Should patients with anaplastic oligodendroglial tumors receive adjuvant chemotherapy?
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Comment↗
Biomedical subjects
Lauren E Abrey
Publications and source records attributed to Lauren E Abrey.
Retinopathy in survivors of primary central nervous system lymphoma.
Radiation retinopathy is a well-known complication of irradiation for diseases of the globe, orbit, or neighboring tissues but is rare after whole-brain radiation therapy (WBRT), even though the treatment port includes the posterior retina. We describe five patients with long-term primary CNS lymphoma who were diagnosed with retinopathy several years after treatment with chemotherapy and WBRT.
Adult↗
Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model.
PURPOSE: The purpose of this study was to analyze prognostic factors for patients with newly diagnosed primary CNS lymphoma (PCNSL) in order to establish a predictive model that could be applied to the care of patients and the design of prospective clinical trials. PATIENTS AND METHODS: Three hundred thirty-eight consecutive patients with newly diagnosed PCNSL seen at Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY) between 1983 and 2003 were analyzed. Standard univariate and multivariate analyses were performed. In addition, a formal cut point analysis was used to determine the most statistically significant cut point for age. Recursive partitioning analysis (RPA) was used to create independent prognostic classes. An external validation set obtained from three prospective Radiation Therapy Oncology Group (RTOG) PCNSL clinical trials was used to test the RPA classification. RESULTS: Age and performance status were the only variables identified on standard multivariate analysis. Cut point analysis of age determined that patients age < or = 50 years had significantly improved outcome compared with older patients. RPA of 282 patients identified three distinct prognostic classes: class 1 (patients < 50 years), class 2 (patients > or =50; Karnofsky performance score [KPS] > or = 70) and class 3 (patients > or = 50; KPS < 70). These three classes significantly distinguished outcome with regard to both overall and failure-free survival. Analysis of the RTOG data set confirmed the validity of this classification. CONCLUSION The MSKCC prognostic score is a simple, statistically powerful model with universal applicability to patients with newly diagnosed PCNSL. We recommend that it be adopted for the management of newly diagnosed patients and incorporated into the design of prospective clinical trials.
Adult↗
Chemotherapy for primary central nervous system lymphoma.
Chemotherapy, with or without radiotherapy, is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, and it is used in doses of 1 to 8 g/m(2), either as a single agent or in combination with other drugs such as corticosteroid agents, cytarabine, procarbazine, vincristine, carmustine, lomustine, thiotepa, cyclophosphamide, temozolomide, and rituximab. To date, an overwhelming number of different regimens in which high-dose MTX is used have been reported. Given the lack of randomized trials, however, the optimal treatment remains controversial. Varying methodology makes the comparison of available studies extremely difficult, yet some common themes can be found throughout the literature. Treatment paradigms vary considerably according to the patient's age. Most studies support the use of chemotherapy-only treatments for elderly patients (> 60 years), given the high risks of neurotoxicity associated with radiotherapy. Nevertheless, the prognosis remains poor regardless of the chemotherapy chosen, and less toxic regimens might be preferable for such elderly patients. Conversely, in younger patients (< 60 years), there is growing evidence that commonly used chemotherapy-only regimens are associated with increased relapse rates that may not justify deferral of radiotherapy. Thus, a significant focus of research has been the development of intensified chemotherapy regimens that could replace radiotherapy. In this article, the authors discuss the principles guiding the use of chemotherapy for PCNSL, and critically review the available literature, including the most recent trials.
Antineoplastic Agents↗
Primary dural lymphomas: a review.
Primary dural lymphoma (PDL) is a rare subtype of primary central nervous system lymphoma (PCNSL) that arises from the dura mater and differs biologically from other CNS lymphomas. The PDL is usually a low-grade marginal zone lymphoma (MZL), whereas other types of PCNSLs are usually high-grade, diffuse, large B-cell lymphomas. A PDL usually presents with single or multiple extraaxial masses that enhance diffusely with addition of contrast material and can be confused with meningioma. The MZLs respond well to local therapy such as surgery and radiation treatment. Most patients attain complete response and have good local disease control. Nevertheless, the risk of systemic relapse appears to be high, probably because the dura mater is outside of the blood-brain barrier.
Dura Mater↗
Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma.
PURPOSE: We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity. PATIENTS AND METHODS: Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations. RESULTS: The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy. CONCLUSION: Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.
Adult↗
A North American brain tumor consortium (NABTC 99-04) phase II trial of temozolomide plus thalidomide for recurrent glioblastoma multiforme.
BACKGROUND: Laboratory and clinical data suggest that the anti-angiogenic agent, thalidomide, if combined with cytotoxic agents, may be effective against recurrent glioblastoma multiforme (GBM). OBJECTIVES: To determine 6-month progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in adults with recurrent GBM. PATIENTS AND METHODS: Eligible patients had recurrent GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was given at 150-200 mg/m(2)/day on days 1-5 of each 28-day cycle. Thalidomide was given orally at 400 mg at bedtime (days 1-28) and increased to 1,200 mg as tolerated. Patients were evaluated with magnetic resonance imaging scans every 56 days. The study was designed to detect an increase of the historical 6PFS for GBM from 10 to 30%. RESULTS: Forty-four patients were enrolled, 43 were evaluable for efficacy and safety. The study population included 15 women, 29 men; median age was 53 years (range 32-84); median Karnofsky performance status was 80% (range 60-100%). Thirty-six (82%) patients were chemotherapy-naïve. There were 57 reports of toxicity of grade 3 or greater. Non-fatal grade 3-4 granulocytopenia occurred in 15 patients (34%). The objective response rate was 7%. The estimated probability of being progression-free at 6 months with this therapy is 24% [95% confidence interval (C.I.) 12-38%]. The median time to progression is 15 weeks (95% C.I. 10-20 weeks). There was no observed correlation between serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and the 6PFS outcome. CONCLUSION: This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone.
Adult↗
Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08.
PURPOSE: Phase I: To determine the maximum tolerated doses, toxicities, and pharmacokinetics of imatinib mesylate (Gleevec) in patients with malignant gliomas taking enzyme-inducing antiepileptic drugs (EIAED) or not taking EIAED. Phase II: To determine the therapeutic efficacy of imatinib. EXPERIMENTAL DESIGN: Phase I component used an interpatient dose escalation scheme. End points of the phase II component were 6-month progression-free survival and response. RESULTS: Fifty patients enrolled in the phase I component (27 EIAED and 23 non-EIAED). The maximum tolerated dose for non-EIAED patients was 800 mg/d. Dose-limiting toxicities were neutropenia, rash, and elevated alanine aminotransferase. EIAED patients received up to 1,200 mg/d imatinib without developing dose-limiting toxicity. Plasma exposure of imatinib was reduced by approximately 68% in EIAED patients compared with non-EIAED patients. Fifty-five non-EIAED patients (34 glioblastoma multiforme and 21 anaplastic glioma) enrolled in the phase II component. Patients initially received 800 mg/d imatinib; 15 anaplastic glioma patients received 600 mg/d after hemorrhages were observed. There were 2 partial response and 6 stable disease among glioblastoma multiforme patients and 0 partial response and 5 stable disease among anaplastic glioma patients. Six-month progression-free survival was 3% for glioblastoma multiforme and 10% for anaplastic glioma patients. Five phase II patients developed intratumoral hemorrhages. CONCLUSIONS: Single-agent imatinib has minimal activity in malignant gliomas. CYP3A4 inducers, such as EIAEDs, substantially decreased plasma exposure of imatinib and should be avoided in patients receiving imatinib for chronic myelogenous leukemia and gastrointestinal stromal tumors. The evaluation of the activity of combination regimens incorporating imatinib is under way in phase II trials.
Adolescent↗
Cognitive functions in low-grade gliomas: disease and treatment effects.
BACKGROUND: The role of radiotherapy and chemotherapy in the treatment of low-grade gliomas (LGG) is controversial regarding their effect on survival and the development of neurotoxicity. The few published studies examining adverse treatment effects on cognition revealed conflicting results. OBJECTIVE: To assess cognitive functioning in LGG patients who received conformal radiation therapy (RT), chemotherapy, or no treatment. DESIGN: 40 LGG patients participated in the study; 16 patients had RT +/- chemotherapy, and 24 patients had no treatment. All patients underwent a neuropsychological evaluation. APOE genotype was obtained in 36 patients who were classified in two groups based on the presence or absence of at least one apolipoprotein E small je, Ukrainian-4 (APOE small je, Ukrainian-4) allele. RESULTS: Treated LGG patients had lower scores than untreated patients on several cognitive domains; patients who completed treatment at intervals greater than 3 years and had long disease duration had significantly lower scores on the Non-Verbal Memory domain. Antiepileptic polytherapy, treatment history, and disease duration jointly contributed to low Psychomotor domain scores. 62% of treated patients showed white matter confluence on MRI, whereas only 9% of the untreated patients had such changes. Preliminary comparisons between APOE small je, Ukrainian-4 carriers (n = 9) and non-carriers (n = 27) on cognitive domain scores revealed no statistically significant differences, but APOE small je, Ukrainian-4 carriers had lower mean scores on the Verbal Memory domain than did non-small je, Ukrainian-4 carriers. CONCLUSIONS: RT +/- chemotherapy, disease duration, and antiepileptic treatment contributed to mild cognitive difficulties in LGG patients.
Adult↗
Primary dural lymphomas: a clinicopathologic study of treatment and outcome in eight patients.
The authors report eight patients with primary dural lymphoma (PDL). All patients had extra-axial masses on MRI that diffusely enhanced after gadolinium. Pathology revealed low-grade non-Hodgkin lymphoma (marginal zone lymphoma of MALT [mucosa-associated lymphoid tissue] type) in all patients. All patients underwent radiation therapy, and three received chemotherapy. Complete response was achieved in 100% of patients, but three developed systemic relapse.
Adult↗
High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up.
We previously reported a phase 2 trial of 69 patients with newly diagnosed anaplastic or aggressive oligodendroglioma who were treated with intensive procarbazine, CCNU (lomustine), and vincristine (PCV) followed by high-dose thiotepa with autologous stem cell rescue. This report summarizes the long-term follow-up of the cohort of 39 patients who received high-dose thiotepa with autologous stem cell support. Thirty-nine patients with a median age of 43 (range, 18-67) and a median KPS of 100 (range, 70-100) were treated. Surviving patients now have a median follow-up of 80.5 months (range, 44-142). The median progression-free survival is 78 months, and median overall survival has not been reached. Eighteen patients (46%) have relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with risk of relapse. Persistent nonenhancing tumor at transplant was identified in our initial report as a significant risk factor for relapse; however, long-term follow-up has not confirmed this finding. Long-term neurotoxicity has developed only in those patients whose disease relapsed and required additional therapy; no patient in continuous remission has developed a delayed neurologic injury. This treatment strategy affords long-term disease control to a subset of patients with newly diagnosed anaplastic oligodendroglioma without evidence of delayed neurotoxicity or myelodysplasia.
Adolescent↗
Response of glioblastomas to EGFR kinase inhibitors.
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ErbB Receptors↗
International study on low-grade primary central nervous system lymphoma.
OBJECTIVE: The aim of this study was to characterize the clinical presentation, course, and outcome of low-grade primary central nervous system lymphoma. METHODS: Cases were assessed in a retrospective series collected from 18 cancer centers in 5 countries. RESULTS: Forty patients (18 men, 22 women; median age, 60 years [range, 19-78]) were identified. Involvement of a cerebral hemisphere or deeper brain structures was seen in 37 patients, only leptomeningeal involvement in 2 patients, and spinal cord disease in 1 patient. Chemotherapy/radiotherapy was conducted in 15 patients, radiotherapy alone in 12, chemotherapy alone in 10, and tumor resection alone in 2, whereas 1 patient received no treatment. The median progression-free, disease-specific, and overall survival were 61.5 (range, 0-204), 130 (range, 1-204), and 79 (range, 1-204) months, respectively. Only age 60 years or older was associated with shorter progression-free (p = 0.009), disease-specific (p = 0.015), and overall survival (p = 0.001) in multivariate analysis. INTERPRETATION: Low-grade primary central nervous system lymphoma differs from the high-grade subtype in its pathological, clinical, and radiological features. It has a better long-term outcome than primary central nervous system lymphoma in general with age 60 years or older adversely affecting survival.
Age Factors↗
Systemic high-dose intravenous methotrexate for central nervous system metastases.
BACKGROUND: Treatment options for patients with recurrent central nervous system (CNS) metastases are limited. Rapid infusion of high-dose intravenous methotrexate (HD IV MTX) penetrates the blood-brain barrier (BBB) and has reported activity in leptomeningeal metastases. METHODS: Medical records were reviewed for all patients treated with HD IV MTX (3.5 g/m2) for CNS parenchymal or leptomeningeal metastases. Radiographic response rate, survival, and toxicity were determined. RESULTS: Thirty-one women and one man with a median age of 52 years (range 33-76) were treated with a total of 141 cycles (median 4, range 1-13). Twenty-nine patients had breast cancer, and one each had cancer of unknown primary (CUP), squamous cell carcinoma of the head and neck, and non-small cell lung cancer (NSCLC). An objective radiographic response and stable disease were each observed in nine patients (28%), and 13 (44%) patients progressed. Prior treatment with low-dose MTX for systemic disease did not affect response (P = 0.8). The median overall survival (n = 32) was 19.9 weeks (range 2.9-135.4+) with one patient alive at 135.4 weeks. Myelosuppression and elevated serum hepatic transaminases were the most common acute toxicities (21% and 9% of HD IV MTX cycles, respectively). CONCLUSIONS: HD IV MTX is effective in the treatment of CNS metastases with disease control (response or stable) as a best response in 56% of assessable patients. Further study is warranted.
Adult↗
Unraveling molecular markers of biologic therapies in glioma.
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Journal Article↗
Chemotherapy and the treatment of brain metastases.
Brain metastases have traditionally been treated with a surgical or radiotherapeutic approach. Chemotherapy is used occasionally as salvage therapy. The blood-brain barrier excludes most chemotherapeutic agents, rendering many systemic options ineffective within the CNS. Intrathecal chemotherapies do not penetrate into brain tissue or bulky parenchymal tumors, so are ineffective in treatment of brain metastases. However, some patients with brain metastases benefit from chemotherapy, and temozolomide or targeted therapies like gefitinib have demonstrated activity. A better understanding of the biological behavior of brain metastases may lead to development of effective treatments for this common complication of systemic cancer. The review discusses the biology of brain metastases and provides an update on current chemotherapeutic strategies.
Antineoplastic Agents↗
Does trastuzumab increase the risk of isolated CNS metastases in patients with breast cancer?
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Antibodies, Monoclonal↗
Identifying and addressing barriers to the delivery of optimal therapy for primary central nervous system lymphoma in the broader community.
Despite recent advances in the management of primary central nervous system lymphoma (PCNSL), recent population-based studies suggest that prognosis in the broader community has not improved substantially over the last 20 years. It is possible that this difference in outcome reflects a significant selection bias in the clinical series and trials reported. However, there is also preliminary evidence suggesting that patients in the community may not receive optimal management. There are many possible reasons that might account for disparities in care and outcome, but these have not been specifically addressed with regard to PCNSL. We have sought to elaborate some potential causes of these disparities; however, future studies are needed to identify and address specific barriers to care in the community.
Aged↗