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Background: SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed. Methods: CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide- ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide- ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs. Results: 296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95% CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI. Conclusion: Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: Meningioma is a rare entity in the pediatric and adolescent population. While maximal resection remains the established standard of care, the role of radiation therapy remains unclear. The aim of this retrospective study was to report the clinical and patient-reported outcomes of a cohort of 10 children and adolescents with intracranial meningioma treated with Pencil Beam Scanning Proton Therapy (PBS-PT) at the Paul Scherrer Institute between 1996 and 2022. The local control rates at three and five years were modest, yet overall survival remained excellent. Some patients reported functional status limitation during first year and 2 years after PBS-PT, with only one reporting limitation after 3 years. The good tolerance of the treatment in terms of acute toxicity and the absence of severe long-term side effects support the safety of the treatment and viability of PBS-PT as a suitable therapeutic option for intracranial meningioma in the pediatric and adolescent population. Purpose: The purpose of this study was to report the clinical and patient-reported outcomes of children and adolescents with intracranial meningioma treated with pencil beam scanning proton therapy (PBS-PT). Material and methods: Out of a total cohort of 207 intracranial meningioma patients treated with PBS-PT between 1999 and 2022, 10 (4.8%) were children or adolescents aged < 18 years. Median age was 13.9 years (range, 3.2–17.2). Six (60%) children were treated as primary treatment (postoperative PT, n = 4; exclusive PT, n = 2) and four (40%) at the time of tumor recurrence. Acute and late toxicities were registered according to Common Terminology Criteria of Adverse Events (CTCAE). Quality of life (QoL) before PBS-PT was assessed using PEDQOL questionnaires. Educational, functional, and social aspects after PT were assessed through our in-house developed follow-up surveys. Median follow-up time was 71.1 months (range, 2.5–249.7), and median time to last questionnaire available was 37.6 months (range, 5.75–112.6). Results: Five (50%) children developed local failure (LF) at a median time of 32.4 months (range, 17.7–55.4) after PBS-PT and four (80%) were considered in-field. One patient died of T-cell lymphoma 127.1 months after PBS-PT. Estimated 5-year local control (LC) and overall survival (OS) rates were 19.4% and 100.0%, respectively. Except for one patient who developed a cataract requiring surgery, no grade ≥3 late toxicities were reported. Before PT, patients rated their QoL lower than their parents in most domains. During the first year after PT, one child required educational support, one needed to attend to a special school, one had social problems and another three children required assistance for daily basic activities (DBA). Three years after PT, only one child required assistance for DBA. Conclusions: The outcome of children with intracranial meningioma treated with PBS-PT is in line with other centers who have reported results of radiation therapy delivered to this particular patient group. This therapy provides acceptable functional status profiles with no high-grade adverse radiation-induced events. [ABSTRACT FROM AUTHOR]

Simple Summary: While gastric carcinoma is prevalent in adults and is one of the most common causes of cancer-related death, the disease is exceptionally rare in children. The aim of this analysis was to present peculiarities of gastric carcinoma in children and adolescents. A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to contribute significantly to the risk of developing gastric carcinoma at a young age. In adolescents, these tumors are often diagnosed at an advanced stage of disease, which is associated with a poor prognosis and emphasizes the need for the development of new therapeutic strategies, such as molecular-targeted treatments. (1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz–Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments. [ABSTRACT FROM AUTHOR]

Background: Craniopharyngioma is a tumor of low histological malignancy resulting from an anomaly of embryonic development. Affected children and adolescents are being studied with respect to their quality of life, progression-free survival, and overall survival in the framework of the ongoing KRANIOPHARYNGEOM 2007 project. Methods: This prospective, multicenter project consists of a randomized trial with an adaptive design combined with a purely observational study. The randomized, unblinded trial includes patients whose tumors have been incompletely resected and is intended to compare the outcomes of immediate postoperative radiotherapy versus radiotherapy on progression. Its primary endpoint is quality of life as assessed subjectively by the patients themselves with the "Pediatric Quality of Life" questionnaire (PEDQOL). In exploratory analyses, linear mixed models were used to study the effect of further factors on quality of life. Results: An interim intention-to-treat analysis of the randomized trial revealed only minor differences between the treatment arms with respect to quality of life (n = 24). The exploratory analyses (n = 131) showed that preoperative involvement of, or operative damage to, the anterior and posterior regions of the hypothalamus was associated with a lower quality of life. Complete resection was followed by a lower quality of life than incomplete resection. Radiotherapy, a common treatment for tumors that progress after incomplete resection, was also associated with a lower quality of life. Conclusion: Hypothalamus-sparing treatment approaches are recommended to optimize the quality of life of children and adolescents with craniopharyngioma. The available evidence does not support any recommendation as to when radiotherapy should be performed after incomplete resection so that the best quality of life can be achieved. [ABSTRACT FROM AUTHOR]

Purpose To assess clinical outcomes in children with rhabdomyosarcoma (RMS) treated with pencil beam scanning (PBS) proton therapy (PT). Methods and materials Eighty-three RMS (embryonal, n = 74; 89%) patients treated between January 2000 and December 2014 were included. The median age was 4.5 years (range, 0.8–15.5). All patients received systemic chemotherapy according to prospective protocols. Patients had low-, intermediate-, and high-risk disease in 24%, 63%, and 13% of cases, respectively. The median total dose delivered was 54 Gy(RBE) (range, 41.4–64.8). Results After a median follow-up time of 55.5 months (range, 0.9–126.3), local failure occurred in 16 patients. The 5-year local-control survival rate was 78.5% [95% confidence interval (CI), 69.5–88.5%]. Significant predictors for local failure were group/stage, tumour location, and size. Fourteen patients (16%) died, all from tumour progression. The 5-year overall survival was 80.6% (95%CI, 71.8–90.0%). The 5-year incidence of grade 3 non-ocular late toxicity was 3.6% (95%CI, 1–12%). No grade 4–5 late toxicities were observed. One radiation-induced malignancy was observed (1.2%). The Quality of Life (QoL) scores increased significantly after PT compared to baseline values. Conclusions PBS PT led to excellent outcome in children with RMS. Late non-ocular toxicity was minimal and QoL good. [ABSTRACT FROM AUTHOR]

Introduction There is increasing recognition of the long-term sequelae of brain tumours treated in childhood. Five year survival rates now exceed 75% and assessing the quality of survival (QoS) in multiple domains is essential to any comparison of the benefits and harms of treatment regimens. Aim The aim of this position statement is to rationalise assessments and facilitate collection of a common data set across Europe. Sufficient numbers of observations can then be made to enable reliable comparisons between outcomes following different tumour types and treatments. Methods This paper represents the consensus view of the QoS working group of the Brain Tumour group of the European Society of Paediatric Oncology regarding domains of QoS to prioritise for assessment in clinical trials. This consensus between clinicians and researchers across Europe has been arrived at by discussion and collaboration over the last eight years. Results Areas of assessment discussed include core medical domains (e.g. vision, hearing, mobility, endocrine), emotion, behaviour, adaptive behaviour and cognitive functioning. Conclusions A ‘core plus’ approach is suggested in which core assessments (both direct and indirect tests) are recommended for all clinical trials. The core component is a relatively brief screening assessment that, in most countries, is a sub-component of routine clinical provision. The ‘plus’ components enable the addition of assessments which can be selected by individual countries and/or tumour-, age-, and location-specific groups. The implementation of a QoS protocol common to all European clinical studies of childhood brain tumours is also discussed [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to cross-sectionally assess quality of life (QoL) in survivors of childhood Hodgkin's disease (HD) in a cohort treated for HD in the successive German-Austrian therapy studies HD-78, HD-82, HD-85, HD-87, HD-90, HD-95, respectively, in accordance with the HD-Interval-Treatment recommendation between 1978 and 2002. Patients and methods: Data from QoL questionnaires were provided by 1,202 (66 %) of 1,819 invited survivors. These included the EORTC QLQ-C30 and socio-demographic variables. Data of a homogenous sub-sample ( n = 725) defined by age (21-41 years) and event- free-survival (no progress, relapse or secondary malignancies) were compared to an age-adjusted German reference sample ( n = 659). Results: While the global and physical QoL scores were comparable to those of the general population, survivors' mean scores were more than 10 points lower on the EORTC QLQ-C30 scales 'Emotional' and 'Social Functioning'. On the symptom scales, higher mean scores, exceeding 10 points, were obtained for the scales 'Fatigue' and 'Sleep'. In general, there was a gender effect showing lower functioning and higher symptom levels in women, most prominently in the group of young women (21-25 years). The results within the group of HD survivors could not be associated with the time since treatment, the age of HD survivors at diagnosis or the extent of therapy burden. Conclusion: Clinicians engaged in follow-up care should be sensitive to aspects of fatigue and related (emotional) symptoms in HD childhood cancer survivors and encourage their patients to seek further support if needed. [ABSTRACT FROM AUTHOR]

Background: Survival after childhood cancer has improved to more than 80% during the last few years, leading to an increased number of childhood cancer survivors. Cancer itself, or its treatment, may cause chronic health conditions, including somatic and mental sequelae, which may affect survivors' health-related quality of life (HRQoL). Objective: The project PanCareLIFE aims to establish a large database with comprehensive data on childhood cancer survivors from different European countries, including data on HRQoL. Within PanCareLIFE, this study aims to describe HRQoL in survivors, investigate predictors of HRQoL, and describe the association of HRQoL with hearing and female fertility impairment. This paper describes the design of the HRQoL study, the origin of data, strategies for data collection, and sampling characteristics of survivors from each contributing country. Methods: A total of 6 institutions from 5 European countries (the Czech Republic, France, Germany, the Netherlands, and Switzerland) provided data on HRQoL assessed with the Short Form 36 and on relevant predictors. The central PanCareLIFE data center aggregated the data and harmonized the variables between the institutions. Survivors were eligible if they received a diagnosis of cancer according to the 12 main groups of the International Classification of Childhood Cancer, 3rd edition, or Langerhans cell histiocytosis; were aged ≤18 years at the time of diagnosis; were residents of the respective country at the time of diagnosis; had survived ≥5 years after cancer diagnosis; were aged ≥18 years at the time of the questionnaire survey; and did not refuse to registration in the national or local childhood cancer cohort. Results: We identified 24,993 eligible survivors. Of those, 19,268 survivors received a questionnaire and 9871 survivors participated, resulting in response rates of 9871/24,993 (39.50%) of eligible survivors and of 9871/19,268 (51.23%) invited survivors. Most participants were diagnosed with cancer between the ages of 10 and 14 years (3448/9871, 34.93%) or <5 years (3201/9871, 32.43%). The median age was 8 years. Of the 9871 participants, 3157 (31.97%) were survivors of leukemia, 2075 (21.02%) lymphoma, and 1356 (13.7%) central nervous system (CNS) tumors. Most participants (9225/9871, 93.46%) had no history of a subsequent tumor; 77.45% (7645/9871) received chemotherapy with or without other treatments. More than half (5460/9871, 55.31%) were aged 25 to 34 years at the time of the HRQoL study. Participating survivors differed from nonparticipants; participants were more often women, survivors of leukemia or lymphoma, and less frequently, survivors of CNS tumors than nonparticipants. Conclusions: PanCareLIFE successfully assessed HRQoL and its predictors in 9871 European survivors of childhood cancer. This large population will permit detailed investigations of HRQoL after childhood cancer, particularly the impact of hearing and female fertility impairment on HRQoL. International Registered Report Identifier (IRRID): RR1-10.2196/21851 JMIR Res Protoc 2021;10(1):e21851 doi:10.2196/21851 We help JMIR researchers to raise funds to pursue their research and development aimed at tackling important health and technology challenges. If you would like to show your support for this author, please donate using the button below. The funds raised will directly benefit the corresponding author of this article (minus 8% admin fees). Your donations will help this author to continue publishing open access papers in JMIR journals. Donations of over $100 may also be acknowledged in future publications. Suggested contribution levels: $20/$50/$100 [ABSTRACT FROM AUTHOR]

Abstract Aims Survival after cancer diagnosed during childhood or adolescence continues to improve with new treatments and supportive therapies. Optimal long-term care requires that risks to vulnerable organs are clearly defined and translated into guidelines that are implemented into practice. PanCareLIFE is a pan-European consortium that addresses survivorship issues comprising fertility, hearing impairment and quality of life. This article describes the scientific basis of PanCareLIFE's studies. Methods PanCareLIFE involves 17 partner institutions from eight European countries, with additional 11 data providers from five other countries. Study designs and methods include molecular genetic, cohort and case-control studies, a longitudinal study and an intervention study. Ethics and data protection issues have been taken into account from the beginning. Results PanCareLIFE will investigate the way that treatment impairs female fertility, by evaluating anti-Müllerian hormone levels and the underlying genetic susceptibility to loss of fertility. For our fertility studies, more than 6000 survivors have completed questionnaires, more than 1500 provided serum samples and more than 400 case-control triads have been identified. Fertility preservation guidelines for boys and girls will be developed. More than 2000 survivors have contributed audiograms for the ototoxicity study. Almost 1000 samples were sent for genetic analysis related to ototoxicity and gonadal reserve. The SF-36 questionnaire will measure quality of life in more than 10,000 survivors. Conclusions The large number of subjects enrolled in PanCareLIFE and the detailed information accumulated will allow in-depth evaluation of important outcomes. Fertility preservation guidelines will help patients and their families make informed decisions and contribute to their long-term well-being. Highlights • PanCareLIFE is a large pan-European study on late effects after childhood cancer. • Studies of hearing loss, fertility impairment and quality of life are included. • Clinical and genetic methods with new guidelines will lead to improved health. [ABSTRACT FROM AUTHOR]

To analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification. Forty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n = 23), French TGM protocols (n = 10), Italian Rare Tumour Project (TREP) registry (n = 6), and the Polish Pediatric Rare Tumour Study group (n = 5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO). Median age was 13.9 (0.5–17.4) years. All patients underwent resection by tumour enucleation (n = 8), ovariectomy (n = 17), adenectomy isolated (n = 18) or with hysterectomy (n = 1). FIGO-stage: Ia 24 pts., Ic 17 pts., II/III 3 pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic–III), eight relapsed, and five patients died. Eleven patients were initially treated with two to six cycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62 months, event-free survival is 0.70 ± 0.07, relapse-free survival 0.81 ± 0.06 and overall survival 0.87 ± 0.05. Prognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated. [ABSTRACT FROM AUTHOR]