Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition

Purpose: Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors.Patients and methods: We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E-mutated glioma treated with BRAF inhibition across 29 centers from multiple countries.Results: Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy (P \u3c .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively (P = .02).Conclusion: Use of BRAF inhibition results in robust and durable responses in BRAF V600E-mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas

Impact of the COVID-19 Pandemic on Influenza Circulation During the 2020/21 and 2021/22 Seasons, in Europe

Publisher Copyright: © 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.Background: The emergence of SARS-CoV-2 in late 2019 saw the implementation of public health and social measures (PHSM) by countries across Europe to reduce its transmission and impact on populations. Consequently, countries reported changes in influenza circulation and extensive disruptions to routine surveillance systems. Methods: We describe the epidemiology of influenza in Europe between Weeks 40/2020 and 39/2022 compared to the 2016/17 to 2019/20 seasons, to assess the impact of the COVID-19 pandemic and PHSM on surveillance systems and influenza circulation. Results: Low detections of influenza were observed through primary care sentinel sources during seasonal influenza periods (Week 40 to 20); 56 (of 39,457 specimens tested; < 1% positivity) in 2020/21 and 7261 (of 64,153 specimens tested; 11% positivity) detections in 2021/22 were observed, compared to an average of 18,383 (of 50,544 specimens tested; 36% positivity) detections in 2016/17 to 2019/20. Similarly, 11 (of 19,989 specimens tested; < 1% positivity) and 1488 (of 23,636 specimens tested; 6% positivity) detections were reported through SARI surveillance sources in 2020/21 and 2021/22, respectively, compared to an average of 2850 (of 10,389 specimens tested; 27% positivity) detections in 2016/17 to 2019/20. However, the 2021/22 interseasonal period saw unusual increases in influenza detections across surveillance site types when PHSM were easing. Conclusion: In conclusion, findings suggest that the restriction and easing of PHSM measures were associated with variations in influenza detections. Our observations of out-of-season influenza activity highlight the importance of an integrated respiratory surveillance strategy to monitor circulating respiratory viruses throughout the year to inform optimal prevention and control strategies.Peer reviewe

Impact of the COVID‐19 Pandemic on Influenza Circulation During the 2020/21 and 2021/22 Seasons, in Europe

Background: The emergence of SARS‐CoV‐2 in late 2019 saw the implementation of public health and social measures (PHSM) by countries across Europe to reduce its transmission and impact on populations. Consequently, countries reported changes in influenza circulation and extensive disruptions to routine surveillance systems.MethodsWe describe the epidemiology of influenza in Europe between Weeks 40/2020 and 39/2022 compared to the 2016/17 to 2019/20 seasons, to assess the impact of the COVID‐19 pandemic and PHSM on surveillance systems and influenza circulation.ResultsLow detections of influenza were observed through primary care sentinel sources during seasonal influenza periods (Week 40 to 20); 56 (of 39,457 specimens tested; < 1% positivity) in 2020/21 and 7261 (of 64,153 specimens tested; 11% positivity) detections in 2021/22 were observed, compared to an average of 18,383 (of 50,544 specimens tested; 36% positivity) detections in 2016/17 to 2019/20. Similarly, 11 (of 19,989 specimens tested; < 1% positivity) and 1488 (of 23,636 specimens tested; 6% positivity) detections were reported through SARI surveillance sources in 2020/21 and 2021/22, respectively, compared to an average of 2850 (of 10,389 specimens tested; 27% positivity) detections in 2016/17 to 2019/20. However, the 2021/22 interseasonal period saw unusual increases in influenza detections across surveillance site types when PHSM were easing.ConclusionIn conclusion, findings suggest that the restriction and easing of PHSM measures were associated with variations in influenza detections. Our observations of out‐of‐season influenza activity highlight the importance of an integrated respiratory surveillance strategy to monitor circulating respiratory viruses throughout the year to inform optimal prevention and control strategies.Data Availability Statement TESSy data are available upon request ([https://www.ecdc.europa.eu/ en/publications-data/european-surveillance-system-tessy])