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M Molls

Publications and source records attributed to M Molls.

At least 55 records · Page 3Linked to original sources
PubMed1999

Blood flow and oxygenation status of human tumors. Clinical investigations.

PURPOSE: There is a large body of evidence suggesting that blood flow and oxygenation of human tumors are important research topics which may explain, in particular, resistance to radiation and to many antineoplastic drugs, which can limit the curability of solid tumors by radiotherapy and chemotherapy. MATERIALS AND METHODS: This manuscript reviews the clinical investigations which have been performed regarding blood flow and oxygenation status of human tumors in radiation oncology. RESULTS: The possible uses and limitations of the prognostic significance and the changes under therapy measuring blood flow and oxygenation in human tumors were discussed. In addition, several approaches were summarized, which can improve the microvascular O2 availability and perfusion-limited O2 delivery. CONCLUSION: The clinical data concerning the prognostic significance of blood flow, vascular function and oxygenation of human tumors are relevant for patient selection in clinical oncology. Strategies to improve traditional cancer therapy by modulation of the oxygenation status remain quite promising but more critical research and sophisticated clinical studies are necessary before its true potential is known.

Animals↗
PubMed1999

Oxygen tension in transplanted mouse osteosarcomas during fractionated high-LET- and low-LET radiotherapy--predictive aspects for choosing beam quality?

PURPOSE: The lower OER of high-LET radiations, compared to conventional (low-LET) radiations, has often been put forward as an argument for using high-LET radiotherapy in the management of hypoxic tumours. Among the different neutron beams used in therapy, the reactor fission neutrons have the lowest OER. The aim of the present study is to follow the variations of tumour oxygenation status during fractionated irradiation with different radiation qualities. Little information is available so far after fractionated high-LET irradiation. In addition, the RBE of reactor fission neutrons for effects on tumours and on normal tissues are compared. MATERIAL AND METHODS: Murine OTS 64-osteosarcomas were transplanted in 102 balb-C mice and irradiated by 36 Gy of photons in fractions of 3 Gy five times a week (group P-36/3) or by 12 Gy of reactor fission neutrons in fractions of 2 Gy two times a week (group N-12/2). Irradiations started at a tumor volume of 500 to 600 mm3. A third group received no radiotherapy, but all investigations (group CG). Tumor volume and tumor oxygenation were measured once a week under therapy and during three weeks after therapy. For in vivo-evaluation of oxygen status a computerized polarographic needle electrode system (KIMOC pO2 histograph, Eppendorf) was used. The median pO2 and the hypoxic fraction (pO2 values < 5 mm Hg) of single tumors and of total groups were calculated from pooled histograms and from row data as well. RESULTS: In correlation with the increase of tumor volume, from day 1 to day 42 of follow-up the median pO2 decreased from 20 mm to 8 mm Hg and the hypoxic fraction increased from 7% to 31%. After fractionated photon therapy a growth delay of three weeks was observed. Six weeks after beginning of the irradiation the median tumor volume had been doubled again. After fission neutron therapy growth delay continued until the end of the follow-up period. In both of the irradiated groups a significant decrease of median pO2 values and an increase of the hypoxic fraction were observed under radiotherapy. Hypoxia was more intensive after neutrons with a decrease of the median pO2 from 20 mm Hg to 1 mm Hg vs. 10 mm Hg after photon therapy and with an increase of the hypoxic fraction from 7% to 78% vs. 36% respectively. Two weeks after the end of therapy the median pO2 and the hypoxic fraction of both treated groups reached the levels prior to irradiation indicating a complete reoxygenation. CONCLUSION: During fractionated irradiation of murine osteosarcomas with photons and reactor fission neutrons, a marked hypoxia was observed for both radiation qualities, but hypoxia was more intense during fractionated neutron irradiation. After irradiation, a complete reoxygenation occurred in both groups independently of the degree of hypoxia observed during the treatment. The RBE of reactor fission neutrons, after fractionated irradiation, was much higher for effects on murine osteosarcomas compared to their RBE observed for normal tissues in previous experiments. Present data are in agreement with our clinical observations on more than 300 patients treated with reactor fission neutrons for advanced and hypoxic tumours with various histologies.

Animals↗
PubMed1999

New drugs for BNCT: an experimental approach.

New kinds of boron-containing drugs were developed and tested in several murine tumor models. The boron-containing ether lipid B-Et-11-OMe was injected in mammary carcinoma (AT17) and osteosarcoma (OTS-64) bearing mice. Furthermore boron-substituted ferrocenium derivatives were tested. Two were excessively toxic; the third could be investigated. Boron accumulation and time-dependent biodistribution were determined using alpha-particle sensitive films and inductively coupled plasma-atomic emission pectrometry (ICP-AES) and -mass spectrometry (ICP-MS) of tumors, organs and tissues. Additionally, a new method of boron detection by NMR is in preparation.

Animals↗
PubMed1999

Changes in head and neck tumor hypoxic fraction during split-course radiochemotherapy.

This study explored patterns of oxygen distribution in human tumors during primary radiochemotherapy. Patients with positive nodes from head and neck squamous cell carcinoma (n = 15) were investigated before therapy, before and after a 2-week respite, and at the end of the treatment. Intratumoral tissue oxygen tension (pO2) was measured with sterile polarographic needle electrodes and a computerized histography system. The 2 lowest pO2 classes, ie, 0 and 5 mm Hg, were designated the hypoxic fraction, and the mean and median pO2 were evaluated for each tumor. In the beginning, a marked variability in tissue pO2 was found. The initial size of the hypoxic fraction ranged from 0% to 61% of measured values. At the end of treatment, 4 tumors showed an increase in mean pO2, and 7 tumors a lower mean pO2 in comparison to the initial values. However, an impressive finding was that the hypoxic fraction of 9 tumors became smaller during the pause, 1 tumor showed no change, and 1 showed an increase in hypoxic fraction. The results show that there is a widely distributed tissue oxygenation with marked hypoxic zones in human neck nodes. During radiochemotherapy, tissue oxygenation changed, with great intertumor variability. A tendency toward a decrease of the hypoxic fraction after the respite could be seen. This change in tumor oxygenation during therapy needs further evaluation.

Adult↗
PubMed1998

The value of F-18-fluorodeoxyglucose PET for the 3-D radiation treatment planning of malignant gliomas.

PURPOSE: The aim of the study was to determine the impact of positron emission tomography using the glucose analogue fluorine-18-fluorodeoxyglucose (FDG-PET) on the delineation of the target volume in three-dimensional radiation treatment planning of primary brain tumors. METHODS AND MATERIALS: In 18 patients with histologically proven (8x biopsy, 10x subtotal resection) primary brain tumors (8 astrocytomas grade III, one mixed glioma grade III, and 9 glioblastomas), magnetic resonance imaging (MRI) with gadolinium-DTPA and FDG-PET were performed in radiation treatment position within the same week. A computer program was developed for fusion of the PET and MR images. On corresponding axial slices, FDG uptake was compared to contrast enhancement in T1-weighted and to signal hyperintensity in T2-weighted MR images. Based on PET and MRI data, three-dimensional treatment planning was performed. All patients underwent linear accelerator (LINAC) radiotherapy. RESULTS: In MRI, all tumors and the surrounding edema were visible as hyperintense lesions in the T2-weighted images. 17/18 tumors showed contrast enhancement. In FDG-PET, 16 tumors showed hypermetabolism compared to normal white matter, whereas only 8/18 tumors showed hypermetabolism compared to normal gray matter. White matter edema was associated with decreased FDG uptake in all patients. The area of increased FDG uptake correlated closely with contrast enhancement, only in one case the volume of increased FDG uptake was larger than the area of contrast enhancement. Mean tumor volumes obtained by MRI T1 + Gd, T2, and PET were 30, 106, and 10 ml, respectively. Survival was comparable to data in the literature with a 1-year survival of 39% and a median survival of 310 days. CONCLUSION: Only in a minority of patients did FDG-PET provide additional information for radiation treatment planning. This is mainly caused by the high intensity of FDG uptake in normal brain tissue. PET may be of greater value in the definition of regions that should obtain a radiation dose boost.

Adult↗
PubMed1998

[3-Dimensional irradiation planning in brain tumors. The advantages of the method and the clinical results].

PURPOSE: Radiotherapy became an important component in the treatment of brain gliomas. The aim of this study is to analyse several advantages of the three-dimensional conformal radiation therapy in comparison with a two-dimensional conventional technique and to present the clinical results of 43 patients with brain gliomas treated according to a three-dimensional planning. PATIENTS AND METHOD: Between January 1994 and December 1995, 43 patients with malignant brain gliomas (WHO III and IV) were treated in our department according to a three-dimensional treatment planning. The patients received a total irradiation dose of 60 Gy, 2 Gy/day, 5 days/week. The rate of survival was analysed in relation with the known prognostical factors: histology, Karnofsky index, age, resection status. In 10 patients a three-dimensional treatment planning was compared with a conventional two-dimensional planning: the volume of the normal brain tissue irradiated to high dose levels (95% isodose) and the normal tissue complication probability (NTCP) for the brain by Kutcher and Lyman were comparatively analysed. RESULTS: The survival rate for the whole group was 14 months. The histology of the tumor, age, Karnofsky index and resection status were important prognostical factors. The three-dimensional planning allows a 15 to 20% reduction in the volume of normal brain tissue irradiated to high dose levels (95% isodose). The NTCP is significantly lower using the three-dimensional technique (range 0.03% to 13%), in comparison with the two-dimensional conventional technique (range 0.1% to 26%). The value of NTCP increases with tumor volume. CONCLUSIONS: Concerning the tumor control and survival rate, the three-dimensional treatment planning shows no advantages compared to the standard conventional methods. The main advantage of the three-dimensional treatment planning is the possibility to spare normal brain tissue. The possibility to integrate mathematical models in the evaluation of the therapy could give this technique new dimensions.

Adolescent↗
PubMed1998

[Use of G-CSF (Neupogen) in multimodal treatment in radiotherapy].

BACKGROUND: Therapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen). PATIENTS AND METHODS: In this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels. RESULTS: In 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light "flu like" symptoms in 14% of the patients, no side effects were observed. CONCLUSIONS: When a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Adult↗
PubMed1998

[Dose-volume histograms and 3-D planning in breast-saving therapy of breast carcinoma].

AIM: Improvement of the dose homogeneity in radiation treatment of the intact breast using 3D-planning and dose volume histograms. PATIENTS AND METHOD: 3D-planning, including the calculation of dose volume histograms of the planning target volume, was performed on 15 patients, who underwent radiation therapy with tangential photon beams. A standard plan and 2 modified or optimized plans were evaluated. Different dosimetric parameters like maximum dose, mean dose, standard deviation and the fractional volume which receives doses from 95 to 105% of the reference dose were compared and correlated with breast size. RESULTS: With increasing breast size standard planning leads to increased overdosage, both in magnitude and volume. Individual optimization by modifying weights and wedges gives no improvement in dose homogeneity, whereas a photon energy of 10 MV results in a more homogeneous dose distribution. The drawback of the higher energy is the increased underdosage of the skin. CONCLUSION: Using the standard geometry of tangential fields the dose homogeneity cannot be improved significantly by 3D-planning, compared to our standard technique.

Breast Neoplasms↗
PubMed1998

Changes in tumor oxygenation during combined treatment with split-course radiotherapy and chemotherapy in patients with head and neck cancer.

PURPOSE: To evaluate the changes in tumor oxygenation during definitive split-course radiochemotherapy in locally advanced head and neck cancer (lymph nodes and primaries). MATERIALS AND METHODS: Twenty-four patients with locally advanced head and neck cancer were investigated pretherapeutically and during a defined course of radiochemotherapy (RCTh) with a total dose of 70 Gy given in 35 fractions over 9 weeks (2-week break after 30 Gy). In weeks 1 and 6, the patients received chemotherapy (5 FU and mitomycin C) concomitant with irradiation. The oxygen partial pressure measurements were carried out using polarographic needle probes in combination with a microprocessor-controlled device (pO2 histograph/KIMOC). Times of measurements were before therapy, at the end of week 3 (30 Gy), after a 2-week break (30 Gy) and at the end of therapy if measurable lesion was found (70 Gy). RESULTS: There was a significant reduction in the median pO2 (P < 0.005, n = 18) and an increase in the hypoxic fraction (defined as the percentage of pO2 values of <5 mm Hg) after application of 30 Gy (P < 0.05, n = 18). This effect was partially reversed at the end of the 2-week break. During the break an increase in the median PO2 (P = 0.05, n = 12) and a decrease in the hypoxic fraction could be observed. Towards the end of therapy (70 Gy) a significant decrease (P = 0.02, n = 13) in the median pO2 occurred. Corresponding to this, the hypoxic fraction increased during the last 4 weeks of therapy (P = 0.06, n = 13). CONCLUSION: Statistically significant changes in oxygenation in locally advanced head and neck cancer were found during a split-course radiochemotherapy. This information was obtained in a homogenous group of patients under well-defined therapeutic conditions. The decrease in the tumor oxygenation status at doses of 30 and 70 Gy are important findings because they are in contrast to the concept of continuous improvement of the oxygenation status during fractionated radiotherapy.

Adult↗
PubMed1998

Oxygen-induced MR signal changes in murine tumors.

Breathing of 100% oxygen was used to challenge vascular autoregulation in 14 mice with either osteosarcomas (n = 6) or mammary carcinomas (n = 8). Reproducible and statistically significant signal intensity changes of -29 +/- 6% to +35 +/- 3% were observed on heavily T2*-weighted images in the tumors during the oxygen challenge. No significant changes were observed in muscle. For the mammary carcinomas a higher percentage of tumor voxels showed significant signal-intensity decrease (31 +/- 8%) compared to the percentage of voxels showing a signal-intensity increase (22 +/- 3%). In contrast, for the osteosarcomas, a higher percentage of tumor voxels showed signal-intensity increase (52 +/- 9%) compared to the percentage of voxels showing signal-intensity decrease (27 +/- 9%). The regional distribution of these signal intensity changes did not correlate with the signal pattern on T1-, T2-,and T2*-weighted and Gd-DTPA enhanced images acquired without breathing 100% oxygen. Most likely, the signal intensity changes represented the inability of the tumor's neovascularization for autoregulation during the oxygen challenge, particularly in hypoxic regions. Although further investigation is needed, the findings that malignant tumor tissue showed signal intensity changes, whereas normal muscle tissue did not, suggests that this technique may prove useful in distinguishing benign from malignant tissue.

Adenocarcinoma↗
PubMed1998

Relevance of oxygen in radiation oncology. Mechanisms of action, correlation to low hemoglobin levels.

At the beginning of this century Schwarz (1909) and Holthusen (1921) observed the influence of oxygen on the radiosensitivity of cells. In 1951 Hollaender et al. described that E. coli needed 3-fold higher radiation doses when treated under anoxic conditions compared to normoxic conditions. This led to the evaluation of the oxygen enhancement ratio (OER) for photons (X-rays), neutrons and heavy ions. It was found that the OER for conventional radiation therapy (RT) with photons is much higher (about 3) than the OER for neutron-RT (only 1.5) or heavy ions. According to a hypothesis free radicals which are produced by radiation are fixed in the presence of oxygen. Radicals are interacting with DNA, macromolecules and membranes. The DNA lesion can be followed by cell death. There is some evidence that tumor cells respond to hypoxia with the expression of a variety of genes coding for oxygen regulated proteins such as c-jun, VEGF or p53. Hypoxia also enhances the genetic instability of tumor cells. Oxygen tensions in malignant tumors can be determined under clinical routine conditions by using a computerized polarographic needle electrode system (Eppendorf, Hamburg, Germany). Several studies in the past years showed that tumors are in general more hypoxic than the surrounding normal tissue and that a marked variability of intra- as well as intertumoral pO2 values exist (for review see Vaupel and Höckel 1998). Moreover, it has been shown in different tumor entities that the oxygenation status influences the local control rate and overall survival. Furthermore, the oxygenation status obtained at one site (primary) is significantly related at other sites (lymph node metastases) in patients with squamous cell carcinoma of the head and neck (SCCHN). In addition, there is a significant correlation between hemoglobin level and tumor oxygenation in patients with SCCHN. There is some evidence that the oxygenation status can be improved by the correction of a low hemoglobin level and consequently, the curative chance might rise.

Cell Hypoxia↗
PubMed1997

Oxygen tensions in rodent tumors after irradiation with neutrons.

We started investigations on intratumoral oxygen tension after irradiations with reactor fission neutrons using the Eppendorf-pO2 Histograph. Isotransplanted AT17-mammary carcinomas on C3H-mice and osteosarcomas OTS-64 on balb C-mice received 2 or 6 Gy neutrons single dose. Before and at certain points of time after treatment the pO2 values were evaluated. Some tumors with initially low median pO2 values showed a short-lasting increase between 2 and 24 h after irradiation. In those tumors with relatively high pretherapeutic pO2 values the pO2 decreased to the range of hypoxia. A third group of tumors showed no marked changes after irradiation. No tumor stopped growth during the observation period.

Animals↗
PubMed1997

Iridium 192 high-dose-rate brachytherapy--a useful alternative therapy for localized prostate cancer?

We report on a novel protocol involving iridium 192 high-dose-rate brachytherapy and follow-up of up to 130 months in patients with prostatic carcinoma. Using regional anesthesia, five to seven hollow needles are placed within the prostate by perineal puncture under ultrasound guidance. A 9-Gy prostate dose is applied followed by 30 min of hyperthermia (since 1991). This treatment is repeated once after 7 days; 2 weeks later, 18 x 2-Gy external beam radiation (small-field prostate) is added as percutaneous dose saturation. Since 1984 we have treated 40 patients with this protocol. Local tumor control was achieved by means of prostatic biopsy at 18 months after therapy and determination of prostate-specific antigen (PSA) values in about 70% of the patients; after a mean follow-up period of more than 6 years (16-130 months), 80% of the patients show either no evidence of disease or stable disease. We therefore conclude that iridium 192 high-dose-rate brachytherapy is a useful alternative in the treatment of localized prostate cancer in patients who are not eligible for radical prostatectomy.

Adult↗
PubMed1997

Gastric Cancer.

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Antineoplastic Agents↗