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Biomedical subjects

L M DeAngelis

Publications and source records attributed to L M DeAngelis.

At least 55 records · Page 3Linked to original sources
PubMed1996

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 patients with acute to subacute tongue paralysis, the base of the ipsilateral side of the tongue appeared expanded and showed increased signal intensity on T2-weighted images. This appearance was suggestive of an infiltrative mass lesion within the tongue. These radiographic findings are due to the pathophysiological process of nerve injury and muscle denervation.

Acute Disease↗
PubMed1996

Carboxypeptidase G2 rescue after high-dose methotrexate.

PURPOSE: This study was a pilot project to assess the safety and efficacy of carboxypeptidase G2 (CPG2) rescue from high-dose (HD) methotrexate (MTX) in patients with recurrent cerebral lymphoma. PATIENTS AND METHODS: Four patients with recurrent primary CNS lymphoma (PCNSL) were studied. Patients received 3.0 g/m2 MTX infused over 2 hours. Twelve hours after the start of MTX, 50 U/kg CPG2 was infused; a second dose of CPG2 was given 6 hours after the first. Blood and CSF were collected and assayed for levels of MTX, CPG2, and 2,4-diamino-N10-methylpteroic acid (DAMPA), a cleavage product of MTX after CPG2. Serum was collected for at least 2 weeks after administration of MTX-CPG2 to assess anti-CPG2 activity antibodies. RESULTS: All patients had at least a 2-log decline in plasma MTX levels to the subtherapeutic range within 5 minutes of CPG2 administration. The second dose of CPG2 did not further diminish the already low plasma MTX level. DAMPA appeared and was detected as the plasma MTX concentration decreased. CSF MTX concentration remained elevated for 4 hours after CPG2, and its decline followed first-order kinetics. Anti-CPG2 activity antibodies were not detected in any patient. No MTX or CPG2 toxicity was observed. CONCLUSION: CPG2 rescue is a safe, effective alternative to leucovorin rescue after HD MTX and may prove particularly useful for the treatment of MTX-sensitive CNS tumors, as it does not affect CSF MTX levels.

Antimetabolites, Antineoplastic↗
PubMed1996

Low-grade oligodendroglioma responds to chemotherapy.

We administered chemotherapy in standard and intensified formulations of procarbazine, lomustine (CCNU), and vincristine to nine symptomatic patients with low-grade oligodendroglioma. Eight patients were treated with chemotherapy at presentation and one was treated for a recurrence after radiotherapy had failed. All patients improved by clinical or MRI criteria, or both. No patient deteriorated while in therapy and the responses were sustained without radiotherapy for a median of 35 months (range, 22-45) in all surviving patients treated at presentation. Chemotherapy was well tolerated; all patients developed myelosuppression, but only those receiving the intensified regimen required dose reduction or premature discontinuation of treatment. As with recurrent and anaplastic oligodendroglioma, low-grade oligodendroglioma responds to chemotherapy.

Adult↗
PubMed1996

Chemotherapy without radiation therapy as initial treatment for primary CNS lymphoma in older patients.

Chemotherapy plus radiation therapy (RT) for primary CNS lymphoma (PCNSL) has significantly improved patient survival over RT alone, but there are late neurologic sequelae of RT, particularly in the elderly. We treated 13 patients over age 50 years (mean age 74 years) with chemotherapy alone as initial treatment for PCNSL. All received methotrexate (MTX) and procarbazine; in addition, five received thiotepa, four vincristine, and four vincristine and cytarabine. Ten achieved a complete response (CR), 2 a partial response (PR), and 1 progressed through treatment. Two patients with ocular lymphoma responded to MTX, procarbazine, and vincristine. Four of six patients who relapsed after achieving a CR or PR were treated with additional chemotherapy or RT; three achieved a CR and one a PR. Five patients remain in CR at 7.5 to 30 months, one is alive at 35 months but with progressive disease, six died of PCNSL at 5 to 30.5 months, and one died in CR of sulfur allergy 2 months after diagnosis. The Karnofsky Performance Status improved in 11 to 13 patients with treatment. Cognitive deficits were present in nine patients at diagnosis and improved in eight of these nine after chemotherapy. Only one patient developed new cognitive deficits, due to progressive tumor and possibly MTX leukoencephalopathy. Chemotherapy alone for PCNSL is effective in the elderly and eliminates the risk of RT-related neurotoxicity. RT can salvage those who relapse after chemotherapy.

Aged↗
PubMed1996

Chemosensitive epidural spinal cord disease in non-Hodgkins lymphoma.

Epidural spinal cord disease (ESCD), an infrequent complication of systemic non-Hodgkins lymphoma (NHL), can occur at diagnosis or at relapse, and is usually treated with radiotherapy, or infrequently surgical decompression. We retrospectively analyzed 140 patients with intermediate-grade NHL (IG-NHL) who were treated on a dose-intense protocol using doxorubicin, vincristine, and high-dose cyclophosphamide (NHL-15). There were seven episodes of ESCD in six (4.3%) patients. Five episodes were asymptomatic at presentation; one patient had back pain, leg numbness, and tingling; and one had radicular pain and mild leg weakness. None had malignant cells in the CSF. One patient received high-dose dexamethasone after laminectomy for diagnostic biopsy; otherwise, dexamethasone was used only as an anti-emetic prior to chemotherapy. Patients who developed ESCD at diagnosis received the planned course of NHL-15 chemotherapy as treatment for ESCD, and those treated with NHL-15 who developed ESCD at relapse were given a regimen containing ifosfamide, carboplatin, and etoposide (ICE). After chemotherapy alone, five of seven episodes showed radiographic resolution of ESCD and improvement of neurologic deficits. One patient received consolidation radiotherapy (2,700 cGy) to the spine after ICE for relapsed ESCD and had a complete response. One patient had progression of systemic lymphoma and ESCD despite chemotherapy. These data suggest that chemotherapy may be effective as initial treatment of ESCD in IG-NHL and may reduce the potential complications of spinal surgery and radiotherapy.

Adult↗
PubMed1996

Motor neuropathy due to docetaxel and paclitaxel.

Paclitaxel and docetaxel are novel chemotherapeutic agents that promote the polymerization and inhibit the depolymerization of microtubules. Sensory neuropathy is common with these agents, particularly paclitaxel. We evaluated 64 patients treated with these drugs; 54 were followed prospectively. Eleven (17%, including six of the 54 prospectively followed patients) developed muscle weakness that was predominantly proximal. The weakness was idiosyncratic, occurring at any stage of treatment, had a variable course, and was reversible upon cessation of drug. All patients developed symptoms or signs of taxane-induced sensory neuropathy. Weakness was likely neuropathic in origin; electrodiagnostic studies suggested a distal axonopathy in some patients and proximal denervation (anterior horn cell or nerve root) in other.

Adult↗
PubMed1996

Medical management of cerebral metastases.

Brain edema, seizures, and venous thromboembolism are frequently encountered complications of cerebral metastases that result in increased morbidity and mortality. Effective medical management of these complications with steroids, anticonvulsants, and anticoagulants can result in symptomatic improvement and a better quality of life for these patients. However, these medical therapies should be administered only when indicated as each is associated with potentially serious toxicity.

Anticoagulants↗
PubMed1995

Central nervous system progression of metastatic breast cancer in patients treated with paclitaxel.

BACKGROUND: The possibility of tumor sanctuary sites in the central nervous system (CNS) of patients receiving paclitaxel has been suggested by laboratory data identifying low concentrations of drug in the brain and cerebrospinal fluid (CSF) of rats. METHODS: The pattern of disease progression in patients with metastatic breast cancer who had an initial response to paclitaxel treatment in five Phase II trials at the Memorial Sloan-Kettering Cancer Center was reviewed. RESULTS: Of 152 patients, 53 had a partial or complete response, and 25 had a minor response. Of the 78 patients who responded to paclitaxel, 52 had subsequent disease progression, 22 changed treatments before progression occurred (as specified by the protocol and/or to receive high dose consolidation chemotherapy), 2 stopped receiving treatment because of toxicity, 1 continued receiving treatment, and 1 died with no evidence of disease progression. Six of the 52 patients who progressed after initially responding to paclitaxel had isolated CNS progression while maintaining their systemic response (leptomeningeal metastasis in three, brain metastases in two, brain and leptomeningeal metastases in one). One patient had CNS progression (brain metastases) associated with other systemic sites of progression. All patients with CNS disease developed neurologic symptoms, prompting neurologic evaluation; one had only a mild headache, which was not recognized until evaluation for paclitaxel-related peripheral neuropathy. CONCLUSIONS: These data suggest that the CNS, and particularly the CSF, is an important sanctuary site for patients with metastatic breast cancer receiving paclitaxel.

Blood-Brain Barrier↗
PubMed1995

Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis.

The diagnosis of leptomeningeal metastasis is often difficult and usually requires the demonstration of malignant cells in the cerebrospinal fluid. Neuroimaging, however, may establish or support the diagnosis in some patients. Radiographic abnormalities consistent with or suggestive of leptomeningeal metastasis include leptomeningeal, subependymal, dural, or cranial nerve enhancement; superficial cerebral lesions; and communicating hydrocephalus. We evaluated 137 cancer patients with clinical symptoms suspicious for leptomeningeal metastasis with neuroimaging or cerebrospinal fluid cytology or both. Neuroimaging findings were abnormal in 70 of 128 tested patients; cytology was performed in 58 of these 70 and the results were positive in 37. Conversely, cytological findings were positive in 53 of 115 tested patients; neuroimaging was performed in 49 of these 53 and the findings were abnormal in 37 (26/29 solid tumors and 11/20 hematological tumors). Of the total series of 137 patients, leptomeningeal metastasis was diagnosed in 77; in 24 (31%) the diagnosis was made on the basis of clinical picture and abnormal neuroimaging alone. Neuroimaging is a valuable tool in the investigation of leptomeningeal metastasis in the cancer population, and the presence of typical clinical features together with appropriate neuroimaging abnormalities is adequate to make the diagnosis of leptomeningeal metastasis even if cerebrospinal fluid cytological results are negative.

Adolescent↗
PubMed1995

Leptomeningeal tumor in primary central nervous system lymphoma: recognition, significance, and implications.

The true incidence of leptomeningeal tumor in primary central nervous system lymphoma is unknown. We studied prospectively the cerebrospinal fluid profile of 96 patients without acquired immunodeficiency syndrome but with primary central nervous system lymphoma at diagnosis, at completion of treatment, and at recurrence. Magnetic resonance images and pathology slides were examined for evidence of leptomeningeal tumor. Leptomeningeal tumor was diagnosed by (1) positive findings on cerebrospinal fluid cytology, (2) leptomeningeal or subependymal enhancement on magnetic resonance imaging, or (3) pathological evidence of leptomeningeal tumor. We recorded whether treatment directed against the leptomeninges was given. Cerebrospinal fluid was examined in 86 of 96 patients at diagnosis and 29 of 42 at recurrence. The incidence of leptomeningeal tumor was 42% at diagnosis and 41% at recurrence. Only elevated levels of protein and lactate dehydrogenase isoenzyme-5 were significantly associated with leptomeningeal tumor (p = 0.012, p = 0.016, respectively). Treatment against the leptomeninges was significantly associated with the probability of achieving a complete response and a longer freedom from relapse. Patients older than 50 years had a worse disease-specific survival but a similar probability of responding to therapy as younger patients. Our data show that leptomeningeal tumor in primary central nervous system lymphoma is more prevalent than originally thought, and indicate the need for therapy inclusive of the leptomeninges in all patients.

Arachnoid↗
PubMed1995

Primary brain tumors in the acquired immunodeficiency syndrome.

Primary central nervous system lymphoma occurs in about 10% of patients with the acquired immunodeficiency syndrome, and is the most common brain tumor in this population. Patients present with an altered mental status and lateralizing signs. Computed tomography or magnetic resonance scan usually demonstrates single or multiple contrast-enhancing masses which are indistinguishable from toxoplasmosis or other central nervous system processes. Brain biopsy or possibly the demonstration of Epstein-Barr viral DNA in the cerebrospinal fluid are the only definitive means of diagnosis. Cranial irradiation has been the cornerstone of therapy, producing regression of tumor in most patients; however, median survival is only a few months. Recent experience of combining chemotherapy with radiotherapy suggests that a subgroup of patients can benefit from this approach, with survival reaching 1-2 years.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Primary central nervous system lymphoma.

The rising incidence of PCNSL has allowed a greater understanding of the clinical features and behavior of this once rare tumor. Factors such as dissemination of tumor within the central nervous system, the presence of tumor behind an intact blood-brain barrier, as well as leptomeningeal and ocular involvement must be considered in the design of treatment protocols for this disease. The addition of chemotherapy has made a significant impact on the treatment of PCNSL, but the prognosis of PCNSL remains worse than for comparable systemic non-Hodgkin's lymphomas. With continued development of chemotherapy regimens, the hope is for improved survival without the need for potentially neurotoxic radiation therapy.

Brain↗
PubMed1994

Hormonal ablation as effective therapy for carcinomatous meningitis from prostatic carcinoma.

BACKGROUND: Metastases to the meninges from prostatic cancer are rare, accounting for less than 0.5% of all solid tumor cases. Management for patients with leptomeningeal metastases of various histologic types includes intrathecal chemotherapy and radiation therapy, but the prognosis is poor. Therefore, the identification of selected patients for whom effective therapy exists is of paramount importance. METHODS: A patient with adenocarcinoma of the prostate presented with leptomeningeal metastases as his first manifestation of metastatic disease. RESULTS: Androgen blockade was initiated with flutamide and ketoconazole. After 5 days of therapy, leuprolide acetate depot was substituted for ketoconazole. The patient responded to therapy and remained asymptomatic with a normal serum prostate-specific antigen levels at 16-plus months with no further evidence of malignant cells in spinal fluid from repeated lumbar punctures. CONCLUSION: Patients with hormone-naive metastatic prostatic carcinoma manifested as carcinomatous meningitis should be considered for hormonal ablative therapy. This is preferred to the use of intrathecal chemotherapy, which has limited efficacy.

Adenocarcinoma↗
PubMed1994

Therapy of venous thromboembolism in patients with brain metastases.

BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are common in patients with brain metastases. Few data exist to help guide the clinician's choice between the two therapeutic options of anticoagulation and inferior vena cava filter placement. METHODS: The authors reviewed their institutions' experience with the treatment of venous thromboembolism in 51 adult patients with known brain metastases since 1980. RESULTS: Ten patients were initially treated with Greenfield filters; four (40%) had recurrent nonfatal thromboembolic events (two PE and two DVT), and three required anticoagulation. Thirty-nine patients were treated initially with anticoagulation; none of these patients later received filters. Two patients with DVT were untreated and both died of PE. Among 42 patients who received anticoagulation, the duration of anticoagulation ranged from 5 to 563 days (mean, 100 days). Two patients who received anticoagulation experienced devastating central nervous system hemorrhage in the setting of supratherapeutic anticoagulation by conventional laboratory criteria. A third patient experienced a minor deterioration, possibly attributable to hemorrhage, for a 7% (3 of 42) incidence of serious central nervous system complications. Three asymptomatic patients developed hyperdensity within metastases on routine follow-up noncontrast computed tomography scan, suggesting possible intratumoral hemorrhage. Three patients taking warfarin had recurrent DVT with prothrombin time between 15.1 and 17.7. Systemic bleeding complications were generally minor and occurred in only eight patients (19%). CONCLUSIONS: Anticoagulation is more effective than Greenfield filters and acceptably safe when maintained in the therapeutic range in most patients with brain metastases and venous thromboembolism.

Adult↗
PubMed1994

Combined-modality therapy in the treatment of primary central nervous system lymphoma in AIDS.

PURPOSE: Conventional therapy--ie, treatment with corticosteroids and cranial radiotherapy (RT)--is inadequate to treat AIDS-related primary central nervous system lymphoma (PCNSL), as it achieves a median survival of only 2 to 5 months. Chemotherapy added to RT in non-AIDS PCNSL improves disease control and prolongs survival. We studied the efficacy of this approach with RT in AIDS-related PCNSL. METHODS: Ten AIDS patients with PCNSL were treated with chemotherapy--nine at diagnosis and one at recurrence. None had evidence of systemic lymphoma. All patients treated at diagnosis received pre-RT methotrexate--eight also received thiotepa and procarbazine--followed by whole-brain RT. The patient treated at recurrence (who had been previously irradiated) received chemotherapy alone, including methotrexate, thiotepa, and procarbazine. RESULTS: All had enhancing lesions on MRI and five (50%) had a single lesion (seven [70%] had a ring-enhancing mass). No patient had a response to corticosteroids. Four of seven (57%) assessable patients had a partial or complete response to chemotherapy prior to RT. Six of seven (86%) assessable patients had a complete response at the end of treatment. Median survival was 3.5 months for all 10 patients and 7 months for the eight patients who completed therapy. Two patients survived for 1 year or longer. Eight patients died--six from infection (two treatment-related), one from progressive dementia, and one from a gastrointestinal hemorrhage. CONCLUSION: AIDS-related PCNSL responds to chemotherapy and RT, but only a few patients benefit with prolonged survival.

Adult↗
PubMed1994

Management of brain metastases.

Brain metastases usually develop in patients with disseminated systemic disease. Effective palliation is available for the vast majority of patients with brain metastases, but many will die within 6 months, usually from progressive systemic tumor. However, in a substantial proportion of patients, a vigorous therapeutic approach using surgery, radiotherapy, and possibly chemotherapy leads to years of productive life. Recurrent brain metastases can often be retreated using newer techniques of brachytherapy and stereotactic radiosurgery as well as conventional treatments. Brain metastases do not necessarily mean imminent death for every patient, and physicians can now offer patients a growing range of therapeutic options. Furthermore, attention to symptomatic therapies can improve the quality of life for all patients, even those whose survival will be relatively short.

Adrenal Cortex Hormones↗