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Peter C Warnke

Publications and source records attributed to Peter C Warnke.

10 recordsLinked to original sources
PubMed2006

Capillary physiology of human medulloblastoma: impact on chemotherapy.

BACKGROUND: Advances in the treatment of medulloblastoma have largely been attributed to the introduction of chemotherapy, although Phase III trials have shown advantages for chemotherapy only in subgroups. Because the efficacy of chemotherapy depends on tumor vascularization, the vascular physiology of human medulloblastomas was evaluated. METHODS: Seven patients with histologically proven medulloblastomas underwent measurements of capillary permeability and vascular plasma volume using contrast-enhanced dynamic computer tomography. Regional blood flow was measured in 5 patients using xenon computed tomography (CT). RESULTS: The capillary permeability-surface product for water-soluble compounds ranged from 1.7 +/- 5.5 to 17.6 +/- 12.3 muL/g/min with a mean of 10.5 +/- 6.3 microL/g/min. The vascular plasma volume ranged from 0.02 +/- 0.021 to 0.045 +/- 0.049 mL/g with a mean of 0.03 +/- 0.01 mL/g. The efflux rate ranged from 0.012 +/- 0.007 to 0.065 +/- 0.064 1/min with a mean of 0.039 +/- 0.020 1/min. Regional tumoral blood flow showed a mean of 19.86 +/- 6.8 mL/100g/min as compared with normal cerebellum with 45.4 +/- 12.03 mL/100g/min (P < .005). CONCLUSIONS: The current study demonstrated a low capillary permeability and blood flow in medulloblastomas that could explain the limited response rates of partially resected tumors even after aggressive high-dose chemotherapy, as recently reported.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours.

INTRODUCTION: The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the -1p/-19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy. METHODS: Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation (exons 5-8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33). RESULTS: 1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student's t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The -1p/-19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss. CONCLUSION: rCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the -1p/-19q genotype.

Adult↗
PubMed2006

Histological growth patterns and genotype in oligodendroglial tumours: correlation with MRI features.

Oligodendroglial neoplasms with the -1p/-19q genotype are more indolent with longer survival and increased therapeutic responsiveness than those with intact 1p/19q, but the biological basis for these clinical differences is unclear. Recent research suggests that oligodendrogliomas with and without the -1p/-19q genotype may be distinguished by their magnetic resonance imaging (MRI) appearance, suggesting possible differences in growth characteristics. This study examined the relationship between genotype and histological growth patterns of oligodendroglial neoplasms in association with MR imaging characteristics. Tumour imaging features assessed on MRI included sharp-versus-indistinct border, smooth-versus-irregular contour, homogeneous-versus-heterogeneous signal, contrast enhancement and paramagnetic susceptibility effect. Growth patterns (solid : mixed : infiltrative), tumour-margin transitions in cellularity and calcification were determined histopathologically. Allelic imbalance in chromosomes 1p36 and 19q13 was determined. Thirty-three oligodendrogliomas (25 with 1p/19q loss) and 53 oligoastrocytomas (18 with 1p/19q loss) were investigated. Solid, mixed or infiltrative growth patterns were seen in grade II and grade III tumours with or without 1p/19q loss, but infiltrative growth was more common in tumours with intact 1p/19q (chi2: P = 0.029). Grade III tumours were more likely to have a solid growth pattern (chi2: P = 0.046) associated with contrast enhancement (chi2: P = 0.011). Transition in cellularity at the radiological margin did not differ according to genotype. All cases with T1 or T2 signal homogeneity had intact 1p/19q. Tumours with sharp/smooth borders were more likely to have intact 1p/19q than those with indistinct/irregular borders (chi2: P < 0.001), but this was not related to histological growth characteristics. This study identified a group of oligodendroglial tumours with intact 1p/19q displaying distinctive MR imaging features that were unrelated to the histopathology characteristics.

Adult↗
PubMed2005

Capillary physiology and drug delivery in central nervous system lymphomas.

To evaluate whether the chemosensitivity of primary central nervous system lymphomas to water-soluble drugs could result from improved drug delivery, we quantitatively assessed pharmacokinetic factors in seven patients. The capillary permeability surface product was found to be significantly increased in central nervous system lymphomas compared with glioblastoma multiforme, medulloblastomas, and metastases. Tumoral blood flow was significantly greater than in normal white matter. Our results suggest favorable pharmacokinetics to water- and lipid-soluble drugs in primary central nervous system lymphomas.

Adult↗
PubMed2005

Molecular pathology and clinical characteristics of oligodendroglial neoplasms.

To evaluate the role of molecular genetics in the routine clinic, we investigated allelic imbalance at 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation in 100 oligodendroglial neoplasms diagnosed at a single treatment center between 2000 and 2003. The -1p/-19q genotype, seen in 64, 34, 77, and 30% of OII, OAII, OIII, and OAIII respectively, was inversely related to p53 mutation and 17p13 loss. Genotype was unrelated to tumor location and could not distinguish high-grade tumors that presented de novo from those that progressed from a previous lower grade malignancy. Presentation with seizures was more common in cases with the -1p/-19q genotype, and these remained stable for longer before treatment. In longitudinal samples, 74% retained their initial histological differentiation, whereas 29% showed new genetic alterations, the -1p/-19q genotype being acquired in three cases. Loss of 1p36 and 19q13, 17p13, chromosome 10, and p53 mutation were significantly associated with survival from presentation in Kaplan-Meier analysis (p < 0.01), and loss of 1p36 and 19q13 and loss of 17p13 retained significance in multivariate analysis. In this recently diagnosed unselected series, clinical differences in tumors with and without the -1p/-19q genotype support a genetic approach to aid diagnosis and prognostication for oligodendroglial neoplasms.

Adult↗
PubMed2005

Brachytherapy for brain tumors.

Over the past several decades neurooncologists have attempted to find an adjuvant treatment that prolongs survival for patients with malignant brain tumors. Brachytherapy, radiotherapy delivered by placing radioactive sources directly into the tumor, was initially thought to be the solution to this problem. Initial single institution studies showed very promising results; however, this technique has failed to show a significant survival advantage in two randomized studies. Despite this, brachytherapy continues to be used in a number of centers throughout the world for the treatment of various types of brain tumors including low-grade gliomas, anaplastic astrocytomas, glioblastomas, meningiomas and metastases. This article reviews brachytherapy's rationale, radiobiology, complications, indications, and results from numerous studies that have focused on its application for brain tumors with emphasis on its application for glial tumors.

Animals↗
PubMed2004

Correlation of molecular genetics with molecular and morphological imaging in gliomas with an oligodendroglial component.

PURPOSE: Since the recognition that oligodendrogliomas may be chemosensitive, their diagnosis and clinical management has become highly controversial. Histopathology diagnosis remains challenging and new tools such as molecular genetics or molecular imaging require evaluation. EXPERIMENTAL DESIGN: In a single-center, population-based prospective study, allelic imbalance in chromosomes 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 has been investigated in 19 oligodendroglioma WHO grade 2 (OII), 20 oligoastrocytoma WHO grade 2 (OAII), 8 oligodendroglioma WHO grade 3 (OIII), and 12 oligoastrocytoma WHO grade 3 (OAIII), and compared with pretherapy histopathology, computed tomography and/or magnetic resonance (CT and/or MR), [fluorine-18]fluoro-2-deoxyglucose (18F-FDG), and thallium-201 single-photon emission computed tomography (201Tl SPECT). RESULTS: In 50 cases, 18F-FDG uptake correlated with 201Tl uptake; however, 8 cases had increased 201Tl uptake but were hypometabolic for 18F-FDG, and 1 case was hypermetabolic with normal 201Tl uptake. Sixteen cases enhanced on CT/MR but failed to show 201Tl uptake; and 2 low-grade non-enhancing oligodendrogliomas had increased 201Tl uptake. Increased metabolism was more likely in high-grade cases, with 201Tl uptake more strongly correlated with grade than was 18F-FDG uptake. Tumors with 1p/19q loss were more likely to show increased 201Tl uptake and, to a lesser degree, increased 18F-FDG uptake than those without these losses. Elevated metabolism in 28% of low-grade tumors was significantly more common in tumors with 1p/19q loss, and increased uptake of both 18F-FDG and 201Tl in low-grade cases was found only in those with 1p/19q loss. CONCLUSIONS: In this study, dissociation of uptake of contrast agents and radiotracers suggests independent deregulation of the blood-brain barrier breakdown and metabolism during disease progression of oligodendroglial neoplasms, and the association of elevated metabolism with 1p/19q loss, particularly in low-grade tumors, may have implications for clinical management.

Adult↗
PubMed2003

Phenotype versus genotype in gliomas displaying inter- or intratumoral histological heterogeneity.

PURPOSE: Molecular classification of gliomas is becoming increasingly important clinically as an adjunct to histopathological diagnosis. Whereas histological heterogeneity of gliomas is well recognized, less is known of the relationship between histological heterogeneity and genetic alterations. Our objective was to investigate the relationship between genotype and phenotype for markers of potential clinical utility in histologically heterogeneous gliomas. EXPERIMENTAL DESIGN: We have used laser capture microdissection to sample the various histological phenotypes present in 42 tumors from 25 glioma cases with either inter- or intratumoral histological heterogeneity, and multiple simultaneous PCR amplification of microsatellite markers and capillary electrophoresis to determine allelic imbalance in chromosomes 1p, 19q, 17p, 10p, and 10q. RESULTS: Loss of 1p36 and 19q13 was seen only in oligodendroglial histology in 7 of 13 oligodendrogliomas. 17p13 loss was found in 14 of 41 tumors in astrocytic, oligoastrocytic, oligodendroglial, and glioblastomatous histologies. Chromosome 10 loss was seen in all of the high-grade histologies in 7 of 7 glioblastomas with an oligodendroglial component and in 1 of 5 low-grade oligodendroglial regions present within high-grade tumors. Seven tumors from 5 cases had no detectable losses of any markers investigated. In 13 tumors with intratumoral heterogeneity, identical genetic losses were present in all areas of histological differentiation. Additional losses were seen in some but not all of the histologies within 2 tumors and were associated with progression in 3 cases. CONCLUSIONS: The gliomas in this study were more homogeneous in their genotype than their histological phenotype with regions of differing histological subtype indistinguishable by the genetic markers investigated, supporting a monoclonal origin of these tumors.

Alleles↗
PubMed2003

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma.

A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to confirm these results. Two hundred forty patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology. Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P </= 0.05). Adverse events were comparable for the 2 groups, except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the placebo-treated group) and intracranial hypertension (9.1% in the BCNU wafer-treated group vs. 1.7% in the placebo group). This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma.

Adult↗