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Biomedical subjects

L M DeAngelis

Publications and source records attributed to L M DeAngelis.

At least 73 records · Page 4Linked to original sources
PubMed1993

The clinical spectrum of ocular lymphoma.

BACKGROUND: Ocular lymphoma is an uncommon cause of chronic vitreitis or uveitis, often refractory to steroid treatment, and frequently representing another site of multifocal primary central nervous system lymphoma (PCNSL). METHODS: The authors reviewed the medical and ophthalmologic records of 24 patients with ocular lymphoma; 23 had associated PCNSL: RESULTS: In half, the eyes were the initial site of disease; in the others central nervous system (CNS) lymphoma developed before, or concurrent with, ocular lymphoma. Most patients had bilateral ocular symptoms; slit-lamp examination revealed asymptomatic disease in four. Vitrectomy was not always diagnostic, particularly in patients who had received steroids. Ocular ultrasound, performed on seven patients, provided an objective measure of disease and treatment response. Patients received a variety of therapeutic combinations of steroids, radiation, and chemotherapy, including high-dose cytosine arabinoside. Despite therapy, eventual ocular or CNS relapse or both was common. Thirteen patients have died, 12 with known recurrent CNS disease. CONCLUSIONS: Ocular lymphoma frequently is associated with PCNSL: The diagnosis should be considered in patients with steroid-resistant chronic vitreitis or uveitis. Patients with PCNSL should be carefully evaluated for ocular involvement, regardless of symptoms. Treatment can contribute to prolonged remission, but eventual ocular or CNS relapse is the rule.

Adolescent↗
PubMed1993

Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies.

We describe three patients with known or suspected small-cell lung cancer (SCLC), paraneoplastic neurological syndromes, and antineuronal antibodies who had unusually benign clinical courses. One patient survived 8 years free of disease and was positive for the anti-Hu antibody. A second patient survived 6 years after spontaneous tumour regression and had an atypical antineuronal antibody. A third patient with both the anti-Hu and atypical antineuronal antibody had spontaneous regression of a lung mass. All three patients had a subacute sensory neuropathy. Since paraneoplastic antineuronal antibodies also bind to tumour cells, these cases suggest that some (paraneoplastic) neurological syndromes without identifiable tumour may result from immune-mediated eradication of tumour cells.

Aged↗
PubMed1993

Cerebral lymphoma presenting as a nonenhancing lesion on computed tomographic/magnetic resonance scan.

Cerebral lymphoma is usually identified on computed tomographic/magnetic resonance scan as a homogeneously contrast-enhancing periventricular mass lesion. We present 10 patients with cerebral lymphoma who had nonenhancing tumor on computed tomographic (2 patients) or magnetic resonance scan (8 patients) either at the time of diagnosis or recurrence. The absence of enhancement caused diagnostic delay in all patients and suggests that tumor resides behind an intact blood-brain barrier, raising important therapeutic implications in the design of chemotherapeutic regimens.

Adult↗
PubMed1992

Epstein-Barr virus in acquired immune deficiency syndrome (AIDS) and non-AIDS primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) still occurs mainly in patients who are immunosuppressed, but its incidence is rising dramatically among immunocompetent individuals. The Epstein-Barr virus (EBV) has been detected by in situ hybridization in PCNSL tumor tissue from patients who are immunodeficient, but not from patients who are immunocompetent. Using the more sensitive polymerase chain reaction (PCR) technique, the authors analyzed PCNSL tissue from 13 patients with acquired immune deficiency syndrome (AIDS) and 13 patients who were immunocompetent for the presence of EBV genome. METHODS: DNA was extracted from paraffin-embedded biopsy or autopsy specimens. PCR was run using primers for EBV (from the first internal repeat segment of the EBV genome), and identical samples were run simultaneously with primers against actin or the p53 gene as controls to establish the presence of DNA in the sample. Reaction products were also Southern blotted to confirm EBV specificity. RESULTS: EBV was detected in the tumor tissue of 11 of 13 patients (85%) with AIDS and of 7 of 13 patients (54%) who did not have AIDS. There was a history of illness that might suggest or predispose to immune compromise in 5 of 13 patients without AIDS; however, prior illness did not predict EBV-positive tumors. CONCLUSIONS: Although mechanisms remain to be clarified, EBV was present in a high percentage of patients with AIDS-related PCNSL and non-AIDS-related PCNSL:

Acquired Immunodeficiency Syndrome↗
PubMed1992

The spectrum of neurological disease in patients with systemic cancer.

To ascertain the range of neurological problems in patients with systemic cancer, we prospectively evaluated neurological symptoms, neurological diagnoses, and primary tumors in all patients with a history of systemic cancer examined by the Department of Neurology at the Memorial Sloan-Kettering Cancer Center, from Jul 1, 1990, to Dec 31, 1990. Of the 815 patients seen for neurological symptoms, less than half (45.2%) had metastatic involvement of the nervous system. The three most common symptoms were back pain (18.2%), altered mental status (17.1%), and headache (15.4%). The most common neurological diagnosis was brain metastasis (15.9%), followed by metabolic encephalopathy (10.2%), pain associated with bone metastases only (9.9%), and epidural extension or metastasis of tumor (8.4%). Of 133 patients with undiagnosed back or neck pain, 44 (33%) had epidural extension or metastases from tumor and 40 (30%) had pain associated with vertebral metastases only. In 15 (11%) the cause for the back pain was unrelated to metastatic disease. Of 132 patients seen on initial consultation for altered mental status, metabolic encephalopathy was the major neurological diagnosis (80; 61%); 20 (15%) had intracranial metastases. Of 97 patients with undiagnosed headache, 59 (61%) had a nonstructural cause. Fifty-three of these patients had either migraine, tension headache, or headache related to systemic illness (e.g., fever, sepsis). These results indicate that even in patients with systemic cancer, a group particularly prone to developing neurological disease that can be diagnosed radiologically, the role of clinicians remains important in helping distinguish noncancer-related and nonmetastatic neurological problems.

Adult↗
PubMed1992

Pharmacokinetics of ara-C and ara-U in plasma and CSF after high-dose administration of cytosine arabinoside.

Cytosine arabinoside (ara-C) and uracil arabinoside (ara-U) levels were measured in the plasma, cerebrospinal fluid (CSF), and urine of 10 patients exhibiting primary central nervous system lymphoma who received 31 infusions of high-dose ara-C (3 g/m2) as part of their treatment regimen. Peak plasma and CSF ara-C levels were 10.8 and 1.5 micrograms/ml, respectively. Ara-C was cleared more rapidly from plasma than from CSF. Ara-U appeared rapidly in both plasma and CSF, reaching a peak that was 10 times higher than the corresponding ara-C concentration (104 and 11.2 micrograms/ml, respectively). Only 4%-6% of the dose was excreted unchanged in the urine, but 63%-73% of it appeared as ara-U within the first 24 h. The presence of leptomeningeal lymphoma did not affect the CSF level of ara-C or ara-U.

Arabinofuranosyluracil↗
PubMed1992

Cutaneous T-cell lymphoma presenting with diffuse lymphomatous infiltration of the peripheral nerves: response to combination chemotherapy.

A patient with nonepidermotropic cutaneous T-cell lymphoma presented with severe diffuse peripheral neuropathy that was the result of lymphomatous infiltration of the peripheral nervous system. There was no other evidence of systemic disease. The diagnosis was delayed because of the unusual presentation. A peripheral nerve biopsy was instrumental in establishing the etiology of the neuropathy. The patient achieved complete clinical remission with combination chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Combined modality therapy for primary CNS lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL), formerly rare, is being seen with increased frequency among apparently immunocompetent patients. Conventional treatment has consisted of whole-brain radiotherapy (RT) and corticosteroids, with a median survival of 15 to 18 months and a 3% to 4% 5-year survival. Chemotherapy has been useful in the treatment of recurrent PCNSL. In 1985 we began a treatment protocol using chemotherapy and cranial irradiation for the initial therapy of non-AIDS PCNSL. PATIENTS AND METHODS: Thirty-one patients (group A) completed the combined modality regimen. All had placement of an Ommaya reservoir and received pre-RT systemic methotrexate, 1 g/m2, plus six doses of intra-Ommaya methotrexate at 12 mg per dose. A full course of cranial RT (4,000-cGy whole-brain RT plus a 1,440-cGy boost) was followed by two cycles of high-dose cytarabine (ara-C), with each course consisting of two doses of 3 g/m2 ara-C separated by 24 hours and infused over 3 hours. During this period, 16 additional patients (group R) were treated with RT alone, either because patients refused chemotherapy or RT was initiated before our consultation; all would have been eligible to participate in the protocol. Follow-up extended through April 1, 1991. RESULTS: Group A had a significantly prolonged time to recurrence (median, 41 months) compared with group R (median, 10 months; P = .003). Although median survival was doubled from 21.7 months for group R to 42.5 months for group A, this was not statistically significant because of small sample size. More importantly, group R patients received systemic chemotherapy for recurrent PCNSL, which improved survival. CONCLUSION: The addition of chemotherapy to cranial RT for initial treatment of PCNSL significantly improved disease-free survival and contributed to overall survival; all non-AIDS patients with newly diagnosed PCNSL should be considered for combined modality therapy.

Adult↗
PubMed1991

Evolution of neuropathy and myopathy during intensive vincristine/corticosteroid chemotherapy for non-Hodgkin's lymphoma.

Neuropathy and myopathy are common sequelae of intensive chemotherapy protocols that contain vincristine and corticosteroids. The authors prospectively monitored the evolution of neuropathy and myopathy during an intensive 12-week chemotherapy program for patients with intermediate and high-grade non-Hodgkin's lymphoma. In this study, vincristine was administered by bolus injection followed by a 3-day continuous intravenous (IV) infusion (total dose of 2.0 mg/m2 every other week); the maximum dose of vincristine was not arbitrarily limited. Cronassial, a mixture of four naturally occurring gangliosides, was administered in a randomized double-blind test to evaluate whether this agent could prevent vincristine-induced neuropathy. High doses of dexamethasone (50 mg/d for 3 days weekly or every other week) were also prescribed. Patients were monitored every 4 weeks with comprehensive physical and neurologic examinations and electrophysiologic studies of peripheral nerve function. Twenty-seven patients were fully evaluable. Weakness was a prominent adverse reaction in this study, and all patients had moderate to severe signs and symptoms of neuropathy and myopathy. Cronassial (100 mg) administered by intramuscular (IM) injection daily provided no protection against the development of neuropathic symptoms. Vincristine typically impaired fine-motor coordination initially, whereas corticosteroids were associated with delayed development of proximal muscle weakness. Results of electrodiagnostic studies did not add to the clinical examination results. The authors conclude that symptomatic weakness due to neuropathy or myopathy appears in a predictable manner during intensive vincristine/corticosteroid-based treatment protocols. Simple clinical tests can be used to rapidly distinguish between toxic effects due either to vincristine or corticosteroids, and routine implementation of these tests can prevent inappropriate dose attenuation of these agents.

Adult↗
PubMed1991

Primary central nervous system lymphoma as a secondary malignancy.

Primary central nervous system lymphoma (PCNSL) is a rare neoplasm, but it is occurring with increased frequency even among apparently immunocompetent patients. Although secondary malignancies frequently involve the lymphoreticular system, PCNSL has been reported as a second neoplasm only once previously. Seven patients are discussed who developed PCNSL after successful treatment for a prior neoplasm. The original cancer was colon (one), breast (one), thyroid (one), Hodgkin's disease (two), and non-Hodgkin's lymphoma (two). Patients with systemic non-Hodgkin's lymphoma were thought to have a separate cerebral lymphoma on the basis of a prolonged disease-free interval from their systemic lymphoma, and the absence of systemic disease, when PCNSL was diagnosed and through subsequent follow-up. The PCNSL developed a median of 10 years after the diagnosis of the first tumor and 6 years after the last evidence of systemic disease. The diagnosis of PCNSL was often delayed because of confusion with brain metastases, and initial shrinkage or disappearance of the lesion after corticosteroids. Formation of PCNSL may be a consequence of treatment for the first malignancy, reflect an unidentified inherent predisposition to neoplastic transformation, or result from the changing epidemiology of PCNSL in the general population. These mechanisms are not mutually exclusive, and a single hypothesis cannot account for all these cases.

Aged↗
PubMed1990

Primary central nervous system lymphoma imitates multiple sclerosis.

Primary central nervous system lymphoma (PCNSL) can be confused with multiple sclerosis (MS) in patients who present with neurological dysfunction, a non-enhancing periventricular lesion, and CSF pleocytosis. Administration of corticosteroid causes clinical improvement and regression of PCNSL in some patients which may be interpreted as a steroid-induced remission from an exacerbation of MS. Sustained clinical dependence upon corticosteroid is unusual in MS, and should lead to consideration of PCNSL. Repeat CSF examination and gadolinium-enhanced MRI scan obtained off corticosteroid should differentiate between the two diagnostic possibilities.

Brain Neoplasms↗
PubMed1990

The role of radiation therapy following resection of single brain metastasis from melanoma.

From 1972 to 1987, 35 patients underwent resection of a single brain metastasis from melanoma; 19 received postoperative radiation therapy (RT) (group A), and 16 did not (group B). Group A had a longer interval to CNS relapse compared with group B, but survival was similar. However, 4/17 (24%) from group A and 11/13 (85%) from group B died of neurologic causes. We conclude that patients with single brain metastasis from melanoma have improved control of CNS disease when postoperative RT is administered, and survival depends upon control of systemic disease.

Adult↗
PubMed1990

Primary CNS lymphoma: combined treatment with chemotherapy and radiotherapy.

Primary central nervous system lymphoma (PCNSL), an uncommon tumor, is occurring with increasing frequency. Conventional therapy with corticosteroids and cranial radiotherapy (RT) usually gives a dramatic initial response, but median survival is only 10 to 18 months. Chemotherapy is more successful in comparable systemic lymphoma and has been employed for PCNSL at relapse, causing remission but not cure. Between June 1985 and June 1988, we prospectively staged 32 patients with PCNSL at Memorial Sloan-Kettering Cancer Center and treated 28 on a new protocol that combined chemotherapy and radiotherapy at diagnosis. None had occult systemic lymphoma, but 19% had ocular and 69% had definite or probable leptomeningeal lymphoma. There were no complications in 19 stereotactic biopsies, but 4/10 patients who had a complete resection suffered a severe postoperative deficit. Four patients received RT alone, and 28 received chemotherapy and cranial RT, 17 of whom (group A) received a combination regimen using pre-RT systemic (1 g/m2) and intra-Ommaya methotrexate (MTX), 4,000 cGy whole-brain RT with a 1,440 cGy boost, and 2 courses of post-RT high-dose cytosine arabinoside; 5 other patients received an identical regimen but with a decreased dose of MTX (200 mg/m2). Sixty-three percent of assessable patients had a response to MTX independent of corticosteroid and prior to RT. Eighteen of 26 (69%) assessable patients who received combined therapy are alive with a median follow-up of 25.4 months. Twelve of 16 (75%) assessable group A patients are alive in the same period. Chemotherapy-related toxicity was minimal, and no late toxicities have occurred to date.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The combined use of radiation therapy and lonidamine in the treatment of brain metastases.

Lonidamine is an indazole carboxylic acid that has been shown to be synergistic with radiotherapy (RT) in tissue culture and animal models. Clinical experience has shown that lonidamine is well-tolerated, and appears to potentiate the activity of conventional chemotherapy in the treatment of brain metastases. A prospective randomized trial was undertaken to evaluate the use of lonidamine in combination with RT in the treatment of brain metastases. All patients received 3000 cGy of whole brain radiotherapy (WBRT). Fifty eight patients were enrolled; 31 received lonidamine plus WBRT and 27 received WBRT alone. There was no significant difference in response rate or survival between the treatment groups. Lonidamine blood levels were measured in 30 of the 31 patients who received the drug, and were therapeutic (greater than or equal to 15 micrograms/ml) in 50%. Survival and response rate were unaffected by the presence or absence of a therapeutic lonidamine level. The most common side-effects of lonidamine were myalgia, testicular pain, anorexia, and ototoxicity; however, only 2 patients had to discontinue the drug because of intolerable myalgias. No serious organ toxicity or myelosuppression was observed.

Adult↗
PubMed1989

Radiation-induced dementia in patients cured of brain metastases.

When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review.

Aged↗
PubMed1989

The role of postoperative radiotherapy after resection of single brain metastases.

To assess the value of whole brain radiotherapy (WBRT) after complete resection of a single brain metastasis we reviewed the records of 98 patients who had elective craniotomy between 1978 and 1985. Seventy-nine patients received postoperative WBRT (Group A) and 19 patients no radiotherapy (RT) (Group B). Neurological relapse was designated as local (i.e., at the site of the original metastasis) or distant (i.e., elsewhere in the brain). Postoperative WBRT significantly prolonged the time to any neurological relapse (P = 0.034) with a 1-year recurrence rate of 22% in Group A and 46% in Group B patients; however, it did not specifically control either local or distant cerebral recurrence. Recurrence of metastatic brain disease was not affected by location of the original lesion; however, meningeal relapse occurred in 38% of cerebellar lesions, but only in 4.7% of supratentorial metastases (P = 0.003). The total radiation dose or fractionation scheme of RT did not affect survival nor time to neurological relapse. The median survival was 20.6 and 14.4 months for Groups A and B, respectively (not statistically different). Forty-eight percent of Group A and 47% of Group B patients survived for 1 year or longer; however, 11% of patients who had received RT and survived 1 year developed severe radiation-induced dementia. All patients with radiation-related cerebral damage received hypo-fractionated RT with high daily fractions as commonly designed for rapid palliation of macroscopic brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗