Review of thoracic neuroblastoma

Twenty-seven cases of thoracic neuroblastoma were reviewed. Thirteen cases (48%) survived, 11 for more than 2 years and two for more than 14 months. Surgery is the treatment of choice and complete excision appears to give the best result. However, radical surgery is discouraged if the tumour is not readily removable. The use of chemotherapy and radiotherapy should be limited to Stage III and Stage IV disease and for palliation of soft tissue and bony secondaries. The clinical presentation was generally non-specific with respect to the final diagnosis in this series. Significantly raised catecholamines were seen in 13 of 16 patients assessed (81%). Prognosis was related to the age at diagnosis, stage of disease and the histological type. The better prognosis seen in thoracic neuroblastoma in comparison with abdominal neuroblastoma may be related to the earlier presentation of the disease and the higher incidence of better differentiated tumours in the thorax. There appears to be an unknown additional factor that confers a better prognosis in patients under 1 year old.     

N-myc oncogene and urinary catecholamines in children with neuroblastoma

This paper reports the analysis of N-myc amplification, urinary vanillylmandelic acid (VMA), and norepinephrine (NE) excretion and survival in 22 children with neuroblastoma and 7 with ganglio-neuroblastoma. Five patients had N-myc amplification (from 30 to more than 200 copies), all of whom had advanced-stage disease. The urinary excretion of VMA was normal in all of them, only one showed increased NE excretion. All patients with stage C-D disease and one copy of N-myc had increased VMA urinary excretion and increased (9/14) or normal (5/14) NE urinary excretion. All patients with stage A or B disease had one copy of N-myc. Half of them showed increased VMA urinary levels, while only 3/10 showed increased NE urinary values. Comparison of cumulative survival curves in relation to N-myc amplification and to VMA and NE urinary excretion showed a clear parallelism. Amplification of N-myc corresponded to normal VMA and NE urinary excretion, and was associated with the worst prognosis (P < 0.01), while increased VMA and/or NE excretion was found in patients with only one copy of N-myc. © 1993 Wiley-Liss, Inc.     

Neuroblastomas treated at the four major child oncologic clinics in Denmark 1943–1980: An evaluation of 180 cases

One hundred and eighty cases of neuro-blastomas from the four child oncology clinics are reviewed. The overall cure rate was 24%. During the 38-year period, there was a significant increase in survival from 0% during the period of 1943–1950 to 32% during the period of 1971–1980. This improved survival rate is most likely a result of adjuvant chemotherapy. Forty percent of the patients appear chronically ill, which reflects the fact that nearly 60% have metastases when they are first seen. In localized disease (stages I–II), the prognosis was favourable (cure rate 69%), while the prognosis for disseminated disease (stage III–IV) was poor (cure rate 5%). A favourable outcome was seen in patients under 1 year (survival rate 46%), and in patients with primary tumours located in the neck or mediastinum (survival rate 48%). When related to stage, however, the survival rates for the former tumours were not significantly better in patients below 1 year or in patients with cervical or thoracic tumours. As is the case in other studies, we found that survival is significantly poorer in males.     

儿童神经母细胞瘤化疗前后免疫功能指标分析

目的观察神经母细胞瘤（neuroblastoma,NB）患儿化疗前后免疫功能指标的变化,并探讨其,临床意义,为进行NB化疗的免疫调节和支持治疗提供依据。方法选择我院自2007年1月至2009年2月收治的NB患儿,分别检测血清中免疫球蛋白（IgG、IgA、IgM、IgE）和血液中细胞免疫,包括总T淋巴细胞（TTL,CD3＋,CD19-）,T辅助淋巴细胞（THL,CD3＋,CD4＋）,T抑制淋巴细胞（TSL,CD3＋,CD8＋）、NK细胞（CD3-,CD16＋／CD56＋）百分比及辅助／抑制T细胞（CD4＋／CD8＋）比率。结果患儿化疗前体液免疫水平基本正常,细胞免疫功能低于正常。化疗后体液免疫IgG、IgA、IgM、IgE均较化疗前降低。细胞免疫中,TTL、CD4＋／CD8＋较化疗前下降,而THL、TSL、NK细胞较化疗前升高。有统计学差异（P〈0．05）。结论联合化疗会造成NB患儿体液及细胞免疫功能紊乱,监测T细胞亚群水平及Ig系列对评估患者细胞及体液免疫功能,以及应用免疫调节和支持治疗,以减少化疗后感染机会,提高生活质量有积极的意义。     

Age-related profile of neuroblastoma: A comparison of tumors detected by mass-screening with those detected clinically

Infants with neuroblastoma are known to have a favorable prognosis compared to those over 1 year of age. However, there is little biological information about the age-related heterogeneity of neuroblastoma. We evaluated the biological profile comparing cases detected by mass screening with those detected clinically. A total of 238 patients with neuroblastoma were classified into four groups according to their age at diagnosis. Patients in group A were 0–5 months of age (n = 31). Patients in group B were detected clinically and were 6–11 months of age (n = 25). Patients in group C were 6–11 months of age and were detected by mass-screening (n = 97). Patients in group D were more than 12 months of age (n = 85). The age-related heterogeneity was evaluated by Kaplan-Meier survival analysis, several clinical markers (neuron specific enolase, ferritin, vanillylmandelic acid and homovanillic acid) at diagnosis, tumor Ha-ras p21 expression and tumor N-myc amplification. Infant neuroblastoma had unique features in comparison to neuroblastoma diagnosed over 12 months of age. Clinical outcome of the patients in groups A and C was quite favorable. Even patients with stage III or IV disease in group A had a favorable prognosis. However, stage IVs disease in group A was not necessarily associated with a good prognosis and the early death after diagnosis was also characteristic. The biological profile of tumors in group C was similar to that in group A but different from the profile in groups B and D. Tumors in group B had a biological profile intermediate between groups A and D. Cases detected by mass screening (group C) provided a new clinical entity with a good prognosis. The difference in biological profiles might affect their clinical outcome of respective age group. These analyses confirm the significance of prognostic markers and may help to direct an appropriate modality of treatment for the individual patient.     

Allelic loss of chromosome 1 and additional chromosome 17 material are both unfavourable prognostic markers in neuroblastoma

In neuroblastoma, N-myc amplification and loss of heterozygosity for the short arm of chromosome 1 (LOH 1p) are common genetic abnormalities. We have recently shown that the presence of additional material of the long arm of chromosome 17 (add.17q) also occurs relatively frequently. In the present study, we analyzed a series of 55 tumors for LOH 1p, N-myc amplification and add.17q, using Southern blot analysis with polymorphic DNA probes of pairs of tumor and constitutional DNA. We determined the correlation of these parameters with clinical variables, such as age, stage, serum lactate dehydrogenase (LDH) and ferritin and also with outcome. LOH 1p occurred in 20 out of 55 cases (36%) and was found more often in stage III/IV tumors and in the older age group, although both correlations were not statistically significant. N-myc amplification was only demonstrated in 12 tumors with concomitant LOH 1p and was not present in the 35 cases without LOH 1p. Add.17q was found in 20/53 (38%) informative cases. LOH 1p was shown to be the most significant predictor of a poor outcome (P < 0.00001), independent of age and stage. LOH 1p is also of prognostic value in those cases without N-myc amplification, indicating a stronger prognostic value for LOH 1p. Add.17q was also associated with an unfavourable prognosis, although this was less significantly then with LOH 1p (P = 0.00004). © 1995 Wi1ey-Liss Inc.     

Trends of survival in neuroblastoma and independent risk factors for survival at a single institution

To assess the progress of survival in neuroblastoma which varies with many risk factors and to evaluate the influence of these factors on survival as independent risk factors. The study subjects were 159 neuroblastoma patients seen from 1965–1994 at the oldest and largest children's hospital in Japan. Trends of survival in three treatment eras 1965–81, 1982–86, 1987–94 were assessed by the Kaplan-Meier method for different sex, age at diagnosis, the clinical stage, the site of onset, and the histological type. Then the influence on survival of these factors as independent prognostic variables was evaluated by the Cox proportional hazards regression analysis. Age at diagnosis, the clinical stage, the site of onset, the histological type, and the treatment era were independent risk factors in the order of their influence on survival. Unfavorable survival outcomes were obtained for patients with age at diagnosis above 1 year, the clinical stage of VI by the Evans classification, adrenal onset, and neuroblastoma rather than ganglioneuroblastoma. Survival improved from the first to the second and from the second to the third treatment era. Improvement of survival in neuroblastoma took place during the past 3 decades. Age at diagnosis, the clinical stage, and the histological type have still remained overwhelming prognostic factors over the progress in treatment. Med. Pediatr. Oncol. 29:197–205, 1997. © 1997 Wiley-Liss, Inc.     

Incidence of bacteremias and invasive mycoses in children with high risk neuroblastoma

BACKGROUND: Information on the incidence of infectious complications during for treatment for high risk neuroblastoma (HR-NB) is limited. Bacteremias and invasive mycoses may be considered surrogate markers of the infection burden. PATIENTS AND METHODS: Data on bacteremias and invasive mycoses occurring during 3 consecutive protocols for front line (NB-89; NB-92; NB-97) or salvage therapy (TVD) for HR-NB were reviewed. The cumulative risk of developing a first episode and the rate of infections during the entire length of each protocol were evaluated. RESULTS: Front line protocols were given to 80 patients for a total of 22,070 days at risk; salvage treatment was given to 24 children for 2,909 days at risk. During front line therapy 41 infectious episodes were diagnosed in 29 (36%) patients, for a 45% cumulative risk and an infection rate (IR) of 0.19/100 patient-days-at risk. Salvage therapy determined five infectious episodes in four (17%) patients, with a 39% cumulative risk, and an IR of 0.17. The IR during the phase of high dose chemotherapy with hematopoietic stem cell rescue (megatherapy) included in the three front line protocols decreased over time (1.54 in NB-89; 0.52 in NB-92 and 0.0 in NB 97; P = 0.001), possibly because of the use of less aggressive conditioning regimens, without radiotherapy. CONCLUSIONS: The IRs of protocols for HR-NB did not change over time. The megatherapy-related phases are those at highest risk.     

The evaluation of induction chemotherapy regimens for high-risk neuroblastoma in South African children*

Abstract

Achieving remission after induction therapy in high-risk neuroblastoma (HR-NB) is of significant prognostic importance. This study investigated remission after induction-chemotherapy using three standard neuroblastoma protocols in the South African (SA) setting. Retrospective data of 261 patients with HR-NB diagnosed between January 2000 and December 2016, who completed induction chemotherapy with standard treatment protocols were evaluated. The treatment protocols were either OPEC/OJEC or the St Jude NB84 protocol (NB84) or rapid COJEC (rCOJEC). The postinduction metastatic complete remission (mCR) rate, 2-year overall survival (OS) and 2-year event free survival (EFS) were determined as comparative denominators. The majority (48.3%; n?=?126) received OPEC/OJEC, while 70 patients received (26.8%) rCOJEC and 65 (24.9%) NB84. Treatment with NB84 had the best mCR rate (36.9%), followed by OPEC/OJEC (32.5%) and rCOJEC (21.4%). The 2-year OS of treatment with NB84 was 41% compared to OPEC/OJEC (35%) and rCOJEC (24%) (p?=?0.010). The 2-year EFS of treatment with NB84 was 37% compared to OPEC/OJEC (35%) and rCOJEC (18%) (p?=?0.008). OPEC/OJEC had the least treatment-related deaths (1.6%) compared to rCOJEC (7.1%) and NB84 (7.5%) (p?=?0.037). On multivariate analysis LDH (p?=?0.023), ferritin (p?=?0.002) and INSS stage (p?=?0.006) were identified as significant prognostic factors for OS. The induction chemotherapy was not significant for OS (p?=?0.18), but significant for EFS (p?=?0.08) Treatment with NB84 achieved better mCR, OS and EFS, while OPEC/OJEC had the least treatment-related deaths. In resource-constrained settings, OPEC/OJEC is advised as induction chemotherapy in HR-NB due to less toxicity as reflected in less treatment-related deaths.     

Secondary central nervous system metastases in children with neuroblastoma

Cerebral and meningeal involvement in patients with primary extracranial neuroblastoma (NB) is unusual although it is generally present in disseminated disease. The intensification of chemotherapy that has prolonged survival in these children has changed the pattern of relapse presentation, as occurs with isolated central nervous system (CNS) disease. We report 4 patients with secondary CNS metastases. Three infants of 16, 14, and 10 months of age, diagnosed with primary abdominal NB stage 4, presented neuromeningeal metastases during maintenance chemotherapy with seizures and cranial hypertension as the first manifestation. Another 8-year-old patient diagnosed with NB stage 3 presented local relapse with later neuromeningeal metastases. All died in the following 3 months. The possibility of CNS relapse in patients with NB should be considered when neurological symptoms and signs appear. These new relapse forms overshadow the prognosis of these children. © 1996 Wiley-Liss, Inc.     

Treatment of stage III neuroblastoma with emphasis on intensive induction chemotherapy: A report from the neuroblastoma group of the spanish society of pediatric oncology

From October 87 to April 92, 172 children were admitted in the N-I-87 protocol of the Spanish Society of Pediatric Oncology for the diagnosis and treatment of neuroblastoma. Forty-eight were considered Evans stage III, 33 of them being older than 1 year. All children were treated with induction chemotherapy (IC) and surgery. IC consisted of three courses of high-dose cisplatin-VM-26 alternating with three further courses of cyclophosphamide-doxorubicin (CAD). Infants less than 1 year received the same drugs at lower doses. After surgery, maintenance chemotherapy was administered to all children during 14 months. It consisted of four pairs of drugs rotated every 4 weeks. Radiotherapy was administered exclusively to patients older than 1 year with residual tumor after IC and surgery. Response was evaluated after IC and surgery. In children older than 1 year, response was obtained in 28/33 (88%). Fifteen of them (47%) achieved complete remission (CR), seven (22%) good partial response (GPR), six (19%) partial response (PR); and in three patients (9%) there was progressive disease (PD). Actuarial survival at 48 months was 0.60 ± 0.10 and EFS was 0.61 ± 0.12. Audiologic impairment was considered the worst toxicity. In children less than 1 year the response rate to IC and surgery was 93% (14/15); nine infants obtained complete response and four had GPR. Only one patient experienced PD in the first 6 months of therapy and died. The other 14 are alive and well at a mean follow-up time of 48 months. Chemotherapy toxicity was mild and reversible. © 1995 Wiley-Liss, Inc.     

Critical observations on neuroblastoma treatment with 131-I-metaiodobenzylguanidine at diagnosis

Results of treatment with 131-I-Metaiodobenzylguanidine (131-I-MIBG) in patients with resistant neuroblastoma appear encouraging if one considers that most of the patients had far advanced, intensively pre-treated disease. To further explore the potential role of this new drug in untreated patients, we treated 3 children with stage III neuroblastoma. All three of our cases received 131-I-MIBG at relatively low dose with the complete disappearance of the tumor mass in case 1, whereas in cases 2 and 3 CT scan showed a significant reduction of the tumor mass and, interestingly enough, no evidence of 131-I-MIBG uptake of a tracer dose in the remaining tumor. Particularly, in case 2, the persistence and subsequent progression of part of the tumor mass without 131-I-MIBG uptake after a therapeutic dose of 131-I-MIBG, which apparently destroyed the 131-I-MIBG-positive cell population, clearly suggest heterogeneity at diagnosis, with a dual neuroblastoma cell population, one with 131-I-MIBG uptake and the other without. Besides the biological implications of the 131-I-MIBG uptake heterogeneity in neuroblastoma at diagnosis, our findings suggest that in stage III neuroblastoma patients even a relatively small dose of 131-I-MIBG administered at diagnosis is sufficient to destroy either the primary tumor completely (case 1) or the part of the tumor (case 2 and 3) which shows 131-I-MIBG uptake, without any significant hematologic toxicity. Furthermore, a single course of 131-I-MIBG at the dosage employed does not appear to jeopardize the subsequent use of chemotherapy. In conclusion, if our data are confirmed by further investigation, 131-I-MIBG may be included as a front line drug shortly followed by chemotherapy in future treatment strategies of advanced neuroblastoma without or with minimal bone marrow infiltration. © 1993 Wiley-Liss, Inc.