Abstract. Gene expression profiling of metastatic brain tumors from primary lung adenocarcinoma, using a 17k-expression array, revealed that 1561 genes were consistently altered. Further functional classification placed the genes into seven categories: cell cycle and DNA damage repair, apoptosis, signal transduction molecules, transcription factors, invasion and metastasis, adhesion, and angiogenesis. Genes involved in apoptosis, such as caspase 2 (CASP2), transforming growth factor-ß inducible early gene (TIEG), and neuroprotective heat shock protein 70 (Hsp70) were underexpressed in metastatic brain tumors. Alterations in Rho GTPases (ARHGAP26, ARHGAP1), as well as down-regulation of the metastasis suppressor gene KiSS-1 were noted, which may contribute to tumor aggression. Overexpression of the invasion-related gene neurofibromatosis 1 (NF1), and angiogenesis-related genes vascular endothelial growth factor-B (VEGF-B) and placental growth factor (PGF) was also evidenced. Brain-specific angiogenesis inhibitors 1 and 3 (BAI1 and BAI3) were underexpressed as well. Examination of cell-adhesion and migration-related genes revealed an increased expression of integrins and extracellular matrices collagen and laminin. The study also showed alterations in p53 protein-associated genes, among these increased gene expression of p53, up-regulation of Reprimo or candidate mediator of the p53-dependent G2-arrest, down-regulation of p53-regulated apoptosis-inducing protein 1 (p53AIP1), decreased expression of tumor protein inducible nuclear protein 1 (p53DINP1), and down-regulation of Mdm4 (MDMX). The results demonstrated that genes involved in adhesion, motility, and angiogenesis were consistently upregulated in metastatic brain tumors, while genes involved in apoptosis, neuroprotection, and suppression of angiogenesis were markedly down-regulated, collectively making these cancer cells prone to metastasis.
Imaging plays several key roles in managing brain tumors, including diagnosis, prognosis, and treatment response assessment. Ongoing challenges remain as new therapies emerge and there are urgent needs to find accurate and clinically feasible methods to noninvasively evaluate brain tumors before and after treatment. This review aims to provide an overview of several advanced imaging modalities including magnetic resonance imaging and positron emission tomography (PET), including advances in new PET agents, and summarize several key areas of their applications, including improving the accuracy of diagnosis and addressing the challenging clinical problems such as evaluation of pseudoprogression and anti-angiogenic therapy, and rising challenges of imaging with immunotherapy.
An F-FDG PET performed for staging of a left lung mass showed a hypermetabolic focus in the left posterior fossa suggestive for brain metastasis. However, subsequent MRI showed restricted diffusion in the left cerebellum indicating a subacute ischemic stroke. Follow-up PET showed resolution of FDG uptake; MRI showed focal left cerebellar encephalomalacia. This case demonstrates visualization of the hypermetabolic inflammatory phase of a subacute ischemic stroke. The rare possibility of a false-positive result for brain metastasis must be recognized, and because focal neurologic symptoms may overlap in brain metastases and stroke, MRI confirmation of positive brain findings on FDG PET is needed.
The occurrence of acute myelopathy in a nontrauma setting constitutes a medical emergency for which spinal MRI is frequently ordered as the first step in the patient’s workup. The emergency department radiologist should be familiar with the common differential diagnoses of acute myelopathy and be able to differentiate compressive from noncompressive causes. The degree of spinal cord compression and presence of an intramedullary T2-hyperintense signal suggestive of an acute cord edema are critical findings for subsequent urgent care such as surgical decompression. Importantly, a delay in diagnosis may lead to permanent disability. In the spinal canal, compressive myelopathy can be localized to the epidural, intradural extramedullary, or intramedullary anatomic spaces. Effacement of the epidural fat and the lesion’s relation to the thecal sac help to distinguish an epidural lesion from an intradural lesion. Noncompressive myelopathy manifests as an intramedullary T2-hyperintense signal without an underlying mass and has a wide range of vascular, metabolic, inflammatory, infectious, and demyelinating causes with seemingly overlapping imaging appearances. The differential diagnosis can be refined by considering the location of the abnormal signal intensity within the cord, the longitudinal extent of the disease, and the clinical history and laboratory findings. Use of a compartmental spinal MRI approach in patients with suspected nontraumatic spinal cord injury helps to localize the abnormality to an epidural, intradural extramedullary, or intramedullary space, and when combined with clinical and laboratory findings, aids in refining the diagnosis and determining the appropriate surgical or nonsurgical management.
BACKGROUND: Pediatric Glioblastoma (pGBM) is an uncommon entity. The importance of concurrent and adjuvant temozolomide is not known in this subset of patients. METHODS: We retrospectively analyzed our database between 2000 and 2015. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation with concurrent daily temozolomide at 75 mg per meter square. Radiation dose was 60 Gy in 30 fractions planned by 3-dimensional conformal radiotherapy. 4 weeks later, adjuvant temozolomide was started at 150 mg per meter square, day 1 to 5 every 28 days and escalated to 200 mg per meter square if well tolerated. Logrank test was used to compare survival distribution. The data was analyzed using SPSS v.16. RESULTS: 51 patients were analyzed. Median age was 13 years (Range: 5 to 21 years). 35 males and 16 females were noted. 8 patients had seizures at presentation. Median symptom duration was 3.25 months.29 patients underwent a gross total resection (GTR) while 16 underwent a subtotal resection, 6 patients underwent decompression. 30 patients received concurrent and adjuvant temozolomide. Median PFS was 1.26 years. 1 and 3 year PFS was 54.4% 3 years-24.6.7%.The median overall survival was 1.45 years. In univariate analysis extent of resection was significantly better favoring GTR (1.45 years vs. 0.96 years; p=0.037) and significance maintained after multivariate analysis p=0.026, HR: 3.069, 95% CI: 1.143-8.238. Survival was better for patients receiving Temozolomide but did not achieve significance, however in multivariate analysis use of Temozolomide was associated with significantly improved survival p=0.036, HR-3.315, 95% CI: 1.078-10.193. CONCLUSIONS: GTR improves survival significantly in pGBM. Temozolomide may have a role in pGBM.
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