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Purpose 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is utilized for staging and treatment planning of head and neck squamous cell carcinomas (HNSCC). Some older publications on the prognostic relevance showed inconclusive results, most probably due to small study sizes. This study evaluates the prognostic and potentially predictive value of FDG-PET in a large multi-center analysis. Methods Original analysis of individual FDG-PET and patient data from 16 international centers (8 institutional datasets, 8 public repositories) with 1104 patients. All patients received curative intent radiotherapy/chemoradiation (CRT) and pre-treatment FDG-PET imaging. Primary tumors were semi-automatically delineated for calculation of SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Cox regression analyses were performed for event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Results FDG-PET parameters were associated with patient outcome in the whole cohort regarding clinical endpoints (EFS, OS, LRC, FFDM), in uni- and multivariate Cox regression analyses. Several previously published cut-off values were successfully validated. Subgroup analyses identified tumor- and human papillomavirus (HPV) specific parameters. In HPV positive oropharynx cancer (OPC) SUVmax was well suited to identify patients with excellent LRC for organ preservation. Patients with SUVmax of 14 or less were unlikely to develop loco-regional recurrence after definitive CRT. In contrast FDG PET parameters deliver only limited prognostic information in laryngeal cancer. Conclusion FDG-PET parameters bear considerable prognostic value in HNSCC and potential predictive value in subgroups of patients, especially regarding treatment de-intensification and organ-preservation. The potential predictive value needs further validation in appropriate control groups. Further research on advanced imaging approaches including radiomics or artificial intelligence methods should implement the identified cut-off values as benchmark routine imaging parameters.

(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco–regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco–regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy.

Background and purpose: Prognosis after chemoradiotherapy (CRT) for anal squamous cell carcinoma (ASCC) shows marked differences among patients according to TNM subgroups, however individualized risk assessment tools to better stratify patients for treatment (de-) escalation or intensified follow-up are lacking in ASCC. Materials and methods: Patients’ data from eight sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG), comprising a total of 605 patients with ASCC, treated with standard defini- tive CRT with 5-FU/Mitomycin C or Capecitabine/Mitomycin C between 2004–2018, were used to evalu- ate prognostic factors based on Cox regression models for disease-free survival (DFS). Evaluated variables included age, gender, Karnofsky performance score (KPS), HIV-status, T-category, lymph node status and laboratory parameters. Multivariate cox models were separately constructed for the whole cohort and the subset of patients with early-stage (cT1-2 N0M0) tumors. Results: After a median follow-up of 46 months, 3-year DFS for patients with early-stage ASCC was 84.9%, and 67.1% for patients with locally-advanced disease (HR 2.4, p < 0.001). T-category (HR vs. T1: T2 2.02; T3 2.11; T4 3.03), N-category (HR versus N0: 1.8 for N1-3), age (HR 1.02 per year), and KPS (HR 0.8 per step) were significant predictors for DFS in multivariate analysis in the entire cohort. The model per- formed with a C-index of 0.68. In cT1-2N0 patients, T-category (HR 2.14), HIV status (HR 2.57), age (1.026 per year), KPS (HR 0.7 per step) and elevated platelets (HR 1.3 per 100/nl) were associated with worse DFS (C-index of 0.7). Conclusion: Classical clinicopathologic parameters like T-category, N-category, age and KPS remain to be significant prognostic factors for DFS in patients treated with contemporary CRT for ASCC. HIV and plate- lets were significantly associated with worse DFS in patients with early stage ASCC.

Biomarkers with relevance for loco-regional therapy are needed in human papillomavirus negative aka HPV(-) head and neck squamous cell carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome-based classifier identifying HPV(-) HNSCC patients at risk for loco-regional recurrence (LR) and all-event progression after postoperative radiochemotherapy (PORT-C). The training cohort consisted of HPV-DNA negative HNSCC patients (n = 128) homogeneously treated with PORT-C in frame of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) multicenter biomarker trial. DNA Methylation analysis was performed using Illumina 450 K and 850 K-EPIC microarray technology. The performance of the classifier was integrated with a series of biomarkers studied in the training set namely hypoxia-, 5-microRNA (5-miR), stem-cell gene-expression signatures and immunohistochemistry (IHC)-based immunological characterization of tumors (CD3/CD8/PD-L1/PD1). Validation occurred in an independent cohort of HPV(-) HNSCC patients, pooled from two German centers (n = 125). We identified a 38-methylation probe-based HPV(-) Independent Classifier of disease Recurrence (HICR) with high prognostic value for LR, distant metastasis and overall survival (P < 10-9 ). HICR remained significant after multivariate analysis adjusting for anatomical site, lymph node extracapsular extension (ECE) and size (T-stage). HICR high-risk tumors were enriched for younger patients with hypoxic tumors (15-gene signature) and elevated 5-miR score. After adjustment for hypoxia and 5-miR covariates, HICR maintained predicting all endpoints. HICR provides a novel mean for assessing the risk of LR in HPV(-) HNSCC patients treated with PORT-C and opens a new opportunity for biomarker-assisted stratification and therapy adaptation in these patients.

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.

Correction to: Strahlenther Onkol 2021 https://doi.org/10.1007/s00066-021-01812-2

Objective: Treatment of symptomatic trigeminal neuralgia (TN) in patients with neurological co-morbidites, e.g., multiple sclerosis remains challenging. Single-fraction Cyberknife radiosurgery (CK) and retrogasserian thermocoagulation (TC) are possible therapeutic options. We aimed to compare treatment[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Purpose: The aim of this study was to identify and validate a gene signature combining machine learning approaches and biological information in order to predict loco-regional control (LRC) in patients with HPV-negative, locally advanced HNSCC who received postoperative radio(chemo)therapy (PORT(-C)). Materials and methods: Gene expression analysis was performed using the GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective training cohort of 128 patients and an independent validation cohort of 114 patients of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) treated with PORT(-C) (figure A). Genes were filtered based on differential gene expression analysis and Cox regression. The identified gene signature was combined with clinical features and with previously identified genes related to cancer stem cells [1-2] and hypoxia [3]. Model performance was evaluated by the concordance index (ci) and Kaplan-Meier analyses. Results: We identified a 6-gene signature consisting of four individual genes CAV1, GPX8, IGLV3-25, TGFBI and one metagene combining the highly correlated genes INHBA and SERPINE1. A multivariable Cox model combining the 6-gene classifier and clinical parameters was fit to the training data (ci=0.81) and was successfully validated (ci=0.66). It stratified patients into two risk groups that significantly differed in the primary endpoint LRC in training (p

Spine metastases affect more than 70% of terminal cancer patients that eventually suffer from severe pain and neurological symptoms. Nevertheless, in the overwhelming majority of the cases, a spinal metastasis represents just one location of a diffuse systemic disease. Therefore, the best practice for treatment of spinal metastases depends on many different aspects of an oncological disease, including the assessment of neurological status, pain, location, and dissemination of the disease as well as the ability to predict the risk of disease progression with neurological worsening, benefits and risks associated to treatment and, eventually, expected survival. To address this need for a framework and algorithm that takes all aspects of care into consideration, we reviewed available evidence on the multidisciplinary management of spinal metastases. According to the latest evidence, the use of stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) for spinal metastatic disease is rapidly increasing. Indeed, aggressive surgical resection may provide the best results in terms of local control, but carries a significant rate of post-surgical morbidity whose incidence and severity appears to be correlated to the extent of resection. The multidisciplinary management represents, according to current evidence, the best option for the treatment of spinal metastases. Noteworthy, according to the recent literature evidence, cases that once required radical surgical resection followed by low-dose conventional radiotherapy, can now be more effectively treated by minimally invasive spinal surgery (MISS) followed by spine SRS with decreased morbidity, improved local control, and more durable pain control. This combination allows also extending this standard of care to patients that would be too sick for an aggressive surgical treatment.

This article compares the expression and applicability of biomarkers, from single genes and gene signatures, identified in patients with locally advanced head and neck squamous cell carcinoma using the GeneChip Human Transcriptome Array 2.0, nCounter, and real-time PCR analyses. Two multicenter, retrospective cohorts of patients with head and neck squamous cell carcinoma from the German Cancer Consortium Radiation Oncology Group who received postoperative radiochemotherapy or primary radiochemotherapy were considered. Real-time PCR was performed for a limited number of 38 genes of the cohort who received postoperative radiochemotherapy only. Correlations between the methods were evaluated by the Spearman rank correlation coefficient. Patients were stratified based on the expression of putative cancer stem cell markers, hypoxia-associated gene signatures, and a previously developed seven-gene signature. Locoregional tumor control was compared between these patient subgroups using log-rank tests. Gene expressions obtained from nCounter analyses were moderately correlated to GeneChip analyses (median rho = approximately 0.68). A higher correlation was obtained between nCounter analyses and real-time PCR (median rho = 0.84). Significant associations with locoregional tumor control were observed for most of the considered biomarkers evaluated by GeneChip and nCounter analyses. In general, all applied biomarkers (single genes and gene signatures) classified approximately 70% to 85% of the patients similarly. Overall, gene signatures seem to be more robust and had a better transferability among different measurement methods.

Objective: Stereotactic radiosurgery (SRS) has been increasingly applied to atypical or anaplastic meningioma after surgery for a better local control instead of conventional fractioned radiation therapy or watch and wait. The aim of our study was the characterization of our patient cohort with atypical[for full text, please go to the a.m. URL], 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Purpose/Objective: In order to improve radiotherapy outcomes, further treatment personalisation is considered beneficial. Radiomics analyses aim to predict treatment outcomes based on medical imaging data. Commonly, hand-crafted imaging features are used that require domain knowledge and further feature selection steps. This may cause relevant information to be lost. Deep convolutional neural networks (CNNs) on the other hand can act as automatic feature detectors and are able to learn highly nonlinear relationships directly from imaging data, thus addressing the drawbacks of conventional radiomics approaches and enabling end-to-end learning. We investigated whether CNNs are capable of quantifying loco-regional tumour control (LRC) based on CT imaging of patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Material/Methods: A multicentre cohort consisting of 302 patients with locally advanced HNSCC was collected and divided into an exploratory and a validation cohort (207 and 95 patients, respectively). All patients received a non-contrast-enhanced CT scan for treatment-planning and were treated by primary radio(chemo)therapy. 9725 transverse CT slices from the exploratory cohort were used to train a CNN with eight convolutional layers. For every patient (with one exception) we used 23 CT slices cranial and caudal of the slice with the largest tumour area, resulting in 47 slices per patient. Discriminative performance was evaluated using 4465 slices of the validation data set. The hazard of loco-regional recurrence was estimated by the CNN maximising the likelihood of the Cox proportional hazards model, which allows for incorporation of nonlinear relationships between the imaging features and the hazard prediction. The final hazard for every patient was obtained by averaging the results of the individual slices. The prognostic value of the model was evaluated by the concordance index (C-Index). Patients were stratified into groups of low and high risk of recurrence using the median hazard in the exploratory cohort. Results: The validation of our CNN model revealed a C-Index of 0.68 (95% confidence interval: 0.57-0.79) for the prognosis of LRC. The estimated hazards were used to stratify patients into two risk groups. LRC significantly differed between these groups, both in the exploratory and the validation cohort (log-rank p

Background: Tumour mutational burden (TMB) estimated from whole exome sequencing or comprehensive gene panels has previously been established as predictive factor of response to immune checkpoint inhibitors (ICIs). Its predictive value for the efficacy of concurrent chemoradiation (cCRTX), a potential combination partner of ICI, remains unknown. Methods: The accuracy of TMB estimation by an in-house 327-gene panel was established in the Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) data set. Interference of TMB with outcome after cCRTX was determined in a multicentre cohort of patients with locally advanced HNSCC uniformly treated with cCRTX. Targeted next-generation sequencing was successfully applied in 101 formalin-fixed, paraffin-embedded pretreatment tumour samples. In a subset of cases (n = 40), tumour RNA was used for immune-related gene expression profiling by the nanoString platform. TMB was correlated with TP53 genotype, human papilloma virus (HPV) status, immune expression signatures and survival parameters. Results were validated in the TCGA HNSCC cohort. Results: A high accuracy of TMB estimation by the 327-gene panel was established. High TMB was significantly associated with an increased prevalence of TP53 mutations and immune gene expression patterns unrelated to T cell-inflamed gene expression profiles. Kaplan-Meier analysis revealed significantly reduced overall survival in the patient group with high TMB (hazard ratio for death: 1.79, 95% confidence interval: 1.02-3.14; P = 0.042) which remained significant after correcting for confounding factors in the multivariate model. The prognostic value of TMB was confirmed in the TCGA HNSCC cohort. Conclusion: High TMB identifies HNSCC patients with poor outcome after cCRTX who might preferentially benefit from CRTX-ICI combinations.