. ΔAPTw and ΔrCBV were calculated as the average signal within the lesion normalized against the average signal in the contralateral white matter. A diagnosis of TP or RN was assessed by histology or imaging at follow-up. Independent samples t-tests of ΔAPTw and ΔrCBV and the areas under the curve (AUCs) were computed. Results: Twenty-one metastases (10 RN, 11 TP) were evaluated. APTw differentiated between RN and TP (U = 120, p < 0.001), in contrast to rCBV (U = 71, p = 0.174). The AUC was 0.991 (95% CI = 0.962–1.020) for ΔAPTw, and 0.636 (95% CI = 0.352–0.921) for ΔrCBV. The optimal cutoff points were 0.4 and 2.1 for ΔAPTw and ΔrCBV, respectively. The sensitivity and specificity for RN-TP were 100% and 90% for ΔAPTw and 63.6% and 36.4% for ΔrCBV. Conclusions: Fluid-suppressed APTw metrics enabled more accurate diagnostic performances than leakage-corrected rCBV metrics in distinguishing between RN and TP. These promising results suggest that APTw imaging could valuably complement current multiparametric MRI protocols in brain metastases follow-ups. Full article

Background/Objectives: Determining whether 3,4-dihydroxy-6-[¹⁸F]fluoro-L-phenylalanine positron emission tomography/computed tomography ([¹⁸F]F-DOPA PET/CT) data indicate brain metastasis progression (MP) or brain radionecrosis (RN) is challenging. The aim of this study was to present a method usable in the clinical setting without dedicated software that relies on less than five minutes of SiPM PET/CT data collected immediately after [¹⁸F]F-DOPA injection. Methods: We prospectively enrolled 15 patients with 19 lesions. Each acquisition was conducted in list mode (LM) for 25 min using a four-ring SiPM PET/CT system. We reconstructed three volumes from the LM file: acquisition duration of 120 s (V120), 270 s (V270), and 10 min for the standard clinical volume (Vclin). We measured each lesion’s maximum voxel activity (LS_max) and the corresponding mean activity with its standard deviation (CL_mean, CL_sd). We then calculated the LS_max/CL_mean ratio and the coefficient of variation (COV), defined as 100 × (CL_sd/CL_mean). Results: Lesions were classified as RN (n = 7) and MP (n = 12). For all volumes, LS_max/CL_mean differed significantly. The COV parameter exhibited significant differences in all comparisons except for V120 vs. V270. The best diagnostic performances were observed for V120 and V270, with an accuracy of 94.7%. The AUC values were 97.6% in both cases. Conclusions: A simple, static [¹⁸F]F-DOPA PET/CT acquisition, starting 1.5 min after injection and lasting less than five minutes, permitted reaching excellent diagnostic performance (100% sensitivity, 91.7% specificity, and 97.6% AUC) in discriminating between RN and MP. Full article

Background/Objectives: 5-aminulevulinic acid (5-ALA)-guided surgery for high-grade gliomas remains a challenge in neuro-oncological surgery. Inconsistent fluorescence visualisation, subjective quantification and false negatives due to blood, haemostatic agents or optical impediments from the external light source are some of the limitations of the present technology. Methods: The preliminary results from this single-centre retrospective study are presented from the first 35 patients operated upon with the novel Nico Myriad Spectra System©. The microdebrider (Myriad) with an additional in situ light system (Spectra) can alternately provide white and blue light (405 nm) to within 15 mm of the tissue surface to enhance the morphology of the anatomical structures and the fluorescence of the pathological tissues. Results: A total of 35 patients were operated upon with this new technology. Eight patients (22.85%) underwent tubular retractor-assisted minimally invasive parafascicular surgery (tr-MIPS). The majority had high-grade gliomas (68.57%). Fluorescence was identified in 30 cases (85.71%), with residual fluorescence in 11 (36.66%). The main applications were better white–blue light alternation and visualisation during tr-MIPS, increase in the extent of resection at the border of the cavity, identification of satellite lesions in multifocal pathology, the differentiation between radionecrosis and tumour recurrence in redo surgery and the demarcation between normal ependyma versus pathological ependyma in tumours infiltrating the subventricular zone. Conclusions: This proof-of-concept study confirms that the novel in situ light-source delivery technology integrated with the usual intraoperative armamentarium provides a spatially, functionally and oncologically informed framework for glioblastoma surgery. It allows for the enhancement of the morphology of anatomical structures and the fluorescence of pathological tissues, increasing the extent of resection and, possibly, the prognosis for patients with high-grade gliomas. Full article

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with a median overall survival (OS) of 15–18 months despite standard treatments. Approximately 8% of GBM cases exhibit genomic alterations in fibroblast growth factor receptors (FGFRs), particularly FGFR1 and FGFR3. Next-generation sequencing techniques have identified various FGFR3 fusions in GBM. This report presents a novel FGFR3 fusion with fatty acid synthase (FASN) in a 41-year-old male diagnosed with GBM. The patient presented with a persistent headache, and imaging revealed a right frontal lobe lesion. Surgical resection and subsequent histopathology confirmed GBM. Initial NGS analysis showed no mutations in the IDH1, IDH2 or H3F3 genes, but revealed a TERT promoter mutation and CDKN2A/2B and PTEN deletions. Postoperative treatment included radiotherapy and temozolomide. Despite initial management, recurrence occurred four months post-diagnosis, confirmed by MRI and histology. A second surgery identified a novel FGFR3-FASN fusion, alongside increased Ki67 expression. The recurrence was managed with regorafenib and bevacizumab, though complications like hand–foot syndrome and radiation necrosis arose. Despite initial improvement, the patient died 15 months after diagnosis. This case underscores the importance of understanding GBM’s molecular landscape for effective treatment strategies. The novel FGFR3-FASN fusion suggests potential implications for GBM recurrence and lipid metabolism. Further studies are warranted to explore FGFR3-FASN’s role in GBM and its therapeutic targeting. Full article

Background: Glioblastoma is the most common malignant brain tumor in adults. Even after maximal safe resection and adjuvant chemoradiotherapy, patients normally relapse after a few years or even months. Standard treatment for recurrent glioblastoma is not yet defined, with re-resection, re-irradiation, and systemic therapy playing key roles. Usually, re-irradiation is combined with concurrent chemotherapy, harnessing the radiosensitizing effects of alkylating agents. Methods: A retrospective analysis of 101 patients with recurrent glioblastoma treated with re-irradiation was conducted, evaluating the survival impact of concurrent chemotherapy regimens, as well as prior resection. Patients were subcategorized according to concurrent chemotherapy (temozolomide vs. CCNU vs. combination of both vs. none) and details are given regarding treatment toxicity and patterns of relapse after first- and second-line treatment. Results: Patients were treated with normo-fractionated re-irradiation (with prescription dose of ~40 Gy to the PTV), resulting in a moderate cumulative EQD2 (~100 Gy). The mean overall survival was 11.3 months (33.5 months from initial diagnosis) and mean progression free survival was 9.5 months. Prior resection resulted in increased survival (p < 0.001), especially when gross total resection was achieved. Patients who received concurrent chemotherapy had significantly longer survival vs. no chemotherapy (p < 0.01), with the combination of CCNU and TMZ achieving the best results. Overall survival was significantly better in patients who received the CCNU + TMZ combination at any time during treatment (first or second line) vs. monotherapy only. The treatment of larger volumes (mean PTV size = 112.7 cm³) was safe and did not result in worse prognosis or increased demand for corticosteroids. Overall, the incidence of high-grade toxicity or sequential radionecrosis (5%) was reasonably low and treatment was tolerated well. While second-line chemotherapy did not seem to influence patterns of relapse, patients who received TMZ + CCNU as first-line treatment had a tendency towards better local control with more out-field recurrence. Conclusions: Normo-fractionated re-irradiation appears to be safe and is accompanied by good survival outcomes, even when applied to larger treatment volumes. Patients amenable to undergo re-resection and achieving concurrent systemic therapy with alkylating agents had better OS, especially when gross total resection was possible. Based on existing data and experiences reflected in this analysis, we advocate for a multimodal approach to recurrent glioblastoma with maximal safe re-resection and adjuvant second chemoradiation. The combination of TMZ and CCNU for patients with methylated MGMT promoter yielded the best results in the primary and recurrent situation (together with re-RT). Normo-fractionated RT enables the use of more generous margins and is tolerated well. Full article

Brain metastases or primary brain tumours had poor prognosis until the use of high dose radiotherapy. However, radionecrosis is a complex challenge in the post-radiotherapy management of these patients due to the difficulty of distinguishing this complication from local tumour recurrence. MRI alone has a variable specificity and sensibility, as does PET-CT imaging. We aimed to investigate the diagnostic performance of dual-phase ¹⁸F-FDG PET-mpMRI to distinguish cerebral radionecrosis from local tumour recurrence after cranial radiotherapy. A retrospective analysis was conducted between May 2021 and September 2022. Inclusion criteria encompassed patients with inconclusive MRI findings post-radiotherapy and history of cerebral radiotherapy for primary or metastatic brain lesions. Lesions are assessed qualitatively and semi-quantitatively. The gold standard to assess radionecrosis was histopathology or a composite criterion at three months. The study evaluated 24 lesions in 23 patients. Qualitative analysis yielded 85.7% sensitivity and 75% specificity. Semi-quantitative analysis, based on contralateral background noise, achieved 100% sensitivity and 50% specificity. Moreover, using contralateral frontal lobe background noise resulted in higher performances with 92% sensitivity and 63% specificity. Stratification by lesion type demonstrated 100% sensitivity and specificity rates for metastatic lesions. The diagnostic performance of dual-phase ¹⁸F-FDG PET-mpMRI shows promising results for metastatic lesions. Full article