Selection ofthe Administration Route

The efficacy of MAb-based targeted therapy of HGG using the vascular injection route, whether intravenous (iv) or intracarotid (ic), has repeatedly been limited by the relative impermeability of the BBB and BTB. Clinical studies have shown that, after systemic administration, only a small fraction of the injected dose of radiolabeled intact MAbs and F(ab')2 fragments can be found within the intracranial tumor (0.001-0.005 ID g) which is insufficient for therapeutic purposes (39,40). Targeting...

Herpes Simplex Virus

HSV has a number of advantages as a gene delivery vector. First, the virus has a propensity to infect only neurons. Moreover, it is readily grown in culture to high-titre. As a result of its large genome, the virus accommodates large transgenes. Considerable progress has been made in effectively disabling the virus so that it does not damage the cells it infects but can still deliver an inserted gene effectively. In addition, it is now possible to obtain long-term expression of the transgene in...

Side Effects Of Radiotherapy Acute Reactions

Acute reactions are those that occur during and immediately following completion of a course of external beam radiation therapy. Using current technologies, these reactions are usually rare and clinically readily manageable. These include skin reactions, typically dry desquamation and some degree of erythema, which are managed with local ointments. Temporary alopecia within the radiation field is a common sequela. Fatigue may be observed with radiation therapy, but is often a function of...

Preirradiation Or Neoadjuvant Chemotherapy

Neoadjuvant chemotherapy refers to treatment given at diagnosis before other modalities such as radiation. It has several potential advantages. First, neoadjuvant chemotherapy allows early treatment of the infiltrating tumor cells that may be at or beyond the border of the radiation field. Second, neoadjuvant chemotherapy allows true assessment of the efficacy of the chemotherapy. Such information is important at the time of tumor progression in deciding whether treatment with the same regimen...

Dorsal Exophytic Brainstem Tumors

Dorsal exophytic brainstem gliomas are a distinct subgroup of neoplasms that account for 20 of all brainstem tumors. They generally have a relatively benign histology and slow growth characteristics, and do not carry the near universal dismal prognosis seen in the intrinsic pontine gliomas. However, some do have higher grade histology, but do not share the same dismal prognosis of the intrinsic pontine glioma. These tumors may present in early infancy and generally appear before puberty. They...

Fatigue

The neurologic disorder in which fatigue has been best evaluated is multiple sclerosis in which at least 78 of these patients suffer from fatigue and is often the most disabling symptom of this disease (55). Similarly, in a study of over 1300 cancer patients, 58 of patients described problems with fatigue, yet less than 52 of those ever reported symptoms to their caregivers, and only 14 had received some type of treatment (56). Perhaps the greatest obstacle to recognizing fatigue is in terms of...

Conclusions And Future Directions

PET provides the opportunity to image multiple dynamic biological processes in situ in brain tumors. Energy metabolism and amino acid transport and incorporation are important components of the pathophysiology of gliomas about which molecular imaging is providing regional biological information that is useful in clinical practice. Imaging hypoxia is straightforward and proliferation imaging with FLT shows significant promise. Neither has been exploited thoroughly enough to allow judgment of...

Amino Acid Transport And Incorporation [c11methionine C11met [f18fluorotyrosine F18tyr [f18fluoroethylltyrosine F18fet

The goal of PET imaging with labeled amino acids is to assess the protein synthetic process in growing tumors (63). Most of the amino acids used for PET are transported by the L system. This has been documented by competition studies with other amino acids that use the same transporter (64). Where the BBB is impaired, the exchange of amino acids can partially bypass the transporter in the capillary wall. Intracellularly, amino acids for protein synthesis come either from the extracellular pool...

Alexander Mason Steven Toms and Aleck Hercbergs

Conventional multimodailty therapies have not altered the dismal prognosis of glioblastoma which has prompted alternative investigational approaches utilising biological modifiers of response.We review here interferon alpha (IFN-a) and beta (IFN-P), interleukin-2 (IL-2), tumor necrosis factor-a TNF, interleukin 4 (IL-4) , monoclonal antibodies to EGFR, EGFRvIII and radiolabeled anti-tenascin monoclonal antibody. A current novel approach is exploitation of some of the biological consequences of...

Critical Issues

There are a number of critical issues that must be addressed if BNCT is to become a useful modality for the treatment of brain tumors. First and foremost, there is a need for more selective and effective boron agents, which when used either alone or in combination, could deliver the requisite amounts ( 20 g g) of boron to the tumor. The superiority of the combination of BPA and BSH over either alone has been demonstrated in experimental animal studies (31,192), this combination was recently...

Spectroscopy

MR spectroscopy (MRS) is becoming more commonplace in the routine evaluation of patients with intracranial masses as the software becomes more widely available and user-friendly on MR machines. Proton MRS can be practically implemented on any 1.5T MR system with clinically useful exam times, signal-to-noise, and spatial resolution. Higher field systems (e.g., 3.0 Tesla T ) provide the theoretical advantages of improved signal to noise, shorter exam times, and improved spectral resolution (peak...

Clinical Presentation

The clinical presentation will depend on the exact location ofthe tumor within the brainstem, the rate of growth, and whether or not the flow of CSF is disturbed. In general, there is often involvement of individual or multiple cranial nerves, long-tract signs and disturbances of coordination. Bulbar symptoms, including swallowing and speech difficulties, are very common. If CSF flow is disrupted, headache and vomiting may occur, along with limitation of upgaze and alteration ofmotor tone....

Alexander M Spence David A Mankoff Mark Muzi and Kristin Swanson

This chapter reviews nuclear imaging of gliomas, both high- and low-grade, with emphasis on results from positron emission tomography (PET) with F-18 -2-fluoro-2-deoxyglucose (FDG) for assessing energy metabolism. There are many additional advances beyond FDG-PET that are very exciting and potentially applicable in the management of gliomas. Biosynthesis in tumors occurs along several important broad fronts for DNA, proteins, and membrane lipids. Molecular imaging of these pathways is coming to...

Glioblastoma Multiforme

Glioblastoma multiforme is classified as a WHO grade IV neoplasm and is among the most common primary intracranial neoplasms. Glioblastomas account for the majority of glial tumors, over half ofastrocytic tumors, and up to 20 of all intracranial tumors (1,11). Although uncommon in the pediatric population, glioblastomas make up more than half of primary intracranial neoplasms in adults with a peak incidence during the sixth and seventh decades of life. Similar to the AA, the glioblastomas...

Diffusion vs Convection

One rationale for applying CED in glioma therapy is based on the limitations of other local delivery methods (injection or wafers) that rely on diffusion together with the fact that glioma cells are present throughout the adjacent and distant brain tissue. Diffusion in tissue depends on the free concentration gradient and the diffusivity of the particular compound or molecule (11). Factors that influence diffusivity are polarity, molecular weight, and metabolic clearance (17,18). It has been...

Medications and Chemotherapy

Patients and families should be educated regarding all medications and treatments prescribed. The drug's indications for use, expected outcomes, appropriate dosing schedules, potential side effects, and symptoms oftoxicity should be reviewed. Patients and families who receive adequate education are more likely to be compliant regarding their medications and treatments. Potential interactions with foods and other drugs including alcohol and over-the-counter (OTC) medications, such as vitamins...

Emotional Distress and Social Support Issues

Diagnosis of a malignant brain tumor is a stressful and traumatic event for patients and families with a wide range of responses from anger, withdrawal, isolation, guilt, anxiety depression, and hopefully, acceptance. Adjustment to the many changes can take a dramatic toll on patients, family and caregivers (19). Patients require varying levels of support depending on the stage of their illness. As care has been shifted from the hospital to the home, caregivers must master a range of tasks that...

Venous Thromboembolism

Venous thromboembolism (VTE) has long been known as a complication ofcancer. Venous thromboembolisms are usually divided into deep venous thrombosis (DVT) and pulmonary embolism (PE). When DVTs affect the proximal veins of the lower extremities they are usually treated as a PE. We discuss VTE with all brain tumor patients at the initial consultation. Mechanism of action for VTE includes, venous stasis (immobility), intimal injury, and alterations in coagulation. In brain tumor patients, Sawaya...

RolfF Barth Jeffrey A Coderre M Graga H Vicente Thomas E Blue and Shin Ichi Miyatake

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when nonradioactive boron-10 is irradiated with low-energy thermal neutrons to yield high-linear energy transfer a particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas (HGG), and either cutaneous primaries or cerebral metastases of melanoma. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the...

Neutron Sources For Bnct Nuclear Reactors

Neutron sources for BNCT currently are limited to nuclear reactors and in the present section we will only summarize information that is described in more detail in a recently published review (138). Reactor derived neutrons are classified according to their energies as thermal (En < 0.5 eV), epithermal (0.5 eV < En < 10 keV), or fast (En > 10 keV). Thermal neutrons are the most important for BNCT because they usually initiate the 10B(n, a)7Li capture reaction. However, because thermal...

Dose Escalation

In most biological systems, radiation exhibits stochastic properties. In cell-culture systems, when survival curves as a function of dose are generated, a dose-dependant response, Radiation Dose Fig. 1. Radiation therapy dose response relationship. Radiation Dose Fig. 1. Radiation therapy dose response relationship. with an initial shoulder and subsequent slope is clearly identified. These cell-survival curves are best described by a linear-quadratic function. In the human context, very clear...

Anaplastic Astrocytoma

Anaplastic astrocytomas (AA) are histologically classified as World Health Organization (WHO) grade III neoplasms. Analagous to infiltrative astrocytomas, these tumors have infiltrative margins on histology. On the other hand, they contain areas of pleomorphism and high cellularity and may demonstrate areas of necrosis and cyst formation like their higher grade counterparts. Up to 75 of AA are felt to arise from lower grade gliomas whereas the anaplastic group may also dedifferentiate into...

Assessing Response to Therapy

Patient Show Report Graph

An important question with implications for clinical practice is whether changes in glucose metabolism are a reliable predictor of the response of malignant gliomas to therapeutic interventions. Successful radiotherapy (RT) of a tumor would be expected to kill tumor cells and cause a reduction of metabolism measured with FDG. That is, tumors that responded to treatment would show reduced metabolism and conversely, tumors that did not respond would show unchanged or increased metabolism. This...

Brainstem Malignant Glioma Subtypes

This tumor may occur at any age but is most common between 5 to 10 yr of age, and is distinctly uncommon before 2 yr of age (38). The typical presentation of this tumor is a triad of cranial nerve palsies, ataxia, and cerebrospinal tract dysfunction. Most often the VIth and VIIth cranial nerves are involved (sometimes unilaterally), and the motor and cerebellar signs often involve contralateral limbs. Symptoms may be present for several weeks but some patients come to medical attention within...

Depression

Patients with malignant gliomas often develop progressive neurobehavioral deficits caused by the disease itself as well as treatments such as radiation and chemotherapy (19). Depression in brain tumor patients can be related to the stress of the diagnosis, treatment, loss of function, or medications. Almost all patients faced with a potentially terminal diagnosis will experience, at minimum, temporary grief and anxiety. Patients may benefit from counseling, psychotherapy, or medication. Some...

Local Delivery Of Herpes Simplex Virus Into Gliomas

Herpes simplex virus type I (HSV-1) is an enveloped, double-stranded, linear DNA virus with a genome of 152 kb which encodes more than 80 genes. About one half of the genes are essential for viral replication whereas the other (nonessential) genes encode proteins which support the viral life cycle within the host cell. The major advantages and disadvantages of HSV-1 for tumor oncolysis are illustrated in Table 1. Several different strategies have been applied to generate tumor-selective HSV-1...

Qualityof Life

Quality-of-life (QOL) is a concept that describes the impact of the disease and treatment on the patient (15). Symptoms experienced by patients with HGG can have a devastating effect on the patient's and family's quality of life. For that reason, most symptom management is aimed at improving the patient's quality of life. Most patients are usually not able to function at the same level as previosuly, but the goal is to restore them to the maximum level of functionality possible. The impact of...

Steroids

Steroid use, its benefits and side effects, have been controversial since the 1960s when French first reported using them regularly in brain tumor patients (31,32). In the 1950s, while studying craniopharyngiomas, Ingraham noted a reduction in cerebral edema in patients using corticosteroids (33). Dexamethasone (DMS) is a potent anti-inflammatory with a relative lack of mineralocorticoid activity. The DMS dose that the French empirically chose was 16 mg d as this was the dose felt to give...

Interfering With the Immune Response Against the Virus

For the viral antitumor effect to succeed, viral replication must out-compete tumor proliferation. However, the fact that oncolytic viruses are attenuated in their replication and that they also provoke an intense immunogenic response may hinder efficient tumor spread and lysis. Therefore, one strategy to improve biologic efficacy may involve interfering with the immune response. The immune response of the body to adenoviruses and HSVs follows a similar pattern consisting of an immediate innate...

Manmeet Singh Ahluwalia and David M Peereboom

The role of systemic chemotherapy in high-grade gliomas (HGG) continues to evolve. The use of chemotherapy for central nervous system (CNS) malignancies poses specific challenges related to drug delivery and interactions with anticonvulsants. Chemotherapy has become standard in the adjuvant therapy of HGG. For patients with chemotherapy-sensitive subgroups of pure and mixed anaplastic oligodendrogliomas, chemotherapy represents the preferred initial therapy. Chemotherapy is often used for...

Radiation Oncology Nurse

Radiation therapy provides an important role in the management of HGG. Nursing care provided by the radiation oncology nurse begins at the initial consult visit and continues into the early post-radiation phase. Patients and families must be educated regarding treatment schedules and expected effects and side effects. Options available to patients include conventional regional radiation, whole brain radiation, stereotactic radiosurgery such as gamma knife or photon beam, brachytherapy, and...

Alternativecomplimentary Treatment

Alternative medicine has been defined as the use of various treatment modalities that are not usually used in traditional medicine, taught in medical schools, or covered by insurance companies. Terminology, however, is changing and these treatments are being incorporated more and more into traditional therapies and hence the term complimentary medicine is now used more frequently (Complimentary-Alternative Medicine CAM ). In 1991, the National Institutes of Health (NIH) established the office...

Toxicity Of Stereotactic Radiosurgery

Acute complications from SRS are generally minimal and usually transient. These side effects may include infection or numbness at a pin site, headache, seizure, nausea, vomiting, fatigue, and exacerbation of existing neurologic symptoms. To prevent some of these side effects, many centers premedicate and discharge patients on corticosteroids. For those patients with a history of seizures, some centers also give antiseizure medications. The most common late toxicities include radiation necrosis,...

Preoperative Education

Preoperative education for the patient with a high-grade CNS malignancy is a unique challenge to nurses. Management of this patient population involves multiple treatment modalities and requires ongoing vigilance of a multidisciplinary team to detect and treat newly diagnosed and recurrent tumors. Multiple studies have indicated that preoperative education significantly reduces pre- and postoperative anxiety. Certainly, with the addition of a potential malignant diagnosis, and the often rapid...

Oxygen Metabolism And Blood Flow [o15o2 [o15h2o [o15co

Oxygen metabolic rate MRO2 , cerebral blood flow CBF , oxygen extraction fraction OEF , and cerebral blood volume CBV in malignant gliomas have all been examined by several groups 2,42-46 . Among these studies there is consistency in showing that oxygen utilization is low relative to normal cortex despite an adequate supply of oxygen, at least macroscopically i.e., there are adequate blood flow and blood oxygen levels to meet the metabolic demands of the tumors . Wise et al. in particular noted...