Activity and safety of bevacizumab plus fotemustine for recurrent malignant gliomas.

BACKGROUND: No established chemotherapeutic regimen exists for the treatment of recurrent malignant gliomas (rMGs). Herein, we report the activity and safety results of the bevacizumab (B) plus fotemustine (FTM) combination for the treatment of rMGs. PATIENTS AND METHODS: An induction phase consisted of B 10 mg/kg days 1, 15 plus FTM 65 mg/m(2) days 1, 8, and 15. Nonprogressive patients entered the maintenance phase with B 10 mg/kg plus FTM 75 mg/m(2) every 3 weeks. The primary endpoint was response rate; secondary endpoints included safety, progression free survival (PFS), and overall survival (OS). RESULTS: Twenty-six patients affected by recurrent MGs (50% glioblastoma) were enrolled. Eight partial responses (31%) were observed. Median PFS and OS were 4 (95% C.I.: 2.8-5.1) and 6 months (95% C.I.: 4.2-7.8), respectively. Responses were significantly associated with both improved PFS and OS (P = 0.002 and P = 0.001, resp.). Treatment adverse events were mostly mild to moderate in intensity. Bevacizumab-related adverse events included grade 3 venous thromboembolic event (8%), grade 2 epistaxis (4%), hypertension (8%), and gastrointestinal perforation (4%). CONCLUSIONS: Bevacizumab plus FTM showed activity and good tolerability in pretreated MGs. Further investigations are needed in order to verify the benefits deriving from the addition of B to a cytotoxic in this clinical setting of patients.

Lacosamide as add-on in brain tumor-related epilepsy: preliminary report on efficacy and tolerability.

Lacosamide (LCM) is an antiepileptic drug (AED) that has demonstrated a good efficacy in controlling seizures as an add-on in adult epilepsy. To date, there have been no studies on LCM in patients with brain tumor-related epilepsy (BTRE). To evaluate efficacy and tolerability of LCM as an add-on in BTRE, we followed 14 patients suffering from BTRE who had already been treated with other AEDs and who had not experienced adequate seizure control. Eleven patients underwent chemotherapy while being treated with LCM. Mean duration of follow up was 5.4 months (min < 1 max 10 months). Mean seizure number in the last month prior to the introduction of LCM had been 15.4. At last follow-up, the mean seizure number was reduced to 1.9/month. Lacosamide mean dosage was of 332.1 mg/day (min 100 max 400 mg/day). Responder rate was 78.6%. One patient discontinued LCM because of side-effects. There were no other reported side-effects. Preliminary data on the use of LCM in add-on in patients with BTRE indicate that this drug may represent a valid alternative as an add-on in this particular patient population. However, larger samples are necessary in order to draw definitive conclusions.

Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report.

BACKGROUND: Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add-on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor-related epilepsy (BTRE). AIM OF THE STUDY: To evaluate efficacy and tolerability of ZNS as add-on in BTRE. METHODS: We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow-up was 8 months. RESULTS: Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow-up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. CONCLUSIONS: Preliminary data on the use of ZNS in add-on in patients with BTRE indicate that this drug may represent a valid alternative as add-on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.

Outcome and tolerability of topiramate in brain tumor associated epilepsy.

Epilepsy in brain tumor patients is often refractory to pharmacological treatments and can complicate the therapeutic management of these patients. We conducted a prospective, observational study. The aim of this study was to investigate the efficacy and tolerability of topiramate (TPM) in brain tumor associated epilepsy. We studied 47 patients with brain tumors and epilepsy. The entire group was administered AEDs. TPM was the first therapeutic choice in 14 patients, while in the remaining 33 patients previous AEDs were modified and TPM was introduced due to side effects or inefficacy of the first drug. Follow-up ranged from 3 to 48 months (mean 16.5 months). Considering the final follow-up of each patient who assumed TPM for at least 3 months, we observed 45 patients: 25 were seizure free (55.6%), 9 had a reduction of seizure frequency (SF) higher than 50% (20%) and 11 were stable (24.4%). TPM responder rate was 75.6%. Three patients (6.4%) discontinued TPM for severe side effects (1 after 4 months and 2 after 1 month) and 4 (8.5%) had mild and reversible side effects. In the group of patients who had been in therapy with other AEDs prior to entering the study (n = 33), 19 patients had side effects (57.6%). During follow-up, the haematological parameters were in the normative ranges. Tumor-related seizures are difficult to control with AEDs; the precise reasons for this difficulty are not yet clear. Using TPM, we obtained good seizure control with a low incidence of side effects.

Home rehabilitation for brain tumor patients.

UNLABELLED: To determine whether a program of post-discharge rehabilitation at home for patients operated for brain tumor was associated with functional gain and improvement in Quality of Life (QoL). One hundred and twenty-one patients affected by malignant brain tumor were enrolled in a program of post-discharge home care including neurorehabilitation. Functional outcome was evaluated with Barthel Index (BI) and Karnofsky Performance Status (KPS) measured before and after rehabilitation. The impact of rehabilitation on quality of life was evaluated with a quality of life questionnaire (EORTC QLQ-C30-BM 20). RESULTS: Barthel Index improved in 47 (39%) patients, was stable in 20 (16%) and worsened in 54 (44%). Only 54 patients completed the QoL questionnaire before and after treatment. After three months of rehabilitation, 72% of patients were found to have an improvement in at least one domain score compared with their baseline QoL scores. Rehabilitation at home in brain tumor patients was associated with significant functional gain measured both with BI and KPS. The benefit of rehabilitation may influence patient's perception of quality of life.

Early post-operative MRI: correlation with progression-free survival and overall survival time in malignant gliomas.

Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST). As demonstrated by early-MR, gross total resection was performed in 17 patients, sub-total and partial resection in 19 and 11 patients, respectively. The PFS was 6 months in gross total resection, 6 and 3 months in sub-total and in partial resection, respectively. The median survival time was 16 months in total resection patients, 13 months and 7 months in sub-total resection and partial resection patients, respectively. The study confirms that early-MR has to be considered an accurate technique for monitoring the extension of malignant glioma surgical resection and shows a good correlation between early-MR findings, PFS and ST.

Cranioplasty performed with a new osteoconductive osteoinducing hydroxyapatite-derived material.

OBJECT: Cranioplasty is required to protect underlying brain, correct major aesthetic deformities, or both. The ideal material for this purpose is autogenous bone. When this is not available, alloplastic or artificial materials may be used. These materials should be malleable, strong, lightweight, inert, noncarcinogenic, nonferromagnetic, and, if possible, inexpensive. The authors reviewed their surgical experience with a new bone substitute and discuss outcomes in patients in whom it was used. METHODS: The 11 patients presented in this series had bone defects resulting from bone-involving tumor (eight cases), trauma (two cases), or aesthetic deformity due to repeated craniotomies (one case). The defects were repaired using Osprogel, a bone substitute that consists of calcium hydroxyapatite combined with synthetic, human bone-derived gelatin, glycerol, and water. Osprogel is not only a bioinert material but also an osteoconductive and osteoinducing substrate; when it is placed in contact with healthy cancellous bone, it induces osteogenesis and angiogenesis, thus permitting the regrowth of nearly normal bone. The sheet of Osprogel was modeled onto the cranial defect intraoperatively and was kept in place either by using a titanium micronet secured to surrounding bone with microscrews (first two cases) or by using a single- or double-layer titanium mesh secured with stitches. No complications due to the procedure were observed. The results, evaluated at least 6 months after surgery by using three-dimensional (3-D) reconstructed computerized tomography scans, were excellent in seven patients, good in three, and fair in one. In the patient with a fair result, the repair was unsatisfactory because there was lack of experience in using the material. In part of the area to be repaired, the Osprogel was used as filler; here it was washed out and resorbed. The cases deemed as having a good result had good bone replacement; however, the curvature was faulty. CONCLUSIONS: In the near future, this technique may be refined to achieve good or excellent results either without the use of supporting material or with the use of individual, computer-designed 3-D prostheses.

[Intracranial meningiomas in the elderly]. / Meningiomi endocranici dell'anziano.

BACKGROUND: Since the introduction of CT and then MRI in the clinical practice, the number of elderly patients with intracranial meningiomas observed in neurosurgical departments has increased to three/four times. Considering that some patients die because of their meningioma and others die with their meningioma, the neurosurgeon should not only be able to eradicate surgically the lesion, but also to decide if that benign tumor should be treated or not. MATERIALS AND METHODS: Forty-three patients with intracranial meningioma, aged over 65 were operated upon between 1989 and 1995. They constitute about one fourth of all the meningioma-patients operated upon in that period at our Department. Main symptoms were focal deficits, psychorganic syndrome, and seizures. Mean duration of symptoms was 15 months, with 30% of the histories lasting less than 3 months. Associate pathologies were those typical of the elderly population with hypertension and senile cardiopathy at the first places. Two patients had insulin-dependent diabetes, 2 prostatic carcinoma, and 8 were obese. MRI was useful either in depicting the location of the tumor or in helping the surgeon to give a correct operative indication and risk evaluation. MRI criteria for risk evaluation were severe edema and venous vascular infiltration. Forty-five operations were performed. Their duration was not a risk factor by itself, it only reflected the difficulty of the removal, due to the location of the tumor. Dissection of tumor remnants from main arteries or veins was never attempted in this group of patients; total removal was achieved in 75.5% of the cases. RESULTS: Immediate postoperative results were good in 71% of cases. Four patients died (9%). Long term results were evaluated in 29 patients (mean follow-up period: 35 months). Twenty-two patients (76%) had excellent or good results, 5 (17%) fair, and 2 (7%) had severe neurological dysfunctions and needed continuous assistance. CONCLUSIONS: Surgical risk factors typical of this age group were identified: cranio-spinal location, damage to the cortical or deep venous system, severe peritumoral edema, and poor neurological preoperative conditions. Systemic risk factors were insulin-dependent diabetes and obesity.

111In-octreotide scintigraphy in pituitary adenomas.

This study reports on 111In-octreotide scintigraphy in 20 patients affected with pituitary adenomas, including tracer uptake ratios and in vitro immunohistochemical characterization of the matostatin receptor state. 111In-octreotide uptake was already observed at 4 hours in 7/8 GH-secreting adenomas, in 5/7 non-secreting adenomas and in 1/5 prolactinomas. Concordance between the scan and the histochemical results was observed in all cases. The uptake ratios evaluated at 24 hours ranged from 2.3 to 4.2. The following conclusions were drawn: 1) 111In-octreotide is a suitable tracer to evaluate the somatostatin receptor state of pituitary adenomas; 2) Semi-quantitative measures of tracer uptake can be easily obtained with static planar scanning, but more refined techniques are needed for receptor kinetics evaluation; 3) This nuclear technique is a promising non-invasive tool to identify patients with somatostatin receptor positive pituitary adenomas who might potentially benefit from pre- and/or post-surgery cold octreotide medical treatment.

The transdural extension of gliomas.

The extraneural spreading of gliomas is an infrequent occurrence which is not necessarily related to either tumor histology or site. This paper reports two cases, a glioblastoma and an oligodendroglioma, both presenting extradural diffusion. In the first case, where there was severe intracranial hypertension, the tumor found its way out from the neurocranium, far from the site of the operation, perforating the dura and the bone of the cranial base. In the second case, the operation may have facilitated the extraneural invasion. This unusual behaviour of glial tumors is probably less rare than presumed. It may go unnoticed if the attention is concentrated on the usually severe neurological syndrome which is present in these patients.

[Mucocele of the paranasal sinus. CT assessment]. / Mucoceli dei seni paranasali. Valutazione TC.

The authors report 7 cases of mucoceles of the paranasal sinuses evaluated with plain films and CT. All patients were submitted to surgery. Five patients were affected with frontal mucoceles and 4 with sphenoid ones. In 2 cases the lesion was double. Symptoms were correlated with both site and compressive changes due to expansile growth. All cases were evaluated by means of axial and coronal pre- and post-contrast scans: a satisfactory morphological depiction of the lesion was always achieved. CT values were also calculated, and the relationship of mucocele to the adjacent structures was demonstrated. The modalities of expansile growth, the lack of enhancement in post-contrast scans, and the possible "ring sign" in cases with intracranial spread allow a correct radiological diagnosis. CT is the diagnostic method of choice for best lesion demonstration: it makes a correct diagnosis possible and allows the thorough evaluation of the involved structures for surgical planning.

Cystic appearance of meningiomas: considerations on a series of 12 patients.

Twelve patients affected with meningiomas with a fluid component are reviewed. Six presented with intratumoral cysts and 6 with extratumoral fluid collections that in 3 cases were of clear CSF. The formation mechanism of the two types are quite different. Intratumoral cysts are caused by biological changes within the tumor, while the extratumoral ones appear to be secondary to local hydrodynamic changes and CSF reabsorption disturbances. The CT (computerized tomography) scan may be equivocal either for the diagnosis of the meningioma or, once the meningioma is suspected, for identifying the type of cyst involved. The angiography is useful for a correct preoperative diagnosis that, once suspected, can be frequently made.

Mucocele of neurosurgical interest: clinical considerations on five cases.

The authors present five patients with mucocele, submitted to neurosurgery. Two had mucoceles spreading from the frontal and/or the anterior ethmoidal sinuses and had only compressive mass symptoms, either on the ocular globe or on the frontal lobe or on both. Three patients had mucoceles growing from the sphenoid and/or posterior ethmoidal sinuses. In these latter, the mass symptoms were less evident. All the patients suffered excruciating retro-ocular pain and two presented cranial nerve damage. The correct diagnosis in these cases is crucial to avoid a too aggressive treatment since these patients are generally sent to a neurosurgeon for a suspected cranial base malignancy or an invasive pituitary adenoma. The principles of a correct differential diagnosis and of operative treatment are outlined based on an analysis of the literature and the authors experience.

Late multifocal gliomas in adolescents previously treated for acute lymphoblastic leukemia.

Three of 37 adolescents in long-term remission from childhood acute lymphoblastic leukemia (ALL) developed malignant multifocal gliomas several years after completing treatment that included central nervous system (CNS) prophylaxis with radiation (RT) and intrathecal methotrexate (IT-MTX). No recurrence of the leukemia was evident when the CNS tumors were discovered. Seventeen other similar cases have been recorded. The occurrence of second malignancies is reviewed in the context of this development and of the oncogenic effects of radiation. It is probable that prolonged exposure to IT-MTX may have had a synergistic effect with radiation in contributing to the unusual incidence of glial tumors in these patients.

Multiple sclerosis plaque simulating cerebral tumor: case report and review of the literature.

Multiple sclerosis rarely may present as a focal cerebral mass with clinical features and computed tomographic scan appearances of cerebral tumor. Distinguishing between these can be difficult or impossible. We report a case of a multiple sclerosis plaque involving the parietal lobe with mass effect; clinical and radiological features had led to a diagnosis of cerebral tumor.