Retrospective analysis of treatment outcome in 315 patients with oligodendroglial brain tumors.

Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53-1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO degrees II vs. degrees III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additional risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors.

Primary CNS lymphoma in immunocompetent patients from 1989 to 2001: a retrospective analysis of 164 cases uniformly diagnosed by stereotactic biopsy.

BACKGROUND: We present outcome data of a cohort of 164 immunocompetent PCNSL patients uniformly diagnosed at a single center for stereotactic neurosurgery, and evaluate the acceptance and impact of combination radiotherapy (RT) and chemotherapy (CHT) with high-dose methotrexate (HD-MTX) over time. METHOD: We assessed choice of treatment and patient survival in a series of 164 PCNSL cases diagnosed from 1989 to 2001, and performed a re-evaluation of histopathology and pre-operative clinical data. FINDINGS: From 1989 to 1993, RT was the predominant therapy, and additional CHT did not improve survival. After 1994, the use of combination CHT/RT increased continuously, consistently contained MTX, and was associated with longer survival than RT only: median survival was 14 months after CHT/RT (2-year survival 35.7%) and 10 months (2-year survival 26.2%) after RT only (not significant). Overall median survival remained poor, increasing from six (1989-1993) to nine months (1994-2001) (p = 0.008). Survival was variable, with a few patients surviving >4 years after diagnosis in the CHT/RT as well as in the RT only group. CONCLUSIONS: Despite considerable improvement of PCNSL therapy, the overall benefit of combined CHT/RT versus RT only was lower than that expected from previous phase II clinical trials. The striking variability of survival in either treatment group may suggest a yet undefined biological heterogeneity of PCNSL, which may also include a more aggressive PCNSL subtype in the group of patients with rapidly progressive disease and not eligible for standard therapy.

Near monochromatic X-rays for digital slot-scan mammography: initial findings.

X-ray spectra are composed of a broad bremsspectrum and anode-characteristic emission lines. In mammography typically molybdenum (Mo), rhodium (Rh) or tungsten (W) anodes are used in combination with Mo, Rh or aluminium filters. Only the photons with energies between 17 and 22 keV of the resulting spectrum are suitable for the soft tissue imaging needed for mammography. The aim of this article is to present first results obtained with a monochromator module mounted at the exit of the X-ray tube of a conventional clinical mammography unit. The experimental setup consists of a Siemens Mammomat 300, an X-ray monochromator module and a linear array detector for image acquisition. The technique is similar to the slot-scan technique known from digital mammography. The experimental machine allows to obtain images both with polychromatic and monochromatic X-rays. Initial evaluation of the system was performed by examination of a contrast-detail phantom (CD-MAM-phantom, Nijmegen, The Netherlands). Images done with the new monochromatic technique were compared to images of the phantom done with polychromatic spectra, with film-screen mammography as well as with digital mammography. The new technique with monochromatic slot-scan mammography resulted in correct identification of 93% of the phantom. Digital slot-scan mammography with polychromatic beam resulted in correct identification of 87%, digital full-field mammography in 83% and conventional film-screen mammography in 70% of the phantom. The results suggest that monochromatization has a potential for improving image quality or decreasing dose in X-ray mammography.

Oral trofosfamide: an active and well-tolerated maintenance therapy for adult patients with advanced bone and soft tissue sarcomas. Results of a retrospective analysis.

OBJECTIVES: Aim of this study was to evaluate the feasibility and toxicity of oral trofosfamide given as maintenance therapy to adult patients with bone and soft tissue sarcomas following first or later line induction chemotherapy, and to determine the clinical efficacy in terms of impact on progression-free and overall survival. PATIENTS AND METHODS: 49 patients with locally advanced or metastatic high-grade soft tissue and bone sarcomas were identified retrospectively according to the inclusion criteria of the analysis. They were treated with oral trofosfamide at a dose of 100-150 mg per day continuously. All patients were pretreated with one or more lines of chemotherapy resulting in partial remission or stable disease. Patients were treated until progression of disease or unacceptable toxicity occurred. Progression- free and overall survival were measured from the beginning of maintenance therapy. RESULTS: Median follow-up for all patients was 33 months (range 10-98). Toxicity was mild and predominantly hematologic. Only 1 patient had to stop treatment due to renal toxicity. The median progression-free survival was 7 months with 27% of patients continuing maintenance treatment at 1 year. Median overall survival is 14 months. Patients with metastatic disease showed a median survival of 23 months from diagnosis of metastases. 3 patients with stable disease following induction chemotherapy reached partial remission while under trofosfamide maintenance. CONCLUSION: Oral maintenance therapy with trofosfamide is well-tolerated and seems to prolong progression-free and overall survival compared to the course of advanced soft tissue and bone sarcomas without maintenance chemotherapy.

Continuous interleukin-6 application in vivo via macroencapsulation of interleukin-6-expressing COS-7 cells induces massive gliosis.

The inflammatory cytokine interleukin-6 (IL-6) was found in senile plaques of Alzheimer's patients and might be involved in the pathology of Parkinson's disease and multiple sclerosis. Interestingly, an astocytosis is also found in these neurodegenerative disorders. To evaluate the direct effects of IL-6 in vivo on glial cells, we created a new in vivo model. IL-6 and mock-transfected (control group) COS-7 cells were encapsulated in a poly-acryl-nitril membrane for implantation into the rat striatum. Afterward, the host immune reaction to the membrane without encapsulated cells and the biological action of IL-6-producing capsules was evaluated. Animals with an implanted membrane without cells showed a moderate astrocytosis 5 days after the operation. Furthermore, microglia and T-cells could be detected and after 30 days the astrocytosis decreased to a small layer around the membrane. In comparison to the control group, which received a sham operation, our results demonstrate that the response of glial cells is caused by the mechanical damage of the surgical procedure itself rather than due to the introduced membrane material. In contrast, we found a massive proliferation and activation of astrocytes and microglia after 10 days by IL-6-secreting capsules, indicating that IL-6 is involved in the induction of gliosis. Control animals that received encapsulated mock-transfected COS-7 cells showed only a weak response. These data point to an involvement of IL-6 in the proliferation and activation of glial cells as seen in neurodegenerative disorders.

Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study.

PURPOSE: To evaluate the feasibility and toxicity of the combination of full-dose epirubicin (EPI) and high-dose ifosfamide (IFO) with granulocyte colony-stimulating factor (G-CSF) support and to determine the clinical efficacy in terms of response and impact on survival. PATIENTS AND METHODS: Forty-six consecutive, previously untreated patients with locally advanced or metastatic high-grade soft tissue sarcomas were treated with IFO 2.5 g/m2/d as a continuous infusion on days 1 to 5 and EPI 45 mg/m2/d as a continuous infusion on days 2 and 3 every 3 weeks. G-CSF 5 microg/kg/d subcutaneously (s.c.) was given on days 6 to 15 or until recovery of leukocytes after all cycles. Response evaluation was performed every two cycles and responding patients were treated with up to six cycles. All patients were evaluated for resectability of residual local or metastatic disease and underwent surgery if possible. RESULTS: All patients experienced grade 3 or 4 myelosuppression. Other toxicities were mild. The overall response rate was 52%, with a complete remission (CR) rate of 22% after chemotherapy alone. Eight additional patients were rendered free of tumor (no evidence of disease [NED]) by surgical procedures. The median overall survival of all patients is 24 months. The CR/NED patients (39%) have a significantly superior survival time compared with all other patients. Thirteen of these 18 patients (72%) are alive, nine free of tumor, with a median follow-up time of 33 months. CONCLUSION: This dose-intensive combination chemotherapy is toxic but feasible and produced a high number of partial remissions (PRs) and especially CRs, which resulted in prolonged survival.

VH genes expressed in peripheral blood IgE-producing B cells from patients with atopic dermatitis.

In this study we analysed the VH genes expressed in IgE-producing peripheral B cells in two patients with severe atopic dermatitis. We found a diverse antibody repertoire containing V(H) genes of five different VH families, no VH2 and 7 genes, with no biased usage of one particular VH gene family. Some VH germ-line segments were found to be used several times within the epsilon transcripts (V3-23, V3-30). Comparison of the IgE-encoding VH genes with the respective germ-line elements revealed the expression of nearly germ-line identical as well as somatically mutated VH genes. In these latter VH genes base substitutions were distributed over both complementarity determining and framework regions. Because of the similarities between the IgE committed B cell repertoire in atopic patients and the peripheral B cell repertoire in non-atopic individuals we conclude that the atopic VH gene repertoire probably reflects the result of an increased class switch of polyclonal B cells, including virgin and mature B cells, in response to a Th2 cytokine profile.