Distinct topographic-anatomical patterns in primary and secondary brain tumors and their therapeutic potential

Journal of Neuro-Oncology - Understanding the topographic-anatomical patterns of brain tumors has the potential to improve our pathophysiological understanding and may allow for anatomical...     

Invasiveness of primary brain tumors

Summary Primary malignant neoplasms of the nervous system differ from other types of malignancy in several ways. Clinical progression is due to local invasive growth, while metastases outside the skull are rare. The tumors show no sharp delimitation from the surrounding normal tissue. At the edge, an ill-defined area of invasive tumor cells, reacting glial cells and inflammatory cells is present. At the same time the primary brain tumors are biologically heterogeneous.In this review, a short survey of markers for malignancy in primary brain tumors is given, and some properties of importance for invasive behavior, are listed. These include different cellular enzymes, phagocytotic property, locomotive and proliferative characteristics.Studies of primary brain tumors in situ show invasive growth into the surrounding brain tissue, often tollowed by hemorrhage and necrosis. In addition spread of tumor cells takes place along preexisting intracranial structures. Recently, several systems for the study of brain tumor invasiveness in culture have been elaborated. Both experimental and human gliomas have been tested. The target tissues include organ culture of embryonic chick heart muscle, chorioallantoic membrane, fetal rat brain tissue and reconstructed vessel walls. It has been shown that glioma cells are able to split junctions between normal cells. They destroy and phagocytose the normal cells and penetrate the normal tissue. The use of brain tissue and reaggregated brain cell cultures as target for glioma cells in culture opens the possibility for an elucidation of invasiveness as one of the most important properties of malignancy in the nervous system.     

Hepatic dearterialization for nonrespectable primary and secondary tumors of the liver.

Seventeen patients with primary or secondary liver tumors were treated by dearterialization of the liver and intraportal infusion of cytotoxic drugs. In 14 cases, ligation of the main (10), right and left (1), right and middle (1), and right (2) hepatic arteries was performed. In three in whom hepatic artery ligation was considered to be contraindicated due to occlusion of the portal vein, temporary occlusion of the hepatic artery was repeated postoperatively. Only one patient died from the cause related to the ligation. Out of 14 patients who survived for more than one month ten showed an apparent regression of tumors radiologically. The mean survival period of the patients excluding those who died from other unrelated causes was 28 weeks. That of the control patients who received only chemotherapy through the hepatic artery was 13 weeks. The results were not always satisfactory, but dearterialization of the liver can be a palliative treatment for nonresectable liver tumors with a forceful combined chemotherapy.     

Chemotherapeutic options for primary brain tumors

Opinion statement Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, treatment for most primary brain tumors remains inadequate. Most are associated with a high rate of recurrence after primary therapy and a dismal outcome following recurrence. Surgery and radiation remain the primary modalities of therapy for malignant brain tumors. The role of chemotherapy in malignant gliomas, especially glioblastoma multiforme, has been inconclusive. However, a recent trial by the European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada combining radiation therapy with temozolomide for newly diagnosed glioblastoma patients showed a significantly improved survival benefit over radiation therapy alone. In addition to this encouraging progress, recent experience has shown that selected malignant brain tumors—for example, anaplastic oligodendrogliomas, primary central nervous system lymphomas, medulloblastomas, and intracranial germ cell tumors—are often highly responsive to chemotherapy. Molecular genetic studies are becoming indispensable aids in the diagnosis and treatment of the malignant gliomas. For example, we have learned that allelic loss of chromosome 1p is a significant predictor of chemosensitivity, whereas combined loss of chromosomes 1p and 19q is a strong predictor of chemosensitivity, progression-free survival, and overall survival in patients with anaplastic oligodendroglioma. Similarly, MGMT promoter methylation is associated with more frequent responses and longer survival in patients with glioblastoma multiforme receiving temozolomide-based therapy. These and other recent advances have led to the development and testing of several novel chemotherapeutic and molecular-targeted agents. Several different approaches and modalities to improve the efficacy of chemotherapy (eg, MGMT promoter methylation) are currently under way. Clinical trials implementing angiogenesis inhibitors, biologic modifiers, or molecular-targeted therapies are also actively being investigated.     

Radiotherapy of primary brain stem tumors

This paper presents results of treatment for 80 patients with primary brain stem tumors who were seen at McGill University Hospitals from 1960–1975. A large proportion of the patients were under 15 years old. The majority of pretreatment diagnoses were based on neuroradiologic procedures. The correlation of these procedures in histologically verified cases is high. Glioblastoma comprised 38.7 % of the histologically proven cases. Radiotherapy was the main modality of the treatment. Of the patients who received over 5000 rod, 44/63 (39.8°10) survived at 3 years, 34.5 % at 5 years and 28.4 % at 10 years. This result is similar to that in Bouchard's series which analyzed the cases from the same source prior to this series. The initial response to treatment was beneficial in the majority of patients and this early response appears to be a dependable prognostic parameter.     

Intra-arterial chemotherapy of primary brain tumors

Opinion statement Intra-arterial (IA) chemotherapy is a form of regional delivery to brain tumors, designed to enhance the intra-tumoral concentrations of a given drug, in comparison with the intravenous route. Drugs that are likely to benefit from IA delivery have a rapid systemic clearance and include carmustine and other nitrosoureas, cisplatin, carboplatin, etoposide, and methotrexate. Clinical studies have demonstrated activity of IA chemotherapy approaches for low- and high-grade gliomas, and for cerebral lymphomas. However, a survival benefit for IA drug delivery, in comparison with intravenous administration, has not been proven in phase III trials. The technique is limited by the potential for significant vascular and neurologic toxicity, including visual loss, stroke, and leukoencephalopathy. More recent studies suggest that toxicity can be reduced by the use of carboplatin- and methotrexate-based regimens. Further clinical studies will be needed to determine the appropriate role for IA chemotherapy in the treatment of primary brain tumors.     

Carcinoembryonic antigen in primary carcinoid tumors of the lung

Antibody staining for carcinoembryonic antigen (CEA) was used in 31 cases of primary pulmonary carcinoids to assess the presence of this marker as a parameter of clinical behavior. Other parameters have also been studied (size, position, and histologic characteristics) in order to determine their value as determinants of eventual disease outcome. Tumor size and position did not influence the progression of disease. Atypical histology was a significant predictor (P = 0.05) of treatment failure. Positive CEA marking was the most strongly significant (P = less than 0.01) of all studied parameters for predicting treatment failure.     

Epidemiologic patterns of primary brain tumors in iran

There appear to be some differences between the patterns of brain tumor epidemiology in Iran and Western countries. Thus, the prevalence of glioma was earlier estimated to be about 45% of all brain tumors, somewhat low in comparison to the western reports at that time, but almost the same as in Southeast Asian countries. A similar low figure was also obtained more recently indicating that the earlier estimate was not simply due to the lack of medical facilities resulting in under-reporting of this particularly malignant form of cancer. There may also be differences regarding incidences of central nervous system (CNS) tumors in females between Iran and Western countries. Clearly this is an area which deserves epidemiological research.     

Palliative care in patients with primary brain tumors

PURPOSE OF REVIEW: Because patients with primary brain tumors often present severe functional impairment as well as behavioral/cognitive dysfunction, they suffer from greater dependency and hopelessness than other cancer patients. Optimal management should not only focus on symptom relief through medication and physiotherapy, but should also take into account the psychosocial burden of the disease on the patients and their caregivers. This review updates available data on supportive care in patients with brain tumor. RECENT FINDINGS: Recent improvements have been made in the management of several complications of brain tumor: pain, epilepsy, and side effects of antiepileptic drugs; disability and related thromboembolic complications; cognitive disorders of mixed (tumoral and/or iatrogenic) origin; side effects of steroids; fatigue; and psychological consequences of the disease. SUMMARY: Avoiding useless "overtreatment" is the governing idea. A very thorough evaluation of the benefit/risk ratios is needed each time a new treatment is being considered. Brain tumor patients are particularly prone to develop severe side effects, increased fatigue, and cognitive deterioration following apparently minor changes in symptomatic treatments. Care is also needed to avoid useless prolongation of a burdensome situation. Another issue is that patients and their caregivers should benefit from the support of a multidisciplinary team to maintain realistic hopes and to anticipate critical decisions. Finally, guidelines from the literature are proposed to improve physicians' communication skills when treating these patients.     

Antiangiogenic therapy for primary and metastatic brain tumors

We first provide the theoretic foundation of antiangiogenic therapy by describing the biology of angiogenesis as it applies to brain tumors. We then outline experimental antiangiogenic therapies that are being applied preclinically to brain tumors, as well as published clinical trial data and ongoing clinical trials in patients. Primary and metastatic brain tumors are covered, although there is far less exploration in the literature of brain metastases.     

Treatment-related myelodysplasia in patients with primary brain tumors

Treatment-related myelodysplastic syndrome (t-MDS) and treatment-related acute myelogenous leukemia (t-AML) represent rare secondary events in patients with primary tumors of the nervous system and predominantly affect those treated with alkylating agents or topoisomerase II inhibitors. Temozolomide has become the standard chemotherapeutic agent for malignant gliomas. The emergence of this alkylating agent with little acute toxicity or cumulative myelosuppression has led to off-label protracted chemotherapy for many patients with malignant and even low-grade infiltrative gliomas, raising concern for increased risk of t-MDS/t-AML in the few long-term survivors. On the basis of an extensive literature search, we provide a discussion of epidemiology, pathogenesis, clinical presentation, diagnosis, and therapy of these disorders. t-MDS/t-AML remain rare complications of chemotherapy in patients with primary brain tumors, and the vast majority of patients die of their primary neoplasm. Prospective randomized studies with long-term follow-up are required to accurately assess the risk of t-MDS/t-AML; however, unless survival in the most common gliomas substantially increases, t-MDS/t-AML incidence will likely remain low in this patient population.     

Hepatic drug-metabolizing enzymes in primary and secondary tumors of human liver

Significant increases in activities of epoxide hydrolase, UDP-glucuronosyltransferase, and glutathione S-transferase, and marked reductions in cytochrome P-450 mixed-function oxidase systems occur in hyperplastic nodules induced in rat liver by chemical mutagens. In contrast, activities of both oxidative (Phase I) and conjugative (Phase II) enzymes are decreased in hepatocellular carcinomas induced by peroxisome proliferators. The present work compares alterations induced by chemical mutagens or peroxisome proliferators with changes in enzyme activities that occur in primary and secondary hepatic tumors in man. The above activities, along with beta-glucuronidase and arylsulfatase, were measured in liver samples from 6 normal livers obtained at immediate autopsy, and liver specimens obtained by surgical biopsy from the following patients: 8 with hepatomas, 5 with nonmetastatic colorectal carcinomas, and 14 with metastatic colorectal carcinomas. Cytochromes P-450MP and P-450NF in addition to epoxide hydrolase were measured by immunoquantitation. Enzymes involved in conjugation reactions were either assayed fluorometrically (UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase) or spectrophotometrically (glutathione S-transferase) using umbelliferyl substrates or 1-chloro-2,4-dinitrobenzene. Secondary hepatic tumors showed no significant change in drug-metabolizing enzymes, in contrast to primary hepatomas, which displayed decreases in all of the measured drug metabolizing enzymes. Arylsulfatase was markedly depressed in primary hepatomas (14% of normal values). Thus, activities of drug-metabolizing enzymes in human primary tumors resemble those associated with altered hepatic foci induced by peroxisome proliferators such as ciprofibrate. The marked decreases in sulfatase that occurred in primary but not in secondary human tumors suggest that sulfation of endogenous compounds and xenobiotics may differ in patients with primary and secondary hepatic tumors.     

Evidence-based radiation therapy for primary brain tumors

Radiation therapy for five primary brain tumors is discussed based on the results of prospective trials. Many randomized studies have revealed the usefulness of radiation and radiochemotherapy for treating malignant gliomas, and the ineffectiveness of many new treatments modalities. However, novel treatments should be tested further against this tumor. In low-grade gliomas, the usefulness of radiotherapy was shown but a dose-effect relationship was not observed in recent randomized studies. In medulloblastoma, the difficulty in reducing the dose to the cerebrospinal axis has been shown even in low-stage patients. On the other hand, reliable randomized studies are still lacking for germinoma and primary central nervous system lymphoma, and the usefulness of combination chemotherapy remains uncertain. In the future, more prospective studies are needed for primary brain tumors other than glioma. Establishment of IMRT and controlled studies to prove its efficacy are important in the field of neuro-oncology.