Biomedical subjects
L M DeAngelis
Publications and source records attributed to L M DeAngelis.
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.
Primary central nervous system lymphoma.
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Telomerase activity in brain and leptomeningeal metastases.
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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.
Brain abscesses in children with cancer.
BACKGROUND: Brain abscesses in pediatric patients are rare events, and the causative organism and prognosis vary with the population under study. Children with cancer seem to be particularly susceptible to the development of brain abscesses because of the immunological changes induced by cancer and its treatment. We reviewed the records of children who developed a brain abscess during treatment of a malignancy to define the clinical characteristics, prognosis, and management of these patients. PROCEDURE: We performed a retrospective review of the clinical and laboratory characteristics of all cancer patients younger than age 20 years who were admitted to our institution between 1980 and 1996 for a brain abscess. RESULTS: Twelve children were identified. Cancer diagnoses were brain tumor in two, systemic PNET in two, and leukemia in eight. Six patients had multiple abscesses. Eleven received prior chemotherapy. Abscesses were surgically excised or aspirated in seven, and empiric antibiotics were given to the other five. At surgery, Listeria monocytogenes, Aspergillus fumigatus (3), Fusarium, and Candida lusitanea were cultured. Aspergillus was identified in other locations in four patients. Abscesses were successfully treated in seven patients, two of whom received antibiotics only; five patients (42%) died from infection. CONCLUSIONS: Mortality is high in this immunosuppressed population, in part due to the preponderance of fungal infection. The finding of very rare organisms suggests that drainage and culture should be performed whenever possible; empiric antibiotics that include an antifungal agent may, on occasion, be successful.
Malignant glioma: who benefits from adjuvant chemotherapy?
We combined two randomized prospective Brain Tumor Study Group data sets to analyze the effects of prognostic factors on survival by treatment group. Adjuvant chemotherapy increased long-term survival regardless of prognostic factors. Pathological review revealed that oligo dendrogliomas were overrepresented among long-term survivors independent of therapy. Prognostic factors do not predict benefit from adjuvant nitrosourea in malignant gliomas, and long-term survival with chemotherapy is not explained by oligodendroglial tumors.
Aging and primary central nervous system neoplasms.
The number of primary brain tumors in the aging population has increased over the past few decades. Although overall survival rates for many patients with primary central nervous system neoplasms have not changed drastically, patients with particular tumor types are benefitting from new treatments. Many factors must be considered when treating primary brain tumors in the elderly, including overall medical condition, tumor biology, and social issues.
Sarcoidosis of the cauda equina mimicking leptomeningeal malignancy.
Isolated neurosarcoidosis can present with a wide range of central nervous system manifestations. We present two cases of cauda equina sarcoidosis misdiagnosed initially as leptomeningeal malignancy, and review the literature. This unusual manifestation of neurosarcoidosis is typified by an indolent, chronic process with limited response to corticosteroid therapy.
Long-term survival in primary CNS lymphoma.
PURPOSE: We have previously reported on 31 patients with primary CNS lymphoma (PCNSL) treated between 1986 and 1992 with methotrexate (MTX), cranial radiotherapy (RT), and high-dose cytarabine who remained free of disease longer than historical controls. PATIENTS AND METHODS: We performed a follow-up analysis of our original cohort and now report their long-term survival and late treatment-related toxicity. RESULTS: The median cause-specific survival was 42 months, with a five-year survival of 22.3% compared with 3% to 4% in historical controls treated with RT alone. Age less than 50 years at diagnosis was a significant prognostic factor for survival (P = .01). Median disease-free survival was 40.3 months; 15 patients relapsed, all but one in the CNS. Late treatment-related toxicity was observed in nearly one third of patients and those more than 60 years of age were at substantially higher risk (P < .0001). CONCLUSION: Combined modality therapy for PCNSL has improved survival, but relapse is common and late neurologic toxicity is a significant complication. Although this approach is highly effective for younger patients, efficacious but less neurotoxic regimens need to be developed for older patients.
111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases.
Abnormal CSF flow can impair the distribution of intrathecally administered drugs. We examined the relationship between 111indium-diethylenetriamine pentaacetic acid (111In-DTPA) CSF flow studies and methotrexate levels in ventricular and lumbar CSF and correlated these findings with outcome in patients with leptomeningeal metastases (LM). Seven men and 10 women with LM (10 solid tumors, 6 lymphoma, 1 leukemia) received 12 mg methotrexate and 0.5 mCi 111In-DTPA by intra-Ommaya injection; images were obtained immediately and after 4, 24, and 48 hours. Ventricular and lumbar CSF methotrexate and radioactivity levels were measured 6 hours after injection. Thirteen patients had abnormal CSF flow studies, 9 with multiple sites of obstruction. CSF flow obstruction was observed at ventricular outlets in 13 patients, cerebral convexities in 9 and in the spine in 2. With one exception, all obstructions were explicable by tumor deposits on MRIs. For all patients, ventricular and lumbar methotrexate and radioactivity levels correlated closely. Three patients with a normal CSF flow study are alive at 15+, 7.5+, and 3.9+ months from treatment. Of 12 with abnormal CSF flow studies, 11 are dead a median of 2 months from diagnosis. Two patients had diffusely delayed flow studies and both developed methotrexate leukoencephalopathy. CSF flow studies using 111In-DTPA reliably predict distribution of intrathecal methotrexate. Abnormal flow studies correlate with structural abnormalities, are an unfavorable prognostic factor, and may predict intrathecal chemotherapy toxicity.
Brain tumor therapy: new horizons, new hope.
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Adult brainstem gliomas.
OBJECTIVE: To evaluate prognostic factors and survival of adult patients with brainstem gliomas. BACKGROUND: Brainstem glioma is a disease found primarily in children, with a median survival of only 9 to 12 months. However, the prognosis and survival of adults with this disease has not been determined with precision. METHODS: We conducted a retrospective analysis of patients older than 16 years at Memorial Sloan-Kettering Cancer Center with histologically proved or presumed brainstem glioma diagnosed between 1989 and 1997. We assessed the effect of gender, age at diagnosis, cranial nerve involvement, duration of symptoms, exophytic component, MRI enhancement, site of disease, treatment, and Karnofsky performance status on survival. RESULTS: Twenty-three patients were identified, but complete information was available in only 19 (12 males and 7 females). Patients ranged in age from 17 to 70 years (median, 40 years). Twelve patients were treated with radiotherapy at diagnosis and seven were observed, three of whom received subsequent radiotherapy. Median survival is 54 months (range, 3 to 98 months) and the 5-year survival is 45%. There was a trend for patients with a higher performance status at diagnosis to have longer survival, but this did not reach statistical significance. Other factors did not affect survival. CONCLUSION: Adults with brainstem gliomas may survive significantly longer than children, suggesting the disease may be less aggressive in adults. Furthermore, some patients with a long duration of symptoms or tectal or cervicomedullary tumors may be managed initially with observation alone.
Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing.
BACKGROUND: Paclitaxel-induced peripheral neuropathy (PN) may be severe and dose-limiting at initial doses > or = 275 mg/M2, but its neurotoxicity at doses < or = 250 mg/M2 has been incompletely characterized. The purposes of this study were to characterize and quantify paclitaxel-induced PN and to determine the utility of quantitative sensory testing (QST). METHODS: We prospectively examined clinically and by QST 37 women with metastatic breast cancer, treated with paclitaxel (200-250 mg/m2) (average number of cycles = 7.3 over an average of 20.1 weeks). QST included thermal threshold (TT) and vibration threshold (VT). RESULTS: Paresthesias appeared in 31 (84%) patients after an average of 1.7 cycles and an average cumulative dose of 371.5 mg/M2. Symptoms occurred after the first or second dose in 26 (84%) patients and then stabilized in 10 (32%), improved in 13 (42%) despite continued treatment, resolved completely in 6 (19%), and were progressive in 2 (7%). Paclitaxel was discontinued in only 1 (3%) patient because of neurotoxicity and no patient required dose reduction because of PN. Thirty-six (97%) developed signs of PN. The most sensitive QST was great toe VT but QST did not predict or identify subclinical PN in any patient. Neurologic syndromes other than PN developed in 12 (32%) patients, and 7 were due to metastatic cancer. CONCLUSIONS: 1) Paclitaxel-induced PN is mostly sensory, and begins after the first or second dose. At these doses the neuropathy is mild, and rarely dose-limiting. 2) QST quantified the neuropathy but was less sensitive than the clinical examination. 3) Knowledge of the features of paclitaxel's PN allows it to be differentiated from other neurologic syndromes which may signal tumor progression.
Neuroimaging abnormalities with hypoglossal nerve palsies.
Seven patients with acute or chronic unilateral hypoglossal nerve lesions were evaluated by magnetic resonance imaging and computed tomography. In the patients with acute to subacute paralysis of the tongue, the base of the ipsilateral side of the tongue appeared expanded with increased signal intensity on T2-weighted images. This appearance suggested an infiltrative mass lesion within the tongue. These radiographic findings are due to the pathophysiological process of nerve injury and muscle denervation.
Steroid myopathy in cancer patients.
We prospectively evaluated 15 adult cancer patients being treated with adrenocorticosteroids (steroids) to determine the frequency and time course of "steroid myopathy." Nine (60%) developed clinically detectable proximal muscle weakness that, in six, was severe enough to interfere with activities of daily living. Proximal muscle weakness developed within 15 days in eight of nine patients and was significantly related to the cumulative dose of steroid. Eight of nine patients with proximal muscle weakness, and two of six without such weakness, experienced a significant decline in respiratory function, leading to symptomatic dyspnea in four patients of the former group. In three patients who could be followed for more than 3 months off steroids, there was either improvement or resolution of the weakness and, when present, of the respiratory impairment. Steroid myopathy is a common complication among cancer patients receiving steroids. It can often affect respiratory function even when proximal limb muscles remain strong. Clinical recognition is important since steroid myopathy can lead to increased morbidity and may be reversible with reduction or discontinuation of steroids.
Challenges in the design and conduct of phase III brain tumor therapy trials.
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Biology and management of AIDS-associated primary CNS lymphomas.
Primary central nervous system (CNS) lymphoma is the most common brain tumor in patients with AIDS and occurs in about 10% of this population. CT/MR scan usually demonstrates single or multiple contrast enhancing masses that are radiographically indistinguishable from other CNS processes such as toxoplasmosis. Brain biopsy, positive cerebrospinal fluid (CSF) cytology, or possibly the demonstration of Epstein-Barr viral DNA in the CSF can establish the diagnosis. Cranial radiotherapy (RT) has been the cornerstone of therapy and produces responses in most patients, but their median survival is still only a few months. The addition of chemotherapy to RT may prolong survival in a sub-group of patients.