Background: Relapses in pediatric high-risk brain tumors remain unmet medical needs. Over the last 15 years, metronomic chemotherapy has gradually emerged as an alternative therapeutic approach. Patients and Methods: This is a national retrospective study of patients with relapsing pediatric brain tumors treated according to the MEMMAT or MEMMAT-like regimen from 2010 to 2022. Treatment consisted of daily oral thalidomide, fenofibrate, and celecoxib, and alternating 21-day cycles of metronomic etoposide and cyclophosphamide associated with bevacizumab and intraventricular chemotherapy. Results: Forty-one patients were included. The most frequent malignancies were medulloblastoma (22) and ATRT (8). Overall, the best responses were CR in eight patients (20%), PR in three patients (7%), and SD in three patients (7%), for a clinical benefit rate of 34%. The median overall survival was 26 months (IC95% = 12.4–42.7), and median EFS was 9.7 months (IC95% = 6.0–18.6). The most frequent grade ¾ toxicities were hematological. Dose had to be adjusted in 27% of the cases. There was no statistical difference in outcome between full or modified MEMMAT. The best setting seems to be when MEMMAT is used as a maintenance and at first relapse. Conclusions: The metronomic MEMMAT combination can lead to sustained control of relapsed high-risk pediatric brain tumors.

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.

(1) Background: Children and young adults with cancer are poorly represented in COVID-19 vaccination studies, and long-term protection conferred by vaccination is not known. (2) Objectives: 1. To determine the adverse effects associated with BNT162B2 vaccination in children and young adults with cancer. 2. To assess its efficacy in stimulating immunological response and in preventing severe COVID-19 disease. (3) Methods: Retrospective single-center study evaluating patients aged 8 to 22 years, with cancer, who underwent vaccination from January 2021 to June 2022. ELISA serologies and serum neutralization were collected monthly from the first injection. Serologies below 26 were considered negative, while those above 264 BAU/mL were considered positive and indicative of protection. Antibodies titers were considered positive above 20. Data on adverse events and infections were collected. (4) Results: 38 patients were included (M/F = 1.7, median age 16 years), of whom 63% had a localized tumor and 76% were undergoing treatment at the time of the first vaccination. Two or three vaccine injections were administered in 90% of patients. Adverse events were mainly systemic and not severe, except for seven grade 3 toxicities. Four cancer-related deaths were reported. Median serology was negative the month following the first vaccination and became protective during the third month. At 3 and 12 months, median serology was 1778 and 6437 BAU/mL, respectively. Serum neutralization was positive in 97% of the patients. COVID-19 infection occurred despite vaccination in 18%; all were mild forms. (5) Conclusions: In children and young adults with cancer, vaccination was well tolerated and conferred effective serum neutralization. COVID-19 infections were mild, and vaccine seroconversion persisted after 12 months in most patients. The value of additional vaccination should be further established.

The overall survival rate after hematopoietic stem cell transplantation (HSCT) for inborn errors of immunity (IEI) has improved considerably, and its indications have broadened. As a consequence, addressing the issue of long-term health-related quality of life (HRQoL) has become crucial. Our study focuses on the health and HRQoL of post-HSCT survivors. We conducted a multicenter prospective follow-up study enrolling IEI patients who underwent transplantation in childhood before 2009. Self-reported data from the French Childhood Immune Deficiency Long-term Cohort and the 36-item Short Form questionnaires were compiled. One hundred twelve survivors were included with a median duration period from HSCT of 15 years (range 5-37), of whom 55 underwent transplantation for a combined immunodeficiency. We show that in patients evaluated at least 5 years after HSCT, 55% are still affected by a poor or very poor health status. Poor and very poor health status correlated with an abnormal graft function, defined as host or mixed chimerism, abnormal CD3+ count, or diagnosis of chronic graft-versus-host disease (poor health: odds ratio [OR] = 2.6, 95% confidence interval [CI], 1.1-5.9, P = .028; very poor health: OR = 3.6, 95% CI, 1.1-13, P = .049). Poor health was directly linked to a poorer HRQoL. Significant improvements in graft procedures have translated into better survival rates, but we show here that about half of the transplanted patients remain affected by an altered health status with a correlation to both abnormal graft function and impaired HRQoL. Additional studies are needed to confirm the impact of those improvements on long-term health status and HRQoL.