Rohan Ramakrishna, Robert Rostomily

Date of publication: 02-May-2013

Abstract

First invoked by Paget, the seed and soil hypothesis suggests that the successful growth of metastatic cells depends on the interactions and properties of cancer cells (seeds) and their potential target organs (soil). In the context of the seed and soil hypothesis this review examines recent advances in the understanding of molecular and cellular features that permit transformed epithelial cells to gain access to the blood stream (intravasation), survive their journey through the blood stream, and ultimately traverse through the microvasculature of target organs (extravsation) to deposit, survive, and grow in a foreign tissue environment. In addition to a review of the clinical and experimental evidence supporting the seed and soil theory to cancer metastasis, additional concepts highlighted include: (i) The role of cancer stem-like cells as putative cells of metastatic origin (the “seeds”); (ii) the mechanism of epithelial to mesenchymal transition (EMT) in driving epithelial cell conthose molecules do no blood stream to avoid anoikis, or anchorage independent cell death; and (iv) the reverse process of EMT, or mesenchymal to epithelial transition (MET), which promotes conversion back to the parent cell morphology and growth of macrometastsis in the target organ. The unique biology of metastases once established in the brain, and in particular the “sanctuary” role that the brain microenvironment plays in promoting metastatic growth and treatment resistance, will also be examined. These issues are of more than academic interest since as systemic therapies gradually improve local tumor control, the relative impact of brain metastasis will inexorably play a proportionally greater role in determining patient morbidity and mortality.

Emilie Le Rhun, Sophie Taillibert, Marc C. Chamberlain

Date of publication: 02-May-2013

Abstract

Leptomeningeal metastasis (LM) results from metastatic spread of cancer to the leptomeninges, giving rise to central nervous system dysfunction. Breast cancer, lung cancer, and melanoma are the most frequent causes of LM among solid tumors in adults. An early diagnosis of LM, before fixed neurologic deficits are manifest, permits earlier and potentially more effective treatment, thus leading to a better quality of life in patients so affected. Apart from a clinical suspicion of LM, diagnosis is dependent upon demonstration of cancer in cerebrospinal fluid (CSF) or radiographic manifestations as revealed by neuraxis imaging. Potentially of use, though not commonly employed, today are use of biomarkers and protein profiling in the CSF. Symptomatic treatment is directed at pain including headache, nausea, and vomiting, whereas more specific LM-directed therapies include intra-CSF chemotherapy, systemic chemotherapy, and site-specific radiotherapy. A special emphasis in the review discusses novel agents including targeted therapies, that may be promising in the future management of LM. These new therapies include anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib in nonsmall cell lung cancer, anti-HER2 monoclonal antibody trastuzumab in breast cancer, anti-CTLA4 ipilimumab and anti-BRAF tyrosine kinase inhibitors such as vermurafenib in melanoma, and the antivascular endothelial growth factor monoclonal antibody bevacizumab are currently under investigation in patients with LM. Challenges of managing patients with LM are manifold and include determining the appropriate patients for treatment as well as the optimal route of administration of intra-CSF drug therapy.

Taylor J. Abel, Timothy Ryken, Maciej S. Lesniak, Patrik Gabikian

Date of publication: 02-May-2013

Abstract

With therapies for systemic malignancy improving, life expectancy for cancer patients is becoming increasingly dependent on control of brain metastatic disease. Despite improvements in surgical and radiotherapy modalities for control of brain metastasis, the prognosis for patients with brain metastases is poor. The development of controlled release polymers has lead to novel new therapies for malignant brain tumors consisting of direct surgical delivery of chemotherapy agents to the tumor bed and sustained chemotherapy release over a prolonged period of time. Although there is a large body of literature in support of BCNU polymer wafer for primary brain malignancy and experimental brain metastases, clinical studies evaluating the BCNU polymer wafer for brain metastatic disease are relatively sparse. In this review, we discuss the role of the BCNU polymer wafer for brain metastasis focusing specifically on rationale for use of locally delivered sustained release polymers, history of the BCNU polymer wafer, and emerging studies examining the role of the BCNU polymer wafer for metastatic brain tumors.

Antonio De Salles

Date of publication: 17-Apr-2013

Benjamin P. Jonker

Date of publication: 17-Apr-2013

Abstract

Stereotactic radiosurgery requires imaging to define both the stereotactic space in which the treatment is delivered and the target itself. Image fusion is the process of using rotation and translation to bring a second image set into alignment with the first image set. This allows the potential concurrent use of multiple image sets to define the target and stereotactic space. While a single magnetic resonance imaging (MRI) sequence alone can be used for delineation of the target and fiducials, there may be significant advantages to using additional imaging sets including other MRI sequences, computed tomography (CT) scans, and advanced imaging sets such as catheter-based angiography, diffusor tension imaging-based fiber tracking and positon emission tomography in order to more accurately define the target and surrounding critical structures. Stereotactic space is usually defined by detection of fiducials on the stereotactic head frame or mask system. Unfortunately MRI sequences are susceptible to geometric distortion, whereas CT scans do not face this problem (although they have poorer resolution of the target in most cases). Thus image fusion can allow the definition of stereotactic space to proceed from the geometrically accurate CT images at the same time as using MRI to define the target. The use of image fusion is associated with risk of error introduced by inaccuracies of the fusion process, as well as workflow changes that if not properly accounted for can mislead the treating clinician. The purpose of this review is to describe the uses of image fusion in stereotactic radiosurgery as well as its potential pitfalls.

Diem Kieu Thi Tran, Randy L. Jensen

Date of publication: 17-Apr-2013

Background:Glioblastoma multiforme (GBM) has a dismal prognosis despite aggressive therapy. Initial diagnosis and measurement of response to treatment is usually determined by measurement of gadolinium-enhanced tumor volume with magnetic resonance imaging (MRI). Unfortunately, many GBM treatment modalities can cause changes in tumor gadolinium enhancement patterns that mimic tumor progression. The lack of a definitive imaging modality to distinguish posttreatment radiographic imaging changes (PTRIC), including pseudoprogression and radiation necrosis, from true tumor progression presents a major unmet clinical need in the management of GBM patients.

Serge Y. Rasskazoff, Konstantin V. Slavin

Date of publication: 17-Apr-2013

Abstract

Headaches (cephalgias) are a common reason for patients to seek medical care. There are groups of patients with recurrent headache and craniofacial pain presenting with malignant course of their disease that becomes refractory to pharmacotherapy and other medical management options. Neuromodulation can be a viable treatment modality for at least some of these patients. We review the available evidence related to the use of neuromodulation modalities for the treatment of medically refractory craniofacial pain of different nosology based on the International Classification of Headache Disorders, 2^nd edition (ICHD-II) classification. This article also reviews the scientific rationale of neuromodulation application in management of cephalgias.

Leonardo Lustgarten

Date of publication: 17-Apr-2013

Abstract

Although there is an ongoing debate about the ideal management of vestibular schwannomas, radiosurgical treatment has become popular in the past decade with good to excellent results reported. Given the young age at presentation, the bilateral nature of vestibular schwanomas, the presence of other associated central nervous system tumors, patients with neurofibromatosis Type 2 (NF2) are very complex and present significant management challenges. Although results do not seem to be as good as for patients with sporadic unilateral tumors, stereotactic radiosurgery has proven a safe, attractive, and effective management modality for NF2 vestibular schwannomas. An overview of the impact stereotactic radiosurgery has had in the management of these tumors is discussed.

Jean-Jacques Lemaire, Hachemi Nezzar, Laurent Sakka, Yves Boirie, Denys Fontaine, Aurélien Coste, Guillaume Coll, Anna Sontheimer, Catherine Sarret, Jean Gabrillargues, Antonio De Salles

Date of publication: 17-Apr-2013

Abstract

The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents.

Bomin Sun, Wei Liu

Date of publication: 17-Apr-2013

Abstract

Eating disorders (EDs) are a group of severely impaired eating behaviors, which include three subgroups: anorexia nervosa (AN), bulimia nervosa (BN), and ED not otherwise specified (EDNOS). The precise mechanism of EDs is still unclear and the disorders cause remarkable agony for the patients and their families. Although there are many available treatment methods for EDs today, such as family therapy, cognitive behavioral therapy, medication, psychotherapy, and so on, almost half of the patients are refractory to all current medical treatment and never fully recover. For treatment-refractory EDs, stereotactic surgery may be an alternative therapy. This review discusses the history of stereotactic surgery, the modern procedures, and the mostly used targets of stereotactic surgery in EDs. In spite of the limited application of stereotactic surgery in ED nowadays, stereotactic lesion and deep brain stimulation (DBS) are promising treatments with the development of modern functional imaging techniques and the increasing understanding of its mechanism in the future.