The aim of this review is to give an overview of the results of prospective and retrospective studies using allogenic reconstruction and postmastectomy radiotherapy (PMRT) in breast cancer and to make recommendations regarding this interdisciplinary approach. A PubMed search was conducted to extract relevant articles from 2000 to 2024. The search was performed using the following terms: (breast cancer) AND (reconstruction OR implant OR expander) AND (radiotherapy OR radiation). Data from the literature on allogenic breast reconstruction and radiation are presented and discussed in relation to toxicity and cosmesis. Breast reconstruction is also feasible if PMRT is necessary. Patients need to be informed about the relevant risk of capsular fibrosis and implant failure. A planned reconstruction is no reason to forgo PMRT nor is an indication for PMRT a reason to forego implant-based breast reconstruction if desired by the patient. It is important to provide detailed information here to enable shared decision-making. There is still no clear consensus regarding implant-based reconstruction (IBR) and PMRT. However, in clinical practice, both a one-stage (immediate “implant-direct” IBR) procedure with PMRT up to the final implant and a two-stage (immediate-delayed IBR) procedure with PMRT up to the tissue expander (TE) and later exchange of the TE are used; both approaches have their specific advantages and disadvantages. Depending on patient-specific factors and the surgeon’s experience and estimates, both IBR procedures are also possible in combination with PMRT. When using a TE/implant approach, completing skin stretching by adequately filling the expander before PMRT may be favorable. This approach is particularly practical when adjuvant chemotherapy is planned but may lead to postponement of radiotherapy when primary systemic therapy is given. According to the latest data, moderate hypofractionation also appears to be safe in the context of the IBR approach. It is important to have a closely coordinated interdisciplinary approach and to fully inform patients about the increased rate of potential side effects.

Purpose/Objective(s) Medulloblastoma is the most common malignant pediatric brain tumor, necessitating normofractionated craniospinal irradiation (CSI) with an additional boost over about 6 weeks in children older than 3 years. This study investigates the sensitivity of pediatric medulloblastoma cell lines to different radiation fractionation schedules. While extensively studied in adult tumors, these ratios remain unknown in pediatric cases due to the rarity of the disease. Materials/Methods Five distinct medulloblastoma cell lines (ONS76, UW228-3, DAOY, D283, D425) were exposed to varying radiation doses and fractionation schemes. In addition, ONS76 and UW2283-3 stably overexpressing c-Myc were analyzed. Alpha/beta values, representing fractionation sensitivity, were quantified using the linear-quadratic model of radiation survival. Results The study unveiled elevated alpha/beta ratios across diverse medulloblastoma cell lines, with a mean alpha/beta value of 25.01 (ranging from 8.42 Gy to 75.09 Gy). Neither TP53 status nor the levels of MYC expression influenced fractionated radiosensitivity. Furthermore, no significant differences in alpha/beta values were observed among various medulloblastoma subgroups. Conclusion These in vitro findings strongly recommend normofractionated or hyperfractionated radiotherapy for pediatric medulloblastoma cases due to consistently high Alpha/Beta values across subgroups. Conversely, hypofractionated radiotherapy is not advisable. This study highlights the potential for personalized dosage prescriptions, improving patient prognosis and safety.

Purpose/Objective(s) Heel spurs, a common cause of foot pain, pose a challenge in orthopedic management. Traditional treatments often involve physical therapy, orthotics, and medications, with varying degrees of success. This study explores low-dose radiotherapy as a potential treatment option, hypothesizing its efficacy and safety in alleviating heel spur symptoms. Materials/Methods The study retrospectively analyzed 100 patients (27 men and 73 women) with an average age of 70.7 years (range = 37-101 years) who underwent low-dose radiotherapy for heel spurs, receiving a total dose of 3 Gy. Parameters assessed included pain levels, mobility, activity limitations, NSAID usage, and skin changes over a 20-year follow-up period. Results More than 70% of patients reported significant symptom improvement post-treatment. There was minimal reliance on NSAIDs, and no skin changes or tumor induction were observed within the treatment area. Notably, no significant radiogenic side effects were reported, highlighting the treatment's safety profile. While some patients experienced slight impairments in mobility and daily activities, most maintained a normal gait. Conclusion Low-dose radiotherapy represents a safe and effective treatment modality for heel spurs, evidenced by high success rates and the absence of adverse effects. These findings suggest that low-dose radiotherapy could be a promising addition to orthopedic practice, emphasizing the need for further research on long-term outcomes and the development of optimized treatment protocols.

ZusammenfassungBei der Behandlung von lokalen bzw. lokoregionären Rezidiven, Zweitkarzinomen oder Residuen von Plattenepithelkarzinomen der Kopf-Hals-Region nach einer Primärtherapie ergeben sich unterschiedliche Ausgangsituationen. Bei der Mehrzahl der Patienten mit lokoregionären Rezidiven ist eine Vorbehandlung bestehend aus Operation und/oder postoperativer Radio- bzw. Radiochemotherapie oder eine primäre Radio- bzw. Radiochemotherapie erfolgt. In jedem Fall handelt es sich um ein erneutes Tumorwachstum in vorbehandeltem Gebiet, das in besonderer Weise für die Therapieentscheidung berücksichtigt werden muss. Die biologischen Hintergründe sind vielfältig und werden in der vorliegenden Arbeit näher beschrieben und klinisch eingeordnet.

There are different initial situations in the treatment of local or locoregional recurrences, secondary carcinomas or residual squamous cell carcinomas of the head and neck region after primary therapy. The majority of patients with locoregional recurrences have had prior treatment consisting of surgery and/or postoperative radiotherapy or radiochemotherapy or primary radiotherapy or radiochemotherapy. In any case, it is a matter of new tumor growth in a previously treated area, which must be taken into account for the therapy decision. The biological backgrounds are diverse and are described in more detail and clinically classified in the present work.

PD-1-inhibitors were found effective in large clinical trials in first- and second-line therapy of recurrent and/or metastatic head and neck squamous cell carcinoma (rmHNSCC). Despite relative low objective response rates (ORR), overall survival (OS) improved significantly. It is generally assumed, that an improvement of the ORR will directly result in a further improvement of OS. Radiotherapy (RT) not only kills tumor cells, but also changes the tumor cell phenotype and the tumor microenvironment, which might result in induction of anti-tumor immune responses. In preclinical experiments the combination of RT and PD-1/PD-L1 pathway blockade improved local tumor control, and also induced systemic tumor immunity. Consequently, metastases distant from the irradiated tumor responded after RT and the survival rate of the animals improved. Thus, local RT, acting as in situ vaccination, is probably able to improve the ORR to pembrolizumab (P) in rmHNSCC. IMPORTANCE (NCT03386357) is an open-label, randomized, prospective, multicenter phase II clinical trial of P with or without local RT in patients (pts) with rmHNSCC after progression to platinum-based therapy or as first line treatment if CPS≥1. All pts will receive P 200 mg administered every third week until confirmed disease progression according to iRECIST criteria, unacceptable toxicity, pts’ wish to stop therapy or a maximal treatment time of 12 months. Pts in treatment arm A will receive RT of one, two or three tumor lesions with a total tumor volume of at least 2 ml (if possible, ≥5 ml) intended to induce immunogenic tumor cell death. RT will be performed conventionally with single doses of 3 Gy to a total dose of 36 Gy. Pts in arm B will only receive P. The objectives are to show that addition of local RT of 1-3 lesions to P improves the ORR, duration of response, progression free survival and OS. Further objective is the assessment of distinct immune changes, safety and tolerability of the combination of P and RT. Recruitment started in July 2018 and is ongoing. Until March 2023, 100 pts were randomized. The planned sample size is 130 patients, the recruitment is estimated to be completed by January 2024. NCT03386357, released: 29.12.2017. Dean of the Medical Faculty of the Friedrich-Alexander University Erlangen-Nürnberg. MSD Merck Sharp & Dohme.

Purpose/Objective(s) After vascular reconstructions in the groin area, a persistent lymph fistula regularly threatens the prognosis of the affected extremity. Rapid, effective treatment of the lymph fistula is therefore essential in order to be able to prevent amputation. As part of a pilot study, we wanted to analyze the chances and limitations of radiotherapy in the treatment of lymphatic fistulas. Materials/Methods As part of an internal quality control, patients were identified for this study who acquired a lymph fistula in the groin as a result of vascular surgery due to peripheral artery disease stage IV and were irradiated at the University Hospital Düsseldorf. Results Eight men aged 66 + 12, 4 years underwent vascular surgery for PAD stage IV. Surgery was performed in these patients via the groin and all men subsequently had a persistent lymphatic fistula with a secretion greater than 50 ml/day. Five patients were irradiated with a fractionation of 10 × 0.4 Gy and 3 patients with a fractionation of 10 × 0.3 Gy. In all patients, the lymphatic fistula dried up within the irradiation series. No higher-grade complications occurred. Conclusion Irradiation of the groin in the case of a persistent lymphatic fistula could be a therapeutic option to avoid amputations due to wound infections after vascular reconstruction in the groin. Prospective randomized studies would be desirable in order to be able to better evaluate the role of radiotherapy in the treatment of lymphatic fistulas.

Zielsetzung Die neoadjuvante Chemotherapie ermöglicht eine engmaschige Überwachung des Tumoransprechens bei Patientinnen mit Mammakarzinom. Dies bietet die Möglichkeit, neue therapeutische Strategien zu evaluieren und die adjuvante Therapie entsprechend dem Ansprechen der initialen Therapie zu eskalieren oder zu de-eskalieren.

An increasing number of stage III non-small-cell lung cancer (NSCLC) patients experience long-term survival (LTS). New treatment principles of checkpoint inhibitor (CPI)-immunotherapy have specific impact on LTS in all LC stages. Therefore, we need to reassess randomized phase-III trial datasets looking at optimum local treatment. We have already reported randomized phase-III ESPATUE-trial results looking at definitive surgery versus definitive boost-radiochemotherapy following complex induction (Eberhardt et al, J Clin Oncol 2015). Here, we update 5- and 10-yrs-LTS-data and report competing risk of deaths for the different Tx-strategies.

Post-surgery chemoradiation (pCRT) is standard in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), although there is still a need to improve the outcome. We performed an open-label, single-arm, multicenter trial (EudraCT No. 2007-002659-17) and investigated safety and efficacy of escalating the multimodal therapy by adding concomitant and maintenance cetuximab (CTX). Patients with surgically resected LA-SCCHN with margins <5mm and/or extracapsular nodal extension (ECE) received adjuvant therapy in nine German sites from Aug 2008 to Jan 2012. Intensity modulated radiation therapy (RT) in three dose levels (61.6/56/50.4 Gy in 28 fractions) was administered. Cisplatin (20 mg/m2) and 5-flurorouracil (600 mg/m2) were given on days 1-5 and 29-33 of RT. CTX was started seven days prior to RT at 400 mg/m2 followed by weekly doses of 250 mg/m2. Maintenance CTX was administered biweekly at 500 mg/m2 for six months. Primary endpoints were serious acute toxicity rate and 2-years disease free survival (DFS). Secondary objectives included incidence of loco-regional relapse (LRR), progression-free survival (PFS), overall survival (OS), and late toxicity. Data was investigated with descriptive statistics and survival analyses using the Kaplan-Meier method. Five of 83 enrolled patients did not meet inclusion criteria leaving 78 for analysis. 66% had oropharyngeal, 8% laryngeal and 26% oral cavity tumor. ECE was present in 63% of the cases, close margin or R1 resection represented with 22% and 54%, respectively. Median age was 56 years (range: 29-70). 81% were male. Mean Charlson Comorbidity Index was 3.7 (range: 2-7). 34% had a smoking history of <10 packyears. Median follow-up was 26.1 months. 2-years DFS was 72.2% (95% CI: 62.2%-83.6%). Probability of LRR was 15% (95% CI: 5-24%) in two years. 1-year OS was 90.3% (95% CI: 79.4-95.4%), 2-years OS was 87.0% (95% CI: 83.7-97.4%). The cumulative rate of severe late toxicity was 53.8%. According to our results, pCRT+CTX followed by a six-months maintenance CTX resulted in a favorable outcome by a relative high toxicity burden.

A. Dietz · A. Rau · J. Hoffmann · B. Wollenberg · J. P. Klussmann · H. Christiansen · W. Budach · V. Grünwald · S. Ochsenreither 1 HNO-Universitätsklinik Leipzig, Leipzig, Deutschland 2 Klinik für MKG-Chirurgie, Universitätsmedizin Greifswald, Greifswald, Deutschland 3 Klinik für MKG-Chirurgie, UniversitätsklinikumHeidelberg, Heidelberg, Deutschland HNO-Klinik, Klinikum rechts der Isar, TU München, München, Deutschland HNO-Uniklinik Köln, Köln, Deutschland 6 Klinik für Radioonkologie, MHH Hannover, Hannover, Deutschland 7 Klinik für Radioonkologie, Universität Düsseldorf, Düsseldorf, Deutschland Uroonkologisches Zentrum, Urologische Universitätsklinik, Essen, Deutschland 9 Klinik für Hämatologie und Onkologie CBF, Charité Berlin, Berlin, Deutschland

6007 Background: Inhibition of the PD-1/PD-L1 pathway is efficient in recurrent/metastatic HNSCC. Targeting the immune checkpoint CTLA-4 may be synergistic to radiotherapy. This trial studies feasibility and efficacy of combined PD-L1/CTLA-4 blockade concomitant to induction chemotherapy and radiotherapy. Methods: Patients with previously untreated stage III-IVB (AJCC 8th edition) HNSCC were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30mg/m² d1-3, docetaxel 75mg/m² d1, durvalumab 1500mg fix dose d5 and tremelimumab 75mg fix dose d5. Patients with at least 20% increase of intratumoral CD8+ immune cell density or pathological complete response (pCR) in the re-biopsy (performed on d22-26) entered radio-immunotherapy (RIT) up to a total dose of 70Gy. Patients received further three cycles of durvalumab/tremelimumab (q4w, two concomitant and one subsequent) followed by eight cycles of durvalumab mono (q4w). Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80% (i.e. dose limiting toxicity/DLT ≤20%; exclusion of patients with other reasons than DLT for treatment discontinuation; feasibility unacceptable if ≤65%). The calculated sample size was 57 patients to enter RIT. Main secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Between Sep 2018 and Mai 2020, 80 patients were enrolled (one excluded). Median age was 60 years, 33 patients (42%) were current smokers, 43 patients (54%) had oropharyngeal tumors (53% p16 positive), 44 patients (56%) were stage IV. Median follow up was 12.5 months. After induction chemo-immunotherapy 41 patients had pCR and 31 an intratumoral CD8+ immune cell increase. Of 60 patients entering RIT (primary endpoint cohort), 10 received DLT and 4 discontinued for other reasons. The feasibility rate of the RIT cohort until cycle 6 was 82%, meeting the primary endpoint of ≥80% (95% confidence interval (CI), one-sided (lower boundary): 72%). The RIT cohort had a PFS rate at 1 year of 79% (CI 69-90%) and at 2 years of 73% (CI 61-87%) and an OS rate at 1 year of 89% (CI 81-98%) and at 2 years of 86% (CI 77-97%). The entire study cohort had a PFS rate at 1 year of 75% (CI 65-85%) and at 2 years of 68% (CI 58-81%) and an OS rate at 1 year of 86% (CI 78-95%) and at 2 years of 80% (CI 70-91%). Toxicity (treatment-related or un-related) ≥grade 3 appeared in 75 patients (95%) and mainly consisted of dysphagia (53%), leucopenia (48%) and infections (29%). DLT mainly consisted of hepatitis (10%). Conclusions: The trial met the primary endpoint feasibility. CD8+ T cell-based pathological patient selection after induction therapy identifies patients with promising PFS rates after chemotherapy-free RIT. Clinical trial information: nct03426657.

Einleitung Das Ziel dieser Studie ist die Evaluation der Durchführbarkeit und Effektivität der Radioimmuntherapie mit Doppel-Checkpoint-Inhibition nach Induktions-Immunchemotherapie bei fortgeschrittenen Kopf-Hals-Karzinomen. Patienten und Methoden: In dieser offenen Phase II-Studie erhielten Patienten mit Stadium III – IVB einen Induktionszyklus einer Chemo-Immuntherapie mit Cisplatin/Docetaxel plus Durvalumab / Tremelimumab gefolgt von einer Radioimmuntherapie. Ein Anstieg der CD8-Zellen im Tumor- und peritumoralen Gewebe diente als Selektionskriterium für die Radioimmuntherapie und wurde an Biopsien vor und nach der Induktionstherapie bestimmt.

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.