Standard treatment of primary and metastatic brain tumors includes high dose megavoltage radiation to the cranial vault. About half of patients survive >6 months, many attain long term control or cure, but 50-90% of survivors overall exhibit disabling cognitive dysfunction. The radiation cognitive syndrome is poorly understood and there is no effective prevention or long-term treatment. Attention has primarily focused on mechanisms of disability appearing at six months to one year after radiotherapy. However, a range of studies have revealed that CNS alterations and dysfunction develop much earlier than 6 months following radiation exposure. This has prompted the recent hypothesis that relatively subtle early forms of radiation induced CNS damage may drive chronic pathophysiology leading to permanent cognitive decline. Within this perspective, the present review presents evidence of acute CNS irradiation triggered inflammation, and injury to neuronal lineages, accessory cells and their progenitors, and loss of supporting structure integrity. Moreover, injury related processes set in motion soon after intracranial irradiation may interact and synergize to alter the neuronal and supporting cell progenitor signaling environment in stem cell niches in the brain, and specifically in the hippocampus, a structure critical to memory and cognition. Changed niche conditions may cause a sustained decline in neurons and progressive deterioration of cognition. The concluding discussion addresses, (1) what further data is needed, and (2) potential treatment interventions, identified via recent findings on acute CNS radiation injury, that may reverse degenerative processes before they can cause permanent cognitive disability.
According to data from 2015 Open Payments reports, 48% of physicians were reported to have received a total of $2.4 billion in industry-related payments, primarily general payments, with a higher likelihood and higher value of payments to physicians in surgical vs primary care specialties and to male vs female physicians.
The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.
Diffusion weighted imaging (DWI) has been at the forefront of cancer imaging since the early 2000’s. Prior to its application in clinical oncology, this powerful technique had already achieved widespread recognition due to its utility in the diagnosis of cerebral infarction. Following this initial success, the ability of DWI to detect inherent tissue contrast began to be exploited in the field of oncology. Although the initial oncologic applications for tumor detection and characterization, assessing treatment response, and predicting survival were primarily in the field of neuro-oncology, the scope of DWI has since broadened to include oncologic imaging of the prostate gland, breast, and liver. Despite its growing success and application, misconceptions as to the underlying physical basis of the DWI signal exist among researchers and clinicians alike. In this review, we provide a detailed explanation of the biophysical basis of diffusion contrast, emphasizing the difference between hindered and restricted diffusion, and elucidating how diffusion parameters in tissue are derived from the measurements via the diffusion model. We describe one advanced DWI modeling technique, called Restriction Spectrum Imaging (RSI). This technique offers a more direct in vivo measure of tumor cells, due to its ability to distinguish separable pools of water within tissue based on their intrinsic diffusion characteristics. Using RSI as an example, we then highlight the ability of advanced DWI techniques to address key clinical challenges in neuro-oncology, including improved tumor conspicuity, distinguishing actual response to therapy from pseudoresponse, and delineation of white matter tracts in regions of peritumoral edema. We also discuss how RSI, combined with new methods for correction of spatial distortions inherent diffusion MRI scans, may enable more precise spatial targeting of lesions, with implications for radiation oncology, and surgical planning.
For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.
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