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.

[Radiotherapy after tumour prostheses-status, indication, coordination]. / Strahlentherapie nach Tumorendoprothesen ­ Stellenwert, Indikation, Koordination.

BACKGROUND: Patients with complex tumour prostheses often require radiotherapy or radiochemotherapy. OBJECTIVES: Possible tumour diagnoses, indications, planning and therapy procedures, and prognosis of radiotherapy in the context of an interdisciplinary treatment for bone sarcomas are reviewed, including interactions of metal prostheses with radiation and possible subsequent complications. METHODS: Literature search, summary of personal experience. RESULTS: Complex prosthetic procedures are usually applied to patients suffering from Ewing sarcoma or osteosarcoma. In patients with Ewing sarcoma, radiotherapy is an integral part of multimodal treatment, while in patients with osteosarcoma radiotherapy is indicated in special situations. Planning and implementation of radiotherapy treatment can be impaired by metal implants within the target volume (artefacts in the planning computerized tomography, interaction of metal with the therapeutic beam). However, it is-to our knowledge-a point of debate whether radiotherapy after implantation of a prosthesis could impair healing or prosthesis fixation to bone. The data available in the literature suggest that prostheses implanted after radiotherapy entail a higher rate of complications. Multidisciplinary treatment improves the prognosis for these patients markedly. CONCLUSIONS: Patients with sarcomas of the bone undergoing interdisciplinary treatment consisting of surgery, radiotherapy and chemotherapy have a favourable prognosis and an acceptable functionality of the limb can be expected.

Multidisciplinary treatment of desmoid tumours in Gardner's syndrome due to a large interstitial deletion of chromosome 5q.

BACKGROUND AND AIMS: Classic autosomal-dominant familial adenomatous polyposis (FAP) is clinically defined by the development of hundreds to thousands of colorectal adenomas beginning in childhood and adolescence. A variant of FAP characterized by polyposis in combination with osteomas or soft tissue tumours is called Gardner's syndrome. FAP is caused by germline inactivation of the APC (adenomatous polyposis coli) tumour-suppressor gene located on the long arm of chromosome 5 (5q21-5q22). Cytogenetically visible deletions of chromosome 5q encompassing APC have very rarely been reported. Here, we aimed to phenotypically and genetically characterize a patient with a heterozygous 5q deletion resulting in Gardner's syndrome. METHODS AND RESULTS: A 26-year-old female patient with mild mental handicap and dysmorphic features due to a cytogenetically visible deletion on chromosome 5q (microscopically estimated region 5q14-5q23) presented at our tertiary referral centre because of mild adenomatous polyposis (<500 polyps). Twenty months after prophylactic proctocolectomy with definitive ileostomy, three rapidly growing desmoids were observed. Tumour-associated complications necessitated a multidisciplinary approach including medical treatment, surgery and radiation therapy. The characterization of the deletion by comparative genomic hybridization identified a large 5q deletion expanding over a 20-Mb region (5q21.3-5q23.3) including the APC gene. CONCLUSION: Chromosome deletions must be suspected in patients presenting with FAP together with mental handicap and dysmorphic features. This case also impressively shows that FAP-associated desmoids need multimodal treatment taking into account the patient's individual symptoms, disease progression and tumour location.

[Individual silicon applicator for nasopharyngeal brachytherapy]. / Ein individueller Silikonstrahlenapplikator für die nasopharyngeale Brachytherapie.

BACKGROUND: Beyond surgery, conventional radiation therapy, and chemotherapy brachytherapy may enrich treatment of primary, residual, or recurrent head and neck cancer. Nasopharyngeal cancer is a proper indication for intracavitary brachytherapy which can be performed using a commercial applicator system or an individual applicator. METHODS AND PATIENTS: Technique for manufacturing an individual nasopharyngeal silicon applicator and its experiences in 3 patients (2 times brachytherapy in treatment regime of primary nasopharyngeal cancer, 1 time for nasopharyngeal lymphoma treatment) are presented. RESULTS: Under general anaesthesia in all 3 patients nasopharyngeal imprinting after placement of two suction tubes was performed with shore 12 silicon and followed by manufacturing the individual silicon applicator with two included tubes after plaster cast of the imprinting form has been performed. This silicon applicator enabled safe endocavitary brachytherapy using the high-dose-rate-afterloading-method. Tumor control was achieved in all 3 patients. CONCLUSIONS: The presented individual silicon applicator is suited for intracavitary brachytherapy of the nasopharynx being an valuable contribution in the primary treatment regime of nasopharyngeal 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.

Prognostic factors in brain metastases: should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classes?

PURPOSE: To determine whether or not Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) derived prognostic classes for patients with brain metastases are generally applicable and can be recommended as rational strategy for patient selection for future clinical trials. Inclusion of time to non-CNS death as additional endpoint besides death from any cause might result in further valuable information, as survival limitation due to uncontrolled extracranial disease can be explored. METHODS: We performed a retrospective analysis of prognostic factors for survival and time to non-CNS death in 528 patients treated at a single institution with radiotherapy or surgery plus radiotherapy for brain metastases. For this purpose, patients were divided into groups with Karnofsky performance status (KPS) <70% and KPS > or =70%, as proposed by the RTOG. RESULTS: Median overall survival was 2.9 months (2.0 months for patients with KPS <70% and 3.6 months for patients with KPS > or =70%, p < 0.001). We did not find other variables splitting patients with KPS <70% in different prognostic groups. However, advanced age, multiple brain metastases, presence of extracranial metastases, and uncontrolled primary tumor each predicted shorter survival in patients with KPS > or =70%. When grouped into the original RTOG RPA classes, our data set split into three subgroups with different prognosis and median survival times of 10.5, 3.5, and 2 months, respectively (p < 0.05). Only 3% of patients fell into the most favorable group. Median time to non-CNS death was 4.1 months (12.9 months in RPA class I, 4.9 months in RPA class II, and 3.8 months in RPA class III, respectively, p > 0.05 for RPA class II versus III). However, it was 8.5 months in RPA class II patients with controlled primary tumor, which was found to be the only prognostic factor for time to non-CNS death in patients with KPS > or =70%. In patients with KPS <70%, no statistically significant prognostic factors were identified for this endpoint. CONCLUSIONS: Despite some differences, this analysis essentially confirmed the value of RPA-derived prognostic classes, as published by the RTOG, when survival was chosen as endpoint. RPA class I patients seem to be most likely to profit from aggressive treatment strategies and should be included in appropriate clinical trials. However, their number appears to be very limited. Considering time to non-CNS death, our results suggest that certain patients in RPA class II also might benefit from increased local control of brain metastases.

Dose-response relationships for radiotherapy of brain metastases: role of intermediate-dose stereotactic radiosurgery plus whole-brain radiotherapy.

The effects of intermediate-dose radiotherapy consisting of whole-brain radiotherapy (WBRT, 10 fractions of 3 Gy) plus stereotactic radiosurgery (SRS) were studied prospectively. Twenty-five adult patients with 31 brain metastases received WBRT plus linear accelerator (LINAC)-based single dose SRS with fixed treatment parameters (10 Gy at the isocenter, target volume enclosed by the 90% isodose). Median age was 63 years, median Karnofsky performance status 80%, and median diameter of brain metastases 2.4 cm. Fifteen patients had non-small-cell lung cancer. Because of some early deaths, only 26 lesions could be evaluated for response. We observed 1 complete and 15 partial remissions. Median time to progression inside or outside the SRS volume was 4.5 months. Actuarial local control of SRS-treated lesions was 61% at 1 year. At that time, only 37% of patients were free from new lesions outside the SRS volume. Median survival and cause-specific survival were 2.3 and 4.5 months, respectively (1-year survival rate 8% and 21%). Ten patients died of progressive brain metastases, 13 from extracranial disease progression (unknown cause of death in 2 cases). Comparable to SRS studies with higher doses, the majority of brain failures occurred outside the SRS volume and more patients died of extracranial progression than of uncontrolled brain metastases. Failure to improve survival can be explained by the high percentage of patients with extracranial metastases (52%). However, the present results appear less favorable than those of previous studies of SRS with 15 Gy to 16 Gy (1-year actuarial local control rates of 66-89%). Therefore, we recommend SRS with 15 Gy to 16 Gy for patients whose favorable prognostic factors justify a boost after WBRT.

Late radiation toxicity after whole brain radiotherapy: the influence of antiepileptic drugs.

This retrospective study had the following aims: (a) calculation of actuarial rate of late radiation toxicity after whole-brain radiotherapy (WBRT), (b) correlation of clinical symptoms with changes of computed tomography (CT) scans, and (c) analysis of potentially predictive factors with special regard to concomitant treatment with antiepileptic drugs. We analyzed 49 adult patients, selected from a preexisting data base. Inclusion criteria were as follows: no previous brain irradiation; WBRT without boost; CT, clinical, and neurologic examination before and more than 3 months after completion of WBRT. Uni- and multivariate tests of various patient- and treatment-related parameters as possible predictive factors for clinical symptoms of late radiation toxicity (scored according to the RTOG/EORTC system) as well as cerebral atrophy and white matter abnormalities were performed. Median age was 54 years. Patients were treated for brain metastases (n = 37), primary cerebral lymphoma (n = 2), primary brain tumors (n = 7), or with prophylactic intention (n = 3). Carbamazepine was given to 15 patients, phenytoin to 12, and barbiturate to 7, respectively; 42 patients also received corticosteroids. The median dose of WBRT was 30 Gy (range 27-66 Gy). Median fraction size was 3 Gy (1-3 Gy). Nine patients received two fractions per day. The biologically effective dose (BED) according to the linear-quadratic model ranged between 90 and 141 Gy (median, 120 Gy; alpha/beta value, 1 Gy). Median follow-up was 10 months (range, 4-130 months). In 16 cases, symptoms of late radiation toxicity grade I-III appeared. Actuarial rates were 32% after 1 year, 49% after 2 years, and 83% after 5 years. Actuarial rates of cerebral atrophy were 50% after 1 year and 84% after 2 years (white matter abnormalities: 25% and 85%, respectively). There was a significant correlation between atrophy and white matter abnormalities, but not between CT changes and clinical symptoms. CT changes were dependent on BED, absence of barbiturate use, and preexisting cerebral atrophy. Clinical symptoms usually were dependent on BED too, but treatment with carbamazepine was more important in the multivariate model. Neither other drugs nor other factors influenced late radiation toxicity. A detailed analysis showed that most carbamazepine-treated symptomatic patients took the drug during WBRT as well as during follow-up. Actuarial rates of grade I-III symptoms were 18% versus 50% after 1 year with or without carbamazepine. Even after exclusion of carbamazepine-treated patients, CT changes and clinical symptoms did not correlate. In conclusion, a BED <120 Gy was associated with a lower rate of late radiation toxicity after WBRT. The anticonvulsant drug carbamazepine showed a surprisingly clear influence on clinical symptoms of late radiation toxicity; that might be explained by the fact that the side effects of long-term drug treatment are indistinguishable from mild or moderate true radiation sequelae, rather than that it has a role in the pathogenesis of radiation-induced changes.

[Implantation metastasis at the exit site after percutaneous endoscopic gastrostomy in esophageal carcinoma]. / Implantationsmetastase an der Austrittsstelle nach perkutaner endoskopischer Gastrostomie bei Osophaguskarzinom.

In patients with esophageal cancer causing obstruction percutaneous endoscopic gastrostomy (PEG) is a well-established procedure with a low complication rate to provide sufficient enteral nutrition. We report on a 68-year-old patient suffering from inoperable squamous cell cancer of the proximal esophagus, who underwent PEG insertion prior to a combined radiochemotherapy. Initially bougienage was performed because of subtotal esophageal stenosis. Four months later a metastasis was found at the PEG exit site with involvement of the gastric wall, most likely caused by spread of tumor cells during insertion of the PEG.

[Palliative accelerated irradiation for advanced non-small-cell lung bronchial carcinoma: results of a pilot study]. / Palliative akzelerierte Bestrahlung beim fortgeschrittenen nicht-kleinzelligen Bronchialkarzinom: Ergebnisse einer Pilotstudie.

In order to reduce the aggressivity of radiotherapy of very advanced non-small-cell lung cancer (NSCLC), and to shorten treatment time, a palliative accelerated irradiation regimen (PAIR) was developed. Before the onset of a randomised study, we performed a one-year pilot study, of which the paper presented here gives the results after complete follow-up. 34 patients (S) with locally inoperable advanced NSCLC stage III (74%) and IV (26%) were irradiated with accelerated fractionation schedule, focussing on tumour and mediastinum, with a total dose of 32 Gy (PAIR, 2 x 2 Gy/d). Treatment results were compared to those of a group of 178 controls (K) treated conventionally, who were selected from a preexisting database according to study inclusion criteria (tab. 2-5 stage III 65%, IV 35%). 105 of them had been treated with a total dose of 60 Gy (K60). After complete follow-up a final evaluation was made. Local control did not differ significantly between both groups, and not between groups S and K60 (tab. 6, fig. 2). Median survival for all patients (S + K) was 6 months. With 8.7 months, that of the study patients (S) was significantly longer than that of the controls (K, fig. 1). This was also true of stage III. Comparison with the 60-Gy-controls (K60) did not reveal significant survival differences. In Cox regression analysis independent prognostic factors were: Karnofsky index, UICC stage, and N stage. Concerning the palliation of tumour-related symptoms, both therapies were comparable (tab. 7). The side-effects were moderate and also comparable. These results induced us start a randomized study comparing both regimens in respect of prognosis and palliation.

18F-deoxyglucose positron emission tomography (FDG-PET) for the planning of radiotherapy in lung cancer: high impact in patients with atelectasis.

PURPOSE: 18F-deoxyglucose positron emission tomography (FDG-PET) is increasingly applied in the staging of lung cancer (LC). This study analyzes the potential contribution of PET in radiotherapy planning for LC with special respect to tumor-associated atelectasis. METHODS AND MATERIALS: Thirty-four patients with histologically confirmed LC, who had been examined by PET during pretreatment staging, were included. All were irradiated after CT-based therapy planning with anterior/posterior (AP) portals encompassing the primary tumor and the mediastinum (CT portals, CP). The result of the PET examination was unknown in treatment planning. In retrospect, a PET portal (PP) was delineated and compared with the CP. RESULTS: In 12/34 cases, the shape and/or size of the portals were changed, primarily (n = 10) the size of the fields was reduced. The median area of CP was 182 cm2 versus 167 cm2 of PP. Seventeen of 34 patients had dys- or atelectasis caused by a central primary tumor. In these cases, differences between CP and PP were significantly more frequent than in the other patients (8/17 vs. 3/17, p = 0.03). CONCLUSION: In this retrospective analysis, the information provided by FDG-PET would have contributed to a substantial reduction of the size of radiotherapy portals. This applies particularly for patients with tumor-associated dys- or atelectasis.

Dose reduction in thorax radiography in simulated neonates with additional filtration and digital luminescence radiography.

PURPOSE: To determine the minimum acceptable radiation dose for an adequate image quality in thorax a.p. radiographs of neonates using mobile X-ray equipment. MATERIAL AND METHODS: The influence of additional filtration (1.0 mm Al + 0.1 mm Cu) on image quality and radiation dose was determined for the speed class 400 screen-film system (SFS) and digital luminescence radiography (DLR) by making radiographs of a test phantom. Conventional and digital thorax a.p. radiographs of a rabbit were produced using various tube current-time products. The quality of the rabbit radiographs was judged by eight radiologists applying image quality criteria according to the German guidelines and the recommendations of the European Community. RESULTS: The added filter resulted in a dose reduction of 39% at 66 kV. DLR gave a further dose reduction of 25% in comparison to the speed class 400 SFS while maintaining adequate image quality, i.e. the radiographs were clinically acceptable with regard to quality criteria. CONCLUSION: The radiation dose resulting from thorax a.p. radiographs of neonates can be reduced by approximately 50% with the use of additional filtration and DLR.

Dose/effect relationships for brain metastases.

PURPOSE: Only in selected patients with brain metastases, e.g. those with controlled or absent extracranial tumour, may application of higher total doses of radiotherapy improve survival. However, local control is the prerequisite for long-term survival. This study aimed to answer the question whether or not local control can be improved by dose escalation. METHODS: Computed tomography scans of 322 patients were analysed in order to evaluate the best local result after radiotherapy and the time to local progression. Total doses of 25-60 Gy were administered (single doses 1.8-5 Gy). The biologically effective dose (BED10) was calculated for statistical evaluation according to the linear-quadratic model assuming an alpha/beta-value of Gy. It ranged between 37.5 Gy and 72 Gy. RESULTS: The best local result was dependent on the number of brain metastases, BED and the histology of the primary tumour (small-cell and breast carcinoma had higher remission rates than squamous-cell carcinoma, non-breast adenocarcinoma and others). Partial remission rates significantly increased with BED, whereas complete remission rates did not improve. Histology was the only significant factor in multivariate tests. The 1-year-failure rate improved with increased BED from 44% to 31% (P > 0.05). Overall survival (median 3 months) was not dependent on total dose. CONCLUSIONS: Previous studies suggested that a prolongation of survival can be achieved through better local management (e.g. surgery plus radiotherapy, radiosurgery). However, it is still uncertain whether conventional external-beam radiotherapy with higher total doses leads to comparable results. The optimum dose level still has to be established. For squamous-cell carcinoma and adenocarcinoma a BED of at least 72 Gy seems to be necessary, for small-cell and breast carcinoma, doses between 48 Gy and 60 Gy might be sufficient. The important influence of tumour histology on local remission and progression-free survival should be considered when planning future clinical trials.

Multivariate logistic analysis of dose-effect relationship and latency of radiomyelopathy after hyperfractionated and conventionally fractionated radiotherapy in animal experiments.

PURPOSE: We examined in rats whether the radiation tolerance of spinal cord is enhanced by using hyperfractionated radiotherapy compared to a conventional schedule. Higher tolerable doses to the spinal cord would allow dose escalation to the tumor and thus possibly lead to higher cure rates, especially in tumors with high cell proliferation. METHODS AND MATERIALS: Cervical spinal cord of 276 healthy rats was irradiated over 6 weeks hyperfractionally with single doses ranging from 0.75-2.5 Gy up to total doses ranging from 45-150 Gy (60 fractions) and conventionally with single doses of 1.5-4.0 Gy up to total doses of 45-120 Gy (30 fractions). The rats were examined neurologically and sacrificed when paralysis of the hind legs occurred. After fixation, spinal cord was removed and examined histologically. Dose-effect relationship and latency from the beginning of radiotherapy to the onset of paralysis were computed and analyzed using a multivariate logistic regression model. RESULTS: The model fitted the observed data excellently. There were highly significant effects both for the dose level and for the treatment regimen. Latency analysis showed earlier and more intense acute side effects after hyperfractionation but radiomyelopathy occurred markedly later. CONCLUSIONS: The sparing effect of hyperfractionation on spinal cord as predicted by radiobiologists could be confirmed in our experiments. Thus, it seems possible to escalate tumor doses using hyperfractionation without enhanced risk to spinal cord but with higher probability of tumor cure.

Accelerated radiotherapy for brain metastases.

BACKGROUND AND PURPOSE: Two novel fractionation schedules for whole-brain irradiation were applied to patients with brain metastases. Both schedules were aimed at reduction of treatment time, whereby tumour control should be increasing with the application of a higher total dose (schedule 2). MATERIALS AND METHODS: We applied 2 x 2.5 Gy/day to a total dose of 30 Gy (schedule 1) or 2 x 1.8 Gy/day to a total dose of 50.4 Gy (schedule 2). The interval between daily fractions was 6 h. Treatment was interrupted on weekends. The 30 Gy schedule was also used in adjuvant treatment for resected brain metastases. We compared the results of 15 patients who underwent the 50.4 Gy schedule and 47 patients who were treated up to 30 Gy with those of a historical patient group, treated with one daily fraction of 3 Gy up to 30 Gy (n = 283). RESULTS: Local result, clinical course and survival were similar for the 30 Gy groups, whereby prognostic factors were equally distributed. Despite a favourable patient selection no therapeutic gain was seen for the 50.4 Gy group. Patients treated with the accelerated 30 Gy schedule had a significantly worse progression-free survival and a higher rate of late radiation toxicity than the historical group. In contrast, no severe acute toxicity was observed. CONCLUSIONS: Considering progression-free survival and late toxicity, the accelerated 30 Gy schedule can not be recommended without hesitation. Radiotherapy with a higher total dose (50.4 Gy) showed no advantage.