Long-term follow-up after surgical removal of meningioma of the inner third of the sphenoidal wing: outcome determinants and different strategies

Meningioma arising in the inner third of the sphenoidal wing has been well recognized since the origin of neurosurgery, yet it still poses a formidable challenge for the surgeon. Treatment strategies can be optimized through a tailored approach to surgical timing and use of a non-surgical armamentarium. The aim of this study was to evaluate the long-term effect of different strategies on progression-free survival and overall survival. We examined the clinical records of brain tumor patients to assess determinants for surgery (extent of tumor removal, postoperative complications) and for progression-free survival and overall survival in relation to timing of surgery eventually followed by stereotactic radiosurgery (SRS). The records of 60 patients were retrospectively reviewed, from preoperative assessment to a median follow-up of 104 months. All were symptomatic with prevalently visual symptoms (42.2%), large tumors (median diameter 3.44 cm), extension into the cavernous sinus (38.3%), and severe vascular involvement of one or more encased or narrowed vessels (50%). Subtotal removal was achieved in 40% of cases, mainly determined by cavernous sinus and vascular involvement; neurological complications occurred in 18.3% (persistent in 6.7% due to oculomotor and vascular injury). The overall rate of symptom improvement was 32.3% at 3 months and 49.5% at 12 months. Radiological monitoring prevented clinical progression; tumor progression occurred in 11.7% of cases. There were significant differences in progression-free survival between patients with (median 46 months) and those without (median 104 months) recurrence (p = 0.002): 12.5% after total removal, 6.2% after subtotal removal and adjuvant SRS, and 28.5% after subtotal removal and observation. The related Kaplan-Meier survival curve showed no significant difference between the three strategies. Further, disease progression after recurrence was noted in 28.6% of cases, but overall survival was not influenced by either tumor recurrence or type of treatment. Treatment failure was recorded in four cases (6.7%): one perioperative death and three later on. Surgery is the mainstay for the treatment of symptomatic meningioma and to restore neurological function; however, resectability is limited by vascular and cavernous sinus involvement. Careful postoperative monitoring prevented clinical progression and adjuvant or adjunctive SRS proved effective in tumor control. A low surgical complication rate and excellent long-term outcomes were achieved with this strategy

miRNAs in serum exosomes for differential diagnosis of brain metastases

Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investigating their role in monitoring the response to therapy as well as the natural evolution of primary or secondary brain tumors. This study aimed to evaluate the modulation of the expression of three miRNAs, miR-21, miR-222 and miR-124-3p, in the serum exosomes of patients with high-grade gliomas (HGGs) and brain metastases (BMs) to verify their usefulness in the differential diagnosis of brain masses; then, it focused on their variations following the surgical and/or radiosurgical treatment of the BMs. A total of 105 patients with BMs from primary lung or breast cancer, or melanoma underwent neurosurgery or radiosurgery treatment, and 91 patients with HGGs were enrolled, along with 30 healthy controls. A significant increase in miR-21 expression in serum exosomes was observed in both HGGs and BMs compared with healthy controls; on the other hand, miR-124-3p was significantly decreased in BMs, and it was increased in HGGs. After the surgical or radiosurgical treatment of patients with BMs, a significant reduction in miR-21 was noted with both types of treatments. This study identified a signature of exosomal miRNAs that could be useful as a noninvasive complementary analysis both in the differential diagnosis of BMs from glial tumors and in providing information on tumor evolution over time

Polymer-coated superparamagnetic iron oxide nanoparticles as T-2 contrast agent for MRI and their uptake in liver

Aim: To study the efficiency of multifunctional polymer-based superparamagnetic iron oxide nanoparticles (bioferrofluids) as a T-2 magnetic resonance contrast agent and their uptake and toxicity in liver. Materials & methods: Mice were intravenously injected with bioferrofluids and Endorem (R). The magnetic resonance efficiency, uptake and in vivo toxicity were investigated by means of magnetic resonance imaging (MRI) and histological techniques. Results: Bioferrofluids are a good T-2 contrast agent with a higher r(2)/r(1) ratio than Endorem. Bioferrofluids have a shorter blood circulation time and persist in liver for longer time period compared with Endorem. Both bioferrofluids and Endorem do not generate any noticeable histological lesions in liver over a period of 60 days post-injection. Conclusion: Our bioferrofluids are powerful diagnostic tool without any observed toxicity over a period of 60 days post-injection. Lay abstract: Several superparamagnetic iron oxide nanoparticles (SPIONs) preparations have been approved by US FDA for clinical use as MRI contrast agents. In recent years, we have been developing a synthetic multifunctional platform for SPIONs based on the use of polymers. In this report, we explored the diagnostic potential of these nanoparticles (herein called bioferrofluids) as an MRI contrast agent and their uptake in liver, without neglecting their toxicological effects. Results show that our bioferrofluids are a good T-2 contrast agent without any observed toxicity in liver

Bioluminescence imaging in brain tumor: a powerful tool

Glioblastoma represents the most malignant and lethal among brain tumours because of its highly infiltration capacity and invasion into the normal brain that account for its resistance to treatments (chemotherapy and radiotherapy). Recent advance and development of technologies to non-invasively image brain tumour growth in living animals can open an opportunity to monitor directly the efficacy of the treatment on tumour development. In vivo bioluminescence imaging is based on light-emitting enzymes, luciferases, which require specific substrates for light production. When linked to a specific biological process/pathway in an animal model of human disease, the enzyme-substrate interactions become biological indicators that can be studied. In order to explore and compare different imaging modalities (MRI and bioluminescence imaging) we have validated the use of bioluminescence imaging to monitor glioblastoma progression in vivo. The human glioma cell line (DBTRG-05MG) derived from an adult patient with glioblastoma multiforme who had been treated with local brain irradiation and multidrug chemotherapy has been used for the experiment. The DBTRG-05MG cell line was stably transfected with TCF-luciferase and orthotopic implantated onto immunodeficient mice. Bioluminescence technology was used to follow tumour growth in parallel with classical MRI on the same animals

Initial clinical experience with frameless optically guided stereotactic radiosurgery/radiotherapy in pediatric patients

The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator. Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1–18 months, with a median follow-up of 6 months. Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3–18 months) with no in-field failures and were able to obtain encouraging toxicity profiles. Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity

Inhibition of tyrosine kinase receptors by SU6668 promotes abnormal stromal development at the periphery of carcinomas

Dynamic contrast-enhanced (albumin-Gd-DTPA) magnetic resonance imaging, performed during 2 weeks of daily administration of an inhibitor of tyrosine kinase receptors (SU6668) in an HT-29 colon carcinoma model, revealed the onset of a hyper-enhancing rim, not observed in untreated tumours. To account for tissue heterogeneity in the quantitative analysis, we segmented tumours into three subunits automatically identified by cluster analysis of the enhancement curves using a k-means algorithm. Transendothelial permeability (Kps) and fractional plasma volume (fPV) were calculated in each subunit. An avascular and necrotic region, an intermediate zone and a well-vascularised periphery were reliably identified. During untreated tumour growth, the identified sub-regions did not substantially change their enhancement pattern. Treatment with SU6668 induced major changes at tumour periphery where a significant increase of Kps and fPV was observed with respect to control tumours. Histology revealed a sub-capsular layer composed of hyper-dense viable tumour cells in the periphery of untreated tumours. The rim of viable neoplastic cells was reduced in treated tumours, and replaced by loose connective tissue characterised by numerous vessels, which explains the observed hyper-enhancement. The present data show a peripheral abnormal development of cancer-associated stroma, indicative of an adaptive response to anti-angiogenic treatment