Jackson Hamilton

Glioblastoma Multiforme Metastasis Outside the CNS: Three Case Reports and Possible Mechanisms of Escape

Introduction Primary brain and CNS tumor incidence is approximately 19 per 100,000 individuals per year in the United States compared with seven per 100,000 individuals worldwide. Worldwide this accounts for 2% of all primary tumors and 7% of years of life lost from cancer before the age of 70 years. Glioblastoma multiforme (GBM) is also the most aggressive brain tumor with poor prognosis; patients with GBM have a median survival time of about 14 months. GBM metastases outside the CNS are rare, so therapeutic experience with these types of tumors is limited. Normally the brain is immunologically and anatomically separated from the body by the blood brain barrier. Herein, we present the cases of three patients with GBM with extra-CNS metastasis. The variety of metastasis locations demonstrated in these cases helps to illustrate the various mechanism and corresponding risk factors that allow GBM to escape the CNS.

Treatment of Patients With Advanced Neurofibromatosis Type 2 With Novel Molecularly Targeted Therapies: From Bench to Bedside

Minimal treatment options exist for advanced, inoperable neurofibromatosis type 2 (NF2), which is a rare tumor-prone disorder. NF2 results from a mutation in the NF2 tumor-suppressor gene on chromosome 22q12. NF2 is genetically and phenotypically distinguished from neurofibromatosis type 1, which results from a mutation in the NF1 tumor-suppressor gene located on chromosome 17q11.1,2 Clinically, NF2 is inherited in an autosomal dominant fashion and manifests through the appearance of bilateral acoustic neuromas (vestibular schwannomas), which lead to progressive hearing loss.3 Vestibular schwannomas and other lesions seen in patients with NF2 that arise progressively from other sites, such as meningiomas, spinal schwannomas, astrocytomas, ependymomas, rarely neurofibromas, and peripheral neuropathies, lead to profound morbidity in this debilitating disease.1,4 Few options are available to these patients outside of surgery, which is the mainstay of treatment for NF2-associated lesions, and, in some instances, radiation therapy.1,2 Despite our understanding of the underlying genetics and molecular pathophysiology of this disorder, patients become debilitated from tumor-related comorbidities. Recently, the anti–vascular endothelial growth factor (VEGF) antibody bevacizumab and erlotinib exhibited promising activity in pilot trials.5–8 Other than these two agents, no medical options are available for patients with NF2 with surgically unresectable disease. Because patients with NF2 harbor an aberration in a single gene, merlin, the protein product of which impacts multiple signals, including PI3-kinase/Akt, Raf/mitogen-activated protein/extracellular signal-regulated kinase, and mammalian target of rapamycin (mTOR), it is conceivable that one of the many agents that target these pathways that have already shown antitumor activity in malignancies will also cause the regression of NF2-related tumors.9–11 Because of its extreme rarity, conducting large clinical trials in NF2 is generally unfeasible.9 Therefore, we enrolled patients with NF2 onto various rationally targeted trials and sought response signals. We reviewed the records of consecutive patients with NF2 who were referred to the Clinical Center for Targeted Therapy (phase I Clinical Trials Program clinic) who were treated in more than one trial starting in January 2007 to December 2010. All trials were approved by the MD Anderson institutional review board, which also granted a waiver of informed consent and a waiver of authorization for this retrospective study. Patients were evaluated every 6 to 8 weeks for response by using RECIST with computed tomography and magnetic resonance imaging.

Deformable anatomic templates improve analysis of gliomas with minimal mass effect in eloquent areas.

BACKGROUND Despite improvements in advanced magnetic resonance imaging and intraoperative mapping, cases remain in which it is difficult to determine whether viable eloquent structures are involved by a glioma. A novel software program, deformable anatomic templates (DAT), rapidly embeds the normal location of eloquent cortex and functional tracts in the magnetic resonance images of glioma-bearing brain. OBJECTIVE To investigate the feasibility of the DAT technique in patients with gliomas related to eloquent brain. METHODS Forty cases of gliomas (grade II-IV) with minimal mass effect were referred for a prospective preoperative and postoperative DAT analysis. The DAT results were compared with the patients functional magnetic resonance imaging, diffusion tensor imaging, operative stimulation, and new postoperative clinical deficits. RESULTS Fifteen of the 40 glioma patients had overlap between tumor and eloquent structures. Immediate postoperative neurological deficits were seen in 9 cases in which the DAT showed the eloquent area both within the tumor and within or at the edge of the resection cavity. In 6 cases with no deficits, DAT placed the eloquent area in the tumor but outside the resection cavity. CONCLUSION This is proof of concept that DAT can improve the analysis of diffuse gliomas of any grade by efficiently alerting the surgeon to the possibility of eloquent area invasion. The technique is especially helpful in diffuse glioma because these tumors tend to infiltrate rather than displace eloquent structures. DAT is limited by tract displacement in gliomas that produces moderate to severe mass effect.

Dynamic Contrast-Enhanced Perfusion Processing for Neuroradiologists: Model-Dependent Analysis May Not Be Necessary for Determining Recurrent High-Grade Glioma versus Treatment Effect

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced perfusion MR imaging has proved useful in determining whether a contrast-enhancing lesion is secondary to recurrent glial tumor or is treatment-related. In this article, we explore the best method for dynamic contrast-enhanced data analysis. MATERIALS AND METHODS: We retrospectively reviewed 24 patients who met the following conditions: 1) had at least an initial treatment of a glioma, 2) underwent a half-dose contrast agent (0.05-mmol/kg) diagnostic-quality dynamic contrast-enhanced perfusion study for an enhancing lesion, and 3) had a diagnosis by pathology within 30 days of imaging. The dynamic contrast-enhanced data were processed by using model-dependent analysis (nordicICE) using a 2-compartment model and model-independent signal intensity with time. Multiple methods of determining the vascular input function and numerous perfusion parameters were tested in comparison with a pathologic diagnosis. RESULTS: The best accuracy (88%) with good correlation compared with pathology (P = .005) was obtained by using a novel, model-independent signal-intensity measurement derived from a brief integration beginning after the initial washout and by using the vascular input function from the superior sagittal sinus for normalization. Modeled parameters, such as mean endothelial transfer constant > 0.05 minutes−1, correlated (P = .002) but did not reach a diagnostic accuracy equivalent to the model-independent parameter. CONCLUSIONS: A novel model-independent dynamic contrast-enhanced analysis method showed diagnostic equivalency to more complex model-dependent methods. Having a brief integration after the first pass of contrast may diminish the effects of partial volume macroscopic vessels and slow progressive enhancement characteristic of necrosis. The simple modeling is technique- and observer-dependent but is less time-consuming.

Change in postsurgical cavity size within the first 30 days correlates with extent of surrounding edema: consequences for postoperative radiosurgery.

Objective Resection cavity diameter of less than 40 mm is required to be eligible for stereotactic radiosurgery (SRS), after gross total resection of brain metastasis at our institution. Our study evaluates the correlation between vasogenic edema and change in cavity size for 30 days. Methods Cavity size was measured on the postoperative and follow-up magnetic resonance imaging. Vasogenic edema was quantified as the largest axial measurement of T2 hyperintensity surrounding the resection cavity (postoperative magnetic resonance imaging). Results Thirty-nine resection cavities (37 patients) were reviewed. There was a statistically significant (Pearson coefficient = −0.35; P = 0.02) negative correlation between edema and change in cavity size. An arbitrary cutoff value of a 15-mm edema yielded a sensitivity of 96% and a specificity of 65% (P < 0.001) to predict 10% decrease in cavity size. Conclusions In patients with cavity size close to the size cutoff for SRS, rescanning closer to the date of SRS should be considered, especially if there is significant edema surrounding the cavity.

Severe everolimus-induced steatohepatis: a case report

The mammalian target of rapamycin inhibitors are normally favored as immunosuppressant agents for solid organ transplantation such as kidney, liver or heart. Only in recent years have they been increasingly administered for the treatment of neuroendocrine tumors. Even though mammalian target of rapamycin inhibitors are known to exhibit specific side effects, everolimus-related severe hepatic steatosis has not as yet been described in the literature. We report the case of a 76-year-old man who developed severe hepatic steatosis within four weeks of treatment with everolimus as concomitant tumor therapy for a progressively growing neuroendocrine carcinoma of the ileum. A diagnosis of hepatic steatosis was established using computer tomography and fibroscan©. Other underlying causes for steatosis hepatis could be excluded. Further studies are warranted to explain the underlying mechanisms.

Residual nodal disease in patients with advanced-stage oropharyngeal squamous cell carcinoma treated with definitive radiation therapy and posttreatment neck dissection: Association with locoregional recurrence, distant metastasis, and decreased survival

Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in frequency. We reviewed patients with advanced‐stage OPSCC treated with chemoradiation to assess the impact of residual neck disease on survival.

Synchronous rosette-forming glioneuronal tumor and diffuse astrocytoma with molecular characterization: A case report

Rosette-forming glioneuronal tumor (WHO grade I) is a rare neoplasm primarily arising in young adults that is characterized by distinctive neurocytic rosette formation, a spindled glial component resembling pilocytic astrocytoma, and a high incidence of PIK3CA mutation. Low-grade diffuse astrocytoma (WHO grade II), on the other hand, is far more common and is characterized by a high incidence of IDH mutation. Here we report a patient with simultaneous presentation of a midbrain-cerebellar rosetteforming glioneuronal tumor and a cerebral diffuse astrocytoma. Molecular characterization of both tumors confirmed characteristic, mutually exclusive, distinct signatures, with the rosette-forming glioneuronal tumor exhibiting a previously unreported novel PIK3CA gene mutation.

Deformable anatomic templates embed knowledge into patient's brain images: Part 1. construction and display

Objective This paper describes the methods used to create annotated deformable anatomic templates (DATs) and display them in a patient’s axial 2-dimensional and reformatted volume brain images. Methods A senior neuroradiologist annotated and manually segmented 1185 color-coded structures on axial magnetic resonance images of a normal template brain using domain knowledge from multiple medical specialties. Besides the visible structures, detailed pathways for vision, speech, cognition, and movement were charted. This was done by systematically joining visible anatomic anchor points and selecting the best fit based on comparisons with cadaver dissections and the constraints defined on the companion 2-dimensional images. Results The DAT is commercially available for use on a picture archiving and communication system or as a standalone workstation. Conclusions The DAT can quickly embed extensive, clinically useful functional neuroanatomic knowledge into the patient’s brain images. Besides labeling visible structures, DAT displays clinically important, previously uncharted subdivisions of the fiber tracts.

Superimposed infection in mandibular osteoradionecrosis: diagnosis and outcomes.

Background Radiation therapy can result in osteoradionecrosis (ORN) and mucosal ulceration predisposing to infection. Methods Fourteen patients presenting with infectious sequelae related to mandibular ORN were retrospectively reviewed. Results In most patients, infection followed diagnosis of ORN; but in 4 patients, ORN was not diagnosed until after the time of infection and imaging. An early imaging finding of ORN was lingual cortical defects near the last molar. Pain followed by erythema, purulent drainage, and subperiosteal abscess by imaging were the most common signs of infection. In most patients, conservative management eventually failed and segmental mandibulectomies were required. Conclusions Soft tissue infection with characteristic bone findings such as subperiosteal abscess and cortical bone erosions helps to distinguish infected ORN from recurrent tumor or sterile ORN. In patients previously treated with radiation who present with infection, pain or an avid PET scan with bone involvement, the mandible should be scrutinized.