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M Molls

Publications and source records attributed to M Molls.

At least 37 records · Page 2Linked to original sources

[Remembering DEGRO 2000-evaluation of the refresher course survey].

BACKGROUND: Refresher courses as presented at the annual DEGRO meeting are important parts in the continuous training of radiotherapists. For further quality improvement, knowledge about the participants' needs is essential. METHODS: During the DEGRO meeting 10/2000 in Munich, participants of refresher courses were encouraged to grade the presentations with regard to six questions with marks from 1 ("very good") to 6 ("not acceptable"). Free comments were welcomed. The individual results were handed over to future organizing committees and the speakers themselves, cumulative results can be read up in the present note. RESULTS: Approximately 1,000 participants of refresher courses filled in 381 questionnaires concerning 24 different training sessions. Altogether 48.5% of all answers said "very good", 31.7% "good" and 11.1% "satisfactory" (all worse marks together 3%, no statement in 5.7%). Free comments dealt mainly with handouts and a later starting time for the refresher courses than 7:30 a.m. CONCLUSION: Participants of the annual DEGRO meeting show a great amount of interest in refresher courses and seem to be quite content with the present findings. First steps are taken to get the proposals under way.

Attitude of Health Personnel↗

[Organizational prerequisites for multimodality therapy concepts].

The increasing use of multimodal therapies confronts clinics with the need to create new organisational structures. The high degree of specialisation necessitates that the separate disciplines seek ways of working closer together. This is particularly the case when staging results have to be evaluated and a multimodal therapy course chosen or when quality management issues and the coordination of different steps of a treatment are being considered. By establishing disease-oriented organisational structures and by institutionalizing interdisciplinary cooperation, e.g. in daily tumor board meetings and in fixed disease management teams, the organisational prerequisites for implementing multimodal therapies are created.

Combined Modality Therapy↗

Rapid detection of radiation-induced chromosomal aberrations in lymphocytes and hematopoietic progenitor cells by mFISH.

Structural chromosome aberrations (SCAs) are sensitive indicators of a preceding exposure of the hematopoietic system to ionizing radiation. Cytogenetic investigations have therefore become routine tools for an assessment of absorbed radiation doses and their biological effects after occupational exposure or radiation accidents. Due to its speed and ease of use, fluorescence in situ hybridization (FISH) with whole chromosome painting (WCP) probes has become a method of choice to visualize SCAs. Until recently, this technique was limited to a rather small number of chromosomes, which could be tested simultaneously. As a result, only a fraction of the structural aberrations present in a sample could be detected and the overall dose effect had to be calculated by extrapolation. The recent introduction of two genome-wide screening techniques in tumor research, i.e., Spectral Karyotyping (SKY) and multicolor FISH (mFISH) now allows the detection of translocations involving any two non-homologous chromosomes. The present study was prompted by our desire to bring the power of mFISH to bear for the rapid identification of radiation-induced SCAs. We chose two model systems to investigate the utility of mFISH: lymphocytes that were exposed in vitro to 3 Gy photons and single hematopoietic progenitor cell colonies isolated from a Chernobyl victim 9 years after in vivo exposure to 5.4 Sv.In lymphocytes, we found up to 15 different chromosomes involved in rearrangements indicating complex radiation effects. Stable aberrations detected in hematopoietic cell colonies, on the other hand, showed involvement of up to three different chromosomes. These results demonstrated that mFISH is a rapid and powerful approach to detect and characterize radiation-induced SCAs in the hemopoietic system. The application of mFISH is expected to result in a more detailed and, thus, more informative picture of radiation effects. Eventually, this technique will allow researchers to rapidly delineate chromosomal breakpoints and facilitate the identification of the genes involved in radiation tumorigenesis.

Adult↗

First experience with I-123-alpha-methyl-tyrosine spect in the 3-D radiation treatment planning of brain gliomas.

PURPOSE: This study compares the results of iodine-123-alpha-methyl-tyrosine single photon computed emission tomography (IMT-SPECT) with magnetic resonance imaging (MRI) in tumor volume definition of brain gliomas. Furthermore, it evaluates the influences of the information provided from IMT-SPECT for three-dimensional (3D) conformal treatment planning. METHODS AND MATERIALS: In 30 patients with nonresected, histologically proven brain gliomas (glioblastoma-13 patients, astrocytoma Grade III-12 patients, astrocytoma Grade II-3 patients, oligodendroglioma Grade III-1 patient, oligodendroglioma Grade II-1 patient), IMT-SPECT and MRI were performed pretherapeutically in the same week. A special software system allowed the coregistration of the IMT-SPECT and MRI data. The gross tumor volume (GTV) defined on the IMT-SPECT/T2-MRI fusion images (GTV-IMT/T2) was compared with the GTV-T2, defined on the T2-MRI alone. On the IMT-SPECT/T1Gd-MRI overlays, the volume of the IMT tumor uptake (GTV-IMT) was compared with the volume of the gadolinium (Gd) enhancement (GTV-T1Gd). The initial planning target volume (PTV) and the boost volume (BV) outlined on the IMT-SPECT/T2-MRI co-images were analyzed comparatively to the PTV and BV delineated using the T2-MRI alone. RESULTS: In all 30 patients a higher IMT uptake of tumor areas, compared to the normal brain tissue was observed. Mean GTV-IMT, mean GTV-T2, and mean GTV-T1Gd were 43, 82, and 16 cm(3), respectively. IMT tumor uptake outside the contrast enhancement regions was observed in all patients. Mean relative increase of tumor volume defined on the fusion images, GTV-IMT/T1Gd versus GTV-T1Gd alone was 78%. IMT tumor uptake areas outside the GTV-T2 were registered in 7 patients (23%). In these patients, the mean increase GTV-IMT/T2 was 33% higher than GTV-T2, defined according to the T2-MRI data alone. The additional information provided by IMT-SPECT modified minimally the initial PTV (mean relative increase PTV-IMT/T2 versus PTV-T2, 5%) but significantly the BV (mean relative increase BV-IMT/T2 versus BV-T2, 37%). CONCLUSION: In a significant number of patients, the IMT-SPECT investigation improves tumor detection and delineation in the planning process. This has important consequences in the 3D conformal treatment planning, especially in the delineation of BV and in dose escalation studies.

Adult↗

Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas.

PURPOSE: To investigate the relationship between tumor oxygenation and the blood hemoglobin (Hb) concentration in patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: A total of 133 patients with SCCHN underwent pretreatment polarographic pO2 measurements of their tumors. In 66 patients measurements were also made in sternocleidomastoid muscles. The patients were divided into three groups according to their Hb concentration-severe anemia (Hb < 11.0 g/dl), mild anemia (female: Hb 11.0-11.9 g/dl; male: Hb 11.0-12.9 g/dl), and normal Hb concentration (female: Hb > or =12.0 g/dl; male: > or =13.0 g/dl). RESULTS: No significant difference in tumor oxygenation could be detected between mildly anemic patients and patients with a normal Hb level. However, the tumor oxygenation in the severely anemic group was significantly below that of each of the other two groups (p < 0.0001). There was no significant difference between the Hb groups in oxygenation of sternocleidomastoid muscles. In a multivariate analysis including Hb group, tumor volume, smoking habits, gender, T-stage, N-stage, and histologic grade a Hb level < 11 g/dl was found to be the strongest predictor for a poor tumor oxygenation. Smoking also had a marginal influence on median pO2. CONCLUSION: Our data suggest that a low Hb concentration and cigarette smoking contribute to inadequate oxygenation of SCCHN and thus for increased radioresistance. Consequently, Hb correction and abstinence from smoking may significantly improve tumor oxygenation.

Anemia↗

[No association between p53 overexpression and polarographically measured tumor oxygenation in patients with head and neck carcinomas].

PURPOSE: Clinical investigation of a potential relationship between the polarographically measured tumor oxygenation and the p53 status in patients with squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: In 99 patients with mostly advanced, histologically proven squamous cell carcinoma of the head and neck we estimated the classical tumor parameters (TNM stage, histological grading) the immunohistochemical p53-overexpression (DO-7) and the tumor oxygenation status (Eppendorf pO2 Histograph). The tumor volume and the hemoglobin concentration were evaluated simultaneously. RESULTS: No statistically significant difference could be detected between immunohistological p53-positive (p53 > or = 10% stained cells) and p53-negative tumors (p53 < 10% stained cells) regarding both the median pO2 and the relative frequency of values < or = 5 mm Hg. Moreover, no statistically relevant differences could be seen between both p53-groups considering the hemoglobin concentration, the TNM stage, the histological grading and the tumor volume. CONCLUSION: Our data imply that there is no association between p53-overexpression and tumor hypoxia in head and neck carcinomas. However, this is not necessarily in contradiction to experimental or clinical data that confirmed a relationship between hypoxia and p53-mediated increased malignancy of tumor cells in other tumor entities. The comparable oxygenation status of p53-positive and p53-negative tumors in our study is associated with an analogous clinical tumor aggressiveness of both groups. That could be caused by a hypoxia related but p53-independent selection of tumor cells with a more malignant phenotype in head and neck carcinomas. However, further research is needed to prove this possible relationship.

Adult↗

Combined radiochemotherapy with docetaxel in patients with unresectable locally advanced head and neck tumors.

BACKGROUND: As the treatment with docetaxel in metastatic head and neck cancer resulted in an encouraging response rate, the following phase-I study examined the effects of a combined radiochemotherapy with weekly docetaxel in patients with inoperable advanced head and neck tumors. PATIENTS AND METHODS: Six patients with Stage IV head and neck cancer were included into the study. Within the treatment regimen the primary tumor and the involved lymph nodes were irradiated up to a total dose of 70 Gy, the non involved cervical and supraclavicular lymph nodes received 50 Gy in conventional fractionation. Simultaneously docetaxel was given 1 hour before radiotherapy. The initial dose was 15 mg/m2. RESULTS: A dose escalation was impossible because of several dose limiting toxicities (NCI-CTC) already in the first dose level. Two patients showed skin reactions Grade 4, 2 patients pulmonary complications Grade 4, 2 patient neurologic side effects Grade 3 and 1 a thrombocytopenia Grade 3. The response rate resulted in 3 complete and 1 partial remission, 1 death, 1 patient was not evaluable. CONCLUSION: Unexpectedly already in the first dose level several dose limiting toxicities were evaluated. For that reason the treatment scheme is not feasible.

Adult↗

Chromosomal aberrations induced in mice bone marrow by treating with cisplatin and irradiation.

BACKGROUND: The aim of this study was to quantify the combined effect of cisplatin and radiation on chromosomal damage with emphasis on the time interval between cisplatin and radiation. METHODS AND MATERIALS: Bone marrow of female NMRI-nu(+) mice was taken as a model system for a highly proliferative tissue irradiated with cobalt-60 (1 to 4 Gy). Cisplatin was injected intraperitoneally (i.p.) at 1.1 to 36 mg/kg. Cisplatin was given at various time intervals before and after radiation. Bone marrow and metaphases were prepared according to standard procedures. RESULTS: The percentage of aberrant metaphases after radiation or cisplatin alone increased in a dose-dependent manner (sigmoidal dose-response curve). Combining both modalities led to additive values at all time points for the percentage of aberrant metaphases. Borderline significant (p < 0.05) supraadditive effects were found 2 hours before or 1 hour after irradiation. However, a supraadditive percentage of aberrant chromosomes was found only at 2 or 1.5 hours with cisplatin before irradiation indicating the dependence of supraadditivity on the chosen parameter. CONCLUSION: It is doubtful to expect a true supraadditive or "radiosensitizing" effect, e.g. in the clinical setting from combined treatment with cisplatin and radiation. Rather, cisplatin might act as an independent cytotoxic agent.

Animals↗

[Prostatic carcinoma: problems in the interpretation of rectal dose-volume histograms].

BACKGROUND: Dose-volume histograms (DVHs) are used for the prediction and calculation of late radiation side effects. In literature the predictive value of rectal DVHs is controversially discussed. Differences in contouring might contribute to the contradicting results. In particular the cranial and caudal border of the contoured organ are not uniformly defined. PATIENTS AND METHODS: The DVHs of 12 patients who were treated with conformal radiotherapy for prostate cancer were investigated. Six of the patients suffered from mild rectal bleeding as a late side effect of radiotherapy. Six patients without rectal bleeding (minimal follow-up 30 months) matched for age, concomitant disease and treatment concept served as controls. Four different DVHs with 4 different definitions of the cranial and caudal rectal border were generated for each patient. For each of the 48 DVHs the percent volume fractions (V50, V80, V95) and absolute volume fractions (aV50, aV80, aV95) were calculated that received more than 50%, 80% and 95% of the reference dose. RESULTS: For every patient there were considerable variations in the volume fractions depending on the definition of the rectum borders (Table 1). The mean and median values of the percent and absolute volume fractions of the bleeding patients were higher than those of the non-bleeders no matter how the rectum borders were defined. None of the volume fractions could totally separate bleeding from non-bleeding patients. CONCLUSION: There is a high variability of absolute and percent volume fractions of rectal DVHs depending on how the rectal borders were defined. For the comparison and for the interpretation of rectal DVHs a uniform definition would be helpful.

Aged↗

O-(2-[18F]fluoroethyl)-L-tyrosine and L-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study.

O-(2-[18F]Fluoroethyl)-L-tyrosine (FET) is a recently described amino acid analogue that has shown high accumulation in animal tumours. The aim of this study was to compare the uptake of FET with that of L-[methyl-11C]methionine (MET) in patients with suspected primary or recurrent intracerebral tumours. Sixteen consecutive patients with intracerebral lesions were studied on the same day by positron emission tomography (PET) using MET and FET. Uptake of FET and MET was quantified by standardized uptake values. Tracer kinetics for normal brain and intracerebral lesions were compared. On the basis of the MET-PET studies, viable tumour tissue was found in 13 patients. All tumours showed rapid uptake of FET and were visualized with high contrast. Mean uptake of FET for normal grey matter, white matter and tumour tissue was 1.1+/-0.2, 0.8+/-0.2 and 2.7+/-0.8 SUV, respectively. In all three tissues, uptake of MET was slightly higher (1.4+/-0.2, 0.9+/-0.1 and 3.3+/-1.0 SUV; P<0.01). However, contrast between tumour and normal tissues was not significantly different between MET and FET. Uptake of FET in non-neoplastic lesions (1.0+/-0.1 SUV) was significantly lower than in tumour tissue (P = 0.007). For all lesions there was a close correlation (r = 0.98) between MET and FET uptake. In conclusion, in PET studies of human brain tumours, the uptake and image contrast of FET appear to be very similar to those of MET. The specificity of FET for tumour tissue is promising but has to be addressed in a larger series of patients with non-neoplastic lesions.

Adult↗

A comparison of treatment results for recurrent malignant gliomas.

Retreatment of malignant gliomas may be performed with palliative intent after careful consideration of the risks and benefits, and with special regards to iatrogenic neurotoxicity and quality of life (QOL). This review compares studies of several retreatment strategies (published between 1987 and 2000) based on the quality of their evidence. Depending on both established prognostic factors and previous treatment, individually tailored retreatment strategies are possible. In all studies that included a multivariate analysis of prognostic factors, performance status was the most important. So far, predictive factors for response, which might facilitate patient selection, have not been unequivocally defined. In terms of QOL, single-agent chemotherapy (temozolomide, nitrosoureas, platinum and taxane derivatives) may offer a better therapeutic ratio than polychemotherapy. For glioblastoma multiforme, progression-free survival and QOL were more favourable after temozolomide than procarbazine (level 1 evidence). The survival of patients after various radiotherapy techniques is broadly similar. However, considerable toxicity is associated with radiosurgery or brachytherapy. Fractionated stereotactic radiotherapy plus radio-sensitizing cytostatic agents has shown promising initial results in small groups of selected patients and awaits further evaluation. Level 2 evidence derived from non-randomized studies does not suggest a substantial prolongation of survival by re-resection as compared with chemotherapy or radiotherapy alone. Level 1 evidence derived from a randomized trial suggests that application of BCNU polymers significantly improves the outcome after re-resection. However, most studies reported median survival in the range of only 25-35 weeks, thereby emphasizing the need for the development and clinical evaluation of new innovative treatment approaches.

Adult↗

[Radiotherapy of non-malignant diseases: principles and recommendations].

The plenty options and high quality of radiation therapy for non-malignant disorders is not well known outside the field of radiology. It is necessary to transfer this information to cooperating general practitioners, surgeons, orthopedics and other specialists. To warrant quality assurance and quality control and to allow a uniform performance of radiotherapy of non-malignant conditions, general guidelines and recommendations according to the German Working Group of Scientific Medical Societies are useful. This paper summarizes the essential aspects of radiotherapy for non-malignant diseases: indication of, informed consent for, documentation and conduct of radiation therapy for non-malignant diseases using orthovoltage equipment and specific recommendations for follow up examinations. Radiotherapy concepts for non-malignant diseases are summarized.

Arteriovenous Malformations↗

Follow-up analysis of translocation and dicentric frequencies, measured by FISH-chromosome painting in breast cancer patients after partial-body radiotherapy with little bone marrow exposure.

Follow-up translocation and dicentric measurements in blood lymphocytes of five breast cancer patients were performed by FISH using painting probes for chromosomes 1, 4, and 12 simultaneously with a pancentromeric DNA probe, during 14 months after fractionated photon therapy affecting only small areas of the bone marrow (about 5%). The analysis of individual time-courses for translocations and dicentrics revealed a significant temporal decline of the yields with comparable half-times, both for these stable and unstable aberration types in two patients. In three patients, the aberration yields remained fairly unchanged during the observation period. Regarding retrospective biodosimetry for cases with partial-body exposures or large dose inhomogeneity, it follows that even FISH chromosome painting is limited in assessing initial doses correctly in terms of stable translocations.

Bone Marrow Cells↗

Influence of the hypoxic subvolume on the survival of patients with head and neck cancer.

PURPOSE: Tumor hypoxia is regarded as an important factor influencing radiation response, disease-free, and overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN). This study was performed to reevaluate the prognostic significance of the "classical oxygenation parameters" hypoxic fraction (percentage of pO2 values < 5 mmHg or < 2.5 mmHg, respectively) and median pO2, and to determine the influence of a new radiobiological factor. This factor was termed the "hypoxic subvolume" (HSV) and was defined as percentage of pO2-values below 5 mmHg multiplied by the total tumor volume. The rationale of this parameter was to quantify approximately the amount of hypoxic tissue which should be correlated to the number of hypoxic cells in the tumor. It is obvious that a tumor of 100 cm3 with a hypoxic fraction of 20% (HSV = 20 cm3) contains more hypoxic cells than a tumor of 1 cm3 with a hypoxic fraction of 50% (HSV = 0.5 cm3). METHODS AND MATERIALS: Pretreatment pO2 was assessed in 59 patients with SCCHN with the Eppendorf histograph, and pretreatment volume was determined by ultrasonography (lymphnode metastases) and computer tomography (primaries). All patients were referred to our departments for radiotherapy (n = 27, median dose 70 Gy) or radiochemotherapy (n = 32; 5-FU, mitomycin C, median dose 70 Gy), respectively. All parameters were evaluated using the Kaplan-Meier analysis, and significance was assumed at a p-value of < 0.05 (log-rank test, Cox-Mantel). A multivariate analysis was performed to control for confounding factors. The median follow-up was 233 days. At the time of the evaluation, 34 of the 59 patients were dead. RESULTS: In univariate analyses, the hypoxic fraction (pO2 < 5 mmHg, PO2 < 2.5 mmHg [p < 0.05]), the hemoglobin concentration (p < 0.05), and the hypoxic subvolume (p < 0.01) were of prognostic significance for overall survival. In multivariate analysis, the hemoglobin concentration and the hypoxic subvolume (p = 0.01) were significant prognosticators. We found no significant correlation between tumor volume or median pO2 and overall survival. No clear correlation was found between tumor volume and hypoxic fraction. CONCLUSION: These data suggest that the total amount of hypoxic tissue, as determined by the hypoxic subvolume, influences the prognosis of patients suffering from SCCHN. In addition, our data confirm the statements of previous studies that low pretherapy pO2-values indicate a worse prognosis.

Analysis of Variance↗

Palliative radiotherapy of malignant melanoma with reactor fission neutron therapy (RENT): a prospective study.

To study the efficacy and safety of relatively low-dosed reactor fission neutron therapy (RENT) at the research reactor of the Technical University Munich, we treated 33 superficial lesions of 20 patients with advanced malignant melanoma by neutron beam alone (n = 22), mixed neutron/electron beam (n = 5), or by neutron beam after incomplete surgery (n = 6). Median tumor volume was 17.0 cm3. Median dose for neutron beam alone was 8.0 Gy and for mixed beam 3.0 Gy n + 45.3 Gy e-. Local tumor response, local control time, survival and treatment related toxicity were followed prospectively over a time period of 52 months. Overall response rate (CR;PR) after neutron beam alone and mixed beam therapy was 64% (CR: 36%) and 100% (CR: 60%), respectively. Observed differences between complete (CR) and incomplete (PR, NC) responding lesions were as follows: median tumor volume: 2.0 vs. 51.5 cm3, local control time: 13.3 vs. 3.7 months, median survival: 19.8 vs. 9.0 months. No severe acute or late sequelae could be observed. In conclusion, low-dosed RENT is an effective and well tolerated palliative treatment of superficial malignant melanoma utilizing the biologic advantage of diminished cellular repair capacity. Because melanoma lesions of small size (< or = 6 cm3) tend to respond completely, neutron beam should be performed at an early stage.

Adult↗

[Radiotherapy of the elderly patient. Radiotherapy tolerance and results in older patients].

BACKGROUND: Despite a growing number of elderly patients receiving radiation therapy little is known about side effects and outcome of irradiation in this section of the population. METHODS: In a review article epidemiologic data, aspects of radiation-biology as well as side effects and outcome of radiation therapy of elderly patients are discussed. RESULTS: Cancer incidence rises with age (Figure 1) and is exceeding 3.5% for males older than 85 years. With a life expectancy of more than 4 years, curative therapy is indicated even at this age. Furthermore several retrospective studies indicate that local control and disease-Specific survival after radiation therapy of elderly patients is comparable with that of younger persons (Tables 3 and 4). The exception contains elderly patients with Grade-III to IV gliomas or with rectal carcinoma who show a reduced survival which is perhaps caused by less aggressive combined treatment (tumor resection). Although some biological and molecular data indicate a rise in radiation sensitivity with growing age like the reduction of the capacity of some DNA-repair enzymes, there is no convincing evidence in animal studies or in retrospective clinical studies that radiation therapy is generally less well tolerated by older individuals (Tables 1 and 2). Some age-depending differences in organ toxicities are described in 3 large studies, which evaluate the data of patients who were enrolled in different EORTC-trials: Older patients suffer more of functional mucositis in case of radiation therapy to the head and neck, they have an increased weight loss and a higher frequency of late esophageal damage when irradiated in the thorax, and they show a higher prevalence of sexual dysfunction when treated with radiation therapy to the pelvis. On the other hand younger patients suffer more from acute toxicity like skin damage, nausea, and deterioration of the performance status during pelvic radiotherapy. When discussing the dose intensity of radiation therapy concomitant disease which leads to extensive atherosclerotic vessel damage should be kept in mind. Old patients should be monitored closely during therapy, since the loss of electrolytes or fluid is often not very well tolerated. CONCLUSION: The indication to radiation therapy of elderly cancer patients should take into account their performance status as well as the extent and the severity of comorbidity. Age per se is seldom a contraindication for radiation therapy. Regarding the available data in literature there is no indication for a dose reduction in radiation therapy only because of age, especially in the curative setting.

Aged↗