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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 evaluate the short-term efficacy and perioperative safety of catheter-based intervention in patients with pulmonary vein stenosis caused by fibrosing mediastinitis (FM). Methods: It was a case series study. Consecutive patients with pulmonary vein stenosis caused by FM, who underwent percutaneous pulmonary vein angioplasty in Gansu Provincial Hospital from January 2018 to June 2020, were retrospective enrolled. The baseline characteristics, comorbidities, exercise capacity and hemodynamic data before and after treatment were compared, and the procedural related complications were evaluated. Results: A total of 30 patients ((64.3±7.1) years, 15 males) were included. Sixty-three pulmonary vein stenosis were treated by 32 percutaneous pulmonary vein angioplasty procedures. Forty-four stents were implanted in 41 pulmonary veins after balloon angioplasty, and the diameter of implanted stents was (8.3±1.2)mm. Balloon angioplasty was performed on 22 pulmonary vein stenosis, the mean balloon diameter was (4.2±2.1)mm. The pulmonary vein diameter increased from (2.6±1.3) to (6.6±2.6) mm (P<0.001) and the pressure gradient across the pulmonary vein stenotic segment reduced from 19 (12, 29) to 2 (0, 4) mmHg (1 mmHg=0.133 kPa) (P<0.001) immediately post procedure. The pulmonary vein flow grade was significantly improved compared with baseline (P<0.001). The most common operation related complications were lung injury (44.0% (11/25)) and hemoptysis (18.8% (6/32)), which did not need special treatment. During the 2.0 (1.3, 3.2) months follow-up, the WHO functional class was significantly improved (P<0.05), the 6-minute walking distance increased from (254.8±114.5) m to (342.8±72.4)m (P<0.05), the mean pulmonary arterial pressure decreased from (40.9±8.3) mmHg to (35.4±7.7) mmHg (P<0.01), 17 out of 19 patients with refractory pleural effusion experienced total remission during the follow-up period (P<0.001). CT pulmonary venography was repeated in 17 patients. The incidence of in-stent restenosis of pulmonary vein was 24.0% (6/25). Conclusions: Percutaneous pulmonary vein angioplasty is effective for the treatment of pulmonary vein stenosis caused by fibrosing mediastinitis. However, it's not so safe, procedural related complication should be paid attention to and the rate of in-stent restenosis is relative high during the short-term follow-up.
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Humans , Male , Angioplasty, Balloon , Catheters , Mediastinitis , Retrospective Studies , Sclerosis , Stenosis, Pulmonary Vein , Stents , Treatment OutcomeABSTRACT
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 analyze the clinical characteristics and prognosis of infants with rhabdomyosarcoma (RMS), thus enhancing the understanding of this disease.Methods:Clinical data of all RMS patients younger than 12 months treated in the Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from May 2006 to June 2019 were retrospectively analyzed, including the age, gender, histological type, tumor primary site, tumor size, and the prognosis.Patients were followed up until December 31, 2019.The 3-year event free survival (EFS) rate of children was performed by plotting the Kaplan-Meier survival curves.Results:A total of 15 RMS children younger than 12 months were enrolled, accounting for 4.9% of all RMS cases in the same period, including 6 males and 9 females.The median age at diagnosis was 7.0 months (3.0-11.5 months). Classified by the primary site, 40.0% (6 cases) located in the head and neck, followed by 26.7% (4 cases) located in the limbs, 26.7% (4 cases) located in other parts, and 6.7% (1 case) located in the urogenital system.Embryonal RMS, alveolar RMS and spindle cell RMS accounted for 46.6% (7 cases), 26.7% (4 cases), and 26.7% (4 cases), respectively.Ten cases (66.7%) were stage Intergroup Rhabdomyosarcoma Study (IRS)-Ⅲ and 1 case (6.7%) was in stage Ⅳ.There were 10 cases (66.6%) in the middle-risk group, 4 cases (26.7%) in the low-risk group, and 1 case (6.7%) in the high-risk group.Two cases had a larger than 5 cm primary tumor; lymph node involvement was confirmed in 3 cases, and pulmonary metastasis occurred in 1 case at the time of diagnosis.All children were treated with chemotherapy, and 13 cases received postoperative chemotherapy and 1 case received preoperative chemotherapy.One case were not operated.Only 3 children underwent radiotherapy, including 1 case underwent particle implantation and 2 cases received external radiotherapy.Among the 15 children with RMS, 5 cases had relapse and disease progression with the 3-year EFS rate of (59.1±14.5)%, and 2 died with the 3-year overall survival rate of (80.8±12.6)%.Conclusions:The median age of diagnosis of RMS in single-center infants is 7 months.Head and neck are the most common primary sites of RMS.Nearly 50% of the children have the primary site of RMS with poor prognosis.More than a quarter of the pathological subtypes are the spindle cell type.Local treatment significantly influences the local progression or recurrence of RMS.
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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 analyze the clinical features and prognosis of pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and further understand these tumors.Methods:Twenty-nine NRSTS children were admitted to the Hematological Oncology Ward of Beijing Children′s Hospital from June 2011 to May 2018.The clinical and pathological data of these children were collected, and the relationships of the prognosis with clinical characteristics Intergroup Rhabdomyosarcoma Study(IRS) stage, Children′s Oncology Group(COG) risk grouping were analyzed.All the patients were followed up until October 31, 2018.The survival analysis was performed by Kaplan-Meier method.Results:There were 14 boys and 15 girls in the enrolled 29 children, aging from 7 to 169 months, with a median age of 59.5 months.There were 10 pathological types, including synovial sarcoma, infantile fibrosarcoma and malignant rhabdomyoid tumors in 5 cases, and other pathological types in 14 cases.Tumors originated from the head and neck in 10 cases, limbs or trunk in 6 cases, visceral sites in 13 cases.Ten cases showed distant metastasis.There were 12 cases at IRS stage Ⅰand Ⅱ, and 17 cases of stage Ⅲ and Ⅳ.All the children were treated with surgery and chemotherapy with or without radiotherapy.Nine cases received preoperative chemotherapy, 17 cases received postoperative chemotherapy, 3 cases could not be resected surgically.The follow-up period ranged from 4 to 89 months, with a median follow-up of 16 months.Six of 29 children died, including 3 cases of malignant rhabdomyoid sarcoma.The 2-year overall survival(OS) rate of all the children was 77.4% and the 2-year event-free survival (EFS) rate of all the children was 53.2%.By analyzing the clinical factors, it was found that the IRS stage, COG risk group, primary sites were related to prognosis.The 2-year EFS rate of children with IRS Ⅰ-Ⅱ and Ⅲ-Ⅳ were 75.0% and 35.9%, respectively ( χ2=7.303, P=0.007), the 2-year OS rate was 100% and 61.8%, respectively( χ2=4.81, P=0.028); The 2-year EFS of children in COG low-risk group and median/high-risk group were 66.7% and 44.7%, respectively( χ2=4.155, P=0.042), the 2-year OS rate of children in COG low and median/high-risk was 100% and 66.3%, respectively( χ2=3.383, P=0.066); the 2-year OS rate of children in visceral and non-visceral sites were 59.3% and 92.9%, respectively ( χ2=4.202, P=0.04). Conclusions:NRSTS in children is heterogeneous, and surgery is the main treatment. Children with primary tumors located in visceral sites and at IRS Ⅲ-Ⅳ had poor outcomes.
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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 analyze the clinical characteristics of newly treated high-risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors.@*Methods@#The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high-risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children′s Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors.@*Results@#The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow-up time was 36 months (1 day-138 months) , and the 5-years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5-years OS between radiotherapy group and non-radiotherapy group (42.3% vs. 38.3%, χ2=3.671, P=0.055). The 5-years OS in transplantation group was significantly better than the non-transplantation group (44.3% vs. 35.5%, χ2=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5-years OS rate than the non-radiotherapy combined transplantation group (45.8% vs. 37.3%, χ2=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥ 1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high-risk NB patients (χ2=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high-risk NB patients by Cox regression models (HR=1.896,1.100, 95%CI: 1.113-3.231, 1.020-1.187, both P<0.05).@*Conclusions@#The prognosis is unfavorable in high-risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high-risk NB patients with bone marrow metastasis.
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Objective@#To summarize the clinical characteristics, treatment response and prognostic factors of rhabdomyosarcoma (RMS) in children.@*Methods@#The clinical characteristics such as age at diagnosis, primary tumor site, tumor size, pathological type, clinical stage, and risk grouping of 213 RMS patients (140 males and 73 females) treated in Hematology Oncology Center of Beijing Children′s Hospital, Capital Medical University, from May 2006 to June 2018 were analyzed retrospectively. The clinical characteristics, overall survival (OS), event free survival (EFS) and prognostic factors of children treated with the Beijing Children′s Hospital-Rhabdomyosarcoma (BCH-RMS) regimen were analyzed. Survival data were analyzed by Kaplan-Meier survival analysis, and single factor analysis was performed by Log-Rank test.@*Results@#The diagnostic age of 213 cases was 48.0 months (ranged 3.0-187.5 months), of which 136 cases (63.8%) were younger than 10 years old. The head and neck region was the most common primary site of tumor (30%, 64 cases), followed by the genitourinary tract (26.8%, 57 cases). Among pathological subtypes, embryonal RMS accounted for 71.4% (152 cases), while alveolar RMS and anaplastic RMS accounted for only 26.8% (57 cases) and 1.9% (4 cases), respectively. According to the Intergroup Rhabdomyosarcoma Study Group (IRS), IRS-Ⅲ and Ⅳ accounted for 85.0% (181 cases) of all RMS patients. In all patients, 9.4% (20 cases) patients were divided in to low-risk group, 52.1% (111 cases) patients in to intermediate -risk group, 25.8% (55 cases) patients in to high-risk group, and 12.7% (27 cases) patients in to the central nervous system invasion group, respectively. All patients with RMS received chemotherapy. The cycles of chemotherapy were 13.5 (ranged 5.0-18.0) for patients without event occurrence, while 14.2 (ranged 3.0-30.0) for patients with event occurrence. Among the 213 patients, 200 patients had surgical operation, of whom 103 patients underwent surgery before chemotherapy and 97 patients at the end of chemotherapy, 21 patients had secondary surgical resection. Radiotherapy was performed in 114 patients. The follow-up time was 23.0 months (ranged 0.5-151.0 months) . There were 98 patients with relapsed or progressed disease and 67 patients with death. The median time to progression was 10 months, of which 67 (68.4%) relapse occurred within 1 year and no recurrence occurred after follow-up for more than 5 years. The 3-year EFS and 5-year EFS were (52±4) % and (48±4) %, while the 3-year OS and 5-year OS were (65±4) % and (64±4) % by survival analysis. The 5-year OS of the low-risk, intermediate-risk, the high-risk were 100%, (74±5) %, (48±8) %, and the 2-year OS of the central nervous system invasion group was (36±11) % (χ2=33.52, P<0.01). The 5-year EFS of the low-risk, intermediate-risk, the high-risk were (93±6) %, (51±5) %, (36±7) % and the 2-year EFS of the central nervous system invasion group was (31±10) % (χ2=24.73, P<0.01) . Survival factor analysis suggested that the OS of children was correlated with age(χ2=4.16, P=0.038), tumor TNM stage (χ2=22.02, P=0.001), IRS group (χ2=4.49, P<0.01) and the risk group (χ2=33.52, P<0.01).@*Conclusions@#This study showed that the median age of newly diagnosed RMS patients was 4 years. The head and neck and the genitourinary tract were the most common primary origin of RMS. The OS was low in single-center RMS children. The median time to recurrence was 10 months, and recurrence was rare 3 years later.
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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 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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<p><b>Background</b>The pro-inflammatory cytokine, interleukin-6 (IL-6), stimulates the metastasis of several neoplasms. An association of its serum level and the single nucleotide polymorphism (SNP) rs1800795 with neuroblastoma (NB) has been reported in American and Italian cohorts. This study was to clarify whether the same association exists in Chinese children.</p><p><b>Methods</b>A total of 130 NB patients, with 77 boys (59%), 53 girls (41%), mean age 41 ± 5 months, were assigned to two groups: high risk (HR) versus intermediate-low risk (non-HR), and 50 healthy children were randomly selected as the age- and gender-matched controls. Peripheral blood samples were analyzed to determine serum IL-6 level using enzyme linked immunosorbent assay and rs1800795 SNPs phenotype using polymerase chain reaction and gene sequencing.</p><p><b>Results</b>There were 87 NB patients in the HR group and 43 NB patients in the non-HR group. A comparison of allele and genotype frequencies of the rs1800795 polymorphism between patients and controls found no association with NB risk (P > 0.05). The frequency of GG+GC genotype was higher in HR-NB patients than in non-HR-NB patients (64.4% vs. 48.8%, P = 0.02), and serum IL-6 level was much higher in HR-NB patients with GG+GC genotype than in HR-NB patients with CC genotype (4.36 ± 1.1 pg/ml vs. 1.83 ± 0.5 pg/ml; P = 0.02), but not in Non-HR-NB patients.</p><p><b>Conclusions</b>The polymorphism rs1800795 is associated with serum IL-6 level and level of NB risk. GG genotype might indicate that the tumor is highly malignant (prone to metastasis) and associated with poor prognosis.</p>
Subject(s)
Child, Preschool , Female , Humans , Male , Asian People , Genetic Predisposition to Disease , Genetics , Genotype , Interleukin-6 , Blood , Genetics , Neuroblastoma , Blood , Genetics , Polymorphism, Single Nucleotide , Genetics , Promoter Regions, Genetic , GeneticsABSTRACT
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.
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Childhood malignant solid tumors exhibit a wide variety of vagueness signs and symptoms in the early stage,which are usually nonspecific,therefore the diagnosis of childhood malignant solid tumor can be challenging when the disease is in the early stage.As a result,the delay of diagnosis causes mistreatment,and which makes childhood malignant solid tumors become a leading cause of death in children.Physicians should recognize the early warning signs of childhood cancer,and a good clinical history and careful physical examination can help physicians determine whether the children have cancer and make referrals in time.Some children with possible cancers require immediate initial treatment before referral to be stabilized in order to make the referrals possible and increase the chance of receiving appropriate treatment in time and the possibility of being cured,saving more children with malignant solid tumors to the maximum extent.
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Proteolysis-targeting chimeras (PROTACs) are small-molecule protein degraders based on the ubiquitin-proteasome system. Recently, the development of specific small-molecule ligands for several E3 ligases (CRL4CRBN, CRL2VHL and cIAP) have significantly advanced the PROTACs technology. Several PROTACs against various oncogenic proteins including bromodomain-containing protein 4 (BRD4), estrogen receptor (ER) and androgen receptor (AR) have been developed and considered a novel approach for therapy of cancers. There are advantages of the new technology over the traditional small-molecule strategies. This review article provides a summary on the recent progress in the small-molecule-based PROTACs as antitumor drugs, and the challenges of this technology.
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<p><b>OBJECTIVE</b>To study the application of three-dimensional reconstruction technique based on CT-MRI fusion in skull base surgery.</p><p><b>METHODS</b>To acquire the thin layer CT scan and MRI scanned images, to achieve image registration, fusion, segmentation and 3D visualization by using self-preparation software, to operate, observe and measure models by using methods of endoscopic observation, volume rendering segmentation, automatically and manually measure.</p><p><b>RESULTS</b>The center of the eye and foramen magnum in CT-MRI were used as point registration. Good coincidence of important anatomic landmarks were formed in the image fusion. The boundary of spotted graphical was clear and complete. The models showed a complete, continuous, smooth surface. Virtual endoscopy could display the inside three-dimensional structures of skull from nasal with fluent operations of rotation and transparency. The boundary of skull stump segmented after volume rendering segmentation was clear and smooth, and it could show bone signs and soft tissue models together. Cooperation of automatic measurement method [(32.007 ± 15.311) mm] and the manual measurement method [(30.240 ± 15.169) mm] for measuring the maximum diameters of the tumor model, the difference was significant (t = 8.409, P < 0.05).</p><p><b>CONCLUSIONS</b>The method of selecting the center of the eye and foramen magnum in point matching is scientific, simple and easy to operate. The models reconstructed based on CT-MRI fusion images can accurately reflect the size of the soft tissue and be better measured through the automatic measurement. Reconstruction models can be observed through the way of virtual endoscopic within the nasal cavity or volume rendering segmentation from outside to inside to frustrate the relationship of skull structures. Three-dimensional reconstruction techniques based on CT-MRI fusion in skull base surgery can be used to plan surgical approach, to assess the risk of surgery and to achieve space measurements, and it laid the foundation for the three-dimensional navigation.</p>