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Ependymomas are the third most common brain tumors in children. Standard of care is surgery followed by adjuvant radiation therapy. Controversy in the literature still exists over optimal radiation therapy dose. We completed a systematic review and meta-analysis to determine the optimal dose for local control (LC), event-free survival (EFS), and overall survival (OS) in pediatric patients. We searched MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and Web of Science through January 2024. We included cohort studies that compared adjuvant radiation therapy of ≤54 Gy with >54 Gy in pediatric patients (≤22 years) with nonmetastatic intracranial ependymomas. We assessed study quality using the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies. We pooled studies using a random effects meta-analysis for hazard ratios (HR), 95% confidence intervals (CI), and assessed statistical heterogeneity via I2. When HRs were unavailable, we transformed risks using established methods. We narratively summarized qualitative outcomes. Seven studies met our inclusion criteria, covering a combined 1321 patients. Studies included a range of doses from 45 to 66.6 Gy. Compared with >54 Gy, we found no difference in LC for those receiving ≤54 Gy (HR, 0.83; 95% CI, 0.56-1.24; I2, 49.1%), in EFS (HR, 1.02; 95% CI, 0.95-1.09; I2, 0.00%), and OS (HR, 0.99; 95% CI, 0.82-1.20; I2, 37.5%). Two studies reported on subtotal resection by radiation therapy dose, neither study reporting statistical differences in LC, EFS, or OS, although the number of patients was small (n ≤ 30). Five studies reported on late effects, with brainstem radionecrosis, radiation-induced vasculopathy, and secondary tumors being the most frequent. Overall study quality was high, although lower scores were consistently seen in comparability of cohorts. To our knowledge, no studies reported on molecular subgroups. We found no difference in LC, EFS, or OS for those treated with ≤54 Gy compared with >54 Gy. There were insufficient data to complete a subgroup meta-analysis on radiation therapy dosing based on extent of resection or molecular subgroups. [ABSTRACT FROM AUTHOR]

This study aimed to assess the disease burden of cancer in young adults globally and the changes between 2012 and 2022. A comprehensive analysis of global cancer statistics of young adults based on data provided by GLOBOCAN 2022. The incidence and mortality estimates for cancer in young adults in 2012 and 2022 were obtained from the publication by Fidler et al. and GLOBOCAN 2022, respectively. Data were displayed descriptively and compared at the sex, global, regional, national and human development index (HDI) levels. Associations between HDI rank and cancer incidence and mortality were explored by Pearson correlation analysis. In 2022, the number of new cancer cases and deaths in young adults were estimated to be 1,227,907 and 349,550, respectively, with the age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR) of 49.5 and 14.2 per 100,000 population. In young adults, 47.22 % of new cases were breast, thyroid and cervical cancer, while the leading causes of cancer-related death were breast, leukaemia and cervical cancer. Compared to 2012, the number of new cases and the ASIR increased by 25.89 % and 14.32 %, respectively, while the number of deaths and the ASMR decreased by 2.03 % and 10.69 %, respectively. However, cancer burden and its changes varied substantially across geographical regions, HDI levels and cancer types. In general, infection-related cancers were more common in less developed regions, but their incidence decreased significantly, while Westernised lifestyle-related cancers were more common in developed countries and their incidence is increasing. Cancer contributes substantially to health-related burdens in young adults and the overall incidence has increased dramatically in the past decade. However, the incidence and mortality of cancer in this age group varied considerably by sex, cancer type, region, country and HDI level. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of rituximab treatment for anti- N -methyl- d -aspartate receptor (NMDAR) encephalitis without tumor in children. Eighteen pediatric patients with NMDAR encephalitis treated with rituximab after failure of intravenous immunoglobulin (IVIG) and methylprednisolone treatment were analyzed retrospectively in terms of their medical history, clinical features, laboratory examination results, and treatments. The modified Rankin scale (mRS) score, peripheral blood CD19+ B cells, recurrence, and adverse events were used to evaluate the efficacy and safety of rituximab. The patients were treated with rituximab 3.2 ± 1.0 days after the end of IVIG and methylprednisolone treatment. After initial rituximab treatment for four weeks, the mRS score and number of CD19+ B cells in all patients were significantly lower than those before treatment (P < 0.05). At the last follow-up (44.1 months, 17.7 S.D.), all patients had recovered well (mRS ≤2), 14 patients (77.8%) recovered completely (mRS = 0), three patients had recurrent seizures, and one patient had mental and language impairment. Two patients had transient mild adverse events during infusion, and none of the other patients experienced severe adverse events during hospitalization or follow-up. Rituximab appears safe and may be effective for the treatment of anti-NMDAR encephalitis without tumor in children refractory to first-line agents. [ABSTRACT FROM AUTHOR]

Pediatric brain tumor (PBT) survivors are at significantly increased risk of cognitive, psychosocial, and educational/vocational sequelae that impact health-related quality of life. These complications and health morbidities result in high burden on survivors and their families, particularly those already vulnerable to disparities in health care access and outcomes. Since neurological comorbidities are common in this population, neurologists are uniquely positioned to screen, treat identified symptoms, and connect families with services and resources. A tiered assessment approach can facilitate early identification of concerns and reduce barriers to care. We review common presenting conditions, highlight risk factors, and provide screening tools and recommendations to facilitate comprehensive survivorship care for PBT survivors. [ABSTRACT FROM AUTHOR]

Mature ovarian dermoid cysts (ODCs) are the most common benign ovarian tumors diagnosed in children. However, there is minimal data on management of ODCs in premenarchal patients. This study assesses characteristics associated with expectant (EM) vs surgical (SM) management in premenarchal patients and the growth rate of ODCs in EM patients at a single institution. Forty-four premenarchal patients, either post-surgical with pathologically-confirmed ODC or having radiologic findings consistent with ODCs, were included. Data collected included demographics, cyst characteristics, imaging findings, presence of symptoms, surgical procedure performed, and ovarian torsion occurrence. Patient age at diagnosis was similar between groups (SM: 8.8 vs EM: 8.0, P =.55). At presentation, 36 patients (82%) underwent SM and 8 (18%) underwent EM. There was a significant difference in cyst size between groups (SM: 8.9 cm vs EM: 3.6 cm, P =.004). Of SM patients, 30% underwent oophorectomy vs cystectomy, with a significant difference in ODC size between procedures (11.8 cm vs 7.7 cm, P =.016). Of EM patients, 75% had at least one and 60% had three follow-up ultrasounds, with average follow-up timeframes of 3.7 and 27 months respectively. Average yearly ODC growth rate for the latter group was 0.8 cm. The average yearly growth rate of ODCs in premenarchal patients within our institution was slower than in older cohorts, and both age and cyst size played significant roles in determining surgical procedure. Continued study on EM in premenarchal ODCs will help define parameters for recommending SM vs EM in this population. [ABSTRACT FROM AUTHOR]

Anatomical models have key applications in radiotherapy, notably to help understand the relationship between radiation dose and risk of developing side effects. This review analyses whether age-specific computational phantoms, developed from healthy subjects and paediatric cancer patient data, are adequate to model a paediatric population. The phantoms used in the study were International Commission on Radiological Protection (ICRP), 4D extended cardiac torso (XCAT) and Radiotherapy Paediatric Atlas (RT-PAL), which were also compared to literature data. Organ volume data for 19 organs was collected for all phantoms and literature. ICRP was treated as the reference for comparison, and percentage difference (P.D) for the other phantoms were calculated relative to ICRP. Overall comparisons were made for each age category (1, 5, 10, 15) and each organ. Statistical analysis was performed using Microsoft Excel (version 16.59). The smallest P.D to ICRP was for Literature (-17.4%), closely followed by XCAT (26.6%). The largest was for RT-PAL (88.1%). The rectum had the largest average P.D (1,049.2%) and the large bowel had the smallest (2.0%). The P.D was 122.6% at age 1 but this decreased to 43.5% by age 15. Linear regression analysis showed a correlation between organ volume and age to be the strongest for ICRP (R2 = 0.943) and weakest for XCAT (R2 = 0.676). The phantoms are similar enough to ICRP for potential use in modelling paediatric populations. ICRP and XCAT could be used to model a healthy population, whereas RT-PAL could be used for a population undergoing/after radiotherapy. [ABSTRACT FROM AUTHOR]

The article delves into the intricacies of administering anesthesia to children diagnosed with cancer. It delves into the challenges and considerations surrounding adjuvant chemotherapy, which is often part of cancer treatment protocols for children. It discusses strategies and guidelines aimed at effectively managing this complication, ensuring the best possible outcomes for children undergoing cancer therapy.

To investigate the incidence rate of primary brain tumors (PBTs) among Palestinian children over a 6-year interval. This study also aimed to identify the predominant histopathologic types identified in these children. This retrospective epidemiologic study focused on PBTs in children (<15 years) in Palestine. The data were collected from the registry system at Al-Makassed Hospital in Jerusalem, a prominent referral institution in Palestine and the largest center for PBTs in the region, over a 6 years period from 2018 to 2023. The incidence rate of PBTs in children (<15 years) was 1.33 per 100,000 person-years, with a 5% mortality rate. Pilocytic astrocytoma was the most common type (24%), followed by medulloblastoma (15.2%) and glioblastoma (6.3%). About one half of the tumors in children were malignant. Headaches were the most common first sign or symptom. About 20% of brain tumors in children were situated within the ventricles, making it the most prevalent location of these tumors, followed by the cerebellum (15.19%) and frontal lobe (11.39%). This is the first national study in Palestine investigating PBTs in children. The crude incidence rate of primary brain tumors among Palestinian children was lower than the incidence rate in many countries around the world. It is recommended that more research be done on the epidemiology and distribution of PBTs in children in Palestine. [ABSTRACT FROM AUTHOR]

The success and safety of modern radiotherapy relies on accurate contouring. Understanding the time taken to complete radiotherapy contours is critical to informing workforce planning and, in the context of a workforce shortfall, advocating for investment in technology and multi-professional skills mix. We aimed to quantify the time taken to delineate target volumes for radical radiotherapy. The Royal College of Radiologists circulated two electronic surveys via email to all clinical oncology consultants in the UK. The individual case survey requested anonymous data regarding the next five patients contoured for radical radiotherapy. The second survey collected data on respondents' usual practice in radiotherapy contouring. The median time to contour one radiotherapy case was 85 minutes (IQR = 50–131 minutes). Marked variability between and within tumour sites was evident: paediatric cancers took the most time (median = 210 minutes, IQR = 87.5 minutes), followed by head and neck and gynaecological cancers (median = 120 minutes, IQR = 71 and 72.5 minutes respectively). Breast cancer contouring required the least time (median = 43 minutes, IQR = 60 minutes). Radiotherapy technique, inclusion of nodes and 4D CT planning were associated with longer contouring times. A non-medical professional was involved in contouring in 65% of cases, but clinical oncology consultants were involved in target volume delineation in 90% of cases, and OARs in 74%. Peer review took place in 46% of cases with 56% of consultants reporting no time for peer review in their job plan. Contouring for radical radiotherapy is complex and time-consuming, and despite increasing involvement of non-medical professionals, clinical oncology consultants remain the primary practitioners. Peer review practice is variable and time is often a limiting factor. Many factors influence the time required for contouring, and departments should take these factors and the need for peer-review into account when developing job plans. • Contouring for radical radiotherapy requires considerable consultant time. • Time needed for contouring varies considerably, and is affected by patient, tumour and treatment related factors. • As more advanced treatment techniques become more commonplace, complexity and time requirements are certain to increase. • Despite involvement of non-medical professionals, clinical oncology consultants remain the primary contouring practitioners. • Time constraints are a major factor limiting peer review practice. [ABSTRACT FROM AUTHOR]

Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation. A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies. Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD2 2 ; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD2 2 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P =.46). Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD2 2 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation. [ABSTRACT FROM AUTHOR]

Posterior fossa tumours (PFTs), which account for two-thirds of paediatric brain tumours, are successfully treated in about 70% of patients, but most survivors experience long-term cognitive impairment. We evaluated arterial spin labelling (ASL), a common, non-invasive magnetic resonance imaging (MRI) technique, as a biomarker of cognitive impairment in a paediatric PFT survivor population. Sixty participants were prospectively analysed. PFT survivors were at least 5 years post-treatment and had been treated as appropriate for their age and type of tumour. Group 1 had received radiotherapy and Group 2 had not. Group 3 were healthy controls matched to Group 1 for age, sex and handedness. All participants underwent cognitive assessment and multimodal MRI, including an ASL perfusion sequence. We used semi-quantitative ASL methods to assess differences in mean perfusion in the thalamus, caudate, putamen and hippocampus. Statistically, no significant associations between cognitive data and radiation doses were identified. Compared with healthy controls, Group 1 patients had significantly lower overall mean perfusion values (20–30% lower, depending on the cerebral structure) and Group 2 had slightly lower mean perfusion values (5–10% lower). Perfusion values did not correlate with total prescribed irradiation doses nor with doses received by different cerebral structures. Episodic and semantic memory test scores were significantly lower in Group 1 and correlated with lower mean absolute perfusion values in the hippocampus (P < 0.04). These preliminary results indicate that radiotherapy affects the perfusion of specific cerebral structures and identify perfusion as a potential biomarker of hippocampus-dependent memory deficit. • A semi-quantitative ASL method was used to quantify cognitive loss in PFT survivors. • Radiotherapy induced long-term overall cerebral semi-quantitative hypoperfusion in a paediatric PFT population. • Perfusion values tend to correlate significantly with the mean radiation dose received by the left hippocampus but not other brain structures examined. • A decrease in hippocampal perfusion is therefore a potential marker of memory impairment in irradiated children. [ABSTRACT FROM AUTHOR]

Brain Stem Gliomas are up to 20% of all brain tumors in children and unusual in adults. Radiotherapy is mainstay of treatment. Surgery for brain stem glioma is difficult because of anatomical location. This study was performed to evaluate the clinical outcomes of radiotherapy in brain stem glioma. Retrospective analysis of brain stem glioma patients treated with radiation therapy (54 Gy/ 30 fractions of IMRT or 3D CRT) with or without surgery or chemotherapy or other agents in Yangon General Hospital, Myanmar. Twenty-four patients (median age 11.8 years) were treated between 2016 and 2020. Male to female ratio was 2:3. Surgical approach (Biopsy and partial removal) was done in 16 patients. Histology revealed that anaplastic ependymoma in 2 patients, low-grade astrocytoma in 2 patients, anaplastic astrocytoma in 8 patients, glioblastoma in 4 patients and remaining 8 patients had no histological diagnosis. Radiotherapy (dose-54Gy/ 30 fractions) was given with the technique of IMRT or 3D CRT. At the time of follow-up, 8 patients had local recurrence, 10 patients died of due to disease and recurrence, 14 patients were alive. Among alive patients, 2 patients were treated with chemotherapy and 12 patients with temozolomide for 12 cycles. Patients who received temozolomide got improvement in performance status and reduced clinical symptoms; among them, 6 patients had more than 50% objective tumor response in radiological findings for follow-up 3-6 months after radiotherapy. The 3-years overall survival (OS) rate was 58.3% and 3 years Event-free Survival (EFS) rate was 50%. The medium survival time was 14 months. There is no Grade 3 or greater acute and late toxicities. As the LMIC country with limited resources, our results of radiotherapy followed by temozolomide in brain stem gliomas have optimal outcomes. However, prospective studies of this select group of patients with larger number and longer follow-up is required. [ABSTRACT FROM AUTHOR]

Reirradiation is increasingly considered for recurrent pediatric brain tumors, but dosimetric guidelines are lacking. To identify composite dose-volume constraints for reirradiation of recurrent brain tumors in children, a prospective trial was conducted. Nine children with recurrent brain tumors previously treated with radiation were prospectively reirradiated. Three had GBM, two had AT/RT, and one each had ependymoma, NGGCT, medulloblastoma, or meningioma. For all patients, DICOM format records of their prior radiation (RT1) fields were obtained and deformed onto the CT simulation for their second course of radiation (RT2). Conventionally fractionated treatment plans for RT2 satisfied dose constraints for RT2 alone and the composite sum of both courses (RT1+RT2). The primary endpoint was the rate of symptomatic brain necrosis at 6 months after RT2. Median age at RT2 was 9.7y (range, 2.9 -6.8 y). Median interval between RT1 and RT2 was 19 months (range, 7–82 months). Treatment modality for RT2 was VMAT for seven patients and proton therapy for two patients. Median prescription dose for RT2 was 45 Gy (range, 30.6-60 Gy). Five patients were evaluable for the primary endpoint; none had symptomatic brain necrosis at 6 months after RT2. Four patients were not evaluble at 6 months due to death (n=2) or transition to hospice (n=2) by 6 months, all due to progression of disease. Median overall survival from RT2 start for all patients was 10.7 months (range, 5.2-46.4 months). This prospective study suggests that conventionally fractionated reirradiation for recurrent brain tumors in children may be performed safely. These results provide a starting point for development of dose-volume constraints for pediatric brain reirradiation. Advanced technologies such as proton therapy may allow for reirradiation dose escalation while minimizing dose to surrounding critical structures. [ABSTRACT FROM AUTHOR]

To explore the clinical utility of psychological intervention during the radiotherapy of young children aged 3-5 years old with neuro-oncological tumors. A total of 105 children aged 3-5 years with neuro-oncological diseases who underwent radiotherapy at Sanjiu Brain Hospital in Guangdong from January 2016 to December 2018 were selected. Fifty-two children who were admitted in 2016 served as the control group and received standard nursing care. Fifty-three children who were hospitalized from 2017 to 2018 were assigned to the experimental group and received psychological interventions in addition to regular care. The psychological interventions included evaluating medical fear ratings and providing pre-radiotherapy psychological interventions such as radiotherapy education, game simulation, systematic desensitization, and other techniques. The proportions of children who actively completed radiotherapy in the control and experimental groups were 30.77% and 86.79%, respectively. The percentage of children who cried was 28.85% in the control group and 3.77% in the experimental group. The experimental group had a considerably lower rate of sedative drug usage compared to the control group. Children in the experimental group had significantly higher compliance than those in the control group. The implementation of psychological intervention could significantly reduce the need for sedative drugs during radiotherapy for children aged 3-5 years, thus preventing unnecessary expenditure of medical resources. [ABSTRACT FROM AUTHOR]

We sought to analyze the evolution of hydrocephalus and enumerate its predictive factors in posterior fossa tumors in children and adults. We also validated the modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) and Frankfurt grading systems as tools to predict cerebrospinal fluid (CSF) diversion in children and adults, respectively. A retrospective review of patients with posterior fossa tumors operated between 2012 and 2019 was performed. Clinical, radiologic, and operative data were obtained. Validation was performed for both scores via receiver operating characteristic (ROC) curves and evaluation of the area under the curve (AUC). We included 116 children and 343 adults in the study. Of the adults, 141 patients had intraaxial tumors and 172 had extraaxial tumors. The insertion of external ventricular drain (EVD), its duration, papilledema was noted to have significant influence on the need for permanent CSF diversion (P < 0.05) in children. The ROC for mCPPRH score was 0.659 (0.501–0.816), Age- 0.496 (0.334–0.658) and Evans index- 0.788 (0.654–0.922). In adults- Intraaxial tumours Age, Frankfurt score, duration of EVD, Diagnosis, Extent of resection and periventricular capping significant predictors and ROC age AUC 0.300 (0.193–0.407), Evans index 0.939 (0.888–0.990), and Frankfurt score 0.908 (0.853–0.964) (P < 0.05), whereas in extraaxial tumors Frankfurt grading, sex, duration of EVD, presence of perilesional edema and extent of resection (P < 0.05) ROC age AUC 0.439 (0.344–0.534), Evans index 0.941 (0.906–0.977), and Frankfurt score 0.847 (0.782–0.912). This is the first external validation study for the 2 predictive systems in use. mCPPRH demonstrated poor predictive accuracy, and Frankfurt grading system demonstrated good accuracy. EVD insertion and its duration was significantly predictive of the need for permanent CSF diversion. [ABSTRACT FROM AUTHOR]

Though rhabdomyosarcoma is the most common soft-tissue tumor diagnosed in children there are no reported cases of prenatally detected prostatic embryonal rhabdomyosarcoma. This report demonstrates the first reported case of this phenomenon and its subsequent workup, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

The indication for performing biopsies in patients with diffuse lesions in the brain stem is controversial. The possible risks associated with the technically challenging interventions must be balanced against clarifying the diagnosis and the possible therapeutic options. We reviewed the feasibility, risk profile, and diagnostic yield of different biopsy techniques in a pediatric cohort. We retrospectively included all patients aged <18 years who had undergone biopsy of the caudal brainstem region (pons, medulla oblongata) at our pediatric neurosurgical center from 2009 to 2022. We identified 27 children. Biopsies were performed using frameless stereotactic (Varioguide; n = 12), robotic-assisted (Autoguide; n = 4), endoscopic (n = 3), and open biopsy (n = 8) techniques. Intervention-related mortality was not observed. Three patients experienced a transient postoperative neurological deficit. No patient experienced intervention-related permanent morbidity. Biopsy yielded the histopathological diagnosis in all 27 cases. Molecular analysis was feasible for 97% of the cases. The most common diagnosis was H3K27M-mutated diffuse midline glioma (60%). Low-grade gliomas were identified in 14% of patients. Overall survival was 62.5% after 24 months of follow-up. Biopsies of the caudal brainstem in children were feasible and safe in the presented setup. The amount of tumor material acquired allowing for an integrated diagnosis and was obtained at reasonable risk. The selection of the surgical technique depends on the tumor location and growth pattern. We recommend the performance of brainstem tumor biopsies in children at specialized centers to better understand the biology and enable possible novel therapeutic options. [ABSTRACT FROM AUTHOR]

There is a lack of clinical protocols for re-irradiation in paediatric central nervous system (CNS) tumours. To fill this void, the Swedish Workgroup of Paediatric Radiotherapy (SBRTG) compiled national guidelines on re-irradiation in paediatric CNS tumours (diffuse intrinsic pontine glioma, ependymoma, germinoma and medulloblastoma). These have been in clinical practice since 2019 in all paediatric radiotherapy centres in Sweden. Since the implementation, the guidelines have been complemented with a yearly review on clinical outcome and toxicities in all paediatric patients treated according to the guidelines. This article presents the Swedish national guidelines on re-irradiation in paediatric CNS tumours. • Re-irradiation of CNS tumours in paediatric patients is becoming more common. • Clinical guidelines for re-irradiation of paediatric CNS tumours are lacking. • We present Swedish national guidelines on re-irradiation in paediatric CNS tumours. [ABSTRACT FROM AUTHOR]

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Pediatric pituitary adenomas are rare lesions and account for approximately 3% of all supratentorial tumors in children. There is a paucity of reports on endoscopic transsphenoidal surgery in children. The aim of this study was to assess the early/late outcomes of endoscopic pediatric pituitary adenoma surgery at a high-volume tertiary center, as well as to characterize the factors associated with aggressive growth, including the histopathological features. Between August 1997 and June 2022, a total of 3256 patients underwent endoscopic transsphenoidal surgery for pituitary adenoma at the Department of Neurosurgery and Pituitary Research Center of the Kocaeli University School of Medicine. Of these, 70 (2.1%) pediatric patients (25 males, 45 females) (age ≤18 years) with a pathological diagnosis of pituitary adenoma were retrospectively reviewed. The mean age of patients was 15.5 ± 2.3 years. Among the hormone-secreting adenomas, 19 (34.5%) were adrenocorticotrophic hormone secreting, 13 (23.6%) were growth hormone secreting, 19 (34.5%) were prolactin secreting, and 4 (7.2%) were both growth hormone-prolactin secreting. Gross total resection was achieved in 93.3% of nonfunctional tumors. The early/late surgical remission rates for hormone-secreting adenomas were 61.5%/46.1% (mean follow-up: 63.7 ± 49.3 months) for acromegaly, 78.9%/68.4% (47.8 ± 51.0 months) for Cushing disease, 57.8%/31.5% (72.2 ± 59.5 months) for prolactinoma, and 25%/25% (35.2 ± 31.4 months) for growth hormone-prolactin–secreting adenomas. Five sparsely granulated corticotroph tumors, 5 sparsely granulated somatotroph tumors, and 11 densely granulated lactotroph tumors were classified as aggressive histopathological subtypes. The unique characteristics of the pediatric population and the aggressiveness of the disease in this population pose considerable therapeutic challenges. To increase treatment success, current adjuvant therapies that are appropriate for the morphological and biological characteristics of the tumor are required in addition to surgical treatment. [ABSTRACT FROM AUTHOR]

Adjuvant radiotherapy is an integral component in the management of soft-tissue sarcomas. Brachytherapy is a very convenient and conformal way of delivering adjuvant radiotherapy in such tumours, which spares the surrounding normal tissue. Randomised studies have established the efficacy of brachytherapy in the adjuvant setting, with a 5-year local control of 80–85%. High dose rate, low dose rate and pulsed dose rate have shown equivalent local control, but high dose rate has gained popularity owing to patient convenience, radiation safety and flexibility in dose optimisation. Freehand insertion perioperative brachytherapy (intraoperative placement and postoperative treatment) is the most commonly used technique in soft-tissue sarcomas, with intraoperative radiotherapy and radioactive seed placement being the less commonly used techniques. Brachytherapy can be used as monotherapy or in combination with external beam radiotherapy, such as in cases of close/positive margins for safe dose escalation. Although the quantum of side-effects with external beam radiotherapy has considerably reduced with the evolution of technology and the introduction of intensity modulation (intensity-modulated radiotherapy), brachytherapy still scores better in terms of dose conformality, especially in recurrent tumours (previously irradiated) and when used to treat paediatric and geriatric patients. • Brachytherapy allows effective disease control and organ and function preservation for soft tissue sarcomas in adult and paediatric age groups. • Appropriate selection of patient and brachytherapy technique are critical in achieving optimal outcomes. • Brachytherapy is particularly useful in children as it allows reduction in volumes of immature normal tissue irradiated. [ABSTRACT FROM AUTHOR]

Immunosuppression of varying degree is present in children with cancer. This can range from mild to severe. Cancer itself, particularly leukaemia and lymphoma, can cause suppression of cellular and humoral immune function. However, cytotoxic antineoplastic therapy is the main contributor. Immune alteration is reflected by decreases in neutrophils, lymphocytes, immunoglobulin levels, and specific antibodies against previous vaccinations and infections. Immune recovery post-treatment occurs in a differential manner, with innate immune function recovering before adaptive immune function, and with B-cell function recovering faster than T-cell function. As a result of these changes children with cancer, and particularly those who are also haematopoietic stem cell transplant (HSCT) recipients, have an acquired immune deficiency, and are at increased risk of significant morbidity and mortality from infections. It is therefore important to ensure that such children are maximally protected against vaccine-preventable diseases. This can be achieved by optimising the vaccination strategy in children during immunosuppressive cancer treatment and after completion of treatment. Vaccination should be routine practice for all children treated for cancer. The vaccination strategy should not only include the patient, but also the household members and healthcare contacts of the patient. [ABSTRACT FROM AUTHOR]

This phase I/expansion study assessed the safety, pharmacokinetics and preliminary antitumor activity of afatinib in paediatric patients with cancer. The dose-finding part enroled patients (2–<18 years) with recurrent/refractory tumours. Patients received 18 or 23 mg/m2/d afatinib orally (tablet or solution) in 28-d cycles. In the maximum tolerated dose (MTD) expansion, eligible patients (1–<18 years) had tumours fulfilling ≥2 of the following criteria in the pre-screening: EGFR amplification; HER2 amplification; EGFR membrane staining (H-score>150); HER2 membrane staining (H-score>0). The primary end-points were dose-limiting toxicities (DLTs), afatinib exposure, and objective response. Of 564 patients pre-screened, 536 patients had biomarker data and 63 (12%) fulfilled ≥2 EGFR/HER2 criteria required for inclusion in the expansion part. A total of 56 patients were treated (17 in the dose-finding and 39 in the expansion part). DLTs were observed in one of six MTD-evaluable patients receiving 18 mg/m²/d and in two of five MTD-evaluable patients receiving 23 mg/m²/d; 18 mg/m²/d was defined as the MTD. There were no new safety signals. Pharmacokinetics confirmed exposure consistent with the approved dose in adults. One partial response (−81% per Response Assessment in Neuro-Oncology) was observed in a patient with a glioneuronal tumour harbouring a CLIP2::EGFR fusion; unconfirmed partial responses were observed in two patients. In total, 25% of patients experienced objective response or stable disease (95% confidence interval: 14–38). Targetable EGFR/HER2 drivers are rare in paediatric cancers. Treatment with afatinib led to a durable response (>3 years) in one patient with a glioneuronal tumour with CLIP2::EGFR fusion. • 12% of 536 paediatric patients screened had ≥2 potential ErbB-activation markers. • 56 paediatric patients with ErbB-dysregulated tumours received afatinib. • MTD in children was 18 mg/m²/d; PK and safety were equivalent to adults. • Objective response observed in one patient (>3 years), with a CLIP2::EGFR fusion. • EGFR gene fusion or driver mutations are rare in paediatric cancer but are sensitive to afatinib. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is one of the most common extracranial solid tumors in children. MYCN gene amplification is highly associated with poor prognosis in high-risk NB patients. In non-MYCN-amplified high-risk NB patients, the expression of c-MYC (MYCC) and its target genes is highly elevated. USP28 as a deubiquitinase is known to regulate the stability of MYCC. We show here USP28 also regulates the stability of MYCN. Genetic depletion or pharmacologic inhibition of the deubiquitinase strongly destabilizes MYCN and stops the growth of NB cells that overexpress MYCN. In addition, MYCC could be similarly destabilized in non-MYCN NB cells by compromising USP28 function. Our results strongly suggest USP28 as a therapeutic target for NB with or without MYCN amplification/overexpression. [ABSTRACT FROM AUTHOR]

Infantile hepatic hemangioma (IHH) is the most common benign liver tumor in children, and multifocal and diffuse tumors often become life-threatening, necessitating therapy. Propranolol is now considered the first choice of therapy with ample data in Caucasian children. We present a series of nine Indian children with multifocal (n = 5) and diffuse (n = 4) IHH treated with propranolol monotherapy. This was a retrospective clinical data-based single-center study. Propranolol was used at a median dose of 3.2 mg/kg/day (range 3–3.3 mg/kg/day) for a median duration of 12 months (range 6–32 months). The presentations of IHH (either in isolation or combination) were hypothyroidism in six patients (diagnosed by elevated serum TSH levels), heart failure in three (diagnosed based on clinical and echocardiographic features), and imaging evidence of macrovascular shunting in two patients. A good response to propranolol monotherapy (with a median dose of 3.2 mg/kg/day for a median duration of 12 months) was observed in eight patients, with a poor response in one. One patient experienced recurrence but responded adequately to propranolol retreatment. Our data reiterate the excellent response (88.9% responded) and safety profile with propranolol monotherapy in complicated IHH and strengthen the data in Asian (Indian) children. It includes the maximum proportion of complicated IHH treated with propranolol in East and South Asia, and the largest series from India. [Display omitted] [ABSTRACT FROM AUTHOR]

Ependymomas are the third most common brain tumors in children. The current standard of care for curative intent treatment is maximal safe resection followed by adjuvant radiotherapy. Controversy in the literature still exists over optimal radiotherapy dose. The most important prognostic factor for these tumors is the extent of resection followed by the addition of adjuvant radiotherapy. We completed a systematic review and meta-analysis of the available literature to determine the optimal radiotherapy dose regarding outcomes, including local control (LC), event-free survival (EFS), and overall survival (OS) in pediatric patients (≤22y). We searched MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and Web of Science from inception to January 2024. We included cohort studies that compared adjuvant radiotherapy doses of ≤54Gy to >54Gy in pediatric patients (≤22y) with non-metastatic intracranial ependymomas treated with curative intent therapy. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies. We quantitatively pooled studies using a random effects meta-analysis for hazard ratios (HR), 95% confidence intervals (CI), and statistical heterogeneity via I2. When HRs were unavailable, we transformed 3-year risks using established methods. We narratively summarized qualitative outcomes. Seven cohort studies met our inclusion criteria, covering a combined 1321 pediatric patients. Studies included a range of doses from 45-66.6Gy. Compared with patients receiving adjuvant radiotherapy dose of >54Gy, we found no difference in LC for those receiving ≤54Gy (HR = 0.83, 95% CI = 0.56-1.24, I2 = 49.1%), in EFS (HR = 1.02, 95% CI = 0.95-1.09, I2 = 0.00%), and OS (HR = 0.99, 95% CI = 0.82-1.20, I2 = 37.5%). Three studies methodically placed younger children in the lower dose cohorts due to concerns of late-effects of therapy. Two studies reported on the extent of resection by radiotherapy dose, with neither study reporting a statistical difference in LC, EFS, or OS, though the number of patients included in each study analysis was small (n≤30). Five studies reported on late effects, with brainstem radionecrosis, radiation-induced vasculopathy, and secondary tumors being the most frequently reported toxicities. Toxicities were not reported in relation to the specific doses of radiotherapy received. Overall study quality was high, though lower scores were consistently seen in the comparability of cohorts. We found no difference in LC, EFS, or OS for those treated with ≤54Gy compared to >54Gy. Many of the children who were in the lower dose cohorts were younger in age, a group with historically worse outcomes, which may artificially increase rates of relapse, events, and mortality. There was insufficient data to complete a subgroup meta-analysis on radiotherapy dosing based on the extent of resection or molecular subgroups, an important question for future research. [ABSTRACT FROM AUTHOR]

Cerebellar mutism syndrome (CMS) is a well-known complication after posterior fossa tumor surgery in pediatric patients. We evaluated the incidence of CMS in our institute and analyzed its association with multiple risk factors, such as tumor entity, surgical approach, and hydrocephalus. All pediatric patients who had undergone intra-axial tumor resection in the posterior fossa between January 2010 and March 2021 were included in the retrospective analysis. Various data points, including demographic, tumor-associated, clinical, radiological, surgery-associated, complications, and follow-up data, were collected and statistically evaluated for an association with CMS. A total of 63 surgeries in 60 patients were included. The median patient age was 8 years. Pilocytic astrocytoma was the most common tumor type (50%), followed by medulloblastoma (28%) and ependymomas (10%). Complete, subtotal, and partial resection was achieved in 67%, 23%, and 10%, respectively. A telovelar approach had been used the most often (43%) compared with a transvermian approach (8%). Of the 60 children, 10 (17%) had developed CMS and showed marked improvement but with residual deficits. The significant risk factors were a transvermian approach (P = 0.03), vermian splitting when added to another approach (P = 0.002), an initial presentation with acute hydrocephalus (P = 0.02), and hydrocephalus present after tumor surgery (P = 0.004). Our CMS rate is comparable to those described in the literature. Despite the limitations of the retrospective study design, we found that CMS was not only associated with a transvermian approach but was also associated with a telovelar approach, although to a lesser extent. Acute hydrocephalus at the initial presentation necessitating urgent management was significantly associated with a greater incidence of CMS. [ABSTRACT FROM AUTHOR]

Determination of optic nerve sheath diameter (ONSD) with transbulbar sonography has become an easily accessible and time-effective tool in the assessment of increased intracranial pressure. The aim of our study was to evaluate the usefulness of transbulbar sonography in the initial diagnosis and in follow-up examinations of children and adolescents with the diagnosis of pseudotumor cerebri syndrome (PTCS). We retrospectively reviewed imaging results of 24 patients aged 0.75–17 years with PTCS. Serial transbulbar sonography examinations were performed between 2011 and 2021. Sonographic evaluation included the ONSD, papilledema and subarachnoid space. 240 sonographic measurements taken at 108 time points in 17 patients met the inclusion criteria. All patients underwent serial lumbar punctures and routine fundoscopy in close relation to transbulbar sonography. We found that ONSD values remained high in all patients. The longest follow-up period was dated 2498 days (6.84 years) after initial diagnosis. Papilledema resolved in close correlation to fundoscopy normalization. In 16/17 patients the subarachnoid space remained cystic in appearance. These findings were independent of clinical symptoms and lumbar puncture opening pressure. We conclude that transbulbar sonography is a useful diagnostic tool in the initial diagnostic workup of children with PTCS. On follow-up however ONSD values and the cystic transformation of the subarachnoid space remained pathologic in the majority of cases while papilledema resolved parallel to fundoscopy findings. Serial measurements of ONSD are therefore of limited value in the follow-up of patients with PTCS and cannot be considered a reliable tool in subsequent therapeutic decisions. • Transbulbar sonography is useful for diagnosis of pediatric pseudotumor cerebri. • On follow-up optic nerve sheath diameter and subarachnoid space remain enlarged. • Sonographic papillary changes normalize parallel to fundoscopy findings. • Serial ONSD measurements are of limited value. • ONSD measures in follow-up are not a reliable tool for subsequent therapy decisions. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is the most common extracranial solid tumor in children, with variable outcomes ranging from spontaneous remission to high-risk cases often leading to relapse or refractory disease. Approximately 50 % of patients with NB have high-risk features, often experiencing relapse or refractory disease despite intensive treatments and the prognosis remains poor, with long-term event-free survival (EFS) rates below 10 %,Radioactive iodine-labeled meta-iodobenzylguanidine (¹³¹I-mIBG) therapy, leveraging NB cells' radiosensitivity and expression of the norepinephrine transporter (NET), has shown promise in treating relapsed or refractory NB. Since 1985, ¹³¹I-mIBG has been studied to determine the maximum tolerated dose and side effects, with recent trials exploring its use in front-line treatment. Our systematic review, based on MEDLINE, EMBASE, and Cochrane CENTRAL databases up to December 2023, evaluates the effectiveness and toxicity of ¹³¹I-mIBG therapy in relapsed/refractory NB. It also discusses its potential role in conjunction with emerging therapies like CAR-T cells, haploidentical stem cell transplantation, and dinutuximab beta. [Display omitted] • Long-term event-free survival rates in relapsed/refractory (RR) neuroblastoma (NB) < 10 %. • ¹³¹I-mIBG therapy seems promising for RR NB. • Toxicity of ¹³¹I-mIBG is manageable. • Role of ¹³¹I-mIBG associated with emerging therapies (such as CAR-T cells) may be investigated and considered in the future strategies for RR NB. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the prognostic factors and survival outcomes of pediatric patients with pineal region tumors (PRTs) using a large population-based registry. We employed a retrospective cohort design, utilizing data from the Surveillance, Epidemiology, and End Results program, covering the period from 2000 to 2019. We included pediatric patients (ages 0–18) with histologically verified malignant PRTs. To determine prognostic indicators, we conducted survival analyses using Kaplan-Meier methods and Cox proportional hazards models. Furthermore, we constructed a predictive nomogram derived from the Cox regression outcomes. The study included 596 pediatric patients with PRTs. Germ cell tumors were the most common subtype (63.3%), followed by pineoblastomas (26.3%) and other subtypes (10.4%). The overall 5-year survival rate was 79.6%. Multivariate analysis revealed that age at diagnosis, Surveillance, Epidemiology, and End Results stage, histological subtypes, and radiation therapy were significant predictors of survival. Patients under 5 years of age and those diagnosed with pineoblastomas had worse survival outcomes. Radiation therapy was associated with improved survival. Early age at diagnosis and aggressive histological types such as pineoblastomas are associated with poorer outcomes. Future research should focus on refining therapeutic protocols that integrate the histological and molecular profiles of these tumors. [ABSTRACT FROM AUTHOR]

• Comprehensive global analysis of neuroblastoma and other peripheral nervous system tumors epidemiology using GBD 2021 data. • Significant geographic and socioeconomic disparities in neuroblastoma burden identified. • Cross-country inequality analysis, Joinpoint, APC, and BAPC models offer nuanced insights. • Findings inform targeted public health strategies to reduce global burden of neuroblastoma and other peripheral nervous system tumors. Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, accounting for >15 % of cancer-related deaths in children. We analyzed the epidemiological statistical indicators of neuroblastoma and other peripheral nervous system tumors patients from 1990 to 2021 in Global Burden of Disease (GBD) 2021 database, aiming to provide valuable insights for public health interventions and clinical practices. Based on the GBD 2021 database, this study analyzed the incidence, mortality, prevalence, and Disability-Adjusted Life-Years (DALYs) of neuroblastoma and other peripheral nervous system tumors from 1990 to 2021, stratified by sociodemographic development index (SDI) and geographic regions. Cross-country inequalities analysis was conducted to quantify the SDI-related inequality of disease burden across countries. In addition, the average annual percentage change (AAPC) and Age-Period-Cohort (APC) model were used to evaluate the trend of disease burden, while the global burden of disease to 2035 was predicted by Bayesian Age-Period-Cohort (BAPC) model. This study reported the disease burden of neuroblastoma and other peripheral nervous system tumors in GBD 2021 database for the first time. Globally, the incidence and mortality of neuroblastoma have increased year by year from 1990 to 2021, especially in regions with low SDI, such as South Asia and sub-Saharan Africa, where the burden of disease has increased significantly. Regions with high SDI, such as North America and Western Europe, have seen a reduction in disease burden due to higher levels of medical care and earlier diagnosis. The age distribution shows that children under 5 years of age are mainly affected, especially in low- and middle-income areas. In addition, the incidence is slightly higher in men than in women. The BAPC model predicts that the global incidence, mortality, and DALYs of neuroblastoma will continue to increase until 2035. Significant regional and population variation in neuroblastoma and other peripheral nervous system tumors worldwide, with a particularly high disease burden in low SDI areas with limited medical resources. This trend highlights the urgent need for global public health interventions and resource allocation, particularly in low-income countries. Future research should focus on improving early diagnosis, risk stratification and target therapy in order to reduce the global burden of disease and improve patients' prognosis. This study was supported by National Natural Science Foundation of China (No. 82293662, No 82172357 and No 81930066), Key project of Shanghai "Science and Technology Innovation Action Plan (22JC1402304) and Research fund of Shanghai Municipal Health Bureau (No. 2019cxjq03). [ABSTRACT FROM AUTHOR]

An increasing number of people face the challenge of providing long-term, unpaid, informal care to children with cancer. The repetitive and staged processes of treatment create inherently rhythmic care practices, imposing a strict schedule on caregivers' daily routines. To explore the rhythmic nature of pediatric cancer informal care, we discuss the rhythms of daily life during intensive chemotherapy and maintenance therapy, and negotiated strategies of caring practice. We draw upon Lefebvre's rhythmanalysis and activity diary, and conduct semi-structured interviews with informal caregivers. We demonstrate the scale, stage, and dynamic nature of the daily life rhythm of caregivers of children with cancer, which is characterized by linear "alienation," arrhythmia, and "metastable" harmony. Structured therapeutic rhythms do not have overwhelming power; rhythms are intervened through insertion, negotiated adjustment, recharging, and alliances to maintain eurhythmia in caregivers of children with cancer. This study provides specific insights into the care of children with cancer in the context of the relationship between time, space, energy, and rhythm, which may help provide support to caregivers and reduce their burden of care. • Reveals the scale of caring rhythms. • Uncovers the rhythmic challenges encountered by informal caregivers at different stages of treatment. • Reconsiders the energetic nature of rhythms. • Reveals the strategies for caregivers to negotiate rhythmic challenges. • Calls for better policies to ensure stability in informal care. [ABSTRACT FROM AUTHOR]

Based on fieldwork conducted in China from November 2018 to January 2020 on biomedical innovation with advanced therapies open to foreigners, in this paper I address the question of why parents of children with incurable cancer decide to access experimental treatment on the other side of the world. While work on the "political economy of hope" has already extensively researched the relation between biomedical technology and hope, I delve into other terrains. In this paper, I will discuss the role of "ontological hope" in the moral project of caring for a child with cancer. Drawing on the Anthropology of Ethics, I conclude that in the postgenomic era, when incurable cancers are recategorize as not-yet-treatable, parents' efforts to access experimental treatment highlight the complex moral work that parents must undergo to imagine a future good life despite their irreparable loss. • Accessing experimental treatment can be understood as part of a moral project. • The moral experience of personal misfortune offers new insights on hope and biomedical innovation. • Access to experimental technology might avoid the moral catastrophe of not having done enough. [ABSTRACT FROM AUTHOR]

Brachytherapy is advantageous for localised rhabdomyosarcomas in children compared with external beam radiotherapy, sparing close organs at risk with highly conformal dosimetry. A methodology for planning and delivering fractionated high-dose-rate paediatric pelvic brachytherapy is detailed, and the dosimetric parameters are presented. This provides a practical template for radiotherapy departments with a similar patient cohort to implement this treatment technique. Patients with localised pelvic rhabdomyosarcomas underwent transrectal ultrasound image-guided transperineal percutaneous implantation of brachytherapy catheters or insertion of intracavitary applicators. Clinical target volumes were delineated on computed tomography imaging, extended cranially to form an internal target volume (ITV) to allow for perineal oedema, and peer reviewed. Dosimetry was manually adjusted to achieve optimal coverage. The prescription dose was 27.5 Gy in five fractions. The dose to 90% (D90%) of the ITV, and the conformity number (CN) were calculated. Replanning was undertaken if measurements or imaging showed suboptimal dosimetry due to internal anatomical changes. Thirty-five patients, aged 8 months to 17 years 6 months (median 2 years 10 months), were treated between 2009 and 2023. The median ITV was 18.5 cc. The median ITV D90% was 5.9 Gy per fraction. The majority of plans had a CN greater than 0.5. Replanning was required in two-thirds of patients. Intraoperative transperineal interstitial implantation of flexible catheters, cervical intrauterine tubes, or vaginal applicators resulted in highly conformal plans, achieving excellent coverage with a D90% exceeding 90% of the prescribed dose in 34 out of 35 cases. Technical and practical measures are crucial for an optimal treatment for each child. • Brachytherapy is advantageous for localised rhabdomyosarcomas in children. • In a specialist centre, highly conformal plans can be achieved. • Careful attention to detail of technical aspects is crucial for optimal treatment. [ABSTRACT FROM AUTHOR]

The uniqueness of paired (tumor and germline) whole genome sequencing (PWGS) in cancer diagnosis and management lies in not just its ability to uncover oncogenic drivers and potential treatment targets but also on the identification of underlying cancer predisposition syndromes, which has significant implications for the patient and their family. This is a descriptive article highlighting the processes taken by our team to incorporate PWGS into routine National Health Service (NHS) clinical care for children with cancer. The main aim of this article is to share our experience with other centers that may wish to set up similar services and set the stage for future quantitative/qualitative research. This article is further supported by an audit focusing on children in whom an underlying cancer predisposition was confirmed. The audit highlights the success of the program to date, with 100% of families identified as being at risk of a cancer predisposition syndrome being offered referral to clinical genetics and 100% of at-risk first-degree relatives being offered predictive counseling and testing. Areas requiring improvement included discussion of reproductive options as only six out of nine families (67%) had a documented discussion. Incorporation of the audit recommendations will improve our service, and sharing of our experience will hopefully encourage more pediatric oncology services to introduce PWGS into routine clinical care and reduce inequity of access. Further work is required to assess the long-term cancer risk reduction and establish the psychosocial impact of PWGS for the child and family. • Paired whole genome sequencing (PWGS) provides additional insights into cancer predisposition. • Cascade testing for a first-degree relative can be offered if an underlying cancer predisposition is identified. • We were able to identify and offer cascade testing to 100% of our children with cancer predisposition. • We describe the process establishing the PWGS pathway, to allow other centers to do the same. [ABSTRACT FROM AUTHOR]

• Osteosarcoma is a malignant bone tumor that affects children and adolescents. • Metastasis at diagnosis significantly decreases the chances of survival. • IGFBP5 expression varies among tumors from metastatic and non-metastatic patients. • IGFBP5 gene may be related to MAPK pathway modulation. • Investigating IGFBP5 and MAPK genes relationship could lead to new insights. Osteosarcoma (OS) is the most frequent primary malignant bone tumor among children and adolescents, with a peak of incidence in the second decade of life. The presence of metastasis at diagnosis in OS patients significantly decreases the chances of survival and new therapy approaches are needed. The IGFBP5 gene is related to osteoblasts metabolism and some studies have pointed out a role of its low expressions in OS development and metastasis. In this study, we aimed to establish an IGFBP5 gene expression profile among metastatic and non-metastatic OS patients throughout the treatment and development of the disease. Fresh-frozen tumor samples were obtained from 40 patients admitted to treatment at the Pediatric Oncology Institute (IOP/GRAACC/UNIFESP) and divided by clinical status: metastatic or non-metastatic disease. For each patient, samples before and after chemotherapy treatment were obtained, as well as metastasis and lung tissue surrounding metastasis samples from the metastatic patients. A quantitative real-time PCR was used to investigate IGFBP5 expression. Our analyses demonstrate that non-metastatic patients presented lower IGFBP5 expression in their pre-chemotherapy samples compared with metastatic patients, suggesting that low expressions of this gene could help triggering the OS tumorigenesis but that its action alone is not sufficient to activate the metastatic process. Heterogeneity in IGFBP5 expressions within groups was also seen. We observed that IGFBP5 and two MAPK genes, a downstream pathway in the IGFBP5 axis, are differentially expressed in OS samples of non-metastatic patients. Further investigation about these genes' modulations might lead to a better understanding of metastasis development in OS. [ABSTRACT FROM AUTHOR]

Despite being extremely rare in children, primary benign cardiac tumors can cause malignant ventricular arrhythmias (VA) or even sudden cardiac death. To assess the predictors of cardiovascular death and malignant VAs, we designed a retrospective single-center study enrolling paediatric patients. We defined as primary outcome a composite of cardiovascular death, sustained VT, ventricular fibrillation and rapid, symptomatic non-sustained VT. Our secondary endpoint was to assess the prevalence of clinically significant arrhythmias in our population. We fitted a multivariate Cox regression model to assess the predictors of the primary outcome. Over a period of 38 years, a total of 97 children were enrolled in the study. Among them, there were 73 rhabdomyomas, 13 fibromas, 3 myxomas, 3 teratomas, 1 lipoma, 2 haemangiomas and 2 fibroelastomas. Over a median follow up of 10.53 years, 16 patients met the primary outcome. Kaplan Meier unadjusted survival estimates showed that tumor dimensions larger than 2.3 cm and diagnosis of fibroma predicted worse outcomes compared with smaller tumors or other histotypes, (log rank p < 0.0002 and < 0.0001 respectively). In multivariate Cox proportional hazards analysis, diagnosis of fibroma and tumor dimensions were independently associated to the primary endpoint (HR: 5.06, 95 %CI (1.3–19); and 1.26 • (1.05–11), respectively). Clinically significant arrhythmias were reported in 24.5 % of the study population. Among paediatric primary cardiac tumors, type and dimensions may predict the hazard of malignant VAs and cardiac death. [Display omitted] • Primary benign cardiac tumors can cause malignant ventricular arrhythmias or sudden cardiac death in paediatric patients. • Optimal management of children with primary benign cardiac tumors is challenging, requiring medical therapy or surgery. • We designed a retrospective single-center study enrolling 97 children with primary benign cardiac tumors. • Clinically significant arrhythmias were reported in 24.5 % of the study population. • Tumor dimensions larger than 2.3 cm and diagnosis of fibroma predicted worse outcomes at multivariate analysis. [ABSTRACT FROM AUTHOR]

Reirradiation is becoming more frequently used in paediatric tumours of the central nervous system (CNS). To fill the void of clinical guidelines, the Swedish Working Group of Paediatric Radiotherapy compiled consensus guidelines on reirradiation in 2019. The aim of this study was to evaluate the outcome of children reirradiated for CNS tumours since implementing the guidelines. All children in Sweden who were reirradiated for CNS tumours between 2019 and 2023 were retrospectively analysed. Data were collected on patient and treatment characteristics, outcome, and severe side effects. Radiation treatment plans were reviewed, and cumulative doses to organs at risk at reirradiation were extracted following rigid registration. Thirty-one patients (male 55%, female 45%) were included, and the median age at start of reirradiation was 10.2 years. The median time between primary irradiation and reirradiation was 19 months (range 2–141). The most common treatment intent at reirradiation was palliative (68%), followed by curative (32%). With a median follow-up of 8.5 months (range 0–49), the median overall survival from the end of reirradiation was 11.4 months. In the 8 patients where the treatment goal at reirradiation was symptom relief, 6 patients (75%) had relief of symptoms. The median cumulative near maximum doses (D2%) to the brain, brainstem, and chiasm/optic nerves were 71 Gy EQD2 (range 44–102), 72 Gy EQD2 (range 0–94), and 40 Gy EQD2 (range 0–76), respectively. Following reirradiation, only 2 patients had grade ≥3 side effects. One with transient neurological deficit and one with rapid onset of blindness that persisted. The implementation of national guidelines has harmonised the way paediatric patients are reirradiated for CNS tumours in Sweden. A structured follow-up shows that severe side effects are rare despite high cumulative doses to organs at risk, and that reirradiation can offer relief of symptoms and/or local control for selected patients. •National guidelines facilitate reirradiation in paediatric patients with CNS tumours. •Severe side effects are rare despite high cumulative doses to organs at risk. •Reirradiation is a possible treatment option in children with recurrent CNS tumours. [ABSTRACT FROM AUTHOR]

Diffuse midline glioma (DMG) continues to be an aggressive brain stem cancer among children and young adults. It has a dismal prognosis, with less than 10% of patients alive two years after diagnosis. Radiotherapy has been demonstrated to be effective, albeit transient. Hence, radiotherapy is considered a cornerstone in the treatment. Reirradiation has, in retrospective studies, shown promising overall survival and palliative effect, but no pan-European consensus for reirradiation exists. The REMIT (Re irradiation of diffuse Mi dline glioma pa T ients) protocol evaluates safety and the palliative efficacy of reirradiation of patients with DMG (clinicaltrials.gov NCT06093165). Patients included in the protocol will be followed with 1) performance status (Karnofsky or Lansky), 2) toxicity monitored with Common Terminology Criteria for Adverse Events (CTCAE), 3) motor and functioning skill with PEDI-CAT (The Pediatric Evaluation of Disability Inventory) and 4) quantification of corticosteroid use. Furthermore, the impact on quality of life and well-being will be assessed qualitatively with interviews as well as with the Pediatric Quality of Life Inventory (PedsQl) Cancer Module questionnaire. The protocol also includes dose accumulation and contouring studies to assess standardization as well as a prescreening log to address selection bias of patients. The safety and palliative efficacy of reirradiation in DMG will be prospectively evaluated, including qualitative patient reported outcomes, through the REMIT protocol. REMIT is planned to open for inclusion in 2024. • Diffuse midline glioma (DMG) unfortunately continues to have a dismal prognosis. •Radiation is a cornerstone in the treatment, and reirradiation is a promising palliative treatment for progressive diffuse midline glioma. •However, prospective trials addressing toxicity, quality of life, both qualitatively and quantitively, as well as selection bias are needed. •REMIT (reirradiation of DMG) is a prospective, feasibility study evaluating the palliative efficacy for DMG, including quality of life (NCT06093165). [ABSTRACT FROM AUTHOR]

The use of the Alexis wound protector-retractor (AWPR) could further improve the laparoscopic techniques for safely removing huge ovarian tumors in children. A 15-year-old patient presented to our emergency department with a history of weeks of persistent abdominal pain. Clinical examination and magnetic resonance imaging demonstrated a 25 × 21 × 21 cm cystic mass arising from the left ovary. An en block unilateral oophorectomy and salpingectomy with the use of a medium-sized AWPR was performed without complications. The patient was discharged on the second postoperative day. The AWPR is a safe and effective tool in treating such children and adolescents with huge ovarian tumors, preserving fertility, minimizing the postoperative pain and hospital stay, and providing an excellent cosmetic outcome. [ABSTRACT FROM AUTHOR]

Lynch syndrome (LS) is an autosomal dominant genetic disorder defined by germline mutations in one of four mismatch repair genes including PMS2, MLH2, MSH1, MSH2, or deletion in the EPCAM gene.1 The most common urologic manifestation of LS is upper tract urothelial carcinoma, which occurs in up to 20% of patients with LS.2 While data are scarce, there is growing evidence of an increased relative risk of bladder malignancy in patients with LS.3,4 Bladder tumors in children are a rare entity and the link between pediatric bladder tumors and LS has not been previously reported to our knowledge. [ABSTRACT FROM AUTHOR]

Vaginal yolk sac tumors are rare pediatric malignant tumors and the most common form of vaginal germ-cell tumors in children. They are almost exclusively found in females under 3 years of age. Treatment involves local excision either with or without chemotherapy. Herein, we describe a case of a 3-year-old girl with vaginal Yolk sac tumor, who underwent buccal mucosa vaginoplasty through an anterior sagittal transrectal approach , as an effective oncological procedure, with preservation of reproductive function. [ABSTRACT FROM AUTHOR]

Precision oncology requires diagnostic accuracy and robust detection of actionable alterations. The Pediatric Targeted Therapy (PTT) 2.0 program aims at improving diagnostic accuracy by addition of molecular analyses to the existing histological diagnosis and detection of actionable alterations for relapsed paediatric oncology patients, in cases with limited availability of tumour material. Paediatric patients diagnosed with relapse or progression of a central nervous system tumour (n = 178), a sarcoma (n = 41) or another solid tumour (n = 44) were included. DNA methylation array, targeted gene panel sequencing on tumour and blood (130 genes), RNA sequencing in selected cases and a pathway-specific immunohistochemistry (IHC) panel were performed using limited formalin-fixed paraffin embedded tissue from any disease episode available. The clinical impact of reported findings was assessed by a serial questionnaire-based follow-up. Integrated molecular diagnostics resulted in refined or changed diagnosis in 117/263 (44%) tumours. Actionable targets were detected in 155/263 (59%) cases. Constitutional DNA variants with clinical relevance were identified in 16/240 (7%) of patients, half of which were previously unknown. Clinical follow-up showed that 26/263 (10%) of patients received mechanism-of-action based treatment matched to the molecular findings. Next-generation diagnostics adds robust and relevant information on diagnosis, actionable alterations and cancer predisposition syndromes even when tissue from the current disease episode is limited. [Display omitted] • International molecular diagnostics study for recurrent paediatric oncology patients. • Robust molecular diagnostics on limited paraffin-embedded tumour material. • Clinically feasible turn-around time and impact on clinical decision making. • Refined and re-classified diagnoses, detection of targetable molecular alterations. • Identification of constitutional DNA variants. [ABSTRACT FROM AUTHOR]

This study systematically reviewed the literature to investigate the value of secondary surgery for children with a high-risk neuroendocrine tumor (NET) of appendix. A systematic search was performed in PubMed, Embase and Web of Science. All randomized controlled trials, cohort studies, and case series reporting on the management and outcomes of patients (<20 years) with a histopathologically proven NET of the appendix were eligible for inclusion. Two authors independently selected eligible articles, assessed risk of bias, and extracted data. The outcomes of patients with a high-risk NET treated with secondary surgery were compared to those treated without secondary surgery. Primary outcomes were recurrence rate and disease-free survival. The literature search yielded 667 articles, of which 29 were included. These studies reported on 1112 patients, of whom 145 (13%) had high-risk NET. Heterogeneity between studies was large and risk of bias was serious in 26 and moderate in three studies. Secondary surgery after primary appendectomy was performed in 64 of 145 patients (44%). Length of follow-up ranged between 0 and 612 months. In both treatment groups no recurrences were reported, and thus disease-free survival was 100%. Based on current literature, the value of secondary surgery for pediatric high-risk NET of the appendix may be questioned. However, evidence is scarce, of low-quality, and heterogeneity between studies is large. Large international studies with adequate follow-up are needed to generate high-quality evidence on this topic. [ABSTRACT FROM AUTHOR]

Cancer (CA) among adolescents and young adults (AYA) presents with unique biological characteristics and histological distributions that differ from children or older adults. CA incidence among AYA (15-39 years) is on the rise despite stable rates among other patient populations, and current literature lacks a consensus as to the etiology behind this trend. Behaviors and characteristics such as tobacco use, alcohol consumption, obesity, diet quality, and sedentary lifestyles have been linked to increased CA risk. To determine if AYA engage in these behaviors at a higher rate compared to previous years, increasing their risk for CA. This descriptive, cross-sectional study collected data between 2005-2023 from a convenience sample of undergraduate students ages 18-24 years enrolled in an entry-level, general education nutrition course at a large, northeastern university. Alcohol/tobacco/vape use, and self/family medical history were self-reported through an online survey. Dietary intake was assessed via 3-day food records and online nutrient analysis software. Daily activity level (steps/day) was measured via research-grade pedometers. Height and weight were measured in duplicate after an overnight fast by research assistants. Most of the final sample (n=11600) were female (68.7%) and reported self or family history of CA (69.3%). Average BMI was 23.6±3.7 kg/m2, and 6.1% of students met criteria for obesity (≥30 kg/m2). Over half (57.9%) reported binge drinking within the past 30 days. While a low proportion of students reported smoking cigarettes (6.5%), almost one in four (23.3%) of students reported using an electronic vape daily or almost daily. A low proportion of students met recommendations for fruit (21.6%), vegetable (22.3%) and fiber intake (16%). Most students (74.3%) were categorized as somewhat active, and 11.4% were sedentary-low active. While most students reported family or self-history of CA, many also reported behaviors link to increased cancer risk including binge drinking, vaping, and poor dietary quality. This data has the potential to inform interventions targeting AYA aiming to reduce CA risk. NIFA [ABSTRACT FROM AUTHOR]