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Biomedical subjects

Silvia Hofer

Publications and source records attributed to Silvia Hofer.

8 recordsLinked to original sources
PubMed2006

Outcome and prognostic factors in cerebellar glioblastoma multiforme in adults: a retrospective study from the Rare Cancer Network.

PURPOSE: The aim of this study was to assess the outcome in patients with cerebellar glioblastoma (GBM) treated in 15 institutions of the Rare Cancer Network. METHODS AND MATERIALS: Data from a series of 45 adult patients with cerebellar GBM were collected in a retrospective multicenter study. Median age was 50.3 years. Brainstem invasion was observed in 9 (20%) patients. Radiotherapy (RT) was administered to 36 patients (with concomitant chemotherapy, 7 patients). Adjuvant chemotherapy after RT was administered in 8 patients. Median RT dose was 59.4 Gy. Median follow-up was 7.2 months (range, 3.4-39.0). RESULTS: The 1-year and 2-year actuarial overall survival rate was 37.8% and 14.7%, respectively, and was significantly influenced by salvage treatment (p = 0.048), tumor volume (p = 0.044), extent of neurosurgical resection (p = 0.019), brainstem invasion (p = 0.0013), additional treatment after surgery (p < 0.001), and completion of the initial treatment (p < 0.001) on univariate analysis. All patients experienced local progression: 8 and 22 had progression with and without a distant failure, respectively. The 1- and 2-year actuarial progression free survival was 25% and 10.7%, respectively, and was significantly influenced by brainstem invasion (p = 0.002), additional treatment after surgery (p = 0.0016), and completion of the initial treatment (p < 0.001). On multivariate analysis, survival was negatively influenced by the extent of surgery (p = 0.03) and brainstem invasion (p = 0.02). CONCLUSIONS: In this multicenter retrospective study, the observed pattern of failure was local in all cases, but approximately 1 patient of 4 presented with an extracerebellar component. Brainstem invasion was observed in a substantial number of patients and was an adverse prognostic factor.

Adult↗
PubMed2006

Local targeting of malignant gliomas by the diffusible peptidic vector 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid-substance p.

PURPOSE: Malignant glial brain tumors consistently overexpress neurokinin type 1 receptors. In classic seed-based brachytherapy, one to several rigid (125)I seeds are inserted, mainly for the treatment of small low-grade gliomas. The complex geometry of rapidly proliferating high-grade gliomas requires a diffusible system targeting tumor-associated surface structures to saturate the tumor, including its margins. EXPERIMENTAL DESIGN: We developed a new targeting vector by conjugating the chelator 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid to Arg(1) of substance P, generating a radiopharmaceutical with a molecular weight of 1,806 Da and an IC(50) of 0.88 +/- 0.34 nmol/L. Cell biological studies were done with glioblastoma cell lines. neurokinin type-1 receptor (NK1R) autoradiography was done with 58 tumor biopsies. For labeling, (90)Y was mostly used. To reduce the "cross-fire effect" in critically located tumors, (177)Lut and (213)Bi were used instead. In a pilot study, we assessed feasibility, biodistribution, and early and long-term toxicity following i.t. injection of radiolabeled 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid substance P in 14 glioblastoma and six glioma patients of WHO grades 2 to 3. RESULTS: Autoradiography disclosed overexpression of NK1R in 55 of 58 gliomas of WHO grades 2 to 4. Internalization of the peptidic vector was found to be specific. Clinically, the radiopharmeutical was distributed according to tumor geometry. Only transient toxicity was seen as symptomatic radiogenic edema in one patient (observation period, 7-66 months). Disease stabilization and/or improved neurologic status was observed in 13 of 20 patients. Secondary resection disclosed widespread radiation necrosis with improved demarcation. CONCLUSIONS: Targeted radiotherapy using diffusible peptidic vectors represents an innovative strategy for local control of malignant gliomas, which will be further assessed as a neoadjuvant approach.

Adult↗
PubMed2006

Gefitinib accumulation in glioblastoma tissue.

Therapeutic agents for brain tumors confront multiple physical and metabolic hurdles. These include the blood brain barrier (BBB), vascular and interstitial barriers, clearing by MDR1 and other ABC transporter proteins, and drug catabolism. Here, we report an accumulation of gefitinib in glioblastoma (GBM) tissue to over a dozen times plasma levels, and propose that some mechanisms converge to achieve such accumulation: (1) small molecular size of gefitinib facilitates access by diffusion; (2) its high water solubility enables thermodynamic retention inside malignant cells; and (3) low CYP3A4 activity in GBM tissue, the main enzyme for gefitinib catabolism, prevents metabolic elimination. Our data confirm the capacity of gefitinib to accumulate in solid human tumors in vivo.

Antineoplastic Agents↗
PubMed2005

Avoiding glucocorticoid administration in a neurooncological case.

Restricting glucocorticoid (GC) use in the treatment of patients with a solid tumor may help improving outcome. Here, we report administration of celecoxib rather than dexamethasone to prevent brain edema in a patient with a cerebellar glioblastoma multiforme WHO grade IV (GBM) upon the patient's request, as well as determining cerebrospinal fluid (CSF) and serum concentrations. CSF concentration (0.04 microM) was 54 times below serum concentration (2.18 microM), or 2500 times below levels inhibiting GBM cells in vitro (100 microM), revealing a blood CSF barrier for celecoxib. The patient did not require dexamethasone for the entire treatment. GC administration hence was avoided successfully in this case. The role of COX-2 inhibitors in treatment of GBM is detailed, leading to the conclusion of a pressing need for a clinical evaluation of non-steroidal COX-2 inhibitors with the ability to penetrate into brain tumors.

Antineoplastic Agents, Alkylating↗
PubMed2004

Delayed-onset and long-lasting severe neutropenia due to rituximab.

BACKGROUND: Rituximab, a monoclonal antibody, is effective in CD20-positive B-cell lymphoma and is now widely used either as a single agent or in combination with chemotherapy. The antibody's toxicity is generally mild and transient. There are reports of protracted neutropenia in patients treated with rituximab. CASE REPORT: We report on a patient with Burkitt's lymphoma treated with the hyper-CVAD chemotherapy regimen combined with rituximab. Four weeks after the five months' treatment marked neutropenia and hypogammaglobulinaemia occurred and persisted for one year. Both laboratory findings were not associated with severe infections in our patient. CONCLUSIONS: Delayed-onset neutropenia is a newly recognised toxicity of rituximab treatment which may last up to one year and be complicated by serious infections.

Adult↗