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Objective:To summarize the clinical features of neuroblastoma (NB) with bone metastasis in infants and the prognostic factors.Methods:A retrospective analysis was performed on 32 patients aged ≤12 months who were enrolled in Beijing Children′s Hospital, Capital Medical University from January 2010 to December 2019 and had imaging findings suggesting signs of distant bone metastasis.The control group was included NB children, aged ≤12 months, who were admitted to Beijing Children′s Hospital, Capital Medical University during the same period, without signs of distant bone destruction.The clinical manifestations and auxiliary examinations of infants with bone metastasis were summarized, and the efficacy evaluation and survival analysis of infants with regular treatment and follow-up were conducted until December 31, 2020. Kaplan- Meier survival analysis was used for prognostic analysis, and Log Rank test was used for univariate prognostic analysis. Results:There were 32 NB infants with bone metastases, involving 12 males (37.5%) and 20 females (62.5%), accounting for 16.0% (32/200 cases) of infants diagnosed with NB du-ring the same period.The median age of onset was 9 (4.5-12.0) months.The main primary site included the retroperitoneal and adrenal region in 24 cases(75.0%) and mediastinum in 3 cases (9.4%). Among the 32 cases, 14 cases (43.8%) had simple bone metastasis, 19 cases (59.4%) had distant lymph nodes, 18 cases (56.3%) had bone marrow, and 3 cases (9.4%) had intracranial and meningeal metastasis.Bone metastasis mainly occurred in the skull, with 11 cases of single bone metastases and the remaining with 2 or more bone metastases.Compared with 168 NB infants without bone metastasis, the prognosis of those with bone metastasis was significantly worse [3-year overall survival(OS) rate 97.6% vs.82.7%, P=0.001]. Univariate analysis showed that the prognosis of NB children with bone marrow metastasis, meningeal and intracranial metastasis, MYCN gene amplification, and high-risk group was poor (all P<0.05). Two patients returned to the local hospital for treatment after diagnosis.A total of 30 children were recruited for efficacy evaluation and prognostic analysis.Twenty-nine children underwent surgery, of which 6 cases received surgery before chemotherapy and 23 cases received surgery after chemotherapy.One case received chemotherapy only.The mean course of chemotherapy was 6.2 (4-13) times.One case was treated with radiotherapy, 1 case was treated with Metaiodobenzylguanidine (MIBG) therapy, and 1 case was treated with stem cell transplantation.A total of 18 cases (62.1%) event-free survived, and 12 cases (40.0%) had a mean event at 7 (1.5-32.0) months.Among them, 7 cases survived and 5 cases died (16.7%). The expected 3-year event-free survival rate and OS rate were 57.1% and 82.7%, respectively. Conclusions:The most common sites of infant NB metastasis are bone and bone marrow, and the most common sites of bone metastasis are skull.Infants with bone metastasis had a worse prognosis than those without bone metastasis, and infants with bone and bone marrow metastasis had a worse prognosis than infants with single bone metastasis.
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Objective:To explore the clinical significance of the MYCN gene, PHOX2B gene and plasma cell-free DNA (cfDNA) in risk stratification and predicting the prognosis of high-risk neuroblastoma (NB). Methods:This was a prospective study involving 94 high-risk NB children admitted to Beijing Children′s Hospital, Capital Medical University from August 2017 to December 2018.Relative levels of MYCN and PHOX2B and cfDNA at diagnosis, and 4 and 6 cycles of chemotherapy were detected, and their differences were compared by the Chi- square test.Kaplan-Meier survival analysis was performed to explore their prognostic potential in high-risk NB. Results:Among the 94 high-risk NB children, 14 cases (14.9%) had MYCN amplification, 76 cases (80.8%) had positive expression of PHOX2B and 56 cases (59.6%) had cfDNA level higher than 100 μg/L.The proportion of high lactate dehydrogenase (LDH, ≥1 500 U/L) level in the MYCN gene amplification group (6/14 cases) was higher than that in the normal group (9/80 cases) ( P=0.009). The proportion of multi-site metastasis (54/76 cases) and high neuron specific enolase (NSE) level (NSE≥370 μg/L, 37/76 cases) in PHOX2B positive group were significantly higher than those in the negative group (5/14 cases, 2/14 cases) ( P=0.015, 0.020). The proportion of high LDH and high NSE in high cfDNA concentration (≥229.6 μg/L)group (13/37 cases, 28/37 cases) were significantly higher than those in low cfDNA concentration group (2/48 cases, 10/48 cases) (all P<0.001). With the decreased tumor burden during the treatment, the copy number of PHOX2B gene and cfDNA level were significantly lower than those at the initial diagnosis [0 (0-719.6) copies vs.1 723.5 (0-186 000.0) copies; 19.0 (1.1-225.5) μg/L vs.200.6 (8.0-5 247.4) μg/L, all P<0.001]. The 2-year event-free survival (EFS) rate of the MYCN gene amplification group was significantly lower than that of the normal group[(33.3±13.1)% vs.(58.5±7.1)%, P=0.020]. The 2-year EFS rate of PHOX2B positive group was significantly lower than that of the negative group[(47.9±7.1)% vs.(79.1±11.1)%, P=0.043]. EFS rate in high cfDNA concentration group was significantly lower than that in cfDNA low concentration group[(38.6±9.8)% vs.( 71.7±8.2)%, P=0.001]. After 6 cycles of chemotherapy, EFS rate in the PHOX2B positive group was significantly lower than that in the negative group [(16.7±14.4)% vs.( 60.6±6.6)%, P=0.014]; which was significantly lower in the Metaiodobenzylguanidine (MIBG) positive group than that of the negative group[(35.2±11.7)% vs.(65.8±7.1)%, P=0.037]. The MYCN gene and cfDNA concentration were not correlated with the prognosis of high-risk NB.Survival analysis of the combination of PHOX2B and MYCN gene ( PHOX2B+ /MIBG + , PHOX2B+ or MIBG + , PHOX2B-/MIBG -) showed a significant difference in the survival among three groups[0 vs.(53.6±1.2)% vs.(65.5±7.4)%, P=0.003]. Conclusions:The MYCN and PHOX2B gene and cfDNA concentration are of significance in risk stratification and predicting the prognosis of high-risk NB.Compared with the MYCN gene and cfDNA concentration, the PHOX2B gene is more suitable for monitoring the curative effect of chemotherapy on high-risk NB.A combined analysis of PHOX2B gene and MIBG before treatment can be more accurate in evaluating the treatment effect and residual lesions.
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Objective:To summarize the clinical characteristics of single-center children with low and intermediate-risk neuroblastoma (NB), report the long-term follow-up results of the growth and survival quality, and provide a basis for further clinical research.Methods:Clinical characteristics, including the sex, age, stage, risk of disease, and metastatic site of 370 newly treated children with low and intermediate-risk NB admitted to Hematology Oncology Center, Beijing Children′s Hospital from March 2007 to June 2019 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.WHO Anthro Plus was used for calculating Z score.Results:A total of 370 eligible children with low and intermediate-risk NB were included, with the mean age at onset of 16.8 months (1-191 months). Among them, 148 cases (40%) were younger than 12 months old.Mediastinal region was the most common primary site of NB (47.8%, 177 cases), followed by retroperitoneum/adrenal gland (41.4%, 153 cases). The median follow-up time of 370 patients was 31 months (0.3-157.0 months), the 5-years event free survival (EFS) and 5-year overall survival (OS) were 86.2% and 96.9%, respectively.Thirty-seven cases had growth and deve-lopment problems, of which 22 cases had stunted growth, 6 cases had low body mass, 9 cases had wasting, and 7.3%(27/370 cases) had scoliosis.5.5% of them had heart damage and 5.0%(18/357 cases) had kidney damage, involving 12 cases related to the primary tumor and 6 cases were surgically related.30.2%(95/315 cases) of them had hair changed after chemotherapy, and curly hair was the most common change.Compared with before treatment, 14.9% of the children had a personality change, with an impatient being the most common.Conclusions:The 5-year overall survival rate of the single-center large sample of low and intermediate-risk NB was high, mediastinal was the most common primary site of tumor, and the long-term quality of life is good, but there were still treatment-related side effects, and further clinical monitoring and long-term follow-up were needed.
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Objective:To investigate the clinical characteristics, treatment effect and prognosis of children with nearly diploid neuroblastoma (NB).Methods:A retrospective analysis of the general clinical characteristics (including age, Gender, risk grouping, location of primary tumor, etc.), laboratory test results, treatment and recent prognosis of NB children with nearly diploidy in bone marrow chromosomes by G-banding technology who admitted to Beijing Children′s Hospital, Capital Medical University from January 2015 to December 2018. Kaplan- Meier method was adopted to calculate survival rate.Univariate analysis was performed using Log- Rank test, and multivariate analysis was conducted with Cox regression model. Results:A total of 43 patients, including 27 males and 16 females, with diagnosis were included, with 14 cases in the hypodiploid group and 29 cases in the hyperdiploid group, and the median age was 35.5 months.The 43 children were all in the high-risk group of International Neuroblastoma Staging System(INSS)-Ⅳ.The primary tumors were mainly located in the retroperitoneal adrenal region (83.7%, 36/43 cases). The largest diameter of the tumors was more than 10 cm (53.5%, 23/43 cases), and often accompanied by 2 or more metastases at the time of consultation.In terms of chromosome karyotype and chromosome karyotype of 14 children in the hypodiploid group was 41-45, the most common karyotype was 45 chromosomes[9 cases(64.3%)]. Among 29 children in the hyperdiploid group of the 47 chromosome karyotypes, 11 cases were common (37.9%). Tumor markers were as follows: neuron enolase (NSE) increased in 41 cases children (95.3%) at first diagnosis, and 25 cases (58.1%)> 370 μg/L; 42 cases (97.7%)had lactate dehydrogenase (LDH). The LDH of children in the hypodiploid group was all> 500 U/L, with 1 case was> 10 000 U/L.Nine cases (20.9%) of MYCN gene were detected by fluorescence in situ hybridization (FISH). Treatment and prognosis: the total course of chemotherapy for 43 patients was 1-12, 19(44.2%) patients received autologous stem cell transplantation, 21 patients (46.5%) received postoperative or autologous radiotherapy or metaiodobenzylguanidine treatment, 28 children developed or relapsed with a median duration of 13.8 months, and 15 cases (34.9%) died.The median follow-up time of the 14 children in the hypodiploid group was 14.9 months (2-38 months), 12 cases progressed or relapsed, and 7 died.The median follow-up of 29 children in the hyperdiploid group was 20.0 months (8.1-51.6 months), with 16 patients progressed or relapsed and 8 cases died. Kaplan- Meier survival analysis illustrated that the 3-year projected event free survival (EFS) rate of 43 children was 18.4%, of which 17.1% were in the hypodiploid group and 29.8% in the hyperdiploid group. Conclusions:Preliminary analysis reveals that children with nearly diploid NB are mostly in the stage Ⅳ high-risk group over the age of 18 months, and 2 or more metastases at the time of consultation.The 3-year estimated EFS of 43 children was 18.4%, and the prognosis was worse in the hypodiploid group.
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Neuroblastoma(NB)is the most common extracranial solid tumor in children, characterized by occult onset, high malignancy, and prone to bone, bone marrow and distant organ metastasis.It shows high heterogeneity in biology, genetics, clinic and morphology.So far, the prognosis of high-risk and refractory relapsed NB is still extremely poor.It has been found that various chromosome abnormalities were related to the occurrence, proliferation and metastasis of NB, including abnormalities chromosome number, gene structure , segmental fragmentation and chromatin remodeling.These researches speculated that the genetic variation among individuals during treatment might be one of the main reasons for tumor progression or recurrence.This study will review the molecular genetics related to chromosome abnormalities of NB and provide evidence for finding potential NB targets.
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Objective To retrospectively analyze the clinical efficacy,safety and influencing factors of radiotherapy in children with stage Ⅳ high-risk neuroblastoma (HR-NB).Methods A total of 120 children with HR-NB who were diagnosed and treated with local radiotherapy according to the BCH-HR-NB-2007 protocol in the Oncology Department of Beijing Children's Hospital from January 2014 to December 2017 were enrolled.Among them,56 children were male and 64 female with a median age of 43 months (9 -148 months).The treatment protocol consisted of 4 cycles of CAV chemotherapy,3 cycles of CVP chemotherapy,surgical resection after 4 cycles,autologous hematopoietic stem cell transplantation after 7 cycles,local radiotherapy at a dose of 15.0-30.6 Gy for 82 cases of primary tumors and 38 cases of primary and metastatic tumors,followed by 13 cis-retinoic acid as maintenance therapy.The entire treatment protocol endured for approximately 18 months.Results The median follow-up time was 21 months.The 3-year local control rate was 84.4％.Before radiotherapy,the 3-year event-free survival rate was 78.4％ in children without metastases,significantly higher compared with 30.4％ in the residual group (P=0.003).The 3-year event-free survival rate was 66.1％ in patients who underwent radiotherapy within 6 months after surgery,significantly higher than 50.6％ in their counterparts receiving radiotherapy at 6 months or more after surgery (P=0.018).Among the children with residual metastases before radiotherapy,the progression rate in children who did not receive radiotherapy was 66.6％,significantly higher compared with 20.0％ in those receiving radiotherapy (P=0.001).All patients had no radiation-related adverse reactions in the liver,kidney and heart,etc.The incidence rate of grade Ⅲ-Ⅳ myelosupression was 24.5％ at 1 week post-radiotherapy,and 8％ at 2 weeks after radiotherapy.Conclusions Radiotherapy yields definite clinical efficacy in the local control of children with stage Ⅳ HR-NB.Early radiotherapy after surgery and radiotherapy for the metastatic lesions can improve the clinical prognosis.No vital organ injuries are observed during the short-term follow-up.At 2 weeks after radiotherapy,the myelosupression is gradually restored.
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Objective@#To analyze the clinical characteristics of children with neuroblastoma (NB) complica-ted with lung or pleural metastasis, further to explore the correlation between characteristics and short-term outcome of NB, so as to provide a basis for clinical diagnosis and treatment.@*Methods@#A retrospective analysis was performed concerning the age of onset, clinical features, treatment and outcome of 36 patients with NB who were admitted at Blood Tumor Center, Beijing Children′s Hospital of Capital Medical University from December 2007 to December 2017.The diagnostic criteria, therapeutic regimen and therapeutic efficacy criteria of the enrolled children were all based on the NB protocol of Beijing Children′s Hospital of Capital Medical University (BCH-NB-2007), the clinical stage was based on international clinical stage of neuroblastoma (INSS stage), and stratified treatment was conducted according to the BCH-NB risk grouping standard.The follow-up period lasted till October 31, 2018.@*Results@#(1)The common clinical features of grouped children: 36 patients were selected into the group, accounted for 5.99% (36/601 cases) in total hospitalized NB children, they were less than 10 years old, 10 cases under 18 months, and the median age was 29.5 months (9-105 months); 20 cases were male, and 16 cases were female; the primary tumor was located in the retroperitoneal site in 19 cases, accounting for 52.78%, 9 cases in adrenal site, accounting for 25.00%, and 8 cases in mediastinal site, accounting for 22.22%.Risk groups: 29 cases were in high-risk group, 6 cases were in medium-risk group and 1 case was in low-risk group.The main symptoms were of pain onset in 8 cases, fever in 6 cases, local mass in 6 cases, abdominal mass in 4 cases, mediastinal mass in 3 cases, paleness in 3 cases, subcutaneous nodules in 2 cases, abdominal distension in 2 cases, lower limb swelling in 1 case, and diarrhea in 1 case. Among them, 16 cases had respiratory system symptoms first, accounting for 44.4%.(2)Laboratory examination: there were 35 patients of neuron-specific enolase (NSE) ≥25 μg/L on the initial diagnosis, of which 11 cases were more than 370 μg/L, the value of serum lactate dehydrogenase (LDH) ≥717.5 U/L in 25 patients, accounting for 69.44%, and 10 cases were accompanied by N-myc gene amplification.(3)Imaging examination: on the first diagnosis, chest/abdomen CT showed 75.75%(24/33 cases) of pleural or lung involvement, PET-CT showed 81.8% (27/33 cases) of pleural or lung involvement, B-ultrasound showed 41.67%(5/12 cases) of pleural or lung involvement; 3 imaging examinations showed: 1 positive in 16 cases, 2 positive in 16 cases, and 3 positive in 4 cases.(4)Comparison of clinical features of pleural and pulmonary involvement: among the 30 children with pleural involvement, 6 cases had respiratory symptoms, 3 cases had respiratory symptoms on the 6 cases with pulmonary involvement only, and 4 cases with pleural and pulmonary involvement had no respiratory symptoms at first diagnosis.(5)Treatment and outcome: 2 cases died because of critical condition after diagnosis, 5 cases didn′t receive the law treatment, 29 cases accepted law stratification treatment, among them, 1 case in low risk group, INSS-Ⅳ, alleviate current (CR); 4 cases in the moderate group, INSS-Ⅳ, CR in 2 cases, partial response (PR) in 1 case, progress in 1 case, new tumor foci occurring after chemotherapy discontinuation for 13 months. Twenty-four cases were in the high-risk group, event occurred in 7 cases (29.17%) of them, 1 case had progression by postoperative evaluation, 4 cases of progression at 1.5, 2.0, 3.0 and 6.0 months after cessation of chemotherapy, and 2 cases had recurrence at 11 and 17 months after cessation of chemotherapy.Overall survival rate (OS) was 41.4% for all children analyzed by Kaplan-Merier, and 32.9% of them were predicted to have 3-year event-free survival.@*Conclusions@#Children with pulmonary or pleural metastasis of neuroblastoma have no specific respiratory symptoms.CT scan might be a useful method for diagnosing the group Ⅳ children with pulmonary or pleural metastasis of neuroblastoma.Moreover, there seemed to be no significant correlation between the N-myc gene expression and survival prognosis of these children.
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Objective To analyze the clinical characteristics of children with neuroblastoma (NB) complicated with lung or pleural metastasis,further to explore the correlation between characteristics and short-term outcome of NB,so as to provide a basis for clinical diagnosis and treatment.Methods A retrospective analysis was performed concerning the age of onset,clinical features,treatment and outcome of 36 patients with NB who were admitted at Blood Tumor Center,Beijing Children's Hospital of Capital Medical University from December 2007 to December 2017.The diagnostic criteria,therapeutic regimen and therapeutic efficacy criteria of the enrolled children were all based on the NB protocol of Beijing Children's Hospital of Capital Medical University (BCH-NB-2007),the clinical stage was based on international clinical stage of neuroblastoma (INSS stage),and stratified treatment was conducted according to the BCH-NB risk grouping standard.The follow-up period lasted till October 31,2018.Results (1) The common clinical features of grouped children:36 patients were selected into the group,accounted for 5.99％ (36/601 cases) in total hospitalized NB children,they were less than 10 years old,10 cases under 18 months,and the median age was 29.5 months (9-105 months);20 cases were male,and 16 cases were female;the primary tumor was located in the retroperitoneal site in 19 cases,accounting for 52.78％,9 cases in adrenal site,accounting for 25.00％,and 8 cases in mediastinal site,accounting for 22.22％.Risk groups:29 cases were in high-risk group,6 cases were in medium-risk group and 1 case was in low-risk group.The main symptoms were of pain onset in 8 cases,fever in 6 cases,local mass in 6 cases,abdominal mass in 4 cases,mediastinal mass in 3 cases,paleness in 3 cases,subcutaneous nodules in 2 cases,abdominal distension in 2 cases,lower limb swelling in 1 case,and diarrhea in 1 case.Among them,16 cases had respiratory system symptoms first,accounting for 44.4％.(2) Laboratory examination:there were 35 patients of neuron-specific enolase (NSE) ≥25 μg/L on the initial diagnosis,of which 11 cases were more than 370 μg/L,the value of serum lactate dehydrogenase (LDH) ≥ 717.5 U/L in 25 patients,accounting for 69.44％,and 10 cases were accompanied by N-myc gene amplification.(3) Imaging examination:on the first diagnosis,chest/abdomen CT showed 75.75％ (24/33 cases) of pleural or lung involvement,PET-CT showed 81.8％ (27/33 cases) of pleural or lung involvement,B-ultrasound showed 41.67 ％ (5/12 cases) of pleural or lung involvement;3 imaging examinations showed:1 positive in 16 cases,2 positive in 16 cases,and 3 positive in 4 cases.(4)Comparison of clinical features of pleural and pulmonary involvement:among the 30 children with pleural involvement,6 cases had respiratory symptoms,3 cases had respiratory symptoms on the 6 cases with pulmonary involvement only,and 4 cases with pleural and pulmonary involvement had no respiratory symptoms at first diagnosis.(5)Treatment and outcome:2 cases died because of critical condition after diagnosis,5 cases didn't receive the law treatment,29 cases accepted law stratification treatment,among them,1 case in low risk group,INSS-Ⅳ,alleviate current (CR);4 cases in the moderate group,INSS-Ⅳ,CR in 2 cases,partial response (PR) in 1 case,progress in 1 case,new tumor foci occurring after chemotherapy discontinuation for 13 months.Twenty-four cases were in the high-risk group,event occurred in 7 cases (29.17％) of them,1 case had progression by postoperative evaluation,4 cases of progression at 1.5,2.0,3.0 and 6.0 months after cessation of chemotherapy,and 2 cases had recurrence at 11 and 17 months after cessation of chemotherapy.Overall survival rate (OS) was 41.4％ for all children analyzed by Kaplan-Merier,and 32.9％ of them were predicted to have 3-year event-free survival.Conclusions Children with pulmonary or pleural metastasis of neuroblastoma have no specific respiratory symptoms.CT scan might be a useful method for diagnosing the group Ⅳ children with pulmonary or pleural metastasis of neuroblastoma.Moreover,there seemed to be no significant correlation between the N-myc gene expression and survival prognosis of these children.