The importance of age as a prognostic predictor of childhood hepatoblastoma: an analysis of single-center childhood hepatoblastoma in China

The importance of age as a prognostic predictor of childhood hepatoblastoma: an analysis of single-center childhood hepatoblastoma in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The importance of age as a prognostic predictor of childhood hepatoblastoma: an analysis of single-center childhood hepatoblastoma in China Zhen Li, Hong Jiang, Yuan-Qi Wang, Wen-Qing Wang, Li-Bin Huang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5240184/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Mar, 2025 Read the published version in BMC Pediatrics → Version 1 posted 10 You are reading this latest preprint version Abstract Objective This study aimed to examine how age at first diagnosis influences the prognosis of Chinese children with hepatoblastoma (HB), and to offer insights for enhancing HB risk stratification. Methods Data from 403 patients with HB diagnosed at the First Affiliated Hospital of Sun Yat-sen University between February 2010 and September 2023 were collected. Kaplan‒Meier survival analysis, Cox regression analysis, and binary logistic regression were employed for statistical analysis. Results The hazard ratios (HRs) for event-free survival (EFS) reduction in HB patients were 1, 0.862, 1.393, 2.008, 1.325, 1.859, 3.667 (P=0.001), and 2.502 (P=0.023) for first–diagnosis ages of 0–1, 1–2, 2–3, 3–4, 4–5, 5–6, 6–8, and ≥8 years, respectively, and the HRs for overall survival (OS) were 1, 0.410, 0.876, 1.713, 1.243, 0.575, 3.012 (P=0.039), and 2.012, respectively. After adjusting for newly diagnosed alpha-fetoprotein (AFP), pretreatment extent of tumor (PRETEXT) stage, and PRETEXT stage annotation factors, the prognosis of HB for patients diagnosed at ≥6 years old and <6 years old remained significantly different. There was no significant difference in the HR for EFS or OS reduction among the 0–1month, 1–3month, 4–6month, 7–9month, and 9–12month groups. Conclusion Age≥6 years is an independent risk factor for poor prognosis in HB patients. Age has no effect on the prognosis of HB during infancy. The inclusion of patients aged ≥6 years at first diagnosis in the high-risk group for risk stratification was deemed appropriate. This age factor can guide adjustments in chemotherapy intensity. Figures Figure 1 Figure 2 Introduction HB is the most common liver tumor in childhood, with an incidence of approximately 0.5–2 per million, and its overall incidence has been increasing in recent years(1). With the advent of platinum-based chemotherapy regimens, the implementation of risk-stratified chemotherapy, and advancements in surgical techniques and multidisciplinary care, the 5-year OS rate for children with HB can reach 80%-90%(2-7). It is believed that the PRETEXT stage, PRETEXT stage annotation factors, and AFP levels at initial diagnosis influence the prognosis of HB patients(2, 8). Numerous studies have demonstrated that age at first diagnosis impacts the prognosis of HB patients(2, 3, 6-14). The latest stratifications by the Childhood Liver Tumors Strategy Group (SIOPEL), Children’s Hepatic Tumors International Collaboration (CHIC), and Chinese Children’s Cancer Group (CCCG) all incorporate age at first diagnosis. SIOPEL's latest risk stratification classifies HB patients diagnosed at >5 years of age into the medium-risk group(15). CHIC generally classifies patients aged ≥8 years in the high-risk group(8). The CCCG's latest stratification places HB patients diagnosed at >8 years of age in the high-risk group. Different HB risk stratification systems vary in the specific age used for classification at first diagnosis. A retrospective study of 606 HB patients diagnosed from 1973–2009 in the Surveillance, Epidemiology, and End Results (SEER) database indicated through univariate and multivariate analyses that the prognosis is better for those diagnosed at 5 years(16). The Japanese JPLT2 study, involving 361 HB patients diagnosed from 1999 to 2012, revealed that the prognosis for the <1 year group was significantly better than that for the 1–2 year and ≥3 year groups(3). Multiple case reports suggest that HBs diagnosed during the neonatal period have a poor prognosis(17-24). A previous retrospective study by our team, which included 86 HB patients diagnosed from 2014–2017, revealed that the prognosis is better for those diagnosed at <3 years than for those diagnosed at ≥3 years(11). Therefore, there is inconsistency among studies regarding the age cut-off used to predict prognosis. Our study, which utilized a substantial dataset of Chinese hepatoblastoma cases, examined the impact of age on the prognosis of children affected by this condition. This study included 403 hepatoblastoma (HB) patients diagnosed at the First Affiliated Hospital of Sun Yat-sen University between February 2010 and September 2023. This study investigated how the age at initial diagnosis influences the prognosis of children, offering a foundation for optimizing HB risk stratification and guiding adjustments in the intensity of chemotherapy. Methods 1. Data collection A total of 403 cases of HB were collected at the Affiliated Hospital of Sun Yat-sen University via biopsy or surgery between February 2010 and September 2023, with diagnoses confirmed through histological examination in the hospital's Department of Pathology. All patients were under 18 years old at first diagnosis and had comprehensive data related to their initial diagnosis and surgery. This allows for accurate stratification of CCCGs and CHIC risk. Basic information, imaging results, and prognostic data were collected. These included age at first diagnosis, distant metastasis (M, discontinuous tumor spread), invasion of the hepatic vein or inferior vena cava (V, invasion of the main hepatic vein, all three branches of the hepatic vein, or inferior vena cava), invasion of the portal vein (P, invasion of the main portal vein or both branches of the portal vein), invasion of adjacent extrahepatic organs (E), multiple tumors (F, two or more tumor nodules separated by normal hepatic parenchyma), tumor rupture (R, tumor rupture at initial diagnosis), and lymph node invasion (N), PRETEXT staging. In this study, 98% (395/403) of HB patients were treated with a platinum-based chemotherapy regimen and/or surgery, all performed by the pediatric surgery team at the First Affiliated Hospital of Sun Yat-sen University, and the patient data were consistent. 2. Statistical methods EFS was defined as the time from the initial diagnosis to disease progression, recurrence, or death. Disease progression (PD) was defined as tumor enlargement of ≥25%, the appearance of new tumors, or increased AFP levels. Recurrence is indicated by biopsy confirmation or clear imaging evidence, along with three consecutive increases in blood AFP levels within four weeks(2). OS was defined as the time from the initial diagnosis to death from any cause(2). The prognosis of HB during follow-up, including the timing of disease progression, recurrence, and death, was recorded retrospectively. The median follow-up duration was 38 months (range: 0.03–159 months), with a follow-up loss rate of 5.7% (23/403). Statistical analysis was conducted via SPSS 26.0, with continuous variables represented by the median. Categorical variables are expressed as frequencies (percentages). The Kaplan‒Meier method was used for survival analysis, 5-year EFS and OS rates were calculated, and the log-rank test was used for comparison. The Cox regression model was utilized for univariate analysis, with P<0.05 considered statistically significant. The age distribution for each risk factor, including the median, maximum, and minimum, was analysed. Binary logistic regression analysis was employed to control for confounding factors such as the AFP level at initial diagnosis, PRETEXT stage, and PRETEXT annotation factors (V, P, E, F, R, M, N), and to compare the prognosis between patients diagnosed before 6 years of age and those diagnosed at 6 years or older. Results 1. Patients The basic data for the 403 HB patients included in this study are presented in Table 1. A total of 84.4% (340/403) of the HB patients were younger than 5 years at initial diagnosis, with a median age of 22 months (range: 0–163 months). Additionally, 6.9% of the HB patients were 8 years or older at diagnosis. 2. Influence of age at initial diagnosis on prognosis. In this study, only 7 patients with HB were diagnosed at ages 7–8 years. To minimize the impact of random error, these cases were combined with those diagnosed at ages 6–7 years into one group. There were 8 patients diagnosed at ages 8–9 years, 6 patients at 9–10 years, 4 patients at 10–11 years, 5 patients at 11–12 years, 1 patient at 12–13 years, and 4 patients at 13–14 years. To reduce the impact of random errors, these errors were combined into one group for statistical analysis. Univariate Cox regression analysis revealed that the HRs for EFS reduction in HBs for children aged 0–1, 1–2, 2–3, 3–4, 4–5, 5–6, 6–8, and ≥8 years at diagnosis were 1, 0.862 (P=0.652), 1.393 (P=0.308), 2.008 (P=0.083), 1.325 (P=0.573), 1.859 (P=0.215), 3.667 (P=0.001), and 2.502 (P=0.023), respectively, and the 5-year EFS rates were 77.7%, 81.1%, 71.8%, 67.9%, 73.9%, 62.7%, 36.0%, and 40.6%, respectively. The HR for EFS reduction in the 6–8-year and ≥8-year groups was significantly different from that in the 0–1-year group, as shown in Table 2. At initial diagnosis ages of 0–1, 1–2, 2–3, 3–4, 4–5, 5–6, 6–8, and ≥8 years, the HRs for decreased OS were 1, 0.410 (P=0.094), 0.876 (P=0.781), 1.713 (P=0.313), 1.243 (P=0.737), 0.575 (P=0.595), 3.012 (P=0.039), and 2.012 (P=0.190), respectively, and the 5-year OS rates were 86.3%, 95.0%, 88.4%, 81.5%, 82.4%, 92.3%, 73.7%, and 76.1%, respectively. The HR for decreased OS in the 6–8-year group was significantly different from that in the 0–1-year group, as shown in Table 2. HB patients diagnosed at <6 years of age were combined into one group, and those diagnosed at ≥6 years of age were combined into another group. The HB survival analysis curves for first diagnosis at ages <6 years and ≥6 years are shown in Fig. 1. The 5-year EFS rates in the <6 years group and the ≥6 years group were 75.8±2.5% and 38.6±10.8% (P < 0.001), respectively, whereas the 5-year OS rates were 88.9±1.9% and 74.7±8.3% (P=0.002), respectively. The influence of the AFP level, PRETEXT stage, and PRETEXT stage annotation factors (V, P, E, F, R, M, N) on prognosis was analysed via Cox regression. Binary logistic regression was employed to control for confounding factors such as the AFP level at initial diagnosis, PRETEXT stage, and PRETEXT annotation factors and to further compare the prognoses between the <6 years and ≥6 years groups. The results are presented in Table 3. To further study the prognosis of HB patients diagnosed at different ages in infancy, patients diagnosed before the age of 1 year were divided into 0–1 month (5 patients), 1–3 months (9 patients), 4–6 months (22 patients), 7–9 months (27 patients), and 9–12 months (42 patients) groups. Univariate Cox regression analysis revealed that the HRs for EFS reduction were 1, 0.487 (P=0.611), 1.045 (P=0.968), 0.289 (P=0.312), and 1.257 (P=0.827) for the 0–1-, 1–3-, 4–6-, 7–9-, and 9–12-month groups, respectively, and the HRs for OS reduction were 1, 0.424 (P=0.546), 0.685 (P=0.736), 0.136 (P=0.160), and 0.526 (P=0.558), respectively, indicating no statistical significance, as shown in Table 4. EFS and OS in children diagnosed before the age of 1 year are shown in Fig. 2. Owing to the small number of cases in the 0–1- and 1–3-month groups, they were combined to reduce the impact of random error. The 5-year EFS rates for the 0–3-, 4–6-, 7–9-, and 9–12-month groups were 85.7±9.4%, 73.5±10.3%, 88.6±7.8%, and 72.5±7.1%, respectively (P=0.200), and the 5-year OS rates were 85.1±9.7%, 77.7±10.0%, 95.0±4.9%, and 87.9±5.1%, respectively (P=0.461). 3. Age distribution of each risk factor. Table 5 presents the age range and median age at first diagnosis of HB in this study, categorized by PRETEXT stage, PRETEXT stage annotation factors, and AFP levels at first diagnosis for each risk factor. Discussion Currently, it is believed that the older the age at first diagnosis of HB is, the worse the prognosis(12). However, the prognostic cut-off age for the first diagnosis of HB remains controversial. The SIOPEL2 and SIOPEL3 studies included 541 HB patients from 1995 to 2006 and reported a significant increase in the hazard ratio (HR) for EFS reduction when the age at first diagnosis was ≥5 years; therefore, in 2012, the new risk stratification of SIOPEL patients classified HB patients diagnosed over 5 years old into the intermediate-risk group(15). In 2017, CHIC risk stratification placed most HB patients who were ≥8 years old into the high-risk group(8). The CHIC study analysed 1605 cases of HB (from 1989 to 2010) on the basis of the age at initial diagnosis and revealed that as diagnostic age increased, the hazard ratio (HR) for EFS tended to increase, the HR for HB diagnosed at ≥8 years was greater than 3.7, and at ≥13 years, it reached 7.3. The study indicated that with age, factors such as distant metastasis, low alpha-fetoprotein (AFP) levels, and tumor rupture had diminishing impacts on prognosis(12). In 2022, the Chinese CCCG risk stratification, which integrates various study results, classified all HB patients diagnosed over 8 years of age into the high-risk group.(12, 15) The studies informing these risk stratifications did not include Chinese HB data. Our study revealed inconsistencies in the cut-off age at first diagnosis of HB compared with the SIOPEL and CHIC studies, possibly due to ethnic differences affecting prognosis. Our previous studies indicated that HBs diagnosed under 3 years of age had a better prognosis than those diagnosed at ≥3 years of age did, but the sample size was small, and the age grouping was not detailed enough(11). In this study, the age at initial diagnosis was divided more carefully, and the influence of the age at initial diagnosis on EFS and OS was analysed in detail. Additionally, we compared the prognosis of HB patients diagnosed at <6 years and ≥6 years, excluding confounding factors such as AFP, PRETEXT stage, and annotation factors. Our study revealed that the HRs for EFS and OS were significantly greater in HBs diagnosed at ≥6 years, with 5-year EFS and OS rates significantly lower than those in those diagnosed at <6 years. The prognosis of patients with HB diagnosed at 6–8 years and ≥8 years was poor. The 5-year EFS and OS rates for HB patients diagnosed at 6–8 years were 36.0% and 73.7%, respectively, which were slightly lower than those for those diagnosed at ≥8 years. Even after confounding factors such as AFP, the PRETEXT stage, and annotation factors were excluded, the prognosis for HB patients diagnosed at ≥6 years remained worse than that for those diagnosed at <6 years. Therefore, including an initial diagnosis age of ≥6 years in the high-risk group for HB stratification is justified. Our study may aid in optimizing HB risk stratification and adjusting the degree of chemotherapy used. The poor prognosis of older HB patients may be related to increased chemotherapy resistance, warranting further study and analysis. However, since this is a retrospective study, its findings require validation through large-scale prospective research. The SIOPEL1 study included 154 HB cases from 1990 to 1994, categorized into 4 years on the basis of age at diagnosis. The analysis revealed no significant differences in EFS or OS among these groups.(25) A retrospective study of 606 HB patients from the SEER database (1973–2009) reported 5-year OS rates of 64% for <1 year, 64% for 1–4 years, 44% for 5–9 years, 34% for 10–14 years, and 20% for 15–19 years (P < 0.001). HBs diagnosed at ≥5 years had a poor prognosis, but the study spanned 33 years, and changes in treatment and chemotherapy regimens may have influenced outcomes(16). These studies did not include data from Chinese hepatoblastoma patients, so it is uncertain whether the findings are applicable to Chinese children with this condition. A multicenter prospective study in China reported HRs of 1, 1.994, and 4.941 for HBs diagnosed at <3 years (311 cases), 3–8 years (77 cases), and ≥8 years (11 cases), respectively, with 4-year EFS rates of 82.0%, 66.7%, and 34.2%, respectively. This study did not provide a more detailed age classification at first diagnosis(2). A case report by Roland et al. suggested that congenital HB has a poor prognosis.(24) Additionally, multiple case reports indicate that HB patients diagnosed during the neonatal period have a poor prognosis.(18-23) Patrizia et al. included 79 cases of HB diagnosed at <6 months in the SIOPEL2 and SIOPEL3 studies, which were divided into 0–3 months (33 cases) and 3–6 months (46 cases). Statistical analysis revealed that the EFS and OS for HB patients diagnosed at 0–3 months were slightly greater than those for those diagnosed at 3–6 months.(26) Trobaugh et al.'s study included 27 patients who were diagnosed with HB during the neonatal period; these patients had a relatively good prognosis, with the OS rate reaching 86% at 3 years.(17) Our study indicated that age had no effect on the prognosis of HB in infancy. Our results contrast with those of Roland et al. but align with those of Patrizia and Trobaugh et al. In this study, the age distributions of various risk factors in HBs were slightly different. However, after these risk factors were excluded, statistical analysis revealed that the prognosis for HBs diagnosed at <6 years was still better than that for those diagnosed at ≥6 years, and the age at first diagnosis was an independent prognostic factor for HBs. Conclusion HB patients who are ≥6 years of age have a poor prognosis. The poorer prognosis for HBs diagnosed at ≥6 years should not be attributed to an imbalance in the age distribution of risk factors. Age at first diagnosis is an independent prognostic factor for HB. Age does not affect the prognosis of HB in infancy. Therefore, it may be appropriate to classify individuals diagnosed at age 6 or older into the stratified high-risk group for hepatoblastoma. This classification could help tailor the degree of chemotherapy to affected children. Abbreviations HB: Hepatoblastoma; HR: Hazard ratio; EFS: Event-free survival; OS: Overall survival; AFP: Alpha-fetoprotein; PRETEXT: Pretreatment extent of tumor; SIOPEL: Childhood Liver Tumors Strategy Group; CHIC: Children’s Hepatic Tumors International Collaboration; CCCG: Chinese Children Cancer Group; M: Distant metastasis; V: Invasion of the hepatic vein or inferior vena cava; P: Invasion of the portal vein; E: Invasion of adjacent extrahepatic organs; F: Multiple tumors; R: Tumor rupture; N: Lymph node invasion; SEER: Surveillance, Epidemiology, and End Results; PD: Disease progression. Declarations Conflicts of interest statement We declare no conflicts of interest. Funding This study did not receive any external funding. Acknowledgements All authors revised the paper critically for important intellectual content and gave final approval of the version to be published. Authors’ contributions All of the authors have read and approved the manuscript. ZL: Study conception and design, Data acquisition, Analysis and data interpretation, Drafting of the manuscript and critical revision. HJ: Data acquisition, analysis and data interpretation. YW: Data acquisition and drafting of the manuscript. W W: Data acquisition, analysis and data interpretation. LH: Study conception and design, critical revision. JL: Study conception and design, critical revision. HX: Study conception and design, critical revision. Ethics approval This study follows the Declaration of Helsinki. This single-center retrospective study was approved by the First Affiliated Hospital of Sun Yat-sen University (No. 2024[242]). This study was a retrospective study, and the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University applied for exemption of informed consent and was approved. Clinical trial number Not applicable. Availability of data and materials All the data generated or analysed during this study are included in this published the article and its supplementary information files. Competing interests All of the authors, including Zhen Li, Hong Jiang, Yuan-Qi Wang, Wen-Qing Wang, Li-Bin Huang, Jun-Cheng Liu and Hong-Man Xue, declare that they have no conflicts of interest. Authors' information ZL: Master of Sun Yat-sen University and resident of the Seventh Affiliated Hospital of Sun Yat-sen University. HJ: M.D., deputy chief physician of pediatric surgery, the First Affiliated Hospital of Sun Yat-sen University, standing member of the Youth Committee of Pediatric Tumor Committee of Guangdong Anti-Cancer Association, member of the Surgery Group of Pediatric Tumor Committee of Chinese Anti-Cancer Association and is a member of the pediatric surgery Committee of Guangdong Health Management Society. YW: M.D., resident doctor of the First Affiliated Hospital of Sun Yat-sen University. WW: M.D., resident doctor of the Seventh Affiliated Hospital of Sun Yat-sen University. LH: M.D., chief physician, doctoral supervisor, Deputy Director of the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University, Chairperson of the Children's Blood Oncology Branch of Guangzhou Medical Association, member of the Pediatrics Branch of Guangdong Medical Association and deputy leader of the Hematology and Oncology Group, Deputy Chairperson of the Pediatric Cancer Professional Committee and Chairperson of the Pediatric Blood Tumor Special Committee of Guangdong Clinical Medical Association, standing member of the Solid Tumor Special Committee, supervisor and standing member of the Treatment Special Committee of Guangdong Thalassemia Prevention and Control Association, Deputy chairperson of the Pediatric Blood Tumor Special Committee of Guangdong Provincial Medical Association, member of the Pediatric branch of Guangdong Provincial Medical Association, standing director of Guangdong Young Scientists Association, Vice Chairperson of the Youth Committee of the Pediatric Cancer Committee of the Chinese Anti-Cancer Association, member of the Youth Committee of the Pediatric Branch of the Chinese Medical Association, member of the second National Health Commission of Children's Hematology and malignant tumor Expert Committee. JL: M.D., chief physician, master's advisor, once served as the director of the pediatric surgery Department of the First Affiliated Hospital of Sun Yat-sen University, the deputy head of the Chinese Pediatric Surgery Hepatology Group, the deputy chairperson of the pediatric Surgery Group of Guangdong Medical Association, the general surgery group of the Pediatric Surgery Society of Guangdong Medical Association, and the deputy chairperson of the Guangdong Branch of the Anticancer Association Children's Professional Committee. HX: M.D., doctoral supervisor, chief physician and postdoctoral cosupervisor, director of the Department of Pediatrics of the Seventh Affiliated Hospital of Sun Yat-sen University, standing member of the first session of the Pediatric Blood Tumor Professional Committee of Guangdong Provincial Medical Association, member of the Cord Blood Application Professional Committee of Guangdong Maternal and Child Health Association, deputy leader of the Clinical Group of Cord Blood Cell Assisted Therapy, Member of the Standing Committee of Pediatric Blood Tumor Professional Committee of Guangdong Clinical Medicine Society, member of Rare Diseases Branch of Guangdong Medical Association, member of the Pediatrics special Committee of Shenzhen Medical Association, member of the blood immunooncology group of Shenzhen Pediatric Special Committee, and member of the Standing Committee of the fourth rare disease Professional Committee of Shenzhen Medical Association. REFERENCES Spector LG, Birch J. The epidemiology of hepatoblastoma. Pediatr Blood Cancer. 2012;59(5):776-9. Tang M-J, Ma X-L, He X-L, Pan W-H, Zhang X-H, Jiang S-Y, et al. A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children’s Cancer Group. World Journal of Pediatrics. 2023. Hiyama E, Hishiki T, Watanabe K, Ida K, Ueda Y, Kurihara S, et al. Outcome and Late Complications of Hepatoblastomas Treated Using the Japanese Study Group for Pediatric Liver Tumor 2 Protocol. J Clin Oncol. 2020;38(22):2488-98. Katzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, et al. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children's Oncology Group, multicentre, phase 3 trial. Lancet Oncol. 2019;20(5):719-27. Feng J, Polychronidis G, Heger U, Frongia G, Mehrabi A, Hoffmann K. Incidence trends and survival prediction of hepatoblastoma in children: a population-based study. Cancer Commun (Lond). 2019;39(1):62. Yuan XJ, Wang HM, Jiang H, Tang MJ, Li ZL, Zou X, et al. Multidisciplinary effort in treating children with hepatoblastoma in China. Cancer Lett. 2016;375(1):39-46. Hiyama E, Ueda Y, Onitake Y, Kurihara S, Watanabe K, Hishiki T, et al. A cisplatin plus pirarubicin-based JPLT2 chemotherapy for hepatoblastoma: experience and future of the Japanese Study Group for Pediatric Liver Tumor (JPLT). Pediatr Surg Int. 2013;29(10):1071-5. Meyers RL, Maibach R, Hiyama E, Häberle B, Krailo M, Rangaswami A, et al. Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration. The Lancet Oncology. 2017;18(1):122-31. Kim PH, Shin HJ, Yoon HM, Choi YH, Namgoong JM, Kim DY, et al. Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) System for Pediatric Patients with Hepatoblastoma: A Retrospective, Hospital-Based Cohort Study in South Korea. Cancer Res Treat. 2022;54(1):253-8. Ke M, Zhou Y, Chang-Zhen Y, Li L, Diao M. A nomogram model to predict prognosis of patients with hepatoblastoma. Pediatr Blood Cancer. 2022;69(12):e29932. Huang J, Hu Y, Jiang H, Xu Y, Lu S, Sun F, et al. CHIC Risk Stratification System for Predicting the Survival of Children With Hepatoblastoma: Data From Children With Hepatoblastoma in China. Frontiers in Oncology. 2020;10. Haeberle B, Rangaswami A, Krailo M, Czauderna P, Hiyama E, Maibach R, et al. The importance of age as prognostic factor for the outcome of patients with hepatoblastoma: Analysis from the Children's Hepatic tumors International Collaboration (CHIC) database. Pediatr Blood Cancer. 2020;67(8):e28350. Beyea JA, Lau C, Cooke B, Hall S, Nathan PC, Gupta S. Long-Term Incidence and Predictors of Significant Hearing Loss Requiring Hearing Assistive Devices Among Childhood Cancer Survivors: A Population-Based Study. J Clin Oncol. 2020;38(23):2639-46. Hishiki T, Matsunaga T, Sasaki F, Yano M, Ida K, Horie H, et al. Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT. Pediatr Surg Int. 2011;27(1):1-8. Maibach R, Roebuck D, Brugieres L, Capra M, Brock P, Dall'Igna P, et al. Prognostic stratification for children with hepatoblastoma: the SIOPEL experience. Eur J Cancer. 2012;48(10):1543-9. Allan BJ, Parikh PP, Diaz S, Perez EA, Neville HL, Sola JE. Predictors of survival and incidence of hepatoblastoma in the paediatric population. HPB (Oxford). 2013;15(10):741-6. Trobaugh-Lotrario AD, Chaiyachati BH, Meyers RL, Häberle B, Tomlinson GE, Katzenstein HM, et al. Outcomes for patients with congenital hepatoblastoma. Pediatr Blood Cancer. 2013;60(11):1817-25. Birsner ML, Hoover-Fong J, Bytyci Telegrafi A, Hueppchen NA. Perinatal detection of familial adenomatous polyposis. Obstet Gynecol. 2012;120(2 Pt 2):500-3. Al-Hussein HA, Graham EM, Tekes A, Huisman TA. Pre- and postnatal imaging of a congenital hepatoblastoma. Fetal Diagn Ther. 2011;30(2):157-9. Ergin H, Yildirim B, Dagdeviren E, Yagci B, Ozen F, Sen N, et al. A prenatally detected case of congenital hepatoblastoma. Pathol Oncol Res. 2008;14(1):97-100. Smith AC, Shuman C, Chitayat D, Steele L, Ray PN, Bourgeois J, et al. Severe presentation of Beckwith-Wiedemann syndrome associated with high levels of constitutional paternal uniparental disomy for chromosome 11p15. Am J Med Genet A. 2007;143a(24):3010-5. Lu M, Greer ML. Hypervascular multifocal hepatoblastoma: dynamic gadolinium-enhanced MRI findings indistinguishable from infantile hemangioendothelioma. Pediatr Radiol. 2007;37(6):587-91. Shih JC, Tsao PN, Huang SF, Yen BL, Lin JH, Lee CN, et al. Antenatal diagnosis of congenital hepatoblastoma in utero. Ultrasound Obstet Gynecol. 2000;16(1):94-7. Ammann RA, Plaschkes J, Leibundgut K. Congenital hepatoblastoma: a distinct entity? Med Pediatr Oncol. 1999;32(6):466-8. Brown J, Perilongo G, Shafford E, Keeling J, Pritchard J, Brock P, et al. Pretreatment prognostic factors for children with hepatoblastoma-- results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1. Eur J Cancer. 2000;36(11):1418-25. Dall'Igna P, Brugieres L, Christin AS, Maibach R, Casanova M, Alaggio R, et al. Hepatoblastoma in children aged less than six months at diagnosis: A report from the SIOPEL group. Pediatr Blood Cancer. 2018;65(1). Tables Table 1 Basic data of 403 HB patients Variables N Variables N Age at diagnosis, years, median (IQR) 1.3(3.4) I 27(6.7%) ＜3 289(71.7%) II 185(45.9%) 3-7 86(21.3%) III 146(36.2%) ≥8 28(6.9%) IV 43(10.7%) Gender NA 2(0.5%) Male 257(63.8%) Annotation factors Female 146(36.2%） VP+ 66(16.4%) AFP (ng/ml) E＋ 12(3.0%) ＜100 4(1.0%) F＋ 85(21.1%) 100-999 18(4.5%) R＋ 27(6.6%) ≥1000 381(94.5%） M＋ 76(18.7%) PRETEXT stage N+ 40(9.9%) HB hepatoblastoma, N number, IQR interquartile range, AFP alpha-fetoprotein, PRETEXT pretreatment extent of tumor, NA not available, VP+ inferior vena cava, hepatic vein or portal vein involvement, E+ extrahepatic tumor extension, F+ multifocal tumor, R+ tumor rupture, M+ metastasis, N+ lymph node metastasis Table 2 Overview of EFS and OS across various age groups Age(Y) N EFS：HR (95%CI) P value 5-year EFS (%) 0-＜1 105 Reference 77.7±4.6 1-＜2 108 0.862(0.451-1.645) 0.652 81.1±4.2 2-＜3 76 1.393(0.736-2.636) 0.308 71.8±5.8 3-＜4 30 2.008(0.913-4.414) 0.083 67.9±8.9 4-＜5 21 1.325(0.497-3.532) 0.573 73.9±10.1 5-＜6 17 1.859(0.697-4.955) 0.215 62.7±13.4 6-＜8 18 3.667(1.663-8.089) 0.001 36.0±14.3 ≥8 28 2.502(1.136-5.509) 0.023 40.6±15.5 Age(Y) N OS：HR (95%CI) P value 5-year OS (%) 0-＜1 105 1 Reference 86.3±3.8 1-＜2 108 0.410(0.144-1.163) 0.094 95.0±2.2 2-＜3 76 0.876(0.345-2.227) 0.781 88.4±4.2 3-＜4 30 1.713(0.602-4.872) 0.313 81.5±7.6 4-＜5 21 1.243(0.350-4.408) 0.737 82.4±9.2 5-＜6 17 0.575(0.075-4.422) 0.595 92.3±7.4 6-＜8 18 3.012(1.058-8.578) 0.039 73.7±11.3 ≥8 28 2.012(0.707-5.725) 0.190 76.1±11.5 HR hazard ratio, Y year, EFS event-free survival, CI confidence interval, OS overall survival Table 3 The impact of risk factors and the adjusted analysis of age-related effects on prognosis Risk factors EFS：HR (95%CI) P values of events occurring at <6 and ≥6 years AFP 0.006 a ≥1000 ng/ml Reference 100-999 ng/ml 0.630(0.199-1.993) ＜100 ng/ml 1.361(0.190-9.779) PRETEXT stage 0.016 b I Reference II 2.979(0.720-12.316) III 3.068(0.734-12.819) IV 5.983(1.375-26.029) VPEFRMN 0.030 c - Reference + 3.044(1.965-4.715) AFP+PRETEXT stage +VPEFRMN 0.049 d - Reference + 1.980(1.002-3.913) Table 3 (continued) Risk factors OS：HR (95%CI) P values of deaths occurring at <6 and ≥6 years AFP 0.013 a ≥1000 ng/ml Reference 100-999 ng/ml 0.467(0.064-3.395) ＜100 ng/ml 2.603(0.356-19.029) PRETEXT stage 0.039 b I Reference II 2.528(0.336-18.999) III 2.689(0.354-21.448) IV 6.672(0.845-52.692) VPEFRMN 0.045 c - Reference + 3.624(1.858-7.070) AFP, PRETEXT stage or VPEFRMN 0.092 d - Reference + 2.061(0.889-4.777) a P value after eliminating the influence of the AFP; b P value after eliminating the influence of the PRETEXT stage; VPEFRMN: V, P, E, F, R, M or N; c P value after eliminating the influence of VPEFRMN; d P value after eliminating the influence of the AFP, PRETEXT stage and VPEFRMN Table 4 Comparison of EFS and OS in various age groups younger than one year at initial diagnosis Age(M) N EFS：HR (95%CI) P value OS：HR (95%CI) P value 0-＜1 5 Reference Reference 1-＜3 9 0.487(0.030-7.807) 0.611 0.424(0.026-6.840) 0.546 3-＜6 22 1.045(0.122-8.985) 0.968 0.685(0.075-6.213) 0.736 6-＜9 27 0.289(0.026-3.202) 0.312 0.136(0.008-2.197) 0.160 9-＜12 42 1.257(0.162-9.750) 0.827 0.526(0.061-4.515) 0.558 M: month Table 5 Age distribution of risk factors for HB Risk factors N Median age(Y) Minimum age(Y) Max age(Y) AFP＜100 ng/ml 4 2.9 0.8 8.4 AFP 100-1000 ng/ml 18 3.4 0.2 10.7 AFP＞1000 ng/ml 381 1.8 0.0 13.6 PRETEXT I stage 27 2.7 0.0 9.8 PRETEXT II stage 185 1.8 0.0 13.3 PRETEXT III stage 146 1.5 0.0 13.6 PRETEXT IV stage 43 2.3 0.5 12.3 PRETEXT stage NA 2 6.8 2.9 10.7 VPEFRMN+ 188 2.3 0.0 13.6 VPEFRMN- 214 1.4 0.0 13.3 VPEFRMN NA 1 0.6 0.6 0.6 Y: year; NA: not available Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.xls Cite Share Download PDF Status: Published Journal Publication published 04 Mar, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 02 Dec, 2024 Reviews received at journal 29 Nov, 2024 Reviewers agreed at journal 22 Nov, 2024 Reviews received at journal 20 Nov, 2024 Reviewers agreed at journal 14 Nov, 2024 Reviewers invited by journal 12 Nov, 2024 Editor invited by journal 21 Oct, 2024 Editor assigned by journal 17 Oct, 2024 Submission checks completed at journal 17 Oct, 2024 First submitted to journal 10 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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13:53:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5240184/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5240184/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-05487-x","type":"published","date":"2025-03-04T15:58:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71559823,"identity":"a6006784-57fa-4af6-8599-4b07b00b7299","added_by":"auto","created_at":"2024-12-16 16:48:48","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":957362,"visible":true,"origin":"","legend":"\u003cp\u003eEFS and OS rates in HBsfirst diagnosed at ages \u0026lt;6 and ≥6 years\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5240184/v1/2ce943099bd88583301f9400.jpg"},{"id":71561078,"identity":"ce822a91-0deb-407e-9ae4-847fc74f776b","added_by":"auto","created_at":"2024-12-16 16:56:48","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":987099,"visible":true,"origin":"","legend":"\u003cp\u003eEFS and OS in children diagnosed before the age of 1 year\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5240184/v1/f9154a9e96e609cee779f99a.jpg"},{"id":78190536,"identity":"22ca9023-7f54-4e49-98a8-e2122c53635d","added_by":"auto","created_at":"2025-03-10 19:49:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2510019,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5240184/v1/34e8d922-b481-457a-9d32-39650c0dd826.pdf"},{"id":71559824,"identity":"0e3eaf37-28b4-4cc7-b191-1f6202dc0d70","added_by":"auto","created_at":"2024-12-16 16:48:48","extension":"xls","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":73216,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.xls","url":"https://assets-eu.researchsquare.com/files/rs-5240184/v1/38c66e88f5c5a1c7a3fd3095.xls"}],"financialInterests":"No competing interests reported.","formattedTitle":"The importance of age as a prognostic predictor of childhood hepatoblastoma: an analysis of single-center childhood hepatoblastoma in China","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHB is the most common liver tumor in childhood, with an incidence of approximately 0.5\u0026ndash;2 per million, and its overall incidence has been increasing in recent years(1). With the advent of platinum-based chemotherapy regimens, the implementation of risk-stratified chemotherapy, and advancements in surgical techniques and multidisciplinary care, the 5-year OS rate for children with HB can reach 80%-90%(2-7). It is believed that the PRETEXT stage, PRETEXT stage annotation factors, and AFP levels at initial diagnosis influence the prognosis of HB patients(2, 8).\u003c/p\u003e\n\u003cp\u003eNumerous studies have demonstrated that age at first diagnosis impacts the prognosis of HB patients(2, 3, 6-14). The latest stratifications by the Childhood Liver Tumors Strategy Group (SIOPEL), Children\u0026rsquo;s Hepatic Tumors International Collaboration (CHIC), and Chinese Children\u0026rsquo;s\u0026nbsp;Cancer Group (CCCG) all incorporate age at first diagnosis. SIOPEL\u0026apos;s latest risk stratification classifies HB patients diagnosed at \u0026gt;5 years\u0026nbsp;of age\u0026nbsp;into the medium-risk group(15). CHIC generally classifies patients aged \u0026ge;8 years in the high-risk group(8). The CCCG\u0026apos;s latest stratification places HB patients diagnosed at \u0026gt;8 years\u0026nbsp;of age\u0026nbsp;in the high-risk group. Different HB risk stratification systems vary in the specific age used for classification at first diagnosis. A retrospective study of 606 HB\u0026nbsp;patients\u0026nbsp;diagnosed from 1973\u0026ndash;2009 in the Surveillance, Epidemiology, and End Results (SEER) database indicated through univariate and multivariate analyses that\u0026nbsp;the\u0026nbsp;prognosis is better for those diagnosed at \u0026lt;5 years\u0026nbsp;than for those diagnosed at\u0026nbsp;\u0026gt;5 years(16). The Japanese JPLT2 study, involving 361 HB\u0026nbsp;patients\u0026nbsp;diagnosed from 1999 to 2012,\u0026nbsp;revealed\u0026nbsp;that\u0026nbsp;the\u0026nbsp;prognosis for the \u0026lt;1 year group was significantly better than\u0026nbsp;that\u0026nbsp;for the 1\u0026ndash;2 year and \u0026ge;3 year groups(3). Multiple case reports suggest that\u0026nbsp;HBs\u0026nbsp;diagnosed during the neonatal period\u0026nbsp;have\u0026nbsp;a poor prognosis(17-24). A previous retrospective study by our team,\u0026nbsp;which included\u0026nbsp;86 HB\u0026nbsp;patients\u0026nbsp;diagnosed from 2014\u0026ndash;2017,\u0026nbsp;revealed\u0026nbsp;that\u0026nbsp;the\u0026nbsp;prognosis is better for those diagnosed at \u0026lt;3 years\u0026nbsp;than for those diagnosed at\u0026nbsp;\u0026ge;3 years(11). Therefore, there is inconsistency among studies regarding the age\u0026nbsp;cut-off\u0026nbsp;used to predict prognosis.\u003c/p\u003e\n\u003cp\u003eOur study, which utilized a substantial dataset of Chinese hepatoblastoma cases, examined the impact of age on the prognosis of children affected by this condition. This study included 403 hepatoblastoma (HB) patients diagnosed at the First Affiliated Hospital of Sun Yat-sen University between February 2010 and September 2023. This study investigated how the age at initial diagnosis influences the prognosis of children, offering a foundation for optimizing HB risk stratification and guiding adjustments in the intensity of chemotherapy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e1. Data collection\u003c/p\u003e\n\u003cp\u003eA total of 403 cases of HB were collected at the Affiliated Hospital of Sun Yat-sen University via biopsy or surgery between February 2010 and September 2023, with diagnoses confirmed through histological examination in the hospital\u0026apos;s Department of Pathology. All patients were under 18 years old at first diagnosis and had comprehensive data related to their initial diagnosis and surgery. This allows for accurate stratification of CCCGs and CHIC risk.\u003c/p\u003e\n\u003cp\u003eBasic information, imaging results, and prognostic data were collected. These included age at first diagnosis, distant metastasis (M, discontinuous tumor spread), invasion of the hepatic vein or inferior vena cava (V, invasion of the main hepatic vein, all three branches of the hepatic vein, or inferior vena cava), invasion of the portal vein (P, invasion of the main portal vein or both branches of the portal vein), invasion of adjacent extrahepatic organs (E), multiple tumors (F, two or more tumor nodules separated by normal hepatic parenchyma), tumor rupture (R, tumor rupture at initial diagnosis), and lymph node invasion (N), PRETEXT staging. In this study, 98% (395/403) of HB patients were treated with a platinum-based chemotherapy regimen and/or surgery, all performed by the pediatric surgery team at the First Affiliated Hospital of Sun Yat-sen University, and the patient data were consistent.\u003c/p\u003e\n\u003cp\u003e2. Statistical methods\u003c/p\u003e\n\u003cp\u003eEFS was defined as the time from the initial diagnosis to disease progression, recurrence, or death. Disease progression (PD) was defined as tumor enlargement of \u0026ge;25%, the appearance of new tumors, or increased AFP levels. Recurrence is indicated by biopsy confirmation or clear imaging evidence, along with three consecutive increases in blood AFP levels within four weeks(2). OS was defined as the time from the initial diagnosis to death from any cause(2). The prognosis of HB during follow-up, including the timing of disease progression, recurrence, and death, was recorded retrospectively. The median follow-up duration was 38 months (range: 0.03\u0026ndash;159\u0026nbsp;months), with a follow-up loss rate of 5.7% (23/403).\u003c/p\u003e\n\u003cp\u003eStatistical analysis was conducted\u0026nbsp;via SPSS 26.0, with continuous variables represented by the median. Categorical variables are expressed as frequencies (percentages). The Kaplan‒Meier method was used for survival analysis, 5-year EFS and OS rates were calculated, and the log-rank test was used for comparison. The Cox regression model was utilized for univariate analysis, with P\u0026lt;0.05 considered statistically significant. The age distribution for each risk factor, including the median, maximum, and minimum, was analysed. Binary logistic regression analysis was employed to control for confounding factors such as the AFP level at initial diagnosis, PRETEXT stage, and PRETEXT annotation factors (V, P, E, F, R, M, N), and to compare the prognosis between patients diagnosed before 6 years of age and those diagnosed at 6 years or older.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e1. Patients\u003c/p\u003e\n\u003cp\u003eThe basic data for the 403 HB patients included in this study are presented in Table 1. A total of 84.4% (340/403) of the HB patients were younger than 5 years at initial diagnosis, with a median age of 22 months (range: 0\u0026ndash;163\u0026nbsp;months). Additionally, 6.9% of\u0026nbsp;the\u0026nbsp;HB patients were 8 years or older at diagnosis.\u003c/p\u003e\n\u003cp\u003e2. Influence of age at initial diagnosis on prognosis.\u003c/p\u003e\n\u003cp\u003eIn this study, only 7 patients with HB were diagnosed at ages 7\u0026ndash;8 years. To minimize the impact of random error, these cases were combined with those diagnosed at ages 6\u0026ndash;7 years into one group. There were 8 patients diagnosed at ages 8\u0026ndash;9 years, 6 patients at 9\u0026ndash;10 years, 4 patients at 10\u0026ndash;11 years, 5 patients at 11\u0026ndash;12 years, 1 patient at 12\u0026ndash;13 years, and 4 patients at 13\u0026ndash;14 years. To reduce the impact of random errors, these errors were combined into one group for statistical analysis. Univariate Cox regression analysis revealed that the HRs for EFS reduction in HBs for children aged 0\u0026ndash;1, 1\u0026ndash;2, 2\u0026ndash;3, 3\u0026ndash;4, 4\u0026ndash;5, 5\u0026ndash;6, 6\u0026ndash;8, and \u0026ge;8 years at diagnosis were 1, 0.862 (P=0.652), 1.393 (P=0.308), 2.008 (P=0.083), 1.325 (P=0.573), 1.859 (P=0.215), 3.667 (P=0.001), and 2.502 (P=0.023), respectively, and the 5-year EFS rates were 77.7%, 81.1%, 71.8%, 67.9%, 73.9%, 62.7%, 36.0%, and 40.6%, respectively. The HR for EFS reduction in the 6\u0026ndash;8-year and \u0026ge;8-year groups was significantly different from that in the 0\u0026ndash;1-year group, as shown in Table 2. At initial diagnosis ages of 0\u0026ndash;1, 1\u0026ndash;2, 2\u0026ndash;3, 3\u0026ndash;4, 4\u0026ndash;5, 5\u0026ndash;6, 6\u0026ndash;8, and \u0026ge;8 years, the HRs for decreased OS were 1, 0.410 (P=0.094), 0.876 (P=0.781), 1.713 (P=0.313), 1.243 (P=0.737), 0.575 (P=0.595), 3.012 (P=0.039), and 2.012 (P=0.190), respectively, and the 5-year OS rates were 86.3%, 95.0%, 88.4%, 81.5%, 82.4%, 92.3%, 73.7%, and 76.1%, respectively. The HR for decreased OS in the 6\u0026ndash;8-year group was significantly different from that in the 0\u0026ndash;1-year group, as shown in Table 2. HB patients diagnosed at \u0026lt;6 years of age were combined into one group, and those diagnosed at \u0026ge;6 years of age were combined into another group. The HB survival analysis curves for first diagnosis at ages \u0026lt;6 years and \u0026ge;6 years are shown in Fig. 1. The 5-year EFS rates in the \u0026lt;6 years group and the \u0026ge;6 years group were 75.8\u0026plusmn;2.5% and 38.6\u0026plusmn;10.8% (P \u0026lt; 0.001), respectively,\u0026nbsp;whereas\u0026nbsp;the 5-year OS rates were 88.9\u0026plusmn;1.9% and 74.7\u0026plusmn;8.3% (P=0.002), respectively. The influence of\u0026nbsp;the\u0026nbsp;AFP level, PRETEXT stage, and PRETEXT stage annotation factors (V, P, E, F, R, M, N) on prognosis was analysed\u0026nbsp;via Cox\u0026nbsp;regression. Binary logistic regression was employed to control for confounding factors such as\u0026nbsp;the\u0026nbsp;AFP level at initial diagnosis, PRETEXT stage, and PRETEXT annotation factors and to further compare the\u0026nbsp;prognoses\u0026nbsp;between the \u0026lt;6 years and \u0026ge;6 years groups. The results are presented in Table 3.\u003c/p\u003e\n\u003cp\u003eTo further study the prognosis of HB patients diagnosed at different ages in infancy, patients diagnosed before the age of 1 year were divided into 0\u0026ndash;1 month (5 patients), 1\u0026ndash;3 months (9 patients), 4\u0026ndash;6 months (22 patients), 7\u0026ndash;9 months (27 patients), and 9\u0026ndash;12 months (42 patients) groups. Univariate Cox regression analysis revealed that the HRs for EFS reduction were 1, 0.487 (P=0.611), 1.045 (P=0.968), 0.289 (P=0.312), and 1.257 (P=0.827) for the 0\u0026ndash;1-, 1\u0026ndash;3-, 4\u0026ndash;6-, 7\u0026ndash;9-, and 9\u0026ndash;12-month groups, respectively, and the HRs for OS reduction were 1, 0.424 (P=0.546), 0.685 (P=0.736), 0.136 (P=0.160), and 0.526 (P=0.558), respectively, indicating no statistical significance, as shown in Table 4. EFS and OS in children diagnosed before the age of 1 year are shown in Fig. 2. Owing to the small number of cases in the 0\u0026ndash;1- and 1\u0026ndash;3-month groups, they were combined to reduce the impact of random error. The 5-year EFS rates for the 0\u0026ndash;3-, 4\u0026ndash;6-, 7\u0026ndash;9-, and 9\u0026ndash;12-month groups were 85.7\u0026plusmn;9.4%, 73.5\u0026plusmn;10.3%, 88.6\u0026plusmn;7.8%, and 72.5\u0026plusmn;7.1%, respectively (P=0.200), and the 5-year OS rates were 85.1\u0026plusmn;9.7%, 77.7\u0026plusmn;10.0%, 95.0\u0026plusmn;4.9%, and 87.9\u0026plusmn;5.1%, respectively (P=0.461).\u003c/p\u003e\n\u003cp\u003e3. Age distribution of each risk factor.\u003c/p\u003e\n\u003cp\u003eTable 5 presents the age range and median age at first diagnosis of HB in this study, categorized by PRETEXT stage, PRETEXT stage annotation factors, and AFP levels at first diagnosis for each risk factor.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCurrently, it is believed that the older the age at first diagnosis of HB is, the worse the prognosis(12). However, the prognostic cut-off age for the first diagnosis of HB remains controversial. The SIOPEL2 and SIOPEL3 studies included 541 HB patients from 1995 to 2006 and reported a significant increase in the hazard ratio (HR) for EFS reduction when the age at first diagnosis was \u0026ge;5 years; therefore, in 2012, the new risk stratification of SIOPEL patients classified HB patients diagnosed over 5 years old into the intermediate-risk group(15). In 2017, CHIC risk stratification placed most HB patients who were \u0026ge;8 years old into the high-risk group(8). The CHIC study analysed 1605 cases of HB (from 1989 to 2010) on the basis of the age at initial diagnosis and revealed that as diagnostic age increased, the hazard ratio (HR) for EFS tended to increase, the HR for HB diagnosed at \u0026ge;8 years was greater than 3.7, and at \u0026ge;13 years, it reached 7.3. The study indicated that with age, factors such as distant metastasis, low alpha-fetoprotein (AFP) levels, and tumor rupture had diminishing impacts on prognosis(12). In 2022, the Chinese CCCG risk stratification, which integrates various study results, classified all HB patients diagnosed over 8 years of age into the high-risk group.(12, 15) The studies informing these risk stratifications did not include Chinese HB data. Our study revealed inconsistencies in the cut-off age at first diagnosis of HB compared with the SIOPEL and CHIC studies, possibly due to ethnic differences affecting prognosis. Our previous studies indicated that HBs diagnosed under 3 years of age had a better prognosis than those diagnosed at \u0026ge;3 years of age did, but the sample size was small, and the age grouping was not detailed enough(11). In this study, the age at initial diagnosis was divided more carefully, and the influence of the age at initial diagnosis on EFS and OS was analysed in detail. Additionally, we compared the prognosis of HB patients diagnosed at \u0026lt;6 years and \u0026ge;6 years, excluding confounding factors such as AFP, PRETEXT stage, and annotation factors. Our study revealed that the HRs for EFS and OS were significantly greater in HBs diagnosed at \u0026ge;6 years, with 5-year EFS and OS rates significantly lower than those in those diagnosed at \u0026lt;6 years. The prognosis of patients with HB diagnosed at 6\u0026ndash;8 years and \u0026ge;8 years was poor. The 5-year EFS and OS rates for HB patients diagnosed at 6\u0026ndash;8 years were 36.0% and 73.7%, respectively,\u0026nbsp;which were\u0026nbsp;slightly lower than those\u0026nbsp;for those\u0026nbsp;diagnosed at \u0026ge;8 years. Even after confounding factors\u0026nbsp;such as\u0026nbsp;AFP,\u0026nbsp;the\u0026nbsp;PRETEXT stage, and annotation factors\u0026nbsp;were excluded, the prognosis for HB patients diagnosed at \u0026ge;6 years remained worse than\u0026nbsp;that\u0026nbsp;for those diagnosed at \u0026lt;6 years. Therefore, including an initial diagnosis age of \u0026ge;6 years in the high-risk group for HB stratification is justified. Our study may aid in optimizing HB risk stratification and adjusting\u0026nbsp;the degree of\u0026nbsp;chemotherapy\u0026nbsp;used. The poor prognosis\u0026nbsp;of\u0026nbsp;older HB patients may\u0026nbsp;be related to increased\u0026nbsp;chemotherapy resistance, warranting further study and analysis. However, since this is a retrospective study, its findings require validation through large-scale prospective research.\u003c/p\u003e\n\u003cp\u003eThe SIOPEL1 study included 154 HB cases from 1990 to 1994, categorized into \u0026lt;0.5 years, 0.5\u0026ndash;4 years, and \u0026gt;4 years on\u0026nbsp;the basis of\u0026nbsp;age at diagnosis. The analysis\u0026nbsp;revealed no significant differences in EFS or\u0026nbsp;OS among these groups.(25)\u0026nbsp;A retrospective study of 606 HB\u0026nbsp;patients\u0026nbsp;from the SEER database (1973\u0026ndash;2009)\u0026nbsp;reported\u0026nbsp;5-year OS rates of 64% for \u0026lt;1 year, 64% for 1\u0026ndash;4 years, 44% for 5\u0026ndash;9 years, 34% for 10\u0026ndash;14 years, and 20% for 15\u0026ndash;19 years (P \u0026lt; 0.001).\u0026nbsp;HBs\u0026nbsp;diagnosed at \u0026ge;5 years had a poor prognosis, but the study spanned 33 years, and changes in treatment and chemotherapy regimens may have influenced outcomes(16). These studies did not include data from Chinese hepatoblastoma patients, so it is uncertain whether the findings are applicable to Chinese children with\u0026nbsp;this\u0026nbsp;condition. A multicenter prospective study in China\u0026nbsp;reported HRs\u0026nbsp;of 1, 1.994, and 4.941 for\u0026nbsp;HBs\u0026nbsp;diagnosed at \u0026lt;3 years (311 cases),\u0026nbsp;3\u0026ndash;8\u0026nbsp;years (77 cases), and \u0026ge;8 years (11 cases), respectively, with 4-year EFS rates of 82.0%, 66.7%, and 34.2%, respectively. This study did not provide a more detailed age classification at first diagnosis(2).\u003c/p\u003e\n\u003cp\u003eA case report by Roland et al. suggested that congenital HB has a poor prognosis.(24) Additionally, multiple case reports indicate that HB patients diagnosed during the neonatal period have a poor prognosis.(18-23) Patrizia et al. included 79 cases of HB diagnosed at \u0026lt;6 months in the SIOPEL2 and SIOPEL3 studies, which were divided into 0\u0026ndash;3 months (33 cases) and 3\u0026ndash;6 months (46 cases). Statistical analysis revealed that the EFS and OS for HB patients diagnosed at 0\u0026ndash;3 months were slightly greater than those for those diagnosed at 3\u0026ndash;6 months.(26) Trobaugh et al.\u0026apos;s study included 27 patients who were diagnosed with HB during the neonatal period; these patients had a relatively good prognosis, with the OS rate reaching 86% at 3 years.(17) Our study indicated that age had no effect on the prognosis of HB in infancy. Our results contrast with those of Roland et al. but align with those of Patrizia and Trobaugh et al. In this study, the age distributions of various risk factors in HBs were slightly different. However, after these risk factors were excluded, statistical analysis revealed that the prognosis for HBs diagnosed at \u0026lt;6 years was still better than that for those diagnosed at \u0026ge;6 years, and the age at first diagnosis was an independent prognostic factor for HBs.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eHB patients who are \u0026ge;6 years of age have a poor prognosis. The poorer prognosis for HBs diagnosed at \u0026ge;6 years should not be attributed to an imbalance in the age distribution of risk factors. Age at first diagnosis is an independent prognostic factor for HB. Age does not affect the prognosis of HB in infancy. Therefore, it may be appropriate to classify individuals diagnosed at age 6 or older into the stratified high-risk group for hepatoblastoma. This classification could help tailor the degree of chemotherapy to affected children.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHB: Hepatoblastoma; HR: Hazard ratio; EFS: Event-free survival; OS: Overall survival; AFP: Alpha-fetoprotein; PRETEXT: Pretreatment extent of tumor; SIOPEL: Childhood Liver Tumors Strategy Group; CHIC: Children\u0026rsquo;s Hepatic Tumors International Collaboration; CCCG: Chinese Children Cancer Group; M: Distant metastasis; V: Invasion of the hepatic vein or inferior vena cava; P: Invasion of the portal vein; E: Invasion of adjacent extrahepatic organs; F: Multiple tumors; R: Tumor rupture; N: Lymph node invasion; SEER: Surveillance, Epidemiology, and End Results; PD: Disease progression.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflicts of interest statement\u003c/p\u003e\n\u003cp\u003eWe declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study did not receive any external funding.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eAll authors revised the paper critically for important intellectual content and\u003c/p\u003e\n\u003cp\u003egave final approval of the version to be published.\u003c/p\u003e\n\u003cp\u003eAuthors’\u0026nbsp;contributions\u003c/p\u003e\n\u003cp\u003eAll of the authors have read and approved the manuscript. ZL: Study\u003c/p\u003e\n\u003cp\u003econception and design, Data acquisition, Analysis and data interpretation,\u003c/p\u003e\n\u003cp\u003eDrafting of the manuscript and critical revision. HJ: Data acquisition, analysis and data interpretation. YW: Data acquisition and drafting of the manuscript. W W:\u0026nbsp;Data acquisition,\u0026nbsp;analysis\u0026nbsp;and data interpretation.\u0026nbsp;LH: Study conception and design,\u0026nbsp;critical\u0026nbsp;revision. JL: Study conception and design,\u0026nbsp;critical\u0026nbsp;revision. HX: Study conception and design,\u0026nbsp;critical\u0026nbsp;revision.\u003c/p\u003e\n\u003cp\u003eEthics approval\u003c/p\u003e\n\u003cp\u003eThis study follows the Declaration of Helsinki. This single-center retrospective study was approved by the First Affiliated Hospital of Sun Yat-sen University\u0026nbsp;(No. 2024[242]). This study was a retrospective study, and the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University applied for exemption of informed consent and was approved.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical trial number\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eAll\u0026nbsp;the data generated or analysed during this study are included in this\u003c/p\u003e\n\u003cp\u003epublished the article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eAll of the authors, including Zhen Li, Hong Jiang, Yuan-Qi Wang, Wen-Qing Wang, Li-Bin Huang, Jun-Cheng Liu and Hong-Man Xue, declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eAuthors' information\u003c/p\u003e\n\u003cp\u003eZL:\u0026nbsp;Master of Sun Yat-sen University and resident of the Seventh\u0026nbsp;Affiliated Hospital of Sun Yat-sen University.\u003c/p\u003e\n\u003cp\u003eHJ: M.D., deputy chief physician of pediatric surgery, the First Affiliated Hospital of Sun Yat-sen University, standing member of the Youth Committee of Pediatric Tumor Committee of Guangdong Anti-Cancer Association, member of the Surgery Group of Pediatric Tumor Committee of Chinese Anti-Cancer Association and is a member of the pediatric surgery Committee of Guangdong Health Management Society.\u003c/p\u003e\n\u003cp\u003eYW:\u0026nbsp;M.D., resident doctor of the First Affiliated Hospital of Sun Yat-sen University.\u003c/p\u003e\n\u003cp\u003eWW:\u0026nbsp;M.D.,\u0026nbsp;resident doctor of the Seventh Affiliated Hospital of Sun Yat-sen University.\u003c/p\u003e\n\u003cp\u003eLH: M.D., chief physician, doctoral supervisor, Deputy Director of the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University, Chairperson of the Children's Blood Oncology Branch of Guangzhou Medical Association, member of the Pediatrics Branch of Guangdong Medical Association and deputy leader of the Hematology and Oncology Group, Deputy Chairperson of the Pediatric Cancer Professional Committee and Chairperson of the Pediatric Blood Tumor Special Committee of Guangdong Clinical Medical Association, standing member of the Solid Tumor Special Committee, supervisor and standing member of the Treatment Special Committee of Guangdong Thalassemia Prevention and Control Association, Deputy chairperson of the Pediatric Blood Tumor Special Committee of Guangdong Provincial Medical Association, member of the Pediatric branch of Guangdong Provincial Medical Association, standing director of Guangdong Young Scientists Association, Vice Chairperson of the Youth Committee of the Pediatric Cancer Committee of the Chinese Anti-Cancer Association, member of the Youth Committee of the Pediatric Branch of the Chinese Medical Association, member of the second National Health Commission of Children's Hematology and malignant tumor Expert Committee.\u003c/p\u003e\n\u003cp\u003eJL:\u0026nbsp;M.D., chief physician, master's advisor, once served as the director of the pediatric surgery Department of the First Affiliated Hospital of Sun Yat-sen University, the deputy head of the Chinese Pediatric Surgery Hepatology Group, the deputy chairperson of the pediatric Surgery Group of Guangdong Medical Association, the general surgery group of the Pediatric Surgery Society of Guangdong Medical Association, and the deputy chairperson of the Guangdong Branch of the Anticancer Association Children's Professional Committee.\u003c/p\u003e\n\u003cp\u003eHX: M.D., doctoral supervisor, chief physician and postdoctoral cosupervisor, director of the Department of Pediatrics of the Seventh Affiliated Hospital of Sun Yat-sen University, standing member of the first session of the Pediatric Blood Tumor Professional Committee of Guangdong Provincial Medical Association, member of the Cord Blood Application Professional Committee of Guangdong Maternal and Child Health Association, deputy leader of the Clinical Group of Cord Blood Cell Assisted Therapy, Member of the Standing Committee of Pediatric Blood Tumor Professional Committee of Guangdong Clinical Medicine Society, member of Rare Diseases Branch of Guangdong Medical Association, member of the Pediatrics special Committee of Shenzhen Medical Association, member of the blood immunooncology group of Shenzhen Pediatric Special Committee, and member of the Standing Committee of the fourth rare disease Professional Committee of Shenzhen Medical Association.\u003c/p\u003e"},{"header":"REFERENCES","content":"\u003col\u003e\n\u003cli\u003eSpector LG, Birch J. The epidemiology of hepatoblastoma. Pediatr Blood Cancer. 2012;59(5):776-9.\u003c/li\u003e\n\u003cli\u003eTang M-J, Ma X-L, He X-L, Pan W-H, Zhang X-H, Jiang S-Y, et al. A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children\u0026rsquo;s Cancer Group. World Journal of Pediatrics. 2023.\u003c/li\u003e\n\u003cli\u003eHiyama E, Hishiki T, Watanabe K, Ida K, Ueda Y, Kurihara S, et al. Outcome and Late Complications of Hepatoblastomas Treated Using the Japanese Study Group for Pediatric Liver Tumor 2 Protocol. J Clin Oncol. 2020;38(22):2488-98.\u003c/li\u003e\n\u003cli\u003eKatzenstein HM, Langham MR, Malogolowkin MH, Krailo MD, Towbin AJ, McCarville MB, et al. Minimal adjuvant chemotherapy for children with hepatoblastoma resected at diagnosis (AHEP0731): a Children\u0026apos;s Oncology Group, multicentre, phase 3 trial. Lancet Oncol. 2019;20(5):719-27.\u003c/li\u003e\n\u003cli\u003eFeng J, Polychronidis G, Heger U, Frongia G, Mehrabi A, Hoffmann K. Incidence trends and survival prediction of hepatoblastoma in children: a population-based study. Cancer Commun (Lond). 2019;39(1):62.\u003c/li\u003e\n\u003cli\u003eYuan XJ, Wang HM, Jiang H, Tang MJ, Li ZL, Zou X, et al. Multidisciplinary effort in treating children with hepatoblastoma in China. Cancer Lett. 2016;375(1):39-46.\u003c/li\u003e\n\u003cli\u003eHiyama E, Ueda Y, Onitake Y, Kurihara S, Watanabe K, Hishiki T, et al. A cisplatin plus pirarubicin-based JPLT2 chemotherapy for hepatoblastoma: experience and future of the Japanese Study Group for Pediatric Liver Tumor (JPLT). Pediatr Surg Int. 2013;29(10):1071-5.\u003c/li\u003e\n\u003cli\u003eMeyers RL, Maibach R, Hiyama E, H\u0026auml;berle B, Krailo M, Rangaswami A, et al. Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children\u0026apos;s Hepatic tumors International Collaboration. The Lancet Oncology. 2017;18(1):122-31.\u003c/li\u003e\n\u003cli\u003eKim PH, Shin HJ, Yoon HM, Choi YH, Namgoong JM, Kim DY, et al. Children\u0026apos;s Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) System for Pediatric Patients with Hepatoblastoma: A Retrospective, Hospital-Based Cohort Study in South Korea. Cancer Res Treat. 2022;54(1):253-8.\u003c/li\u003e\n\u003cli\u003eKe M, Zhou Y, Chang-Zhen Y, Li L, Diao M. A nomogram model to predict prognosis of patients with hepatoblastoma. Pediatr Blood Cancer. 2022;69(12):e29932.\u003c/li\u003e\n\u003cli\u003eHuang J, Hu Y, Jiang H, Xu Y, Lu S, Sun F, et al. CHIC Risk Stratification System for Predicting the Survival of Children With Hepatoblastoma: Data From Children With Hepatoblastoma in China. Frontiers in Oncology. 2020;10.\u003c/li\u003e\n\u003cli\u003eHaeberle B, Rangaswami A, Krailo M, Czauderna P, Hiyama E, Maibach R, et al. The importance of age as prognostic factor for the outcome of patients with hepatoblastoma: Analysis from the Children\u0026apos;s Hepatic tumors International Collaboration (CHIC) database. Pediatr Blood Cancer. 2020;67(8):e28350.\u003c/li\u003e\n\u003cli\u003eBeyea JA, Lau C, Cooke B, Hall S, Nathan PC, Gupta S. Long-Term Incidence and Predictors of Significant Hearing Loss Requiring Hearing Assistive Devices Among Childhood Cancer Survivors: A Population-Based Study. J Clin Oncol. 2020;38(23):2639-46.\u003c/li\u003e\n\u003cli\u003eHishiki T, Matsunaga T, Sasaki F, Yano M, Ida K, Horie H, et al. Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT. Pediatr Surg Int. 2011;27(1):1-8.\u003c/li\u003e\n\u003cli\u003eMaibach R, Roebuck D, Brugieres L, Capra M, Brock P, Dall\u0026apos;Igna P, et al. Prognostic stratification for children with hepatoblastoma: the SIOPEL experience. Eur J Cancer. 2012;48(10):1543-9.\u003c/li\u003e\n\u003cli\u003eAllan BJ, Parikh PP, Diaz S, Perez EA, Neville HL, Sola JE. Predictors of survival and incidence of hepatoblastoma in the paediatric population. HPB (Oxford). 2013;15(10):741-6.\u003c/li\u003e\n\u003cli\u003eTrobaugh-Lotrario AD, Chaiyachati BH, Meyers RL, H\u0026auml;berle B, Tomlinson GE, Katzenstein HM, et al. Outcomes for patients with congenital hepatoblastoma. Pediatr Blood Cancer. 2013;60(11):1817-25.\u003c/li\u003e\n\u003cli\u003eBirsner ML, Hoover-Fong J, Bytyci Telegrafi A, Hueppchen NA. Perinatal detection of familial adenomatous polyposis. Obstet Gynecol. 2012;120(2 Pt 2):500-3.\u003c/li\u003e\n\u003cli\u003eAl-Hussein HA, Graham EM, Tekes A, Huisman TA. Pre- and postnatal imaging of a congenital hepatoblastoma. Fetal Diagn Ther. 2011;30(2):157-9.\u003c/li\u003e\n\u003cli\u003eErgin H, Yildirim B, Dagdeviren E, Yagci B, Ozen F, Sen N, et al. A prenatally detected case of congenital hepatoblastoma. Pathol Oncol Res. 2008;14(1):97-100.\u003c/li\u003e\n\u003cli\u003eSmith AC, Shuman C, Chitayat D, Steele L, Ray PN, Bourgeois J, et al. Severe presentation of Beckwith-Wiedemann syndrome associated with high levels of constitutional paternal uniparental disomy for chromosome 11p15. Am J Med Genet A. 2007;143a(24):3010-5.\u003c/li\u003e\n\u003cli\u003eLu M, Greer ML. Hypervascular multifocal hepatoblastoma: dynamic gadolinium-enhanced MRI findings indistinguishable from infantile hemangioendothelioma. Pediatr Radiol. 2007;37(6):587-91.\u003c/li\u003e\n\u003cli\u003eShih JC, Tsao PN, Huang SF, Yen BL, Lin JH, Lee CN, et al. Antenatal diagnosis of congenital hepatoblastoma in utero. Ultrasound Obstet Gynecol. 2000;16(1):94-7.\u003c/li\u003e\n\u003cli\u003eAmmann RA, Plaschkes J, Leibundgut K. Congenital hepatoblastoma: a distinct entity? Med Pediatr Oncol. 1999;32(6):466-8.\u003c/li\u003e\n\u003cli\u003eBrown J, Perilongo G, Shafford E, Keeling J, Pritchard J, Brock P, et al. Pretreatment prognostic factors for children with hepatoblastoma-- results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1. Eur J Cancer. 2000;36(11):1418-25.\u003c/li\u003e\n\u003cli\u003eDall\u0026apos;Igna P, Brugieres L, Christin AS, Maibach R, Casanova M, Alaggio R, et al. Hepatoblastoma in children aged less than six months at diagnosis: A report from the SIOPEL group. Pediatr Blood Cancer. 2018;65(1).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Basic data of 403 HB patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"595\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003eAge at diagnosis, years,\u0026nbsp;median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e1.3(3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e27(6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003e＜3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e289(71.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e185(45.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003e3-7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e86(21.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e146(36.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003e\u0026ge;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e28(6.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e43(10.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e2(0.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e257(63.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eAnnotation factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e146(36.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eVP+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e66(16.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003eAFP (ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eE＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e12(3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003e＜100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e4(1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eF＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e85(21.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003e100-999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e18(4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eR＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e27(6.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003e\u0026ge;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e381(94.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eM＋\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e76(18.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.2521%;\"\u003e\n \u003cp\u003ePRETEXT stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.9916%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33.2773%;\"\u003e\n \u003cp\u003eN+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.479%;\"\u003e\n \u003cp\u003e40(9.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eHB hepatoblastoma, N number, IQR interquartile range, AFP alpha-fetoprotein, PRETEXT pretreatment extent of tumor, NA not available, VP+ inferior vena cava, hepatic vein or portal vein involvement, E+ extrahepatic tumor extension, F+ multifocal tumor, R+ tumor rupture, M+ metastasis, N+ lymph\u0026nbsp;node\u0026nbsp;metastasis\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 Overview of EFS and OS across various age groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003eAge(Y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003eEFS：HR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e5-year EFS (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e0-＜1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e77.7\u0026plusmn;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e1-＜2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e0.862(0.451-1.645)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.652\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e81.1\u0026plusmn;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e2-＜3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e1.393(0.736-2.636)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e71.8\u0026plusmn;5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e3-＜4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e2.008(0.913-4.414)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e67.9\u0026plusmn;8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e4-＜5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e1.325(0.497-3.532)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.573\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e73.9\u0026plusmn;10.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e5-＜6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e1.859(0.697-4.955)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e62.7\u0026plusmn;13.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e6-＜8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e3.667(1.663-8.089)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e36.0\u0026plusmn;14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e\u0026ge;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e2.502(1.136-5.509)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e40.6\u0026plusmn;15.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003eAge(Y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003eOS：HR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e5-year OS (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e0-＜1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e86.3\u0026plusmn;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e1-＜2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e0.410(0.144-1.163)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e95.0\u0026plusmn;2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e2-＜3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e0.876(0.345-2.227)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.781\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e88.4\u0026plusmn;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e3-＜4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e1.713(0.602-4.872)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e81.5\u0026plusmn;7.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e4-＜5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e1.243(0.350-4.408)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.737\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e82.4\u0026plusmn;9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e5-＜6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e0.575(0.075-4.422)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.595\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e92.3\u0026plusmn;7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e6-＜8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e3.012(1.058-8.578)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e73.7\u0026plusmn;11.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 12.6923%;\"\u003e\n \u003cp\u003e\u0026ge;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.03846%;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.9615%;\"\u003e\n \u003cp\u003e2.012(0.707-5.725)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.2692%;\"\u003e\n \u003cp\u003e0.190\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.0385%;\"\u003e\n \u003cp\u003e76.1\u0026plusmn;11.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eHR hazard ratio, Y year, EFS event-free survival, CI confidence interval, OS overall survival\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 The impact of risk factors and the adjusted analysis of age-related effects on prognosis\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"539\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eRisk factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eEFS：HR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003eP values of events occurring at \u0026lt;6 and \u0026ge;6 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eAFP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e0.006\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026ge;1000 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e100-999 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e0.630(0.199-1.993)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e＜100 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e1.361(0.190-9.779)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003ePRETEXT stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e0.016\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e2.979(0.720-12.316)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e3.068(0.734-12.819)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e5.983(1.375-26.029)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eVPEFRMN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e0.030\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e3.044(1.965-4.715)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eAFP+PRETEXT stage +VPEFRMN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e0.049\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e1.980(1.002-3.913)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 100%;\"\u003e\n \u003cp\u003eTable 3 (continued)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eRisk factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eOS：HR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003eP values of deaths occurring at \u0026lt;6 and \u0026ge;6 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eAFP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e0.013\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026ge;1000 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e100-999 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e0.467(0.064-3.395)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e＜100 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e2.603(0.356-19.029)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003ePRETEXT stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e0.039\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e2.528(0.336-18.999)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e2.689(0.354-21.448)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e6.672(0.845-52.692)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eVPEFRMN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e0.045\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e3.624(1.858-7.070)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eAFP, PRETEXT stage or VPEFRMN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e0.092\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.8701%;\"\u003e\n \u003cp\u003e2.061(0.889-4.777)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 40.2597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e P value after eliminating the influence of the AFP; \u003csup\u003eb\u003c/sup\u003e P value after eliminating the influence of the PRETEXT stage; VPEFRMN: V, P, E, F, R, M or N; \u003csup\u003ec\u003c/sup\u003e P value after eliminating the influence of VPEFRMN; \u003csup\u003ed\u003c/sup\u003e P value after eliminating the influence of the AFP, PRETEXT stage and VPEFRMN\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 Comparison of EFS and OS in various age groups\u0026nbsp;younger than one year at initial diagnosis\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"564\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003eAge(M)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.72566%;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003eEFS：HR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003eOS：HR (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.9204%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e0-＜1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.72566%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.9204%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e1-＜3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.72566%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003e0.487(0.030-7.807)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e0.611\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003e0.424(0.026-6.840)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.9204%;\"\u003e\n \u003cp\u003e0.546\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e3-＜6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.72566%;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003e1.045(0.122-8.985)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e0.968\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003e0.685(0.075-6.213)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.9204%;\"\u003e\n \u003cp\u003e0.736\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e6-＜9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.72566%;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003e0.289(0.026-3.202)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003e0.136(0.008-2.197)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.9204%;\"\u003e\n \u003cp\u003e0.160\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e9-＜12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.72566%;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003e1.257(0.162-9.750)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.4513%;\"\u003e\n \u003cp\u003e0.827\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.7257%;\"\u003e\n \u003cp\u003e0.526(0.061-4.515)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.9204%;\"\u003e\n \u003cp\u003e0.558\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eM: month\u003c/p\u003e\n\u003cp\u003eTable 5 Age distribution of risk factors for HB\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003eRisk factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003eMedian age(Y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003eMinimum age(Y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003eMax age(Y)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003eAFP＜100 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003eAFP 100-1000 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e10.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003eAFP＞1000 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e381\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003ePRETEXT I stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003ePRETEXT II stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003ePRETEXT III stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003ePRETEXT IV stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003ePRETEXT stage NA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e10.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003eVPEFRMN+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e188\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003eVPEFRMN-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29.5139%;\"\u003e\n \u003cp\u003eVPEFRMN NA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.15972%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.3542%;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.9167%;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.0556%;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eY: year; NA: not available\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5240184/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5240184/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjective This study aimed to examine how age at first diagnosis influences the prognosis of Chinese children with hepatoblastoma (HB), and to offer insights for enhancing HB risk stratification.\u003c/p\u003e\n\u003cp\u003eMethods Data from 403 patients with HB diagnosed at the First Affiliated Hospital of Sun Yat-sen University between February 2010 and September 2023 were collected. Kaplan‒Meier survival analysis, Cox regression analysis, and binary logistic regression were employed for statistical analysis.\u003c/p\u003e\n\u003cp\u003eResults The hazard ratios (HRs) for event-free survival (EFS) reduction in HB patients were 1, 0.862, 1.393, 2.008, 1.325, 1.859, 3.667 (P=0.001), and 2.502 (P=0.023) for first–diagnosis ages of 0–1, 1–2, 2–3, 3–4, 4–5, 5–6, 6–8, and ≥8 years, respectively, and the HRs for overall survival (OS) were 1, 0.410, 0.876, 1.713, 1.243, 0.575, 3.012 (P=0.039), and 2.012, respectively. After adjusting for newly diagnosed alpha-fetoprotein (AFP), pretreatment extent of tumor (PRETEXT) stage, and PRETEXT stage annotation factors, the prognosis of HB for patients diagnosed at ≥6 years old and \u0026lt;6 years old remained significantly different. There was no significant difference in the HR for EFS or OS reduction among the 0–1month, 1–3month, 4–6month, 7–9month, and 9–12month groups.\u003c/p\u003e\n\u003cp\u003eConclusion Age≥6 years is an independent risk factor for poor prognosis in HB patients. Age has no effect on the prognosis of HB during infancy. The inclusion of patients aged ≥6 years at first diagnosis in the high-risk group for risk stratification was deemed appropriate. This age factor can guide adjustments in chemotherapy intensity.\u003c/p\u003e","manuscriptTitle":"The importance of age as a prognostic predictor of childhood hepatoblastoma: an analysis of single-center childhood hepatoblastoma in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-16 16:48:43","doi":"10.21203/rs.3.rs-5240184/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-02T08:14:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-29T07:05:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"267756441315061690071624796605881638469","date":"2024-11-22T10:21:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-21T01:39:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"128345641546521215945070717364193384449","date":"2024-11-14T12:48:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-12T12:36:56+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-10-21T15:35:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-18T02:25:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-18T02:24:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2024-10-10T13:48:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a2c6f523-3070-4573-92e5-22cd57ecb7d2","owner":[],"postedDate":"December 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-10T19:46:16+00:00","versionOfRecord":{"articleIdentity":"rs-5240184","link":"https://doi.org/10.1186/s12887-025-05487-x","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-03-04 15:58:17","publishedOnDateReadable":"March 4th, 2025"},"versionCreatedAt":"2024-12-16 16:48:43","video":"","vorDoi":"10.1186/s12887-025-05487-x","vorDoiUrl":"https://doi.org/10.1186/s12887-025-05487-x","workflowStages":[]},"version":"v1","identity":"rs-5240184","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5240184","identity":"rs-5240184","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}