(1) Background: Autosomal dominant polycystic kidney disease (ADPKD) is a frequent monogenic diso... more (1) Background: Autosomal dominant polycystic kidney disease (ADPKD) is a frequent monogenic disorder that leads to progressive renal cyst growth and renal failure. Strategies to inhibit cyst growth in non-human cyst models have often failed in clinical trials. There is a significant need for models that enable studies of human cyst growth and drug trials. (2) Methods: Renal tissue from ADPKD patients who received a nephrectomy as well as adult mouse kidney slices were cultured on a chorioallantoic membrane (CAM) for one week. The cyst volume was monitored by microscopic and CT-based applications. The weight and angiogenesis were quantified. Morphometric and histological analyses were performed after the removal of the tissues from the CAM. (3) Results: The mouse and human renal tissue mostly remained vital for about one week on the CAM. The growth of cystic tissue was evaluated using microscopic and CT-based volume measurements, which correlated with weight and an increase in angiogenesis, and was accompanied by cyst cell proliferation. (4) Conclusions: The CAM model might bridge the gap between animal studies and clinical trials of human cyst growth, and provide a drug-testing platform for the inhibition of cyst enlargement. Real-time analyses of mouse kidney tissue may provide insights into renal physiology and reduce the need for animal experiments.
Background: Radiotherapy and chemoradiation are well-established therapies for patients with squa... more Background: Radiotherapy and chemoradiation are well-established therapies for patients with squamous cell carcinoma of the head and neck (SCCHN). In aging societies, also the incidence of SCCHN in elderly patients is rising. Because of the underrepresentation of elderly patients in scienti c trials, we evaluated the feasibility of adjuvant radiotherapy and chemoradiation in patients with SCCHN aged >70 years. Methods: All patients had been >70 years at the time of diagnosis and received adjuvant radiotherapy or, if feasible, chemoradiation at the University Medical Centre Regensburg between 2004 and 2018. 71 patients-most with SCCHN UICC stage IVa-with a median age of 75 years were included; 9 patients received concomitant chemoradiation. Median follow-up was 27 months (IQR 18-62 months). Results: Radiotherapy and chemoradiation was well tolerated. 62 patients (87.3%) underwent treatment without interruption, and 65 patients (91.5%) completed radiotherapy with 95% of the initially prescribed dose. Median dose for all patients was 64 Gy (IQR: 60-66 Gy). 6/9 patients received at least 75 % of the planned chemotherapy dose. 37 patients (52.1%) developed acute toxicity CTC grade III or IV. Overall survival was 87 % after 12 months, 67 % after 24 months and 41 % after 60 months. Median overall survival was 51 months (IQR: 19-99 months). Local tumour control was 99 % after 12 months, 88 % after 24 months and 76 % after 5 years. Conclusion: Feasibility of adjuvant radiotherapy and chemoradiation in our collective of elderly patients with SCCHN was good. Particularly local tumour control was satisfactory. Overall survival does not seem to differ between elderly and younger patients or patients unselected for age. De-intensi cation of treatment because of age does not seem justi ed. Background: Squamous cell carcinoma of the head and neck (SCCHN) is a common type of malignant tumours worldwide. In 2019, 53,000 cases of cancer of the oral cavity and pharynx and 12,410 cases of laryngeal cancer were projected for the United States (US), 3.7% of all new cancer cases in the US are SCCHN. (National Comprehensive Cancer Network 2019b) (Siegel et al. 2019). The worldwide proposed incidence of SCCHN for 2018 was 834,860 cases (4.6% of all newly diagnosed malignancies) (Bray et al. 2018).
Introduction Radiotherapy of pituitary adenomas is often applied as postoperative therapy of tumo... more Introduction Radiotherapy of pituitary adenomas is often applied as postoperative therapy of tumors that cannot be removed completely. Fluence modulating techniques like IMRT or VMAT support the use of the flatness filter free (FFF) mode in modern linear accelerators. In this mode a considerably higher dose rate is achieved by omitting the flatness filter. This planning study compares different plans for patients with pituitary adenoma. The plans were optimized using both modes: flattened beam (FB) and FFF. The aim of this study is to evaluate the plan quality. Material and Methods Data sets of 11 patients with pituitary adenoma were used for this retrospective planning study. The objectives for the PTV were set to a minimum dose of 49.4Gy and a maximum dose of 51.4Gy in 28 fractions, aiming for a fraction dose of 1.8Gy. Further objectives were set for the following regions of interest (ROI): brain, brainstem, chiasm, and both lenses, bulbs, lacrimal glands, and parotids. The planni...
; for the German Rectal Cancer Study Group IMPORTANCE Total neoadjuvant therapy has been increasi... more ; for the German Rectal Cancer Study Group IMPORTANCE Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. OBJECTIVE To report the long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population
Background: Following the PACIFIC trial, durvalumab has been approved by the European Medicines A... more Background: Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.2017 to 15.10.2018 allowing analysis of its efficacy and safety. Methods: Data from 56 centres were analysed for adverse events (AE), progression-free survival (PFS), overall survival (OS). Results: 126 patients actually received at least 1 cycle durvalumab. Compared to the PACIFIC trial, the EAP population had more advanced stage and included "oligometastatic" stage IV patients and patients with autoimmune disease. PFS (20.1 months) and OS (not reached) were similar in the EAP and the PACIFIC trial. 42.9 % completed 12 months of durvalumab without deaths during FU. Stage IV patients (n = 7) had encouraging OS (not reached at 27 months). Autoimmune disease did not affect survival. PFS and OS were similar in PD-L1negative patients (n = 32) and PD-L1-positive patients (n = 79). Conclusions: Survival in the EAP was comparable to the PACIFIC trial. Selected stage IV patients and patients with autoimmune disease may benefit from durvalumab consolidation and should be included in future immunooncological trials. PD-L1 did not predict survival challenging the exclusion of PD-L1-negative patients from durvalumab consolidation. In summary, durvalumab consolidation is safe and effective in a European real-world setting.
Background This planning study compares different radiotherapy techniques for patients with pitui... more Background This planning study compares different radiotherapy techniques for patients with pituitary adenoma, including flatness filter free mode (FFF), concerning plan quality and secondary malignancies for potentially young patients. The flatness filter has been described as main source of photon scatter. Material and methods Eleven patients with pituitary adenoma were included. An Elekta Synergy™ linac was used in the treatment planning system Oncentra® and for the measurements. 3D plans, IMRT, and VMAT plans and non-coplanar varieties were considered. The plan quality was evaluated regarding homogeneity, conformity, delivery time and dose to the organs at risk. The secondary malignancy risk was calculated from dose volume data and from measured dose to the periphery using different models for carcinoma and sarcoma risk. Results The homogeneity and conformity were nearly unchanged with and without flattening filter, neither was the delivery time found substantively different. VM...
Osteoarthritis is a common disease, with a prevalence of symptomatic disease of 8.9%. One treatme... more Osteoarthritis is a common disease, with a prevalence of symptomatic disease of 8.9%. One treatment option is radiotherapy. Most published samples were treated with an orthovoltage technique or with a telecobalt device. A lot of radiotherapy institutions are nowadays using linear accelerators for treatment of osteoarthritis. There is a discussion on whether the treatment results achieved with a linear accelerator are comparable to those with the orthovoltage technique. The aim of this study is to analyze the results of radiotherapy for osteoarthritis with a linear accelerator and compare the results with reference to different joints. The analysis was performed in patients of two German radiotherapy institutions and included 295 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 65 years, with 39.0% male and 61.0% female patients. Most frequently, osteoarthritis of the knee (34.6%) or the finger (15.9%) was treated. We could find a significant response to radiotherapy. Median pain for the whole sample was 7 on the NRS before radiotherapy, 4 after 6 weeks, and 3 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 33.8% 12 months after radiotherapy. All investigated subgroups had a significant reduction of pain. Radiotherapy of osteoarthritis with a linear accelerator is an effective treatment which is very well tolerated. All analyzed subgroups show a good response to radiotherapy for at least 24 months. Orthovoltage therapy seems to be superior to treatment with a linear accelerator in a case-related analysis of the published samples. Further investigations should be performed for a definitive answer to this question.
Purpose Osteoarthritis of the ankle and tarsal joints is less common than osteoarthritis of the k... more Purpose Osteoarthritis of the ankle and tarsal joints is less common than osteoarthritis of the knee or hip, but the associated disability is at least as severe as that of the other major joints of the lower limb. The results for total arthroplasty are still not satisfactory. For this reason, arthrodesis is still the gold standard of non-joint-conserving surgery. For the reason of functionality, joint-conserving therapies play a major role in treatment of ankle and tarsal osteoarthritis. Low-dose radiotherapy has a long history of treatment of osteoarthritis. The aim of this survey was to examine the results of low-dose radiotherapy for osteoarthritis of the ankle and tarsal joints. Materials and methods The analysis was performed on patients of three German radiotherapy institutions and included 66 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 68 years, with 24.5% male and 75.5% female patients. The upper ankle was treated in 37.9%, the lower ankle in 27.3% and the tarsal joints in 34.8%. Results We could find a significant response to radiotherapy. For the whole sample, the median pain was 7 on the NRS before radiotherapy, 5 after 6 and 12 weeks, and 4 after 12 months. The percentage of patients with 0 or 1 on the NRS was 19.6% 12 months after radiotherapy. An improvement of joint mobility could be detected in 56.7% of the cases. All investigated subgroups had a significant reduction in pain. Conclusion Radiotherapy of ankle and tarsal osteoarthritis is an effective treatment without showing side effects. All analysed subgroups show a good response to radiotherapy for at least 24 months.
Ionizing radiation is able to cause severe damage to cardiac implantable electronic devices (CIED... more Ionizing radiation is able to cause severe damage to cardiac implantable electronic devices (CIED). In Germany, the DEGRO/DGK guideline recommends close monitoring of patients with CIEDs undergoing radiotherapy (RT). Nevertheless, especially in the era of intensity-modulated techniques and predominant use of 6 MV photons, errors of CIEDs are rare events. Therefore, we performed daily CIED controls and hypothesized that no relevant device interaction would occur in our cohort. From 2014 to 2018, we collected data of 51 patients (62 courses) with daily interrogation (n = 1046) of CIED. The dose to the skin above the CIED was measured by semiconductor or ion chamber dosimetry at least once per RT course. In many cases the dose was also calculated. The prescribed dose to the planning target volume (PTV) ranged from 7.5 to 78.0 Gy (IQR 27.8–61.0 Gy). The median measured cumulative dose to the skin above the CIED was 0.17 Gy, whereas the median calculated dose was 1.03 Gy. No error occurred in the group with maximum beam energy >10 MeV. Three events without clinical relevance could be recognized in the group with an intensity-modulated technique at 6 MV. None of the three concerned devices were located directly within the PTV. Errors of CIEDs during RT are rare events. The approach according to the DEGRO/DGK guideline is safe, but also consumes resources. In our cohort it was not compulsory to relocate any CIED. Clinically relevant events are uncommon, so it remains debatable which procedure is necessary. Daily controls could be avoided in some selected cases without compromising patient safety.
Purpose Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the aver... more Purpose Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the average population. One treatment option is low-dose radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of re-irradiation have not been analysed systematically, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. Methods and materials The analysis was performed on patients of three German radiotherapy institutions and included 217 re-irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as at the follow-up of 24 months. The median age of the patients was 67 years, with 40% male and 60% female patients. Re-irradiation was indicated because the initial radiotherapy resulted in no response in 21.2%, in partial response in 41.5%, and in recurrent pain in 37.3%. Results We found a significant response to re-irradiation. For the whole sample, the median pain was 6 before re-irradiation, 4 after 6 weeks, and 3 after 12 weeks, 6 months, 12 months, and 24 months. The percentage of patients being free of pain or with very little pain was approximately 25% 12 months after re-irradiation. All subgroups, notably those with no response to the first course versus partial response to the first course versus recurrent pain, had significant reduction of pain. Conclusion Re-irradiation of osteoarthritis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.
Background Humeral epicondylitis is a common elbow disease. The prevalence is about 1.7%. One of ... more Background Humeral epicondylitis is a common elbow disease. The prevalence is about 1.7%. One of the most effective treatment options is radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of a re-irradiation have not been systematically analyzed, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. Material and methods The analysis was performed on patients from three German radiotherapy institutions and included 99 re-irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as for the follow-up of 24 months. The median age of the patients was 51 years with 48.8% male and 51.2% female patients. Repeated radiation was indicated because the initial radiotherapy resulted in 39.7% of no response, in 41.0% of partial response and in 19.3% of recurrent pain. Results A significant response to re-irradiation was found. For the whole sample the median pain score was 6 before re-irradiation, 3 after 6 weeks, 2 after 12 months and 1 after 24 months. The percentage of patients being free of pain or with very little pain was 50.9% 24 months after re-irradiation. All subgroups, notably those with no response, partial response and recurrent pain had a significant reduction of pain. Conclusion Re-irradiation of humeral epicondylitis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months. Hintergrund Die Epicondylitis humeri ist eine der häufigsten Erkrankungen des Ellenbogens. Die Prävalenz liegt bei etwa 1,7 %. Eine der wirkungsvollsten Therapieoptionen stellt die Strahlentherapie dar. Dabei beschreiben viele Autoren die Durchführung einer oder mehrerer weiterer Bestrahlungsserien bei rezidivierten Schmerzen bzw. unzureichendem oder keinem Ansprechen auf die initiale Bestrahlungsserie. Da eine strukturierte Auswertung der Rebestrahlung bisher nicht existiert, war das Ziel dieser Arbeit, die Ergebnisse einer wiederholten Strahlenbehandlung zu dokumentieren und Patienten zu identifizieren, die von einer Rebestrahlung profitieren. Material und Methode Ausgewertet wurden Patienten aus drei strahlentherapeutischen Institutionen. Insgesamt konnten 99 rebestrahlte Ellenbogen analysiert werden. Die Schmerzintensität wurde mit Hilfe der numerischen Ratingskala (NRS) quantifiziert und zu den Zeitpunkten vor Bestrahlungsbeginn, direkt nach Radiatio, 6 und 12 Wochen sowie 6, 12 und 24 Monate nach Bestrahlung erfasst. Von den Patienten waren 48,8% männlich und 51,2% weiblich, bei einem medianen Alter von 51 Jahren. Grund der Rebestrahlung war in 39,7% kein Ansprechen und in 41,0% ein unzureichendes Ansprechen auf die erste Bestrahlungsserie sowie in 19,3% rezidivierte Schmerzen. Ergebnisse Es zeigte sich für das Gesamtkollektiv eine signifikante Schmerzreduktion. Die mediane Schmerzintensität war 6 vor der Rebestrahlung, 3 nach 6 Wochen und 2 bzw. 1 nach 12 und 24 Monaten. Nach 24 Monaten waren 50,9% der Patienten schmerzfrei oder nahezu schmerzfrei. Alle Subgruppen, insbesondere Patienten ohne und Patienten mit unzureichendem Ansprechen auf die initiale Bestrahlung bzw. Patienten mit rezidivierten Schmerzen verzeichneten eine signifikante Schmerzreduktion. Schlussfolgerung Zusammenfassend zeigt diese Arbeit, dass die Rebestrahlung bei der Epicondylitis humeri eine effektive und sichere Therapie darstellt. Alle Patientengruppen profitieren über mindestens 24 Monate von der Rebestrahlung.
Purpose Osteoarthritis of the knee is a common disease, often associated with a Baker's cyst. Bes... more Purpose Osteoarthritis of the knee is a common disease, often associated with a Baker's cyst. Besides osteoarthritis, also other joint pathologies of the knee can be causative for a Baker's cyst. Radiotherapy is known to be an effective treatment for osteoarthritis, with an anti-inflammatory effect. As the excessive production of synovia usually is associated with intraarticular inflammation, our hypothesis was that radiotherapy might positively influence the synovial production and reduce the volume of a Baker's cyst. Materials and methods We performed a prospective trial, including 20 knees receiving radiotherapy for knee arthritis. Besides documentation of NRS (numeric rating scale), WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and Knee Society Score, the volume of the Baker's cyst was calculated for a short-(6 to 12 weeks) and long-term (9 to 12 months) follow-up. Ultrasonic volumetry was performed using an ultrasound device with a high-resolution multifrequency linear probe (6-9 MHz). Results Low-dose radiotherapy improved NRS, WOMAC score and Knee Society Score significantly. The mean volume of Baker's cyst decreased from 22.3 ml to 10.7 respectively 3.1 ml during follow-up. A decrease in volume of more than 25% compared to the baseline could be achieved for 75% of the patients in the short-term and 79% of the patients in the long-term follow up. Conclusion Radiotherapy of knee osteoarthritis is an effective treatment that decreases the volume of a Baker's cyst. Most patients respond to the treatment. Whether radiotherapy is an effective treatment for Baker's cyst without associated osteoarthritis has to be further examined.
BackgroundEpicondylitis humeri is a common disease with a prevalence of 1.7%. One of the treatmen... more BackgroundEpicondylitis humeri is a common disease with a prevalence of 1.7%. One of the treatment options is radiotherapy. Most published cases were treated with the orthovoltage technique or with a telecobalt device. Many radiotherapy institutions are nowadays using linear accelerators for treatment of epicondylitis humeri. There is a discussion whether the treatment results with linear accelerators are comparable to the orthovoltage technique. The aim of this study was to analyze the results of radiotherapy with a linear accelerator for epicondylitis humeri.Material and methodsThe analysis was performed on patients of 2 German radiotherapy institutions and included 138 irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 49 years with 48.4% male and 51.6% female. In all, 81.0% were suffering from from epicondylitis humeri radialis while 16.7% were treated because of epicondylitis humeri ulnaris. In 65.4% the dominant arm was treated.ResultsA significant response to radiotherapy could be found. For the whole sample the median pain was 7 on the NRS before radiotherapy, 4 after 6 weeks and 0 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 64.6% 12 months after radiotherapy. All subgroups, notably those with epicondylitis humeri radialis and epicondylitis humeri ulnaris had a significant reduction of pain.ConclusionRadiotherapy of epicondylitis humeri with a linear accelerator is an effective treatment without showing side effects. All analyzed subgroups showed a good response to radiotherapy for at least 24 months.ZusammenfassungHintergrundDie Epicondylitis humeri ist eine der häufigsten degenerativen Erkrankungen. Die Prävalenz liegt bei etwa 1,7 %. Eine etablierte Therapieoption stellt die Strahlentherapie dar. Viele der publizierten Kollektive wurden mittels Orthovolttherapie behandelt oder an Telekobaltgeräten bestrahlt. Zahlreiche strahlentherapeutische Institutionen therapieren die Epicondylitis humeri mittlerweile mit Linearbeschleunigern. Es wird diskutiert, ob die Therapie am Linearbeschleuniger genauso effektiv ist wie die Orthovolttherapie. Ziel dieser Arbeit war die strukturierte Auswertung der Bestrahlung mittels Linearbeschleuniger bei Epicondylitis humeri.Material und MethodeAusgewertet wurden Patienten aus zwei strahlentherapeutischen Institutionen. Es konnten 138 bestrahlte Ellenbogen analysiert werden. Die Schmerzintensität wurde mithilfe der numerischen Rating-Skala (NRS) quantifiziert und vor Bestrahlungsbeginn, direkt nach Radiatio sowie über einen Follow-up-Zeitraum von 24 Monate nach Bestrahlung erfasst. Ein Anteil von 48,4 % der Patienten war männlich, 51,6 % waren weiblich. Das mediane Alter betrug 49 Jahre. 81,0 % der Patienten litten an einer radialen Epikondylitis, bei 16,7 % wurde eine mediale Epikondylitis behandelt. Bei 65,4 % der Patienten wurde der dominante Arm bestrahlt.ErgebnisseEs zeigte sich für das Gesamtkollektiv eine signifikante Schmerzreduktion. Die mediane Schmerzintensität auf der NRS war 7 vor der Bestrahlung, 4 nach 6 Wochen und 0 nach 12 und 24 Monaten. Ein Anteil von 64,6 % der Patienten waren 12 Monate nach Bestrahlung schmerzfrei oder nahezu schmerzfrei (NRS 0 oder 1). Alle Subgruppen, sowohl mit Epicondylitis humeri radialis als auch mit Epicondylitis humeri ulnaris, hatten eine signifikante Schmerzreduktion.SchlussfolgerungDie Bestrahlung mit Linearbeschleuniger ist bei Epicondylitis humeri eine effektive und sichere Therapie. Alle analysierten Patientengruppen profitierten für mindestens 24 Monate von der Therapie.
Background: 5-Fluorouracil (5-FU) is an antimetabolite, which is frequently used as chemotherapeu... more Background: 5-Fluorouracil (5-FU) is an antimetabolite, which is frequently used as chemotherapeutic agent for combined chemoradiotherapy. The purpose of this study was to present the clinical course of three patients who developed severe cardiac toxicity by 5-FU and to give a review of the literature on the cardiotoxic potential of 5-FU. Results: Cardiotoxicity is a rare, but relevant side effect of fluoropyrimidines. It comprehends a wide spectrum of side effects, from electrocardiogram changes (69% of cardiac events) to myocardial infarction (22%) and cardiogenic shock (1%). In this case series three patients with cardiotoxic events during chemoradiotherapy including 5-FU, the reaction's characteristics and their influence on further therapy are described. Two of the patients could not be treated with 5-FU any more because they had developed a myocardial ischemia, which was most likely caused by fluorouracil. Another patient, who complained about typical angina pectoris during 5-FU-infusion and had a new left anterior hemiblock, was reexposed with prophylactic administration of nitrendipine. Conclusion: Cardiotoxicity caused by 5-FU is an underestimated problem in radiooncology. Especially patients without history of cardiac disease are often treated as outpatients and therefore without cardiac monitoring. Consequently asymptomatic and symptomatic cardiac events may be overlooked. The benefit of prophylactic agents remains unclear, so close cardiac monitoring is the most established method to prevent manifest cardiotoxic events.
(1) Background: Autosomal dominant polycystic kidney disease (ADPKD) is a frequent monogenic diso... more (1) Background: Autosomal dominant polycystic kidney disease (ADPKD) is a frequent monogenic disorder that leads to progressive renal cyst growth and renal failure. Strategies to inhibit cyst growth in non-human cyst models have often failed in clinical trials. There is a significant need for models that enable studies of human cyst growth and drug trials. (2) Methods: Renal tissue from ADPKD patients who received a nephrectomy as well as adult mouse kidney slices were cultured on a chorioallantoic membrane (CAM) for one week. The cyst volume was monitored by microscopic and CT-based applications. The weight and angiogenesis were quantified. Morphometric and histological analyses were performed after the removal of the tissues from the CAM. (3) Results: The mouse and human renal tissue mostly remained vital for about one week on the CAM. The growth of cystic tissue was evaluated using microscopic and CT-based volume measurements, which correlated with weight and an increase in angiogenesis, and was accompanied by cyst cell proliferation. (4) Conclusions: The CAM model might bridge the gap between animal studies and clinical trials of human cyst growth, and provide a drug-testing platform for the inhibition of cyst enlargement. Real-time analyses of mouse kidney tissue may provide insights into renal physiology and reduce the need for animal experiments.
Background: Radiotherapy and chemoradiation are well-established therapies for patients with squa... more Background: Radiotherapy and chemoradiation are well-established therapies for patients with squamous cell carcinoma of the head and neck (SCCHN). In aging societies, also the incidence of SCCHN in elderly patients is rising. Because of the underrepresentation of elderly patients in scienti c trials, we evaluated the feasibility of adjuvant radiotherapy and chemoradiation in patients with SCCHN aged >70 years. Methods: All patients had been >70 years at the time of diagnosis and received adjuvant radiotherapy or, if feasible, chemoradiation at the University Medical Centre Regensburg between 2004 and 2018. 71 patients-most with SCCHN UICC stage IVa-with a median age of 75 years were included; 9 patients received concomitant chemoradiation. Median follow-up was 27 months (IQR 18-62 months). Results: Radiotherapy and chemoradiation was well tolerated. 62 patients (87.3%) underwent treatment without interruption, and 65 patients (91.5%) completed radiotherapy with 95% of the initially prescribed dose. Median dose for all patients was 64 Gy (IQR: 60-66 Gy). 6/9 patients received at least 75 % of the planned chemotherapy dose. 37 patients (52.1%) developed acute toxicity CTC grade III or IV. Overall survival was 87 % after 12 months, 67 % after 24 months and 41 % after 60 months. Median overall survival was 51 months (IQR: 19-99 months). Local tumour control was 99 % after 12 months, 88 % after 24 months and 76 % after 5 years. Conclusion: Feasibility of adjuvant radiotherapy and chemoradiation in our collective of elderly patients with SCCHN was good. Particularly local tumour control was satisfactory. Overall survival does not seem to differ between elderly and younger patients or patients unselected for age. De-intensi cation of treatment because of age does not seem justi ed. Background: Squamous cell carcinoma of the head and neck (SCCHN) is a common type of malignant tumours worldwide. In 2019, 53,000 cases of cancer of the oral cavity and pharynx and 12,410 cases of laryngeal cancer were projected for the United States (US), 3.7% of all new cancer cases in the US are SCCHN. (National Comprehensive Cancer Network 2019b) (Siegel et al. 2019). The worldwide proposed incidence of SCCHN for 2018 was 834,860 cases (4.6% of all newly diagnosed malignancies) (Bray et al. 2018).
Introduction Radiotherapy of pituitary adenomas is often applied as postoperative therapy of tumo... more Introduction Radiotherapy of pituitary adenomas is often applied as postoperative therapy of tumors that cannot be removed completely. Fluence modulating techniques like IMRT or VMAT support the use of the flatness filter free (FFF) mode in modern linear accelerators. In this mode a considerably higher dose rate is achieved by omitting the flatness filter. This planning study compares different plans for patients with pituitary adenoma. The plans were optimized using both modes: flattened beam (FB) and FFF. The aim of this study is to evaluate the plan quality. Material and Methods Data sets of 11 patients with pituitary adenoma were used for this retrospective planning study. The objectives for the PTV were set to a minimum dose of 49.4Gy and a maximum dose of 51.4Gy in 28 fractions, aiming for a fraction dose of 1.8Gy. Further objectives were set for the following regions of interest (ROI): brain, brainstem, chiasm, and both lenses, bulbs, lacrimal glands, and parotids. The planni...
; for the German Rectal Cancer Study Group IMPORTANCE Total neoadjuvant therapy has been increasi... more ; for the German Rectal Cancer Study Group IMPORTANCE Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. OBJECTIVE To report the long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population
Background: Following the PACIFIC trial, durvalumab has been approved by the European Medicines A... more Background: Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.2017 to 15.10.2018 allowing analysis of its efficacy and safety. Methods: Data from 56 centres were analysed for adverse events (AE), progression-free survival (PFS), overall survival (OS). Results: 126 patients actually received at least 1 cycle durvalumab. Compared to the PACIFIC trial, the EAP population had more advanced stage and included "oligometastatic" stage IV patients and patients with autoimmune disease. PFS (20.1 months) and OS (not reached) were similar in the EAP and the PACIFIC trial. 42.9 % completed 12 months of durvalumab without deaths during FU. Stage IV patients (n = 7) had encouraging OS (not reached at 27 months). Autoimmune disease did not affect survival. PFS and OS were similar in PD-L1negative patients (n = 32) and PD-L1-positive patients (n = 79). Conclusions: Survival in the EAP was comparable to the PACIFIC trial. Selected stage IV patients and patients with autoimmune disease may benefit from durvalumab consolidation and should be included in future immunooncological trials. PD-L1 did not predict survival challenging the exclusion of PD-L1-negative patients from durvalumab consolidation. In summary, durvalumab consolidation is safe and effective in a European real-world setting.
Background This planning study compares different radiotherapy techniques for patients with pitui... more Background This planning study compares different radiotherapy techniques for patients with pituitary adenoma, including flatness filter free mode (FFF), concerning plan quality and secondary malignancies for potentially young patients. The flatness filter has been described as main source of photon scatter. Material and methods Eleven patients with pituitary adenoma were included. An Elekta Synergy™ linac was used in the treatment planning system Oncentra® and for the measurements. 3D plans, IMRT, and VMAT plans and non-coplanar varieties were considered. The plan quality was evaluated regarding homogeneity, conformity, delivery time and dose to the organs at risk. The secondary malignancy risk was calculated from dose volume data and from measured dose to the periphery using different models for carcinoma and sarcoma risk. Results The homogeneity and conformity were nearly unchanged with and without flattening filter, neither was the delivery time found substantively different. VM...
Osteoarthritis is a common disease, with a prevalence of symptomatic disease of 8.9%. One treatme... more Osteoarthritis is a common disease, with a prevalence of symptomatic disease of 8.9%. One treatment option is radiotherapy. Most published samples were treated with an orthovoltage technique or with a telecobalt device. A lot of radiotherapy institutions are nowadays using linear accelerators for treatment of osteoarthritis. There is a discussion on whether the treatment results achieved with a linear accelerator are comparable to those with the orthovoltage technique. The aim of this study is to analyze the results of radiotherapy for osteoarthritis with a linear accelerator and compare the results with reference to different joints. The analysis was performed in patients of two German radiotherapy institutions and included 295 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 65 years, with 39.0% male and 61.0% female patients. Most frequently, osteoarthritis of the knee (34.6%) or the finger (15.9%) was treated. We could find a significant response to radiotherapy. Median pain for the whole sample was 7 on the NRS before radiotherapy, 4 after 6 weeks, and 3 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 33.8% 12 months after radiotherapy. All investigated subgroups had a significant reduction of pain. Radiotherapy of osteoarthritis with a linear accelerator is an effective treatment which is very well tolerated. All analyzed subgroups show a good response to radiotherapy for at least 24 months. Orthovoltage therapy seems to be superior to treatment with a linear accelerator in a case-related analysis of the published samples. Further investigations should be performed for a definitive answer to this question.
Purpose Osteoarthritis of the ankle and tarsal joints is less common than osteoarthritis of the k... more Purpose Osteoarthritis of the ankle and tarsal joints is less common than osteoarthritis of the knee or hip, but the associated disability is at least as severe as that of the other major joints of the lower limb. The results for total arthroplasty are still not satisfactory. For this reason, arthrodesis is still the gold standard of non-joint-conserving surgery. For the reason of functionality, joint-conserving therapies play a major role in treatment of ankle and tarsal osteoarthritis. Low-dose radiotherapy has a long history of treatment of osteoarthritis. The aim of this survey was to examine the results of low-dose radiotherapy for osteoarthritis of the ankle and tarsal joints. Materials and methods The analysis was performed on patients of three German radiotherapy institutions and included 66 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 68 years, with 24.5% male and 75.5% female patients. The upper ankle was treated in 37.9%, the lower ankle in 27.3% and the tarsal joints in 34.8%. Results We could find a significant response to radiotherapy. For the whole sample, the median pain was 7 on the NRS before radiotherapy, 5 after 6 and 12 weeks, and 4 after 12 months. The percentage of patients with 0 or 1 on the NRS was 19.6% 12 months after radiotherapy. An improvement of joint mobility could be detected in 56.7% of the cases. All investigated subgroups had a significant reduction in pain. Conclusion Radiotherapy of ankle and tarsal osteoarthritis is an effective treatment without showing side effects. All analysed subgroups show a good response to radiotherapy for at least 24 months.
Ionizing radiation is able to cause severe damage to cardiac implantable electronic devices (CIED... more Ionizing radiation is able to cause severe damage to cardiac implantable electronic devices (CIED). In Germany, the DEGRO/DGK guideline recommends close monitoring of patients with CIEDs undergoing radiotherapy (RT). Nevertheless, especially in the era of intensity-modulated techniques and predominant use of 6 MV photons, errors of CIEDs are rare events. Therefore, we performed daily CIED controls and hypothesized that no relevant device interaction would occur in our cohort. From 2014 to 2018, we collected data of 51 patients (62 courses) with daily interrogation (n = 1046) of CIED. The dose to the skin above the CIED was measured by semiconductor or ion chamber dosimetry at least once per RT course. In many cases the dose was also calculated. The prescribed dose to the planning target volume (PTV) ranged from 7.5 to 78.0 Gy (IQR 27.8–61.0 Gy). The median measured cumulative dose to the skin above the CIED was 0.17 Gy, whereas the median calculated dose was 1.03 Gy. No error occurred in the group with maximum beam energy >10 MeV. Three events without clinical relevance could be recognized in the group with an intensity-modulated technique at 6 MV. None of the three concerned devices were located directly within the PTV. Errors of CIEDs during RT are rare events. The approach according to the DEGRO/DGK guideline is safe, but also consumes resources. In our cohort it was not compulsory to relocate any CIED. Clinically relevant events are uncommon, so it remains debatable which procedure is necessary. Daily controls could be avoided in some selected cases without compromising patient safety.
Purpose Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the aver... more Purpose Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the average population. One treatment option is low-dose radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of re-irradiation have not been analysed systematically, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. Methods and materials The analysis was performed on patients of three German radiotherapy institutions and included 217 re-irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as at the follow-up of 24 months. The median age of the patients was 67 years, with 40% male and 60% female patients. Re-irradiation was indicated because the initial radiotherapy resulted in no response in 21.2%, in partial response in 41.5%, and in recurrent pain in 37.3%. Results We found a significant response to re-irradiation. For the whole sample, the median pain was 6 before re-irradiation, 4 after 6 weeks, and 3 after 12 weeks, 6 months, 12 months, and 24 months. The percentage of patients being free of pain or with very little pain was approximately 25% 12 months after re-irradiation. All subgroups, notably those with no response to the first course versus partial response to the first course versus recurrent pain, had significant reduction of pain. Conclusion Re-irradiation of osteoarthritis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.
Background Humeral epicondylitis is a common elbow disease. The prevalence is about 1.7%. One of ... more Background Humeral epicondylitis is a common elbow disease. The prevalence is about 1.7%. One of the most effective treatment options is radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of a re-irradiation have not been systematically analyzed, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. Material and methods The analysis was performed on patients from three German radiotherapy institutions and included 99 re-irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as for the follow-up of 24 months. The median age of the patients was 51 years with 48.8% male and 51.2% female patients. Repeated radiation was indicated because the initial radiotherapy resulted in 39.7% of no response, in 41.0% of partial response and in 19.3% of recurrent pain. Results A significant response to re-irradiation was found. For the whole sample the median pain score was 6 before re-irradiation, 3 after 6 weeks, 2 after 12 months and 1 after 24 months. The percentage of patients being free of pain or with very little pain was 50.9% 24 months after re-irradiation. All subgroups, notably those with no response, partial response and recurrent pain had a significant reduction of pain. Conclusion Re-irradiation of humeral epicondylitis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months. Hintergrund Die Epicondylitis humeri ist eine der häufigsten Erkrankungen des Ellenbogens. Die Prävalenz liegt bei etwa 1,7 %. Eine der wirkungsvollsten Therapieoptionen stellt die Strahlentherapie dar. Dabei beschreiben viele Autoren die Durchführung einer oder mehrerer weiterer Bestrahlungsserien bei rezidivierten Schmerzen bzw. unzureichendem oder keinem Ansprechen auf die initiale Bestrahlungsserie. Da eine strukturierte Auswertung der Rebestrahlung bisher nicht existiert, war das Ziel dieser Arbeit, die Ergebnisse einer wiederholten Strahlenbehandlung zu dokumentieren und Patienten zu identifizieren, die von einer Rebestrahlung profitieren. Material und Methode Ausgewertet wurden Patienten aus drei strahlentherapeutischen Institutionen. Insgesamt konnten 99 rebestrahlte Ellenbogen analysiert werden. Die Schmerzintensität wurde mit Hilfe der numerischen Ratingskala (NRS) quantifiziert und zu den Zeitpunkten vor Bestrahlungsbeginn, direkt nach Radiatio, 6 und 12 Wochen sowie 6, 12 und 24 Monate nach Bestrahlung erfasst. Von den Patienten waren 48,8% männlich und 51,2% weiblich, bei einem medianen Alter von 51 Jahren. Grund der Rebestrahlung war in 39,7% kein Ansprechen und in 41,0% ein unzureichendes Ansprechen auf die erste Bestrahlungsserie sowie in 19,3% rezidivierte Schmerzen. Ergebnisse Es zeigte sich für das Gesamtkollektiv eine signifikante Schmerzreduktion. Die mediane Schmerzintensität war 6 vor der Rebestrahlung, 3 nach 6 Wochen und 2 bzw. 1 nach 12 und 24 Monaten. Nach 24 Monaten waren 50,9% der Patienten schmerzfrei oder nahezu schmerzfrei. Alle Subgruppen, insbesondere Patienten ohne und Patienten mit unzureichendem Ansprechen auf die initiale Bestrahlung bzw. Patienten mit rezidivierten Schmerzen verzeichneten eine signifikante Schmerzreduktion. Schlussfolgerung Zusammenfassend zeigt diese Arbeit, dass die Rebestrahlung bei der Epicondylitis humeri eine effektive und sichere Therapie darstellt. Alle Patientengruppen profitieren über mindestens 24 Monate von der Rebestrahlung.
Purpose Osteoarthritis of the knee is a common disease, often associated with a Baker's cyst. Bes... more Purpose Osteoarthritis of the knee is a common disease, often associated with a Baker's cyst. Besides osteoarthritis, also other joint pathologies of the knee can be causative for a Baker's cyst. Radiotherapy is known to be an effective treatment for osteoarthritis, with an anti-inflammatory effect. As the excessive production of synovia usually is associated with intraarticular inflammation, our hypothesis was that radiotherapy might positively influence the synovial production and reduce the volume of a Baker's cyst. Materials and methods We performed a prospective trial, including 20 knees receiving radiotherapy for knee arthritis. Besides documentation of NRS (numeric rating scale), WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and Knee Society Score, the volume of the Baker's cyst was calculated for a short-(6 to 12 weeks) and long-term (9 to 12 months) follow-up. Ultrasonic volumetry was performed using an ultrasound device with a high-resolution multifrequency linear probe (6-9 MHz). Results Low-dose radiotherapy improved NRS, WOMAC score and Knee Society Score significantly. The mean volume of Baker's cyst decreased from 22.3 ml to 10.7 respectively 3.1 ml during follow-up. A decrease in volume of more than 25% compared to the baseline could be achieved for 75% of the patients in the short-term and 79% of the patients in the long-term follow up. Conclusion Radiotherapy of knee osteoarthritis is an effective treatment that decreases the volume of a Baker's cyst. Most patients respond to the treatment. Whether radiotherapy is an effective treatment for Baker's cyst without associated osteoarthritis has to be further examined.
BackgroundEpicondylitis humeri is a common disease with a prevalence of 1.7%. One of the treatmen... more BackgroundEpicondylitis humeri is a common disease with a prevalence of 1.7%. One of the treatment options is radiotherapy. Most published cases were treated with the orthovoltage technique or with a telecobalt device. Many radiotherapy institutions are nowadays using linear accelerators for treatment of epicondylitis humeri. There is a discussion whether the treatment results with linear accelerators are comparable to the orthovoltage technique. The aim of this study was to analyze the results of radiotherapy with a linear accelerator for epicondylitis humeri.Material and methodsThe analysis was performed on patients of 2 German radiotherapy institutions and included 138 irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 49 years with 48.4% male and 51.6% female. In all, 81.0% were suffering from from epicondylitis humeri radialis while 16.7% were treated because of epicondylitis humeri ulnaris. In 65.4% the dominant arm was treated.ResultsA significant response to radiotherapy could be found. For the whole sample the median pain was 7 on the NRS before radiotherapy, 4 after 6 weeks and 0 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 64.6% 12 months after radiotherapy. All subgroups, notably those with epicondylitis humeri radialis and epicondylitis humeri ulnaris had a significant reduction of pain.ConclusionRadiotherapy of epicondylitis humeri with a linear accelerator is an effective treatment without showing side effects. All analyzed subgroups showed a good response to radiotherapy for at least 24 months.ZusammenfassungHintergrundDie Epicondylitis humeri ist eine der häufigsten degenerativen Erkrankungen. Die Prävalenz liegt bei etwa 1,7 %. Eine etablierte Therapieoption stellt die Strahlentherapie dar. Viele der publizierten Kollektive wurden mittels Orthovolttherapie behandelt oder an Telekobaltgeräten bestrahlt. Zahlreiche strahlentherapeutische Institutionen therapieren die Epicondylitis humeri mittlerweile mit Linearbeschleunigern. Es wird diskutiert, ob die Therapie am Linearbeschleuniger genauso effektiv ist wie die Orthovolttherapie. Ziel dieser Arbeit war die strukturierte Auswertung der Bestrahlung mittels Linearbeschleuniger bei Epicondylitis humeri.Material und MethodeAusgewertet wurden Patienten aus zwei strahlentherapeutischen Institutionen. Es konnten 138 bestrahlte Ellenbogen analysiert werden. Die Schmerzintensität wurde mithilfe der numerischen Rating-Skala (NRS) quantifiziert und vor Bestrahlungsbeginn, direkt nach Radiatio sowie über einen Follow-up-Zeitraum von 24 Monate nach Bestrahlung erfasst. Ein Anteil von 48,4 % der Patienten war männlich, 51,6 % waren weiblich. Das mediane Alter betrug 49 Jahre. 81,0 % der Patienten litten an einer radialen Epikondylitis, bei 16,7 % wurde eine mediale Epikondylitis behandelt. Bei 65,4 % der Patienten wurde der dominante Arm bestrahlt.ErgebnisseEs zeigte sich für das Gesamtkollektiv eine signifikante Schmerzreduktion. Die mediane Schmerzintensität auf der NRS war 7 vor der Bestrahlung, 4 nach 6 Wochen und 0 nach 12 und 24 Monaten. Ein Anteil von 64,6 % der Patienten waren 12 Monate nach Bestrahlung schmerzfrei oder nahezu schmerzfrei (NRS 0 oder 1). Alle Subgruppen, sowohl mit Epicondylitis humeri radialis als auch mit Epicondylitis humeri ulnaris, hatten eine signifikante Schmerzreduktion.SchlussfolgerungDie Bestrahlung mit Linearbeschleuniger ist bei Epicondylitis humeri eine effektive und sichere Therapie. Alle analysierten Patientengruppen profitierten für mindestens 24 Monate von der Therapie.
Background: 5-Fluorouracil (5-FU) is an antimetabolite, which is frequently used as chemotherapeu... more Background: 5-Fluorouracil (5-FU) is an antimetabolite, which is frequently used as chemotherapeutic agent for combined chemoradiotherapy. The purpose of this study was to present the clinical course of three patients who developed severe cardiac toxicity by 5-FU and to give a review of the literature on the cardiotoxic potential of 5-FU. Results: Cardiotoxicity is a rare, but relevant side effect of fluoropyrimidines. It comprehends a wide spectrum of side effects, from electrocardiogram changes (69% of cardiac events) to myocardial infarction (22%) and cardiogenic shock (1%). In this case series three patients with cardiotoxic events during chemoradiotherapy including 5-FU, the reaction's characteristics and their influence on further therapy are described. Two of the patients could not be treated with 5-FU any more because they had developed a myocardial ischemia, which was most likely caused by fluorouracil. Another patient, who complained about typical angina pectoris during 5-FU-infusion and had a new left anterior hemiblock, was reexposed with prophylactic administration of nitrendipine. Conclusion: Cardiotoxicity caused by 5-FU is an underestimated problem in radiooncology. Especially patients without history of cardiac disease are often treated as outpatients and therefore without cardiac monitoring. Consequently asymptomatic and symptomatic cardiac events may be overlooked. The benefit of prophylactic agents remains unclear, so close cardiac monitoring is the most established method to prevent manifest cardiotoxic events.
Uploads
Papers by Felix Steger