Ivo W. Tremont-Lukats

A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma

BACKGROUND Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. METHODS In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab. RESULTS A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group. CONCLUSIONS First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged but did not reach the prespecified improvement target. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00884741.).

Brain metastasis from prostate carcinoma: The M. D. Anderson Cancer Center experience.

The objective of this study was to estimate the incidence and describe distribution, clinical presentation, and prognosis of brain metastases in patients with prostrate carcinoma who were seen at The University of Texas M. D. Anderson Cancer Center (MDACC).

Neurocognitive and functional assessment of patients with brain metastases: A pilot study

The outcome of patients with brain metastases is generally poor. Survival alone is not necessarily a good measure of clinical outcome. Measures of neurocognitive function and the impact of the disease and treatments on functional status also need to be considered. Although these parameters have been measured in patients with primary brain tumors, they have not been as thoroughly evaluated in patients with brain metastases. The Mini-Mental State Examination provides limited assessment of neurocognitive domains impaired in brain tumor patients. It is less sensitive to mild impairment, does not avoid memorized learning from repeat administration, and does not have validated alternative forms necessary for non-English speaking patients. To determine the feasibility of using a more comprehensive neurocognitive test battery, motor, verbal, executive, and daily functions were assessed in 30 patients with brain metastases. The test battery included the Hopkins Verbal Learning Tests, Controlled Oral Word Association Test, Grooved Pegboard Test, Trailmaking Tests A and B, and the Barthel Index. In this study, there was complete patient compliance, with average test completion time of 23 ± 6 minutes. Despite high functional status, most patients demonstrated impairment in memory and fine motor domains. Neurocognitive test batteries can and should be used in patients with brain metastases enrolled in clinical trials.

Response of neoplastic meningitis from solid tumors to oral capecitabine

Neoplastic meningitis (NM) is a major challenge for the neuro-oncologist as it constitutes a relatively common clinical problem in systemic and central nervous system cancers, and is very difficult to treat. NM portends a significant worsening in prognosis. Chemotherapeutic treatment options are limited, and not particularly effective. We report two cases of NM from breast carcinoma and a third with esophageal carcinoma, which responded to treatment with capecitabine, an oral prodrug for 5-flurouracil. We believe capecitabine warrants further investigation in patients with NM. In some patients, its use may result in clinical and radiographic tumor responses, improved quality of life, and possibly increased survival.

Lambrolizumab induced central nervous system (CNS) toxicity

Programmed death 1(PD-1) is a strategic receptor on activated T-cells that mediates immunosuppression in cancer. Lambrolizumab is a humanized monoclonal IgG4–kappa isotype antibody designed to block the negative immune regulatory signaling of the PD-1 receptor expressed by T cells.1 Anti–PD-1 monoclonal antibodies have activity against several solid tumors.2 Recently, the FDA designated lambrolizumab as a breakthrough therapy for patients with advanced melanoma. We describe a patient with metastatic melanoma placed on a clinical trial with lambrolizumab who developed CNS toxicity.

Paraneoplastic chorea: Case study with autopsy confirmation

A 67-year-old man presented with a 7-month history of insidiously progressive chorea, ataxia, and vertigo. Neurologic examination revealed deficits referable to the basal nuclei, cerebellar vermis, and vestibular nuclei. Small-cell lung cancer was diagnosed by fine-needle biopsy of a parahilar mass. After chemotherapy, the patients chorea worsened. Anti-Hu antibodies were present in serum and cerebrospinal fluid. Microscopic examination of the brain at autopsy revealed diffuse perivascular lymphocytic infiltrates, microglial activation, and neuronophagia throughout the neuraxis, including the brainstem, cerebellum, lenticular nuclei, striatum, and cerebral cortex. Prominent loss of Purkinje cells was seen in the cerebellar vermis and hemispheres to a lesser degree. Chorea is extremely rare as a paraneoplastic manifestation of cancer. The florid presentation and the positive findings contrasted with an unremarkable MRI of the brain. This case illustrates the preeminence of symptoms and signs over negative MRI findings in paraneoplastic encephalitis.

N-type calcium channel antibody-mediated paraneoplastic limbic encephalitis: A diagnostic challenge

BACKGROUND The etiology of encephalitis presents a diagnostic challenge and often remains a mystery. However, current technological advances using antibodies can enable a definitive diagnosis in cases that would previously have been suspected to be idiopathic or viral encephalitis. Our objective is to show that tonsil neuroendocrine carcinoma can present initially as limbic encephalitis mediated by N-type calcium channel antibodies and to highlight the diagnostic confusion before cancer detection. METHODS We report a rare case of neuroendocrine cancer presenting as limbic encephalopathy, Lambert-Eaton myasthenic syndrome and neuropathy. The patient was diagnosed and treated at The University of Texas MD Anderson Cancer Center in November 2011. RESULTS Paraneoplastic limbic encephalitis was diagnosed based on clinical presentation of seizures, short-term memory loss, retrograde amnesia, disorientation, distractibility, and abulia; on the exclusion of brain metastases, CNS infection, stroke, metabolic or nutritional deficits, or medication-related events; and on CSF results with inflammatory findings and an abnormal electroencephalography study that showed seizure activity in the left temporal lobe. Serum paraneoplastic panel was positive for P/Q-type calcium channel antibody and N-type calcium channel antibody. Magnetic resonance imaging of brain was unremarkable. CONCLUSION This case highlights limbic encephalitis as an atypical presentation of neuroendocrine cancer. It also illustrates how treatment of the underlying cancer can reverse limbic encephalitis and Lambert-Eaton myasthenic syndrome in a neuroendocrine carcinoma patient even before the paraneoplastic panel becomes negative.

Imaging mimics of primary malignant tumors of the central nervous system (CNS).

Imaging has become a central part of the evaluation of lesions of the central nervous system. Despite patterns of the appearances of several types of central nervous system malignancies and improving resolution of imaging techniques, there are other processes that can display similar characteristics. Time and again, vascular, inflammatory, and vascular lesions will mimic a neoplastic process, requiring tissue diagnosis. With the introduction of advanced magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging in the evaluation of the brain tumor, there has been improvement in determining whether a lesion is neoplastic, and further advances may lead to noninvasive pathological and molecular diagnoses.

The CT halo sign in invasive aspergillosis

In immunocompromised patients, the pulmonary computed tomography halo sign is highly suggestive of angioinvasive aspergillosis. Early recognition may be life‐saving.

Sinking skin flap syndrome in glioblastoma.

Sinking skin flap syndrome (SSFS) is a rare neurological complication in patients with traumatic haemorrhage, stroke or cerebral oedema who undergo decompressive craniectomy to relieve increased intracranial pressure. Hallmark of SSFS is the sinking of the scalp to a plane lower than the edges of the skull defect in the setting of neurological deterioration. Our objective is to report that SSFS can present after small craniotomy without cerebral cortex compression and to share our diagnostic/therapeutic approach. A 62-year-old woman with a glioblastoma developed SSFS after a small craniectomy and tumour resection without cerebral cortex compression but a decrease in the surgical cavity volume. Brain MRI showed decreased size of the surgical cavity. Interestingly, the patient also developed posterior reversible encephalopathy syndrome (PRES). This case highlights an atypical presentation of SSFS and the possible association with PRES. It also illustrates how an early cranioplasty can successfully reverse SSFS.