Objective To investigate the correlation between induction therapy response and prognosis in children with high-risk neuroblastoma,and to analyze factors associated with the induction therapy response.Methods Data of 55 children with high-risk neuroblastoma diagnosed and treated at Shanghai Children's Hospital from January 2019 to December 2023 were retrospectively reviewed.Induction response was assessed according to the International Neuroblastoma Response Criteria and patients were categorized into a good-response group(complete response or very good partial response)and a poor-response group(partial response,progressive disease,mixed response,or no response).Clinical and biological characteristics,treatments,and prognostic factors were analyzed.Results Among the 55 children,29 were male and 26 were female;the median age at onset was 39 months.Follow-up was performed until December 31,2024.The 3-year overall survival(OS)and event-free survival(EFS)rates were(83.8±5.3)%and(47.0±10.3)%,respectively.Neuron-specific enolase level at initial diagnosis,induction therapy response,radiotherapy,and recurrence were prognostic factors for EFS and OS(P<0.05).The 3-year OS was(83.5±7.4)%in the good-response group and(66.7±13.6)%in the poor-response group(P=0.012),while the 3-year EFS was(62.8±10.4)%and(27.8±14.8)%,respectively(P<0.001).Intracranial metastasis at initial diagnosis was associated with a poor induction response(P=0.033).A platelet count≥400×109/L was associated with a better induction response(P=0.002).Conclusions Induction therapy response is a significant prognostic factor in high-risk neuroblastoma.Absence of intracranial metastasis and a platelet count≥400×109/L at initial diagnosis are associated with a favorable induction therapy response.

Background: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma, with survival dependent on risk stratification and multimodal therapy. This single-center study explored the clinical characteristics, treatment outcomes and prognostic factors of pediatric RMS to optimize local management. Methods: Data of RMS patients treated at Shanghai Children's Hospital from 2011 to 2024 were analyzed to estimate event-free survival (EFS) and overall survival (OS), and factors associated with survival. Patients received the Rs-99 (pre-2019) regimen or a modified Rs-2018 (post-2019) regimen. Results: A total of 76 RMS patients were identified. The 5-year EFS and OS for the entire cohort were 71.1% (95% CI, 62.3% to 83.3%) and 72.4% (95% CI, 64.0% to 84.5%), respectively. No statistically significant differences were observed in EFS and OS between the Rs-2018 and Rs-99 regimens. Univariate survival analysis indicated that metastasis was associated with prognosis: the 5-year EFS and OS of patients with metastatic disease were 35.0% (95% CI, 18.3% to 57.6%) and 40.0% (95% CI, 27.3% to 75.3%), while both the 5-year EFS and OS of patients with localized disease reached 83.9% (95% CI, 69.3% to 93.6%). Primary tumor resection status was a key prognostic factor for patients with localized disease, with a 5-year EFS of 100% for R0 resection and 46.7% (95% CI, 25.2% to 74.0%) for R2 resection. For patients with localized disease, EFS was comparable between those who underwent delayed primary excision (DPE) and upfront resection. Conclusions: Outcomes for patients with metastatic RMS remain poor. For those with localized disease, primary tumor resection status correlates with improved EFS and OS; additionally, DPE represents a feasible therapeutic option for localized RMS involving complex anatomical sites.

Neuroblastoma (NB) is one of the most common extracranial solid tumors in children. Patients with high-risk metastatic disease remain at substantial risk of relapse and have poor long-term outcomes. No standard salvage regimen has been established for relapsed/refractory (R/R) NB, and the role of immune checkpoint inhibitors in pediatric NB remains investigational. Here, we report two pediatric patients with R/R high-risk NB who received a tislelizumab-containing multi-agent regimen consisting of tislelizumab, an anti-GD2 monoclonal antibody, GM-CSF support, and sequential mICE/VIT chemotherapy. The anti-GD2 antibody, dinutuximab beta or naxitamab, was selected according to each patient’s insurance coverage. Both patients tolerated treatment well, and no severe immune-related adverse events were observed during the reported follow-up period. After four cycles of combination therapy, Patient 1 showed marked regression of soft-tissue lesions and clearance of bone marrow involvement. Patient 2 achieved a complete response and remained disease-free during the 5-month follow-up period after treatment completion. However, the durability of this response remains uncertain because of the limited follow-up duration. These preliminary short-term observations suggest that this multi-agent regimen may be a feasible salvage approach for selected pediatric patients with R/R high-risk NB. However, the durability of these antitumor responses cannot be confirmed given the limited surveillance period. Notably, this retrospective two-case observation cannot distinguish the independent antitumor contribution of tislelizumab alone, as multiple therapeutic components were administered simultaneously without control groups to isolate single-agent efficacy. Larger prospective studies are warranted to further evaluate the efficacy and safety of this approach.

Abstract Purpose An immune-mediated pathogenesis has been postulated for aplastic anemia (AA), and impaired Tregs and other immune abnormalities have been identified in patients with AA. However, the process by which abnormal immunity specifically damages hematopoietic stem cells (HSCs) remains unclear. We conducted primary clinical studies to investigate whether the depletion of HSCs in AA could be attributed to the collapse of immune privilege (IP) afforded by regulatory T cells (Tregs). Methods The distribution of Tregs in the bone marrow of children with AA, myelodysplastic syndrome (MDS), and control participants was separately detected by immunohistochemistry. T-helper 1 (Th1), T-helper 2 (Th2), and T-helper 17 (Th17) cells, cytokines, and HSCs in the bone marrow of the AA and control groups were examined using flow cytometry. Results Patients with AA showed significantly lower FoxP3 + /CD4 + ratios (AA vs. normal: 18.09% ± 5.38% vs. 21.72% ± 4.21%, P = 0.014; AA vs. MDS: 18.09% ± 5.38% vs. 22.63% ± 5.98%, P = 0.030) and reduced Treg counts (AA vs. normal: 4.07 ± 1.41 vs. 5.25 ± 1.86 cells/HP, P = 0.014; AA vs. MDS: 4.07 ± 1.41 vs. 5.30 ± 1.49 cells/HP, P = 0.024) near the endosteum. The bone marrow in patients with AA exhibited Th1 dominance (AA vs. normal: 39.80% ± 5.20% vs. 22.1% ± 2.9% in controls, P < 0.001) and Th2 reduction (AA vs. normal: 59.20% ± 5.30% vs. 77.20% ± 2.60%, P < 0.001), indicating IP dysfunction. Significant elevation of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-17 levels was observed in the bone marrow of patients with AA. Long-term (LT)-HSCs were severely depleted in patients with AA (AA vs. normal: 0.13% vs. 1.22%, P = 0.035), with moderate reduction in short-term (ST)-HSCs. Conclusions Patients with AA showed endosteal Treg reduction, Th1 dominance, elevated proinflammatory cytokine levels, and severe LT-HSC depletion, linking bone marrow IP dysfunction to HSC damage. These findings provide a mechanistic explanation for the specific loss of HSCs in AA and highlight the IP niche as a therapeutic target.

Hepatoblastoma (HB) has a subtle onset and poor prognosis in high-risk group patients. Due to the adverse reactions and drug resistance associated with traditional systemic chemotherapy, there is an urgent need for new treatment strategies. Photothermal therapy (PTT) has been proposed as an advanced, patient-centered approach for cancer treatment. However, the safety concerns regarding traditional photothermal agents and the existence of intracellular self-protective autophagy mechanisms have hindered the clinical application and efficacy of PTT. This paper reports the development of a two-dimensional (2D) MXene-based composite nanoplatform for efficient synergistic autophagy inhibition and PTT for HB. Here, by directly coating a mesoporous silica layer on the surface of 2D Nb2C MXene nanosheets, the hydrophilicity/dispersion was enhanced. An autophagy inhibitor nanogenerator was designed, wherein the mesopores provide a reservoir for the autophagy inhibitor chloroquine (CQ), and the MXene core acts as a photothermal trigger under a near-infrared II (NIR-II) biowindow. In vitro experimental results showed that CQ/Nb2C@MSNs-PEG, after entering the tumor, induced rapid release of the encapsulated CQ to inhibit pro-survival autophagy in cells under 1064 nm NIR-II laser irradiation, enhancing the photothermal cytotoxicity of Nb2C@MSNs-PEG on tumor cells. Importantly, the CQ/Nb2C@MSNs-PEG therapeutic platform demonstrated effective antitumor activity in the HuH-6 tumor-bearing mouse model, validating the synergistic strategy of PTT and protective autophagy blockade for enhanced efficacy. This study provides a promising strategy for hepatoblastoma treatment by combining autophagy inhibition to enhance the photothermal therapeutic effect.

ObjectiveTo summarize the clinical characteristics and analyze prognostic factors of neuroblastoma (NB) in infants (≤12 months) at a single center. MethodsA retrospective analysis was conducted on the clinical data of infant patients (≤12 months) diagnosed with NB and treated between January 2014 and December 2022. Clinical features were analyzed, and comparisons between two sample rates were performed using the χ2 test. Univariate prognostic analysis was conducted using the log-rank test, and survival outcomes were analyzed using the Kaplan-Meier method. ResultsA total of 42 infants (≤12 months) with NB were enrolled. Low-risk patients underwent surgical resection alone; intermediate-risk patients received surgery combined with chemotherapy with or without maintenance therapy; high-risk patients were treated with surgery and chemotherapy with or without maintenance therapy or radiotherapy. The 5-year event-free survival (EFS) rate was (92.7±4.9)%, and the 5-year overall survival rate was (95.2±3.6)%. Only two patients died because of tumor recurrence or progression. Univariate analysis identified MYCN amplification and the initial lactate dehydrogenase (LDH) level ≥ five times the upper limit of the normal were significantly associated with poor prognosis (5-year EFS: 33.3% vs. 97.4% and 60.0% vs. 97.3%, P<0.0001 and P=0.0035). ConclusionInfant NB has a favorable overall prognosis. MYCN amplification and markedly elevated initial LDH are associated with poor outcomes.

Primary mediastinal malignant germ cell tumors (PMMGCTs) in children are highly aggressive and associated with a poor prognosis. We herein report the case of a male pediatric patient who presented with a large mediastinal mass and extensive metastases to the lungs, brain, kidneys, and multiple bones, illustrating the aggressive nature of this disease. The patient received a multi-drug combination chemotherapy regimen before and after tumor resection and successfully achieved complete remission. Notably, he has survived for 12 months and remains in complete remission to date. This case underscores the potential efficacy of multi-agent combination chemotherapy as a component of a multimodal treatment strategy for advanced PMMGCTs.

BackgroundRhabdomyosarcoma (RMS) of the trunk and extremities is associated with unfavorable outcomes due to high rates of metastasis and relapse. However, large-scale studies focusing specifically on this anatomical subsite remain limited. This study aimed to investigate the clinical characteristics and risk factors associated with relapse/progression in pediatric patients with trunk and extremity RMS.PurposeTo investigate the clinical features and risk factors associated with relapse/progression in pediatric patients with rhabdomyosarcoma (RMS) of the trunk and extremities.MethodsA retrospective analysis was conducted on clinical data from 15 children with trunk and extremity RMS treated at Shanghai Children’s Hospital between January 2011 and December 2024. All patients received multimodal therapy, including surgery, chemotherapy, and radiotherapy. Associations between clinical characteristics and relapse/progression rates were analyzed using descriptive statistics and Fisher’s exact test.ResultsThe median follow-up duration was 48 months. The 5-year event-free survival (EFS) was 60% (95% CI: 34.5%-85.5%), and the 5-year overall survival (OS) was 66.7% (95% CI: 42.1%-91.3%). The overall relapse/progression rate was 40% (95% CI: 16.8%-68.7%). Significantly higher relapse/progression rates were observed in patients with metastasis at diagnosis (85.7% vs 0%, P<0.001), high-risk stratification (75.0% vs 0%, P=0.010), and macroscopic residual disease after surgery (100% vs 10.0%, P<0.001). Regional lymph node involvement showed a trend toward a higher relapse/progression rate (66.7%) compared to no involvement (22.2%), although the difference was not statistically significant (P=0.123).ConclusionPediatric trunk and extremity RMS is associated with a high risk of relapse/progression. Metastasis at diagnosis and macroscopic residual tumor after resection are major adverse prognostic factors. Regional lymph node involvement may confer an increased risk, warranting validation in larger cohorts.

IntroductionPediatric aplastic anemia (AA), a rare and potentially fatal disease, demonstrates significant heterogeneity in pathogenesis, disease severity, therapeutic regimens, and clinical outcomes.MethodsIn this study, clinical features and outcomes of 70 children with AA, including severe AA (SAA, n = 30), very severe AA (vSAA, n = 21) and nonsevere AA (nSAA, n = 19), were retrospectively analyzed, with a median follow-up of 60.7 months (range, 0.4-136.5 months).ResultsPatients with nSAA were mainly treated with cyclosporine A, whereas SAA/vSAA patients primarily received allogeneic hematopoietic stem cell transplantation (HSCT) followed by standard immunosuppressive therapy (IST). Ultimate therapy regimens differed significantly between patients with SAA/vSAA and nSAA (p = 0.001). SAA/vSAA group exhibited a higher overall response rate at the 2-year follow-up (85.5% vs. 55.6%, p = 0.019). The 2-year overall survival (OS) and event-free survival (EFS) for the entire cohort were 97.1% and 48.5%, respectively. In patients with SAA/vSAA, HSCT was associated with higher and faster cumulative complete response (CR) rate (p < 0.0001) and superior EFS (p = 0.0297) compared with IST. Two IST-resistant patients were observed to achieved CR with eltrombopag (EPAG) salvage therapy.Discussionpediatric AA carries excellent OS but suboptimal EFS. HSCT tends to yield more favorable EFS compared with IST in SAA/vSAA patients, and EPAG may act as an effective salvage option for appropriately selected IST-resistant individuals. Further multicenter prospective research is warranted prior to implementing these findings in routine clinical practice.

Vaginal malignant germ cell tumors (MGCTs), predominantly yolk sac tumors, are extremely rare, with no established consensus on optimal management. This study evaluated whether post-chemotherapy surgery is necessary for vaginal MGCTs. A retrospective analysis was conducted on patients diagnosed with vaginal MGCTs from 1996 to 2023. Progression-free survival (PFS), overall survival (OS), the impact of surgical intervention, and the presence of post-chemotherapy residual mass (RM) were assessed. Seventy-five patients (median age:11 months) were included. Six underwent initial tumor resection, and all received platinum-based chemotherapy. RM was detected post-chemotherapy in 57

OBJECTIVES:To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS:This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS:Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS:The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.

Background Patients with immunocompromise were suspected to encounter a high risk for severe coronavirus disease 2019 (COVID-19) infection on early period; however, data is lacking nowadays and immune response remain unclear. Methods In this retrospective study, internet questionnaire survey and medical records were acquired in pediatric hematology oncology patients. Clinical severity, immunological characteristics, and outcomes were analyzed from December 1, 2022 to January 31, 2023 at the 3rd year of pandemic in China. Results A total of 306 patients were included, with 21 patients (6.9%) asymptomatic, 262 (85.6%) mild severity, 17 (5.6%) moderate severity, 5 (1.6%) severe severity, and 1 (0.3%) critical severity. Seventy-eight (25.5%) patients were on intensive chemotherapy, and 32.0% children were on maintenance chemotherapy. Delays in cancer therapy occurred in 86.7% patients. Univariable analysis revealed active chemotherapy (P < 0.0001), long duration of symptom (P < 0.0001), low lymphocytes count (P = 0.095), low CD3 + and CD8 + T cell count (P = 0.013, P = 0.022), high percentage of CD4 + TCM (P = 0.016), and low percentage of transitional B cells (P = 0.045) were high risk factors for severe COVID-19 infection. Cox regression model showed that the absolute lymphocytes count (P = 0.027) and long duration of symptom (P = 0.002) were the independent factors for severity. Patients with CD8 + dominant and B cell depletion subtype wasn't related with severity, but had higher percentage of CD8 + effector memory T cells (TEM) and terminally differentiated effector memory T cells (TEMRA) (P < 0.001, P < 0.001), and a longer COVID-19 duration (P = 0.045). Conclusion The severity was relatively mild in children with immunodeficiencies in the third year of COVID-19 pandemic. Low lymphocyte count and long duration of symptom were the independent risk factors with COVID-19 severity. Delays in cancer care remain a major concern and the long outcome is pending.

BACKGROUND:The capacity of presurgical image-defined risk factors (IDRFs) to predict secondary surgical outcomes in patients with neuroblastoma is controversial. METHODS:The International Neuroblastoma Surgical Report Form (INSRF) was employed to retrospectively collect the clinical data of 53 patients diagnosed with neuroblastoma at our hospital from April 2014 to April 2020. IDRFs were identified at the time of diagnosis and reassessed during the course of neoadjuvant chemotherapy. Various statistical tests were used to evaluate the correlation between IDRFs and secondary surgical outcomes. RESULTS:A total of 195 IDRFs were identified. Notably, by two courses of neoadjuvant chemotherapy, the number of "two body compartments," "intraspinal tumor extension," and "trachea-compressing" IDRFs decreased significantly (p = .001). The primary tumor volumes and the number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy, especially in "intraspinal tumor extension" IDRFs (p = .034). The median number of IDRF per patient was four (interquartile range [IQR]: 1-5) at diagnosis, which diminished to one (IQR: 1-3) subsequent to neoadjuvant chemotherapy. The presence of preoperative IDRFs was not associated with surgical complications (p = .286) or the extent of surgery (p = .188). However, the number of preoperative IDRFs linked to the extent of surgery (p = .002), not to operative complications (p = .669). Specifically, presurgery "renal vessel contact" IDRFs were predictive of surgical complications, while presurgery "infiltration of vital structures" IDRFs were associated with the extent of surgery. CONCLUSION:The number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy. The number and type of presurgery IDRFs may predict secondary surgical outcomes, surpassing the mere consideration of their presence or absence.

BACKGROUND:Although clear cell sarcoma of kidney (CCSK) is rare, it is the second most common renal tumor in children after Wilms' tumor. NWTS and SIOP are two major groups which had made tremendous efforts on renal tumors, but the strategies are different, for NWTS follows the upfront surgery principle providing definite pathology and the SIOP follows the upfront chemotherapy principle, each has its own advantages. Here we aimed to evaluate the outcomes of CCSK in China following NWTS strategies to analyze the prognostic factors. METHODS:For this multicenter retrospective study, a total of 54 patients were enrolled from three children's hospitals, between April 2003 and December 2021. Treatment comprised upfront radical nephrectomy, followed by radiotherapy and intensive chemotherapy. Clinical records were regularly updated. Prognostic factors and survival rates were evaluated. RESULTS:The 54 enrolled patients had a median age of 37 months (range, 4 months to 11.4 years). The stage distribution was 16% stage I (n = 9), 30% stage II (n = 16), 39% stage III (n = 21), and 15% stage IV (n = 8). Among stage IV, metastasis sites included the lung (n = 6), bone (n = 1), and intra-orbital/cervical lymph node (n = 1). After a median follow-up of 5.6 years, the 5-year event-free survival (EFS) was 82.4±5.4%, and overall survival was 88.1±4.6%. The EFS was 100% for stage I, 93.8 ±6.1% for stage II, 71.1±10.0% for stage III, and 68.6±18.6% for stage IV. Univariate analysis revealed that staging (III/IV), tumor rupture, and inferior vena cava tumor thrombus were inferior prognostic factors. Multivariate analysis revealed that tumor rupture was independent poor prognostic factor (P = 0.01, HR 5.9). Among relapsed patients, relapse occurred a median of 11 months after diagnosis (range, 4-41 months), and 50% (4/8) achieved a second complete remission after multiple treatment. None of the six lung metastasis patients received lung RT, only one patient developed a relapse and was salvaged by RT after relapse. CONCLUSIONS:Tumor rupture was independent poor prognostic factor. Upfront surgery of NWTS strategies can make a definite pathology diagnosis, but how to reduce tumor rupture during surgery is important especially in developing countries. The outcomes of patients with stage I-III CCSK in China were comparable to findings in other developed countries. Better outcomes were achieved in stage IV CCSK by using an intensive chemotherapy regimen including carboplatin, which require further confirmation by AREN0321. Lung RT may be safely omitted in selected patients who achieve a compete radiographic response after 6 weeks of systemic treatment (including surgery). Treatment should be encouraged even in CCSK cases with metastasis and relapse.

OBJECTIVE:The aim was to describe the clinical features of extracranial germ cell tumors (GCTs) in pediatrics and study the clinical risk factors related to survival for malignant germ cell tumors (MGCTs) in order to optimize therapeutic options.METHODS:The clinical data of children with extracranial GCTs in three children's medical centers in Shanghai were retrospectively analyzed.RESULTS:In total, 1007 cases of extracranial GCTs diagnosed between 2010 and 2019 were included in this study, including teratomas (TERs) 706 (70.11%) and MGCTs 301 (29.89%). There were twice as many TER cases as MGCT cases. Approximately 50% of children with GCTs were <3 years old (43.39% for TERs, 67.13% for MGCTs). GCTs in children of different ages show differences in tumor anatomical locations and pathological subtypes. The 5-year event-free survival (EFS) and overall survival (OS) of all patients with MGCTs were 82.33% (95% CI, 77.32%, 86.62%) and 94.13% (95% CI, 90.02%, 96.69%), respectively. The multivariate Cox regression analysis identified a primary site in the mediastinum and alpha fetoprotein (AFP) levels ≥10,000 ng/mL as independent adverse prognostic factors (p < 0.0.0001, χ2 = 23.6638, p = 0.0225, χ2 = 5.2072.). There were no significant differences in OS among children receiving various chemotherapy regimens, such as the BEP, PEB, JEB and other regimens (VBP/VIP and AVCP/IEV) (p < 0.05).CONCLUSIONS:The clinical features of GCTs in Chinese pediatrics are similar to those reported in children in Europe and America. The age distribution of pathological types and primary sites in GCTs reflect the developmental origin of type I and type II GCTs transformed from mismigration primordial germ cells (PGCs). Optimizing the current platinum-based chemotherapy regimens and exploring the treatment strategies for MGCTs of the mediastinum are future research directions.