NUT carcinomas (NC) are very rare and highly aggressive tumors, molecularly defined by an aberrant gene fusion involving the NUTM1 gene. NCs preferentially arise intrathoracically or in the head and neck region, having a highly adverse prognosis with almost no long-term survivors. Here, we report on a cohort of 35 adult NC patients who were evaluated at University Hospital Tuebingen in an eight year time span, i.e. between 2016 and 2023. Primary objectives were overall survival (OS) and influence of primary tumor locations, fusion gene types and staging on OS. Secondary objectives were patient baseline characteristics, risk factors, tumor markers, treatment decisions and responses to therapy comparing thoracic vs non-thoracic origins. Further, data from tumor genome sequencing were analyzed. In this monocentric German cohort, 54 % of patients had thoracic tumors and 65 % harbored a BRD4-NUTM1 fusion gene. Median OS was 7.5 months, being significantly dependent on primary tumor location and nodal status. Initial misdiagnosis was a problem in 31 % of the cases. Surgery was the first treatment in most patients (46 %) and 80 % were treated with polychemotherapies, showing longer progression free survival (PFS) with ifosfamide-based than with platinum-based regimens. Patients treated with an immune checkpoint inhibitor (ICI) in addition to first-line chemotherapy tended to have longer OS. Initial LDH levels could be identified as a prognostic measure for survival prognosis. Sequencing data highlight aberrant NUTM1 fusion genes as unique tumor driver genes. This is the largest adult European cohort of this orphan tumor disease, showing epidemiologic and molecular features as well as relevant clinical data. Awareness to prevent misdiagnosis, fast contact to a specialized nation-wide center and referral to clinical studies are essential as long-term survival is rarely achieved with any of the current therapeutic regimes.

Objectives: Multidisciplinary tumor boards (MDTs) are critical for the personalized management of soft tissue sarcomas (STS), but they are limited by time, costs, and resource demands. With recent advances in large language models (LLMs) like ChatGPT, there is growing interest in evaluating their potential role in augmenting MDT workflows. This study aimed to assess the clinical performance of ChatGPT-4o in real-world STS cases using predefined evaluation criteria, comparing its treatment suggestions with expert MDT decisions. Materials and methods: This retrospective study included 152 patients presented to the multidisciplinary sarcoma tumor board. ChatGPT-4o was prompted to generate guideline-based treatment recommendations based on anonymized tumor board registration letters. Outputs were scored by blinded expert reviewers using a five-domain framework: diagnostic modalities, therapeutic modalities, treatment sequencing/timing, chemotherapy regimen, and clinical contextualization. Descriptive statistics and non-parametric ANOVA with post hoc tests assessed performance, including subgroup analysis by sarcoma subtype. Results: ChatGPT-4o scores were significantly lower than the maximum achievable value of 1.0 across all five criteria (all p < 0.0001). Among individual domains, clinical contextualization significantly outperformed all other criteria in pairwise comparisons (all p < 0.05). No significant performance differences were observed across sarcoma subtypes (H = 19.74, p = 0.138). Conclusions: ChatGPT-4o demonstrated substantial expert-rated performance in generating tumor board recommendations for soft tissue sarcoma cases, particularly excelling in personalized contextualization. Discrepancies in treatment sequencing and chemotherapy selection highlight the need for expert oversight. These findings support the feasibility of LLM integration into oncology workflows, warranting further refinement toward safe, supportive clinical use.

Introduction: Sarcoma is a rare and highly heterogeneous family of mesenchymal tumors. The experience and interdisciplinary approach of specialized high-volume sarcoma centers has a significant impact on disease treatment and outcome for patients. The aim of this retrospective, real-world, multicenter study was to evaluate geographic distribution of sarcoma cases in Southwest Germany and visually depict possible underrepresented areas of sarcoma primary diagnoses. Such descriptive information may indirectly guide future referral patterns and outreach activities of specialized sarcoma centers. Methods: The absolute number and incidence of sarcoma patients obtained from the Baden-Württemberg Cancer Registry were compared with the data from five individual, high-volume, specialized sarcoma centers. Furthermore, we used a “White-Spot Analysis” as a novel cost-effective approach in epidemiological and public health research for analyzing health care coverage in sarcoma care. Results: A total of 4,087 sarcoma patients living in the German Federal State of Baden-Württemberg between 2019 and 2022 were included in this study. Of these, 1,650 patients (40%) were treated primarily in specialized sarcoma centers whilst 2,437 patients (60%) received treatment for sarcoma outside of the five main high-volume centers, in underrepresented areas identified through White-Spot Analysis. The sarcoma incidence in Baden-Württemberg was calculated with our data to be 9.18/100,000 inhabitants per year. Discussion: In future, the access to high-volume centers needs to be facilitated in order to minimize the observed discrepancies between treatment in specialized sarcoma centers and low-volume centers in Southwest Germany. Our analysis highlights such discrepancies and may support future efforts to improve outcomes for sarcoma patients.

Purpose: Imatinib resistance is conferred by secondary mutations within the ATP-binding pocket or the activation loop of KIT in gastrointestinal stromal tumors (GIST). Ponatinib is active against KIT secondary activation loop and the gatekeeper mutation T670I in vitro. We evaluated the safety, activity, and inhibitory profile of lower-dose (30 mg) ponatinib in pretreated patients with KIT-mutant GIST. Patients and Methods: POETIG was a multicenter phase II trial in patients with advanced, unresectable GIST progressing after imatinib (cohort A, KITV654A–, and cohort B, KITV654A+) or at least imatinib, sunitinib, and regorafenib (cohort C). The primary endpoint was the clinical benefit rate at 16 weeks (modified RECIST 1.1). ctDNA was analyzed for mutations V654A and T670I, and ponatinib was characterized in silico and in vitro using a panel of GIST cell lines. Results: A total of 46 patients were enrolled, and the median follow-up was 1.3 years. The 16-week clinical benefit rate in cohorts A + B was five of 19 (26.3%) and nine of 27 (33.3%) in cohort C, with a median progression-free survival of 2.1 and 3.4 months with four (cohorts A + B) and five (cohort C) patients responding for >6 months. These patients were characterized by exon 11 and/or T670I mutations. Cardiovascular events occurred in four of 46 patients; most common grade 3/4 side effects were hypertension, gamma-glutamyl transferase (GGT)/lipase increase, abdominal pain, and infections. Clinical observations were reproduced by cell line screening and structural modeling. Conclusions: The trial did not meet its primary endpoint, but lower-dosed ponatinib provided clinical benefit in a subset of patients with expected toxicities. Patients harboring primary exon 11 and/or resistance mutations in T670I and/or exons 17/18 may represent a relevant therapeutic niche for ponatinib.

DdPCR primer and probe sequences

Empirical evidence shows that treatment of adult soft tissue sarcoma (STS) according to clinical guidelines has a survival benefit for patients. In 2021, the first evidence-based guidelines for STS were published in Germany including 14 measurable quality indicators (QIs). This paper examines the quality of care of STS in Germany across all treatment institutions prior to the publication of the clinical guideline using the QIs. A comprehensive population-based cohort of 20,922 sarcoma patients from 11 of 16 federal states, diagnosed between 2015 and 2021 was extracted from the cancer registry data using the ICD-O-3-codes for topography and histological subtype. The QI measurements are based on the calculation rules of a group of experts. Annual percentage changes (APCs) were calculated to identify trends over time. QI 1 (Pre-therapeutic presentation in the tumor board (initial diagnosis of STS)) increased from 9 % to 24 %. QI 7 (R0 resection for STS) showed a stable rate of over 80 %. For QI 8 (hysterectomy without morcellation for sarcoma confined to the uterus), the rate was 82 % in 2015 and rose significantly until 2017 to 94 %. QI 12 (First-line chemotherapy for STS without GIST) remained at the same level as the overall value of 79 %. For QI 14 (Postoperative mortality in retroperitoneal sarcoma), the value for the entire period was 1.4 %. The extensive database enables QI analysis for sarcoma care. Improvements in defined QIs confirm progress, while unmet targets are identifiable. Using cancer-registry data ensures comprehensive coverage of all institutions treating sarcoma patients, extending beyond accredited sarcoma centers. Results may serve as baseline values for future evaluations of improvements in patient care following implementation of the S3 guideline.