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Tobias Hölscher

Publications and source records attributed to Tobias Hölscher.

6 recordsLinked to original sources
PubMed2006

Influence of connective tissue diseases on the expression of radiation side effects: a systematic review.

BACKGROUND AND PURPOSE: Patient related co-factors may increase the risk of radiation morbidity. Connective tissue diseases (CTD) are among the co-morbidities that are relatively well studied and have been shown to be of potential clinical relevance for radiotherapy. The aim of this systematic review is to quantify the contribution of CTD to the risk of radiation related side effects. PATIENTS AND METHODS: Relevant publications reporting the outcome of radiotherapy in patients with CTD were retrieved according to a standardized query and evaluated for their methodology and quality of reporting, using defined quality criteria. A quantitative estimate of the relative risk of developing side effects in patients with CTD was derived from the observed proportions of responders in patients with or without CTD. Risk estimates were synthesized across studies. RESULTS: Eight studies which include data of 9-209 patients who had CTD and were treated with radiotherapy were identified and reviewed. Three of these studies included data suited for further quantitative analysis. The test of the uni-directional hypothesis that patients with CTD had an increased risk of late effects after radiotherapy reached statistical significance, the one-tailed P-value being 0.03. The pooled relative risk was 2.0 with 95% confidence interval (0.99, 4.1). CONCLUSIONS: CTD is associated with an increased risk of late radiation induced normal tissue reaction. The literature published to date provides some support for this assertion although most of the reports are plagued by methodological weaknesses, thus calling for a large coordinated study.

Connective Tissue Diseases↗
PubMed2005

Effects of radiotherapy on olfactory function.

BACKGROUND AND PURPOSE: Changes in olfactory function have been reported in patients receiving significant doses of radiation to the olfactory epithelium. Aim of this study was to investigate severity and time course of changes in olfactory function in patients irradiated for tumours of the head and neck region. MATERIAL AND METHODS: Forty-four patients receiving radiotherapy (RT) for tumours in the area of the head and neck participated (16 women, 28 men; age 11-81 y; mean 55 y). Olfactory function was measured before and bi-weekly during RT for 6 weeks. A subgroup (25 patients) was followed for 12 months. Patients were divided into two groups according to the dose to the olfactory epithelium. Twenty-two patients ('OLF group') had radiation doses to the olfactory epithelium between 23.7 and 79.5 Gy (median 62.2 Gy). In the 22 patients of the 'non-OLF group' the dose applied to the olfactory epithelium was significantly lower (2.9-11.1 Gy, median 5.9 Gy). Total tumour dose (30-76.8 Gy), age, sex distribution, and baseline chemosensory function were not significantly different between groups. Testing was performed for odour identification, odour discrimination, and olfactory thresholds. RESULTS: Odour discrimination, but not odour identification or odour threshold, was significantly decreased 2-6 weeks after begin of therapy in the OLF group. In addition, a significant effect of the radiation dose was observed for odour discrimination. More than 6 months after therapy, OLF group patients had significantly lower odour identification scores compared to the non-OLF group. CONCLUSION: As indicated through the non-significant change of olfactory thresholds, the olfactory epithelium is relatively resistant against effects of radiation. It is hypothesized that RT has additional effects on the olfactory bulb/orbitofrontal cortex responsible for the observed changes of suprathreshold olfactory function.

Adolescent↗
PubMed2005

Molecular markers predicting radiotherapy response: report and recommendations from an International Atomic Energy Agency technical meeting.

PURPOSE: There is increasing interest in radiogenomics and the characterization of molecular profiles that predict normal tissue and tumor radioresponse. A meeting in Amsterdam was organized by the International Atomic Energy Agency to discuss this topic on an international basis. METHODS AND MATERIALS: This report is not completely exhaustive, but highlights some of the ongoing studies and new initiatives being carried out worldwide in the banking of tumor and normal tissue samples underpinning the development of molecular marker profiles for predicting patient response to radiotherapy. It is generally considered that these profiles will more accurately define individual or group radiosensitivities compared with the nondefinitive findings from the previous era of cellular-based techniques. However, so far there are only a few robust reports of molecular markers predicting normal tissue or tumor response. RESULTS: Many centers in different countries have initiated tissue and tumor banks to store samples from clinical trials for future molecular profiling analysis, to identify profiles that predict for radiotherapy response. The European Society for Therapeutic Radiology and Oncology GENEtic pathways for the Prediction of the effects of Irradiation (GENEPI) project, to store, document, and analyze sample characteristics vs. response, is the most comprehensive in this regard. CONCLUSIONS: The next 5-10 years are likely to see the results of these and other correlative studies, and promising associations of profiles with response should be validated in larger definitive trials.

Biomarkers, Tumor↗
PubMed2005

Does heterogeneity of pimonidazole labelling correspond to the heterogeneity of radiation-response of FaDu human squamous cell carcinoma?

BACKGROUND AND PURPOSE: Pimonidazole is a marker for hypoxic cells which are radioresistant and thereby important for the outcome of radiotherapy. The present study evaluates heterogeneity in pimonidazole binding within and between tumours and relates the results to the heterogeneity of radiation response in the same tumour cell line. MATERIALS AND METHODS: FaDu, a poorly differentiated human squamous cell carcinoma line, was transplanted subcutaneously into the right hind-leg of NMRI nude mice. Tumours were irradiated with graded single doses either under ambient or clamped blood flow conditions and local tumour control was evaluated after 120 days. Complete dose-response curves for local tumour control were generated and the slope, a measure of heterogeneity of radiation response, was determined. In parallel, 12 unirradiated tumours were examined histologically. Seven serial 10 microm cross-sections per tumour were evaluated using fluorescence microscopy and computerised image analysis to determine the pimonidazole hypoxic fraction (pHF). Heterogeneity in pHF was quantified by its coefficient of variation (CV). Poisson-based model calculations considering the intertumoural heterogeneity of pHF were performed and the slopes of the predicted and the observed dose-response curves were compared. RESULTS: The mean pHF was 11% [CV 50%] when one central section per tumour was evaluated. Measurements of multiple sections per tumour resulted in a mean pHF of 12% [CV 46%] (P=0.7). Intertumoural heterogeneity in pHF was more pronounced than heterogeneity in individual tumours by a factor of 2. Model calculations based on the variability in pHF resulted in similar slopes of the dose-response curve for local tumour control in comparison with the observed slope when the heterogeneity in an unknown and arbitrarily chosen additional radiobiologically relevant parameter, in this example clonogen density, was taken into account. CONCLUSIONS: While the average pimonidazole hypoxic fraction in FaDu tumours corresponds well to the radiobiological hypoxic fraction, the variability of pHF in FaDu tumours was not sufficient to explain the heterogeneity of radiation response in the same tumour line. Information on at least one additional parameter is expected to substantially enhance the predictive power of histological markers of tumour hypoxia.

Animals↗
PubMed2003

Differences in responses to nociceptive stimulation of the oral and aboral oesophagus.

The present study examined the role of vagal innervation of the rat esophagus in nociception. Electromyographic recordings from neck muscles were used as indicators of pseudoaffective reactions in lightly anaesthetized animals; responses were obtained during mechanical (distension) and chemical (HCl) nociceptive stimulation of the upper cervical (4.5 cm from incisors) and midthoracic (7 cm from incisors) esophagus. Compared to midthoracic esophageal stimulation, stimulation of the upper esophagus produced more vigorous responses. Bilateral transections of the cervical vagus and superior laryngeal nerves led to a gradual diminution of responses to upper stimulation, while the same manoeuvre increased responses to lower esophagus stimulation. These results suggest a contribution of vagal afferents to pseudoaffective responses elicited by noxious stimulation of the upper esophagus.

Animals↗