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Bevacizumab, a humanized recombinant anti-vascular endothelial growth factor antibody, was approved in Canada in 2010 for the treatment of high-grade glioma. We report the effectiveness and safety of bevacizumab in the treatment of patients with recurrent high-grade gliomas at a single institution.
Twenty-seven consecutive patients with high-grade glioma (anaplastic glioma and glioblastoma) at first or subsequent relapse were treated with bevacizumab alone or in combination with chemotherapy. The primary endpoint was progression-free survival (PFS) and secondary endpoints were objective response rate, six month PFS, overall survival (OS), and safety profile.
The clinical benefit rate (complete and partial responses plus stable disease) was 59%. Median PFS was 4.3 (95% CI, 3.0-10.9) months, with a six month PFS rate of 43%. Median OS after current relapse was 8.9 (95% CI, 5.8-not reached) months. Ten episodes of grade 3/4 adverse events were observed in nine patients, including fatigue (n = 3), thrombocytopenia (n = 4), and myelotoxicity, febrile neutropenia, and pulmonary embolism (each n = 1).
We consider the efficacy and safety profile of bevacizumab is comparable to other cohorts of patients treated for recurrent high-grade glioma at other international institutions.
This chapter speaks about a 75-year-old woman admitted with a 4-year history of progressive social withdrawal, decreased fluency, and difficulty handling complex tasks. Magnetic Resonance Imaging (MRI) of the brain showed prominent mesencephalic atrophy, dilation of the third ventricle, and mild cerebral atrophy. Based upon her history and examination, the patient met National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) diagnostic criteria for probable Progressive Supranuclear Palsy (PSP). Available data showed that the diagnosis of PSP was pathologically confirmed in essentially 100% of patients who meet these criteria. The patient's motor function progressively worsened, and she died from respiratory complications, approximately 6 years following symptom onset. Progressive supranuclear palsy is a sporadic neurodegenerative disease, which is defined clinicopathologically by the constellation of atypical parkinsonism, supranuclear vertical gaze palsy, and a characteristic pattern of tau accumulation within the brainstem and basal ganglia.
Polymicrogyria has been related to mutations of several genes including SRPX2, PAX6, TBR2, KIAA1279, RAB3GAP1, COL18A1 and copy-number variations. The spectrum of clinical manifestations associated with polymicrogyria ranges from normal individuals with only selective impairment of cognitive functions. Generalized polymicrogyria is often accompanied by microcephaly and severe-profound cognitive and motor delay, as well as epilepsy. Both polymicrogyria and schizencephaly have been reported in the same family and both may occur with prenatal cytomegalovirus infection. Clinical findings include focal seizures present in most patients usually beginning before age 3 years if bilateral clefts are present. Epilepsy, motor impairment, and disorders of higher cortical functions are the most common clinical manifestation of polymicrogyria. Specific electroclinical features of Aicardi syndrome include early onset infantile spasms and partial seizures. Electroencephalography in polymicrogyria and schizencephaly shows variable patterns of abnormality. Selected patients with schizencephaly have been treated with surgery for epilepsy.
Scedosporial infections are usually encountered in the immunocompromised patients. However, they are now emerging in the immunocompetent population and have an affinity for the central nervous system. They represent a therapeutic challenge, since they are highly resistant to most antifungal medications.
We report the case of an immunocompetent patient with multiple cerebral abscesses secondary to Scedosporium apiospermum following extracorporeal membrane oxygenation (ECMO) and review the literature about this challenging cerebral infection.
A previously healthy 33-year-old male admitted to the hospital for a community-acquired pneumonia requiring ECMO subsequently developed multiple cerebral abscesses. He was empirically treated with caspofungin, which was changed to voriconazole once surgical aspiration revealed Scedosporium apiospermum. Despite multiple aspirations, decompressive craniectomy to alleviate intracranial pressure, and an appropriate antifungal agent, the patient did not survive this aggressive infection.
Brain abscesses with Scedosporium apiospermum present a therapeutic challenge. High clinical suspicion leading to early appropriate antifungal therapy and combined surgical interventions might improve the prognosis.
Since temozolomide (TMZ) entry into routine practice in the first-line management of glial tumors, post-TMZ recurrences present a growing challenge. Without standard chemotherapy for TMZ failure, care in such palliative settings requires consideration not only of efficacy but of toxicity and convenience.
At our institution, a combination regimen has been used: oral alkylating agents procarbazine (PCB) (100-150 mg/m2/day) and TMZ (150-200 mg/m2/day) administered on days 1-5 of a 28-day cycle. This treatment has been initiated upon radiological and/or clinical disease progression, and continued until evidence of further progression or toxicity. We retrospectively reviewed our experence with this regimen.
Since November 2004, 17 patients (median age 53) were treated for histologically confirmed glioma (glioblastoma multiforme (GBM), N=12; Grade 3 glioma, N=3; Grade 2 glioma, N=2) after a median of 2 recurrences. TMZ was previously given either as adjuvant therapy (post-chemoradiotherapy maintenance in 8 of 13 cases) or as salvage monotherapy (4 cases). Of 16 evaluable cases, 14 (13 high grade tumors) showed O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Two patients achieved partial response and one had complete response by RECIST criteria. Disease progressed after a median of 4 cycles (range 1 to 11+), with an actuarial progression-free survival of 42% after 6 cycles. Grade 3/4 toxicity was rare, and no dose reductions were needed. One patient discontinued treatment due to procarbazine hypersensitivity.
Combination PCB-TMZ is well-tolerated, with modest activity in TMZ-exposed glioma.
Hemangiopericytoma is an aggressive vascular tumour that rarely affects the central nervous system and is even more rarely spinal in presentation. The clinical features of a patient with a recurrent extraspinal hemangiopericytoma presenting with an epidural spinal cord compression by local invasion are described, including a review of the literature on metastatic hemangiopericytoma to the spine.
A case of a 53-year-old male, with a recurrent extraspinal hemangiopericytoma which metastasized to the thoracic spine five years after detection of the primary tumour is presented. A chart review was conducted where all pertinent history, physical, laboratory, and radiological data were collected. A Pub-Med search using the keyword “hemangiopericytoma” identified all reported cases documenting clinical features, treatment, recurrence and outcome with respect to metastatic hemangiopericytoma to the spine.
Nine patients have been reported to have metastatic hemangiopericytoma to the spine. The median patient age was 47 years and there was a slight male preference. An unusual feature of the hemangiopericytoma is the prolonged period, up to 16 years, between the diagnosis of the primary hemangiopericytoma and the metastases to the spine. All patients were treated with a combination of radiation and surgery.
Hemangiopericytomas show a slow clinical evolution with a strong propensity to relapse long after previous treatment and thus, once identified, prolonged follow-up for recurrence is indicated. A close follow-up of these patients is required because of frequent recurrences and delayed metastases even if the primary lesion was well-controlled. Although overall uncommon, hemangiopericytoma should be kept in mind in the differential diagnosis of vascular epidural spinal cord tumours.
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