Biomedical subjects

Susan M Chang

Publications and source records attributed to Susan M Chang.

53 records · Page 3Linked to original sources

PubMed2004

Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study.

This study was conducted to determine the maximum tolerated dose and dose-limiting toxicity of irinotecan (CPT-11) administered every 3 weeks to adults with progressive malignant glioma who were treated with enzyme inducing antiepileptic drug (EIAED) therapy, and to compare the pharmacokinetics with those in patients not on EIAED therapy treated at the recommended phase 2 dose for other cancers. The CPT-11 dose was 350 mg/m(2) i.v. every 3 weeks and remained fixed in patients not on EIAED therapy, but the dose was escalated by 50-mg/m(2) increments in patients on EIAED therapy. CPT-11 and its metabolites SN-38, SN-38 glucuronide (SN-38G), and APC (7-ethyl-10[4-N-(5 aminopentanoic acid)-1-piperidine]-carbonyloxycamptothecin) were characterized in both groups. Patients on EIAEDs received 350 to 800 mg/m(2) of CPT-11. Dose-limiting toxicity was due to grade 3 diarrhea despite maximal doses of loperamide. The systemic levels of CPT-11, APC, SN-38G, and SN-38 were all lower in the EIAED group. There was a moderate-to-fair relationship between CPT-11 dose and the area under the curve (AUC) for CPT-11 and APC over the 2, but no relationship dosage range of 350 to 800 mg/m between CPT-11 dose and the AUC for SN-38 or SN-38G. At the 750-mg/m(2) dose, the AUC for CPT-11 (21.6 microg x h/ml) matched the AUC (21.6 microg x h/ml) in the non-EIAED group treated with 350 mg/m(2) of CPT-11. We conclude that the recommended phase 2 dose of CPT-11 for patients on EIAEDs is 750 mg/m(2) when given every 3 weeks. A phase 2 study of patients with recurrent malignant glioma is ongoing to assess the efficacy of CPT-11 when the dose is stratified according to the use of EIAEDs.

Adult↗

PubMed2004

Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American Brain Tumor Consortium study.

The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m(2) i.v. followed in 2 h by temozolomide 550 mg/m(2) as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.

Adult↗

PubMed2004

Permanent iodine 125 brachytherapy in patients with progressive or recurrent glioblastoma multiforme.

This study reports the initial experience at the University of California San Francisco (UCSF) with tumor resection and permanent, low-activity iodine 125 (125I) brachytherapy in patients with progressive or recurrent glioblastoma multiforme (GM) and compares these results to those of similar patients treated previously at UCSF with temporary brachytherapy without tumor resection. Thirty-eight patients with progressive or recurrent GM were treated at UCSF with repeat craniotomy, tumor resection, and permanent, low-activity 125I brachytherapy between June 1997 and May 1998. Selection criteria were Karnofsky performance score > or =60, unifocal, contrast-enhancing, well-circumscribed progressive or recurrent GM that was judged to be completely resectable, and no evidence of leptomeningeal or subependymal spread. The median brachytherapy dose 5 mm exterior to the resection cavity was 300 Gy (range, 150-500 Gy). One patient was excluded from analysis. Median survival was 52 weeks from the date of brachytherapy. Age, Karnofsky performance score, and preimplant tumor volume were all statistically significant on univariate analyses. Multivariate analysis for survival showed only age to be significant. Median time to progression was 16 weeks. Both univariate and multivariate analysis of freedom from progression showed only preoperative tumor volume to be significant. Comparison to temporary brachytherapy patients showed no apparent difference in survival time. Chronic steroid requirements were low in patients with minimal postoperative residual tumor. We conclude that permanent 125I brachytherapy for recurrent or progressive GM is well tolerated. Survival time was comparable to that of a similar group of patients treated with temporary brachytherapy.

Adolescent↗

PubMed2004

Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis.

Survival for patients with glioblastoma multiforme is short, and current treatments provide limited benefit. Therefore, there is interest in conducting phase 2 trials of experimental treatments in newly diagnosed patients. However, this requires historical data with which to compare the experimental therapies. Knowledge of prognostic markers would also allow stratification into risk groups for phase 3 randomized trials. In this retrospective study of 832 glioblastoma multiforme patients enrolled into prospective clinical trials at the time of initial diagnosis, we evaluated several potential prognostic markers for survival to establish risk groups. Analyses were done using both Cox proportional hazards modeling and recursive partitioning analyses. Initially, patients from 8 clinical trials, 6 of which included adjuvant chemotherapy, were included. Subsequent analyses excluded trials with interstitial brachytherapy, and finally included only nonbrachytherapy trials with planned adjuvant chemotherapy. The initial analysis defined 4 risk groups. The 2 lower risk groups included patients under the age of 40, the lowest risk group being young patients with tumor in the frontal lobe only. An intermediate-risk group included patients with Karnofsky performance status (KPS) >70, subtotal or total resection, and age between 40 and 65. The highest risk group included all patients over 65 and patients between 40 and 65 with either KPS<80 or biopsy only. Subgroup analyses indicated that inclusion of adjuvant chemotherapy provides an increase in survival, although that improvement tends to be minimal for patients over age 65, for patients over age 40 with KPS less than 80, and for those treated with brachytherapy.

Adult↗

PubMed2004

Volume of residual disease as a predictor of outcome in adult patients with recurrent supratentorial glioblastomas multiforme who are undergoing chemotherapy.

OBJECT: For patients with recurrent glioblastomas multiforme (GBMs) the prognosis is poor. Although chemotherapy may provide a survival advantage, the role of the extent of tumor resection, or the volume of the residual tumor at the time of recurrence, before instituting chemotherapy, is unclear. This study was designed to assess the response to chemotherapy based on the volume of residual disease (VRD) at the start of treatment in patients with recurrent GBMs. To accomplish this, the authors evaluated a homogeneous group of patients with recurrent GBMs who received the same chemotherapeutic agent. METHODS: One hundred nineteen adult patients with recurrent supratentorial GBMs received temozolomide chemotherapy at the time of tumor recurrence. In this cohort the authors analyzed the prognostic significance of volumetrically assessed tumor mass on time to tumor progression (TTP) and survival time (ST). Multivariate analysis demonstrated that the VRD at the beginning of chemotherapy was a statistically significant predictor of both TTP (p < 0.0001) and ST (p < 0.006) when adjusted for the patient's age, performance score, and time from the initial diagnosis. Patients in whom the VRD was less than 10 cm3 at the start of chemotherapy had a 6-month progression-free survival rate of 32% compared with 8% for patients with a VRD between 10 and 15 cm3 and 3% for patients with a VRD larger than 15 cm3. Patients in whom the VRD was smaller than 10 cm3 had a 1-year survival rate of 37% compared with 9% for patients with a VRD between 10 and 15 cm3 and 18% for patients with a VRD larger than 15 cm3. CONCLUSIONS: These data indicate that patients with recurrent GBMs who start chemotherapy with a smaller volume (< 10 cm3) of residual disease may have a more favorable response to chemotherapy and a more favorable outcome.

Adolescent↗

PubMed2004

Proton magnetic resonance spectroscopy imaging in the evaluation of patients undergoing gamma knife surgery for Grade IV glioma.

OBJECT: The purpose of this study was to assess the differences in spatial extent and metabolic activity in a comparison of a radiosurgical target defined by conventional strategies that utilize the enhancing lesion and a metabolic lesion defined by proton magnetic resonance spectroscopy (MRS) imaging. The authors evaluated whether these differences manifest themselves in the clinical outcome of patients and assessed the value of incorporating 1H-MRS imaging-derived spatial information into the treatment planning process for gamma knife surgery (GKS). METHODS: Twenty-six patients harboring Grade IV gliomas who had previously been treated with external-beam radiation therapy were evaluated by comparing the radiosurgically treated lesion volume with the volume of metabolically active tumor defined on 1H-MRS imaging. The cohort was evenly divided into two groups based on the percentage of overlap between the radiosurgical target and the metabolic lesion volumes. Patients with a percentage of overlap greater than 50% with respect to the metabolic lesion volume were classified as low risk and those with an overlap less than 50% were classified as high risk. Kaplan-Meier estimators were calculated using time to progression and survival as dependent variables. The metabolite levels within the metabolic lesion were significantly greater than those within the radiosurgical target (p < or = 0.001). The median survival was 15.7 months for patients in the low-risk group and 10.4 months for those in the high-risk group. This difference was statistically significant (p < 0.01). CONCLUSIONS: Analysis of the results of this study indicates that patients undergoing GKS may benefit from the inclusion of 1H-MRS imaging in the treatment planning process.

Adult↗

PubMed2003

The role of PCV chemotherapy in the treatment of central neurocytoma: illustration of a case and review of the literature.

BACKGROUND: Most central neurocytomas follow a benign clinical course. However, more aggressive variants have been described requiring additional surgical resection, radiation, or chemotherapy. Chemotherapy has rarely been used as an adjuvant therapy for central neurocytomas. METHODS: We report a case of a 20-year-old girl who underwent four subtotal resections, over the course of 3 years, for a large central neurocytoma that continued to progress. She was not a candidate for stereotactic radiosurgery, given the large tumor size. To avoid radiation injury in a young patient, she was treated with six cycles of chemotherapy including procarbazine, CCNU, and vincristine. Procarbazine was stopped after 2 cycles because of the development of a rash. Serial magnetic resonance imaging was used to follow treatment response. RESULTS: Her tumor started to decrease in size after 2 cycles of chemotherapy and continued to shrink until it stabilized after 5 cycles of chemotherapy. A small area of residual tumor with minimal enhancement persisted along the left lateral ventricle and remained stable for at least 16 months after the completion of chemotherapy. CONCLUSIONS: To our knowledge, this is only the fourth report describing the use of chemotherapy for progression of central neurocytomas as a treatment alternative to radiation therapy. The use of procarbazine, CCNU, and vincristine has not been previously described for the treatment of a central neurocytoma and presents an additional treatment option.

Adolescent↗

PubMed2003

Intraventricular neurocytomas.

The literature to date on the treatment of CNC reflects an evolution of clinical practice in neurooncology. The advent of sophisticated tools, such as MRS and molecular pathology, has facilitated more efficient diagnosis of CNC. Decreased morbidity associated with surgical intervention has resulted in better outcomes in patients undergoing resection of CNC. Prospective monitoring of treated patients with MRI coupled with judicious use of radiosurgery will likely further decrease treatment-related morbidity.

Brain↗

PubMed2003

A study of a different dose-intense infusion schedule of phenylacetate in patients with recurrent primary brain tumors consortium report.

PURPOSE: To compare two different infusion schedules of phenylacetate (PA) in patients with primary brain tumors and to assess the feasibility of the administration in a multi-institutional setting. PATIENTS AND METHODS: Adult patients with recurrent primary brain tumors were treated with PA on two different schedules. The first schedule (I) consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off) at a dose of 400 mg/kg/day based on ideal body weight. This was repeated once and the 8-week period defined as a cycle. The second schedule (II) consisted of a 12-day continuous infusion at a dose of 400 mg/kg/day based on IBW with a 2-day rest period. This was repeated four times for a duration of 8 weeks which defined one cycle of therapy. Cycles were repeated until tumor progression, unacceptable toxicity, or a delay of more than 28 days from the last day of the preceding infusion. Tumor response was assessed every 8 weeks. The National Cancer Institute toxicity criteria were used to assess toxicity. Dose adjustments were specified for toxicities. Plasma concentrations achieved during the patients' first cycle of therapy were assessed. RESULTS: The clinical results of the phase II study of patients treated on schedule I were previously reported [8]. Of the nine eligible patients treated on schedule II, seven were assessable for radiographic response. There were no objective responses. One patient had stable disease and six had progressive disease. The median survival was 9 months (95% confidence intervals of 3-12 months). The steady state plasma concentrations of PA and phenylacetylglutamine were comparatively the same between the two dosing schedules. However a 1.7-fold greater amount of PA was delivered by schedule II. CONCLUSION: The infusions were well tolerated. Despite the feasibility of administering this agent in an outpatient setting, there were no responses seen with the more intensive schedule of PA.

Adult↗

PubMed2003

Treatment of progressive or recurrent glioblastoma multiforme in adults with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration: a phase I/II multi-institutional trial.

To determine the safety and evaluate the efficacy of repeated administration of virus-producing cells (GLI 328) containing the herpes simplex virus thymidine-kinase gene followed by ganciclovir treatment in adults with recurrent glioblastoma multiforme, we conducted a phase I/II multi-institutional trial. Eligible patients underwent surgical resection of tumor, followed by injections of vector producing cells (VPC) into the brain adjacent to the cavity. An Ommaya reservoir placed after surgery was used to inject a further dose of VPC seven days after surgery, followed seven days later by ganciclovir. Further gene therapy was given at 28-day intervals for up to a total of five cycles. Toxicity and anti-tumor effect were assessed. Of 30 patients who enrolled in the study, 16 experienced serious adverse events possibly related to the experimental therapy. Laboratory testing, including polymerase chain reaction analysis to detect replication-competent retrovirus in peripheral blood lymphocytes and tissues, as well as co-cultivation bioassays, were negative. Before receiving ganciclovir, 37% of the patients showed evidence of transduced peripheral blood leukocytes, but only 12% showed a persistence of transduced cells at the end of the first cycle of ganciclovir. Median survival was 8.4 months. Twenty percent of the patients (n = 6) survived more than 12 months from the date of study entry. This treatment modality is feasible and appears to have some evidence of efficacy. Toxicity may be related in part to the method of gene delivery.

Adult↗

PubMed2003

Repeated operations for infiltrative low-grade gliomas without intervening therapy.

OBJECT: Progression of infiltrative low-grade gliomas (LGGs) has been reported previously. The limitations of such studies include diverse histological grading systems, intervening therapy, and the lack of histological confirmation of malignant tumor progression. The aim of this study was to determine tumor progression in adult patients with an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation, but no other intervening therapy. The authors examined factors that may be associated with tumor progression. METHODS: The authors retrospectively reviewed a database of 300 patients with the initial diagnosis of LGG and who had been treated at their institution between 1990 and 2000. One hundred four of these patients had undergone a second surgery. Patients with infiltrative LOGs who had undergone two surgical procedures at least 3 months apart without intervening therapy were selected; the authors identified 40 patients who fit these criteria. Clinical, neuroimaging, and pathological data were centrally reviewed. There were 29 men and 11 women in the study, whose median age was 35.5 years (range 23-48 years). At the time of the second surgery, 50% of patients had experienced tumor progression. Patients whose tumors had progressed had a longer median time to repeated operation (49 compared with 22.5 months). Patients who had undergone gross-total resection, as demonstrated on postoperative magnetic resonance images, had a median time to repeated operation of 49 compared with 25 and 24 months in patients who underwent subtotal resection and biopsy, respectively (p = 0.02). The extent of resection did not influence the likelihood of tumor progression (p > 0.3). CONCLUSIONS: Fifty percent of patients with initially diagnosed infiltrative LGOs had tumor progression at the time of a repeated operation. A gross-total resection was associated with an increased time to repeated surgery. There was no statistically significant effect of gross-total resection as a predictor of tumor progression.

Adult↗

PubMed2003

Perioperative complications and neurological outcomes of first and second craniotomies among patients enrolled in the Glioma Outcome Project.

OBJECT: In many new clinical trials of patients with malignant gliomas surgical intervention is incorporated as an integral part of tumor-directed interstitial therapies such as gene therapy, biodegradable wafer placement, and immunotherapy. Assessment of toxicity is a major component of evaluating these novel therapeutic interventions, but this must be done in light of known complication rates of craniotomy for tumor resection. Factors predicting neurological outcome would also be helpful for patient selection for surgically based clinical trials. METHODS: The Glioma Outcome Project is a prospectively compiled database containing information on 788 patients with malignant gliomas that captured clinical practice patterns and patient outcomes. Patients in this series who underwent their first or second craniotomy were analyzed separately for presenting symptoms, tumor and patient characteristics, and perioperative complications. Preoperative and intraoperative factors possibly related to neurological outcome were evaluated. There were 408 patients who underwent first craniotomies (C1 group) and 91 patients who underwent second ones (C2 group). Both groups had similar patient and tumor characteristics except for their median age (55 years in the C1 group compared with 50 years in the C2 group; p = 0.006). Headache was more common at presentation in the C1 group, whereas papilledema and an altered level of consciousness were more common at presentation in patients undergoing second surgeries. Perioperative complications occurred in 24% of patients in the C1 group and 33% of patients in the C2 group (p = 0.1). Most patients were the same or better neurologically after surgery, but more patients in the C2 group (18%) displayed a worsened neurological status than those in the C1 group (8%; p = 0.007). The Karnofsky Performance Scale score and, in patients in the C2 group, tumor size were important neurological outcome predictors. Regional complications occurred at similar rates in both groups. Systemic infections occurred more frequently in the C2 group (4.4 compared with 0%; p < 0.0001) as did depression (20 compared with 11%; p = 0.02). The perioperative mortality rate was 1.5% for the C1 group and 2.2% for the C2 group (p = not significant). The median length of the hospital stay was 4 days in each group. CONCLUSIONS: Perioperative complications occur slightly more often following a second craniotomy for malignant glioma than after the first craniotomy. This should be considered when evaluating toxicities from intraoperative local therapies requiring craniotomy. Nevertheless, most patients are neurologically stable or improved after either their first or second craniotomy. This data set may serve as a benchmark for neurosurgeons and others in a discussion of operative risks in patients with malignant gliomas.

Central Nervous System Neoplasms↗

PubMed2002

Clinical trial participation among patients enrolled in the Glioma Outcomes Project.

BACKGROUND: Patient participation in well-designed and conducted clinical trials enables researchers to test new therapies. An understanding of the variables that possibly influence patient enrollment may help in patient recruitment for future trials. The authors evaluated factors that influenced patient enrollment in clinical trials using a prospective, large, multi-institutional registry of patients with malignant glioma. METHODS: Data were examined from 708 patients who underwent first or second surgery for a malignant glioma who were enrolled in the Glioma Outcomes Project, which is a prospective observational data base that captures clinical practice patterns. The frequency of clinical trial participation and the variables that may have been associated with trial participation were evaluated. These variables included age, gender, race, household income, educational level, first versus second craniotomy, histology, and whether the patient was treated at an academic institution. RESULTS: One hundred fifty-one of 708 patients (21.3%) participated in a clinical trial, which was higher than the participation reported typically for patients with other types of primary malignancies. In univariate analysis, race, histology, and first craniotomy were significant between the two groups, with Caucasian patients and patients with glioblastoma histology showing higher participation rates. In a multivariate logistic regression model, significant predictors included young age and glioblastoma multiforme histology. CONCLUSIONS: The authors present information on factors that may influence clinical trial participation among patients with malignant glioma and compare their data with information described previously on patients with other types of malignant disease. The percent of participation among the patients in the current study was greater than among patients with other primary tumor sites. Strategies should be implemented to improve recruitment to neuro-oncology trials, especially in elderly and minority populations.

Age Factors↗

PubMed2002

Malignant pineal parenchymal tumors in adult patients: patterns of care and prognostic factors.

OBJECTIVE: The aim of our study was to analyze patterns of care and to identify prognostic factors in patients at least 18 years of age who received radiotherapy for malignant pineal parenchymal tumors. METHODS: In a multicenter, retrospective study, we analyzed data for 37 previously published cases and 64 patients treated at the participating institutions. RESULTS: A total of 56 patients received postoperative radiotherapy, and 45 patients received primary radiotherapy. Chemotherapy was administered to 34 patients. The median follow-up period was 38 months, and median overall survival was 100 months. The variables that significantly influenced overall survival were the extent of disease (localized versus disseminated; P = 0.0002), differentiation (pineal parenchymal tumor of intermediate differentiation versus pineoblastoma; P = 0.001), and residual disease (> or = 50% versus < 50% reduction in size; P < 0.0001). In a multivariate analysis, the parameters turned out to be independent risk factors. The median survival in patients with local or spinal failure was 15 months. Local control was better in older patients (> or = 32 yr versus < 32 yr; P = 0.02). Spinal control was more successful in patients with pineal parenchymal tumors of intermediate differentiation than it was in patients with pineoblastomas (P = 0.03). Nine of 45 treatment failures occurred later than 5 years after treatment. CONCLUSION: Stage, histological characteristics, and response are independent risk factors in adults with malignant pineal parenchymal tumors. Late relapses are common.

Adolescent↗

PubMed2002

A phase II trial of thymidine and carboplatin for recurrent malignant glioma: a North American Brain Tumor Consortium Study.

This phase II study in recurrent high-grade glioma evaluated the response rate, toxicities, and time to treatment failure of high-dose carboplatin modulated by a 24-h infusion of thymidine (75 g/m(2)). The trial was based on preclinical data and a prior phase I study ( J. Clin. Oncol. 17, 2922-2931, 1999); a phase II recurrent high-grade glioma study was initiated in July of 1998. Thymidine was given over 24 h; carboplatin was given over 20 min at hour 20 of the thymidine infusion. The starting dose of carboplatin had a value of 7 for the area under the curve (AUC), with allowance for dose escalation of 1 AUC unit per cycle if grade 2 toxicity was observed. Treatment cycles were repeated every 4 weeks. Accrual as of September 1999 was 45 patients [4 were unevaluable]: 76% with glioblastoma multiforme (GBM), 20% with anaplastic oligodendroglioma, 2% with mixed type, and 2% with anaplastic astrocytoma. Most patients had prior chemotherapy (78%). As observed in the earlier phase I study (in which carboplatin pharmacokinetics were unaltered by thymidine or antiseizure medications), thymidine was myeloprotective, resulting in a minimal need for dose reduction for patients having a >2 grade toxicity (in only 4% of the courses of treatment). Of 101 total courses, the number of courses (at the AUCs) was 3 (5), 4 (6), 58 (7), 20 (8), 11 (9), and 5 (10). Grade 3 nonhematologic toxicities included headache (4%), altered consciousness (3%), fatigue (1%), and nausea (3%). Responses included 2 partial (1 oligodendroglioma, 1 GBM; 5%); 3 minor (1 anaplastic astrocytoma, 2 GBM; 7.3%); 6 stable disease (14.6%); and 30 progressive disease (73.2%). For GBM patients, median survival was 23 weeks (with a 95% confidence interval of 20 to 50 weeks), and progression-free survival was 8 weeks (with a 95% confidence interval of 7-16 weeks). These results in GBM were comparable to other phase II GBM trials and thus do not represent a therapeutic advance in the treatment of GBM. Taken collectively, however, results are consistent with continued investigation of thymidine in combination with chemotherapeutic agents for high-grade glioma and other malignant diseases. The significant myeloprotection afforded by thymidine may have particular relevance to polychemotherapeutic regimens.

Adult↗

PubMedDate not supplied

Current chemotherapy for glioblastoma.

INTRODUCTION: Glioblastoma multiforme continues to be associated with a dismal prognosis, despite aggressive therapy. What limited therapeutic impact that has been made has come via multimodality treatment in which chemotherapy plays an important role. In this manuscript, we review current chemotherapy options for glioblastomas. METHODS: The current literature concerning glioblastoma multiforme chemotherapy was reviewed. In addition to a review of landmark references, a MEDLINE search of the literature published from January 2000 to November 2002 was performed using the key words "chemotherapy AND malignant glioma" and limiting responses to clinical trials. RESULTS: Several cytotoxic chemotherapeutic agents that are efficacious in treating glioblastoma are in common clinical use. These can be classified as first-line or second-line agents, depending on their efficacy. In addition, cytostatic chemotherapy agents are beginning to play a role in glioblastoma treatment. Finally, new methods to deliver high chemotherapy doses to brain tumors hold promise for future therapies. CONCLUSIONS: Despite the overall poor prognosis of patients with glioblastoma multiforme, multimodality treatment and chemotherapy in particular improve outcome, and chemotherapeutic options are beginning to have an increased impact. Strategies currently in clinical trials may improve this impact more in the future.

Antineoplastic Agents↗

PubMedDate not supplied

Dynamic susceptibility-weighted perfusion imaging of high-grade gliomas: characterization of spatial heterogeneity.

BACKGROUND AND PURPOSE: The advent of new anti-angiogenic therapies has created the need for better defining regions of abnormal vascularity in order to add specificity to the classification of high-grade gliomas. This study investigated MR imaging parameters corresponding to the peak height and percent recovery of the T2* relaxivity curve to characterize angiogenesis and microvascular leakage within the T2 and contrast-enhancing abnormalities in high-grade gliomas. METHODS: Dynamic susceptibility-weighted MR imaging was performed in 41 patients with untreated high-grade glioma during the first pass and recirculation phase of a gadolinium bolus injection. Normalized peak height and percent recovery of the post-bolus signal were calculated on a voxel by voxel basis within the T2 and contrast-enhancing lesions (T2L, CEL) and compared between grade III and grade IV gliomas. RESULTS: Grade IV gliomas showed significantly larger volumes of abnormal peak height and recovery compared to grade III patients (P < .01). Within the CEL, grade IV gliomas exhibited significantly higher peak height values than grade III patients (P < .05). Enhancing grade III patients (n = 7) demonstrated higher minimum values of percent recovery within both regions compared to grade IV patients. Non-enhancing grade III gliomas (n = 11) had significantly elevated minimum percent recovery values when compared to the T2L-CEL region in grade IV patients (n = 23; P < .05). CONCLUSION: Direct measurement of the spatial distribution of tumor microvasculature characteristics has shown considerable heterogeneity within different regions of grade III and grade IV gliomas. Peak height and percent recovery parameters help to improve the specificity for characterization of the degree of angiogenesis and microvascular leakage in these tumors and may be useful in evaluating response to treatment.

Brain Neoplasms↗