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Biomedical subjects

Henry Brem

Publications and source records attributed to Henry Brem.

At least 37 records · Page 2Linked to original sources
PubMed2004

Systemic BCNU enhances the efficacy of local delivery of a topoisomerase I inhibitor against malignant glioma.

PURPOSE: To investigate the ability of systemically delivered BCNU to enhance the activity of either systemically delivered irinotecan (CPT-11) or locally delivered camptothecin from a biodegradable polymer for treatment of an intracranial 9L gliosarcoma. METHODS: We used a single systemic dose of BCNU on treatment day 1 in combination with systemic doses of CPT-11 on treatment days 1-5 and 8-12 against an intracranial rat 9L gliosarcoma model implanted into female Fischer 344 rats. We also used the same systemic dose of BCNU given on treatment day 1, followed by a local dose of a 20% loaded camptothecin biodegradable polymer implanted on the same day. RESULTS: Two doses of CPT-11 (10 and 60 mg/kg) were delivered systemically against intracranial 9L. Neither dose showed an increase in survival compared to controls ( P>0.2 for 10 mg/kg and P=0.17 for 60 mg/kg). Systemic delivery of CPT-11 (10 mg/kg per day) in combination with systemic BCNU (15 mg/kg) did not show a significant effect on survival compared to systemic BCNU alone ( P>0.2), even at the maximally tolerated systemic dose of CPT-11 (60 mg/kg per day; P=0.06). The combination of systemic BCNU (15 mg/kg) and intracranial delivery of camptothecin (20% loaded polymer), however, significantly extended survival compared to systemic BCNU alone ( P<0.001) and compared to intracranial delivery of camptothecin alone ( P=0.01). CONCLUSIONS: In a 9L gliosarcoma model, systemic delivery of CPT-11 showed no benefit in survival when delivered alone or in combination with systemic BCNU, because CPT-11 is unable to cross the blood-brain barrier in cytotoxic levels. When cytotoxic levels of a topoisomerase I inhibitor are delivered directly to the brain tumor via a biodegradable polymer, however, the systemic delivery of the alkylating agent BCNU significantly enhances the antitumor effects of camptothecin in a 9L gliosarcoma model.

Animals↗
PubMed2004

Recent advances in brain tumor therapy: local intracerebral drug delivery by polymers.

New approaches to malignant glioma are being actively investigated. Local drug delivery directly to the site of the tumor is one novel approach that has been approved by the US FDA and other regulatory agencies worldwide. This agent, Gliadel, delivers the chemotherapeutic drug carmustine (BCNU) from a biodegradable polymer placed in the resection cavity after brain tumor surgery. Gliadel represents the first clinical application of polymer delivery for brain tumors, but the potential for this new methodology is far greater. In this review, we will briefly summarize the development of Gliadel from a laboratory idea to its current role as an approved treatment for gliomas. Then we will present the most recent work being done to expand the potential benefits of polymeric delivery for brain tumors. This work includes trials for its use as the initial therapy for gliomas, as well as its use against metastasis. Further clinical trials exploring the maximum-tolerated dose and the combination of Gliadel with systemic chemotherapeutic treatments such as temozolamide and O(6)-benzylguanine will be reviewed. Finally, we will present preclinical work on the efficacy of polymeric methods for delivering other chemotherapeutic agents, and a variety of novel compounds that modify brain tumor biology. This latter work represents potential future clinical applications of local polymeric drug delivery to the brain and other sites where cancers can occur.

Animals↗
PubMed2004

Dexamethasone mediated inhibition of local IL-2 immunotherapy is dose dependent in experimental brain tumors.

Local delivery of cytokines has been shown to have a potent anti-tumor activity against a wide range of malignant brain tumors. In this study, we examined the role of systemic immunosuppression using dexamethasone on the efficacy of local IL-2 immunotherapy in treating experimental murine CNS tumors. An endothelial cell line secreting hIL-2 (NTC-121) was injected intracranially in C57BL/6 mice (n = 10/ group) along with B16/F10 (wild type) melanoma cells. A separate set of animals also received daily injections of either 1 mg/k or 10 mg/kg of dexamethasone. Sixty percent of mice treated with IL-2 (P < 0.001 vs. control) vs. 55% (P < 0.005) of mice treated with IL-2 and 1 mg/kg of dexamethasone were long-term survivors (LTS) of > 120 days. There was no difference in survival between control animals that received only wild type cells or animals that were treated with IL-2 and 10 mg/kg of dexamethasone. Histopathological examination of brains from animals sacrificed at different times showed an accumulation of CD8 + T-cells around the site of the injected tumor only in the IL-2 group and the group that received 1 mg/kg of dexamethasone. These results suggest that while high doses of dexamethasone can completely inhibit the immune response observed with IL-2, lower and more likely therapeutic doses of dexamethasone do not inhibit local IL-2 immunotherapy.

Animals↗
PubMed2004

Clinical course and pathologic findings after Gliadel and radiotherapy for newly diagnosed malignant glioma: implications for patient management.

Randomized trials have demonstrated Gliadel improves survival for appropriately selected patients with newly diagnosed malignant glioma. As only limited information is available to guide the management of patients who have Gliadel controlled-release BCNU wafers implanted in the cranial resection cavity prior to radiotherapy (RT), this retrospective review was conducted to describe clinical course, toxicity, and pathologic findings after this therapy for newly diagnosed malignant glioma. Forty-six consecutive patients receiving Gliadel (3.8% BCNU impregnated wafers) followed by radiotherapy for newly diagnosed malignant glioma at Johns Hopkins Hospital from 1990 to August 1999 were identified, although one was lost to follow up and is excluded. Patients were evaluated for postoperative infection, pathology at reoperation, and survival. Twenty-eight patients received radiotherapy at Johns Hopkins and these patients are also evaluable for toxicity experienced during and one month after completion of RT. The median age of all patients is 57 years. Eighty-nine percent had glioblastoma, and median follow-up of surviving glioblastoma patients is 16.8 (12-20) months. Postoperative infection or need for reoperation within 30 days was uncommon after Gliadel placement. Full-dose radiotherapy was tolerable after Gliadel implantation. Five patients (19%) developed neurologic symptoms during radiotherapy responding to increased steroids and/or anticonvulsants, whereas an additional 8 of 27 (30%) developed neurologic symptoms during dexamethasone taper that responded to increases in dexamethasone dose. At one month after RT, 58% of patients were still on dexamethasone despite attempted taper. Fifteen of 45 patients, 33% underwent reoperation or biopsy for a new local contrast-enhancing lesion. In five of 15 (33%) the reoperation revealed necrosis or treatment effect without active tumor. Two of five patients with treatment/effect necrosis has a third surgery 2.9 and 3.2 months after the initial reoperation, and treatment effect/necrosis without tumor was demonstrated in both cases. The Kaplan-Meier median survival for all the glioblastoma patients is 12.8 (95% CI 9.6, 15.9) months. For glioblastoma patients under 55 years old, median survival is 15.9 (95% CI 13.5, too few events) months whereas for older patients it is 9.6 (7.7, 14.4) months. We conclude that Gliadel followed by full-dose standard radiotherapy is acutely well tolerated, although, close supervision should be emphasized during dexamethasone taper. Median survival in excess of one year suggests that there are not complications that result in overall premature death. The finding of necrosis/treatment effect was noted in five of 45 (11%) of all patients and five of 15 (33%) of those undergoing reoperation. Therefore, the possibility of necrosis/treatment effect should be considered for each patient with radiographic findings suspicious for local recurrence.

Adult↗
PubMed2004

Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas.

OBJECTIVE: Pilocytic astrocytoma (PA) is a common type of pediatric brain tumor that can arise within the hypothalamic/chiasmatic region and typically has an excellent outcome. We identified a group of tumors, previously classified as PAs, with unique histological features and aggressive behavior. This article describes the clinicopathological features of these unusual neoplasms, which are currently known as pilomyxoid astrocytomas (PMAs), to better differentiate them from typical PAs. METHODS: Medical information and surgical specimens were obtained for 42 PA cases and 21 PMA cases. Patient demographic features, treatment modalities, progression-free survival (PFS) times, overall survival (OS) times, and outcomes were compared between the groups with nonparametric tests. RESULTS: The PMA group included 12 male and 9 female patients. The PA group included 27 male and 15 female patients. The mean ages at diagnosis for the PMA and PA groups were 18 months (range, 2-84 mo) and 58 months (range, 4-189 mo), respectively (P < 0.01). The mean PFS times for the PMA and PA groups were 26 and 147 months, respectively (P < 0.001). The mean OS times for the PMA and PA groups were 63 and 213 months, respectively (P < 0.001). Sixteen patients with PMAs (76%) experienced local recurrence, and three of those patients demonstrated evidence of cerebrospinal fluid dissemination. Twenty-one patients with PAs (50%) experienced local recurrence, none with evidence of cerebrospinal fluid dissemination. Within the follow-up period, seven patients with PMAs (33%) and seven patients with PAs (17%) died as a result of their disease. In an age-matched set, the mean PFS times for the PMA and PA groups were 25 and 163 months, respectively (P < 0.01), and the mean OS times for the PMA and PA groups were 60 and 233 months, respectively (P < 0.001). CONCLUSION: Hypothalamic/chiasmatic PMAs occurred in a significantly younger population and were associated with substantially shorter PFS and OS times than were typical PAs. Increased recognition of these lesions could affect the prognosis and treatment of pediatric astrocytomas.

Adolescent↗
PubMed2004

Astroglia induce cytotoxic effects on brain tumors via a nitric oxide-dependent pathway both in vitro and in vivo.

OBJECTIVE: In the central nervous system, astroglia produce nitric oxide (NO) in response to cytokines. We investigated whether cytokine stimulation of astroglia could inhibit brain tumor cell growth in vitro and prolong survival in vivo via an NO-dependent pathway. METHODS: Astroglia cultures were stimulated with the cytokines lipopolysaccharide and interferon-gamma and subsequently seeded with tumor cell lines. Wild-type mice and inducible NO synthase-knockout mice received in vivo cytokine stimulation followed by B16F10 murine melanoma challenge. RESULTS: Our in vitro studies demonstrate that astroglia stimulated to produce NO by the addition of cytokines dose-dependently inhibit the growth of one primary rat brain tumor cell line (9L) and three primary human brain tumor cell lines (H80, U87, and U373). This inhibition of tumor cell growth is also observed in metastatic cell lines (B16F10 melanoma, Lewis lung carcinoma, and CT26 colon). Cultured astrocytes from inducible NO synthase-knockout mice, which are incapable of induction of NO, are without the enhanced tumoricidal effect. Furthermore, when C57BL/6 mice are primed to produce NO through stereotactic intracranial administration of lipopolysaccharide plus interferon-gamma and subsequently challenged with B16F10 murine melanoma, survival is significantly prolonged, with a median survival of 26 days versus 16 days in the control group (P < 0.001). The addition of an NO synthase inhibitor (N(G)-nitro-l-arginine methyl ester) decreases this beneficial effect (median survival, 21 d). CONCLUSION: These findings suggest that NO may have an important role as a defense mechanism molecule against brain tumors; stimulation or modification of this mechanism may represent a new approach to the treatment of primary and metastatic brain tumors.

Animals↗
PubMed2003

Polilactofate microspheres for Paclitaxel delivery to central nervous system malignancies.

PURPOSE: The purpose of this study was to demonstrate that surgically implanted, controlled-release, biodegradable polilactofate microspheres (Paclimer) can be used safely to bypass the blood-brain barrier and deliver paclitaxel to malignant brain tumors. EXPERIMENTAL DESIGN: The rate of paclitaxel release from Paclimer microspheres submerged in PBS was measured in vitro by high-performance liquid chromatography. In vivo studies of Paclimer were performed as intracranial implants in Fischer 344 rats in the presence or absence of 9L gliosarcoma. Mantel-Cox statistics were used to assess the efficacy of Paclimer at extending survival of tumor-bearing animals compared with control implants. Paclimer implants tagged with [(3)H]paclitaxel were used to measure biodistribution of paclitaxel from the Paclimer implant. RESULTS: Paclimer released paclitaxel at a constant rate for up to 3 months in vitro. In vivo, Paclimer implants placed intracranially in rats released active drug for up to 30 days after implantation and doubled the median survival of rats bearing established 9L gliosarcomas (median survival of paclitaxel-treated animals = 35 days; median survival of control-treated animal = 16 days; P < 0.0001). Active drug was distributed throughout the rat brain based on liquid scintillation counting and TLC. Rats implanted with Paclimer demonstrated no overt signs of neurotoxicity and exhibited local cytopathological changes consistent with exposure to an antimicrotubule agent. CONCLUSIONS: Paclimer extends survival in a rodent model of glioma with minimal morbidity and optimal pharmacokinetics.

Animals↗
PubMed2003

Advancing the field of drug delivery: taking aim at cancer.

Drug delivery systems for cancer therapeutics have now been used by millions of patients and have resulted in the creation of new therapies as well as significantly improving existing ones. Here we discuss a number of the drug delivery systems that have been approved by regulatory authorities and that are currently in clinical use, such as controlled delivery of cancer therapeutics, local chemotherapy, polymer drug conjugates, liposomal systems, and transdermal drug delivery patches. The next generation of "smart" drug delivery approaches such as controlled release microchips are discussed as are some of the future challenges and directions in this field.

Absorbable Implants↗
PubMed2003

Local delivery of minocycline and systemic BCNU have synergistic activity in the treatment of intracranial glioma.

Minocycline, a tetracycline derivative, has been shown to inhibit tumor angiogenesis through inhibitory effects on matrix metalloproteinases. Previous studies have shown this agent to be effective against a rodent brain tumor model when delivered intracranially and to potentiate the efficacy of standard chemotherapeutic agents. In the present study, the in vivo efficacy of intracranial minocycline delivered by a biodegradable controlled-release polymer against rat intracranial 9L gliosarcoma was investigated to determine whether it potentiates the effects of systemic 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). Minocycline was incorporated into the biodegradable polymer polyanhydride poly[bis(p-carboxyphenoxy)propane-sebacic acid] (pCPP:SA) at a ratio of 50:50 by weight. The release kinetics of minocycline from the polymer were assessed. For the efficacy studies, female Fischer 344 rats were implanted with 9L glioma. Treatment with minocycline delivered by the pCPP:SA polymer at the time of tumor implantation resulted in 100% survival in contrast to untreated control animals that died within 21 days. Treatment with the minocycline-polymer 5 days after tumor implantation provided only modest increases in survival. The combination of intracranial minocycline and systemic BCNU extended median survival by 82% compared to BCNU alone (p < 0.0001) and 200% compared to no treatment (p < 0.004). We conclude that local intracranial delivery of minocycline from biodegradable controlled-release polymers inhibits tumor growth and may have clinical utility when combined with a chemotherapeutic agent.

Absorbable Implants↗
PubMed2003

Multi-pulse drug delivery from a resorbable polymeric microchip device.

Controlled-release drug delivery systems have many applications, including treatments for hormone deficiencies and chronic pain. A biodegradable device that could provide multi-dose drug delivery would be advantageous for long-term treatment of conditions requiring pulsatile drug release. In this work, biodegradable polymeric microchips were fabricated that released four pulses of radiolabelled dextran, human growth hormone or heparin in vitro. Heparin that was released over 142 days retained on average 96 +/- 12% of its bioactivity. The microchips were 1.2 cm in diameter, 480-560 microm thick and had 36 reservoirs that could each be filled with a different chemical. The devices were fabricated from poly(L-lactic acid) and had poly(D,L-lactic-co-glycolic acid) membranes of different molecular masses covering the reservoirs. A drug delivery system can be designed with the potential to release pulses of different drugs at intervals after implantation in a patient by using different molecular masses or materials for the membrane.

Absorbable Implants↗
PubMed2003

Local immunotherapy with interleukin-2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

OBJECTIVE: Local delivery of carmustine (BCNU) from biodegradable polymers prolongs survival against experimental brain tumors. Moreover, paracrine administration of interleukin-2 (IL-2) has been shown to elicit a potent antitumor immune response and to improve survival in animal brain tumor models. We report the use of a novel polymeric microsphere delivery vehicle to release IL-2. We demonstrate both in vitro release of cytokine from the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from the microspheres in the rat brain. These microspheres are used to deliver IL-2, and biodegradable polymer wafers are used to deliver BCNU, directly at the site of an intracranially implanted glioma in the rat. The two agents administered locally show a synergistic effect. METHODS: Fischer 344 rats challenged intracranially with 9L gliosarcoma received an intracranial implant of either empty microspheres or microspheres containing IL-2 (IL-2 MS). Five days later, animals in each group were randomized to receive polymer implants loaded with 0, 3.8, or 10% BCNU at the tumor site. RESULTS: Animals that received the combination of IL-2 MS and 3.8% BCNU polymer (median survival, 28.5 d) or IL-2 MS and 10% BCNU polymer (median survival, 45.5 d) showed significantly improved survival compared with animals that received monotherapy with IL-2 microspheres (median survival, 24 d), 3.8% BCNU polymer (median survival, 24 d), or 10% BCNU polymer (median survival, 32.5 d). Control animals had a median survival of 18 days. The combination of either 3.8 or 10% BCNU polymer with IL-2 MS resulted in 7 and 25% long-term survivors, respectively. CONCLUSION: By showing synergy of IL-2 and BCNU in an animal glioma model and using a reproducible synthetic delivery system for each agent (i.e., one that did not rely on genetically engineered cells or viruses), we hope that the combination of local immunotherapy and chemotherapy can take an important step closer to clinical application in patients with malignant brain tumors.

Animals↗
PubMed2003

The surgical bed after BCNU polymer wafer placement for recurrent glioma: serial assessment on CT and MR imaging.

OBJECTIVE: The objective of our study was to describe the CT and MR imaging appearances of the surgical bed in the brains of patients receiving biodegradable polymers impregnated with N, N'1, 3-Bis-(2-chloroethyl)-N-nitrosourea (BCNU) for recurrent glioma and to determine whether patients receiving placebos could be differentiated from those receiving BCNU based on the pattern and growth kinetics of tumor recurrence. MATERIALS AND METHODS: The CT and MR images of 20 patients who underwent surgery for resection of recurrent high-grade gliomas and placement of intratumoral wafers (11 received BCNU polymer wafers, nine received control wafers) were analyzed for wafer appearance, volume of gas in the tumor bed, and volume of enhancement on serial scans. RESULTS: Wafers appeared as linear hyperdense structures on CT and as linear low-signal-intensity structures on MR imaging and caused no significant enhancement. In the BCNU polymer group, gas volume was 4.0 +/- 3.4 cm(3) (mean +/- SD), whereas gas volume was 1.6 +/- 3.0 cm(3) for the placebo group (Mann-Whitney test, p = 0.03). A trend toward linear rather than exponential recurrent tumor growth was identified for the BCNU polymer group but not for the placebo group. CONCLUSION: BCNU polymer wafers have a specific appearance on CT and MR imaging with which radiologists should be familiar: gas in the surgical bed is an expected transient finding, and tumor regrowth in patients receiving BCNU polymer wafers appeared to occur at a slower rate than in those receiving the placebo.

Adult↗
PubMed2003

Camptothecin analogs in malignant gliomas: comparative analysis and characterization.

OBJECT: The authors compared and characterized several new classes of camptothecin (CPT) analogs (a total of 22 drugs) directed against human and murine glioma cell lines in vitro, trying to identify CPT analogs that can be used for local therapy in future clinical trials. Camptothecin is a naturally occurring alkaloid that inhibits the DNA-replicating enzyme topoisomerase I. Moreover, CPT and its analogs have shown promising antitumor activity against both systemic and intracranial neoplasms. Because the CPTs have poor bioavailability and are unable to cross the blood-brain barrier, they may best be delivered to the central nervous system by polymers. The authors have previously shown that local delivery of Na-CPT by implantable polymers prolongs survival in a rat intracranial glioma model. In recent years, a number of newly synthesized CPT analogs have been developed that exhibit more potency and stability than Na-CPT. METHODS: Cytotoxicities of the drugs were tested using modified clonogenic and monotetrazolium assays in three glioma cell lines. A potassium chloride-sodium dodecyl sulfate coprecipitation assay was used to determine the frequency of drug-stabilized cleavable complexes. Of the CPT analogs analyzed, the 10,11-methylenedioxy (MD) class consistently demonstrated the greatest cytotoxicity. Three of these analogs, 10,11-MD-20(RS)-CPT, 10,11-MD-20(S)-CPT-glycinate ester (Gly).HCl, and 9-amino-10,11-MD-20(S)-CPT-Gly, exhibit significantly greater antiproliferative activities than CPT, Na-CPT, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against all three glioma cell lines. In addition, the 10,11-MD-20(RS)-CPT analog induces more cleavable complexes than Na-CPT at every concentration. CONCLUSIONS: The increased potency and greater stability of CPT analogs hold promise for more effective local antitumor treatments against malignant intracranial brain tumors. The greater cytotoxicity of 10,11-MD CPTs in comparison with other CPT analogs as well as CPT, BCNU, or Na-CPT, may present an ideal candidate drug class for development against both primary and metastatic brain tumors.

Animals↗
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↗
PubMed2003

Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project.

OBJECT: The Glioma Outcomes Project represents a contemporary analysis of the management of malignant (Grade III and Grade IV/GBM) gliomas in North America. This observational database was used to evaluate the influence of resection, as opposed to biopsy, on patient outcome as measured by the length of survival. Attempts were made to reduce the impact of selection bias by repeating the data analysis after omitting patients with major negative prognostic factors. METHODS: Outcome data from 788 patients accrued from multiple sites over a 4-year period (1997-2001) were analyzed with the primary outcome measure being length of survival. Of these, 565 patients with recent diagnoses formed the basis of the present analysis. Patients were systematically followed up until death or up to 24 months after enrollment in the study, and survival data were correlated with the histopathological grade and location of the tumor, the extent of surgery, the patient's performance status, and demographic factors. The median length of survival was 40.9 weeks for patients with recently diagnosed GBMs. The true median length of survival for patients with Grade III gliomas was not reached, although there was a 58% survival rate at 104 weeks. In multivariate analysis, resection rather than biopsy (p < 0.0001), age 60 years or younger (p < 0.0001), and a Karnofsky Performance Scale (KPS) score of 70 or greater (p = 0.0004) were associated with a prolonged survival time for patients with Grade III or IV gliomas. The prognostic value of resection compared with biopsy was maintained (p < 0.0001), even after eliminating patients considered to be "poor risk" (those with age > 60 years, KPS score < 70, or presence of multifocal tumors), who may have been overrepresented in the biopsy group. Survival "tails" at 24 months were 58% for Grade III gliomas and 11% for GBMs. CONCLUSIONS: These data provide Class II evidence to support tumor grade, patient's age, and patient's functional status as prognostic factors for survival in individuals with recently diagnosed malignant gliomas. Resection (compared with biopsy) is also a strong prognostic factor; however, no quantitative attempt was made to assess the true extent of the resection.

Adult↗
PubMed2003

Outcome and cost of craniotomy performed to treat tumors in regional academic referral centers.

OBJECTIVE: Improved clinical and economic outcomes for high-risk surgical procedures have been previously cited in support of regionalization. The goal of this study was to examine the effects of regionalization by analyzing the cost and outcome of craniotomy for tumors and to compare the findings in academic medical centers versus community-based hospitals. METHODS: Outcomes and charges were analyzed for all adult patients undergoing craniotomy for tumor in 33 nonfederal acute care hospitals in Maryland using the Maryland Health Service Cost Review Commission database for the years 1990 to 1996. A total of 4723 patients who underwent craniotomy for tumor were selected on the basis of Diagnostic Related Group 1 (craniotomy except for trauma, age 18 or older) and International Classification of Diseases-9th Revision diagnosis code for benign tumor, primary malignant neoplasm, or secondary malignant neoplasm (codes 191, 192, 194, 200, 225, 227, 228, 237, and 239). Hospitals were categorized as high-volume hospitals (>50 craniotomies/yr) or low-volume hospitals (<or=50 craniotomies/yr). In-hospital mortality, length of stay, and charges were evaluated. RESULTS: The mortality rate was 2.5% at high-volume centers and 4.9% at low-volume hospitals with an adjusted relative risk of 1.4 (P < 0.05), assuming equivalence of disease severity. Adjusted average length of stay in high-volume centers was 6.8, as compared with 8.8 days in low-volume hospitals (P < 0.001). Adjusted average total charges were $15,867 at high-volume centers and $14,045 at low-volume centers (P < 0.001). If all patients in the state had been treated at centers with survival rates equal to those achieved by the high-volume centers, then 46 patients would not have died of operation; that is, 48.6% fewer patients would have died, at an additional adjusted cost of $76,395 dollars per patient saved. CONCLUSION: High-volume regional medical centers are capable of providing services with improved mortality rates and fewer hospital days, although with adjusted costs slightly higher than those at low-volume hospitals.

Academic Medical Centers↗