26 – 28 April 2018
Skull base meningioma
Meningiomas of the floor of the middle fossa are uncommon and tend to grow quite large before diagnosis.
Efforts to achieve a radical resection with dural margin are not suitable in many cases of skull base meningiomas, because of the neurovascular structures around the tumors.
Gamma knife radiosurgery (GKRS) is well established in the management of inaccessible, recurrent, or residual benign skull base meningiomas. Most series report clinical outcome parameters and complications in the short intermediate period after radiosurgery.
GKRS offers a highly durable rate of tumor control for World Health Organization grade 1 meningioma, with an acceptably low incidence of neurological deficits. The Karnofsky Performance Scale at the time of radiosurgery serves as a reliable long-term predictor of overall outcome 1).
Peritumoral edema (PTE) in skull base meningiomas correlates to the absence of an arachnoid plane and difference in outcome.
A subset of benign (WHO grade I) skull base meningiomas show early progression/recurrence (P/R) in the first years after surgical resection.
Ko et al. retrospectively investigated the preoperative CT and MR imaging features for the prediction of P/R in skull base meningiomas, with emphasis on quantitative ADC values. Only patients had postoperative MRI follow-ups for more than 1 year (at least every 6 months) were included. From October 2006 to December 2015, total 73 patients diagnosed with benign (WHO grade I) skull base meningiomas were included (median follow-up time 41 months), and 17 (23.3%) patients had P/R (median time to P/R 28 months). Skull base meningiomas with spheno-orbital location, adjacent bone invasion, high DWI, and lower ADC value/ratio were significantly associated with P/R (P < 0.05). The cut-off points of ADC value and ADC ratio for prediction of P/R are 0.83 × 10- 3 mm2/s and 1.09 respectively, with excellent area under curve (AUC) values (0.86 and 0.91) (P < 0.05). In multivariate logistic regression, low ADC values (< 0.83 × 10- 3 mm2/s) and adjacent bone invasion are high-risk factors of P/R (P < 0.05), with odds ratios of 31.53 and 17.59 respectively. The preoperative CT and MRI features for prediction of P/R offered clinically vital information for the planning of treatment in skull base meningiomas 2).
From a prospectively maintained database of 2022 meningioma patients who underwent Leksell stereotactic radiosurgery (SRS) during a 30-year interval, we found 98 patients with petroclival, 242 with cavernous sinus, and 55 patients with cerebellopontine angle meningiomas. Primary radiosurgery was performed in 245 patients. Patients included in this report had at least one CN deficit at the time of initial presentation and a minimum of 12 month follow up. Median age at the time of SRS was 58 years. Median follow up was 58 months (range 12-300 months), Median tumor volume treated with SRS was 5.9 cm3 (range 0.5-37.5 cm3), and median margin dose was 13 Gy (range 9-20Gy).
Tumor control was achieved in 229 patients (93.5%) at a median follow up of 58 months. Progression free survival rate (PFS) after SRS was 98.7% at 1 year, 96.4% at 3 years, 93.7% at 5 years, and 86.4% at 10 years Overall, 114 of the 245 patients (46.5%) reported improvement of CN function. Patients with CP angle meningiomas demonstrated lower rates of CN improvement compared to petroclival and cavernous sinus meningioma patients. Deterioration of CN function after SRS developed in 24 patients (10%). The rate of deterioration was 2.8% at 1 year, 5.2% at 3 years, and 8% at 10 years.
Primary SRS provides effective tumor control and favorable rate of improvement of preexisting CN deficit 3).
Fourty-six patients harboring a skull base meningioma underwent an endoscope-assisted microsurgical resection. In 30 patients (65%), tumor parts which could not be visualized under the microscope were detected with the endoscope. In 26 patients (56%), these tumor remnants were removed under endoscopic view. Gross total resection was achieved in 35 patients (76%) and near-total resection in 11 (24%). There was no surgical mortality. The major complication was new cranial nerve deficit. The application of endoscopes was most useful in the small supraorbital craniotomies to look under the ipsilateral optic nerve and internal carotid artery as well as to visualize the diaphragm sellae and olfactory groove. In the retrosigmoid craniotomies, the endoscope was beneficial to inspect the internal auditory canal, to look into Meckel’s cave, or to inspect areas hidden behind the jugular tubercle and tentorial edge. There was no obvious complication related to the application of the endoscope. Endoscope assistance is particularly of value when skull base meningiomas are to be removed via small craniotomies to inspect blind corners which cannot be visualized in a straight line with the microscope. In addition, there is a benefit of using endoscopes with various angles of view in standard craniotomies and skull base approaches to look around bony and dural corners or to look behind neurovascular structures, by which the amount of skull base drilling and retraction to expose the tumor can be reduced 4).
GKRS plays a significant role in the treatment of non-functioning [NFA] and hormonal-active [HAA] pituitary adenoma. It affords high rate of tumor control and offers low risk of collateral neurological or endocrine axis injury. A study showed that control of tumor growth was achieved in 90% patients, shrinkage of tumor in 54% and arrest of progression in 36% cases after GKRS treatment. The biochemical remission rate in GH secreting adenoma was 57%, ACTH adenoma was 67% and prolactinoma was 40%. Age less than 50 years and tumor volume less than 5cm3 were associated with a favourable radiosurgical outcome 2).
Radiotherapy as an alternative and adjuvant treatment for prolactinomas has been performed at the Department of Radiation Oncology, Prince of Wales Cancer Centre, Sydney, New South Wales, Australia, with the linear accelerator since 1990.
In a retrospective review of 13 patients managed with stereotactic radiosurgery (SRS) and 5 managed with fractionated stereotactic radiotherapy (FSRT), as well as 5 managed with conventional radiotherapy, at the Prince of Wales Hospital. Patients with a histopathologically diagnosed prolactinoma were eligible. Those patients who had a confirmed pathological diagnosis of prolactinoma following surgical intervention, a prolactin level elevated above 500 μg/L, or a prolactin level persistently elevated above 200 μg/L with exclusion of other causes were represented in this review.
At the end of documented follow-up (SRS median 6 years, FSRT median 2 years), no SRS patients showed an increase in tumour volume. After FSRT, 1 patient showed an increase in size, 2 showed a decrease in size and 2 patients showed no change. Prolactin levels trended towards improvement after SRS and FSRT, but no patients achieved the remission level of <20 μg/L. Seven of 13 patients in the SRS group achieved a level of <500 μg/L, whereas no patients reached this target after FSRT.
A reduction in prolactin level is frequent after SRS and FSRT for prolactinomas; however, true biochemical remission is uncommon. Tumour volume control in this series was excellent, but this may be related to the natural history of the disease. Morbidity and mortality after stereotactic radiation were very low in this series 3).
Cohen-Inbar et al., reviewed the outcome of patients with medically and surgically refractory prolactinomas treated with Gamma Knife radiosurgery (GKRS) during a 22 years follow-up period.
They reviewed the patient database at the University of Virginia Gamma Knife center during a 25-year period (1989-2014), identifying 38 patients having neurosurgical, radiological and endocrine follow-up.
Median age at GKRS treatment was 43 years. Median follow-up was 42.3 months (range 6-207.9). 55.3 % (n = 21) were taking a dopamine agonist at time of GKRS. 63.2 % (n = 24) had cavernous sinus tumor invasion. Endocrine remission (normal serum prolactin off of a dopamine agonist) was achieved in 50 % (n = 19). GKRS induced hypopituitarism occurred in 30.3 % (n = 10). Cavernous sinus involvement was shown to be a significant negative prognosticator of endocrine remission. Taking a dopamine agonist drug at the time of GKRS showed a tendency to decrease the probability for endocrine remission.
GKRS for refractory prolactinomas can lead to endocrine remission in many patients. Hypopituitarism is the most common side effect of GKRS 4).
evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm3 (range 0.3–11.6). The marginal tumor dose (median= 15 Gy, range 12–25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12–185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined asa decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six(27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging-defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy 5).
Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%).
Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most 6).
Twenty patients with prolactinomas were followed after GKS. Five patients were treated successfully; their prolactin (PRL) levels dropped into the normal range and dopaminergic drugs could be discontinued. Two spontaneous pregnancies were observed and 11 patients experienced improvement. Improvement was defined as normal PRL levels with the continued possibility of reduced medical treatment or a substantially reduced medical treatment dose with some degree of hyperprolactinemia maintained. The treatment failed in three patients who experienced no improvement. Patients treated with dopaminergic drugs during GKS did significantly less well in comparison with the untreated group when a cumulative distribution function (Kaplan-Meier estimate) was used. CONCLUSIONS:
The results of GKS for prolactinomas in this investigation are better than the results published by others. This may be an effect of case selection because there were no “salvage cases” in our group of patients. Because a dopamine agonist seemed to induce radioprotection in this series, it is suggested that GKS be performed during an intermission in drug therapy when the dopamine agonist is discontinued 7).
In hemophilia A and von Willebrand disease, it should only be used for mild to moderate cases.
It may be given in the nose, by injection into a vein, by mouth, or under the tongue.
More potent and longer acting than vasopressin.
A synthetic analogue of antidiuretic hormone (ADH), desmopressin is available in subcutaneous, IV, intranasal, and oral preparations.
Generally, it can be administered 2-3 times per day. Patients may require hospitalization to establish fluid needs. Frequent electrolyte monitoring is recommended during the initial phase of treatment.
Alternatives to desmopressin as pharmacologic therapy for DI include synthetic vasopressin and the nonhormonal agents chlorpropamide, carbamazepine, clofibrate (no longer on the US market), thiazides, and nonsteroidal anti-inflammatory drugs (NSAIDs). Because of side effects, carbamazepine is rarely used, being employed only when all other measures prove unsatisfactory. NSAIDs (eg, indomethacin) may be used in nephrogenic DI, but only when no better options exist. In central DI, the primary problem is a hormone deficiency; therefore, physiologic replacement with desmopressin is usually effective. Use a nonhormonal drug for central DI if response is incomplete or desmopressin is too expensive.
They performed an observational cohort study of patients enrolled in the Columbia University SAH Outcome Project between August 1996 and July 2015. They compared the rate of rebleeding between patients who were and those who were not treated with DDAVP. After adjustment for known predictors, logistic regression was used to measure the association between treatment with DDAVP and risks of rebleeding.
Among 1639 patients with SAH, 12% were treated with DDAVP. The main indication for treatment was suspected exposure to an antiplatelet agent. The overall incidence of rebleeding was 9% (1% among patients treated with DDAVP compared with 8% among those not treated). After adjustment for antiplatelet use and known predictors, treatment with DDAVP was associated with a 45% reduction in the risks of rebleeding (adjusted OR 0.55, 95% CI 0.27-0.97). DDAVP was associated with a higher incidence of hyponatremia but not with thrombotic events or delayed cerebral ischemia.
Treatment with DDAVP was associated with a lower risk of rebleeding among patients with SAH. These findings support further study of DDAVP as first-line therapy for medical hemostasis in patients with SAH 1).
Bilateral inferior petrosal sinus sampling (IPSS) with desmopressin is a sensitive approach in the diagnosis of Cushing’s disease (CD) and has moderate accuracy in tumour lateralization, making it an alternative choice to IPSS with CRH 3).
Endoscopic and Keyhole Cranial Base Surgery
by James J. Evans and Tyler J. Kenning
17 – 19 January 2018