Weighing the benefits and risks of radiation therapy for low-grade glioma.
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Brain Neoplasms↗
Biomedical subjects
L M DeAngelis
Publications and source records attributed to L M DeAngelis.
Leptomeningeal metastasis from an intracranial epidermoid cyst.
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Brain Diseases↗
Brain tumors.
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Antineoplastic Combined Chemotherapy Protocols↗
Long-term outcome of low-grade oligodendroglioma and mixed glioma.
BACKGROUND: Low-grade oligodendrogliomas and mixed gliomas can be indolent and remain unchanged for years. Optimal timing and effectiveness of initial treatment is uncertain and therapy can be associated with toxicity. METHODS: Retrospective review of patients diagnosed between 1979 and 1997 with low-grade oligodendroglioma or mixed glioma. Time to progression, survival, prognostic factors, and treatment toxicities were evaluated. RESULTS: A total of 106 patients (77 oligodendroglioma, 29 mixed glioma) were identified; median age was 36.7 years. Initial presenting symptoms were seizures in 76 (72%) and headache in 11 (10%); tumor was diagnosed as an incidental finding in five patients. Tumor progression was diagnosed in 72 patients (68%). Overall median time to progression (MTTP) was 5.0 years (range 0.5 to 14.2). Median overall survival (OS) was 16.7 years. No prognostic factors reached statistical significance. MTTP and OS were not significantly affected by treatment. Of 62 patients who received radiation therapy, 9 (15%) developed radiation necrosis and 13 developed radiation therapy-related cognitive changes, requiring ventriculoperitoneal shunting in six. Significant myelosuppression was seen in 35 of 76 (46%) patients treated with chemotherapy. CONCLUSIONS: Low-grade oligodendroglioma and mixed glioma have a long median overall survival. There were no apparent differences in either immediate versus deferred treatment or choice of initial therapy on disease-free or overall survival. Chemotherapy was associated with significant acute toxicity in almost one half of patients; radiation therapy produced late neurotoxicity in one third, justifying deferred treatment until clinically necessary.
Adolescent↗
Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients.
OBJECTIVE: To report the characteristics of cerebral sinus thrombosis (CST) in cancer patients diagnosed by MRI and MR venography (MRV). BACKGROUND: CST is a complication of cancer with multiple etiologies and variable symptoms at presentation. Most reports in cancer patients were before the use of MRI and MRV, which has simplified the diagnosis of CST. METHODS: The neurology database at Memorial Sloan-Kettering Cancer Center was used to identify cancer patients with a diagnosis of CST between January 1994 and April 1998. RESULTS: Twenty patients were identified. Nine had hematologic malignancies (HMs) and 11 had solid tumors (STs). The median interval from cancer diagnosis to presentation was 4 months for HMs and 20 months for STs. The most common symptom was headache. MRI and MRV correlated in all but three patients, and MRV was more sensitive in four patients. The most frequently involved cerebral sinus was the superior sagittal sinus. Multiple sinuses were affected in 8 of 19 patients. Five patients had a cerebral or subarachnoid hemorrhage and three had infarction. Disorders of coagulation were the most frequent etiology in patients with HM; compression or invasion of the cerebral sinus from dural/calvarial metastasis was the main cause in those with ST. Treatment was directed at the underlying cause. Ten of 20 patients improved clinically and 3 of 6 patients improved radiologically. CONCLUSION: MRI and MRV can diagnose CST accurately in cancer patients. Causes of CST depend on cancer type, and treatment varies with etiology. Most patients have a good outcome.
Adolescent↗
Altered mental status in patients with cancer.
OBJECTIVE: To identify the causes of an altered mental status in a cancer population. METHODS: We studied 140 confused patients with cancer (100 prospectively and 40 retrospectively) between January 1, 1991, and June 30, 1992, to determine clinical findings, causes, and outcome. RESULTS: All patients had non-central nervous system cancers. The most common primary cancer types were lung (20%), gastrointestinal tract (18%), leukemia and lymphoma (17%), and breast (11%). Median patient age was 73 years, and 49% were men. Disseminated systemic metastases were present in 50% of patients; 34% were confused at hospital admission and 66% developed confusion during hospitalization. Symptoms included lethargy or coma in 61% of patients, agitation in 44%, disorientation in 83%, lateralizing signs in 41%, delusions or hallucinations in 28%, and seizures in 9%. A single cause of the altered mental status was found in 33% of patients, whereas 67% had multiple causes. Drugs, especially opioids, were associated with altered mental status in 64% of patients, metabolic abnormalities in 53%, infection in 46%, and recent surgery in 32%. A structural brain lesion was the sole cause of encephalopathy in 15% of patients. Although delirium improved in 67% of patients, it was a poor prognostic factor for overall outcome. Thirty-day mortality was 25%, and 44% of patients died within 6 months, usually from progression of the underlying cancer. Prolonged delirium suggested infection or coagulopathy. Younger patients and those with hypoxemia or kidney or liver dysfunction were more likely to die (P<.05). CONCLUSION: Patients with cancer usually have multiple causes of delirium, many of which are treatable, with rapid improvement in their cognitive status.
Adult↗
An integrated functional magnetic resonance imaging procedure for preoperative mapping of cortical areas associated with tactile, motor, language, and visual functions.
OBJECTIVE: To evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions. METHODS: Sensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6). RESULTS: For healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke's area, and 93% for the putative Broca's area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke's area, and 77% for the putative Broca's area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results. CONCLUSION: This integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.
Adolescent↗
Treatment for primary CNS lymphoma: the next step.
PURPOSE: The use of preradiotherapy (RT) methotrexate (MTX) has improved disease control and survival in patients with primary CNS lymphoma (PCNSL). The reported protocol was designed to optimize and enhance the chemotherapeutic component of treatment. PATIENTS AND METHODS: Fifty-two patients were treated with five cycles of high-dose MTX 3.5 g/m(2), procarbazine 100 mg/m(2)/d, and vincristine 1.4 mg/m(2). Thirty patients received whole-brain RT (45 Gy). Twenty-two older patients deferred RT to diminish the risk of delayed neurotoxicity; these patients are compared with 12 older patients who completed the entire treatment regimen. Most patients (n = 35) received high-dose cytarabine after RT. RESULTS: Objective response rate to the induction chemotherapy regimen was 90%; overall median survival is 60 months. Grade 3 or 4 myelosuppression was seen in 30 patients, primarily in association with cytarabine; grade 3 nephrotoxicity due to MTX was seen in two patients. Older patients had similar median survival with or without the addition of RT: 32 versus 33 months, respectively. However, late neurotoxicity was significantly more common in those older patients who received RT (P: =.00004). Patients younger than 60 years who received the complete treatment regimen have not reached median disease-free or overall survival. CONCLUSION: Increasing the dose of MTX and adding procarbazine and vincristine improved disease control and overall survival in patients with newly diagnosed PCNSL. Younger patients in particular fared extremely well with this treatment regimen. In older patients, deferring whole-brain RT did not compromise overall survival but did reduce treatment-related toxicity.
Adult↗
Update on the management of primary CNS lymphoma.
Primary central nervous system (CNS) lymphoma is a non-Hodgkin's lymphoma restricted to the nervous system. The incidence of this lymphoma is rising in the immunocompetent population but may be decreasing in patients with the acquired immune deficiency syndrome (AIDS) due to the introduction of highly active antiretroviral therapy. A periventricular, diffusely enhancing lesion on magnetic resonance imaging (MRI) is suggestive of primary CNS lymphoma, but a stereotactic biopsy is needed to make a definitive diagnosis. Concurrent leptomeningeal and ocular involvement is common in this brain tumor. Because primary CNS lymphoma is exquisitely sensitive to steroids, these drugs should be withheld until tissue is obtained for diagnosis. Age and performance status are important prognostic factors, regardless of specific treatment. Methotrexate in high doses is the single most effective chemotherapeutic agent for primary CNS lymphoma. It substantially improves survival when combined with radiation therapy and is better than radiotherapy alone as a single agent. Multimodality treatment results in delayed cognitive neurotoxicity, particularly in older patients. New treatment protocols have focused on the use of chemotherapy alone.
Antineoplastic Agents↗
Neurologic emergencies in the cancer patient.
Neurologic complications of cancer and its therapy are varied and common, but there are few true neurologic emergencies. However, when a neurologic emergency does occur, rapid diagnosis and treatment can preserve neurologic function and, in some circumstances, save a life. Epidural spinal cord compression, raised intracranial pressure (ICP), status epilepticus, and intracerebral hemorrhage (ICH) are the most common neurologic emergencies in the cancer patient. This chapter details the clinical features, possible etiologies, diagnostic tests, and treatment options for each of these complications.
Antineoplastic Agents↗
Herpes varicella zoster encephalitis in immunocompromised patients.
The authors describe specific MRI features that suggest the diagnosis of varicella zoster encephalitis. MRI initially revealed discrete, subcortical, nonenhancing lesions that coalesced and developed enhancement. Gray matter involvement was seen later. Autopsy revealed spherical lesions of demyelination and hemorrhagic cavitation confirmed as varicella zoster encephalitis. Characteristic MR features may suggest the diagnosis of varicella zoster encephalitis, enabling definitive diagnostic testing and early institution of antiviral treatment.
Adult↗
Primary CNS lymphoma: treatment with combined chemotherapy and radiotherapy.
Primary central nervous system lymphoma (PCNSL) is a relatively uncommon primary brain tumor, but it has become the focus of many clinical trials because of its rising incidence and unique sensitivity to systemic chemotherapeutic agents. Radiotherapy can achieve high response rates and remissions in most patients, but survival is usually only 12-18 months because disease recurs. The addition of systemic chemotherapy, particularly intravenous methotrexate, had markedly improved disease control and many patients can achieve a durable remission and occasionally cure of their disease. Conventional systemic lymphoma drug combinations such as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are ineffective. High-dose methotrexate is the single most active and important agent in the treatment of this disease. Whether improved disease control can be accomplished by adding other drugs to high-dose methotrexate or whether it is sufficient as a single agent has yet to be answered. High-dose methotrexate combined with cranial irradiation yields a median survival of at least 40 months and five year survival rates of 22%. However, neurotoxicity is substantial in a significant proportion of patients, particularly those over the age of 60 at the time of treatment. As many as 50% of such patients develop severe dementia. This is particularly important in a disease where approximately half of patients above the age of 60 had presentation. Efforts are now being directed towards not only improving disease control but also minimizing late neurotoxicity. Most efforts are currently directed towards using chemotherapy as the sole modality in the treatment of PCNSL, but both an optimal chemotherapy regimen, and the role of radiotherapy remain to be determined.
Antineoplastic Combined Chemotherapy Protocols↗
Is primary CNS lymphoma really becoming more common? A population-based study of incidence, clinicopathological features and outcomes in Alberta from 1975 to 1996.
BACKGROUND: The incidence of primary CNS lymphoma (PCNSL) is believed to be increasing in immunocompetent patients but this may not be universally true. The objective of this study was to determine in a population if the incidence of PCNSL is increasing, if the histologic subtypes are changing, and to describe the clinicopathologic and outcome characteristics of PCNSL. PATIENTS AND METHODS: We identified all Alberta residents with a histologic diagnosis of PCNSL from 1 January 1975 to 31 December 1996 using the Alberta Cancer Registry. Annual age-standardized incidence rates (ASIR), clinicopathologic and outcome characteristics were determined. RESULTS: There were 50 immunocompetent PCNSL patients; the median age was 64 and 30 were male. Their median survival was 10.15 months. Histology was available for review in 37 (74%) patients: 19 (51%) were diffuse large cell, 16 (43%) were immunoblastic and 2 (5%) were unclassifiable malignant lymphomas. The ASIR ranged from 0.178-1.631/10(6) and no change in ASIR was found (test for trend, P = 0.26) for gender or age. The ASIR of malignant gliomas did not change either but increased for all other non-Hodgkin's lymphoma (94.95-138.7610(6); test for trend, P = 0.0001) The number of brain biopsies increased from 1979-1985 (test for trend, P < 0.0001) but remained stable from 1986-1996 (test for trend, P = 0.99). CONCLUSIONS: Unlike several other populations, PCNSL is not becoming significantly more common in Alberta. If this difference is real (i.e., not due to differences in cancer registry coding practices etc.) comparisons between Albertans and other populations in whom the incidence is rising may provide clues regarding the etiology of PCNSL.
Adolescent↗
Primary central nervous system lymphoma.
Primary central nervous system (CNS) lymphoma is an unusual but increasingly frequent brain tumor being identified by neurologists. Considerable improvements in survival have been accomplished by the addition of chemotherapy to cranial radiotherapy. In addition, many patients achieve substantial disease free survival with chemotherapy alone, and survival is superior to radiotherapy alone. Currently, every patient should be considered for chemotherapy as the first line of treatment. Subsequent cranial radiotherapy may or may not be necessary depending upon the patient's clinical condition, age and response to initial chemotherapy. Intensification of multi-agent chemotherapy is under study and it is anticipated that the incidence of neurotoxicity will reduce with elimination of combined modality treatment.
Central Nervous System Neoplasms↗
Primary central nervous system lymphoma.
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Central Nervous System Neoplasms↗
Telomerase activity in brain and leptomeningeal metastases.
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Brain↗
Hydrocephalus in radiation leukoencephalopathy: results of ventriculoperitoneal shunting.
OBJECTIVE: To assess the clinical benefit of ventriculoperitoneal shunting in patients suffering from radiotherapy-induced leukoencephalopathy. DESIGN: Retrospective review of a single institutional experience. PATIENTS: Thirty-one patients with the postradiotherapy syndrome received ventriculoperitoneal shunts. All had a history of cranial irradiation, progressive ventriculomegaly visible on neuroimaging scans, and neurologic decline; other causes of hydrocephalus were excluded. All 31 patients had cognitive deficits: 30 had gait disturbance and 24 were incontinent. RESULTS: Twenty-four (80%) of 30 assessable patients achieved symptomatic improvement an average of 1.6 months after ventriculoperitoneal shunting. Incontinence and gait problems were more likely to improve than cognition. Sixteen (53%) of 30 patients achieved a good overall functional outcome, and incontinence was the only feature significantly associated with good outcome (P=.04). Neither cerebrospinal fluid-opening pressure nor tap tests predicted improvement from ventriculoperitoneal shunting. Median duration of improvement was 6 months, and median survival after receiving the shunt was 14.5 months. Shunt-related complications occurred in 10 (33%) of 30 patients, with 1 fatal outcome. CONCLUSIONS: Our results from ventriculoperitoneal shunting in selected patients with radiation-induced hydrocephalus suggest potential benefit. Improvement is incomplete and temporary, but can improve quality of life. Reliable predictors of successful shunt outcome were not identified.
Adult↗