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Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.
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Objective:To observe and analyze the clinical characteristics of children who died of intraocular retinoblastoma (RB).Methods:A retrospective clinical study. Fourteen children (23 eyes) with intraocular RB who died after receiving treatment in Beijing Children's Hospital from 2009 to 2017 were included in the study. Among the children, there were 7 males (10 eyes) and 7 females (13 eyes); 5 had unilateral and 9 had bilateral tumor. Age were 17.2±15.5 months. All children underwent RetCam examination. RB was staged according to the international intraocular RB classify. Among the 23 eyes, 1 eye was in stage B, 2 eyes were in stage C, 12 eyes in stage D, and 8 eyes in stage E. Treatment methods included a systemic (vincristine, etoposide and carboplatin) chemotherapy (VEC chemotherapy), enucleation surgery, and vitrectomy. The basic conditions including age, time of diagnosis, pathological diagnosis, treatment and main causes of death were retrospectively analyzed.Results:Among the 14 cases, the first symptom was leukemia in 12 cases, red eye in 1 case, and squintin in 1 case. Systemic VEC chemotherapy was used for 1-6 courses of treatment; 5 cases were enucleated, 3 cases underwent histopathological examination; 3 cases were treated with vitrectomy. Among the 3 cases who underwent histopathological examination, the sclera and optic nerve, optic nerve and optic disc were invasted respectively. Seven patients died of tumor metastasis and/or intracranial lesions (50.0%, 7/14); the median survival time was 19 months. Four patients died of treatment (28.6%, 4/14), including 3 patients died of chemotherapy-related side effects, and 1 died of organ failure after enucleation surgery (7.1%); the median survival time was 3.5 months. Early abandonment of treatment died in 3 cases (21.4%, 3/14); the median survival time was 15 months.Conclusion:Intracranial metastasis is the main cause of death in children with intraocular RB.
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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 causes of death and severe complication in the early diagnosis of children with neuroblastoma (NB), and to analyze the relative factors of early death of children with NB, so as to raise awareness and reduce early mortality by early detection and early intervention.Methods:Patients with newly diagnosed NB in the Hematology Oncology Center of Beijing Children′s Hospital from April 2007 to December 2017 were included consecutively, and those died within 1 month after diagnosis were retrospectively analyzed.The general data of patients, immediate causes of death, complications, time elapsed between death and diagnosis, whether to receive chemotherapy and other information were collected.Results:A total of 654 cases were included for diagnosis, treatment and follow-up, 31 cases of which died in early stage, accounting for 4.7% of the total.The major complication were pulmonary infection in 18 cases (58.1%) and bone marrow suppression after chemotherapy in 17 cases (54.8%), tumor rupture hemorrhage in 16 cases (51.6%), multiple organ failure in 8 cases (25.8%). Risk factor analysis of the 31 early death cases with NB was conducted.Single factor analysis: there were statistical differences between early death group and non-early death group in risk grouping ( P=0.006 6), bone marrow invasion ( P=0.020 7), site of primary tumor ( P=0.016 7), age ( P=0.003 3), lactate dehydrogenase (LDH) level ( P<0.000 1), neuron-specific enolase (NSE) level ( P<0.000 1), serum ferritin level ( P=0.016 0), D dimer level ( P<0.000 1), fibrinogen level ( P=0.002 7), diameter of tumor ( P<0.000 1), hemoglobin ( P<0.000 1), platelet level ( P<0.000 1), serum albumin level ( P<0.000 1). Multiple-factor analysis: age younger than 30 months, OR=2.824 (95% CI: 1.084-7.359), LDH level greater than 1 004 IU/L, OR=6.991 (95% CI: 2.135-22.887), albumin level less than 36 g/L, OR= 65.237 (95% CI: 2.024-13.545), hemoglobin level less than 92 g/L, OR=5.358 (95% CI: 2.024-13.545), platelet level less than 192×10 9/L, OR=3.554 (95% CI: 1.267-9.965). Conclusions:Strengthening vital signs detection after admission, identifying severe life-threatening complications such as rupture of tumors as early as possible, implementing symptomatic interventions such as appropriate sedation and active transfusion of blood products as early as possible after invasive operation, and transferring to intensive care unit for respiratory support when necessary are important means to avoid early death.
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Objective:To summarize the clinical features, therapeutic effects and prognostic factors of children with extracranial malignant germ cell tumor (MGCT), and further to improve the recognition of this disease.Methods:The clinical information and therapeutic effects of children patients diagnosed with MGCT and treated in Hematology-Oncology Center in Beijing Children′s Hospital, Capital Medical University from January 2008 to December 2018 were analyzed retrospectively, and the risk factors affecting the prognosis were discussed.Results:A total of 35 patients were collected in this study, including 19 girls and 16 boys, with a median age of 71 months.Forty-two point four percent (14/33 cases) of them were <3 year-old, and 39.3% (13/33 cases) of them were >6 year-old.The primary tumors were located at the gonad in 9 cases (6 cases in the ovary and 3 cases in the testis), and extragonadal sites in 26 cases (8 cases in the pelvic cavity, 8 cases in the mediastinum, and 10 cases in the sacrococcygeal region). Five cases were in stage Ⅱ, 16 cases in stage Ⅲ, and 14 cases in stage Ⅳ.Eleven cases were at intermediate risk, and 24 cases were at high risk.All children were followed up for (25.43±4.82) months, and given standard treatment of surgery plus chemotherapy.The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 87.4% and 67.1%, respectively.The 2-year OS rate and EFS rate in patients at stage Ⅱ and Ⅲ (93.8% and 80.4%, respectively) were significantly higher than those at stage Ⅳ (66.7% and 45.1%, respectively) ( χ2=0.649, 0.739; P=0.021, 0.037). The 2-year EFS rate in patients with and without distant metastasis at the early stage of the disease was 43.8% and 86.9%, respectively, and the differences were significant ( χ2=0.694, P=0.028). The complete remission (CR) rates of intermediate-risk and high-risk children with tumor completely resected at the early stage of the disease were 100.0% (8/8 cases) and 71.4% (5/7 cases), respectively.The CR rate of patients who received 2-4 cycles of chemotherapy and had complete tumor resection after diagnosis by puncture was 72.7% (8/11 cases), and 40.0% (2/5 cases) of the children with incomplete resection got tumor progression.For eight patients with events, their alpha-fetoprotein (AFP) levels decreased slowly at the early stage of the disease and increased significantly as the disease progressed. Conclusions:The onset-age of MGCT is mainly <3 year-old and >6 year-old.The stan-dard treatment that combines surgery and chemotherapy can achieve a good overall prognosis.Incomplete surgical resection and a slow decline of AFP during treatment contribute to adverse prognosis.The outcomes of patients with tumor progression can be improved by increasing chemotherapy courses, secondary surgery and autologous stem cell transplantation.
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Objective To explore the significance of the initial clinical symptoms and clinical manifestations of neuroblastoma(NB)to achive early identification of NB. Methods A retrospective study was performed on patients diagnosed with NB,who attended the Hematology Oncology Center,Beijing Childrenˊs Hospital from March 31st ,2007 to March 31st,2015. The clinical characteristics were compared between the children 〈1_year_old and≥1_year_old. The result was analyzed to compare the difference in clinical symptoms and tumor biologic characteristics of patients with different initial clinical symptoms between 2 groups. Results A total of 330 patients were included in the study,43 of them were younger than 1 year old,and their most common symptoms were cough and fever( each 17 cases,and accounted for 39. 5%,respectively);while the most common symptoms in patients≥1_year_old(287 cases)was fe_ver(177 cases,61. 7%),followed by lymphadenopathy(107 cases,37. 3%),bone pain(97 cases,33. 8%)and anemia (48 cases,16. 7%). The frequency of symptoms differed significantly between 2 groups(all P〈0. 05),such as fever (39. 5% vs. 61. 7%,χ2 ﹦6. 68),anemia(4. 7% vs. 16. 7%,χ2 ﹦6. 00),bone pain(0 vs. 33. 8%,χ2 ﹦18. 99),abdo_minal pain(0 vs. 25. 3%,χ2 ﹦10. 19),diarrhea(16. 3% vs. 3. 0%,χ2 ﹦12. 73),lymphadenopathy(7. 0% vs. 37. 3%, χ2 ﹦14. 12)and anorexia(9. 3% vs. 33. 4%,χ2 ﹦9. 21). Datients had fever,anemia,lymphadenopathy,cutaneous hemorrhagic spot or periorbital ecchymosis,bone pain,abdominal pain,exophthalmos,and anorexia early in the initial course of the disease,whose serum lactate dehydrogenase values were significantly increased(P〈0. 05). Datients suf_fered from fever,anemia,lymphadenopathy,bone pain,limbs dysfunctions,abdominal pain at the beginning of the disease,whose urine vanillymandelic acid values were higher than normal(P〈0. 05). Conclusions The study of sympto_mology suggests the most common symptoms in patients with NB 〈1_year_old are cough and fever,while those ≥1_year_old are fever,lymphadenopathy,bone pain,and anemia. Por patients with symptoms mentioned,carrying out the necessary NB_diagnose_related laboratory and imaging studies was statistically relevant to patientsˊ ages(〈1_year_old and≥1_year_old),which may contribute to earlier identification and diagnosis of NB.
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Objective To summarizk clinical charactkristics,thkrapkutic kffkct and prognosis of rhabdomeosar-coma(AMS)childrkn of lkss-than-2 -ekar old and its rklatkd factors,to improvk thk awarknkss of this agk group with AMS. Methods Thk clinical information and thkrapkutic kffkct of 20 AMS patiknts of lkss-than-2-ekar old wkrk diagnoskd and trkatkd at thk hkmatologe -oncologe ckntkr in Bkijing Childrkn＇s Hospital( BCH),from Januare 2012 to Lpril 2017,and thk clinical data wkrk analezkd rktrospkctivkle. Lccording to thk intkrnational critkria for thk trkatmknt of solid tumors in childrkn,thk patiknts wkrk dividkd into a complktk rkmission group and a progrkss╱rklapsk group,and thk risc factors affkcting thk prognosis wkrk analezkd. ResuIts Twknte casks of lkss-than-2 ekar old chil-drkn with AMS wkrk collkctkd,accounting for 12. 4﹪ of all AMS during thk samk pkriod in BCH hkmatologe-oncologe ckntkr. Thk mkdian follow-up timk was(16. 1 ± 1. 8)months,5 patiknts got progrkss╱rklapsk at 9-12 months during trkatmknt and 2-3 months aftkr thkrape finishkd. Thk ratk of 2 -ekar-kvknt-frkk survival( EPS)ratk and ovkrall survival(OS)ratk wkrk 48﹪ and 61﹪,rkspkctivkle. Thk 2-ekar EPS ratk of kmbreonal AMS childrkn was significant-le highkr than that of alvkolar AMS childrkn,and thk diffkrknck was statisticalle significant(χ2 ﹦0. 854,P﹦0. 034). In thk progrkss╱rklapsk group and thk childrkn with complktk rkmission childrkn,factors lick boe,kmbreonal tepk,primare tumor location of not bad,and of mkdium risc might rkduck thk risc of progrkss╱rklapsk of AMS,whilk tumor diamktkr ＞5 cm and clinical stagk Ⅳ might incrkask thk risc of progrkss╱rklapsk of AMS,but thk diffkrknck was not statisticalle significant(P＞0. 05). ConcIusions Thk prognosis of AMS childrkn lkss-than-2-ekar old was vkre poor,and thk ratks of 2 ekars EPS and OS ratks wkrk lowkr than ovkrall indkx of childrkn with AMS. Thksk patiknts nkkd to undkrgo a varikte of trkatmknt mkthods flkxible,including dklaekd radiothkrape and 125 I radioactivk skkds brachethkrape,to improvk thkrapkutic kfficace and long-tkrm outcomks.
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Objective To analezk thk altkrations in blood urka nitrogkn( BRN)and skrum crkatinink( Scr) in childrkn with rktinoblastoma( Ab)bkfork and aftkr chkmothkrape and thk clinical significanck of thk chkmothkrape kffkct,and to providk thk kvidknck for thk furthkr improvkmknt of thk safkte of trkatmknt. Methods L total of 280 chil-drkn with Ab wkrk knrollkd in thk stude,and kach of thkm was trkatkd with CEV( Carboplatin+Etoposidk+Vincris-tink)mkthods. Thkrk subjkcts includkd 153 malks and 127 fkmalks,with a mkan trkatmknt of 4. 5 ceclks(rangk 2 to 12 ceclks)and a mkan agk of 21. 5 months(rangk 1 to 84 months). Lmong thkm,149 casks wkrk diagnoskd clinicalle,131 casks wkrk diagnoskd pathologicalle. Eight casks wkrk in thk kxtraocular stagk,3 casks wkrk in glaucoma and 269 casks in intraocular pkriod(101 casks of singlk keks and 168 casks of doublk keks). BRN and Scr wkrk dktkctkd bkfork thk first coursk of chkmothkrape and aftkr thk last coursk of chkmothkrape. ResuIts BRN and Scr valuks wkrk analezkd bk-fork and aftkr chkmothkrape. BRN was 3. 05 mmol╱F bkfork chkmothkrape and 3. 46 mmol╱F aftkr chkmothkrape in thk group agkd from 4 months to lkss than 12 months(73 casks),thk valuks of BRN aftkr chkmothkrape was highkr than that bkfork chkmothkrape,and onle in this group thk changk was statisticalle diffkrknt(t﹦ -2. 829,P﹦0. 006),but all BRN valuks in this group wkrk not bkeond thk highkst rkfkrknck valuk(1. 70 mmol╱F-7. 10 mmol╱F). Bkfork initial chkmothkrape,149 patiknts( 53. 2﹪)had Scr bklow thk rkfkrknck rangk( malk:30 -104 μmol╱F,fkmalk:30 -84 μmol╱F),and 20 casks(7. 0﹪)had thk BRN bklow thk rkfkrknck valuk. In 2 casks,BRN(7. 25 mmol╱F and 7. 34 mmol╱F, rkspkctivkle)bkfork thk initial chkmothkrape was slightle highkr than thk normal valuk,but thk valuk was normal(5. 01 mmol╱F and 4. 98 mmol╱F,rkspkctivkle)aftkr thk last chkmothkrape. In onk cask,thk BRN(5. 62 mmol╱F)was normal bkfork thk initial chkmothkrape,but it was klkvatkd(7. 33 mmol╱F)aftkr thk last chkmothkrape. In anothkr onk cask,thk BRN was normal bkfork and aftkr chkmothkrape,but thk valuk aftkr chkmothkrape was 4. 69 timks highkr than that bk-fork chkmothkrape. ConcIusions Aknal function of Ab childrkn bkfork trkatmknt is normal. Skvkn pkrcknt of thksk patiknts havk BRN undkr thk BRN rkfkrknck rangk,and 53. 2﹪ of thksk patiknts havk Scr undkr thk Scr rkfkrknck rangk. It suggkstkd that thk rkfkrknck valuks of BRN and Scr nkkd to bk adjustkd. BRN of infant Ab mae incrkask signifi-cantle aftkr chkmothkrape,but it doks not mkkt thk currknt diagnostic critkria of mild nkphrotoxicite. Still,thk karle rknal damagk nkkds to bk notickd.
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Objective To explore the short-term efficacy in children with head and neck rhabdomyosarcoma (HN-RMS) treated by multidisciplinary therapy,and to analyze the prognostic factors,so as to guide the diagnosis and treatment.Methods Patients with HN-RMS admitted at Hematology Oncology Center of Beijing Children's Hospital (BCH),Capital Medical University between December 2012 and May 2017,were included in this case-observation study.The clinical characteristics were analyzed and the treatment effect and prognostic factors were summarized.Results A total of 48 cases were collected,including 36 boys and 12 girls,with a median age of 4.6 years.Primarysite parameningeal RMS(PM-RMS) (34 cases,70.8％),orbital (2 cases,4.2％) and non-orbital,non-parameningeal region(12 cases,25.0％) were found.Twenty cases belonged to alveolar type(41.7％),and 28 cases were of embryonaltype(58.3％).The diameter of the tumor was ＞5 cm(n =25,52.1％),and ≤5 cm(n =23,47.9％).IRS staging:there were 29 cases(60.4％) of stage Ⅱ-Ⅲ,19 cases (39.6％) of stage Ⅳ;29 cases (60.4％) of low-medium risk,and 19 cases (39.6％) of high risk.Twenty-three patients (47.9％) received surgery,and 25 cases (52.1％) received biopsy only.All patients (48 cases) received systemic chemotherapy.Twenty patients (41.6％) received external radiation,15 cases (31.3％) received 125I particle implantation,6 cases (12.5％) received proton therapy,but 3 cases (6.2％)did not receive radiation.The follow-up time lasted 13-57 months[(24.1 ± 12.3) months].The 2-year overall survival(OS) rate was (66.4 ± 7.2)％,and 2-year event free survival (EFS) rate was (59.9 ± 7.5) ％.Patients with tumor diameter ≤ 5 cm had higher OS and EFS than patients with tumor diameter ＞5 cm [2-year OS (87.4±6.8)％ vs.(42.9 ±6.8)％,2-year EFS (78.8 ±8.6％) vs.(38.5 ±10.8)％],and the differences were statistically significant (all P =0.006).Patients with orbital and non-orbital,non-parameningeal RMS had higher OS and EFS than PM-RMS [2-year OS 100％ vs.(87.5％ ± 11.7) ％ vs.(57.0 ± 8.8) ％;2-year EFS 100％ vs.(88.9 ± 10.5)％ vs.(51.1 ± 8.9)％],and the differences were statistically significant (P =0.008,P =0.030).Patients who received surgery had higher OS and EFS than those who did not received surgery [2-year OS (80.7±8.8)％ vs.(53.3 ± 10.4)％;2-year EFS (71.1 ±10.1)％ vs.(49.5±10.4)％],and the differences were statistically significant (P =0.008,P =0.026).COX regression analysis showed tumor diameter ＞ 5 cm was an adverse prognostic factor (OR =4.124,95％ CI:1.213-14.025,P =0.023).Conclusions PM-RMS accounted for a high proportion in RMS patients.The primary site and the size of the tumor are the main prognostic factors.Intensive therapy is expected to improve the prognosis of HN-RMS with meningeal invasion.
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Objective To explore the feasibility of immunotherapy intermittently with high dose intravenous immunoglobulin(HD-IVIG)impact therapy combined with prednisone on the basis of systematic chemotherapy to control the clonic symptoms of children with neuroblastoma(NB).Methods A retrospective analysis was made based on the clinical data of 8 NB children with combined clonus,who were admitted in Beijing Children's Hospital,Capital Medical University from May 2011 to February 2017.And analysis and summary were also made according to patients' clinical data,neurological symptoms,therapy methods and prognosis.The follow-up visiting was ended on March 1,2017.Results Eight patients were investigated,3 male and 5 female,with onset age ranged from 10.0 to 35.5 months (the median age was 17.5 months),and the period from occurrence of clonic symptoms to a definite diagnosis and starting treatment was 1.25 to 6.50 months (the median time was 3.60 months).All patients developed kinds of neurological syndrome clinically,such as clonus on the trunk and limbs,and 5 cases of them were involved in combined opsoclonus-myoclonus syndrome (OMS).All patients went for their first-time consultancy at the Neurology Department of Beijing Children's Hospital,Capital Medical University or local hospitals.The primary tumor focus was found in unilateral adrenal gland in 2 cases,1 case in bilateral adrenal glands,2 case in retroperitoneal region,2 cases in mediastinum and 1 cases in presacral region.The image examination indicated 1 case with a tumor focus,the diameter of it more than 5 cm.Except for 1 case involved in the local invasion of tumor in vertebral body,the images examination of all other patients showed the focus in the primary location,without visible distant metastasis or no abnormality was seen by head magnetic resonance imaging (MRI) examination.Initially,four cases had normal neuronal specific enolase (NSE) and 4 had higher NSE;one case had higher urine vanillylmandelic acid (VMA) and 7 normal;3 cases had higher urine homovanillic acid(HVA) and 5 normal.Among 8 patients,the pathological pattern of 6 cases was NB,in which 4 cases were of differentiated type and 2 cases of poorly differentiated type;the pathological pattern of 2 cases was ganglion cell NB,in which 1 case was of nodular type and 1 case of mixed type.N-MYC was not amplified.Clinical staging:5 cases of stage Ⅱ and 3 cases of stage Ⅲ.Clinical grouping:7 cases of intermediate risk group and 1 case of low risk group.So far,1 case lost follow-up in that the child didn't receive regular diagnosis and treatment due to economic problem,so significant improvement of clonic symptoms was not seen,all other patients were given the immunotherapy with intermittent HD-IVIG impact therapy and oral administration of prednisone based on systematic chemotherapy:immunoglobulin was applied respectively before,during and after chemotherapy in multiple impact treatments;3 cases received 4 courses of treatment,2 cases received 3 courses of treatment and 2 cases received 2 courses of treatment.Prednisone was given orally during the application of immunoglobulin,from the full dose and with the course of treatment of 1.0 to 5.5 months,3 months on average;then the dose was gradually reduced.With the follow-up up to now,hormone was discontinued in 4 cases and the total course of treatment was 8 to 12 months,10 months on average.One month after the treatment of patients in 4 cases,the clonic symptoms were improved or disappeared in 5 to 12 months;the clonus of patients in 2 cases was improved respectively 3 months after treatment and half a year after drug withdrawal,in which the symptoms of 1 case disappeared completely 1 year after treatment and the slight clonic symptoms of 1 case still existed by the update follow-up.Except for 1 case of patient lost to follow-up,the regular primary tumor focus of all patients indicated that the disease conditions were in a stable state.Conclusions The immunotherapy intermittently applied with HD-IVIG impact therapy in combination with prednisone based on regular systematic chemotherapy can effectively control the clonic symptoms of children with NB.The earlier the intervene treatment for clonic symptoms is recommended,so that the faster recovery of symptoms can be achieved.Early diagnosis and early treatment play a helpful role in the recovery of children with neurological symptoms.
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Objective To summarize the clinical features of neuroblastoma (NB)with N - myc gene amplifi-cation in order to analyze tumor shrinkage and bone marrow remission in the early stage of chemotherapy,and to eva-luate the children's initial sensitivity to chemotherapy. Methods The medical records of 38 patients with N - myc am-plification of NB were reviewed (bone marrow or tumor tissues were positive during fluorescence in situ hybridization probe),who were treated between February 2012 to December 2016 at the Hematology Oncology Center,Beijing Chil-dren's Hospital,Capital Medical University. The regimens included chemotherapy,surgery,stem cell transplantation, radiotherapy,and maintenance treatment. The data were reviewed for the medical history. The variations of biomarker, bone marrow cells and the primary site were analyzed before and after 2 courses of CAV (Cyclophosphamide + Adriamy-cin + Vincristine)regimen chemotherapy,in order to observe the short - term effect of chemotherapy and the results were described with statistics. Results Total 38 cases were studied,22 boys(58. 9％)and 16 girls(42. 1％). The median age was 30 months. The primary sites of 37 cases of tumor were located in the retroperitoneal and adrenal area,1 case located in the posterior mediastinum. Bone marrow cytology was negative in 12 cases of them,but bone marrow biopsy suggested bone marrow metastasis,while bone marrow cytomorpholigic examinations were positive in the other 26 cases. Of all the 37 cases the lactate dehydrogenase (LDH)levels were reported higher than the normal value. LDH level was under 500 U/ L in one case,9 cases above 4000 U/ L. The neuron specific enolase (NSE)level of all the cases was higher than the normal and NSE level in 36 cases was higher than 100 μg/ L. In one patient the diameter of tumor was less than 5 cm,lager than 10 cm in 32 cases. The lesion of 33 tumor cases before chemotherapy by enhanced CT was ≤100 cm3 in 12 cases,> 100 - 500 cm3 in 11 cases,among which 6 cases ranged from 500 - 1000 cm3 ,4 cases larger than 1000 cm3 . All the 38 cases received 2 courses of chemotherapy. LDH levels of 4 cases became normal,and LDH levels fell under 500 U/ L in 18 cases,while LDH levels of the other 3 cases were above 1000 U/ L. Among 38 cases, the NSE level in 6 cases was reduced to normal,and 16 cases reduced to 25 - 100 μg/ L. The bone marrow examination of 36 cases reversed to negative. According to the image examination,the overall response rate after 2 courses of chemo-therapy was 84. 8％ . One case achieved very good partial remission,21 cases achieved partial response,7 cases a-chieved metastatic remission,2 cases had no remission,while 2 cases showed progression. After 2 courses of chemother-apy,the tumor diameter in 7 cases was less than 5 cm,while that of 22 cases was above 10 cm. Conclusions The ma-jority primary site of NB with N - myc gene amplification is located in retroperitoneal and adrenal area. Patients with the huge tumor have a heavy burden and the biomarker is always high at the early stage. NB with N - myc gene amplifica-tion is sensitive to chemotherapy. After 2 courses of chemotherapy,there is a sharp decrease in the level of biomarker and the tumor burden. Chemotherapy can diminish the burden of tumor in early stage. But because of the huge burden and the huge size of tumor,it's not the best time for surgery and stem cell collection. The patients should go on receiving chemotherapy for remission of disease.
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Objective To summarize the clinical data and characteristics of neuroblastoma (NB) with pancreatic infiltration and to assess the clinical features and the prognosis of NB.Methods According to NB protocol at Beijing Children's Hospital,Capital Medical University(BCH-NB-2007),based on Hong Kong NB protocol,the patients were divided into 3 groups of low-risk (LR) group,medium risk (MR) group and high-risk (HR) group.All children were followed up till March 31,2017.Diagnosis of pancreatic infiltration of NB was made by abdominal enhancement of CT,enhanced magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose-positron emission tomography-computed tomography(18F-FDG-PET/CT),any of which could suggest NB pancreatic infiltration or postoperative pathology prompted NB to infiltrate the pancreas.Retrospective summary and analysis of indicators were performed,which included the initial diagnosis of primary tumor and metastatic tumor site,tumor markers,clinical stage,risk group,imaging features and treatment.Results (1) Totally 50 eligible patients were included:27 females,23 males,median age of 33 months (7-129 months),10 cases ≤ 18 months,40 cases ＞ 18 months;3 cases were of International Neuroblastoma Staging System(INSS)-Ⅲ,47 cases of INSS-Ⅳ;2 caes of LR,3 cases of MR,45 cases of HR;28 cases had a fever,27 cases with abdominal mass,14 cases with abdominal pain,9 cases with limb pain,5 cases with vomiting,4 cases with diarrhea,and 1 case with jaundice.Forty-nine cases of primary tumor were located in the retroperitoneal adrenal gland,and 1 case in the pelvic cavity.Thirty-two cases had tumor diameter≥ 10 cm.(2)Tumor markers and imaging features:the median serum lactate dehydrogenase (LDH) value in 50 cases was 669 U/L (263-6 762 U/L),of them 19 cases ＞ 1 000 U/L.A total of 80％ cases had neuron specific enolase (NSE) ＞ 0.15 ng/L.Nine cases had elevated amylase (AMY),and 7 cases had elevated lippase (LPS),and all the levels were elevated in 5 cases.A total of 41 cases had pancreas infiltration by abdominal ultrasound,44 cases had pancreas infiltration by abdominal enhancement computed tomography (CT),100％ (14/14 cases)of pancreas infiltration was confirmed by abdominal reconstruction enhancement nuclear imaging MRI,and NB pancreas infiltration was proved in 41.3％ (19/46 cases) by 18F-FDG-PET/CT.Comparison of the above 4 imaging studies:one imaging examination index was positive in 7 cases,accounting for 14.0％,2 positive in 26 cases,accounting for 52.0％,3 positive in 15 cases,accounting for 30.0％,and 4 positive in 2 cases,accounting for 4.0％.(3) Treatment outcomes:totally 50 cases received treatment,including 2 cases of LR,all cases were of INSS-Ⅲ,and 1 case with complete remission (CR).Three cases of MR belonging to INSS-Ⅳ had complete resection of the tumor,1 case had recurrence and died,and the other two were stable.Forty-five cases with HR,median follow-up lasting for 15 (4-53) months,16 cases had occurrence (35.6％),3 cases were relapsed after stopping treatment for 2,3,18 months,respectively;tumor progressed in 12 patients during treatment,and 1 case got severe intracranial infection and gave up treatment before death.Kaplan-Meier analysis showed the expected 3-year event free survival(EFS) rate was 22.1％,and 3-year overall survival(OS) rate was 38.5％.Conclusions Preliminary results show that 90％ with pancreatic infiltration of NB belong to Ⅳ HR group of children,and almost primary tumor is almost located in the retroperitoneal ragion.NB with pancreatic infiltration clinical manifestations is hidden and nonspecific.More than half of the children have no obvious abdominal pain or vomiting,and so imaging examination is needed to determine the situation of pancreatic metastasis further.Abdominal reconstruction enhancement MRI has a high sensitivity and specificity for pancreatic metastatic lesions,which can be used as the basis for early diagnosis.The overall prognosis is poor.The expected 3-year EFS rate can be 22.1％,3-year OS rate was 38.5％.
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Objective To explore the significance of 18 F-fluorodeoxyglucose positronemission tomography/ computed tomography (18F-FDG PET/CT) scanning for childhood neuroblastoma clinical staging.Methods From December 2014 to December 2015,59 patients confirmed as NB in Beijing Children's Hospital,Capital Medical University,and finding or clinical features were selected by histopathology.Those patients underwent 18 F-FDG PET/CT,bone scan,cranial magnetic resonance image (MRI),bone marrow puncture (two sites) and biopsy,regional CT,ultrasound,serum tumor markers like lactic dehydrogenase and neuronspecific enolase.In comparison of 18F-FDG PET/CT image findings with other detective methods,the differences were analyzed between the primary sites and metastasis were analyzed.Results (1) General features:Out of 59 children with NB,31 were males,28 were females.Primary lesions were as follows:14 cases located in the postmediastinum,44 cases in the retroperitoneum (1 case in retroperitoneum + postmediastinum),1 case in left neck.International Neuroblastoma Staging System Ⅰ to Ⅳ:O,1,9 and 49 cases,respectively.(2)18F-FDG PET-CT manifestations:The maximum of standardized uptake value (SUVmax):before-treatment group was (2.34 ± 1.06) which was larger than the post-surgery group value of (1.08 ± 0.50),and the difference was significant(F =5.699,P =0.000);bone marrow metastasis ranged from 1.5 to 2.9,regional lymphatic metastasis ranged from 1.0 to 2.1.(3)18F-FDG PET-CT imaging compared with other detection:in bone metastases,the whole body bone scan finding were normal in 3 cases,while PET/CT showed disseminated bone and bone marrow involvement and bone scanning showed 2 cases had metastases,combined with 18 F-FDG PET/CT,which were considered as postoperative inflammatory reaction or residual tumor tissues invade adjacent intervertebral foramen.Bone cytology was positive in 30 cases,while PET/CT showed 34 patients with bone marrow metastasis,and 1 case was suspicious.In central metastasis,1 case of PET/CT showed epidural metastasis,while cranial MRI was negative;Cranial MRI showed 9 cases had skull metastasis,1 case had orbital metastasis,1 case had meningeal metastases;while 18F-FDG PET/CT showed no abnormality.All children had no parenchymal metastasis.Corresponding tumor markers as LDH was related to the maximum value of primary tumor focal SUVmax (rs =0.581,P ＜ 0.01).Conclusions 18 F-FDG PET/CT can fully display the distribution of primary sites and metastases,and can be served as medical imaging evidence for both the diagnosis and staging of neuroblastoma.But as for cranial bone and central metastasis,it has high false negative rate.Clinical practice should be combined with cranial MRI to improve relevance ratio.