Epithelial Growth Factor Receptor Inhibitors for treatment of recurrent or progressive high grade glioma: an exploratory study.

INTRODUCTION: Erlotinib and Gefitinib (EGFRi) are small molecules specifically inhibiting epidermal growth factor receptor (EGFR). We present here data of an exploratory study evaluating EGFRi monotherapy in patients with recurrent or progressive malignant glioma. PATIENTS: 21 patients with recurrent or progressive malignant glioma were included in this study. EGFRi treatment was started at a median of 1.8 years (range 0.54 to 10.95) after initial surgery. 20/21 patients had undergone radiotherapy and all patients had received at least one (range 1 to 5, median 2) line of systemic antineoplastic therapy. Patients received 100 or 150 mg Erlotinib or 250 mg Gefitinib orally per day. RESULTS: Median age at primary diagnosis was 47.9 years (range 31.9 to 76 years). 18 patients received a total of 92.8 months (median 3.03) of Erlotinib treatment and 3 patients received a total of 16.1 months (median 6.06) of Gefitinib treatment. The best responses were partial remission in one patient receiving Erlotinib and in two patients receiving Gefitinib, respectively. Median time to progression was 3.05 months. Six months after start of EGFRi treatment, 4/21 (19%) patients were progression-free and 6/21(29%) patients were alive. Expression of EGFRwt, EGFRvIII, PTEN, phospho-Akt or EGFRvIII/PTEN co-expression in tumor cells did not significantly associate with time to progression or survival time. In one patient EGFRi administration had to be discontinued due to toxicity (grade 3 rash). CONCLUSION: EGFRi monotherapy is associated with therapeutic efficacy in only a small fraction of patients with malignant gliomas. Biomarkers reliably predicting tumor response to EGFRi need to be identified.

Epidural metastasis of a glioblastoma after stereotactic biopsy: case report.

Tumor seeding along the biopsy tract is a rare complication in stereotactic biopsy. We present the unique case of a 42-year-old male with epidural tumor seeding along the needle tract after computer tomography-guided stereotactic biopsy of a glioblastoma in the right basal ganglia. Three months after the biopsy and one week following fractionated radiation therapy, the patient died of brain edema and cardiac dilatation. Besides further tumor growth at the primary site, autopsy revealed a right frontal epidural, nodular metastatic tumor at the site of dura incision of the stereotactic biopsy. Histological examination showed a glioblastoma that spread epidurally along the needle tract. This is the first report of an epidural intracranial implantation metastasis of a glioblastoma after stereotactic biopsy.

Gamma knife radiosurgery of acoustic neurinomas.

The authors report on their series of 40 patients with 41 acoustic neurinomas (ACNs), including one patient with bilateral acoustic neurinomas suffering from neurofibromatosis type 2 (NF II) who were treated with the gamma knife unit at their institution between August 1992 and October 1995. Of these 41 tumours, 21 ACNs had been operated on before (1 to 4 times), 20 ACNs were exclusively treated by gamma knife radiosurgery (GKRS). The maximal axial tumour diameter ranged from 6 to 33 mm (median: 25 mm), the maximal transverse tumour diameter ranged from 7 mm to 36 mm (median: 16 mm). The dose distributed to the tumour margin was 10 to 17 Gy (median: 12 Gy) by enclosing the tumour with the 40% to 95% isodose line (median: 50% isodose line) and using 1 to 12 isocenters (median: 5 isocenters). Central loss of contrast enhancement was observed in 78% of the patients within six to 12 months after radiosurgery. Thirty-two patients were observed over a minimum follow up period of at least 36 months, 9 patients were lost to follow up as they died of unrelated causes or refused further check-ups. Within the follow up period of up to seven years, magnetic resonance imaging (MRI) control scans revealed the tumour diameter stable or decreased in 29 cases and increased in three tumours. Of 14 patients with useful hearing before treatment, 9 patients were examined in addition to pure tone audiogramm by measurement of brainstem auditory evoked potentials (BAEPs) one to four years after radiosurgery. None of these patients showed a postoperative loss of the cochlea function. According to slight alterations of the cochlea function (cochlea summating action potential), pure tone audiometry of those patients revealed only slight changes of the hearing level (HL) within a maximum range of +/-15 Decibel (dB). The hearing threshold improved in two, was stable in four and deteriorated in three patients, respectively. We observed postradiosurgical aggravation of a pre-existing facial weakness in two out of 13 patients, a new occurrence of facial palsy was seen in two cases (four years after treatment), one of them was previously operated on and both suffered from cystic degeneration with mass effect. Tinnitus improved in six out of 13 patients, deteriorated in two and never appeared as a new permanent sequela. Trigeminal hypaesthesia did also not appear as a new permanent symptom, improved in three out of 9, and deteriorated in one out of 9 patients. Vertigo increased in six out of 23, was stable in 8 and decreased in nine out of 23 patients each. GKRS proves to be a safe and highly satisfactory therapeutical option or addition to open surgery, especially for radiologically verified regrowing residual ACNs, but also as primary treatment in selected patients. A high rate of tumour control can be achieved with an acceptable rate of neurological deficits.

An intramural macrocyst of an acoustic neurinoma rupturing after gamma knife radiosurgery: a case report.

We want to describe the rare case when an intramural macrocyst within an acoustic neurinoma (ACN) treated by gamma knife radiosurgery (GKRS) ruptured, followed by an impressive decrease of tumor volume and improvement of neurological symptoms. In a 59-year-old female patient, a large ACN with a hugh intramural macrocyst was diagnosed. As she refused open surgery, we performed GKRS covering the tumor margin and the cyst with 11 Gy. Seven months after treatment symptoms worsened slightly. Magnetic resonance imaging (MRI) revealed no significant change of tumor volume. One year after GKRS she felt a sensation behind her treated ear, followed by an immediate improvement of all her symptoms. Trigeminal hypaesthesia and vertigo disappeared, tinnitus ameliorated. A control MRI showed the cystic compartment no longer, the solid part shrunk within the following six years. Within the whole follow-up period hearing was stable. To our knowledge this is the first report of a macrocyst within an ACN to rupture after GKRS.

Intracranial hemorrhage from an aneurysm encased in a pilocytic astrocytoma--case report and review of the literature.

The authors present an unusual complication of a recurrent chiasmal/hypothalamic pilocytic astrocytoma. From his second year of life onwards, the patient was repeatedly operated on and also underwent external radiation therapy (54 Gy total dose) 1 month after the first subtotal tumor resection. Nine years after irradiation, the patient was referred to our center with a sudden onset of severe headache, vomiting and neck stiffness. Computed tomography, magnetic resonance imaging, and cerebral angiography demonstrated an intratumoral, intraventricular, and subarachnoidal hemorrhage from an anterior communicating artery aneurysm encased in the pilocytic astrocytoma. The aneurysm was clipped and the patient recovered nicely from the hemorrhage. Three years later, the patient suddenly died of cardiac failure. Autopsy disclosed vessel wall changes compatible with radiation-induced vasculopathy. In light of this finding, the importance of radiation therapy and intracranial neoplasms for aneurysm formation is discussed.

Gamma knife radiosurgery of recurrent central neurocytomas: a preliminary report.

OBJECTIVES: A series of three recurrent central neurocytomas treated by gamma knife radiosurgery (GKRS), which were initially totally resected, are described. Up to now, no reports exist on this treatment modality for this rare tumour entity. METHODS: Three male patients, aged between 20 and 25 years, presented with large intraventricular tumours. Total tumour removal was achieved by a single surgical procedure (one patient) or two operations (two patients). Neuropathological investigation showed a central neurocytoma, immunohistochemically all three tumours expressed a neuronal antigenic profile typical for neurocytomas, and the MIB-1 proliferation index ranged from 2.4% to 8.7%. Each patient experienced a tumour recurrence after 5 to 6 years. The recurrence was multifocal in two and a singular tumour mass in one patient. Gamma knife radiosurgery was performed. The tumours were enclosed within the 30% to 60% isodoseline, and delivered a tumour marginal dose of 9.6 to 16 Gy. During the follow up period, the patients were tested clinically and the volume of the tumours was measured on MRI. RESULTS: Within follow up periods of 1 to 5 years, control MRI showed a significant decrease of the tumour mass in all cases. None of the patients developed new neurological symptoms after GKRS. Two patients returned to work in their previous employment, whereas one patient remained permanently disabled due to a pre-existing visual impairment and abducens palsy. CONCLUSION: GKRS proved to be a useful tool in the treatment of recurrent central neurocytomas. Tumour control and even tumour shrinkage can be achieved with a single procedure and a low risk of morbidity.

Treatment of dural arteriovenous fistulae (dAVF's) at the superior sagittal sinus (SSS) using embolisation combined with micro- or radiosurgery.

DAVF's at the SSS are extremely rare and usually present with intracranial haemorrhage (ICH) or a progressive neurological deficit. Due to their midline location and multiple arterial supply, endovascular treatment alone often fails in eliminating the fistula. Therefore, endovascular, combined with neurosurgical and/or radiosurgical treatment is often needed to cure the patient. We summarized our experience with three male patients over a ten-year period who suffered from dAVF's involving the middle and posterior third of the SSS. Two of them presented with an ICH during the clinical course. Despite multiple transarterial embolisations, complete fistula occlusion could not be achieved in any of them. Nevertheless, neurological symptoms improved in all cases. One patient refused further treatment and died six years later due to an ICH. Another patient was finally cured by microsurgical coagulation of the fistula. In the remaining patient stereotactic radiosurgery (SRS) was performed after nearly complete endovascular occlusion. We strongly recommend microsurgery and/or radiosurgery as adjunctive measures, if embolisation alone fails to eliminate these dangerous fistulae.

Gamma knife radiosurgery of skull base meningiomas.

BACKGROUND: The standard surgical treatment of meningiomas is total resection of the tumour. The complete removal of skull base meningiomas can be difficult because of the proximity of cranial nerves. Stereotactic radiosurgery (SRS) is an effective therapy, either for adjuvant treatment in case of subtotal or partial tumour resection, or as solitary treatment in asymptomatic meningiomas. METHOD: Between September 1992 and October 1995. SRS using the Leksell Gamma Knife was performed on 46 patients (f:m 35:15), ranging in age from 35 to 81 years, with skull base meningiomas at the Neurosurgical Department of the University of Vienna. According to the indication of gamma knife radiosurgery (GKRS) the patients (n = 46) were divided into two subgroups. Group I (combined procedure: subtotal resection followed by GKRS as a planned procedure or because of a recurrent meningioma), group II (GKRS as the primary treatment). Histological examination of tumour tissue was available for 31 patients (67%) after surgery covering 25 benign (81%) and 6 malignant (19%) meningioma subtypes. FINDINGS: The overall tumour control rate after a mean follow-up period of 48 months (ranging from 36 to 76 months) was 96% (97.5% in benign and 83% in malignant meningiomas). Group I displayed a 96.7% tumour control rate, followed by group II with 93.3% respectively. Neurological follow-up showed an improvement in 33% stable clinical course in 58%) and a persistent deterioration of clinical symptoms in 9%. Remarkable neurological improvement after GKRS was observed in group II (47%), whereas in group I (26%) the amelioration of symptoms was less pronounced. INTERPRETATION: GKRS in meningiomas is a safe and effective treatment. A good tumour control and low morbidity rate was achieved in both groups (I, II) of our series, either as a primary or adjunctive therapeutic approach. The planned combination of microsurgery and GKRS extends the therapeutic spectrum in the treatment of meningiomas. Reduction of tumour volume, increasing the distance to the optical pathways and the knowledge of the actual growing tendency by histological evaluation of the tumour minimises the risk of morbidity and local regrowth. Small and sharply demarcated tumours are in general ideal candidates for single high dose-GKRS, even after failed surgery and radiation therapy, and in special cases also in larger tumour sizes with an adapted/reduced margin dose.

Growing blood clot mimicking an aneurysm on postoperative computerized tomography and magnetic resonance imaging studies. Case report and review of the literature.

The authors describe the case of a 15-year-old boy who underwent resection of a large left temporal tumor. During a normal postoperative course, computerized tomography (CT) scanning demonstrated a spherically hyperdense structure near the internal carotid artery, enlarging on a control CT scan. A suspected false aneurysm was confirmed on magnetic resonance imaging; angiographic studies were negative. The authors believed they were dealing with a thrombosed false aneurysm and they performed operative revision. Intraoperatively the "aneurysm" could be dissected off the internal carotid artery and no lesion of the arterial wall was obvious. Histological findings showed a fresh blood clot. This case demonstrates that a blood clot may mimic an aneurysm on CT and magnetic resonance studies, which has not been described earlier. The origin of the blood clot remains unclear.

The Medos Hakim programmable valve in the treatment of pediatric hydrocephalus.

The programmable Medos Hakim valve offers the possibility of adjusting the valve's operating pressure noninvasively. We retrospectively analyzed a series of 78 children who underwent a shunting procedure using this programmable valve within the last 4 years: 46 children underwent a primary shunt placement and 32 children underwent a shunt revision with a different valve replaced by the Medos programmable valve. There were 23 complications, 9 infections, 13 mechanical complications and 1 subileus in all children. Treatment was successful with no need for further shunt revision in 29 of the children with primary shunt placements and 27 of the children with shunt revisions. In 10 cases of overdrainage this was adequately corrected by readjustment of the valve operating pressure alone. As there are no criteria for prediction of the valve operating pressure needed for any individual patient we consider this valve to be beneficial in various forms of shunt-dependent pediatric hydrocephalus.