Intra-operative MRI facilitates tumour resection during trans-sphenoidal surgery for pituitary adenomas

Background During trans-sphenoidal microsurgical resection of pituitary adenomas, the extent of resection may be difficult to assess, especially when extensive suprasellar and parasellar growth has occurred. In this prospective study, we investigated whether intra-operative magnetic resonance imaging (iMRI) can facilitate tumour resection. Methods Twenty patients with macroadenomas, (16 non-functioning, three growth-hormone secreting and one pharmaco-resistant prolactinoma) were selected for surgery in the iMRI. The mean tumour diameter was 27 mm (range 11–41). The mean parasellar grade, according to the Knosp classification, was 2.3. Pre-operative coronal and sagittal T1-weighted and T2-weighted images were obtained. The trans-sphenoidal tumour resection was performed at the edge of the tunnel of a Signa SP 0.5-Tesla MRI. The surgeon aimed at a radical tumour resection that was followed by a peri-operative MRI scan. When a residual tumour was visualised and deemed resectable, an extended resection was performed, followed by another MRI scan. This procedure was repeated until the imaging results were satisfactory. In all patients, we were able to obtain images to assess the extent of resection and to classify the resection as either total or subtotal. Results After primary resection, eight out of 20 cases were classified as total resections. A second resection was performed in 11 of 12 cases classified as subtotal resections, and in four of these, total resection was achieved. A third resection was performed in three of the remaining seven cases with subtotal resections, but we did not achieve total resection in any of these cases. Therefore, the use of iMRI increased the number of patients with total resection from 8/20 (40%) to 12/20 (60%). The only observed complication was a transient spinal fluid leakage. Conclusion Intra-operative MRI during trans-sphenoidal microsurgery is useful in selected patients for a safe and more complete resection. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited

First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59 ± 10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments

Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme

Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan–Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6–16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma

Iodine-125 brachytherapy for brain tumours - a review

Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even though the physical and biological characteristics make these implants particularly attractive for minimal invasive treatment, the place for stereotactic brachytherapy is still poorly defined

Intraoperative magnetic resonance imaging-guided transsphenoidal surgery for giant pituitary adenomas

Giant pituitary adenomas (GPAs), defined as >/=40 mm in one extension, present a challenging subgroup of pituitary adenomas in terms of radical tumor removal and complication rates. The potential impact of intraoperative magnetic resonance imaging (iMRI) is investigated in a consecutive series and the results compared to the literature. From November 2004 until February 2005, six (five male) patients were operated for GPAs via an iMRI-guided transsphenoidal approach in the PoleStar N20. Clinical, endocrinological, and neuroradiological outcomes (at 3 months and yearly postoperative over 4 years) were assessed. Mean age was 46 years (range, 34-60). All patients presented with preoperative visual field defects, five with pituitary failure. Five adenomas were clinically nonfunctioning, one was producing GH and TSH. Preoperative imaging showed invasion of the cavernous sinus in all and extension to the interventricular foramen in two patients (one with occlusive hydrocephalus). Resection was total in four and subtotal (small cavernous sinus remnants) in two patients, leading to transsphenoidal reoperation in one patient. Visual acuity and fields improved in all six patients. The patient with occlusive hydrocephalus developed a postoperative cerebrospinal fluid leak (subsequently revised), two patients developed temporary, one permanent central diabetes insipidus, and one of them transient hyponatremia. Compared to the preoperative situation, endocrine status in the long-term follow-up (mean, 25 months) remained unchanged in four and worsened in two. Two patients were considered not to require hormone replacement therapy. IMRI supports transsphenoidal resections of GPAs because residual adenoma and related risk structures are easily detected and localized intraoperatively, extending the restricted visual access of the microscope beyond mere surface anatomy to a three-dimensional view. More radical removal of adenomas in a single surgical session combined with low complication rates are accomplished. This may add to a favorable clinical and endocrinological outcome in GPAs

Management of Malignant Glioma: Steady Progress With Multimodal Approaches

Despite recent successes in the treatment of cancer with multidisciplinary multimodal treatment approaches, the duration of survival for patients with malignant glioma remains limited. Malignant gliomas represent a class of infiltrative, aggressive neoplasms that are generally resistant to combination therapies. The basic approach to treatment has involved a combination of surgery and radiotherapy. The use of chemotherapy has been met with skepticism because of its limited efficacy and the significant side effects demonstrated in clinical trials. Nevertheless, based on findings in randomized trials of new agents, it has been suggested that further evaluation of the role of chemotherapy is warranted. Temozolomide and Gliadel (carmustine wafers) are generally well tolerated due to their limited systemic toxicity. These agents appear particularly well suited for incorporation into multimodal treatment strategies. Proposed investigations and ongoing clinical trials will be conducted to assess the use of these agents in novel combination therapies. Future treatment strategies may include a wide variety of biological response modifiers, but will need to continue to address local control with surgery, radiation, and adjuvant chemotherapy