Olgahospital

Abstract Pediatric solid high-risk malignancies mostly lack established molecular biomarkers for early detection, minimal residual disease assessment, or treatment monitoring. Challenges include small patient numbers, limited sample volumes, low tumor mutational burden, and few recurrent alterations. Within the prospective multicenter pediatric precision oncology program INFORM, we collected liquid biopsies from 130 pediatric patients and optimized cfDNA isolation and analysis. Whole-genome, whole-exome, and targeted panel sequencing were performed using liquid biopsy-adapted protocols. Integrating tissue-derived molecular profiles and orthogonal validation revealed that low-coverage whole-genome sequencing reliably detects circulating tumor DNA. An in silico ctDNA estimation score, combining fragment length and genome segment alterations, improved sensitivity and specificity to 95%, enabling plasma-based tumor detection in 93% of patients. Whole-exome and panel sequencing effectively identified clinically relevant, potentially druggable molecular targets; however, their utility varied substantially across different tumor entities, underscoring the need for entity-specific considerations in the interpretation and application of these methodologies. In-depth analyses demonstrated liquid biopsy’s potential to track tumor evolution, identifying common tumor ancestors and refining patient stratification. This study advances liquid biopsy methodologies in pediatric oncology and provides a rationale for the molecular alteration-informed selection and implementation of these complementary approaches within molecular tumor boards, with the aim of optimizing clinical management strategies for high-risk pediatric cancer patients. Significance Systematic liquid biopsy analyses within the pediatric precision oncology INFORM registry enabled a real-world, multicenter comparison of sequencing approaches across high-risk malignancies. By optimizing preanalytical and bioinformatic tools for pediatric settings, we improved plasma-based cancer detection, molecular tumor characterization, and identification of targetable alterations—laying the groundwork for integration into personalized medicine programs and clinical trials.

Here we report the results of the first comprehensive European trials for all soft tissue sarcoma entities, which aimed to develop a new risk stratification system, limit radiotherapy and chemotherapy for low-/standard-risk patients, and evaluate different chemotherapy regimens for high-risk patients. The prospective CWS-96 and CWS-2002P trials stratified patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) by Intergroup Rhabdomyosarcoma Study (IRS) group, histology and grade (CWS-96) or IRS group, lymph node status, tumour histology and size (CWS-2002P). Low-risk patients received no additional treatment. Standard-risk patients were treated with 44.8Gy radiotherapy, and in CWS-96, adjuvant chemotherapy was added for high-grade tumours (vincristine, actinomycin-D, ifosfamide, 160-240mg/m2 adriamycin/VAIA). High-risk patients received VAIA in CWS-96 or an intensified adriamycin regimen in CWS-2002P (VAIA-III, 320mg/m2 adriamycin), resection and/or 44.8Gy radiotherapy, followed by maintenance treatment with cyclophosphamide and vinblastine in certain NRSTS in CWS-2002P. The trials enrolled 1249 patients with localised NRSTS, of whom 483 (CWS-96) and 445 (CWS-2002P) were eligible for survival analysis. Histological classifications were retrospectively standardised, including recent data from the soft tissue sarcoma registry. Overall survival (OS) was significantly improved (5-year OS: 81% vs. 73%, p = 0.024) for patients treated in CWS-2002P compared to CWS-96, partly explained by the inclusion of more low-grade entities in CWS-2002P. The higher anthracycline dose in the VAIA-III regimen (CWS-2002P) did not improve survival (EFS: p = 0.23, OS: p = 0.73; matched pairs analysis). Re-classification revealed a higher proportion of malignant entities according to WHO in CWS-96 compared to CWS-2002P (90% vs. 81%, p < 0.001). Complete resection alone is sufficient to cure low-risk NRSTS. Survival was not improved by dose-intensified adjuvant chemotherapy (with/without maintenance treatment). Patients with completely resected high-risk disease may not profit from adjuvant radiotherapy.

The patient was a 56-year-old woman who had previously undergone living-donor kidney transplantation, followed by urinary diversion surgery due to recurrent pyelonephritis. Nine years after the urinary diversion, abdominal computed tomography performed for evaluation of lower abdominal pain revealed a renal calculus in the transplanted kidney. Percutaneous nephrolithotomy resulted in satisfactory stone fragmentation, but had to be performed again 14 months later to remove a residual stone that had increased in size.

Background/Objectives: Evaluating coronary artery abnormalities (CAAs) in Kawasaki disease (KD) is essential for treatment decisions and long-term management and prognosis. Accurate diagnosis is challenging due to differing criteria across guidelines. This study aimed to assess the variability in CAA prevalence using Japanese Ministry of Health (JMH) criteria and Z score formulas and identify the formula pair with the highest CAA diagnostic agreement. Methods: Echocardiographic data from 309 patients with acute KD were collected. CAA prevalence was evaluated using JMH criteria and Z score formulas of Kobayashi, de Zorzi, Kurotobi, McCrindle, Olivieri and Dallaire. Prevalence differences were analyzed using McNemar’s t-tests, Z score values with paired samples t-test, and agreement between Z score formula pairs with Cohen’s Kappa (κ) coefficients and Bland–Altman plots. Results: The CAA prevalence varied significantly across definitions. For the right CA, prevalence was lower by JMH criteria than by Z scores (32.7% vs. 37.2–39.8%). For the left main CA, JMH (47.6%) and Kobayashi (44.8%) showed higher prevalence compared to other formulas (25.8–42.9%). Variability was greater at higher Z score values (>5 mm, medium/large aneurysm). Overall, the Kobayashi–Dallaire and McCrindle–Dallaire pairs showed the highest agreement (κ = 0.745–0.831 and 0.569–0.870, respectively); however, the McCrindle–Dallaire reached only moderate agreement for the left main CA (κ = 0.569). Conclusions: The Kobayashi and Dallaire formulas appear most suitable for evaluating CAA in predominantly Caucasian populations. Larger validation studies are warranted to refine diagnostic criteria and optimize global KD care.

Background/Objectives: Complex cases in pediatric surgery involving multiple congenital anomalies pose significant diagnostic and therapeutic challenges. These conditions require coordinated interdisciplinary care tailored to the individual patient. We present a case of syndromic congenital anomalies in a neonate, later diagnosed with CHARGE syndrome, to illustrate the importance of staged, multidisciplinary management. Methods: A 34-year-old woman in her third pregnancy developed significant polyhydramnios at 31 weeks of gestation, followed by preterm labor. The neonate presented with esophageal atresia with tracheoesophageal fistula (EA/TEF), intrathoracic stomach, aortic coarctation, patent ductus arteriosus, atrial septal defect, and bilateral choanal atresia. A structured treatment protocol was developed and implemented at Klinikum Stuttgart by an interdisciplinary team comprising gynecology, pediatric surgery, cardiology, ENT, neonatology, and genetics. Results: Initial pediatric surgical procedures included ligation of the tracheoesophageal fistula, repositioning of the intrathoracic stomach, and primary esophageal anastomosis. Cardiovascular anomalies were managed through staged interventions. Bilateral choanal atresia was surgically corrected. Genetic testing confirmed CHARGE syndrome. Postoperative care included respiratory support, enteral nutrition, and regular esophageal dilations. Due to persistent reflux esophagitis, antireflux surgery is planned. Conclusions: This case underscores the importance of a highly individualized and interdisciplinary approach in the management of syndromic congenital anomalies. The presence of CHARGE syndrome with multiple system involvement required careful staging of surgical interventions and long-term coordination of follow-up care. Early genetic diagnosis and integrated team planning were critical in optimizing outcomes in this complex neonatal case.

assessed the impact of the quality of initial and subsequent surgeries on the survival of patients with nonmetastatic and metastatic paratesticular rhabdomyosarcoma enrolled in the two Cooperative Weichteilsarkom Studiengruppe (CWS) trials (CWS-96, 2002P) and the Soft Tissue Sarcoma Registry (SoTiSaR).The quality of local surgical control has revealed unsatisfactory results, with a high prevalence of protocol violations during primary surgery (42%) and pretreatment re-excision (20%).