Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

Individual response of humans to ionising radiation: governing factors and importance for radiological protection.

Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.

Identification of the most significant electrode positions in electromyographic evaluation of swallowing-related movements in humans.

Surface electromyography (sEMG) is a well-established procedure for recording swallowing-related muscle activities. Because the use of a large number of sEMG channels is time consuming and technically sophisticated, the aim of this study was to identify the most significant electrode positions associated with oropharyngeal swallowing activities. Healthy subjects (N = 16) were tested with a total of 42 channels placed in M. masseter, M. orbicularis oris, submental and paralaryngeal regions. Each test subject swallowed 10 ml of water five times. After having identified 16 optimal electrode positions, that is, positions with the strongest signals quantified by the highest integral values, differences to 26 other ones were determined by a Mann-Whitney U test. Kruskal-Wallis H test was utilized for the analysis of differences between single subjects, subject subgroups, and single electrode positions. Factors associated with sEMG signals were examined in a linear regression. Sixteen electrode positions were chosen by a simple ranking of integral values. These positions delivered significantly higher signals than the other 26 positions. Differences between single electrode positions and between test subjects were also significant. Sixteen most significant positions were identified which represent swallowing-related muscle potentials in healthy subjects.

Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe.

Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.

Multi-centre calibration of an adaptive thresholding method for PET-based delineation of tumour volumes in radiotherapy planning of lung cancer.

PURPOSE: To evaluate the calibration of an adaptive thresholding algorithm (contrast-oriented algorithm) for FDG PET-based delineation of tumour volumes in eleven centres with respect to scanner types and image data processing by phantom measurements. METHODS: A cylindrical phantom with spheres of different diameters was filled with FDG realizing different signal-to-background ratios and scanned using 5 Siemens Biograph PET/CT scanners, 5 Philips Gemini PET/CT scanners, and one Siemens ECAT-ART PET scanner. All scans were analysed by the contrast-oriented algorithm implemented in two different software packages. For each site, the threshold SUVs of all spheres best matching the known sphere volumes were determined. Calibration parameters a and b were calculated for each combination of scanner and image-analysis software package. In addition, "scanner-type-specific" calibration curves were determined from all values obtained for each combination of scanner type and software package. Both kinds of calibration curves were used for volume delineation of the spheres. RESULTS: Only minor differences in calibration parameters were observed for scanners of the same type (Δa ≤4%, Δb ≤14%) provided that identical imaging protocols were used whereas significant differences were found comparing calibration parameters of the ART scanner with those of scanners of different type (Δa ≤60%, Δb ≤54%). After calibration, for all scanners investigated the calculated SUV thresholds for auto-contouring did not differ significantly (all p>0.58). The resulting sphere volumes deviated by less than -7% to +8% from the true values. CONCLUSION: After multi-centre calibration the use of the contrast-oriented algorithm for FDG PET-based delineation of tumour volumes in the different centres using different scanner types and specific imaging protocols is feasible.

Update on relapses in unilateral nephroblastoma registered in 3 consecutive SIOP/GPOH studies - a report from the GPOH-nephroblastoma study group.

INTRODUCTION: Treatment and stratification of progressive/relapsed unilateral nephroblastoma (PD) has significantly evolved over the last 20 years. Early PD (≤ 6 months), initial high risk histology, local stage III, multiple site PD and stage IV have been implemented as high risk classification factors and novel drugs have been introduced. PATIENTS AND METHODS: We analysed all 251 patients having had a unilateral nephroblastoma (Stage I-IV) and progressive disease who had been treated according to SIOP9/GPO (n = 77), SIOP93-1/GPOH (n = 93) and SIOP2001/GPOH (n = 81) initially. RESULTS: 3y-overall survival (OS) increased from 43% to 61% and 59% respectively (both p<0.01). 3y-OS for localized stage I-III rose from 43% to 65% and 68% respectively while only little improvement can be seen for initial stage IV patients with 43%, 53% and 44% respectively. Multivariate analysis confirmed high risk histology, local stage III, shorter time to PD, combined relapse as independent risk factors. 26 patients had received high-dose chemotherapy showing 64% 3y-OS compared to 54% for all non-transplanted (p=0.11). CONCLUSION: Structuring the treatment of progressive nephroblastoma as well as introducing new drugs have improved the outcome significantly. However improvement is depending on the specific risk profile. Very high risk tumours are often resistant to conventional treatment, hence an international uniform treatment concept is needed to achieve conclusive results in this small group.

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.

[Register for the evaluation of side effects after radiation in childhood and adolescence--first results]. / Register zur Erfassung von Spätfolgen nach Strahlentherapie im Kindes- und Jugendalter--erste Ergebnisse.

BACKGROUND: Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Therefore the German Group of Pediatric Radiation Oncology (APRO) established the "RegIster for the evaluation of late Side effects after radiation in childhood and adolescence" (RiSK). After a pilot phase starting in 2001 documentation has been performed all over Germany since 2004. This analysis shows the first results of "RiSK". PATIENTS AND METHODS: Radiation parameters including detailed organ doses as well as toxicity evaluations were collected prospectively from centers all over Germany in the study center. Standardized documentation forms were used. Documentation is planned for all children who receive radiotherapy in one of the German pediatric therapy trials. RESULTS: Until December 31st 2006, 696 documentations of radiotherapy and 526 acute as well as 836 late follow-up documentation forms have been collected. Altogether, 41 patients with late grade 3 and 16 patients with late grade 4-side effects were identified. Side effects mainly concerned joints with functional impairment (after combined radiotherapy and surgery), the bowel, skin and subcutis as well as blood parameters under continued chemotherapy. Patients with late side effects of a higher grade were mainly treated for Ewing's or soft tissue sarcomas (n=235 patients), representing 33.8% of all patients in this study. CONCLUSION: Fortunately, up to now only a few late grade 3 or 4 side effects of radiotherapy are shown for almost 700 documented patients. For further results, especially for the characterization of dose-effect-relationships, this study has to be continued with a higher patient number and a longer follow-up.

[Requirements and performance profile of the Paediatric Radiation Oncology Working Group (APRO): evaluation of the present situation and description of future developments]. / Anforderungen und Leistungsprofile der Arbeitsgemeinschaft Pädiatrische Radioonkologie (APRO): Eine Bestandsaufnahme und Darstellung zukünftiger Entwicklungen.

BACKGROUND: Radiation therapy is an integral component in the management of childhood malignancies and undergoes a continuous process of optimization within the prospective trials of the GPOH. At present there are approximately 20 active protocols, some specifying radio-oncological study questions, in which about 500 to 600 children annually are given radiotherapy. MATERIALS/METHODS: The Pediatric Radiation Oncology Working Group (APRO) of the German Society for Radiation Oncology (DEGRO) represents the organizational link between GPOH and DEGRO. Their activities range from phrasing guidelines of radio-oncological therapy, through writing a protocol for a prospective study on radiation-induced late effects (RISK--in co-operation with GPOH, 695 patients registered so far) and organizing meetings for information transfer, to implementing radio-oncology within the prospective studies of the GPOH by establishing study chairs for radio-oncology when radio-oncological questions are a primary focus and/or to function as a reference institution for quality assurance. These activities also include individual case consultations outside the study proper. Twice annually the members of the APRO meet for an update on current knowledge and future directions where a representative of the GPOH is invited to contribute special aspects of pediatric oncology. CONCLUSIONS: In the future, modern technology (intensity modulated radiotherapy, proton therapy, inclusion of imaging in treatment planning) will be part of disease management in pediatric oncology. A working group for modern radiotherapy technology was established to enhance this development. Prospective studies of the GPOH with primary or secondary radio-oncological questions require the implementation of corresponding tasks (documentation, monitoring, etc.) in order to meet future demands on clinical trials and to achieve the aims of the protocol. Consequently adequate financial support is indispensable.

[Modeling developmental aspects of sensorimotor control of speech production]. / Ein neuronales Modell zur sensomotorischen Entwicklung des Sprechens.

BACKGROUND: Detailed knowledge of the neurophysiology of speech acquisition is important for understanding the developmental aspects of speech perception and production and for understanding developmental disorders of speech perception and production. METHOD: A computer implemented neural model of sensorimotor control of speech production was developed. The model is capable of demonstrating the neural functions of different cortical areas during speech production in detail. RESULTS: (i) Two sensory and two motor maps or neural representations and the appertaining neural mappings or projections establish the sensorimotor feedback control system. These maps and mappings are already formed and trained during the prelinguistic phase of speech acquisition. (ii) The feedforward sensorimotor control system comprises the lexical map (representations of sounds, syllables, and words of the first language) and the mappings from lexical to sensory and to motor maps. The training of the appertaining mappings form the linguistic phase of speech acquisition. (iii) Three prelinguistic learning phases--i. e. silent mouthing, quasi stationary vocalic articulation, and realisation of articulatory protogestures--can be defined on the basis of our simulation studies using the computational neural model. These learning phases can be associated with temporal phases of prelinguistic speech acquisition obtained from natural data. CONCLUSIONS: The neural model illuminates the detailed function of specific cortical areas during speech production. In particular it can be shown that developmental disorders of speech production may result from a delayed or incorrect process within one of the prelinguistic learning phases defined by the neural model.

[MRT sequences as a database for a visual articulatory model]. / MRT-Sequenzen als Datenbasis eines visuellen Artikulationsmodells.

Articulatory models can be used in phoniatrics for the visualisation of speech disorders, and can thus be used in teaching, the counselling of patients and their relatives, and in speech therapy. The articulatory model developed here was based on static MRI data of sustained sounds. MRI sequences are now being used to further refine the model with respect to speech movements. Medio-sagittal MRI sections were recorded for 12 consonants in the symmetrical context of the three point vowels [i:], [a:] and [u:] for this corpus. The recording-rate was eight images/s. The data show a strong influence of the vocalic context on the articulatory target-positions of all consonants. A method for the reduction of the MRI data for subsequent qualitative and quantitative analyses is presented.

Evaluation of impedance spectroscopy for the characterization of small biological samples in tissue-based test systems.

Marker free techniques are needed for the construction of efficient tissue-based test and sensor systems. In principle biological tissue can be characterized by impedance spectroscopy. In this paper we investigate by simulation how sensitive parameters of small biological tissue samples can be determined by impedance spectroscopy under optimal measurement conditions. Further, we experimentally evaluate whether the effects of different clinical relevant radio therapy variants on 3D in vitro tumor models are determinable and distinguishable by impedance spectroscopy using a tissue-based test system. The simulations demonstrate that changes in tissue parameters related to the extracellular space are determinable with a high sensitivity. The experiments show that the effect of different radiation dose levels on 3D in vitro tumor models can be determined and distinguished by using a capillary measurement system and impedance spectroscopy. These results are relevant for the development of tissue-based test and sensor systems using impedance spectroscopy to evaluate personalized therapy variants or new therapy approaches.

Vocal cord palsy resulting from spontaneous carotid dissection.

OBJECTIVES/HYPOTHESIS: Vocal cord palsy has a variety of causes, such as malignant tumors of the thyroid, lung, or upper mediastinum, aortic aneurysm, surgery of the thyroid, and infectious diseases. STUDY DESIGN: Case report. METHODS: A 43-year-old biologist had a holocephalic headache and right-sided neck pain for 1 day. Five days later, he developed paralysis of the right-side vocal cord. In addition, an angiotensin converting enzyme (ACE) inhibitor was administered because the patient had high systolic and diastolic blood pressures, which were formerly not known to the patient. Five days after admission, a temporary sensorimotor hemiparesis occurred. RESULTS: Neurological examination revealed, in addition to the known paralysis of the right-side vocal cord, right-side palatoplegia, right-side hypoglossal nerve palsy, and mild dysphagia. Duplex sonography showed evidence of lumen narrowing of the right-side internal carotid artery caused by an hypoechogenic mural hematoma. Magnetic resonance imaging (0.5 T, Philips Gyroscan) revealed a circumscribed dissection of the right-side internal carotid artery from the carotid bifurcation to the petrosal segment. The diffusion-weighted magnetic resonance imaging scan of the brain also demonstrated multiple embolic ischemic lesions in the right hemisphere. CONCLUSION: Internal carotid artery dissection must be included in the differential diagnosis of lower cranial nerve palsy and should be assessed by duplex ultrasonography and magnetic resonance imaging.

Radiotherapy in the treatment of locoregional relapses of breast cancer.

Locoregional recurrences of breast cancer are associated with considerable morbidity and frequently present with concurrent metastatic disease. Yet patients without systemic spread can be treated with curative intent. In a retrospective analysis, the results of treatment of these patients have been evaluated at our institution. Between 1987 and 1996, 113 patients with locoregional breast cancer relapse, without systemic manifestation, received irradiation after local tumour excision. 13 patients (11.5%) had already received radiotherapy as part of their primary treatment. In these cases, only the area involved was treated. In all other patients, the chest wall and the ipsilateral lymph nodes were irradiated. Median dose was 50 Gy (range 20-65 Gy). Median follow-up was 4.4 years. 76 patients (67.3%) presented with chest wall recurrence only, 25 patients (22.1%) with nodal relapse only and 12 patients (10.6%) with combined relapses. 93% of patients had local control of disease after treatment. Local control rate after 5 years was 59%. 63 patients (55.8%) died within the follow-up interval, 45 patients (39.8%) owing to metastases, 4 patients (3.5%) owing to local failure and 8 patients (7%) owing to causes unrelated to tumour. Overall survival after 5 years was 43%. In multivariate analysis, positive hormone receptor status, small tumours on relapse and chest wall relapses alone were associated with improved survival. Radical local therapy is necessary in order to achieve and maintain local control and to prevent secondary dissemination in patients with only local recurrence of breast cancer.

Postoperative radiotherapy in localized non-small cell lung cancer.

Surgery alone can cure 40-85% of patients with localized non-small cell lung cancer, depending on tumor stage and metastatic lymph-node involvement. As local failure rates occur in up to 50% of the cases, postoperative radiotherapy as an adjuvant treatment option has been evaluated in several trials. This review briefly summarizes the published data mainly from randomized trials. While most of the studies showed a decrease in local recurrence rate, especially in stage-III/N2 tumors after postoperative radiotherapy, no impact could be shown on overall survival. In early stages a detrimental effect of postoperative radiotherapy has been postulated, but those findings have to be interpreted with caution as radiation techniques used were suboptimal and probably not today's state of the art. A carefully designed randomized trial using modern radiotherapy techniques is warranted to define the impact of irradiation on completely resected NSCLC.