Prognostic impact of meningeal dissemination in primary CNS lymphoma (PCNSL): experience from the G-PCNSL-SG1 trial.

BACKGROUND: We evaluated the frequency and prognostic impact of meningeal dissemination (MD) in immunocompetent adult patients with primary central nervous system lymphoma treated in a randomized phase III trial. PATIENTS AND METHODS: MD was evaluated at study entry and defined by lymphoma proof in the meningeal compartment detected by at least one of the following methods: cerebrospinal fluid (CSF) cytomorphology, detection of clonal B cells by IgH PCR in CSF or contrast enhancement of the leptomeninges on magnetic resonance imaging (MRI). RESULTS: Data on MD were available in 415 patients, of those, MD was detected in 65 (15.7%): in 44/361 (12.2%) by CSF cytomorphology, in 16/152 (10.5%) by PCR and in 17/415 (4.1%) by MRI. Major patients' characteristics and therapy did not significantly differ between patients with MD (MD+) versus those without MD (MD-). There was a significant correlation of MD with CSF pleocytosis (>5/µl; P < 0.0001), but no correlation with CSF protein elevation (>45 mg/dl). Median progression-free survival was 6.7 months [95% confidence interval (CI) 0-14.5] in MD+ and 8.3 months (5.7-10.8) in MD- patients (P = 0.95); median overall survival was 21.5 months (95% CI 16.8-26.1) and 24.9 months (17.5-32.3), respectively (P = 0.98). CONCLUSION: MD was detected infrequently and had no impact on outcome in this trial.

Treatment of PTLD with rituximab and CHOP reduces the risk of renal graft impairment after reduction of immunosuppression.

We addressed the effect of post-transplant lymphoproliferative disorder (PTLD) treatment with rituximab monotherapy or CHOP-based chemotherapy (+/- rituximab) after upfront immunosuppression reduction (IR) on renal graft function in a longitudinal analysis of 58 renal transplant recipients with PTLD and 610 renal transplant controls. Changes in the estimated glomerular filtration rate over time were calculated from a total of 6933 creatinine measurements over a period of >1 year using a linear mixed model with random and fixed effects. Renal graft function significantly improved with treatment of PTLD, especially in the chemotherapy subgroup. Patients treated with IR+chemotherapy +/- rituximab had a noninferior graft function compared with untreated controls suggesting that the negative impact of IR on the renal graft function can be fully compensated by the immunosuppressive effect of CHOP. The immunosuppressive effect of single agent rituximab may partially compensate the negative impact of IR on the graft function. Thus, it is possible to reduce immunosuppression when using chemotherapy to treat PTLD.

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).

BACKGROUND: The addition of etoposide to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone [etoposide to combination chemotherapy with cyclophosphamide, vincristine and prednisone (CHOEP)] improved outcome of young patients with good-prognosis aggressive lymphoma. To improve results further, the maximal dose-escalated version of CHOEP-21 tolerable without stem-cell support (high CHOEP: cyclophosphamide 1400 mg/m2, doxorubicin 65 mg/m2, vincristine 2 mg, etoposide 175 mg/m2 x3, prednisone 100 mg x5) was compared with CHOEP-21. PATIENTS AND METHODS: Intention-to-treat analysis of 389 young (18-60 years) patients with good-prognosis (age-adjusted International Prognostic Index = 0, 1) aggressive lymphoma randomized to CHOEP-21 (n = 194) or high CHOEP (n = 195). RESULTS: There was no difference in 3-year event-free (64% versus 67%; P = 0.734) or overall survival (83% versus 87%; P = 0.849). Neither low-risk nor low-intermediate risk patients benefited from high CHOEP. High CHOEP was more toxic than CHOEP-21 (grades 3 and 4 leukocytopenia 100% versus 87.2%, P < 0.001; thrombocytopenia 80.8% versus 9.6%, P < 0.001; infections 35% versus 11%, P < 0.001; therapy-associated deaths 3.1% versus 0%, P = 0.03). CONCLUSION: Dose-escalated CHOEP-21 does not provide clinical benefit for young patients with good-prognosis aggressive lymphomas. Since differences between chemotherapy regimens are compressed by the addition of rituximab, the results of this trial have bearing on strategies aiming to improve outcome of good-prognosis aggressive lymphomas in the rituximab era.

Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986.

PURPOSE: To demonstrate that adding irinotecan to a standard weekly schedule of high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can prolong progression-free survival (PFS). PATIENTS AND METHODS: Four hundred thirty patients with measurable or assessable metastatic colorectal cancer were randomly assigned to receive either FA 500 mg/m(2) as a 2-hour infusion and FU 2.6 g/m(2) by intravenous 24-hour infusion, both administered weekly for 6 weeks, followed by a 2-week rest (Arbeitsgemeinschaft für Internistische Onkologie [AIO] arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m(2) preceded by irinotecan 80 mg/m(2) administered over 30 minutes (experimental group, n = 214). RESULTS: The median PFS time in the experimental group was 8.5 months (95% CI, 7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the AIO arm (P < .0001). The median overall survival time was increased from 16.9 to 20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to 69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO arm (P < .0001). CONCLUSION: The addition of irinotecan to the standard AIO FU/FA regimen was associated with a highly significant improvement in PFS and response rate and was well tolerated. The results of this study confirm that irinotecan in combination with high-dose infusional FU/FA is a reference first-line treatment.

Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia.

The purpose of our study was (i) to evaluate the impact of all-trans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged >or=61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day +3 after the initiation of chemotherapy (ATRA-arm, n=122) or no ATRA (standard-arm, n=120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n=31) or 1-year oral maintenance therapy (n=30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA- and the standard-arm (52 vs 39%; P=0.05). Event-free (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P=0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (P<0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.

Kinetics of myeloid progenitor cells in human micro long-term bone marrow cultures.

Hemopoiesis was analyzed in a miniaturized long-term culture of human bone marrow cells by quantifying the production of granulocyte-macrophage progenitor cells. As in the conventional long-term culture system, hemopoiesis was dependent on the presence of a marrow-derived adherent layer. Adipocytes proved to be essential for long-term proliferation. Optimal growth conditions were maintained by incubation in McCoy's medium supplemented with hydrocortisone, fetal calf serum, and horse serum. When calculated back to the volume of conventional cultures, the numbers and kinetics of nucleated cells and granulocyte-macrophage colony-forming cells were comparable in both culture systems. The microsystem is therefore suitable for performing multiple analyses on small samples of cells.

The effect of two different types of colony-stimulating factor on the expression of aminopeptidase on marrow-derived murine macrophages.

The expression of aminopeptidase, a surface-membrane-bound enzyme, on macrophages formed in liquid cultures of hemopoietic progenitor cells was studied over a period of 20 days. The cultures were stimulated by two biochemically distinct types of colony-stimulating factor (CSF) derived from mouse-lung-conditioned medium (MLCM) and L-cell-conditioned medium (LCCM), respectively. The enzyme content of single cells was determined microphotometrically after staining with Fast Blue B salt and leucine 4-methoxy-2-naphthylamide. In LCCM-stimulated cultures the number of cells expressing aminopeptidase, the enzyme content per cell and the enzyme concentration increased markedly from day 10 onward, while macrophages from MLCM-stimulated cultures only showed borderline yet significantly positive aminopeptidase levels. Maximum enzyme concentrations were found earlier than maximum enzyme content indicating an early local increase in the aminopeptidase concentration on the membrane and subsequently a more uniform distribution over the cell surface. The two types of CSF differ not only in their effect on macrophage production but also in their influence on the expression of the surface enzyme aminopeptidase on these cells.

The response of murine splenic granulocyte-macrophage colony-forming cells to lipid A in vivo.

The physical and biological properties of murine splenic granulocyte-macrophage colony-forming cells (GM-CFC) were analyzed after the injection of the splenic hemopoiesis stimulating agent lipid A. In continuous gradients of Percoll, the majority of the splenic GM-CFC of untreated mice peaked at a buoyant density of 1.090 g/cm3, while a small second GM-CFC peak could be detected at 1.065 g/cm3. One day after the injection of lipid A, the splenic GM-CFC were almost equally distributed among these two density peaks. This altered proportion was still detectable 72 to 96 h later, although to a smaller extent. No difference in the responsiveness to the colony-stimulating factor (GM-CSF) from mouse-lung conditioned medium (MLCM) was observed between these two density subpopulations. The differentiation pattern of splenic GM-CFC was altered after the injection of lipid A. However, this altered pattern was the same in both density subpopulations. The percentage of splenic GM-CFC as well as the percentage of multipotent hemopoietic stem cells (CFUs) in DNA synthesis were markedly elevated after the injection of lipid A. A striking difference in the proliferative activity was found between high- and low-density GM-CFC in post-lipid A spleens. 24 h after the injection of lipid A, 43% of the high-density GM-CFC subpopulation was found in S according to the suicide technique using tritiated thymidine, whereas in the low-density fraction only 10% of the population was killed. This finding allows alternative interpretations.

HLA-class II antigens on hemopoietic and stromal cells in human micro long-term bone marrow cultures.

Using a complement-dependent cytotoxicity assay (CDC), we analyzed the presence of HLA-class II antigens on both stromal and hemopoietic cells in a miniaturized human long-term bone marrow culture system. 4-Hydroperoxycyclophosphamide (4-HC)-resistant hemopoietic stem cells capable of restoring in vitro hemopoiesis on irradiated stromal cell layers were HLA-DR, -DP, and -DQ negative. In addition, these cells failed to bind the monoclonal antibody (mAb) Tü 39, previously proposed as a candidate for the recognition of a novel class II antigen, "-DY." On the other hand, the formation of confluent stromal cell layers was inhibited by HLA-DR- or -DP-specific mAbs, but not by the HLA-DQ-specific mAb Tü 22. This suggests the presence of HLA-DR- and/or HLA-DP-positive, but HLA-DQ-negative stromal precursor cells.

Recombinant murine interleukin 9 enhances the erythropoietin-dependent colony formation of human BFU-E.

Murine interleukin 9 (mIL-9) is a novel T-cell-derived lymphokine previously described as a T-cell growth factor (P40/TCGFIII) and as a mast cell growth-enhancing activity (MEA). In the present study we examined the potency of recombinant (r)mIL-9 to exhibit hemopoietic growth factor activity in the human system. In semisolid cultures of normal human bone marrow-derived mononuclear cells, rmIL-9 alone at a concentration range from 25 to 200 U/ml did not reveal any colony-stimulating activity on human granulocyte-macrophage colony-forming cells (GM-CFC), erythroid colony-forming units (CFU-E), and erythroid burst-forming units (BFU-E). Furthermore, we did not observe synergistic effects of rmIL-9 on the number, size, and morphological composition of human granulocyte-macrophage colonies in cultures stimulated with giant cell tumor-conditioned medium. However, a synergistic effect of rmIL-9 in the human erythropoietic culture system was clearly demonstrated in the presence of recombinant human erythropoietin (rhEpo). Recombinant murine IL-9 at a concentration of 200 U/ml enhanced the number of BFU-E-derived day-14 colonies about 3.6-fold as compared to control cultures stimulated with Epo alone. The formation of CFU-E-derived day-7 colonies was not significantly altered under the same conditions. Our results demonstrate that in the presence of rhEpo, rmIL-9 is synergistically active in human bone marrow cultures as an erythroid burst-promoting factor. The development of granulocyte-macrophage colonies obviously is not affected. This finding strongly suggests that mIL-9 can mediate signals via human IL-9 receptors and further extends the range of biological activities hitherto ascribed to mIL-9.

Gemcitabine for palliative treatment in metastatic breast cancer.

Gemcitabine is one of the recently developed drugs with a high efficacy in various malignant tumours and a mild toxicity profile. As monochemotherapy in metastatic breast cancer, gemcitabine yielded response rates up to 46% as first- and second-line treatment. Neutropenia is the clinically most relevant unwanted effect. Haematological and nonhaematological toxicities are mild, making dose reductions, delays of treatment or withdrawal from treatment very rare. The first phase I and phase II studies of gemcitabine in combination with anthracyclines have shown a good toxicity profile and promising remission rates. Phase I experiences with long-time infusion schedules reveal good feasibility and high patient acceptance.

Further evidence for oxidant-induced vascular endothelial growth factor up-regulation in the bronchoalveolar lavage fluid of lung cancer patients undergoing radio-chemotherapy.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of physiological and neoplastic blood vessel growth. Moreover, in vitro studies have demonstrated that VEGF can be up-regulated by conditions associated with the generation of free radicals and reactive oxygen species. In a previous study we reported on strongly increased VEGF concentrations in the bronchoalveolar lavage fluid (BALF) of patients with lung cancer under therapy. In this study we aimed to reveal whether this increase was due to the therapy-associated intrapulmonary oxidative burden. PATIENTS AND METHODS: A total of 103 BALF samples from 94 patients with lung cancer (82 patients with non-small-cell lung cancer, 12 patients with small-cell lung cancer) were studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins of epithelial lining fluid (ELF) were determined. RESULTS: As reported previously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Increased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in patients undergoing only chemotherapy. Similarly, VEGF concentrations in the ELF were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antioxidant imbalances in these patients. CONCLUSION: Systemic chemotherapy is associated with oxidative stress in vivo, which is more pronounced if patients are additionally treated with radiation. VEGF levels in the ELF are increased by this condition as well as by the activity of the tumour itself.

Comparative in vitro toxicity of mitoxantrone and adriamycin in human granulocyte-macrophage progenitor cells.

Mitoxantrone (MIT) has recently been introduced into cancer therapy as a possible substitute for the structurally related drug, adriamycin (ADR), because it causes less cardiotoxicity and fewer gastrointestinal side effects. However, the dose-limiting toxicity of MIT is pronounced neutropenia. The in vitro hematoxicity of both drugs in granulocyte-macrophage precursor cells (GM-CFCs) was analyzed using drug-exposure schedules analogous to the principles of the in vivo pharmacokinetics of MIT. Bone-marrow and peripheral-blood cells were exposed to 0.075-20 ng/ml MIT or ADR for 5, 20, 60, and 120 min, and for 14 days. The 14-day exposure resulted in Do values of 0.95 and 0.68 ng/ml for bone-marrow and peripheral-blood GM-CFCs subjected to MIT. Exposure to ADR resulted in Do values of 5.43 and 5.13 ng/ml, respectively. As was the case after 14-day exposure to MIT or ADR, short-term exposure again revealed that peripheral-blood GM-CFCs were more sensitive to both drugs. Moreover, at low concentrations, ADR was less toxic than MIT in both types of GM-CFCs, but was more toxic than MIT when a concentration of 20 ng/ml was used. The intracellular concentration of MIT, as measured by high-performance liquid chromatography, was constantly below 1 ng per 2 X 10(7) cells, even when it was applied at a concentration of 20 ng/ml for an exposure time of 2 h. The fact that such low concentrations of MIT are toxic for hemopoietic precursor cells may explain the myelotoxicity of this drug. However, the difference between the precursor-cell toxicity of MIT and that of ADR was small when their respective therapeutic doses were taken into consideration. Further analyses of their toxicity in stem cells and/or the microenvironment would appear to be needed.

The course of the urinary DPD-crosslink secretion in metastatic breast cancer--a possibility for response assessment.

BACKGROUND: Urinary deoxypyridinoline (DPD)-crosslinks have been shown to be a highly specific parameter for type I collagen metabolism. MATERIALS AND METHODS: In a prospective breast cancer study, urine samples were collected in after-care patients and in patients with bone metastases. DPD-crosslinks were measured every three weeks using a fully automated chemiluminescence immunoassay. Bone metastases were confirmed by bone scan and/or x-ray, and were followed-up over six months. To validate the test, a receiver operating characteristics (ROC)-curve was set up to find the DPD cut-off concentration which separates patients with no evidence of disease (NED) from patients with bone metastases. RESULTS: 73 breast cancer patients (41 with NED, 32 with bone metastases) were included into the ROC analysis. At a DPD cut-off value of 8 nmol/mmol creatinine, we found the best sensitivity (84.4%) for the detection of bone metastases with a specificity of 70.7%. Patients with stable bone disease under intravenous pamidronate treatment (90 mg q3w) and specific therapy had a significant (p = 0.007) fall of the DPD-crosslinks in comparison to the progressive subset with 72.7% falling below 8 nmol/mmol. CONCLUSIONS: We conclude that the net bone turnover is not increased at a DPD-crosslinks elimination < 8 nmol/mmol.

Adjuvant high-dose chemotherapy with epirubicin and ifosfamide in nodal positive breast cancer.

INTRODUCTION: Morbidity and mortality, disease-free- and overall survival were analysed in an adjuvant high-dose chemotherapy (HDCT) study with ifosfamide and epirubicin for high-risk (> or = 10 positive lymph nodes) breast cancer. PATIENTS AND METHODS: A total of 21 patients (pts) were treated with 4 cycles of ViEC (vindesine, epirubicin, cyclophosphamide) as standard chemotherapy. After the second cycle, CD34+ stem cells were mobilised with G-CSF. HDCT consisted of epirubicin 100 mg/m2 on days (-5)-(-4) before stem-cell rescue and ifosfamide 5000 mg/m2 on days (-5)-(-2). RESULTS: No therapy-related deaths occurred. Mucositis WHO grade III/IV in 52% and neutropenic fever in 81% were the most relevant toxicities. Nausea and vomiting WHO grades III/IV were found in 62.2%. The median duration of leucopenia grade IV was 7 days (range: 4-11) with a median time to platelet recovery > 50,000/microliter of 6 days (range: 4-11). After a median follow-up time of 21 months (range: 12-49 months), six of 21 pts (28.6%) relapsed. Two patients died 12 and 18 months after initial diagnosis. CONCLUSIONS: Adjuvant HDCT with epirubicin and ifosfamide is safe and shows good tolerability for high-risk breast cancer.

Proliferation and maturation of human bone marrow cells in infectious diseases.

In 6 patients with various types of infectious disease an extended study of proliferation and maturation of erythropoiesis and granulocytopoiesis was performed. By means of quantitative 14C-autoradiography DNA synthesis time and labeling index were determined in every morphologically defined cell compartment of both lineages. With these parameters and the relative frequency of cells in the various compartments cell cycle times, relative cell production rates and maturation indices were determined. A general labeling index reduction and prolongation of DNA synthesis time was observed which was statistically significant in the majority of compartments. As a consequence, cell cycle times were prolonged throughout, the deviation from normal increasing with advancing maturation in both lineages. Relative cell production was normal in myelocytes, but elevated in myeloblasts and promyelocytes. On the other hand, proerythroblasts and basophilic erythroblasts showed normal relative cell production rates, while a significantly reduced value was found in polychromatic erythroblasts. The maturation index in both lineages was reduced by roughly 50%. Since cell cycle times were generally prolonged, the most significant deviations from normal being present in the latest proliferative compartments, the low maturation indices are discussed in the light of ineffective erythro- and granulocytopoiesis. Premature cell death in the bone marrow is suggested to be a significant factor in particular cases of infectious disease.

131 I-cG250 monoclonal antibody immunoscintigraphy versus [18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative study.

The aims of this study were to establish the percentage of metastatic renal cell carcinoma (RCC) lesions detected by radioimmunoscintigraphy (RIS) with the chimeric monoclonal antibody 131I-cG250 versus positron emission tomography (PET) with 18F-labelled deoxyglucose ([18F]FDG), and to evaluate the use of these radionuclide imaging modalities compared with routinely used imaging techniques. Twenty patients with metastatic RCC disease were examined with [18F]FDG-PET and 131I-cG250 RIS within 1 week. Total body gamma camera images were obtained up to 120h after injection of 232MBq 131I-cG250. Total body PET scanning was performed 45-60 min after intravenous injection of 370MBq [18F]FDG. Nuclear medicine techniques were compared to routine imaging procedures. Routine imaging modalities revealed a total of 79 metastases. [18F]FDG-PET and 131I-cG250 RIS detected 33 previously unknown metastases, of which 32 were [18F]FDG positive and seven were 131I-cG250 positive. Of the 112 tumour lesions that were documented, [18F]FDG-PET detected 69% (77 out of 112), whereas 131I-cG250 RIS detected only 30% (34 out of 112). In conclusion, [18F]FDG-PET is superior to 131I-cG250 RIS in detecting metastases in patients with metastatic RCC, and therefore seems a promising tool for (re)staging patients with RCC. The usefulness of RIS with a diagnostic dose of 131I-cG250 seems to be restricted to selecting patients for radioimmunotherapy with 131I-cG250.

Oxidant-induced lung injury in anticancer therapy.

Lung injury is one of the most frequent side effects in anticancer therapy. Especially simultaneous application of high doses of ionising radiation and radiosensitising cytotoxic drugs is considered to cause deleterious pneumonitis and pulmonary fibrosis. Growing evidence indicates that reactive oxygen species (ROS) play a key role in the development of these disorders. They are capable of causing cell component alterations and changing cellular protein expression. Observing these disease mechanisms reveals an impressive self-amplifying cascade of secondary ROS generation. Through intricate interactions between cells, cytokines and growth factors, fibroblasts are activated and thus pulmonary matrix content is massively increased. - As clinical appearance is uniform and unspecific, an early, reliable diagnosis of therapy-associated lung damage is not possible so far. However, improving this situation could enable us to take advantage of new multimodal therapeutic facilities. This review discusses mechanisms of ROS generation during radio-chemotherapy in the lung, antioxidant defense strategies and responses to oxidants, thereby assessing current diagnostic tools.

Increased levels of vascular endothelial growth factor in bronchoalveolar lavage of patients with bronchial carcinoma effect of tumour activity and oxidative stress due to radio-chemotherapy?

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a crucial role in physiological and neoplastic angiogenesis. Moreover, VEGF has been found to be upregulated by conditions associated with the generation of free radicals and reactive oxygen intermediates. In patients with cancer, studies to evaluate VEGF as a measure of tumour activity were carried out. We tested the hypothesis that VEGF is additionally affected by oxidative stress due to anticancer therapy. Moreover, the suitability of epidermal growth factor (EGF) to estimate tumour activity was studied. PATIENTS AND METHODS: 60 patients with non-small cell lung cancer (NSCLC) covering different therapy progress and modalities underwent bronchoalveolar lavage. VEGF-, EGF-, albumin- and total protein-concentrations in bronchoalveolar lavage fluid (BALF) and VEGF-levels in blood plasma were studied. RESULTS: BALF VEGF-levels were increased in patients with advanced NSCLC before and in anticancer therapy. In patients who had received radiotherapy to the lung prior to chemotherapy, VEGF concentrations were noticeably higher than under sole chemotherapy. Pulmonary endothelial hyperpermeability was found in patients with recently diagnosed tumours and patients undergoing anti-cancer therapy. Evaluation of EGF-levels in BALF revealed no significant influence of tumour activity or cancer therapy on this parameter. CONCLUSION: BALF-levels of VEGF are affected by tumour activity and oxidative stress due to anticancer therapy.

Quality monitoring, standardized documentation and management with a computerized system in oncology.

Within the last years the prerequisite was prepared to develop a computerized tumor--patient documentation system including quality monitoring and oncological therapy recommendations for every day use. In medicine today, there is an increasing need for quality oriented low cost and transparent management--what is especially true in the field of oncology. The German Federal Authority of Health demands the documentation of all tumor disorders for the establishment of an cancer registry. For these reasons our study group established the program "OncoDoc" in cooperation with the laboratory for Artificial Intelligence of the University Bremen.