Showing papers in "Journal of Neuro-oncology in 1996"
TL;DR: The most promising studies are those of cytogenetics, and future elucidation of factors associated with the loss of one copy of chromosome 22, another phenomenon that has been identified in meningiomas, may lead to screening tests and gene therapy.
Abstract: The frequency of meningiomas has been the topic of relatively few reports. Hospital-based brain tumor series indicate that the incidence is approximately 20% of all intracranial tumors; population-based studies indicate an overall incidence of 2.3/100,000. Although intracranial tumors as a whole show a higher prevalence in males than in females, meningiomas have a 2: 1 female-to-male ratio. Between Caucasians and Africans, African-Americans, and Asians, certain differences also have been noted. Meningiomas in children are rare and differ from those in adults and other childhood tumors; they are even more rare in infants. Several features indicating etiologic factors have been identified, among which are ionizing radiation, head injury, hormones, and other receptor binding sites, genetic factors, and viruses. The most common source of exposure of the head to ionizing radiation is dental radiographic examination. Since 1922, head trauma has been considered a possible risk factor, but recent large studies do not support this link. Several factors have prompted studies of estrogens and progestogens as risk factors for meningiomas. Other studies have sought to determine if certain individuals have an inherited predisposition for developing a meningioma and/or if viruses, which may act alone or with other mutagens, figure into the formation of a meningioma. The most promising studies are those of cytogenetics, and future elucidation of factors associated with the loss of one copy of chromosome 22, another phenomenon that has been identified in meningiomas, may lead to screening tests and gene therapy.
329 citations
TL;DR: In this highly selected group, GBM patients with little or no necrosis and with less tumor nodule enhancement on preoperative MRI survive longer than patients with greater amounts of Necrosis and greater degrees of tumor enhancement.
Abstract: Tumor necrosis, enhancement, and associated edema in patients with glioblastoma multiforme (GBM) represent biological variables that can be quantitated on preoperative MRI scans. We reviewed 48 highly selected patients, all of whom had supratentorial lesions, had undergone gross total tumor resection, and had received adjuvant treatments (radio- and chemotherapies). None of these patients had had surgery for recurrent tumor resection and none had harbored multifocal tumors. The median age was 50 years. The median Karnofsky performance score was 80. Multivariate analysis using the Cox regression model revealed that the strongest prognostic variable was the amount of tumor necrosis on preoperative scan (P < 0.001), with median survivals of 42, 24, 15, and 12 months for tumor necrosis grades of 0 (7 ‘pts’), I (11 ‘pts’),11 (9 ‘pts’), and III (21 ‘pts’), respectively. The intensity of enhancement of the tumor nodule was another prognostic factor (P = 0.003), with median survivals of 35, 18, and 13.5 months for enhancement grades of 0 (2 ‘pts’), I (22 ‘pts’), and II (24 ‘pts’), respectively. The extent of peritumoral edema had a quadratic effect (P = 0.001), with grades I (19 ‘pts’), II (22 ‘pts’), and III (7 ‘pts’) surviving for 24,12, and 20 months respectively. Location and volume of tumors were not statistically significant predictors of survival (P < 0.05). In conclusion, in this highly selected group, GBM patients with little or no necrosis and with less tumor nodule enhancement on preoperative MRI survive longer than patients with greater amounts of necrosis and greater degrees of tumor enhancement. In addition, a moderate degree of peritumoral edema is associated with worse prognosis.
236 citations
TL;DR: IQ results suggest that children with childhood medulloblastoma progressively fail to assimilate new verbally-based knowledge at a developmentally-appropriate rate, which is important for understanding the academic attainments and continuing rehabilitation needs of childhood MB survivors.
Abstract: When a malignant tumor invades the child's cerebellum, the cost of successful treatment is often significant cognitive morbidity. A review of neuropsychological outcome revealed that survivors of childhood medulloblastoma (MB) have long-term deficits in intelligence, memory, language, attention, academic skills, psychosocial function, and a compromised quality of life. These deficits varied with chronological age at tumor diagnosis and/or adjuvant treatment, type and duration of presenting symptoms, tumor extension beyond the cerebellum, a history of adjuvant radiation treatment, and time since treatment. The effects on neuropsychological outcome of other factors, such as post-surgical hydrocephalus, were less clear. To understand the interaction between two factors predictive of outcome, age at diagnosis and time since treatment, we analyzed IQ results for a new sample of 25 surgically-treated and radiated MB survivors, and found that age at diagnosis and time since treatment made separable contributions to intellectual morbidity. PIQ appeared to measure some general effects of diffuse cerebral insult because it varied with chronological age of the child at tumor diagnosis but was relatively constant in magnitude, once established. VIQ, in contrast, was somewhat less sensitive to age at diagnosis in treated MB survivors, but declined with time since treatment. These results are important for understanding the academic attainments and continuing rehabilitation needs of childhood MB survivors, because they suggest that these children progressively fail to assimilate new verbally-based knowledge at a developmentally-appropriate rate.
188 citations
TL;DR: Neuropsychological tests may be useful for distinguishing between the diffuse side effects of brain tumor therapy and the focal effects of tumors and surgery on brain functions, and any differences in cognitive function due to tumor malignancy are eliminated or reduced following surgical intervention.
Abstract: This study examined the relationship between cognitive function, tumor malignancy, adjunctive therapy, and lesion lateralization following surgery for intracerebral glioma. Neuropsychological test battery results showed no difference between patients with highly malignant gliomas and those with less malignant gliomas, but differences were found for tumor lateralization and type of therapy. Scores on a test of graphomotor speed were lowest for patients who had received radiation or a combination of radiation and chemotherapy, regardless of lesion location. Other test results did not differ according to type of prior treatment but were related instead to tumor lateralization. Left hemisphere lesions were associated with lower scores on verbal tests, while right hemisphere lesions were related to lower scores on a test of facial recognition. These findings suggest that neuropsychological tests may be useful for distinguishing between the diffuse side effects of brain tumor therapy and the focal effects of tumors and surgery on brain functions. In addition, it appears that any differences in cognitive function due to tumor malignancy are eliminated or reduced following surgical intervention.
178 citations
TL;DR: A longer follow-up is necessary to demonstrate whether, after a local relapse, HDC could replace craniospinal irradiation as prophylaxis against CNS metastases.
Abstract: Cranio-spinal irradiation is the gold standard treatment used in non metastatic medulloblastoma as prophylaxis against central nervous system (CNS) metastases. However, given the severe late effects caused by this procedure in children under 3 years of age, most pediatric oncologists are currently treating these patients with conventional chemotherapy in order to postpone or even avoid irradiation. In the French Society of Pediatric Oncology ('FOP) this attitude has been adopted since 1987.
117 citations
TL;DR: Prolonged low-dose oral VP16 is modestly effective treatment for patients with recurrent malignant glioma and is more effective for anaplastic astrocytoma and anaplastics oligodendroglioma than glioblastoma multiforme.
Abstract: Because the percentage of dividing cells in malignant glioma is small, cell cycle specific drugs such as VP16 are most effective if given continuously over prolonged periods. In this study, we chose a dose of 50 mg/day to minimize therapy interruptions for myelosuppresion. VP16 was given until the neutrophil count dropped to < 1.0 × 109/L or the platelets fell to < 75 × 109/L and resumed when the counts rose to normal levels. We treated 46 patients with supratentorial malignant glioma (15 anaplastic astrocytoma, 21 glioblastoma multiforme, 9 anaplastic oligodendroglioma, l undifferentiated primary malignant brain tumor) at the time of tumor progression. All had KPS ≥ 70 at study entry. All patients had prior RT,13 with adjuvant nitrosourea. Twenty-four had prior nitrosourea chemotherapy for tumor progression, 7 had no prior chemotherapy. We treated 20 patients with VP16 at first progression and 26 at second or later progression. All patients had CT or MR scans and clinical evaluation every 8 weeks. Median time to tumor progression (TTP) was 8.8 weeks for all evaluable patients, 8.6 weeks for those treated at first progression and 8.4 weeks for those treated at second progression, 9.1 weeks for anaplastic astrocytoma, 7.5 weeks for glioblastoma multiforme and 17.1 weeks for anaplastic oligodendroglioma. There were 8 responses and 11 patients with stable disease for at least 8 weeks (R + SD = 42%). Prolonged low-dose oral VP15 is well tolerated, with minimal myelosuppression. Prolonged low-dose oral VP16 is modestly effective treatment for patients with recurrent malignant glioma and is more effective for anaplastic astrocytoma and anaplastic oligodendroglioma than glioblastoma multiforme.
108 citations
TL;DR: A retrospective review of 36 children diagnosed with a supratentorial primitive neuroectodermal tumor (PNET) at the Hospital for Sick Children was performed and it was recommended that all children undergo gross total resection followed by chemotherapy.
Abstract: A retrospective review of 36 children diagnosed with a supratentorial primitive neuroectodermal tumor (PNET) at the Hospital for Sick Children was performed for the period 1970-1995 All children but one received their initial treatment at our institution There were 18 males and 18 females and the median age at diagnosis was 35 months Twenty-two PNETs were lobar, 3 were deep in the hemisphere, and 10 were located in the pineal region One child presented with intracranial leptomeningeal disseminated disease The tumors were mostly undifferentiated although 22 had some evidence of differentiation along one or more neuroepithelial lines Five children had a biopsy, 24 had subtotal resection, and 7 had gross total resection Twenty-six children had adjuvant radiotherapy and 13 had chemotherapy At last follow-up 30 patients were dead and 6 were alive The median survival was 23 months and the 2, 3, and 5 year survivals were 50%, 34%, and 18% respectively All of the survivors received craniospinal radiation and 4 received chemotherapy There was a statistically significantly worse survival in young children There was a trend to better survival in children treated since 1984, and in children undergoing gross total resection Because of the extremely poor survival, we recommended that all children undergo gross total resection followed by chemotherapy For children older than 3 years of age craniospinal radiation should also be given
105 citations
TL;DR: Careful analysis of tumor- and patient-related factors has helped to predict which features can lead to postoperative problems in patients allowing surgeons to appropriately modify their behavior, and can greatly reduce postoperative morbidity in patients.
Abstract: The management of petroclival and foramen magnum meningiomas has been revolutionized by the techniques of cranial base surgery. However, these tumors are still among the most difficult cranial base lesions to treat. In this report, we discuss the classification, presenting symptoms, preoperative investigation, treatment indications, operative approaches and technique, postoperative complications and care, and results of surgery of petroclival and foramen magnum meningiomas. Careful analysis of tumor- and patient-related factors has helped us to predict which features can lead to postoperative problems in patients allowing surgeons to appropriately modify their behavior. The application of cranial base tecniques - combined with new knowledge about the limitations of microsurgical resection - can greatly reduce postoperative morbidity in these patients.
102 citations
TL;DR: Hypoxic exposure is associated with substantial drug resistance in brain tumor cell lines, and the lack of correlation between the induced phenotype and known drug resistance genes suggests other mechanisms may be acting in these tumors in hypoxic conditions.
Abstract: Recurrent gliomas are most often treated by chemotherapy. However, these tumors typically acquire resistance to most drugs administered, and patients will usually die of recurrent tumor. Factors which may play a role include overexpression of putative multidrug resistance genes, such as the multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), 06-alkylguanine, DNA alkyltransferase gene (06MT) and excision repair cross complementing gene 1 (ERCC1). Tumor hypoxia has also been shown to be associated with drug resistance in other soft tissue tumors. Since gliomas have regions of diminished oxygenation, and have clinical resistance to chemotherapy, the relationship between phenotypic resistance to chemotherapy after hypoxic exposure and expression of drug resistance genes was investigated in glioma cell lines (U373 MG, PFAT-MT). After a 24 hour exposure to hypoxia, drugs 1, 3-bis, 2-chloroethyl-1-nitrosurea (BCNU) and cis-diammine, dichloroplatinum II (CDDP) were administered, and cell survival was determined. Hypoxic exposure was associated with increased survival of the cell lines after administration of BCNU and CDDP, with resistance to BCNU 15 to 30-fold when compared to cells which did not undergo hypoxic exposure. Both tumor cell lines also showed some degree of resistance to CDDP, although not to the extent of BCNU (2 to 3-fold increased resistance). The expression of the drug resistance genes was found to be unchanged when comparing cells which had undergone hypoxic exposure and those which had not. Thus, hypoxic exposure is associated with substantial drug resistance in brain tumor cell lines. The lack of correlation between the induced phenotype and known drug resistance genes suggests other mechanisms may be acting in these tumors in hypoxic conditions.
100 citations
TL;DR: It is suggested that some malignant gliomas in infants are chemotherapy sensitive and may be associated with a good prognosis, and why infants with these high-grade glioma fare better than adults is not clear.
Abstract: Although survivals of infants with malignant brain tumors are worse than any other age group, one possible exception to this rule are the malignant gliomas. Eighteen children less than 3 years of age with malignant gliomas (glioblastoma multiforme, anaplastic astrocytoma and malignant glioma) were treated on the Pediatric Oncology Group regimen of prolonged postoperative chemotherapy and delayed irradiation, (1986–1990). Of 10 children evaluable for neuroradiologic response, 6 had partial responses (> 50% reduction) to two cycles of cyclophosphamide and vincristine. Progression free survivals at l, 3 and 5 years were 54.25% ± 12, 43% ± 16 and 43% ± 23 respectively. Survivals at 5 years were 50% ± 14. Four children were not irradiated after 24 months of chemotherapy due to parental refusal and none have developed recurrent disease. Neither degree of surgical resection, presence or absence of metastases, nor pathology influenced survival but this may reflect small sample size. This study suggests that some malignant gliomas in infants are chemotherapy sensitive and may be associated with a good prognosis. Why infants with these high-grade gliomas fare better than adults is not clear. It is likely that there is something intrinsically different about them that cannot be identified on routine pathologic examination.
98 citations
TL;DR: The use of a multidimensional approach or a global index of well-being that also reflects psychosocial and cognitive aspects proved to be more appropriate than traditional functional instruments in assessing the QL of brain tumor patients and in detecting the extent of the disease.
Abstract: With the aim of evaluating the quality of life (QL) of 101 brain tumor patients, a multidimensional approach was adopted, using the Functional Living Index - Cancer (FLIC) as a global measure of well-being, the Karnofsky Performance Scale (KPS) and the Index of Independence in Activity of Daily Living (ADL) as indices of physical and functional dimensions, the State-Trait Anxiety Inventory (STAI) and the Self-Rating Depression Scale (SRDS) for psychological assessment, and neuropsychological tests for abstract reasoning, attention, memory and frontal lobe functions. The patients were grouped on the grounds of disease stage and treatment The FLIC and KPS ratings increased from the patients who had just undergone surgery to patients who were disease-free after completing chemotherapy and radiotherapy, thus showing that the QL may improve during the disease despite aggressive treatments, providing there is no tumor recurrence. However, only the FLIC consistently discriminated the patients' stratification. The ADL revealed no between-group differences, whereas the STAI and SRDS revealed the presence of emotional troubles at the beginning and at the end of treatment. Cognitive impairment was more serious after radiotherapy and chemotherapy, as well as in patients with tumor recurrence. The FLIC significantly correlated with all of the other scales used, showing that it is useful in summarizing both the physical and psychosocial impairment of brain tumor patients. Of the pathological variables, a tumor location in the anterior right hemisphere or diencephalon was associated with high FLIC ratings, may be due to the minor cognitive impairment observed in patients with these tumor sites. Of the demographic variables, the level of education was associated with high FLIC ratings, thus highlighting the role of psychosocial environment in improving the QL. The use of a multidimensional approach or a global index of well-being that also reflects psychosocial and cognitive aspects proved to be more appropriate than traditional functional instruments (such as the KPS) in assessing the QL of brain tumor patients and in detecting the extent of the disease.
TL;DR: The clinical presentation, preoperative evaluation, and surgical procedures used for treating tumors of the tuberculum sella, the olfactory groove, and the anterior clinoid are addressed.
Abstract: Meningiomas of the anterior skull base account for 40% of all intracranial meningiomas. Of these, almost half are sphenoid wing meningiomas; the other half are tuberculum sella tumors or olfactory groove tumors. Anterior clinoidal (medial sphenoid wing) meningiomas are a subcategory of the sphenoid wing meningiomas; they fall into one of three categories according to the presence of an interfacing arachnoidal membrane between the tumor and the cerebral vessels. Meningiomas of the tuberculum sella arise from the tuberculum sella, chiasmatic sulcus, limbus sphenoidale, and the diaphragma sella; they may extend into both optic canals. Olfactory groove meningiomas arise more anteriorly than do the tuberculum sella meningiomas and may be symmetrical around the midline or extend to one side or the other; at least 15% grow into the ethmoid sinuses. This paper addresses the clinical presentation, preoperative evaluation, and surgical procedures used for treating tumors of the tuberculum sella, the olfactory groove, and the anterior clinoid.
TL;DR: Results suggest that inactivation of another tumor suppressor gene or genes located on 17p is important in medulloblastoma tumorigenesis, as the loss of DNA sequences located on this chromosome arm is strongly associated with a negative prognosis for these patients.
Abstract: Although primary intracranial neoplasms are the most common type of solid cancer in children, little is known about their etiology at the molecular genetic level. Recently, studies have shown that a class of genes known as tumor suppressors play an important role in the origin of several different types of human tumors, including those located in the central nervous system (CNS). Using a variety of techniques, selective loss of DNA sequences has been identified in tissue specimens from children with medulloblastoma, one of the most common pediatric brain tumors. The most consistent losses to date have been shown for probes located on distal chromosome arm 17p. Although the known tumor suppressor p53 is located on this chromosome, and deletion and mutation of the p53 gene are the most common genetic events in human cancers of many types, such alterations have been infrequently detected in medulloblastoma specimens. These results suggest that inactivation of another tumor suppressor gene or genes located on 17p is important in medulloblastoma tumorigenesis. Deletion of 17p has also been shown to have implications for clinical management, as the loss of DNA sequences located on this chromosome arm is strongly associated with a negative prognosis for these patients. The identification and cloning of this tumor suppressor gene or genes will aid in understanding of the pathogenesis of medulloblastoma, as well as guiding the development of novel and more effective strategies for a cure.
TL;DR: The results comparing surgery versus radiosur surgery, which show that patients who undergo surgical treatment live longer and have better tumor control than those treated with radiosurgery, and the patient's prognosis are compared are reviewed.
Abstract: The most common structural neurologic complication of systemic cancer is brain metastasis For the most part, treatment is palliative because the majority of patients (≥ 50%) have uncontrollable systemic cancer However, for patients in whom the only metastasis is to the brain, death is more likely to result from the metastasis than from the systemic disease; hence, treatment of the metastasis is vitally important Although radiotherapy is generally considered the preferred treatment, surgical removal of the mass, whether single or multiple, may be the most effective palliation, especially for tumors from radio-resistant diseases such as melanoma, kidney and colon cancer We review the information regarding therapeutic decision-making; advances in surgical procedures, namely computer-assisted stereotactic and/or intraoperative ultrasound and mapping techniques; the efficacy of postoperative WBRT; complications and benefits of surgery; our experience with reoperation for recurrent metastatic brain tumors, the results of which indicate that reoperation for recurrent brain metastasis can prolong survival and improve quality of life for most individuals; our results comparing surgery versus radiosurgery, which show that patients who undergo surgical treatment live longer and have better tumor control than those treated with radiosurgery; and the patient's prognosis The conclusion is that surgery should remain the treatment of choice whenever possible
TL;DR: The most effective immunotherapy appears to be administration of interferon-alpha, which is relatively non-toxic and easily tolerated, but more studies are needed to better define the roles of these agents in the management of a recurrent, unresectable, or malignant meningiomas.
Abstract: The most efficacious treatment for meningiomas is surgery. For incompletely resected or recurrent tumors, radiotherapy can be given. However, when the meningioma is unresectable and/or all other previous treatments have failed, immunotherapy or chemotherapy may be considered for malignant tumors and immunotherapy and hormone therapy may be considered for benign ones. Various chemotherapy treatments that have shown some efficacy in individual cases include combinations of Adriamycin and Dacarbazine or Ifosfamide and Mesna. The most effective immunotherapy appears to be administration of interferon-alpha, which is relatively non-toxic and easily tolerated. However, more studies are needed to better define the roles of these agents in the management of a recurrent, unresectable, or malignant meningiomas.
TL;DR: Cerebellar astrocytomas, as a group, carry a more favorable prognosis than most other brain tumors, because these neoplasms generally are histologically benign and amenable to extensive resection.
Abstract: Cerebellar astrocytomas, as a group, carry a more favorable prognosis than most other brain tumors, because these neoplasms generally are histologically benign and amenable to extensive resection. However, it is clear that a number of factors have an impact on prognosis. In particular, resection extent has been strongly associated with progression-free survival: patients undergoing gross total resection appear to have a substantially better prognosis than those undergoing incomplete resection. Brainstem invasion, which is the factor that most often precludes a complete resection, has also been associated with a less favorable prognosis. In addition, histological features indicative of malignancy are clearly associated with a poor outcome.
TL;DR: Pediatric meningiomas are rare and are usually seen in association with neurofibromatosis type 2 (NF-2) or following radiation therapy, and tend to recur more frequently.
Abstract: Pediatric meningiomas are rare. They are usually seen in association with neurofibromatosis type 2 (NF-2) or following radiation therapy. The tumors are more frequently intraventricular, cystic, and infratentorial than are those in adult patients. Pathologically they are more histologically aggressive than in adults and tend to recur more frequently. Complete resection is the surgical goal. The treatment of subtotally resected meningiomas, particularly in NF-2, remains controversial.
TL;DR: Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity.
Abstract: Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma (PCNSL). To circumvent the potential emergence of drug resistance, we combined high-dose MTX with agents highly active against systemic lymphoma. Patients received three week cycles of CHOD (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 [2 mg maximum] on day 1; dexamethasone 10 mg/m2 days 1–5), and MTX (3.5 gm/m2) with leucovorin rescue on day 8 (or on recovery from the CHOD nadir). Whole brain irradiation (WBRT) was planned after at least three cycles. Eighteen patients were treated. Complete responses were seen in eleven patients, and partial responses in three. Four progressed during therapy, three succumbing to progressive disease and one subsequently responding to WBRT Response duration was 37.5 months in those responding to therapy. The time to progression for all eighteen patients was 19.5 months. Medial survival was 25.5 months. Disease-free survival was 50% at 38 months in MCHOD responders. Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles. There were three instances of neutropenic fever, three of azotemia, two of deep vein thrombosis, and one each of community-acquired pneumonia, intracranial hemorrhage, superior vena cava syndrome, and hepatotoxicity. Late radiation-related toxicities were seen in two patients. Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity.
TL;DR: The results of this preliminary study reveal limitations of the regional intratumoral adoptive immunotherapy using currently available techniques and provide sufficient evidence of its effectiveness to warrant further investigations.
Abstract: Ten patients with recurrent malignant primary brain neoplasms were treated with adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2). Nine patients had supratentorial glioma and they received multiple intratumoral instillations of LAK cells through reservoir-catheter system or burrhole. The other patients with disseminated subarachnoid metastases from posterior fossa medulloblastoma received immunotherapy via lumbar subarachnoid route. A partial and transient clinical response was observed in two patients following the therapy, and a cystic transformation of the essentially solid tumor was noted on the CT scans of these two patients. No significant clinical or radiological response to the treatment was observed in the remaining 8 patients. The results of this preliminary study reveal limitations of the regional intratumoral adoptive immunotherapy using currently available techniques and provide sufficient evidence of its effectiveness to warrant further investigations.
TL;DR: The studies established the feasibility of conducting controlled studies of the anti-tumor effects of tumor antigen-specific cellular immunotherapy in patients with recurrent astrocytoma.
Abstract: Brain tumors are highly resistant to treatment Their diffuse infiltrative nature and the relative inaccessibility of the brain to blood and lymph are barriers to surgical and cytotoxic treatments alike Preclinical animal studies demonstrated that intravenously administered tumor antigen-specific T lymphocytes will reject tumors growing in the brain Specifically activated effector T lymphocytes may be generated by in vivo immunization followed by restimulation of antigen-primed T cells with autologous tumor cells in vitro In order to apply these findings to humans, feasibility studies of combined active immunization and specific adoptive cellular immunotherapy were performed on fifteen patients with recurrent astrocytoma The objective was to determine whether; 1) T cells could be grown from peripheral blood of patients immunized with autologous tumor cells, and 2) whether stimulated cells could be safely readministered to patients Patients were immunized with a combination of their own irradiated tumor cells and Bacillus of Calmette and Guerin Two weeks later a mononuclear cell-rich fraction of blood was obtained by leukapheresis Mononuclear cells were cultured with irradiated autologous tumor cells and interleukin-2 Selective expansion of CD4+ and CD8+ T lymphocytes occurred Intravenous transfer of stimulated cells to the fifteen patients on twenty-four separate occasions with or without systemic administration of interleukin-2 was tolerated with limited toxicity The studies established the feasibility of conducting controlled studies of the anti-tumor effects of tumor antigen-specific cellular immunotherapy
TL;DR: The ability of meningiomas to proliferate, invade, and provoke neovascularization will be better understood as general theories of neoplasia crystallize in other systems.
Abstract: Meningiomas, long neglected as a subject for biological studies, are now being examined more widely as their potential for clinical recurrence and malignancy has been recognized. Most laboratory studies have focused on descriptive analyses of the content of various molecules in ex vivo specimens removed at surgery. Perturbative experiments using cultured cells are possible, but they are complicated by senescence of the cells. The respective importance of the sex steroids (estrogen, progesterone, and androgens), classical growth factors, angiogenic factors, and proteolytic enzymes in the biological behavior of meningiomas is now apparent and is coming under more detailed scrutiny. As general theories of neoplasia crystallize in other systems, the ability of meningiomas to proliferate, invade, and provoke neovascularization will be better understood.
TL;DR: This b r i e f rev iew focuses on b ra in metas tases , in pa r t i cu la r on new d e v e l o p m e n t s in the i r manage ment .
Abstract: A cancer tha t ar ises ou t s ide the cent ra l ne rvous syst e m can affect the b ra in by one of th ree mechan i sms (Table 1): 1) The b ra in can be i nvaded or comp ressed by tumor . The cancer can reach the b ra in by h e m a t o g e n o u s metas tas i s or by d i rec t ex tens ion f rom a les ion in the skull or o the r s t ruc ture surr o u n d i n g the in t rac ran ia l cavi ty (e.g. nasa l sinuses). 2) The cancer can affect the b ra in ind i rec t ly by causing me tabo l i c , nu t r i t iona l , vascu la r or i m m u n e abno rma l i t i e s tha t l ead to b ra in dysfunct ion. 3) The k n o w l e d g e tha t the pa t i en t has cancer can cause severe psycho log ica l defects tha t in te r fe re with normal b ra in funct ion. A l l of these abno rma l i t i e s are c o m m o n in pa t ien t s wi th cancer . M a n y p r e sen t imp o r t a n t d iagnos t ic and t h e r a p e u t i c p rob lems . Re cent reviews discuss m a n y of these topics in de ta i l [1-3]. This b r i e f rev iew focuses on b ra in metas tases , in pa r t i cu la r on new d e v e l o p m e n t s in the i r manage ment . M o r e ex tens ive r ecen t rev iews can be found
TL;DR: Results suggest that MMP-2 plays an important role in the ECM invasion of T98G human glioma cells in vitro.
Abstract: Human glioma cells (T98G and A172 cell lines) were cultured on various extracellular matrix (ECM) components including type I, IV and V collagens, fibronectin, laminin, and reconstituted basement membrane (Matrigel), and the role of matrix metalloproteinases (MMPs) in their growth and invasion was examined. T98G glioma cells grew well on these ECM components and invaded the reconstituted basement membrane. In contrast, A172 glioma cells showed growth inhibition on collagen types IV and V and Matrigel without invasion of the Matrigel. Gelatin zymography and enzyme immunoassays demonstrated that T98G glioma cells, but not A172 cells, secrete a large amount of matrix metallproteinase-2 (MMP-2, 72 kD gelatinase/type IV collagenase = gelatinase A), and this was confirmed by immunoblotting and immunohistochemistry. Of the two different tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), T98G cells produced only TIMP-1 during culture on Matrigel, whereas A172 cells secreted both. Although both human recombinant TIMP-1 and TIMP-2 stimulated T98G cell growth slightly on Matrigel, the in vitro invasiveness was significantly reduced by only recombinant TIMP-2. These results suggest that MMP-2 plays an important role in the ECM invasion of T98G human glioma cells in vitro.
TL;DR: It is suggested that in contrast to many other human cancers, p53 mutation is not important in the pathogenesis or progression of ependymomas.
Abstract: Ependymomas, which comprise 5% of central nervous system tumors, have not been extensively characterized genetically. The p53 tumor suppressor gene is frequently mutated in human cancer, and is important in the pathogenesis of other central nervous system (CNS) tumors. Chromosomal DNA corresponding to the p53 tumor suppressor gene was amplified by the polymerase chain reaction (PCR) from 31 archival ependymoma specimens. DNA was screened for the presence of p53 mutations by single strand conformational polymorphism (SSCP) analysis; samples with altered mobility were further tested for the presence of mutation by direct DNA sequence analysis. Of the 31 ependymomas tested, one contained a detectable DNA sequence change in the p53 gene. Sequencing revealed a silent mutation in exon 6, at codon 213, which represents a known p53 sequence polymorphism. These findings suggest that in contrast to many other human cancers, p53 mutation is not important in the pathogenesis or progression of ependymomas.
TL;DR: There is evidence to suggest that Topo I inhibitors may be beneficial in the treatment of CNS neoplasms on the basis of their antineoplastic activity alone, as well as their radiosensitizing effects.
Abstract: Despite innovations in imaging, surgery, and radiation therapy, local failure remains the principle clinical problem in most CNS malignancies. To date, chemotherapy has not made a major impact in the treatment of most adult CNS tumors. The inroads made by chemotherapy in pediatric CNS malignancies suggest that novel drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I) inhibitors are a relatively new group of chemotherapy drugs with a novel mechanism of action. Drugs in this group currently undergoing clinical trials are the Camptothecin analogues Topotecan, CPT-11, and 9-aminocamptothecin. There is substantial preclinical and some clinical evidence to suggest that these drugs could be useful in the treatment of CNS malignancies. Preclinical studies with the water soluble Topo I inhibitor, Topotecan, demonstrate antineoplastic activity in a variety of CNS malignancies. In addition, Topotecan has good CNS penetration in primates, and recent preliminary phase I and II clinical trials of Topotecan in pediatric and adult CNS malignancies have been promising. In this paper, we describe the unique mechanism of action, antineoplastic activity, and radiosensitizing properties of Topo I inhibitors. We present the first report demonstrating potentiation of radiation lethality by Topotecan in a human glioma (1354) cell line. The dose enhancement ratio was 3.2 at 10% survival. Thus, there is evidence to suggest that Topo I inhibitors may be beneficial in the treatment of CNS neoplasms on the basis of their antineoplastic activity alone, as well as their radiosensitizing effects. Two clinical trials which utilize concurrent Topotecan and radiation in the treatment of pediatric and adult CNS malignancies are discussed.
TL;DR: Effective prophylaxis exists and should be considered for lymphopenic patients and those requiring DXM for > five weeks, and in these patients attributable to use and duration of corticosteroids and in some cases cytotoxic chemotherapy.
Abstract: We reviewed the clinical features and risk factors for Pneumocystis carinii pneumonia (PCP) in patients with brain tumors (BTs) seen at our institution between 1980 and 1992. Previously rare, this opportunistic infection appears to be increasing among HIV-negative cancer patients receiving immunosuppressive medications. Recent reports have noted PCP among BT patients receiving corticosteroids, and suggested that these patients are particularly likely to develop PCP when corticosteroids are tapered. Nine BT patients, eight with high-grade gliomas, experienced ten episodes of PCP None were known HIV-positive. All were on dexamethasone (DXM) at PCP onset, and had continuously been receiving it for 47–398 days (median 69). Daily DXM dose at PCP onset ranged from 1–16 mg (median 9). Five episodes occurred in patients receiving a stable DXM dose and five during DXM taper. Nine episodes occurred in patients receiving chemotherapy. All patients had absolute lymphopenia at PCP onset, ranging from 80–900 × 106 lymphocytes/l (median 222 × 106/l, normal > 1000 × 106). Three episodes were fatal despite appropriate antibiotic therapy. Unlike others, we did not find that corticosteroid taper predisposed to developing PCP As in HIV, PCP in BT patients appears related to lymphopenia, in these patients attributable to use and duration of corticosteroids and in some cases cytotoxic chemotherapy. Effective prophylaxis exists and should be considered for lymphopenic patients and those requiring DXM for > five weeks.
TL;DR: The treatment of visual pathway gliomas is controversial as discussed by the authors, with many retrospective studies reporting outcome data for patients with chiasmatic/hypothalamic glioma are difficult to interpret for several reasons.
Abstract: The treatment of visual pathway gliomas is controversial. The many retrospective studies reporting outcome data for patients with chiasmatic/hypothalamic gliomas are difficult to interpret for several reasons. First the natural history of these tumors is erratic with some reports suggesting that most visual pathway gliomas are hamartomas and follow an indolent course, and others reporting 10-year survival rates of close to 60%. Second, earlier studies did not clearly indicate which patients had neurofibromatosis type 1 (NF1) and recent evidence suggests that the natural history of optic gliomas is more favorable in patients with NFL Third the methods and accuracy of diagnosis have changed dramatically and patients diagnosed before and after the[/p] advent of CT/MR imaging have often been included in the same series. While surgical resection is usually not a viable option for definitive treatment of these tumors, recent studies have shown favorable results after subtotal resection in selected patients. The efficacy of radiotherapy has not been unequivocally demonstrated and treatment-related morbidity has become a major concern, in particular, adverse effects on cognition and growth. Chemotherapy has been advanced as an viable alternative to avoid or delay the adverse affects of RT, but the long-term outcome benefits and adverse effects of treatment are just being defined. Despite the limitations of currently available information, sufficient data are now available to rational management quotelines for the majority of children with chiasmatic/hypothalamic gliomas.
TL;DR: There is a subset of GBM defined by the accumulation of wild-type p53 and that the over-expression of EGF-R does not preclude long-term survival, according to previous reported studies for GBM in general.
Abstract: Long term survival is rare in patients with glioblastoma multiforme (GBM). To determine if the tumors of patients with long survivals constitute a subgroup of patients with identifiable molecular genetic characteristics, we studied the p53 gene and Epidermal Growth Factor Receptor (EGF-R) expression in long-term survivors of GBM. A review of the Tumor Registry of Memorial Hospital for Cancer and Allied Diseases documented that 521 patients were treated for GBM between 1954 and 1987 and that 12 patients had seven-year or longer survivals. Six additional long-term survivors were identified from other institutions. After pathological re-examination, the diagnosis of 8 of these 18 (44%) tumors was changed to other histologic tumor types. Using immunohistochemical analysis, 4 of 10 confirmed malignant gliomas had over-expression of p53. Polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis and sequence analysis of these 4 tumors showed no p53 mutations in exons 5–8, the region where most mutations have been reported in human malignancies. Immunohistochemical analysis for EGF-R was performed on the tumors of the 10 long-term survivors. EGF-R over-expression was identified in 4 (40%), which is consistent with previous reported studies for GBM in general. These findings suggest that there is a subset of GBM defined by the accumulation of wild-type p53 and that the over-expression of EGF-R does not preclude long-term survival. The seven-year survival rate for confirmed GBM in patients from the Memorial Hospital Tumor Registry was at least 1%.
TL;DR: The goals of surgery include a complete removal, in most circumstances, with an attempt to alleviate an associated seizure disorder when intractable, in nearly every type of hemispheric glioma with the aid of intraoperative navigational systems.
Abstract: Pediatric brain tumors occur within a frequency of 24 to 27 cases/year within a cohort of 1 million children. Nearly 25% of these lesions will involve the cerebral hemisphere, with the low-grade glioma representing the most common group of tumors in this location. Pilocytic and fibrillary astrocytomas are the most frequently encountered glioma, although other variants, such as the ganglioglioma, pleomorphic xanthoastrocytoma, astroblastoma, ependymoma, and oligodendroglioma, must also be considered in the differential diagnosis. The etiology of these tumors remains obscure, although may be linked to therapeutic radiotherapy, previous history of hematopoietic malignancy, and maternal exposure to nitrosamine-laden foods. An associated link to a phakomatosis, e.g., neurofibromatosis, tuberous sclerosis, has also been documented to exist with astrocytomas, in particular. The goals of surgery include a complete removal, in most circumstances, with an attempt to alleviate an associated seizure disorder when intractable. This is possible in nearly every type of hemispheric glioma with the aid of intraoperative navigational systems, i.e., frameless stereotaxy, neurophsyiological based stimulation mapping, and electrocorticography. In the setting where a complete removal is possible, no further therapy is warranted. For those lesions that are incompletely resected, conservative management with routine diagnostic imaging follow-up is appropriate. Reoperation is necessary if recurrence is documented and radiotherapy is utilized for those lesions that are incompletely resected following recurrence.
TL;DR: Peritumoral edema on computed tomographic (CT) scan or magnetic resonance (MR) imaging was found to be an important feature of metastasis developing at this site.
Abstract: Three cases of cancer metastasis to the choroid plexus of the lateral ventricle are reported. The metastases were from sigmoid colon cancer, renal cell carcinoma and pulmonary cancer, and were located in the trigone in two cases and the right inferior horn in one. Total removal was accomplished in all cases without any complications. In addition, eight reported cases of single brain metastasis to the choroid plexus of the lateral ventricle, including clinical and radiological features, are discussed. Peritumoral edema on computed tomographic (CT) scan or magnetic resonance (MR) imaging was found to be an important feature of metastasis developing at this site.