German Cancer Society

Increasing evidence suggests that RT and ICI have synergistic effects on anti-tumor immune response, and abscopal responses (AR) have been described more frequently with this combination. Here, we analyzed the frequency and factors associated with AR in NSCLC patients receiving ICI and RT. In ARTIC (ARO 2022-10, DRKS00032390), a multicenter, retrospective study, patients treated with RT for progressive disease during or after receiving ICI were analyzed for abscopal benefit (AB) and overall survival (OS). Patients were grouped by non-irradiated lesion response; logistic and Cox regression were used to analyze factors linked to AR, AB, and OS. Fifty-six patients from 13 centers with 137 non-irradiated lesions were analyzed. Most received hypofractionated or stereotactic RT. The most common RT sites were lung, bone, and brain. Thirty-three patients showed AB, with 15 patients developing an AR in at least one non-irradiated lesion. In the logistic regression analysis, older age was associated with a higher rate of AP (odds ratio (OR): 1.07, 95%-CI: 1.00-1.14; p=0.05). Male sex showed a trend towards higher risk of AP (OR=3.13; 95%- CI: 0.93-11.86; p=0.075). In the multivariable Cox analysis, ECOG performance score at the start of RT (hazard ratio (HR): 0.29, 95%-CI: 0.12-0.69; p<0.01) and oligometastatic disease (HR: 0.34, 95%-CI: 0.12-0.94; p=0.039) were significantly associated with improved OS. RT was able to induce AR in some NSCLC patients who were progressive under ICI, possibly delaying a switch in systemic treatment. AB was less frequent in older patients and in men.

Circadian clocks regulate essential cellular functions and influence cancer development and treatment outcomes. Aligning therapy with circadian rhythms can improve efficacy and reduce toxicity, yet whether neuroblastoma, a heterogeneous pediatric tumor, maintains circadian function remains unclear. Here, we systematically profiled circadian dynamics across 12 neuroblastoma cell models using long-term bioluminescence assays and computational analysis. Our findings reveal heterogeneous circadian patterns ranging from robust to arrhythmic, which we linked to distinct neuroblastoma genetic features. By integrating drug sensitivity data, we identified candidate compounds whose effectiveness correlates with circadian expression profiles. Moreover, time-of-day treatment assays with the ALK inhibitor lorlatinib and frontline chemotherapeutics revealed distinct temporal drug responses that were more pronounced in circadian-competent than weakly rhythmic cell lines. Together, these findings establish circadian heterogeneity as a previously unrecognized dimension of neuroblastoma biology and highlight the therapeutic potential of chronotherapy approaches for improved treatment efficacy.

Childhood overweight and obesity pose a growing public health problem with increasing prevalence both in Europe and globally. Reasons can be found in behavioural factors such as a sedentary lifestyle, eating habits or low exercise levels and to a lesser extent in a genetic predisposition or a metabolic disorder. Preventing children with obesity and overweight to grow into obese teenagers is therefore of high importance. However, there are currently no established care and prevention programmes in Germany for the early reduction of overweight and prevention of obesity in children aged 3-6 years. fruehstArt aims to close this gap with a cross-sector outreach and family-centred personal counselling approach, where parents receive support from paediatricians and trained coaches who conduct consultations in the home of the family. The main research question is whether the fruehstArt programme reduces overweight and obesity in children aged 3-6 years within 12 months, as measured by the body mass index-standard deviation score (BMI-SDS). fruehstArt has been developed as a new form of care, which includes a family intervention with motivational interviews provided by paediatricians and individual home-based counselling provided by a trained coach on eating behaviour, exercising, sleeping behaviour and age-appropriate use of electronic devices. fruehstArt will be accompanied by an efficacy study (summative evaluation of change in BMI-SDS). In addition to German, the project is also offered in Turkish in order to reach families with a migration background and language barriers. 812 children with overweight or obesity and their families in the region North Rhine will be included and observed over 12 months. Recruitment of children occurred from December 2023 to April 2025 with the final visits scheduled for April 2026. The study is conducted as a randomised controlled trial with a social-ecological intervention approach, considering children in their living environment and conditions. Moreover, a formative evaluation at the process level, and the system level will be carried out and complemented by a health economic analysis. Those are carried out to provide information about the intervention's success and relevant costs. Thus, fruehstArt is realised in the form of an effectiveness-implementation hybrid design that combines the analysis of effectiveness with an evaluation of the implementation process. The study received ethics approval in a coordinated procedure from the ethics committee of the Medical Faculty University hospital of Cologne and the ethics committee of the North Rhine Medical Association. For all collected data, the relevant national and European data protection regulations will be considered. All personal data (contact details) will be removed for the data analysis in order to ensure pseudonymisation. Dissemination strategies include reports and quality workshops for organisations, peer-reviewed publications and the presentation of results at conferences. The aim of the unique form of care fruehstArt is to improve the care of preschool children with overweight or obesity through innovative home-based counselling, cross-sectoral service integration and to address the cultural needs of Turkish families. DRKS00030749 (29-09-2023).

We demonstrate a hybrid system combining Raman spectroscopy and partial wave spectroscopy, improving tissue classification accuracy and detecting variation in tissues from an intestinal tumorigenesis mouse model, showcasing the system’s potential for field cancerization studies.

Abstract Resistance to cancer treatment remains the leading cause of cancer-related deaths. In tumors with low mutational burden such as pediatric cancers, alternative transcripts, including circular RNAs (circRNAs), have been identified as involved in treatment resistance. However, their isoforms are often missed by commonly used short-read sequencing. Here, we employ long-read sequencing to identify full-length circRNA isoforms associated with resistance in ALK -driven pediatric cancers. Using cell models and a cohort of ALK -translocated anaplastic large-cell lymphoma (ALK+ ALCL) patients, two circRNAs were detected as specifically upregulated in resistant cases and associated with worse disease outcomes. Similar findings were observed in the pediatric cancer neuroblastoma. These circRNAs were also more abundant in liquid biopsies from ALKi-resistant ALK+ ALCL and neuroblastoma patients. This demonstrates that long-read sequencing allows for uncovering disease-relevant circRNA isoforms that could serve as biomarkers for resistance detection in a clinical setting.

Abstract BACKGROUND Positron emission tomography (PET) is increasingly used in patients with brain tumors, yet its adoption varies across institutions. METHODS To assess the current landscape, a cross-sectional survey was conducted among European Organization for Research and Treatment of Cancer (EORTC) – Brain Tumour Group (BTG) sites between June 2024 and August 2024. RESULTS Out of the 312 sites invited, 103 replies from 20 countries in the Europe/Middle East region were received. PET availability was reported by 96/103 (93.2%) sites, of whom 74 reported PET use in patients with brain tumors. Most frequently, PET was performed in glioma (69/74, 93.2%), followed by brain metastasis (58/74, 78.4%), meningioma (52/74, 70.3%), and CNS lymphoma (46/74, 62.2%). Amino acid PET was used at 62/71 centers (87.3%), mainly in glioma (58/59, 98.3%) and for differentiation of tumor progression from treatment-related changes (58/59, 98.3%), differential diagnosis (54/59, 91.5%), and hotspot delineation (47/59, 79.7%). Somatostatin receptor (SSTR) PET was performed at 50/68 sites (73.5%), predominantly in meningioma (48/49, 98.0%), and for patient selection before radioligand therapy (41/49, 83.7%) as well as for target volume definition in radiotherapy (33/49, 67.3%) and differential diagnosis (27/49, 55.1%). PET was covered by statutory health insurance at 46/59 (78.0%) centers for amino acid PET and 33/49 (67.3%) for SSTR PET according to self-reported information. Main reasons for not performing PET in clinical routine included limited availability of tracers (14/29, 48.3%), high cost (11/29, 37.9%), and PET considered unnecessary by referring physicians (8/29, 27.6%). CONCLUSION PET is widely used among EORTC-BTG sites, although implementation varies and is influenced by factors such as tracer availability, cost, and institutional perceptions. While further data from broader surveys including non-academic institutions is needed, the findings support the implementation of PET as clinical trial endpoint.

Hypothesis-driven academic research identifies interventions with likely disease-specific effects. Yet, many candidate drugs fail upon further development, emphasizing the need for acquisition of more robust preclinical data. We demonstrate that planning and executing multicentre confirmatory preclinical studies in an academic setting by applying the quality standards of early phase clinical trials is feasible. Randomization, blinding, stratification by sex of and quality control measures were carried out successfully. The primary objective of our specific study - to confirm synergistic effects of BET bromodomain protein 4 (BRD4) and cyclin-dependent kinase 9 (CDK9) inhibitors against PAX3::FOXO1 (P3F)-positive rhabdomyosarcoma (RMS) - was not met. Post-hoc analyses support that single-agent BRD4 inhibition by JQ1 effectively reduced the growth and viability of P3F+ RMS cells ex vivo with adequate on-target activity as evidenced by reduced expression of P3F, MYCN, MYOG, and MYOD. The antiproliferative effects of JQ1 and vincristine were comparable, and there was trend towards reduced and delayed xenograft growth in JQ1-treated mice. Yet, in vivo assays were flawed by lower xenograft penetrance, variable xenograft latency, gastrointestinal toxicity, and inadequate on-target activity of drugs. We conclude that confirmatory preclinical trials allow for robust assessment of the efficacy of candidate interventions and reduce bias in academic research. The study platform established here provides a framework that may be of particular benefit for the development of new drugs for rare cancers.