German Cancer Research Center

Pineoblastoma is a clinically aggressive childhood brain tumor composed of distinct molecular subgroups with divergent driver genes, demographics, and clinical outcomes. To identify developmental origins and mechanisms governing disease pathogenesis, we derive single-cell transcriptomes from pineal parenchymal tumors, aligning malignant cells with developmental counterparts to retrace cellular origins. Integrative computational analyses map pineoblastoma origins to transient, cycling pinealocyte progenitors during development. Lineage-specific perturbation of suspected drivers in the early pineal gland yields preclinical models representative of consensus molecular subgroups. Multi-omic characterization of patient tumors and these models uncover a tumor-associated photoreceptor signature (TAPS) common to pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this signature within respective cellular origins establishes a developmental basis for molecular similarities between entities. Photoreceptor signature constituents are selective dependencies across these anatomically distinct central nervous system malignancies, motivating future studies evaluating developmentally encoded programs of malignancy as potential therapeutic liabilities.

To assess variability of maximum diameter measurements of prostate lesions in MRI assessing patient repositioning, rater and sequence effects. Forty-two patients were included retrospectively, who received a clinical bi-/multiparametric prostate MRI examination and agreed to have the T2-weighted (T2WI) and diffusion weighted-imaging (DWI) sequences scanned twice. Maximum diameter measurements of prostate lesions mentioned in the clinical radiologist reports were performed by four readers in multiple reading sessions for determination of inter-sequence (between two DWI sequences), inter-scan (between clinical and additional scan), intra-rater and inter-rater variability. The primary calculated metrics were the repeatability and reproducibility coefficient (RC/RDC), including pooled RC/RDC. Variability measured by RCs/RDCs was lowest for measurements obtained within the same reading session, with inter-scan RCs up to 5.6mm/6.5mm for T2WI/DWI, pooled RCs of 4.8mm/5.8mm, respectively, and inter-sequence RDCs of 5.4mm-5.9mm, pooled RDC 5.8mm. Measurements performed in separate reading sessions demonstrated significantly higher variability for both settings in the majority of cases (RCs: up to 10.9mm/11.7mm/10.2mm for T2WI/DWI/inter-sequence, p≤0.002), pooled RCs/RDCs 9.2mm-9.9mm. Measurements necessarily generated in different reading sessions, i.e., intra-rater or inter-rater, demonstrated high variability (RCs/RDCs up to 11.4mm/11.5mm for T2WI/DWI). Prostate lesion measurements demonstrate considerable variability. When measured in one reading session by one rater, lesion diameter differences below the pooled RCs of 4.8mm, 95%-CI [3.9, 5.6] for T2WI and 5.8mm, 95%-CI [4.7, 7.1] for DWI should not necessarily assumed to be true biological change, as these differences may result from measurement- or repositioning-based variability alone. Caution needs to be taken assessing size changes.

Functional asymmetry and sensorimotor control impairments often persist in patients following total knee arthroplasty (TKA), yet they remain under-evaluated in routine clinical settings using simple, scalable tools. Understanding the relationship between these deficits and postoperative outcomes is critical for optimizing rehabilitation strategies. To assess the prevalence and degree of functional asymmetry in individuals 6-12 months post-TKA using standardized physical therapy assessments, and to evaluate the predictive value of asymmetry and sensorimotor deficits on both functional performance and patient-reported outcomes. A cross-sectional study was conducted on 125 patients aged 55-80 years, 6-12 months after unilateral primary TKA. Functional asymmetry was measured using the Single-Leg Sit-to-Stand (SLSST), Step-Down Test, and modified Star Excursion Balance Test (mSEBT). Functional outcomes included the Timed Up and Go (TUG) and 30-Second Chair Stand Test (30CST). In contrast, self-reported outcomes were assessed he KOOS-ADL and the KOOS-Function in Sport and Recreation (KOOS-Sport/Rec) subscales were administered. Correlations and multiple regression models were used to analyze relationships between asymmetry measures and outcomes. Significant correlations were found between asymmetry measures and both functional and self-reported outcomes (e.g., SLSST asymmetry and TUG: r = 0.47, p = 0.005; KOOS-ADL: r = -0.45, p = 0.007). Regression models identified SLSST, Step-Down, and mSEBT asymmetry as significant predictors of TUG (R2 = 0.48, p < 0.001) and KOOS-ADL (R2 = 0.53, p < 0.001). Patients with high asymmetry exhibited significantly poorer outcomes across all measures (all p < 0.01). Functional asymmetry and sensorimotor deficits are independently associated with poorer mobility and self-reported function post-TKA and can be effectively identified using clinically accessible tools, supporting their integration into routine postoperative assessment and rehabilitation planning.

Radiology is integral to the multimodal diagnostic and treatment pathway of extremity soft tissue sarcomas in DGK-certified sarcoma centers (DGK: Deutsche Krebsgesellschaft, German Cancer Society), working in close interdisciplinary collaboration with sarcoma surgery, pathology, radiation oncology, and medical oncology. Treatment decisions rely on guideline- and recommendation-based imaging and histological confirmation by biopsy. When clinical warning signs (red flags) are present, radiological imaging is essential for triage and early referral to asarcoma center. For local staging, magnetic resonance imaging (MRI) is the modality of choice. It provides crucial information for diagnosis, prognosis, and treatment within the sarcoma board and serves as the basis for adequate biopsy planning. Diagnostic pitfalls arise from overlapping MRI appearances, particularly within the lipomatous spectrum and in lesions with myxoid and cystic patterns. Afurther focus is on avoidable procedural biopsy errors, inadequate targeting, and an inadequate biopsy tract that is not amenable to enbloc resection or that contaminates additional compartments/joints or neurovascular structures. The article outlines arisk-adapted diagnostic approach and provides practice-oriented principles for biopsy planning. It highlights typical problem MRI constellations to avoid misdiagnosis and underestimation of malignancy (grading), ultimately establishing optimal prerequisites for therapy.

Peripheral T cell lymphomas (PTCLs) are a diverse group of aggressive malignancies that arise from mature, post-thymic T cells. Recent genomic and mechanistic studies reveal that these cancers frequently 'hijack' signalling pathways that normally govern T cell activation at the immunological synapse. Specifically, numerous gain-of-function alterations in TCR proximal regulators and mediators of antigen-induced NF-κB activation, as well as mutations or overexpression of co-stimulatory receptors and dysregulated cytokine receptor signalling, promote the constitutive proliferation and survival of malignant clones. Conversely, loss-of-function mutations in PDCD1 or disruption of PD1-mediated inhibitory control, coupled with altered metabolic and epigenetic reprogramming, have emerged as a major tumour-suppressor mechanism in PTCL pathogenesis. This framework conceptualizes PTCLs as 'cancers of aberrant immune synapse signalling pathways' and posits that genetic dissection of PTCL pathogenesis can uncover fundamental aspects of T cell biology to guide the design of safer, more effective next-generation T cell therapies.

Abstract Numerous variance estimators exist for the normal distribution, yet the unbiased estimator–commonly known as Bessel’s correction–remains the most widely used in practice. This article reviews various alternative estimators, that result from using different standardization factors for the sum of squares. It is demonstrated that there is no compelling reason to favor the unbiased variance estimator over other estimators and that better alternatives are available. Implications of these findings for applications involvings small sample size are discussed.

IntroductionSézary syndrome (SS) is a rare neoplasm associated with poor prognosis. Due to the rarity of the disease, large-scale investigations are scarce, while identifying prognostic factors is essential for improving treatment outcomes. The primary objective was to investigate prognostic factors in a large population of SS patients on survival and infections. The secondary objective was to validate a previously suggested prognostic index model.MethodsWe conducted a propensity score-matched retrospective cohort study using real-world data from 1277 patients in the TriNetX database. Risk factors examined included age, elevated lactate dehydrogenase (LDH), anemia, elevated white blood cell count (WBC), sex, and race. Examined outcomes were: 5-year survival, Systemic Inflammatory Response Syndrome (SIRS), sepsis and pneumonia. The prognostic index model was simplified into factors assessable through TriNetX.ResultsAge > 60 years, elevated LDH, anemia and elevated WBC were risk factors for 5-year overall survival. Elevated LDH, anemia, elevated WBC and African American/black race were significantly associated with sepsis. Anemia and elevated WBC were also linked to higher risk of pneumonia. Additionally, we devised and validated a simplified prognostic index model (sPIM) accounting for patient focus on SS (stage IV) patients.ConclusionIn the largest group of SS patients assessed for risk stratification to-date, we confirm age and elevated LDH as risk factors in SS and their applicability in the prognostic index model. This study introduces anemia as a novel risk factor and demonstrates the prognostic value of leukocytosis in SS. While race requires further investigation, sex appears to have no significant impact on survival.