Background and Objectives: Head and neck cancer in patients aged 40 years or younger represents a rare and heterogeneous entity with conflicting data regarding prognosis and risk factors. This study aimed to evaluate oncological outcomes and independent prognostic factors in young patients treated with radio(chemo)therapy. Materials and Methods: This retrospective multi-center analysis included patients aged ≤ 40 years with histologically confirmed HNC who received definitive or adjuvant radio(chemo)therapy between 2002 and 2023 at the University Hospital Regensburg and affiliated partner hospitals. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Independent prognostic factors were identified by Cox proportional hazard regression with backward stepwise elimination. Results: A total of 88 patients were included. The median age at diagnosis was 38.2 years (IQR 35.8-39.8). Median OS was 91.0 months in the adjuvant and 23.7 months in the definitive treatment group. In multivariate analysis, four independent predictors of OS were identified: nicotine abuse (HR 2.887; p = 0.004), pre-existing comorbidities (HR 2.871; p = 0.005), absence of complete remission 12 weeks after radiotherapy (HR 25.676; p < 0.001), and locoregional recurrence or distant metastases (HR 8.183; p < 0.001). Failure to achieve complete remission was the sole independent predictor of PFS (HR 4.479; p < 0.001). Conclusions: In young HNC patients, early treatment response and disease recurrence are the strongest determinants of survival, alongside modifiable lifestyle factors and comorbidity burden. These findings support the need for intensified response monitoring and tailored follow-up strategies in this patient population.

Background: Despite the availability of contouring guidelines and advanced imaging modalities, interobserver variability (IOV) in the delineation of the planning target volume and organs at risk remains a critical factor influencing treatment quality in radiotherapy. The aim of this study was to examine variations in contour delineation with respect to anatomical landmarks, as well as differences in the inclusion of lymph node levels within the PTV. Methods: Ten senior radiation oncologists from six different institutions participated in the study and contoured PTV1, PTV2 and 16 OARs in a patient with oropharyngeal carcinoma. Interobserver variation was quantified by volume statistics such as mean, standard deviation (SD) and ranges, as well as using coefficient of variance (CoV) and conformity index (CI). Results: High agreement was observed in the inclusion of the ipsilateral lymph node levels Ib-IVa and VIIa+b, whereas notable discrepancies were identified in the delineation inclusion of the cervical triangle group and lateral supraclavicular nodes. Regarding OARs, the greatest variability was observed in the delineation of the left and right inner ear, with volume ranges of 0.12-2.84 cm3 and 0.11-2.38 cm3, respectively. Conclusions: This study reaffirms the presence of significant interobserver variability in the delineation of PTVs and OARs in patients with oropharyngeal carcinoma. Especially inclusion of elective lymph node levels and definition of margins around the gross tumor volume are substantial factors for IOV. By emphasizing structured anatomical assessment as a standard approach, variability can be minimized, treatment consistency enhanced, and ultimately, patient outcomes improved.

Molecular tumor boards (MTBs) are essential for selecting therapies for patients with rare and advanced cancers. We hypothesized that integrating biomarkers beyond targeted DNA/RNA next-generation sequencing (NGS) could increase actionable findings. Human epidermal growth factor receptor 2 (HER2)-low status has emerged as a critical biomarker in breast cancer, with potential relevance across other tumor types. Homologous recombination deficiency (HRD) is pivotal for the application of Poly(ADP-Ribose)-Polymerase (PARP) inhibitors in ovarian and breast cancer, although its role in other malignancies remains unclear. Antibody–drug conjugates (ADCs) are expanding precision oncology, with promising biomarkers like Trop-2, Nectin-4, and folate receptor alpha (FRα) showing potential across multiple tumor entities. Tumors were analyzed using the TSO500® panel, enabling tumor mutational burden (TMB) readout. HER2 status was assessed via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), alongside antibody–drug conjugate (ADC) IHC, microsatellite instability (MSI) polymerase chain reaction (PCR), mismatch repair (MMR) IHC, programmed death-ligand 1 (PD-L1) IHC, and HRD analysis. Cases were discussed weekly, and outcomes were systematically tracked. Data analysis evaluated the benefit of additional biomarker assessments. Among 658 patients, 329 received therapy recommendations, 182 based on supplementary biomarker analyses. One hundred recommendations were implemented, with 37

Immunological biomarkers are increasingly relevant for personalized cancer treatment, but peripheral blood-derived biomarkers are not yet used to guide therapy in head and neck squamous cell carcinoma (HNSCC). The prospective non-randomized DIREKHT study (ClinicalTrials.gov: NCT02528955, 2015-08-19) therefore integrated immune monitoring into postoperative radio(chemo)therapy (R(C)T) to explore blood-based biomarkers. In 70 oral cavity and oropharyngeal cancer patients receiving curative R(C)T, the peripheral immune status was assessed before and after therapy and during follow-up by flow cytometry-based immunophenotyping of 45 immune parameters. A machine learning workflow identified predictors of disease-free survival (DFS), using Repeated Elastic Net Technique (RENT) feature selection within repeated stratified K-fold cross-validation and nested cross-validation for tuning and assessment. This approach identified a 29-parameter immune signature from pre- and post-therapeutic profiles, with key contributors including HLA-DR + T cells, HLA-DR+ monocytes, and basophils. The best model achieved a Matthews correlation coefficient of 0.681, with pre- and post-therapeutic parameters contributing equally, highlighting immune dynamics during R(C)T. Adding clinical parameters did not improve performance (MCC = 0.678), but yielded a comparable model integrating immune and clinical variables. Blood-based immune signatures may have prognostic relevance for DFS after R(C)T in HNSCC. Validation in larger cohorts is required to confirm clinical applicability and reduce the signature.

Background: With aging populations, the incidence of squamous cell carcinoma of the head and neck (SCCHN) among elderly patients is increasing. Although adjuvant radiotherapy or chemoradiation is a well-established component of multimodal treatment, elderly patients remain underrepresented in clinical trials. This study evaluates the feasibility of adjuvant radiotherapy and chemoradiation in patients over 70 years with SCCHN and explores the correlation between treatment feasibility and various comorbidity scores. Methods: We retrospectively analyzed patients over 70 years of age who received adjuvant radiotherapy or chemoradiation at the University Hospital Regensburg between 2004 and 2018. A total of 71 patients, with a median age of 75 years, were included. The majority were classified as UICC stage IVa. Median follow-up was 27 months. Results: Sixty-two patients completed treatment without interruption, and sixty-five received at least 95% of the prescribed radiation dose. The median total dose was 64 Gy. Acute toxicity of grade III or IV (CTC) occurred in 37 patients. Local tumor control rates were 99% at 12 months, 88% at 24 months, and 76% at 5 years. Overall survival rates were 87% at 12 months, 67% at 24 months, and 41% at 60 months, with a median overall survival of 51 months. The Elixhauser Comorbidity Score showed significant predictive value for treatment feasibility (p = 0.006). Conclusions: Adjuvant radiotherapy and chemoradiation are feasible and effective treatment options for elderly patients with SCCHN. The favorable local and locoregional control rates reported here suggest, in line with other recent reports in the literature, that age alone should not be a justification for treatment de-intensification.

Cerebral metastases in patients with metastatic lung cancer are found in more than 30% of patients at baseline and manifest themselves in two out of three patients during disease evolution. For a long time, the cerebral manifestation of the disease was classified as prognostically unfavorable and hence such patients were regularly excluded from therapy studies. In the context of targeted molecular therapy strategies and established immuno-oncological systemic therapies, the blood-brain barrier no longer represents an insurmountable barrier. However, the treatment of brain metastases requires decision making in a multidisciplinary team within dedicated lung cancer and/or oncology centers. The differentiated treatment decision is based on the number, size and location of the brain metastases, neurology and general condition, comorbidities, potential life expectancy and the patient's wishes, but also tumor biology including molecular targets, extra-cranial tumor burden and availability of a CNS-effective therapy. Systemic therapies as well as neurosurgical and radiotherapeutic concepts are now often combined for optimized and prognosis-improving therapeutic strategies.

BackgroundCurrent standard treatment concepts in head and neck squamous cell carcinoma (HNSCC) are based on former studies using 2D and 3D treatment plans. However, modern radiation techniques allow for a more precise and individual dose application. Therefore, in a clearly defined patient population, de-intensified risk-adapted radiation is investigated.MethodsPatients with newly diagnosed HNSCC after surgery (with resection margins ≥1 mm and cM0) with the following tumor stages (TNM 7th Edition) were eligible for the study: oral cavity, oropharynx, or larynx: pT1–3, pN0–pN2b; hypopharynx: pT1–2, pN1. The patients should have either a low risk of local recurrence [≤pT2, resection margin ≥5 mm, no peritumoral lymphangiosis (L0), and no perineural invasion] or contralateral lymph node metastasis (≤3 ipsilateral lymph node metastases, in case of well-lateralized oropharyngeal or oral cavity cancer contralateral cN0, otherwise pN0). Patients were assigned to three different treatment regimes with reduction of the treated volume, radiation dose, or both, according to tumor stage and results of surgery performed. The primary objective was to show an LRR of <10% after 2 years.FindingsA total of 150 patients were enrolled. Tumor localizations were as follows: n = 53 (35.3%), oral cavity; n = 94 (62.7%), oropharynx (82% HPV-positive); n = 2 (1.3%), hypopharynx; and n = 1 (0.7%), larynx. A total of 61 patients (41.0%) were stage IVA, 81 (54.0%) were stage III, and 8 (5.3%) were stage II. Median follow-up was 36 months. Cumulative incidence of 2y-LRR was 5.6% (95% CI: 1.7%–9.2%) in the whole study population and 14.1% (95% CI: 3.8%–23.2%) in patients with oral cavity cancer. Cumulative incidence of 2y-LRR in non-irradiated or dose-reduced regions was 3.5% (95% CI: 0.4%–6.5%). After 2 years, disease-free survival was 92% (95% CI: 87%–96%) and overall survival was 94% (95% CI: 90%–98%) for the complete study cohort. Acute III° toxicity was as follows: dysphagia, 30%; xerostomia, 7%; mucositis, 19%; and dermatitis, 4%. Dysphagia and xerostomia decrease over time. After 27 months, late dysphagia III° and xerostomia II° were 1% and 9%, respectively.InterpretationThe study met its primary objective. De-intensification of postoperative radiotherapy irrespective of HPV status in a predefined patient population is associated with a favorable toxicity profile without compromising LRR. In an unplanned subgroup analysis, a significantly increased risk of LRR was observed in patients with oral cavity cancer. In these patients, de-intensified radiotherapy should be applied with caution.

Cerebral metastases in patients with metastatic lung cancer are found in more than 30% of patients at baseline and manifest themselves in two out of three patients during disease evolution. For a long time, the cerebral manifestation of the disease was classified as prognostically unfavorable and hence such patients were regularly excluded from therapy studies. In the context of targeted molecular therapy strategies and established immuno-oncological systemic therapies, the blood-brain barrier no longer represents an insurmountable barrier. However, the treatment of brain metastases requires decision making in a multidisciplinary team within dedicated lung cancer and/or oncology centers. The differentiated treatment decision is based on the number, size and location of the brain metastases, neurology and general condition, comorbidities, potential life expectancy and the patient's wishes, but also tumor biology including molecular targets, extra-cranial tumor burden and availability of a CNS-effective therapy. Systemic therapies as well as neurosurgical and radiotherapeutic concepts are now often combined for optimized and prognosis-improving therapeutic strategies.

Background Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021. Methods and results In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278). Conclusion The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly.

(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.

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. 211 patients were registered by 90 German centres. Data were collected retrospectively by questionnaire and queries. 56 centres reported data on 126 patients who actually received at least one cycle of durvalumab. In contrast to the PACIFIC-trial population, some patients with oligometastatic disease and a history of autoimmune disease are included in the EAP population. Information on PD-L1 status was obtained for 111 patients. Baseline data include age, gender, ECOG, stage (IASLC 8th ed.), and smoking history. Treatment data include mode of chemoradiotherapy, used chemotherapy agent, and duration of durvalumab therapy. Adverse evants were documented according to CTAEC 5.0. Data were analysed for progression-free survival (PFS), overall survival (OS), and adverse events (AE). The results were published in Lung Cancer [1].

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-L1-negative 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 immuno-oncological 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 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.