Novel strategies in glioblastoma surgery aim at safe, supra-maximum resection in conjunction with local therapies.

The biggest challenge in neuro-oncology is the treatment of glioblastoma, which exhibits poor prognosis and is increasing in incidence in an increasing aging population. Diverse treatment strategies aim at maximum cytoreduction and ensuring good quality of life. We discuss multimodal neuronavigation, supra-maximum tumor resection, and the postoperative treatment gap. Multimodal neuronavigation allows the integration of preoperative anatomic and functional data with intraoperative information. This approach includes functional magnetic resonance imaging (MRI) and diffusion tensor imaging in preplanning and ultrasound, computed tomography (CT), MRI and direct (sub)cortical stimulation during surgery. The practice of awake craniotomy decreases postoperative neurologic deficits, and an extensive supra-maximum resection appears to be feasible, even in eloquent areas of the brain. Intraoperative MRI- and fluorescence-guided surgery assist in achieving this goal of supra-maximum resection and have been the subject of an increasing number of reports. Photodynamic therapy and local chemotherapy are properly positioned to bridge the gap between surgery and chemoradiotherapy. The photosensitizer used in fluorescence-guided surgery persists in the remaining peripheral tumor extensions. Additionally, blinded randomized clinical trials showed firm evidence of extra cytoreduction by local chemotherapy in the tumor cavity. The cutting-edge promise is gene therapy although both the delivery and efficacy of the numerous transgenes remain under investigation. Issues such as the choice of (cell) vector, the choice of therapeutic transgene, the optimal route of administration, and biosafety need to be addressed in a systematic way. In this selective review, we present various evidence and promises to improve survival of glioblastoma patients by supra-maximum cytoreduction via local procedures while minimizing the risk of new neurologic deficit.

What intervention is best practice for vestibular schwannomas? A systematic review of controlled studies.

OBJECTIVE: Largely, watchful waiting is the initial policy for patients with small-sized or medium-sized vestibular schwannoma, because of slow growth and relatively minor complaints, that do not improve by an intervention. If intervention (microsurgery, radiosurgery or fractionated radiotherapy) becomes necessary, the choice of intervention appears to be driven by the patient's or clinician's preference rather than by evidence based. This study addresses the existing evidence based on controlled studies of these interventions. DESIGN: A systematic Boolean search was performed focused on controlled intervention studies. The quality of the retrieved studies was assessed based on the Sign-50 criteria on cohort studies. DATA SOURCES: Pubmed/Medline, Embase, Cochrane Central Register of Controlled Trials and reference lists. STUDY SELECTION: Six eligibility criteria included a controlled intervention study on a newly diagnosed solitary, vestibular schwannoma reporting on clinical outcomes. Two prospective and four retrospective observational, controlled studies published before November 2011 were selected. DATA ANALYSIS: Two reviewers independently assessed the methodological quality of the studies and extracted the outcome data using predefined formats. RESULTS: Neither randomised studies, nor controlled studies on fractionated radiotherapy were retrieved. Six studies compared radiosurgery and microsurgery in a controlled way. All but one were confined to solitary tumours less than 30 mm in diameter and had no earlier interventions. Four studies qualified for trustworthy conclusions. Among all four, radiosurgery showed the best outcomes: there were no direct mortality, no surgical or anaesthesiological complications, but better facial nerve outcome, better preservation of useful hearing and better quality of life. CONCLUSIONS: The available evidence indicates radiosurgery to be the best practice for solitary vestibular schwannomas up to 30 mm in cisternal diameter.

Primary radiotherapy in progressive optic nerve sheath meningiomas: a long-term follow-up study.

BACKGROUND/AIMS To report the outcome of primary radiotherapy in patients with progressive optic nerve sheath meningioma (ONSM). METHODS The clinical records of all patients were reviewed in a retrospective, observational, multicentre study. RESULTS Thirty-four consecutive patients were included. Twenty-six women and eight men received conventional or stereotactic fractionated radiotherapy, and were followed for a median 58 (range 51-156) months. Fourteen eyes (41%) showed improved visual acuity of at least two lines on the Snellen chart. In 17 (50%) eyes, the vision stabilised, while deterioration was noted in three eyes (9%). The visual outcome was not associated with age at the time of radiotherapy (p=0.83), sex (p=0.43), visual acuity at the time of presentation (p=0.22) or type of radiotherapy (p=0.35). Optic disc swelling was associated with improved visual acuity (p<0.01) and 4/11 patients with optic atrophy also showed improvement. Long-term complications were dry eyes in five patients, cataracts in three, and mild radiation retinopathy in four. CONCLUSION Primary radiotherapy for patients with ONSM is associated with long-term improvement of visual acuity and few adverse effects.

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma.

UNLABELLED: Therapy using the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) has been used primarily in gastroenteropancreatic neuroendocrine tumors. Here we present the effects of this therapy in a small number of patients with metastasized or inoperable paragangliomas, meningiomas, small cell lung carcinomas (SCLCs), and melanomas. METHODS: Twelve patients with paraganglioma, 5 with meningioma, 3 with SCLC, and 2 with eye melanoma were treated. Three meningiomas were very large and exophytic and all standard treatments had failed. Patients with melanoma had rapidly progressive disease (PD). The intended cumulative dose of 177Lu-octreotate was 22.2-29.6 GBq. Effects of the treatment on tumor size were evaluated using the Southwest Oncology Group criteria. RESULTS: Two of 4 patients with progressive paraganglioma had tumor regression and 1 had stable disease (SD). Of 5 patients with stable paraganglioma, 2 had SD, 2 had PD, and in 1 patient treatment outcome could not be determined. Paraganglioma was stable in 3 patients in whom the disease status at the beginning of therapy was unknown. One of 4 patients with progressive meningioma had SD and 3 patients had PD. One patient with stable meningioma at the beginning of therapy had SD. All patients with SCLC or melanoma died within 5 mo after starting therapy because of tumor progression. Although not statistically significant, a positive trend was found between high uptake on pretherapy somatostatin receptor scintigraphy and treatment outcome. CONCLUSION: 177Lu-octreotate can be effective in patients with paraganglioma and meningioma. Response rates are lower than those in patients with gastroenteropancreatic neuroendocrine tumors. Most meningiomas were very large. Further studies are needed to confirm the treatment outcome because of the limited number of patients. 177Lu-octreotate did not have antitumor effects in patients with small lung carcinoma and melanoma.