Search Results (75)

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

Objective: The prognosis of patients with advanced melanoma remains poor, particularly in those with brain metastases. To date, no standardized later-line treatment regimen has been established for this patient population. This study aimed to explore prognostic factors in patients with advanced melanoma and brain metastases, with a specific focus on the prognostic significance of baseline lactate dehydrogenase (LDH) levels and cranial radiotherapy. Materials and Methods: This retrospective cohort study consecutively enrolled 145 patients diagnosed with melanoma brain metastases (MBM) between 1 December 2015 and 31 August 2024. Baseline LDH data were available for 139 patients (95.9%), while the remaining six cases were excluded from LDH-stratified analyses. Patients were divided into an elevated LDH group (>250 U/L) and a normal LDH group (≤250 U/L). Collected clinical variables included brain intensity-modulated radiotherapy (IMRT), systemic treatment strategies (immunotherapy, targeted therapy, and chemotherapy), the number of prior treatment lines, and neurological symptoms at diagnosis. The completeness of all other clinical variables reached 100%. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS). All statistical analyses were conducted using SPSS 21.0. Results: The median OS of the entire cohort was 6.7 months (range: 0.4–101.0 months). Multivariate Cox regression identified three independent protective factors for superior OS and PFS: brain IMRT administration (OS: HR = 0.565, 95% CI: 0.365–0.874, p = 0.010; PFS: HR = 0.623, 95% CI: 0.420–0.924, p = 0.019), normal baseline LDH (OS: HR = 2.091, 95% CI: 1.425–3.069, p < 0.001; PFS: HR = 1.456, 95% CI: 1.023–2.071, p = 0.037), and ≤3 prior lines of systemic therapy before MBM diagnosis (OS: HR = 0.853, p = 0.004; PFS: HR = 1.679, p = 0.015). Moreover, the absence of neurological symptoms at baseline was an independent favorable prognostic factor for OS (HR = 1.919, p = 0.001) but not for PFS. Patients with normal LDH combined with brain IMRT exhibited the best OS and PFS outcomes (p < 0.001). Conclusions: Baseline LDH level and cranial radiotherapy are robust independent prognostic indicators for survival in MBM patients. More prior treatment lines and the presence of neurological symptoms correlate with inferior clinical outcomes. These findings provide evidence for clinical risk stratification and individualized treatment decision-making for this high-risk and challenging population. Full article

Metastatic melanoma is one of the most common malignancies associated with the spread of the primary tumor. The primary site is usually the skin or the eyes. The most frequent site of metastases is the gastrointestinal tract, accounting for 60% of cases at autopsy. In 2% of patients, metastases occur without a detectable primary tumor. We present a rare case of upper digestive bleeding caused by multiple gastrointestinal tract metastases from an amelanotic melanoma. This case report describes a 65-year-old male who arrived at the emergency department after experiencing an episode of upper gastrointestinal bleeding (melena). One week prior to admission, he had been treated with nonsteroidal anti-inflammatory drugs for lower back pain due to L4–L5 disc herniation. Upper digestive endoscopy revealed multiple polypoid masses in the stomach and duodenum, and capsule endoscopy showed additional lesions in the small bowel. Histopathological examination confirmed the diagnosis: metastases from an amelanotic malignant melanoma. Abdominal and cranial computed tomography scans revealed multiple secondary lesions in the brain, gallbladder, retroperitoneal area, gastrointestinal tract, and peritoneum. Localized radiotherapy was applied to the cerebral metastasis, and systemic chemotherapy with dacarbazine was initiated, resulting in a partial clinical response. Unfortunately, the disease progressed, and the patient died one month after diagnosis. Metastatic melanoma of the gastrointestinal tract is an exceedingly rare cause of upper digestive bleeding. Full article

Background: Schwannomas of the third cranial nerve are exceedingly rare benign tumors, and standardized management guidelines are lacking. Their close relationship with critical neurovascular structures makes diagnosis and treatment challenging, with a significant risk of postoperative neurological deficits. Methods: A systematic review of the literature was conducted according to the PRISMA guidelines, including case reports and clinical studies on oculomotor nerve schwannomas (ONSs). Demographic data, clinical presentation, tumor location, diagnostic methods, treatment strategies, and functional outcomes were analyzed. In addition, an illustrative case treated with a multimodal approach is presented. Results: Ninety-six cases met the inclusion criteria. The mean age at diagnosis was 34 years, with a slight female predominance. The most common presenting symptoms were diplopia and ptosis. Contrast-enhanced magnetic resonance imaging was the diagnostic modality of choice. Surgical resection was the primary treatment in most cases but was associated with worsening oculomotor nerve function in 43.1% of surgically treated patients. Stereotactic radiotherapy demonstrated favorable tumor control with lower neurological morbidity. In the presented case, subtotal resection followed by stereotactic radiotherapy resulted in sustained tumor stability at the one-year follow-up. Conclusions: Management of oculomotor nerve schwannomas should be individualized. For small or mildly symptomatic lesions, stereotactic radiotherapy appears to be an effective and less invasive option, while surgery should be reserved for large tumors causing a mass effect or progressive neurological deterioration. Full article

Radiation-induced brain injury (RBI) is a severe complication of cranial radiotherapy that poses a significant clinical challenge due to a lack of effective treatments. Ferroptosis, an oxidative stress-driven cell death pathway, has been implicated in its pathogenesis. Here, we report that 75% ethanol (GBF-8), a novel subfraction isolated from male Ginkgo biloba flowers, confers significant protection against RBI. In a murine RBI model, GBF-8 administration restored cognitive function and alleviated neuroinflammation. We demonstrated that this neuroprotective effect is mechanistically linked to ferroptosis inhibition. Integrated proteomic and metabolomic profiling identified the Solute carrier family 7 member 11 (Slc7a11)–Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (Eif4ebp1) axis as the primary target of GBF-8. This work not only establishes GBF-8 as a promising therapeutic candidate but also delineates a previously unrecognized regulatory axis for combating ferroptosis in RBI. Full article

Small cell lung cancer (SCLC) is an aggressive malignancy with a high incidence of brain metastases. Prophylactic cranial irradiation (PCI) was developed to reduce central nervous system (CNS) relapses and has been shown to improve survival, particularly in limited-stage disease. The pivotal Auperin meta-analysis and subsequent studies confirmed its role in patients achieving a complete response to initial therapy. In extensive-stage SCLC, earlier trials demonstrated reduced brain metastases and modest survival gains, but more recent studies incorporating routine magnetic resonance imaging (MRI) surveillance failed to show overall survival benefits, supporting MRI monitoring with salvage therapy as an alternative. Neurocognitive toxicity remains the major limitation of PCI, especially in older adults. Common effects include memory impairment, cognitive changes, and a reduced quality of life. Advances such as hippocampal avoidance PCI and neuroprotective strategies like memantine have shown the ability to mitigate long-term decline. Modern radiotherapy techniques, including intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), enable the precise sparing of critical structures while maintaining intracranial control. The integration of immunotherapy has shifted treatment paradigms in SCLC. While checkpoint inhibitors have improved systemic outcomes, their impact on brain relapses and interactions with PCI remain uncertain. This review provides an overview of the evolution of PCI in SCLC, while emphasizing current challenges and future directions. Full article

Acute lymphoblastic leukemia (ALL) remains the most frequent pediatric malignancy, accounting for approximately 34% of all pediatric cancers, with remarkable improvements in survival (approximately 85%) due to advances in chemotherapy, radiotherapy, and supportive care. However, as survival rates have increased, new challenges have emerged—particularly the growing prevalence of obesity and metabolic syndrome among survivors. This review compiles evidence from the past decade on the relationship between leukemia treatment, obesity, and metabolic risk. The findings indicate that cranial radiotherapy, corticosteroid use, and younger age at diagnosis are key risk factors for excessive weight gain and long-term metabolic disturbances. Genetic factors such as FTO, MC4R, and LEPR polymorphisms may further influence susceptibility to obesity. Nutritional analyses highlight poor diet quality, insufficient micronutrient intake, and high-fat, energy-dense dietary patterns in survivors. Beyond endocrine dysfunction, obesity and metabolic syndrome are associated with elevated cardiovascular morbidity and reduced quality of life. Personalized medicine approaches—integrating genomics, metabolomics, and lifestyle data—hold promise for targeted prevention and intervention strategies. Early detection, continuous metabolic monitoring, and health education remain essential components in the long-term management of childhood leukemia survivors. In this review, we analyzed the dietary patterns of children and long-term leukemia survivors explaining why higher rates of obesity and comorbidities appear during or after treatments, and discussed interventions to prevent these conditions. Full article

Stereotactic body radiotherapy (SBRT) has been increasingly used in dogs for mediastinal tumors and is generally considered a precise and relatively safe treatment, with clinically significant complications reported only rarely. A cranial mediastinal mass was incidentally identified in a 10-year-old Pomeranian dog and cytologically diagnosed as a carcinoma. SBRT was performed using volumetric-modulated arc therapy, with a total dose of 27 Gy delivered in three fractions on alternate days. One day after completing treatment, the dog developed acute dyspnea and anemia. Thoracic radiography revealed mediastinal widening and pleural effusion. Subsequent imaging and hematological assessments suggested intra-tumoral hemorrhage and hematoma formation. The patient was managed conservatively with supportive therapy, resulting in gradual clinical improvement. Follow-up computed tomography (CT) demonstrated a 25% reduction in contrast-enhancing tumor volume, accompanied by a large non-enhancing region presumed to represent hematoma. Despite these changes, the patient remained clinically stable during follow-up. This case represents the first documented report of an acute hemorrhagic complication following SBRT in a veterinary patient, emphasizing the importance of awareness of this rare adverse event during treatment planning and client communication. Full article

Background: Vitamin A deficiency (VAD) can occur due to malnutrition or reduced intestinal absorption, such as in short bowel syndrome (SBS). The main causes of SBS in adults include post-radiotherapy and surgery (e.g., repeated bowel resections). VAD mostly involves rods producing nyctalopia and reduced amplitudes of the electroretinogram (ERG) in scotopic conditions, with a characteristic negative ERG pattern (b/a < 1). Case Report: We report a 67-year-old woman with a history of gastric adenocarcinoma and several surgeries, who developed a progressive 3-month clinical picture of night blindness. Results: Urgent blood tests, biomicroscopy, intraocular pressure measurements, fundoscopy, and a cranial MRI were all normal. Visual evoked potentials showed increased latencies in both eyes, and full-field ERG showed a significant alteration in responses under scotopic conditions, and, to a lesser extent, under photopic conditions. Laboratory tests confirmed VAD, probably due to post-surgery and radiotherapy SBS. After parenteral vitamin replacement, VAD was clinically, analytically, and electroretinographically resolved. Discussion: VAD diagnosis is based on history, neuro-ophthalmological examination, and serum levels of retinol (<0.3 µg/mL) and/or retinol/retinol-binding protein (<0.8). In cases of a history of SBS, acquired nyctalopia, negative ERG, and clinical, analytical, and electroretinographic improvement with restoration of vitamin A levels, VAD should be suspected. ERG is crucial for early and appropriate management. Conclusions: As far as we know, this is the first reported VAD case secondary to SBS following surgical resections and radiotherapy of gastric adenocarcinoma with neuro-ophthalmological, laboratory, and electroretinographic monitoring of VAD recovery. Full article

Introduction: Tympanojugular paragangliomas (TJ-PGs) showing intradural growth into the cerebellopontine angle (Fisch classification Di) represent a surgical challenge, with their proper surgical management still under debate. Methods: This is an international multicenter retrospective review of patients with Di TJ-PGs who underwent surgery in three high-volume skull base surgery centers. We aimed to establish practice patterns for treating Di TJ-PGs, namely the surgical approach, total versus partial resection, and whether a staged procedure was needed. We also examined the status of the facial and lower cranial nerves (LCNs), postoperative complications, and residue management after partial resection. Results: Thirty-two patients were included in this study with an average follow-up of 66 months. Preoperative angiography with selective embolization was performed in all patients, and a type A infratemporal fossa approach was the most common surgical technique. Total resection was achieved in 16 cases. A single-stage procedure was performed in 26 patients and a staged procedure in 6. CSF leakage in the neck was the main reported complication. Most patients had an HB I-II-grade facial nerve at the last follow-up, and three patients experienced worsened lower cranial neuropathies. In 16 patients residual disease was present after surgery and was managed with either radiotherapy or observation. Conclusions: Di TJ-PGs pose a complex treatment challenge for which clear-cut management recommendations have not been established. Surgical resection, when indicated, may be total, the preferred option in young healthy candidates, or partial, mainly employed in elderly or high-risk patients, always considering the tumor’s relationship to critical structures. When residual tumor is present, both radiological surveillance and adjuvant radiotherapy can be effective strategies. Full article

Background/Objectives: Non-small-cell lung cancer (NSCLC) frequently metastasizes to the brain, significantly impacting patient prognosis and quality of life. Anlotinib, a novel tyrosine kinase inhibitor, has shown promise in treating NSCLC with brain metastasis. So, we aimed to evaluate the clinical efficacy of anlotinib and various types of radiotherapy combinations used to treat NSCLC patients with brain metastasis regarding overall survival and the treatment of internal and external lesions. Methods: A comprehensive literature search was conducted in the databases PubMed, Scopus, WoS, MedLine, and Cochrane Library up to April 2024. Studies assessing the efficacy of anlotinib combined with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or other radiotherapy modalities in NSCLC patients with brain metastasis were included. The primary outcomes were (a) the efficacy of anlotinib and radiotherapy on the intracranial lesions and OS and (b) the effectiveness of combined anlotinib and radiotherapy versus radiotherapy alone in NSCLC patients with brain metastasis. The secondary outcome was the efficacy of anlotinib and radiotherapy on extracranial progression. We used a combination of keywords and MeSH terms including ‘non-small cell lung cancer’ OR ‘NSCLC’, ‘brain metastases’, ‘anlotinib’, ‘radiotherapy’, ‘radiation therapy’, and ‘combined treatment’, among others. Boolean operators (AND, OR) were applied as appropriate to optimize the search strategy across databases. Results: Nine studies met the inclusion criteria, comprising 210 patients in the combination group and 228 patients in the radiotherapy alone group. The combination of anlotinib with radiotherapy showed a significant improvement in iPFS compared to radiotherapy alone, with a pooled risk ratio (RR) for iORR of 1.18 (95% CI: 1.00–1.39) and a pooled SMD for OS of 0.03 (95% CI: −0.29, 0.36). Radiotherapy combined with anlotinib also demonstrated enhanced intracranial and extracranial control rates. Conclusions: Anlotinib combined with radiotherapy, especially WBRT, offers a promising treatment strategy for NSCLC patients with brain metastasis, improving intracranial control. Further large-scale randomized controlled trials are needed to confirm these findings and optimize treatment protocols. Full article

Malignant Triton Tumors (MTTs) are rare, high-grade malignant peripheral nerve sheath tumors (MPNSTs) frequently associated with Type 1 Neurofibromatosis (NF1). NF1, an autosomal dominant disorder, predisposes approximately 10% of affected individuals to developing MPNSTs, with 50% of these tumors occurring in NF1 patients, while others arise sporadically or in association with radiation exposure. MTTs predominantly affect anatomical regions rich in large nerves, such as the limbs, spinal root, and cranial nerves. Mediastinal presentations are exceedingly rare, posing significant diagnostic and therapeutic challenges. Current treatment strategies include surgical resection, chemotherapy, radiotherapy, and lung-sparing procedures for metastatic disease. Molecular studies of MPNSTs have revealed that NF1 mutations lead to dysregulation of the RAS signalling pathway, while epigenetic alterations (e.g., SUZ12/EED mutations) further contribute to tumor progression. Dysregulated phylogenetically conserved pathways, including Wnt/beta-catenin and non-canonical SHH signalling, play a role in sarcoma progression and Schwann cell transformation. Recent advances in miRNA research highlight their involvement in tumor invasion and progression, with dysregulated miRNA expression and chromatin remodeling contributing to the pathogenesis of these neoplasms. However, the distinct molecular profiles for MTTs remain incompletely understood. Further investigation of the genetic and epigenetic landscape is essential for improving our understanding and identifying potential therapies. Herein, we present a single-center retrospective case series of three patients with an intrathoracic triton tumor treated at our University Hospital between 2000 and 2024, serving as a starting point for future insights into MPNST pathobiology. Full article

Glioblastoma (GBM) remains a challenging cancer to treat with limited effective therapies. Standard treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, offer marginal survival benefits but are often limited by side effects and drug resistance. Temozolomide is the most commonly used chemotherapy; however, resistance and lack of efficacy in recurrent GBM hinder its success. Tumor treating fields (TTFields), a novel non-invasive modality that utilizes alternating electric fields, have recently emerged as a promising treatment for GBM. TTFields work by disrupting the function of the mitotic spindle and inducing apoptosis in cancer cells. They can be especially effective when combined with other therapies. TTFields enhance drug delivery when paired with chemotherapy by increasing the permeability of the blood–brain barrier and cell membranes, leading to more effective tumor inhibition. Similarly, TTFields increase cancer cell sensitivity to radiation therapy and improve the efficacy of targeted therapies, such as sorafenib and immunotherapy, particularly in extra-cranial tumors. The Optune device, the primary medical device for TTFields’ delivery, offers a convenient and versatile treatment option, allowing remote care and exhibiting fewer adverse effects. This review discusses the potential of TTFields as a valuable addition to GBM treatment, particularly in combination therapies, and highlights the device’s clinical applications. Full article

Background/Objectives: Resection of tumors invading the cavernous sinus (CS) carries a risk of injury to the cranial nerves and internal carotid artery. Therefore, radical surgery involving lesions around the CS remains challenging, especially for lesions invading the CS, optic sheath, and oculomotor cave. Here, we describe a surgical strategy for meningiomas invading these structures and report on the clinical outcomes. Methods: Surgical resection was indicated in patients with neurological symptoms or rapid tumor growth for the restoration of cranial nerve function. We investigated 13 patients who had preoperative images of CS invasion, underwent surgical resection, and were followed-up with magnetic resonance imaging for at least 1 year between July 2017 and July 2024. Their preoperative symptoms, postoperative course, adjuvant therapy, postoperative complications, degree of resection, and recurrence were evaluated. Results: The mean patient age was 59.1 years (range, 23–73 years), and 10 were female. Major preoperative symptoms included oculomotor nerve paresis in 8 patients (61.5%), abducens nerve paresis in 6 (46.2%), visual disturbance in 7 (53.8%), and brain swelling in 3 (23.1%). These symptoms improved at least partially after surgery in 7 (87.5%), 5 (83.3%), 7 (100%), and 3 (100%) patients, respectively. Major postoperative complications included contralateral visual deterioration in 1 patient (7.7%) and brief transient slight hemiparesis caused by internal carotid vasospasm or dissection in 2 (15.4%). Four patients with residual atypical meningioma in the CS underwent intensity-modulated radiotherapy (IMRT). The lesions in 6 patients recurred or regrew, resulting in additional treatment with stereotactic radiosurgery in 2 patients, IMRT in 3, and resection in 1. Conclusions: Our surgical strategy for the surgical resection of meningiomas in and around the CS for the restoration of cranial nerve function is safe and effective, with only transient acceptable injuries. Even if the tumor in the CS is too stiff to be removed, it is important to open the optic nerve sheath and oculomotor cave widely to effectively remove the tumor. Full article

Background/Objectives. Adult medulloblastoma (AMB) patients should receive postoperative craniospinal irradiation (CSI) as a standard treatment. Volumetric intensity-modulated arc therapy (VMAT) is a promising method for CSI. This report summarizes the repositioning and dosimetric data outcomes for six AMB patients. Methods. Complete CSI and posterior cranial fossa irradiation, or tumor bed boost irradiation with Linac-based VMAT, was performed and evaluated. Patients were immobilized in the supine position with two thermoplastic masks (head-neck and abdomen). To ensure inter-fraction reproducibility during radiotherapy (RT), a single cone-beam CT (CBCT) scan for each isocenter and real-time surface-guided RT using AlignRT^® were performed daily before and during the RT session. Match values of all three translational axes (x = lateral, y = longitudinal, z = vertical) were recorded. Results. From August 2022 to September 2023, six AMB patients were treated with CSI: three women and three men with a median age of 32 (22–42). All cases were classical MB, four were low risk, and two were defined as high risk due to the metastatic disease. All patients underwent surgery; two received a gross total resection. Low-risk patients received 36 Gy for CSI and a 54 Gy boost, while high-risk patients received 39 Gy for CSI. No significant toxicities greater than G2 were observed during RT, and only two cases reported decreased platelet counts. The dose to the organs at risk was low and acceptable. The mean dose to the heart, lungs, eyes, stomach, and thyroid were 4.4 Gy, 8.5 Gy, 12 Gy, 8.7 Gy, and 11 Gy, respectively. In terms of repositioning data, 124 CBCT scans were analyzed. Inter-fraction CBCT mean values for the study population in all translational directions were inferior to 2 mm in more than 90% of cases. Conclusions. VMAT is a convenient and effective treatment for AMB. Positioning and immobilization with masks (head and neck plus abdomen) reduce inter-fraction motion. Full article