Early advice on managing children with cancer during the COVID-19 pandemic and a call for sharing experiences

We are living very difficult times. The pandemic caused by SARS‐CoV‐2 (COVID‐19) is rapidly affecting the delivery of care for children with cancer around the world. We have written this commentary to facilitate the dissemination of helpful information and useful links, and to place in perspective what we do and do not know about the COVID‐19 pandemic and its impact in the practice of paediatric oncology. Generally speaking, the impact that this virus may have on the paediatric population, and the management of children with cancer, remains unclear and poorly documented. The next two sections outline what has been published or communicated via academic websites, both in children and adults with cancer

Science and health for all children with cancer

Each year approximately 429,000 children and adolescents aged 0-19 years are expected to develop cancer. Five-year survival rates exceed 80% for the 45,000 children with cancer in highincome countries (HIC), but are less than 30% for the 384,000 children in low- and middle-income countries (LMIC). Improved survival rates in HIC have been achieved through multidisciplinary care and research, with treatment regimens utilizing mostly generic medicines and optimized risk stratification. Children’s outcomes in LMIC can be improved by adapting effective treatments to local resources and clinical needs, and addressing common problems such as delayed diagnosis and treatment abandonment. By supporting local leaders to increase service capacity and achieve measurable clinical improvements, collaborative partnerships can stimulate governmental and nongovernmental investments. These approaches should bring the new WHO childhood cancer survival target of 60% within reach of all by 2030

Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators

Introduction Inalignment with the World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC), the International Society of Pediatric Oncology initiated a program to map global pediatric oncology services. As survival rates in Africa are low and data are scant, this continent was mapped first to identify areas with greatest need. Methods Beginning November 2018, an electronic survey was sent to all known stakeholders, followed by email communications and internet searches to verify data. Availability of pediatric oncologists, chemotherapy, surgical expertise, and radiotherapy was correlated with geographic region, World Bank income status, Universal Health Coverage, population < 15 and < 24 years, percentage of gross domestic product spent on healthcare, and Human Development Index (HDI). Results Responses were received from 48/54 African countries. All three treatment modalities were reportedly available in 9/48 countries, whereas seven countries reported no pediatric oncology services. Negative correlations were detected between provision of all three services and geographic region (P = 0.01), younger median population age (P = 0.002), low-income country status (P = 0.045), and lower HDI (P < 0.001). Conclusion This study provides a comprehensive overview of pediatric oncology care in Africa, emphasizing marked disparities between countries: some have highly specialized services, whereas others have no services. A long-term strategy to eliminate disparities in African pediatric cancer care should be aligned with the WHO GICC aims and facilitated by SIOP Africa. Meeting abstracts SIOP maps pediatric oncology services in Africa to address inequalities in childhood cancer services. Geel J, Ranasinghe N, Davidson A, Challinor J, Howard S, Wollaert S, Myezo K, Renner L, Hessissen L, Bouffet E. 51st Annual Congress of the International Society of Paediatric Oncology (SIOP), Lyon, France, October 2019. Pediatric Blood and Cancer Vol 66 S219-S219. Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators

Efficacy and Safety of Dabrafenib in Pediatric Patients with BRAF V600 Mutation-Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I/IIa Study

PURPOSE: Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor. Patients with BRAF V600 mutation-positive pLGG may benefit from treatment with dabrafenib. Part 2 of a phase I/IIa study, open-label study (NCT01677741) explores the activity and safety of dabrafenib treatment in these patients. PATIENTS AND METHODS: Patients ages 1 to <18 years who had BRAF V600-mutant solid tumors (≥1 evaluable lesion) with recurrent, refractory, or progressive disease after ≥1 standard therapy were treated with oral dabrafenib 3.0 to 5.25 mg/kg/day (part 1) or at the recommended phase II dose (RP2D; part 2). Primary objectives were to determine the RP2D (part 1, results presented in a companion paper) and assess clinical activity (part 2). Here, we report the clinical activity, including objective response rates (ORRs) using Response Assessment in Neuro-Oncology criteria and safety across parts 1 and 2. RESULTS: Overall, 32 patients with pLGG were enrolled (part 1, n = 15; part 2, n = 17). Minimum follow-up was 26.2 months. Among all patients, the ORR was 44% [95% confidence interval (CI), 26-62] by independent review. The 1-year progression-free survival rate was 85% (95% CI, 64-94). Treatment-related adverse events (AE) were reported in 29 patients (91%); the most common was fatigue (34%). Grade 3/4 treatment-related AEs were reported in 9 patients (28%). CONCLUSIONS: Dabrafenib demonstrated meaningful clinical activity and acceptable tolerability in patients with BRAF V600-mutant pLGG

Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse?

Early detection of relapse has been advocated to improve survival in children with recurrent medulloblastoma. However, the prognostic factors and the longer term outcome of these patients remains unclear. Pattern of recurrences were analysed in three consecutive protocols of the Société Française d'Oncologie Pédiatrique (1985-91). A uniform surveillance programme including repeated lumbar puncture combined with computerized tomography (CT) or magnetic resonance imaging (MRI) scan was applied for all registered patients. Forty-six out of 116 patients had progressive or recurrent disease. The median time from diagnosis to recurrence was 10.5 months and 76% relapses occurred during the first 2 years. Seventeen patients had asymptomatic relapses that were detected by the surveillance protocol. Forty-one patients were treated at time of progression. Twenty-three responded to salvage therapy and 11 achieved a second complete remission. The median survival time after progression was 5 months (<1-41 months), and only two patients remained alive at time of follow-up. Length of survival is primarily related to some specific patterns of relapse (time from diagnosis to recurrence, circumstances of relapse, extent of relapse) and to the response to salvage therapy. No evidence of long-term benefit appeared from any form of treatment

SIOP Ependymoma I: Final results, long term follow-up and molecular analysis of the trial cohort: A BIOMECA Consortium Study

BACKGROUND: SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3 to 21 years treated with a staged management strategy. A further aim was to assess the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide and cyclophosphamide (VEC). We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers. METHODS: 74 participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation, 1q, hTERT, ReLA, Tenascin-C, H3K27me3 and pAKT status were evaluated. RESULTS: Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (p=0.003, HR=2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (p=0.005, HR=2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (p=0.003, HR=2.70, 95%CI 1.49-6.10 and p=0.014, HR=5.8, 95%CI 1.2-28) and H3K27me3 loss with worse OS (p=0.003, HR=4.6, 95%CI 1.5-13.2). Methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, best chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding the prespecified 45%. CONCLUSIONS: Participants with totally resected ependymoma had the best outcomes. RR of STR to VEC exceeded the pre-specified efficacy criterion. However, cases of inaccurate stratification highlighted the need for rapid central review. 1q gain, H3K27me3 loss and hTERT expression were all associated with poorer survival outcomes