Prevention of cisplatin-induced hearing loss in children: achievements and challenges for evidence-based implementation of sodium Thiosulfate.

Ototoxicity is a devastating direct, irreversible side effect of platinum use in children with cancer, with its consequent effect on speech, language and social development, quality of life and adult productivity. Cisplatin, an essential chemotherapeutic agent for the treatment of solid tumors in children, is a DNA cross-linking agent. Which causes hearing loss in 50-70% of cisplatin treated children. Fortunately, to prevent hearing loss, sodium thiosulfate (STS), which binds to cisplatin, and reduces the superoxides in both tumor and outer hair cells of the cochlea has now been discovered to be an effective and safe otoprotectant if administered correctly. The aim of this perspective paper is to explore the key safety issues and challenges important for pediatric oncologists and pharmacists when considering the clinical use of STS as an otoprotectant for children and adolescents receiving cisplatin. These include: the choice of the formulation; the timing, both that of the STS in relation to cisplatin as well as the timing of the cisplatin infusion itself; the dosing; the challenge left by the definition of localized versus disseminated disease and the difference in indication for STS, between cisplatin treated patients and those receiving another platinum chemotherapeutic agent, carboplatin.

Exploring Inflammation and Stress as Biological Correlates of Symptoms in Children With Advanced Cancer: A Longitudinal Feasibility Study.

Background: Few studies have examined biomarkers of stress and inflammation as underlying mechanisms of symptoms in adolescents and young adults with cancer. This study determined the feasibility of collecting blood and saliva samples across time, described the range and distribution of biomarkers, and explored the association of biomarkers with symptom adverse events (AEs). Method: This longitudinal, prospective repeated-measures single-site feasibility study recruited N = 10 children (M = 12.5 years) receiving treatment for advanced cancer. Symptom AE data and inflammation (cytokines and C-reactive protein) and physiologic response to stress (salivary cortisol and salivary alpha-amylase) biomarker levels were collected at three time points. Descriptive statistics were used to examine feasibility and acceptability and to summarize symptom AE, stress, and inflammatory biomarker data. A linear regression model was used to determine cortisol diurnal slopes. The relationship between symptom and inflammatory biomarker data was explored and Hedges's g statistic was used to determine its effect size. Results: Participants provided 83% of saliva samples (n = 199/240) and 185 samples were sufficient to be analyzed. Nurses collected 97% (n = 29/30) of blood samples. Participants reported the saliva collection instructions, kits, and reminders were clear and helpful. Insomnia, pain, fatigue, and anxiety demonstrated the most medium and large negative effects with inflammatory markers. Symptom AEs demonstrated the highest number of medium and large negative effects with interleukin-8 and tumor necrosis factor-alpha (-0.53 to -2.00). Discussion: The results indicate longitudinal concurrent collection of symptom and biomarker data is feasible and inflammatory and stress biomarkers merit consideration for inclusion in future studies.

Outcomes of pediatric extracranial germ cell tumors: A single center experience in a developing country.

The purpose of this study was to analyze the outcomes of extracranial GCT in children in a developing country and to assess prognostic factors. The data on 141 children (<18 years old) with extracranial GCT, confirmed histopathologically, collected over the past 9 years (from February 2013 to June 2022) were retrospectively studied. The patients underwent the same therapy with platinum-containing chemotherapy regimens. In the malignant GCT group, OS and EFS were 81.0 ± 4% and 73 ± 5%, respectively. OS and EFS in the teratoma group were 90 ± 5% and 85 ± 6%. In univariate analysis, parameters like stage of disease, tumor localization, AFP level ≥10,000 ng/mL, serum AFP kinetics and resection status were found to be statistically significant prognostic factors. In the multivariate analysis, the significant adverse factors were the resection status, initial AFP level ≥10,000 ng/mL and serum AFP kinetics slow down (p = .000). Good survival rates can be achieved in developing countries with adequate compliance with treatment protocols. The analysis demonstrates high efficacy of platinum-containing chemotherapy regimens. In our opinion, the protocol used in high-income countries can be implemented in low-income countries with the financial support from the government. The qualification of specialists is also important.

Helical tomotherapy craniospinal irradiation in primary brain tumours: Toxicities and outcomes in a peadiatric and adult population.

Objective: As craniospinal irradiation (CSI) is delivered more frequently by helical tomotherapy (HT) with few reports about late effects, we analysed all patients treated in our centre over an 11-year period. Methods and materials: Our study included all patients that underwent CSI by HT, between September 2009 and January 2020, in the Department of Radiation Oncology of the Toulouse Cancer Institute. Acute radiotherapy toxicities were reported and medium- to long-term outcomes analysed. Results: Among the 79 patients included, 70.9 % were younger than 18 years at diagnosis, the median age was 13 (range: 1-52) at the time of radiation therapy, 67.1 % of patients had medulloblastoma. Half of them (49.4 %) had a metastatic disease at diagnosis. The median dose of CSI was 36 Gy (range, 18-36). Seventy-seven patients received a radiation boost to the original location of the primary tumour (97.5 %), 32 patients also received a boost to their metastatic sites (40.5 %). Median follow-up was 55.5 months (95 %CI = [41.2; 71.8]). The 3-year event-free survival rate was 66.3 % (95 %CI = [54.2; 75.9]). Most patients presented with acute haematological toxicities during CSI (85.9 %), predominantly severe thrombocytopenia (39.7 %). Among the 64 patients assessed for medium- and long-term outcomes, 52 survived and 47 were alive and disease-free at the latest follow-up visit on record. There were 3.8 % secondary tumours: two meningiomas and one diffuse intrinsic pontine glioma. Adult and paediatric patients respectively presented with secondary cataract (4.3 % vs 22.0 %), persistent hearing disorders (26.1 % vs 29.3 %), pulmonary or cardiac late effects (4.3 % vs 2.4 %), hormonal pituitary gland deficiencies (30.0 % vs 56.8 %) and psycho-cognitive disorders (56.5 % vs 53.7 %). Conclusion: CSI dispensed by HT, did not result in any additional acute or late toxicities when compared to 3D-CSI. There was no increase in the secondary tumour rate compared to that reported in the literature.

Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Causes of Childhood Cancer: A Review of the Recent Literature: Part I-Childhood Factors.

PURPOSE: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). METHODS: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. RESULTS: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy.

Unhealthy lifestyle behaviors, overweight, and obesity among childhood cancer survivors in the Netherlands: A DCCSS LATER study.

BACKGROUND: The objective of this study was to examine the prevalence of unhealthy lifestyle behaviors, overweight, and obesity in Dutch childhood cancer survivors (CCSs) compared with sibling controls and the Dutch general population. Other aims were to assess associated factors of unhealthy lifestyle behaviors, overweight, and obesity and to identify subgroups of CCSs at risk for these unhealthy statuses. METHODS: The authors included 2253 CCSs and 906 siblings from the Dutch Childhood Cancer Survivor Study-Late Effects After Childhood Cancer cohort, part 1, and added data from the Dutch general population. Questionnaire data were collected on overweight and obesity (body mass index >25.0 kg/m2), meeting physical activity guidelines (>150 minutes per week of moderate or vigorous exercises), excessive alcohol consumption (>14 and >21 alcoholic consumptions per week for women and men, respectively), daily smoking, and monthly drug use. Multivariable logistic regression analyses and two-step cluster analyses were performed to examine sociodemographic-related, health-related, cancer-related, and treatment-related associated factors of unhealthy lifestyle behaviors and to identify subgroups of CCSs at risk for multiple unhealthy behaviors. RESULTS: CCSs more often did not meet physical activity guidelines than their siblings (30.0% vs. 19.3%; p < .001). Married as marital status, lower education level, nonstudent status, and comorbidities were common associated factors for a body mass index ≥25.0 kg/m2 and insufficient physical activity, whereas male sex and lower education were shared associated factors for excessive alcohol consumption, daily smoking, and monthly drug use. A subgroup of CCSs was identified as excessive alcohol consumers, daily smokers, and monthly drug users. CONCLUSIONS: The current results emphasize the factors associated with unhealthy behaviors and the potential identification of CCSs who exhibit multiple unhealthy lifestyle behaviors.

Off-label prescribing of immune checkpoint inhibitor therapy at a single pediatric cancer center.

BACKGROUND: Immune checkpoint inhibitors (ICI) have improved outcomes in a variety of adult cancers and are prescribed with increasing frequency across oncology. However, patterns of off-label use of ICI in pediatrics remain unclear. METHODS: This is a single-institution, retrospective cohort study evaluating off-label ICI use in pediatric and young adult patients with cancer treated at our institution from 2014 to 2022. Response was based on clinician assessment derived from clinical records. Immune-related adverse events (iRAEs) were classified according to CTCAE v5.0. RESULTS: We identified 50 unique patients treated with off-label ICI (28 with solid tumors, 20 with central nervous system (CNS) tumors, 2 with hematologic malignancies). At time of ICI initiation, only five patients (10%) had localized disease, and all but one patient was treated in the relapsed/refractory setting. All patients were treated with the FDA-approved weight-based dosing recommendations. Overall, there was disease control in 21 patients (42%), with best response including one complete response (melanoma), two partial responses (high-grade glioma, CNS nongerminomatous germ cell tumor), and 18 patients with stable disease. Forty-four patients (88%) eventually experienced disease progression. Among 22 patients (44%) experiencing iRAEs, 10 (20%) had a grade ≥3 irAE, 12 (24%) required corticosteroids, and 14 (28%) required ICI discontinuation. irAE occurrence was associated with significantly improved progression-free survival (HR 0.35; 95% CI: 0.18 to 0.68; p = 0.002) and overall survival (HR 0.33; 95% CI: 0.17 to 0.66; p = 0.002). CONCLUSIONS: At our institution, ICI was most commonly prescribed in the relapsed/refractory setting to patients with metastatic disease. The treatment was generally well-tolerated in the pediatric population. The overall response rate was low, and the majority of patients eventually experienced disease progression. A few patients, however, had durable treatment responses. Further studies are needed to identify which pediatric patients are most likely to benefit from ICI.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

Increasing pediatric radiation oncology capacity in sub-saharan Africa using technology: a pilot of a pediatric radiation oncology virtual training course.

BACKGROUND: The shortage of skilled healthcare professionals in pediatric oncology and the limited access to training programs remain significant challenges in Nigeria and sub-Saharan Africa. The the Pediatric Radiation Oncology (Virtual) Course, 'PedROC' project aims to contribute to improving pediatric cancer outcomes in Nigeria by increasing the capacity of radiation oncology professionals. To address the gap in access to pediatric radiation oncology professional development, the PedROC project was created, harnessing technology to improve radiation oncology training via a curriculum delivered through web-conferencing. This study aimed to evaluate the effectiveness of the PedROC pilot in enhancing the capacity, confidence, and skill of radiation oncologists in decision-making, prescribing, and treatment planning of radiotherapy for children diagnosed with cancer. METHODS: A multidisciplinary faculty of specialists in radiation oncology, pediatric oncology, oncology nursing, radiation therapy technology, and medical physics collaborated to identify the key learning needs in pediatric radiation oncology in the country. The team collaborated to develop a comprehensive curriculum covering the most common pediatric cancers in sub-Saharan Africa for the training program. The training course was conducted over two days, delivering twenty-four half-hour sessions for a total of 12 h, from July 31 to August 01, 2021. RESULTS: Analysis of pre and post - training surveys showed a significant increase in self-reported confidence measures across all domains among radiation oncologists. The program successfully improved participants' knowledge and confidence levels in managing common pediatric cancers using radiotherapy, particularly addressing radiotherapy-specific issues such as appropriate dose, target volume delineation, treatment planning, dose constraints, and plan evaluation. CONCLUSION: The PedROC pilot showed the efficacy of this model in enhancing the capacity and confidence of radiation oncology professionals involved in the treatment of pediatric cancer. The findings indicate that technology holds significant potential to increase pediatric radiation oncology capacity in Africa, ensuring improved access to proper treatment and ultimately improving pediatric cancer outcomes.

Reintegration into school, kindergarten and work in families of childhood cancer survivors after a family-oriented rehabilitation program.

Objective: To describe the situation of childhood cancer survivors and their parents before and one year after a family-oriented rehabilitation program (FOR) and to identify factors influencing reintegration. Methods: We included parents of children diagnosed with leukemia or central nervous system tumor. We assessed parental functioning using the functioning subscale of the Ulm Quality of Life Inventory for Parents (ULQIE) and children's school/kindergarten related quality of life (parental assessment, subscale KINDL-R). Descriptive analyses, group comparisons and multiple regression analyses on data of 285 parents of 174 children diagnosed with leukemia or central nervous system tumor. Results: Parents reported changes in their work situation (e.g., reduction of working hours) due to their child's diagnosis. Parental functioning increased significantly over time. Children's leukemia diagnosis and shorter time since the end of treatment were associated with higher functioning in parents one year after FOR. Parents reported difficulties in the child's work pace, concentration, stress resilience and empathy. The school/kindergarten-related quality of life (QoL) of the children was lower than in the general population. One year after FOR, most children reintegrated fully in school/kindergarten, partly with support (e.g., integration assistant). No significant predictors for children's reintegration were identified. Discussion: Parents and children experience major changes in their work/school/kindergarten life. One year after FOR most parents reported a reintegration of their children, however the children's school/kindergarten-related QoL remained below average compared to norm values. Even after rehabilitation families of childhood cancer survivors might benefit from psychosocial and practical support offers to support families with the reintegration into work/school/kindergarten.

Rhabdoid tumor predisposition syndrome: A historical review of treatments and outcomes for associated pediatric malignancies.

Rhabdoid tumor predisposition syndrome (RTPS) is a rare disorder associated with malignant rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and/or other extracranial, extrarenal rhabdoid tumors (EERT), and these pediatric malignancies are difficult to treat. Presently, most of the information regarding clinical manifestations, treatment, and outcomes of rhabdoid tumors comes from large data registries and case series. Our current understanding of treatments for patients with rhabdoid tumors may inform how we approach patients with RTPS. In this manuscript, we review the genetic and clinical features of RTPS and, using known registry data and clinical reports, review associated tumor types ATRT, RTK, and EERT, closing with potential new approaches to treatment. We propose collaborative international efforts to study the use of SMARC (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin)-targeting agents, high-dose consolidative therapy, and age-based irradiation of disease sites in RTPS.

Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Plexiform Neurofibroma Cells at Doses That Do Not Affect Patient-Matched Schwann Cells.

Neurofibromatosis Type 1 (NF1) is a common neurogenic condition characterized by heterozygous loss of function mutations in the neurofibromin gene. NF1 patients are susceptible to the development of neurofibromas, including plexiform neurofibromas (pNFs), which occurs in about half of all cases. Plexiform neurofibroma are benign peripheral nerve sheath tumors originating from Schwann cells after complete loss of neurofibromin; they can be debilitating and also transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). Here, our data indicates that silver nanoparticles (AgNPs) may be useful in the treatment of pNFs. We assessed the cytotoxicity of AgNPs using pNF cells and Schwann cells derived from the same NF1 patient. We found that AgNPs are selectively cytotoxic to pNF cells relative to isogenic Schwann cells. We then examined the role of neurofibromin expression on AgNP-mediated cytotoxicity; restoration of neurofibromin expression in pNF cells decreased sensitivity to AgNP, and knockdown of neurofibromin in isogenic Schwann cells increased sensitivity to AgNP, outlining a correlation between neurofibromin expression and AgNP-mediated cytotoxicity. AgNP was able to selectively remove pNF cells from a co-culture with patient-matched Schwann cells. Therefore, AgNPs represent a new approach for clinical management of NF1-associated pNF to address significant clinical need.

Cumulative Dosage of Intrathecal Chemotherapy Agents Predicts White Matter Integrity in Long-Term Survivors of Acute Lymphoblastic Leukemia: A PETALE Study.

Acute lymphoblastic leukemia (ALL) stands as the most prevalent form of pediatric cancer in North America, with a current five-year survival rate of 85%. While more children achieved ALL remission and transition into adulthood, the prevalence of long-term treatment-related effects, especially neurocognitive sequelae, remains significant. This study pursues two objectives. Firstly, it investigates if Magnetization Transfer Ratio (MTR), a method assessing myelin integrity, is sensitive to white matter (WM) microstructural changes in long-term ALL survivors and whether these relate to cognitive impairments. Secondly, it examines the dose-related effects of chemotherapy agents on the MTR and its relationship to other risk factors such as female sex, early age diagnosis, and cranial radiotherapy. Magnetization transfer imaging was utilized to assess WM integrity in 35 survivors at a mean of 18.9 years after the onset of ALL (range since diagnosis: 6.9-26.8). Additionally, 21 controls matched for age, sex, and education level, with no history of cancer, were included. MTR was extracted from both the entire brain's WM and the corpus callosum through semi-automated procedures. The results indicated lower MTR means in survivors, which is linked to cognitive function. Negative associations between MTR means and intrathecal agents' (MTX, cytarabine, and hydrocortisone) cumulative doses received were highlighted. This study offers valuable insights into the connections between myelin deterioration, cognitive impairment, and the implications of IT chemotherapy, enhancing our understanding of ALL survivorship dynamics. It underscores MTR's relevance in monitoring neurotoxicity during oncological drug follow-up examinations.

Clinical Potential of Transcranial Focused Ultrasound for Neurorehabilitation in Pediatric Cancer Survivors.

Cancer survivors are at a high risk for treatment-related late effects, particularly neurocognitive impairment in the attention and executive function domains. These can be compounded in pediatric populations still undergoing neural development, which has increased interest in survivorship studies and neurorehabilitation approaches to mitigate these effects. Cognitive training regimens have shown promise as a therapeutic intervention for improving cognitive function. Therapist-guided and computerized training programs with adaptive paradigms have been successfully implemented in pediatric populations, with positive outcomes on attention and working memory. Another interventional approach is neuromodulation to alter plasticity. Transcranial electrical stimulation can modulate cortical surface activity, and cranial nerve stimulation alters autonomic activity in afferent brainstem pathways. However, they are more systemic in nature and have diffuse spatial targeting. Transcranial focused ultrasound (tFUS) modulation overcomes these limitations with high spatial specificity and the ability to target deeper brain regions. In this review, we discuss the efficacy of tFUS for modulating specific brain regions and its potential utility to augment cognitive training programs as a complementary intervention.

Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis.

The 5-year overall survival of children and adolescents with osteosarcoma has been in plateau during the last 30 years. The present systematic review (1976-2023) and meta-analysis aimed to explore factors implicated in the prognosis of children and young adults with high-grade osteosarcoma. Original studies including patients ≤30 years and the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data (2010-2021) referred to children ≤14 years were analysed. Individual participant data (IPD) and summary estimates were used to assess the n-year survival rates, as well as the association of risk factors with overall survival (OS) and event-free survival (EFS). IPD and the n-year survival rates were pooled using Kaplan-Meier and Cox regression models, and random effects models, respectively. Data from 8412 patients, including 46 publications, NARECHEM-ST data, and 277 IPD from 10 studies were analysed. The summary 5-year OS rate was 64% [95% confidence interval (95%CI): 62%-66%, 37 studies, 6661 patients] and the EFS was 52% (95%CI: 49%-56%, 30 studies, 5010 patients). The survival rates generally differed in the pre-specified subgroups. Limb-salvage surgery showed a higher 5-year OS rate (69%) versus amputation (47%). Good responders had higher OS rates at 3 years (94%) and 5 years (81%), compared to poor responders at 3 years (66%), and 5 years (56%). Patients with metastatic disease had a higher risk of death [Hazard Ratio (HR): 3.60, 95%CI: 2.52, 5.15, 11 studies]. Sex did not have an impact on EFS (HR females/males: 0.90, 95%CI: 0.54, 1.48, 3 studies), whereas age>18 years seems to adversely affect EFS (HR 18+/<10 years: 1.36, 95%CI: 1.09, 1.86, 3 studies). Our results summarize the collective experience on prognostic factors of high-grade osteosarcoma among children and young adults. Poor response to neoadjuvant chemotherapy and metastatic disease at diagnosis were confirmed as primary risk factors of poor outcome. International collaboration of osteosarcoma study groups is essential to improve survival.

Anti-PD-1 Therapy in Advanced Pediatric Malignancies in Nationwide Study: Good Outcome in Skin Melanoma and Hodgkin Lymphoma.

BACKGROUND/AIM: The role of immune checkpoint inhibitors (ICIs; anti-PD1) in the treatment of childhood cancers is still evolving. The aim of this nationwide retrospective study was to assess the safety and effectiveness of ICIs used in a group of 42 patients, with a median age of 13.6 years, with various types of advanced malignancies treated in pediatric oncology centers in Poland between 2015 and 2023. RESULTS: The indications for treatment with anti-PD1 were as follows: Hodgkin lymphoma (11); malignant skin melanoma (9); neuroblastoma (8); and other malignancies (14). At the end of follow-up, complete remission (CR) was observed in 37.7% (15/42) of children and disease stabilization in 9.5% (4/42), with a mean survival 3.6 (95% CI = 2.6-4.6) years. The best survival (OS = 1.0) was observed in the group of patients with Hodgkin lymphoma. For malignant melanoma of the skin, neuroblastoma, and other rare malignancies, the estimated 3-year OS values were, respectively, 0.78, 0.33, and 0.25 (p = 0.002). The best progression-free survival value (0.78) was observed in the group with malignant melanoma. Significantly better effects of immunotherapy were confirmed in patients ≥ 14 years of age and good overall performance ECOG status. Severe adverse events were observed in 30.9% (13/42) patients.

Survey of Transitional Care Between Pediatrics and Obstetrics/Gynecology in Japan.

Purpose: This study's aim was to determine the actual status of transitional care for patients with pediatric cancer (PPCs) in Japan by surveying obstetricians/gynecologists. Methods: A questionnaire survey on transitional medicine was conducted in the form of an online questionnaire at 579 major training facilities nationwide, which were registered with the Japanese Society of Obstetrics and Gynecology. Results: While 40% of the facilities had received referrals for PPCs, only 13% provided transitional care specifically for PPCs. The most common problems with referrals were related to "insufficient explanation." In addition, at facilities with no experience treating PPCs, many respondents commented that they did not know how to follow the progression of the disease. Regarding the necessity of obstetrics/gynecology visits for PPCs, more than half of the respondents at facilities with experience treating PPCs answered that such visits were "necessary"; only 1% answered that they were "unnecessary." On the other hand, 37% of the facilities that had no experience treating PPCs answered that it was "necessary," whereas 4% answered that it was "unnecessary." Conclusions: This survey of the actual status of transitional care between pediatrics and obstetrics/gynecology in Japan identified issues to be addressed for the spread of transitional care. The results suggest that, in the future, health care professionals need education to increase their knowledge, and that patient education that leads to patients' awareness of their own self-management is necessary.

Pediatric, Adolescent and Young Adult (AYA) Peritoneal and Pleural Mesothelioma: A National Cancer Database Review.

PURPOSE: Malignant peritoneal and pleural mesothelioma are rare in young patients, with a paucity of data regarding clinical characteristics and outcomes. We aimed to describe the clinical characteristics, treatment strategies, and outcomes for pediatric and adolescent/young adult (AYA) patients. METHODS: The National Cancer Database (NCDB) was queried for malignant peritoneal and pleural mesothelioma in pediatric and AYA patients (ages 0-39) from 2004 to 2019. Stratification was performed for pediatric (age 0-21) and young adult (age 22-39) patients. Chi-squared, multivariable cox regression, and Kaplan-Meier analyses were performed. RESULTS: We identified 570 total patients, 46 pediatric and 524 young adult, with mesothelioma (363 peritoneal and 207 pleural). There were significant differences in sex distribution as patients with peritoneal mesothelioma were more frequently female (63.1%). Patients with peritoneal mesothelioma were more likely to have radical surgery compared to pleural mesothelioma (56.7% v. 24.6%, respectively). A majority of patients with peritoneal and pleural mesothelioma received chemotherapy (66.4% and 61.4%, respectively). For peritoneal mesothelioma, surgical resection was associated with improved overall survival, whereas male sex, neoadjuvant chemotherapy, and radiation were associated with worse overall survival. For pleural mesothelioma, intraoperative chemotherapy was associated with improved overall survival, whereas Black race was associated with worse overall survival. Mean overall survival was greater for patients with peritoneal mesothelioma (125 months) compared to those with pleural mesothelioma (69 months), which remained significant after stratification of pediatric and young adult patients. CONCLUSION: By analyzing a large cohort of pediatric and AYA mesothelioma, this study highlights clinical, prognostic, and survival differences between peritoneal and pleural disease. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective.