Biomedical subjects

M C Chamberlain

Publications and source records attributed to M C Chamberlain.

At least 73 records · Page 4Linked to original sources

PubMed1993

Quantitative cerebrospinal fluid cytology in patients receiving intracavitary chemotherapy.

Cytological evaluation of cerebrospinal fluid (CSF) is an important means of following response to intracavitary chemotherapy for leptomeningeal malignancy. We studied the feasibility of quantitative cytological evaluation by retrospective analysis of serial CSF specimens from 7 patients receiving phase I intracavitary chemotherapy for leptomeningeal malignancy who had persistent malignant cytology. Three to 34 CSF specimens per patient obtained over a 3- to 48-week period were reviewed. Significant (five- to 10-fold or greater) reductions in numbers of malignant cells in CSF during treatment could be identified in specimens otherwise diagnosed as positive. Quantitative CSF cytological evaluation is neither overly time consuming nor tedious to perform and may provide useful clinical information.

Adult↗

PubMed1993

Recurrent brainstem gliomas treated with oral VP-16.

12 patients: (7 males and 5 females) with recurrent brainstem gliomas were treated with the oral topoisomerase inhibitor VP-16 (Etoposide). Patients ranged in age from 3 to 49 years with a median age of 7 years. All patients had been previously treated with radiation therapy (conventional fractionation: 4; hyperfractionation: 8) and 5 had received prior nitrosourea-based chemotherapy at time of tumor recurrence. Tumor recurrence was documented by radiographic tumor enlargement utilizing brain MRI with gadolinium enhancement (12) and clinical neurologic deterioration (9). Two patients underwent biopsy pathologically documenting tumor recurrence. Each cycle of therapy consisted of 21 days of VP-16 (50 mg/m2/day) followed by a 14 day rest followed by an additional 21 days of VP-16 (50 mg/m2 day). Complete blood counts were followed bi-weekly and a neurologic examination and brain MRI scan with contrast were performed prior to initiation of each cycle of therapy. Treatment related complications included: partial alopecia (5); diarrhea (5); weight loss (4); neutropenia (2); and thrombocytopenia (4). No patient required transfusion or antibiotic treatment of neutropenic fever. There were no treatment related deaths. 12 patients were evaluable of whom 6 demonstrated a radiographic response (1 complete; 3 partial; 2 stable disease) with a median duration of response of 8 months. In summary; oral VP-16 is a well tolerated and relatively non-toxic chemotherapeutic agent with apparent activity in this small cohort of patients with recurrent brainstem gliomas.

Administration, Oral↗

PubMed1993

Pediatric AIDS: a longitudinal comparative MRI and CT brain imaging study.

Fourteen consecutive children with acquired immune deficiency syndrome (AIDS) (age range, 4 months to 11 years; median 4 years) were studied prospectively comparing nonenhanced cranial magnetic resonance imaging (MRI) and computed tomographic (CT) scans. MRI and CT were performed twice: at time of entry into protocol and again at 1 year. In addition, sequential neurologic (every 2 months) and neuropsychological examinations (every 6 months) were performed. At entry, 12 children had abnormal neurologic examinations; of these, 10 had developmental delay; two children were normal by developmental history and neurologic examination. Five children performed in the normal range on a standardized neuropsychological test, whereas nine children showed significant delays in verbal or motor/perceptual development. Following 1 year of study, four children had normal and six had abnormal neurologic examinations (six stable and four improved). Neuropsychological examinations were normal in five children and abnormal in five (seven stable, one improved, and two deteriorated). At entry, the following neuroradiographic abnormalities were seen: brain parenchymal volume loss (eight, MR = CT), cervical lymphatic enlargement (four, MR = CT), striatal-thalamic calcification (one, CT > MR), delayed myelination (one, MR > CT), and focal white-matter lesions (one, MR > CT). At 1 year the following neuroradiographic changes were seen: brain parenchymal volume loss (10, MR = CT; two improved, eight stable); cervical lymphatic enlargement (one, MR = CT; three improved, one stable), striatal-thalamic calcification (one, CT > MR; one new), and focal white-matter lesions (one, MR > CT; one stable).(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗

PubMed1993

Involved-field radiotherapy and intra-Ommaya methotrexate/cytarabine in patients with AIDS-related lymphomatous meningitis.

PURPOSE: To evaluate combined limited-field radiotherapy and concentration times time (C X T) intra-CSF chemotherapy in patients with AIDS-related lymphomatous meningitis (LM). PATIENTS AND METHODS: Fourteen men and one woman with AIDS had cytologically documented LM. Eleven patients had systemic non-Hodgkin's lymphoma (NHL) (all B-cell histology, including six immunoblastic, four large cell, one small cell) with leptomeningeal metastases and four patients had primary CNS lymphoma (PCNSL) (all B-cell histology, including two immunoblastic, two large cell) with CSF dissemination. Presenting neurologic examinations included cranial neuropathies (n = 7), normal (n = 4), abulia (n = 2), paraparesis (n = 2), ataxia (n = 1), hemiparesis (n = 1), and aphasia (n = 1). Standardized pretreatment evaluations included contrast cranial magnetic resonance/computed tomography (MR/CT), placement of an intraventricular reservoir, CT myelogram/contrast spine MR, ophthalmologic examination, and indium 111-pentetic acid (DTPA) CSF flow studies. Regions of bulky or symptomatic disease were treated with limited-field radiation therapy, which included whole brain in 10 patients combined with spinal cord irradiation in five patients. Concurrent systemic chemotherapy was administered in 12 patients. All patients were scheduled to receive intraventricular methotrexate (MTX) 2 mg/d for 5 consecutive days biweekly for 8 weeks (induction), followed in cytologically responding patients by MTX administered in a similar manner every 4 weeks (maintenance). In MTX-responsive and consenting patients with cytologic relapse, intraventricular cytarabine (ara-C) was administered, 25 mg/d for 3 consecutive days weekly for 4 weeks (induction), followed by ara-C administered in a similar manner every 4 weeks (maintenance). CSF cytology and neurologic examinations were performed biweekly. RESULTS: In 13 assessable patients (two patients refused CNS directed therapy following standardized pretreatment evaluations), median time to tumor progression was 60 days (range, 3 to 260) and median survival duration was 125 days (range, 44 to 260). Response rate, determined clinically (four of 13 patients) and cytologically (nine of 13), was 69%. Complications included reservoir infection (n = 2) and myelosuppression (n = 11); the latter was felt to be a consequence of coadministered systemic chemotherapy. CONCLUSION: There were no treatment-related deaths. We conclude that involved-field irradiation and intraventricular MTX/ara-C is effective palliative treatment of AIDS-related LM.

Adult↗

PubMed1993

Extended CSF cytarabine exposure following intrathecal administration of DTC 101.

PURPOSE: The aims of the present study were to determine ventricular and lumbar CSF pharmacokinetics and the maximum-tolerated dose (MTD) of DTC 101 (DepoFoam; DepoTech Corp, La Jolla, CA) following intraventricular administration. PATIENTS AND METHODS: Twelve patients with neoplastic meningitis were treated with escalating doses of DTC 101. CSF samples were obtained from the right lateral ventricle or from the lumbar subarachnoid space and cytarabine concentrations were determined by high-performance liquid chromatography. RESULTS: Therapeutic ventricular CSF concentrations were maintained for 9 +/- 2 days following administration of a single dose of DTC 101 into the lateral ventricle. Lumbar cytarabine concentrations became equal to those in the ventricle within the first 6 hours after intraventricular injection, and the subsequent decay in concentrations of free and total cytarabine were the same at both sites. Following intralumbar administration, the peak ventricular concentration of free cytarabine was reached within 1 day, and therapeutic ventricular CSF levels were maintained for several days. Therapeutic intralumbar concentration of free cytarabine was maintained for up to 14 days. The MTD was 75 mg of DTC 101, and seven of nine patients manifested cytologic responses. CONCLUSION: Extended CSF exposure to therapeutic cytarabine concentrations was achieved after a single intraventricular or intralumbar dose of DTC 101, permitting drug administration once every 2 weeks.

Adolescent↗

PubMed1992

Primary central nervous system lymphoma: a role for adjuvant chemotherapy.

Sixteen immunocompetent patients, 10 of whom were previously reported, with primary non-Hodgkins lymphoma of the central nervous system (PCNSL) were treated and followed longitudinally by the Neuro-oncology Service at the University of California, San Francisco (UCSF) and the University of California, San Diego (UCSD). After undergoing surgery (biopsy or resection), these patients received radiation therapy (RT) with hydroxyurea (HU) followed by adjuvant chemotherapy with the combination of procarbazine, CCNU, and vincristine (PCV) as previously reported. All patients ultimately died of progressive recurrent PCNSL. Toxicity using the HU + RT followed by PCV schedule was tolerable. Median and quartile survival data (41 and 65 months, respectively) suggest efficacy for this chemotherapy schedule and further emphasizes a role for adjuvant chemotherapy in the primary treatment of PCNSL.

Adolescent↗

PubMed1992

Current concepts in leptomeningeal metastasis.

Leptomeningeal metastasis is a common neurologic disorder affecting the entire neuraxis in patients with metastatic systemic cancer and primary brain tumors. The clinical presentation of leptomeningeal metastasis is pleomorphic and commonly affects the cerebral hemispheres, cranial nerves, or spinal cord and its roots. Diagnosis is confirmed by the presence of malignant cells in the cerebrospinal fluid or by clinical and neuroradiographic pattern compatible with leptomeningeal metastasis. Treatment is palliative and is directed at the entire neuraxis combining involved-field radiotherapy and intra-cerebrospinal fluid drug administration. Regional chemotherapy pharmacokinetically is best administered by intraventricular instillation employing frequent drug administration, thereby insuring prolonged cytotoxic drug exposure. Chemotherapeutic drug distribution is dependent on bulk flow of cerebrospinal fluid. This review will summarize current information regarding the incidence, clinical presentation, laboratory findings, pathology, pathophysiology, staging, treatment, and survival of patients with leptomeningeal metastasis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Spinal cord tumors: gadolinium-DTPA-enhanced MR imaging.

To assess the utility of gadolinium-DTPA (Gd) and of MR imaging in the evaluation of spinal cord tumors, ten consecutive patients were prospectively evaluated. T1-proton density-, and T2-weighted images were obtained in sagittal or axial planes. T1-weighted images were obtained before and after intravenous administration. Five tumors were within the cervical spinal cord; 3 neoplasms were within the thoracic cord; 1 neoplasm extended from the cervical to the thoracic cord and 1 neoplasm extended from the cervical cord to the conus medullaris. Four tumors were ependymomas; 3 were astrocytomas; 1 was an hemangioblastoma, and 1 was a metastatic malignant peripheral nerve sheath tumor. The remaining patient died prior to spinal surgery and no autopsy was obtained. Of the precontrast sequences, tumors were best evaluated using T1-weighted images. Abnormal findings included cord widening, presence of a tumor mass, intratumoral or other associated cyst(s), and hemorrhage. Nevertheless, T1-weighted images obtained following the administration of GD were superior relative to all other pre- and post-contrast sequences for defining tumor margins, characterizing cyst(s) and delineating tumor masses. Based primarily on their appearance on post-contrast T1-weighted images, tumor-associated cysts could be subcategorized into 3 types: intratumoral cysts (found within the contrast-enhancing soft tissue mass); nonenhancing extratumoral cysts (found eitherrostral or caudal to the enhancing tumor mass); and enhancing extratumoral cysts (having an enhancing wall or containing an enhancing nodule).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Leptomeningeal metastases: 111indium-DTPA CSF flow studies.

Thirty consecutive patients with cytologically documented leptomeningeal metastases (LM) underwent intraventricular 111indium-DTPA (In) CSF flow studies (FS). Sixteen patients (53%) had normal In FS. Fourteen patients (47%) had documented compartmentalization of the CSF system. In four patients unsuspected CSF block was confined to the base of brain with limited spinal descent and poor cerebral convexity ascent of In. All patients received whole-brain irradiation and two were subsequently shown to have normal In FS. In 10 other patients, suspected (eight) and unsuspected (two) spinal blocks were seen. Patients with spinal blocks underwent CT myelography or spine MR and were subsequently treated with involved-field irradiation. Following radiation therapy, normal In FS were achieved in only two patients with documented spinal cord blocks. In conclusion, antegrade In FS in patients with LM are useful in defining levels of CSF blocks. Following treatment of patients with CSF blocks with involved-field irradiation, normal In FS can be restored in approximately one third.

Adult↗

PubMed1991

Evaluation and management of seizures in the patient with cancer.

Seizures are common in patients with cancer. They can be caused by the tumor itself, metabolic disturbances, radiation injury, chemotherapy-related encephalopathies, cerebral infarctions, or central nervous system infections. Evaluation requires a meticulous history and search for the precipitating cause. Treatment is directed at the underlying etiology and entails the rational and precise use of anticonvulsant drugs.

Anticonvulsants↗

PubMed1990

Poorly differentiated gliomas of the cerebellum. A study of 18 patients.

Eighteen patients with poorly differentiated gliomas of the cerebellum were treated by the University of California San Francisco Neuro-Oncology Service between January 1977 and January 1987. Within this group pathologic diagnosis included five glioblastoma multiforme (28%), nine anaplastic astrocytomas (50%), and four mixed malignant gliomas (22%). The group included 13 male and five female patients with a median age at diagnosis of 23 years (range, 4-46 years). All patients underwent surgical resection, 16 of 18 received radiation therapy (12 limited-field irradiation and four whole-brain with or without a posterior fossa boost), and 16 of 18 received chemotherapy. Overall median survival was 31.5 months (range, 5-366 months). Ten patients (55%) died of recurrent disease with a median survival of 32 months (range, 5-128 months), two of whom manifested metastatic disease within the central nervous system (one parietal lobe and one cervical cord). Of the two extracerebellar metastatic recurrences, one patient failed at the junction of whole-brain irradiation and the cervical cord and one patient failed after inadequate posterior fossa irradiation. Eight patients (45%) are alive with a median follow-up of 27.5 months (range, 14-366 months). In this series recurrences of primary cerebellar anaplastic gliomas were locoregional failures. As a consequence, the authors suggest high-dose limited-field irradiation directed at the primary tumor as in their current strategy utilized for supratentorial gliomas.

Adolescent↗

PubMed1990

Adjuvant chemotherapy for primary lymphoma of the central nervous system.

Ten immunocompetent patients with primary non-Hodgkin's lymphoma of the central nervous system were treated by the neuro-oncology service at the University of California at San Francisco (UCSF). After undergoing surgery for biopsy or removal of their tumors, these patients (group 1) received irradiation with hydroxyurea followed by adjuvant chemotherapy with the combination of procarbazine, lomustine (CCNU), and vincristine. The outcome of treatment in this group was compared with that in three other groups of patients with primary CNS lymphoma: patients treated at the UCSF Cancer Research Institute who underwent surgery and radiation therapy (RT) (group 2); patients described in the literature who had surgery and RT (group 3); or patients described in the literature who had surgery, RT, and chemotherapy (group 4). Median and quartile survival times were greater in patients who received adjuvant chemotherapy (group 1, 30 and 50 months; group 4, 20 and 25 months) than in patients who did not receive chemotherapy after RT (group 2, 13 and 20 months; group 3, 15 and 24 months). These results suggest that adjuvant chemotherapy is useful in the treatment of primary CNS lymphoma.

Adolescent↗

PubMed1990

Temporal lobe ganglioglioma in refractory epilepsy: CT and MR in three cases.

Three patients (ages 5, 16 and 21 years) with chronic, refractory, partial epilepsy and temporal lobe ganglioglioma were evaluated for surgical treatment. Noncontrast CT revealed a low attenuation, cystic temporal lesion in 2 patients. One neoplasm demonstrated focal calcification and temporal altrophy, while the other had mass effect and surrounding edema. Contrast enhancement of the mass was seen in one instance. Non-contrast and post-contrast CT were completely normal in the remaining patient. MR was abnormal in both patients in which it was performed (including the patient with a normal CT examination). Lesions were hyperintense on T2W inmages and iso-to-hypointense on T1W images when compared to normal parenchyma. Regions of calcification were missed on standard spin-echo sequences. Continuous video EEG monitoring captured habitual partial seizures in all patients; focal onset correlated with tumor location in each instance. Intraoperative electrocorticography corroborated the EEG results. Two of three patients underwent gross total resection. Pathologic features were characteristic of ganglioglioma in all instances. All patients have been seizure-free postoperatively [mean follow-up: 16 months (range 13-18 months)] and without evidence of tumor recurrence. Although ganglioglioma is an unusual cause of refractory temporal lobe epilepsy, our short term follow-up suggests excellent outcome with both partial and gross total resection.

Adolescent↗

PubMed1990

Leptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain.

We evaluated 14 consecutive patients with leptomeningeal metastasis prospectively, using both T1-weighted (T1W) gadolinium-DTPA-enhanced MR (Gd-MR) and contrast-enhanced CT (CE-CT). Thirteen had positive CSF cytology; the remaining patient had an atypical CSF lymphocytosis and primary CNS lymphoma. The patients (8M/6F) ranged in age from 8 to 70 years (median, 42 years). Tumor histology included 3 systemic and 2 primary CNS lymphomas, 3 breast carcinomas, 2 leukemias, 1 malignant schwannoma, 1 small cell lung cancer, 1 prostate cancer, and 1 melanoma. Both imaging methods demonstrated parenchymal volume loss equally well in all patients. Gd-MR revealed abnormal enhancement of meninges or parenchyma in 10 patients, including all 5 patients with positive CE-CT. Neither technique revealed any foci of abnormal enhancement in 4 patients. Gd-MR was superior to CE-CT in demonstrating and quantifying enhancing subarachnoid and parenchymal nodules in 6 patients and in demonstrating sulcal, dural, cisternal, tentorial, and ependymal enhancement. Our findings indicate that T1W Gd-MR is the preferred imaging modality in leptomeningeal metastasis and suggest that CE-CT is unnecessary.

Adolescent↗

PubMed1989

Chemotherapeutic treatment of the diencephalic syndrome. A case report.

Tumors of the hypothalamus present with a variety of clinical syndromes. Such syndromes appear to be both age and histology dependent. The diencephalic syndrome, an entity classically seen in infancy, presents as failure to thrive. In essentially all cases the pathologic substrate is a tumor with a predominance of gliomas. The traditional approach to treatment of the diencephalic syndrome has been surgery both for decompression and pathologic diagnosis followed by irradiation. Because of the tumor location, surgery is often confined to biopsy rather than radical extirpation. Furthermore, in infancy focal brain irradiation is not without significant morbidity. Within this context, we would like to present a case discussion regarding a 27-month-old boy with a hypothalamic-midbrain protoplasmic glioma treated with primary chemotherapy after surgical biopsy and pathologic documentation. The schedule of drugs utilized was based on the hypothesis of biochemical modulation of nitrosourea chemotherapy. Successful response to therapy was documented by sequential computed tomography (CT) studies and serial neurologic examinations beginning at age 5 months and every 2 months thereafter. The response of a single patient with the diencephalic syndrome treated primarily with chemotherapy makes extrapolation premature. Rather, the authors suggest chemotherapy as an alternative to focal brain irradiation. Such therapy could be utilized either in the event of recurrent tumor or as late consolidation after primary treatment with chemotherapy. The latter approach would allow a patient to have radiation therapy deferred until a later age at which time morbidity attending brain irradiation may be minimized.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

A phase I/II study of 24 hour intravenous AZQ in recurrent primary brain tumors.

This study was undertaken to determine the maximum tolerated dose of aziridinylbenzoquinone (AZQ) given as a 24-hour intravenous infusion every 21-28 days. Thirty-four patients with recurrent or progressive gliomas received AZQ at a dose of 25, 30, 35, 40, or 45 mg/m2. At a dose of 45 mg/m2, leukopenia and thrombocytopenia of grade 3 or greater was observed in 42% and 25% of patients respectively; no patient required transfusion or antibiotics for fever. For administration of AZQ at a 24-hour intravenous infusion, we recommend a starting dose of 40 mg/m2 for patients without previous exposure to cytotoxic agents, and 35 mg/m2 for patients treated with such agents. In 14 patients with glioblastoma, tumor regression was observed in 1 patient (14%) and stabilization of disease was demonstrated in 7 patients (50%). In 17 patients with anaplastic astrocytomas there were no responses, but 8 patients (47%) stabilized. Of two patients with an oligodendroglioma, one continues without progression at 34 weeks after initial response. One patient with malignant ependymoma stabilized and had not progressed at 39 weeks. The median time to tumor progression in patients who stabilized and responded was 18 weeks for those with glioblastoma multiforme and 16 weeks in those with anaplastic astrocytomas.

Antineoplastic Agents↗

PubMed1988

A phase II trial of oral melphalan in recurrent primary brain tumors.

Thirty-seven patients with recurrent primary brain tumors were treated with oral melphalan at a dose of 8 mg/m2/day for 5 days every 4-6 weeks. All patients had failed prior nitrosourea-based chemotherapy. Oral melphalan had no activity against glioblastoma, and minimal activity against other anaplastic astrocytomas. One recurrent medulloblastoma did have a clinical and radiographically sustained response that continued for greater than 14 months. We concluded that oral melphalan was not effective in the treatment of recurrent astrocytomas, but might have efficacy in medulloblastoma.

Administration, Oral↗

PubMed1988

Absence of contrast enhancement on CT brain scans of patients with supratentorial malignant gliomas.

The medical records of 229 consecutive patients with supratentorial malignant gliomas were reviewed with respect to histology, age at diagnosis, tumor location, and enhancement pattern on the CT obtained after the administration of contrast material at the time of operation. Nonenhancing tumors were identified in four (4%) of 93 patients with glioblastoma multiforme (GM), three (30%) of ten with gemistocytic astrocytoma (GA), 23 (31%) of 74 with highly anaplastic astrocytoma (HAA), and 28 (54%) of 52 with moderately anaplastic astrocytoma (MoAA). The age-related incidence of the various glioma histiotypes (both enhancing and nonenhancing) was reflected by the median age at diagnosis: 50 years in GM, 52 years in GA, 40 years in HAA, and 34 years in MoAA. The age and CT contrast enhancement pattern were similar in patients with GM, GA, and MoAA; patients with nonenhancing HAAs tended to be younger at presentation. The tumor location and the frequency of enhancing and nonenhancing lesions were similar for all groups except MoAA, in which nonenhancing tumors were most often frontotemporal and enhancing tumors were usually frontoparietal. Our results demonstrate that it is important to obtain histologic confirmation of the diagnosis in patients with supratentorial gliomas regardless of the presence or absence of contrast enhancement of the tumor on CT, because neither of these characteristics correlates with the tumor histology.

Adolescent↗