Hypoxia strongly affects the growth, invasion, and therapeutic response of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Despite intensive research, only a few substances have progressed to clinical trials as radiosensitizers. Therefore, new clinically relevant tumor models are needed to identify agents that overcome radiation resistance in hypoxic tumors. To study radiosensitivity of hypoxic and normoxic cells, we developed a two-color spheroid model using two HNSCC cell lines, SAS and FaDu, with GFP-labeled inner cell layers and mCherry-labeled outer layers. Optimizing the ratios of fluorescent cells enabled formation of hypoxic and normoxic zones, confirmed by pimonidazole, HIF1α, and CA IX staining. A newly established fluorescence clonogenic survival assay demonstrated transferability of results from 2D normoxia and hypoxia assays to these 3D model. The inner GFP-labeled cells showed significantly lower plating efficiency and increased radiation resistance compared to outer mCherry-labeled cells, similar to 2D hypoxic cells. To improve the model by reducing normoxia-induced HIF1α expression in the outer layer, we added physiological concentrations of ascorbic acid. Ascorbic acid also increased spheroid growth, clonogenic survival, and radioresistance under normoxia, while hypoxic responses remained unchanged. These two-layer spheroid model with distinct fluorescent labels provide a simple, robust assay to distinguish hypoxic from normoxic tumor areas in radiotherapy research. Addition of ascorbic acid further refines the physiological relevance of 3D tumor models and modulates radiosensitivity of the outer mCherry-labeled cell layer in both HNSCC models.

Abstract Merkel cell carcinoma (MCC) is a rare malignancy with an annual incidence in Germany of 5.2 per million for men and 3.8 per million for women, predominantly affecting sun-exposed areas in older adults. Despite a frequently unfavorable prognosis, outcomes are multifactorial and depend on tumor site, disease stage, performance status, patient age, sex, and immune competence. The current standard of care prescribes surgical resection followed by adjuvant radiotherapy of the tumor bed, ideally initiated within 8 weeks after surgery to optimize clinical outcomes. In case of lymph node involvement, lymph node dissection and/or radiotherapy of the involved nodal basin are recommended. Furthermore, new evidence supports the effectiveness of shorter radiotherapy approaches, with moderate hypofractionated or even ultrahypofractionated schedules serving as effective options for certain patients, particularly those with frailty or comorbidities, or when it is clinically necessary to minimize the treatment burden. In cases of inoperability, refusal of surgery, or significant frailty, definitive local radiotherapy can achieve sufficient disease control. The synergistic potential of combining immunotherapy with radiation in advanced cases remains a key area for ongoing research.

Der vorliegende Text fasst die aktuelle Literatur zum Thema perioperative systemische Therapie zusammen. Dabei wird auf pragmatische Weise der Weg des Patienten von der Diagnostik über die Tumorkonferenz zur Therapie skizziert. Wir werden dabei kritische Punkte zur Diskussion stellen. Die Darstellung wird von der klinischen Erfahrung der Autoren geleitet, wodurch Lücken in der wissenschaftlichen Evidenz interponiert werden. Eine umfassende detaillierte Diskussion der Literatur sowie eine stark individualisierte Fallplanung können nicht erwartet werden und würden den Rahmen dieses Artikels sprengen.

Die molekulare Klassifikation ist mittlerweile fundamentaler Bestandteil der aktuellen S3-Leitlinie der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; [1]) wie auch der europäischen ESGO/ESTRO-ESP(European Society of Gynaecological Oncology, European Society for Radiotherapy and Oncology, European Society of Pathology)-Leitlinie [2] und stellt die Grundlage für Empfehlungen zur adjuvanten Therapie beim Endometriumkarzinom dar. Sie integriert klinische Risikofaktoren und molekulare Subgruppen. Insbesondere die ESGO-ESTRO-ESP-Leitlinie 2025 leitet ihre Therapieempfehlungen konsequent aus der Einteilung in Risikogruppen ab, wobei die aktuelle Konsultationsfassung der AWMF-S3-Leitlinie „Diagnostik und Therapie des Endometriumkarzinoms“ die molekulare Klassifikation vorwiegend für die Diagnose und individuelle Prognose heranzieht. Wesentliche Erkenntnisse zur adjuvanten Therapie gründen auf den Ergebnissen der PORTEC(Postoperative Radiation Therapy in Endometrial Cancer)-Studienserie (1–4). Neben dem Stellenwert der postoperativen Strahlentherapie für die lokale Kontrolle wurde hier auch der Mehrwert einer begleitenden Chemotherapie für eine Subgruppe von Patientinnen demonstriert. Die Ergebnisse der PORTEC-4a-Studie sind Anfang des Jahres in einer Vollpublikation erschienen. Wesentliche Verbesserungen in der adjuvanten Systemtherapie für Hochrisikopatientinnen mit postoperativem Tumorrest und bei primär metastasierten Patientinnen konnten in mehreren Studien durch den Einsatz von Immuncheckpointinhibitoren demonstriert werden. Vergleichbare Daten, die den Einsatz in der adjuvanten High-risk-Situation ohne Tumorrest nagelegen, fehlen bisher und wurden daher in der aktuellen AWMF-S3-Leitlinie auch nicht berücksichtigt. In diesem Beitrag sollen anhand der Konsultationsfassung der AWMF-S3-Leitlinie einerseits die Indikationen sowie die verfügbaren Optionen zur adjuvanten Therapie in Abhängigkeit von der jeweiligen Risikogruppe aufgezeigt werden.

Lung cancer is the most frequent source of brain metastases (BMs), with 20-40

Abstract Children and adolescents with classical Hodgkin lymphoma have a progression-free survival (PFS) rate of ≥ 90% with current treatments. The current challenge is to reduce adverse late-effects while maintaining high survival. Distinguishing lung involvement (Stage IV) from benign lung lesions remains a staging challenge in pediatric Hodgkin lymphoma (pHL). This study analyzed the prevalence, morphological patterns, and prognostic impact of lung lesions on progression-free survival (PFS) within the EuroNet-PHL-C1 trial. A retrospective analysis was conducted on chest CT scans from 1,298 pHL patients enrolled in the EuroNet-PHL-C1 trial. Patients were stratified by established treatment groups (TG-1, TG-2, TG-3). Lesions were classified by morphological pattern, and Kaplan-Meier analysis was used to compare 60-month PFS between groups with and without lung lesions. Lung lesions were identified in 60.2% (782/1298) of patients, with nodules being the predominant pattern (89%). In the combined TG-1 and TG-2 cohort (early/intermediate stages), the presence of any lung lesion correlated with significantly lower 5-year PFS (85.5% vs. 91.7%; p = 0.0197). Importantly, this lower PFS was driven by non-nodule morphologies. In the TG-3 (advanced stage) cohort, neither the presence of lung lesions nor stage IV classification significantly affected PFS. Lung lesions are highly prevalent in pHL. However, the presence of pulmonary nodules does not confer an inferior prognosis. The prognostic impact of lung lesions is primarily limited to non-nodule patterns in early-stage disease. These findings suggest that incorporating morphological patterns may be beneficial for refining risk stratification in future pHL trials.

The ESGO-ESTRO-ESP guideline 2025 integrates the molecular classification into prognostic risk stratification and therapeutic decisions for patients with endometrial cancer (EC). In particular, a refined stratification of the molecular subgroup No-Specific-Molecular-Profile (NSMP) has been recently introduced to better reflect its pronounced prognostic heterogeneity. Retrospective analyses by Jamieson et al. and Vermij et al. demonstrate that histological tumor grade and immunohistochemical estrogen receptor expression represent independent prognostic factors within the NSMP subgroup, allowing for the identification of a large subgroup with an excellent prognosis and a small subgroup with a poor prognosis. Additional exploratory post hoc analyses suggest a potential differential benefit of adjuvant chemotherapy in ER-negative NSMP EC. However, these observations remain hypothesis-generating and lack prospective validation. In addition, the exact cut-off for ER-positivity remains unclear. The ESGO guideline defines prognostic risk groups according to the estimated 5-year risk of recurrence and derives recommendations for adjuvant therapy accordingly. Key randomized trials, including PORTEC-1, PORTEC-2, PORTEC-3, GOG-249 and GOG-258, are incorporated alongside molecular subgroups, whose biological characteristics increasingly inform treatment intensity. In contrast, the German S3 guideline adopts a more conservative methodological approach, incorporating molecular markers primarily as supportive information, particularly in the absence of prospective evidence guiding specific therapeutic decisions. With respect to surgical management in early-stage disease (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] I-II), both guidelines show substantial agreement, especially regarding the preference for minimally invasive surgery and the avoidance of unnecessary radicality. Differences mainly relate to the indication for sentinel lymph node staging. This statement aims to provide a balanced contextualization of these conceptual differences and to support an informed discussion of current international developments.

BACKGROUND:Cochlear implantation has become an effective method of hearing rehabilitation for selected patients with vestibular schwannoma (VS) and nonserviceable hearing who are treated by microsurgical tumor resection, radiotherapy, or observation. However, very little information is available on radiotherapy for VS in the presence of a cochlear implant (CI) in cases in which tumor growth occurs following observation, or when residual tumor growth occurs after microsurgery. OBSERVATIONS:The authors report the case of a 60-year-old woman with successful tumor control of a growing VS by radiosurgery after partial resection of a separate, ipsilateral transfundal inner ear schwannoma (IES) with involvement of the modiolus and CI placement. Hearing with the CI could be preserved for the reported observation time of 3 years postradiosurgery. LESSONS:Even though they are extremely rare, the presence of unilateral multifocal IES and VS must be considered. Although results from a single observation should be interpreted with caution, this case suggests that VS tumor control using radiosurgery appears, in principle, to be possible despite the presence of a CI. Further studies are needed to determine whether radiosurgery could prove to be a potential treatment option for VS despite the presence of a CI in carefully selected cases. https://thejns.org/doi/10.3171/CASE26389.