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Abstract The number of patients surviving ≥5 years after initial cancer diagnosis has significantly increased during the last decades due to considerable improvements in the treatment of many cancer entities. A negative consequence of this is that the emergence of long-term sequelae and endocrine disorders account for a high proportion of these. These late effects can occur decades after cancer treatment and affect up to 50% of childhood cancer survivors. Multiple predisposing factors for endocrine late effects have been identified, including radiation, sex, and age at the time of diagnosis. A systematic literature search has been conducted using the PubMed database to offer a detailed overview of the spectrum of late endocrine disorders following oncological treatment. Most data are based on late effects of treatment in former childhood cancer patients for whom specific guidelines and recommendations already exist, whereas current knowledge concerning late effects in adult-onset cancer survivors is much less clear. Endocrine sequelae of cancer therapy include functional alterations in hypothalamic-pituitary, thyroid, parathyroid, adrenal, and gonadal regulation as well as bone and metabolic complications. Surgery, radiotherapy, chemotherapy, and immunotherapy all contribute to these sequelae. Following irradiation, endocrine organs such as the thyroid are also at risk for subsequent malignancies. Although diagnosis and management of functional and neoplastic long-term consequences of cancer therapy are comparable to other causes of endocrine disorders, cancer survivors need individually structured follow-up care in specialized surveillance centers to improve care for this rapidly growing group of patients.

Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitute a distinct clinicopathological entity in the current World Health Organization (WHO) classification. However, its genomic features remain sparsely characterized. Here, we combine whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS), and fluorescence in situ hybridization (FISH) from 47 EBV + DLBCL (NOS) cases to delineate the genomic landscape of this rare disease. Integrated WGS and tNGS analysis clearly distinguished this tumor type from EBV-negative DLBCL due to frequent mutations in ARID1A (45%), KMT2A/KMT2D (32/30%), ANKRD11 (32%), or NOTCH2 (32%). WGS uncovered structural aberrations including 6q deletions (5/8 patients), which were subsequently validated by FISH (14/32 cases). Expanding on previous reports, we identified recurrent alterations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%), and YY1 (6%). Lastly, functional annotation of the mutational landscape by sequential gene set enrichment and network propagation predicted an effect on the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL6/JAK/STAT (SOCS1/3, STAT3), and WNT signaling (FRAT1, SFRP5) alongside aberrations in immunological processes, such as interferon response. This first comprehensive description of EBV + DLBCL (NOS) tumors substantiates the evidence of its pathobiological independence and helps stratify the molecular taxonomy of aggressive lymphomas in the effort for future therapeutic strategies.

This study investigated sleep quality and health-related quality of life (HRQOL) among long-term survivors of Hodgkin (HL) and non-Hodgkin lymphoma (NHL). The aim was to explore the impact of personal and health-related factors on sleep quality as well as associations between sleep quality and HRQOL. For the postal survey, participants with a minimum age of 18 years initially treated between 1998 and 2008 were recruited via the population-based cancer registry in Schleswig-Holstein, Northern Germany. Questionnaires included amongst others the Pittsburg Sleep Quality Index (PSQI) and the 36-Item Short Form Health Survey (SF-36v1). Descriptive and comparative statistics were performed. Additionally, a regression analysis was conducted to identify predictors of sleep quality. In total, we recruited 515 participants (398 NHL, 117 HL) with a mean age of 63.1 years. Approximately half of the survivors were classified as good sleepers. HRQOL scores differed between good and poor sleepers with lower scores in poor sleepers. In a prediction model, self-reported depression, exhaustion, higher age, inability to work, endocrinological disorders and female gender classified as predictors of sleep quality. This study highlights the impact of sleep quality on HRQOL in long-term survivors of NHL and HL. Thus, sleep quality should be routinely assessed during follow-up of cancer survivors with special attention to patients with potential risk factors.

Many childhood cancer survivors (CCS) develop treatment-related late effects, including an increased risk of obesity and metabolic syndrome. A healthy lifestyle can reduce the risk of associated comorbidities. Therefore, at-risk CCS could benefit from lifestyle counseling during regular long-term follow-up (LTFU). We implemented a new form of care to decrease the long-term morbidity among CCS and to gain new insights into the lifestyle of those patients. Over a 1-year study period, lifestyle counseling was integrated into LTFU care. Metabolic disorders, including hypercholesterolemia, diabetes mellitus, overweight or underweight, and low activity levels, were assessed as screening parameters for various risk groups. The perspectives of CCS, physicians, and sports scientists were compared to identify those with the highest needs. Each lifestyle counseling included general recommendations for physical activity, as well as an assessment of individual preferences for and barriers to the implementation of a healthy lifestyle. A follow-up appointment after 1 month was performed. Of the 155 CCS aged 18 to 63 years (n=100, 65% female and n=55, 35% male), 112 (72%) had an indication for lifestyle counseling, identified by physicians, sports scientists, or the CCS themselves. Metabolic disorders affected 45% (n=70) of these CCS, and 46% (n=72) did not meet recommended activity levels. A total of 120 (77%) CCS received lifestyle counseling, including 8 initially uninterested individuals who became open to recommendations. Those with intensive cancer treatment history showed the greatest need. A total of 65 (54%) CCS were advised to change their lifestyle in both areas (diet and exercise) while 51 (43%) CCS received recommendations for only exercise (n=43 CCS, 36%) or diet (n=8 CCS, 7%). A total of 4 (3%) CCS, although interested in counseling, received no advice, as they already met the recommendations. Follow-up revealed high adherence to recommendations and successful integration into daily lives. In total, 97% (n=150) of survivors indicated that the provision of lifestyle counseling during LTFU would be generally beneficial. Incorporating specialized health care professionals such as sports scientists into survivorship care enhances the multidisciplinary approach of LTFU care. Promoting a healthy lifestyle by offering guideline-based lifestyle counseling is broadly accepted among CCS and may reduce long-term morbidity.

Background Long‐term childhood cancer survivors (CCS) may develop anthracycline‐induced cardiomyopathy. Our cross‐sectional study focused on the question of whether a central echocardiographic reference assessment is associated with a higher detection rate of cardiac dysfunction in a population‐based cohort of affected children with neuroblastoma or nephroblastoma. We also examined the prevalence of anthracycline‐induced cardiomyopathy and its risk factors. Methods and Patients The cohort of this subproject comprises 370 nephroblastoma or neuroblastoma survivors diagnosed with cancer between 1990 and 2012. At study entry, participants were younger than 18 years old, had been treated with anthracyclines, and had no documented previous cardiac disease. Data were collected via patient questionnaires, cardiologic examinations in the network of adults with congenital heart defects (Erwachsene mit angeborenem Herzfehler [EMAH]) and a reference assessment of the recorded echocardiography. Results The prevalence of cardiomyopathy in the study cohort (mean age: 12 years) was 6.3% at a median of 9.1 years after initial cancer diagnosis. Risk factors were an age under 5 years at tumor diagnosis and concomitant treatment with cyclophosphamide or radiation. As a central and novel finding, the detection rates by the EMAH cardiologists and the reference center are similarly high but discrepant. Discussion Limitations were mainly due to the low responder rate and incomplete data. This study established a nationwide competence network linking pediatric oncology and cardiology centers across six university hospitals in Germany, enabling data collection on pediatric CCS. Despite lower case numbers compared to adult CCS cohorts, meaningful data were gathered and analyzed. Conclusion Cardiac late effects after anthracycline‐based therapy in childhood affect a relevant proportion of long‐term CCS at pediatric age. In order to enable timely diagnosis and treatment, preventive examinations are essential and might benefit from additional central reference assessments. Discrepancy in detection of cardiomyopathy by reference and EMAH cardiologists requires further investigation.

Background In Germany, around 2.250 children and adolescents are diagnosed with cancer each year. Despite generally positive long-term survival rates, many patients must cope with late effects of the disease and its treatment. This highlights the need for a well-structured, long-term approach addressing both physical and mental health issues. Currently, the German healthcare system lacks such comprehensive structures. Our study aims to evaluate the effectiveness of a structured, multidisciplinary long-term approach compared to conventional “treatment as usual” (TAU). Methods A prospective, multicenter study with ten pediatric university clinics in Germany will be conducted. The cluster-randomization takes place at the clinic level. Children and adolescents who completed their cancer treatment at least five years ago and their parents will be eligible to participate. While the control group (CG) receives TAU, the intervention group (IG) participates in a structured program. This program includes risk-based medical treatment and psychosocial interventions tailored to each patient’s individual needs within a two-month timeframe. The primary outcome is the improvement of self-efficacy. Secondary outcomes are satisfaction with health care, improvement of health-related quality of life (HRQoL), reduction of mental health problems, and improvement of transition readiness. Discussion This approach has the potential to optimize the health care for individuals who survived cancer during childhood or adolescence. It addresses the challenges of overuse, underuse, and misuse of health care resources. By considering both medical and psychosocial factors and promoting increased self-efficacy, independent from parental involvement, it may facilitate a smoother transition to adult medicine and enhance adherence to lifelong aftercare. If proven successful, this approach will contribute to the integration of multidisciplinary strategies into standard healthcare practice. Trial registration German Clinical Trials Register DRKS00029269. Registered on December 23, 2022.

Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations. We analyzed retrospectively long-term follow-up data of 36 childhood cancer survivors after initial diagnosis with acute leukemia (n = 18) or brain tumor (n = 18), all treated with cranial radiotherapy. Detected RIC in long-term follow-up brain MRI (1.5 or 3 Tesla) were classified following the Zabramski MRI classification and were categorized into \"high\" (Zabramski type I, II or V) or \"low\" (type III or IV) risk of hemorrhage. 18 patients (50%) showed RIC with a significant relation to the original tumor entity (p = 0.023) and the cumulative radiation dose to the brain (p = 0.016): all 9 childhood cancer survivors diagnosed with medulloblastoma developed RIC. We classified RIC in only 3/36 childhood cancer survivors (8%) (1 patient with acute lymphoblastic leukemia [Zabramski type II] and 2 patients with medulloblastoma [type I and type II]) as high risk for hemorrhage, the remaining RIC were classified as Zabramski type IV with low risk for hemorrhage. None of the childhood cancer survivors with RIC showed symptomatic hemorrhages. RIC are common late effects in childhood cancer survivors treated with cranial radiotherapy affecting half of these patients. However, only a few RIC (occurring in 8% of all reviewed childhood cancer survivors) were classified as high risk for hemorrhage and none of the childhood cancer survivors with RIC developed symptomatic hemorrhages. Thus, we conclude that RIC are low-risk findings in brain MRI and the course is mainly benign.

In childhood cancer survivors (survival of 5 years or more after diagnosis), cardiac toxicity is the most common nonmalignant cause of death attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. The use of genetic markers has been proposed, together with clinical risk factors, to predict individual risk of cardiac toxicity from cancer therapies, such as doxorubicin. The primary aim of this study is to evaluate the value of multimarker genetic testing for RARG rs2229774, UGT1A6 rs17863783, and SLC28A3 rs7853758 for predicting doxorubicin-induced cardiotoxicity. The secondary aim is to replicate previously described associations of candidate genetic markers with doxorubicin-induced cardiotoxicity. Moreover, we will evaluate the prevalence of cardiovascular dysfunction in childhood cancer survivors after neuroblastoma or nephroblastoma. This is the pharmacogenetic substudy of the research project Structural Optimization for Children With Cancer After Anthracycline Therapy (LESS-Anthra). We invited 2158 survivors of childhood neuroblastoma or nephroblastoma treated with doxorubicin according to the trial protocols of SIOP 9/GPOH, SIOP 93-01/GPOH, SIOP 2001/GPOH, NB 90, NB 97, or NB 2004 to participate in this prospective cross-sectional cohort study. The study participants underwent a cardiological examination and were asked to provide a blood or saliva sample for genotyping. The study participants' health statuses and cardiovascular diagnoses were recorded using a questionnaire completed by the cardiologist. Digital echocardiographic data were centrally evaluated to determine the contractile function parameters. Medical data on the tumor diagnosis and treatment protocol were taken from the study documentation. Survivors were screened for variants of several candidate genes by TaqMan genotyping. This study includes 657 survivors treated with doxorubicin for childhood cancer, the largest German cohort assembled to date to investigate cardiovascular late effects. Data analyses are yet to be completed. This study will define the genetic risk related to 3 marker genes proposed in a pharmacogenetic guideline for risk assessment. Moreover, the results of this study will show the prevalence of cardiovascular dysfunction in survivors of pediatric neuroblastoma or nephroblastoma who were treated with doxorubicin. The results will help to improve primary treatment and follow-up care, thus reducing cardiovascular late effects in the growing population of childhood cancer survivors. German Clinical Trials Register DRKS00015084; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015084. DERR1-10.2196/27898.

In this teaching tip, we describe our approach to elevating the quality of group work in an information technology (IT) project management course by implementing three practices of experiential and peer learning that work more effectively when combined. The first practice addresses slacking in group work by applying a flipped classroom style that allowed students to acquire individual skills and then reflect on those skills in pairs with the instructor's support and supervision. The second practice uses concept maps to deepen the understanding of relevant tools and concepts and to foster the synthesis of topics and big-picture composition. The third practice addresses the prevalent divide-and-conquer culture in group work, in which we structured intense work sessions in the classroom with instructor guidance and supervision to complete group projects. In this proposed framework, the work sessions mimic the concept of a dojo that is widely used in martial arts. Even though it is still rare in information systems (IS) education, this concept has been applied in the context of software engineering and IT projects--both in higher education and in industry for employee training. The three-pronged approach described in this paper is intended to provide students with an experiential learning experience that transforms group work from an inefficient process to an intense and focused short-term period of work. Based on our observations and student feedback, the approach is effective and can positively impact group experience by countering common pitfalls, such as the divide-and-conquer mentality and social loafing, and by enhancing peer learning efficacy. We also provide suggestions for its application in the context of an IT project management course.