The prognosis of high-risk neuroblastomas (NB) that are resistant to first-line induction chemotherapy is relatively poor. This study explored the mechanism of resistance to first-line chemotherapeutics mediated by TXNDC17 and its potential solutions in NB. The genetic and clinical data of patients with NB were obtained from the Therapeutically Applicable Research to Generate Effective Treatments dataset. TXNDC17 and BECN1 expressions in NB cells were up- and downregulated by transfection with plasmids and shRNA, respectively. Autophagy-related proteins were detected by western blot. Cell viability was determined using cell proliferation and toxicity experiments. Apoptotic cells were detected using flow cytometry. Overall, 1076 pediatric and adolescent patients with NB were enrolled in this study. The 10-year overall survival (OS) rates and event-free survival (EFS) rates for the patients with mutation of BECN1 were 37.4% ± 9.1% and 34.5% ± 8.8%, respectively. For patients with mutation of TXNDC17, the 10-year OS and EFS were 41.4% ± 5.9% and 24.3% ± 5.1%, respectively, which were significantly lower than those in the unaltered group. The overexpression of BECN1 and TXNDC17 reduced NB sensitivity to cisplatin (DDP), etoposide (VP16), and cyclophosphamide (CTX). Autophagy mediated by BECN1 was regulated by TXNDC17, and this process was involved in the resistance to DDP, VP16, and CTX in NB. Suberoylanilide hydroxamic acid (SAHA) can enhance the sensitivity of NB cells to chemotherapeutics by inhibiting TXNDC17, ultimately decreasing autophagy-mediated chemoresistance. Acquired resistance to first-line chemotherapeutics was associated with autophagy mediated by BECN1 and regulated by TXNDC17, which can be reversed by SAHA.

Background: Emerging evidence exhibited the importance of life quality of children with pediatric cancers and their parents. The child patients generally have poor life quality and pyschological status under the intensive comprehensive therapies. Procedure: The cultural and psychological program named Ward School Program (WSP) may ease the psychological stress for the child patients. The purpose of this study is to systemically evaluate the impact of the WSP on the quality of life and psychological behavior of children with pediatric cancers. We evaluated the life quality and negative emotions of the children and their parents individually. Results: 46 child patients and their parents have accepted the invitation. compared to the occasional participation group (OP), the WSP has significantly improved the life quality satisfaction, enhanced self-conception, and promoted learning ability and attitude of the In-depth participation group (IDP), while their parents have different opinions. The parents believe that the WSP could significantly improve children’s personality problems and relieve children’s anxiety, but it has not much help on their learning skills, it indicated that it is necessary to enhance communication between parents and children for better understanding of each other. Conclusion: The WSP have postive effects on the improvement of life quality and pyschosocial behaviors for the children with pediatric cancers.

Purpose: The prognosis of the relapsed or refractory Wilms tumor (R/R WT) was dismal and new salvage chemotherapy was needed. This study aimed to evaluate the efficacy of the combination of irinotecan and doxorubicin hydrochloride liposome regimen (AI) for R/R WT. Methods: The present study enrolled the R/R WT who were treated with AI regimen at Sun Yat-Sen University Cancer Center from July 2018 to September 2020. The response was defined as the best observed response after the last two cycle and toxicity was evaluated. Result: Total of 16 patients with median age of 4.2 years (0.5 to 11 years) were enrolled, including 14 patients with relapsed disease and 2 patients with refractory disease. These patients received 1 to 8 courses (median 3 courses).14 patients were assessable for response: 2 complete response (CR), 5 partial response (PR), 2 stable disease (SD), 5 progression disease (PD). The objective response rate was 50% (2 CR, 5 PR) and the disease control rate was 64% (2 CR, 5 PR, and 2 SD). The median progression-free survival was 3.5 months (range 0.5-12 months), and the median survival duration was 8 months (range 1-28 months). Sixteen patients were assessable for toxicity, with most common grade 3 or 4 adverse events were alopecia (62%), leucopenia (40%), abdominal pain (38%), etc. No fatal adverse events have been observed. Conclusion: The AI regimen has positive efficacy with tolerated toxicity, it may provide an alternative option for the treatment of R/R WT.

Objective: We investigated the influence of methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms on the survival of pediatric non-Hodgkin lymphoma (NHL) cases in south China treated with the modified Berlin-Frankfurt-Münster 95 protocol. Methods: We reviewed the medical records of 374 patients newly diagnosed at our center between 2014 and 2020. A subgroup of 158 patients was genotyped based on polymorphisms C677T and A1298C. Results: Overall, there were 283 male (75.7%) and 91 female patients (24.3%); the median age was 9 years (range, 1–18 years). The tumor types included Burkitt lymphoma (BL; n = 180), lymphoblastic lymphoma (LBL; n = 95), anaplastic large cell lymphoma (ALCL; n = 64), and diffuse large B cell lymphoma (DLBCL; n = 35). At diagnosis, 327 patients (87.4%) had advanced-stage disease; 159 (42.5%) and 152 patients (40.6%) were stratified into the intermediate- and high-risk group, respectively. Seventy (18.7%) and 36 cases (9.6%) had bone marrow and central nervous system (CNS) involvement, respectively. The median follow-up time was 28.5 months (range, 1–76 months); complete remission rate, estimated 5-year event-free survival, and 5-year overall survival rate was 86.1%, 74.2%, and 85.7%, respectively. The C677T variant allele was correlated with favorable survival in BL/DLBCL, while ALCL, CNS involvement, advanced stage, and intermediate/high risk were associated with poor survival in NHL. Conclusion: Analysis of the C677T polymorphism could be used for survival prediction and potential risk stratification for further treatment protocols for Chinese pediatric NHL. Further larger studies are needed to verify the clinical value of the C677T polymorphism.

Background. The criteria for response evaluation in pediatric and adolescent Hodgkin lymphoma (HL) are controversial. We compared different criteria for the interpretation of interim and post-treatment PET/CT to predict the outcome of pediatric and adolescent HL. Procedure. Baseline, interim, and post-treatment 18F-FDG-PET/CT scans of 147 pediatric and adolescent HL patients were interpreted according to the International Harmonization Project Criteria (IHPC) and Deauville Criteria (DC). Two thresholds of positivity were used for the DC: DC-3, scores of 3–5; and DC-4, scores of 4–5. Diagnostic performance of interim and post-treatment PET in outcome prediction was evaluated. Progression-free survival (PFS) was analyzed by the Kaplan-Meier method and Cox proportional hazards model. Results. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of interim FDG-PET/CT were 82%, 33%, 15%, 93%, and 39%, respectively, for IHPC, 82%, 51%, 19%, 95%, and 55%, respectively, for DC-3, and 27%, 78%, 15%, 88%, and 72%, respectively, for DC-4. The corresponding values for post-treatment PET/CT were 73%, 74%, 23%, 96%, and 74% for IHPC, 67%, 80%, 27%, 96%, and 79% for DC-3, and 47%, 90%, 33%, 94%, and 86% for DC-4. PFS significantly differed between patients with positive and negative post-treatment PET/CT according to IHPC, DC-3, and DC-4 (P < 0.01 for all), but only DC-4 was an independent prognostic factor for PFS (hazard ratio: 7.82). Conclusion. Compared to interim PET/CT, post-treatment PET/CT better predicted the outcomes of pediatric and adolescent HL. DC-4 had superior diagnostic performance over IHPC and DC-3.

Multimodal treatment of children with sacrococcygeal yolk sac tumor: retrospective analysis of clinicopathology characteristics and relapse-free survivalJia Zhu,1∗Huadong Chen,2∗ Tingting Chen,1∗Zijun Zhen,1* Juan Wang,1 Feifei Sun,1 Suying Lu,1 Junting Huang,1 Yizhuo Zhang,1 Xiaofei Sun1△1 Department of Pediatric Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P.R.China2 Department of Pediatric Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Zhongshan Er Lu, Guangzhou, 510080, P.R.China.Running title: Relapse-free survival of sacrococcygeal yolk sac tumor△Corresponding author: Xiaofei Sun MD, Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, 651 Dongfengdong Road, Guangzhou, China, 510060; Tel: +86-20-87342468; Fax: +86-20-87342468; Email:sunxf@sysucc.org.cn∗Jia Zhu, Huadong Chen and Tingting Chen contributed equally to the article.List of Abbreviations