Background Efforts to improve the quality of end‐of‐life (EOL) care depend on better knowledge of the care that children, adolescents, and young adults with cancer receive, including high‐intensity EOL (HI‐EOL) care. The objective was to assess the rates of HI‐EOL care in this population and to determine patient‐ and hospital‐related predictors of HI‐EOL from the French national hospital database. Methods This was a population‐based, retrospective study of a cohort of patients aged 0 to 25 years at the time of death who died at hospital as a result of cancer in France between 2014 and 2016. The primary outcome was HI‐EOL care, defined as the occurrence of ≥1 chemotherapy session <14 days from death, receiving care in an intensive care unit ≥1 time, >1 emergency room admission, and >1 hospitalization in an acute care unit in the last 30 days of life. Results The study included 1899 individuals from 345 hospitals; 61.4% experienced HI‐EOL care. HI‐EOL was increased with social disadvantage (adjusted odds ratio [AOR], 1.30; 95% confidence interval [CI], 1.03‐1.65; P = .028), hematological malignancies (AOR, 2.09; 95% CI, 1.57‐2.77; P < .001), complex chronic conditions (AOR, 1.60; 95% CI, 1.23‐2.09; P = .001) and care delivered in a specialty center (AOR, 1.70; 95% CI, 1.22‐2.36; P = .001). HI‐EOL was reduced in cases of palliative care (AOR, 0.31; 95% CI, 0.24‐0.41; P < .001). Conclusion A majority of children, adolescents, and young adults experience HI‐EOL care. Several features (eg, social disadvantage, cancer diagnosis, complex chronic conditions, and specialty center care) were associated with HI‐EOL care. These findings should now be discussed with patients, families, and professionals to define the optimal EOL.

Background: to evaluate the safety and efficacy of a physical activity program (PAP) in children and adolescents with cancer. Methods: children and adolescents with cancer were randomly assigned in a 1:1 ratio to the six-month PAP (intervention group) or to the control group. The first evaluation was performed at the end of the PAP (T0 + 6 mo). At T0 + 6 mo, both groups received the six-month PAP with a second evaluation at T0 + 12 mo. The primary outcome was the evolution of exercise capacity measured using the six-minute walk test (6 MWT) at T0 + 6 mo. Secondary outcomes included PAP safety and changes in other physical functions, self-esteem, and quality-of-life parameters. Results: The trial involved 80 children and adolescents (age range 5.0–18.4 years), of whom 41 were assigned to the interventional group and 39 to the control group. Underlying malignancies were leukemia (39%) and a broad range of solid tumors (61%). No adverse events occurred. At T0 + 6 mo, the evolution of the 6 MWT distance (±SEM) was improved in the intervention group vs. the control group (86 ± 12 m vs. 32 ± 6 m, p < 0.001). Several other physical parameters were significantly improved in the intervention group. Global self-esteem and parent-reported quality-of-life were significantly increased in the intervention group. Analysis at T0 + 12 mo showed persistence of the benefits in the intervention group on exercise capacity evolution (115 ± 18 m vs. 49 ± 11 m, p = 0.004) and on most physical and QoL parameters. Conclusion: In children and adolescents with cancer, a physical activity program is safe, improves exercise capacity, and may have physical and psychological benefits.

Background and Aims COVID-19 infection in pediatric cancer patients is severe or critical in 20% of the patients. It can therefore directly affect pediatric cancer patients and/or their care. We aimed at evaluating the safety and efficacy of BNT162b2 mRNA Covid-19 vaccine in AYA with solid tumor. Methods Retrospective analysis of safety and efficacy of BNT162b2 mRNA Covid-19 vaccine administered to patients, >= 16 years old, under treatment for a solid tumor or within 6 months’ post-treatment from 15/2/2021 to 15/4/2021. Two administrations of the vaccine 3 weeks apart were given. Sera were tested for anti-SARS-Cov-2 IgG antibodies directed against the S1 domain of the spike protein. In case of positive serology, neutralization of SARS-Cov-2 was tested. Results Twenty-three patients with solid tumors were identified and proposed to get vaccinated. Nine patients refused and 1 previously developed COVID-19 infection with positive serology. At time of writing, 13 patients (10 M/2F); median age: 17) started vaccination. All patient received 2 injections except 2 patients who stopped vaccination because of tumor progression. Ten patients were under treatment (chemotherapy-7pts, immunotherapy-2 pts, targeted therapy-2 pts-follow-up 3 patients). Overall, vaccines were well tolerated. Five patients did not report any side-effect after the first injection and 4 after the second injection. Main local reactivity symptom was mild pain at the site of injection (6 and 2 pts). Fatigue (2pts and 5 pts) was the most frequent systemic symptom. One patient refused serology testing. All patients but 1 had pre-vaccination negative serology, 7/10 tested had positive serology before second vaccine injection, 9/10 had positive serology one month after the second injection. All patients with seroconversion had positive COVID-19 neutralization test. No patient developed COVID infections. Conclusions We report the good safety profile and good efficacy BNT162B2 vaccine in AYA with solid tumors. Larger series and monitoring of the kinetics of anti-Sars-Cov-2 IgG antibodies for several months are mandatory to confirm these preliminary results and to determine long-term vaccination.

To update the 2015 clinical practice guideline for the prevention of oral mucositis in pediatric cancer or hematopoietic stem cell transplant (HSCT) patients. Methods: We performed seven systematic reviews of mucositis prevention. Three reviews included randomized controlled trials (RCTs) conducted in pediatric and adult patients evaluating cryotherapy, keratinocyte growth factor (KGF) or photobiomodulation therapy with a focus on efficacy. Three reviews included studies of any design conducted in pediatric patients evaluating these same interventions with a focus on adverse events and feasibility. One review included all RCTs of any intervention for mucositis prevention in pediatric patients. Primary outcome was severe oral mucositis.

PURPOSE Low- and middle-income countries (LMICs) experience the burden of 80% of new childhood cancer cases worldwide, with cure rates as low as 10% in some countries. Metronomics combines frequent administrations of low-dose chemotherapy with drug repurposing, which consists of using already-approved drugs for new medical applications. With wide availability, limited costs, and little infrastructure needs, metronomics can be part of constraint-adapted regimens in these resource-limited settings—with the understanding that metronomics shall not be a substitute for standard treatments when available and doable. Our study aims to describe the experience, practices, opinions, and needs in metronomics of physicians working in LMICs. METHODS An online questionnaire was sent to more than 1,200 physicians in pediatric oncology networks in LMICs. Items included the type of center, physician’s demographics, experience in pediatric oncology, and experience with current knowledge of metronomics. Opinions and perspectives were explored using multiple-answer and open questions. RESULTS Of physicians, 17% responded. Of respondents, 54.9% declared that they had already used a metronomic regimen. The most frequently cited repositioned drugs were celecoxib (44%) followed by propranolol and valproic acid (17%). Respondents highlighted the advantages of outpatient use (20%) and expected low toxicity (24%). In considering the drawbacks of metronomics, 47% of responses highlighted the lack of scientific evidence or guidelines, 33% the availability or affordability of drugs, and 18% the problem of acceptance or compliance. Of physicians, 79% believed that use of metronomics will spread in LMICs in the near future and 98% of them were willing to participate in international metronomic protocols or registries. CONCLUSION Metronomics is already used in LMICs and is a potential answer to unmet needs in pediatric oncology. There is room for improvement in the availability of drugs and a necessity to develop collaborative protocols and research to generate level A evidence.

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Background: Pediatric low-grade glioma (pLGG) represents the most common brain tumor in childhood. Previous studies have reported that a therapeutic strategy on the basis of the association of bevacizumab alone (B) or in combination with irinotecan (BI) could produce rapid tumor response and clinical improvement in children with pLGG. Nevertheless, a majority of patients relapses shortly (median, 5 mo) after stopping B or BI treatment. We proposed metronomic maintenance with weekly vinblastine added after a 6 months induction of B/BI to prevent early relapse. Patients and Methods: Monocentric retrospective analysis of a patient with pLGG treated with B or BI for 6 months followed by a 12-month maintenance with weekly vinblastine (6 mg/m²) from October 2012 to September 2019 in a single institution. Results: In total, 18 patients (7 males and 11 females) were identified. Because of progression during the B or BI induction 2/18 children were excluded. In total, 16 patients were analyzed with a median age of 10 years (range, 4 to 16 y). A total of 13 patients received BI and 3 patients received B alone. The mean duration of induction was 6.2 months (range, 2 to 12 mo). After induction 5/16 patients had a partial radiologic response, 11/16 patients had stable disease. All patients started maintenance (median duration, 12 mo; range, 3 to 12 mo). With a median follow-up of 3.9 years after the end of B or BI (range, 11 mo to 7.2 y), 15/16 patients were alive and 9/16 patients were progression-free. Seven of 16 children progressed with a median time to progression of 23 months (ranges, 5 to 39 mo). Three of 16 (18%) children progressed during vinblastine maintenance and 4/16 (25%) patients after the end of maintenance. After the total duration of treatment, clinical improvement was noted in 4 patients, 9 patients had stable symptoms, and only 3 patients progressed. One and 2-year event-free survival were, respectively, 81.2% and 56.2%. Two-year overall survival was 93.7%. Conclusions: We report here, the potential benefit and the improvement of progression-free survival by adding metronomic maintenance with weekly vinblastine after initial induction with B or BI in children with low-grade glioma.

Precision oncology requires tumor molecular profiling to identify actionable targets. Tumor biopsies are considered as the gold standard, but their indications are limited by the burden of procedures in children. Blood-derived liquid biopsy (LB) is a potential alternative that is not yet documented in real-world settings, especially in pediatric oncology. We performed a retrospective analysis of children and teenagers with a relapsing or refractory disease, upon whom LB was performed using the Foundation One® liquid CDx from 1 January 2020 to 31 December 2021 in a single center. Forty-five patients (27 boys) were included, with a median age of 9 years of age (range: 1.5–17 years old). Underlying malignancies were neuroblastoma (12 patients), bone sarcoma (12), soft tissue sarcoma (9), brain tumors (7), and miscellaneous tumors (5). Forty-three patients had metastatic disease. Six patients had more than one biopsy because of a failure in first LB. Median time to obtain results was 13 days. Overall, analysis was successful for 33/45 patients. Eight patients did not present any molecular abnormalities. Molecular alterations were identified in 25 samples with a mean of 2.1 alterations per sample. The most common alterations concerned TP53 (7 pts), EWS-FLI1 (5), ALK (3), MYC (3), and CREBBP (2). TMB was low in all cases. Six patients received treatment based on the results from LB analysis and all were treated off-trial. Three additional patients were included in early phase clinical trials. Mean duration of treatment was 85 days, with one patient with stable disease after eight months. Molecular profiling using Foundation One® Liquid CDx was feasible in pediatric patients with high-risk solid tumors and lead to identification of targetable mutations in a subset of patients.