Adolescent- and adult-onset neuroblastic tumor: A retrospective multicenter observational study of patients diagnosed in France between 2000 and 2020.

BACKGROUND: Adult- and adolescent-onset neuroblastomas are rare, with no established therapy. In addition, rare pheochromocytomas may harbor neuroblastic components. This study was designed to collect epidemiological, diagnostic and therapeutic data in order to better define the characteristics of malignant peripheral neuroblastic tumors (MPNT) and composite pheochromocytomas (CP) with MPNT. PROCEDURE: Fifty-nine adults and adolescents (aged over 15 years) diagnosed with a peripheral or composite neuroblastic tumor, who were treated in one of 17 institutions between 2000 and 2020, were retrospectively studied. RESULTS: Eighteen patients with neuroblastoma (NB) or ganglioneuroblastoma (GNB) had locoregional disease, and 28 patients had metastatic stage 4 NB. Among the 13 patients with CP, 12 had locoregional disease. Fifty-eight percent of the population were adolescents and young adults under 24 years of age. The probability of 5-year event-free survival (EFS) was 40% (confidence interval: 27%-53%). CONCLUSIONS: Outcomes were better for patients with localized tumor than for patients with metastases. For patients with localized tumor, in terms of survival, surgical treatment was the best therapeutic option. Multimodal treatment with chemotherapy, surgery, radiotherapy, and immunotherapy-based maintenance allowed long-term survival for some patients. Adolescent- and adult-onset neuroblastoma appeared to have specific characteristics associated with poorer outcomes compared to pediatric neuroblastoma. Nevertheless, complete disease control improved survival. The presence of a neuroblastic component in pheochromocytoma should be considered when making therapeutic management decisions. The development of specific tools/resources (Tumor Referral Board, Registry, biology, and trials with new agents or strategies) may help to improve outcomes for patients.

Image-defined risk factor assessment of neurogenic tumors after neoadjuvant chemotherapy is useful for predicting intra-operative risk factors and the completeness of resection.

BACKGROUND: Patients with neuroblastoma are now stratified at diagnosis according to the presence and number of image-defined risk factors (IDRFs). We examined the added value of IDRF assessment after neoadjuvant chemotherapy for predicting surgical resection. MATERIAL AND METHODS: From 2009-2012, 39 out of 91 patients operated on in our institution for neuroblastic tumors received neoadjuvant chemotherapy based on ongoing SIOPEN protocols or treatment guidelines. IDRFs were assessed both at diagnosis and preoperatively on CT and/or MRI. RESULTS: Median age at diagnosis was 30 months [range 2-191]. The tumor locations were adrenal (n = 20), paravertebral (n = 13) and perivascular (n = 6). INRGSS stages were L2 (n = 13), M (n = 25) and Ms (n = 1). Eleven tumors (28%) were MYCN-amplified. Chemotherapy reduced the number of IDRFs in 54% of patients overall (21/39): 61.5% (16/26) of M and Ms patients, and 38.5% (5/13) of non metastatic patients (P < 0.001). The number of IDRFs lost after chemotherapy was proportional to the degree of tumor shrinkage (P = 0.002), independent of the primary tumor location (P = 0.73), although the number was higher in patients with left versus right adrenal locations (P = 0.004). Patients with neuroblastoma on post-surgical histology lost more IDRFs (median: 1[0-9]) than patients with ganglioneuroblastoma (median: 0[0-4]) (P < 0.001). The completeness of resection was related only to the number of preoperative IDRFs (P = 0.028). CONCLUSION: IDRF assessment after neoadjuvant chemotherapy is useful for predicting completeness of resection of neurogenic tumors. A larger international study is needed to confirm these results and to explore a possible correlation between preoperative IDRF status and survival.

Divergent Patterns of Incidence in Peripheral Neuroblastic Tumors.

BACKGROUND: Prior research on trends in neuroblastoma incidence has conflicted. We aimed to compare how ganglioneuroblastoma and neuroblastoma incidence have changed. PROCEDURE: Using the Surveillance Epidemiology and End Results (SEER) 9 population-based registry, we identified 2081 malignant peripheral neuroblastic tumors in patients 0 to 14 years from 1973 to 2009. Age-adjusted annual incidence rates were calculated using SEER*Stat, and Joinpoint Regression Program was used to calculate annual percent change (APC) and analyze trends. Data were stratified by histology, age, and stage. RESULTS: Overall peripheral neuroblastic tumor incidence increased by an APC of 0.47 (P=0.045). However, ganglioneuroblastoma incidence decreased (APC=-1.48; P=0.003), whereas neuroblastoma incidence increased (APC=0.79; P=0.008). When divided by age and stage, locoregional neuroblastoma incidence increased in infants until a significant inflection point in 1996 (APC=4.19; P<0.001) and then decreased sharply (APC=-6.80; P=0.160). CONCLUSIONS: Ganglioneuroblastoma incidence has decreased, whereas neuroblastoma incidence has increased. These changes could be real, or reflect bias from classification changes or increased detection. Neuroblastoma incidence increased most markedly in infants with locoregional disease only until 1996, then declined, which may reflect changes in tumor ascertainment and folate supplementation.

Temporal clustering of neuroblastic tumours in children and young adults from Northern England.

BACKGROUND: The aetiology of neuroblastic tumours is unclear with both genetic and environmental factors implicated. The possibility that an infectious agent may be involved has been suggested. 'Temporal clustering' occurs if cases display an irregular temporal distribution and may indicate the involvement of an agent that exhibits epidemicity. We tested for the presence and nature of temporal clustering using population-based data from northern England. METHODS: We extracted all cases of neuroblastic tumours diagnosed in children and young adults aged 0-24 years during 1968-2011 from the Northern Region Young Persons' Malignant Disease Registry. This is a population-based registry, covering a population of approximately 900,000 young persons, and includes all cases resident in northern England at the time of diagnosis. Tests for temporal clustering were applied using a modified version of the Potthoff-Whittinghill method. Estimates of extra-Poisson variation (ß) and standard errors (SEs) were obtained. RESULTS: 227 cases of neuroblastic tumours were diagnosed during the study period. All the analyses between fortnights and between months found significant extra-Poisson variation, with ß = 0.846 (SE = 0.310, P = 0.004) for the analysis between fortnights within months. Restricting the analyses to the 76 cases diagnosed at ages less than 18 months showed significant extra-Poisson variation between fortnights within months (ß = 1.532, SE = 0.866, P = 0.038), but not between months. In contrast, analyses of cases aged 18 months to 24 years showed significant extra-Poisson variation between quarters within years, as well as over shorter timescales. CONCLUSIONS: Transient environmental agents may be involved in the aetiology of neuroblastic tumours. The initiating factor might be a geographically-widespread agent that occurs in 'mini-epidemics'.

Epidemiology of neuroblastoma: analysis of a single institution.

BACKGROUND: Neuroblastoma is the fourth most frequent cancer among all pediatric neoplasms Epidemiological studies may shed more light on the disease and aid in improving treatment of patients with neuroblastoma. PATIENTS AND METHODS: Epidemiology data are presented for 333 children with neuroblastoma or ganglioneuroblastoma and 11 children with ganglioneuroma who were treated at the Institute of Mother and Child in Warsaw, Poland, from 1962 to 1996. RESULTS: Analysis of the stage of the disease, age, sex and survival of children with neuroblastoma demonstrated comparable distribution of good and intermediate stages versus the stages with a poor prognosis. CONCLUSION: Comprehensive analysis of epidemiological data on the stage of cancer, age, sex and survival in patients with neuroblastoma provides a basis for better prognosis of the disease and cost-efficient treatment.

[Kinsbourne syndrome: review of our cases]. / Síndrome de Kinsbourne: revisión de nuestra casuística.

INTRODUCTION: The childhood opsoclonus-myoclonus or Kinsbourne syndrome, is a uncommon process, of acute or subacute beginning, which affects infant and children. It's course is characterized by opsoclonus, polimyoclonias and cerebellar ataxia. The disease is frequently associated to neuroblastoma (46%). MATERIAL AND METHODS: We present a retrospective study on 9 patients, emphasizing the clinical presentation and the evolution aspects. RESULTS AND CONCLUSIONS: We found changes in the EEG in three cases. Most surprising is the scarce incidence of neuroblastoma, which has been found only in a one out of nine patients. We found three cases with relapse during the treatment or on withdrawal and one of them relapsed twice again. The evolution has been variable, since 5/9 patient have presented some type of mild or moderate neuro-psychological sequelae. Out of three patient with relapses, two presented permanent neurological sequelae. A patient which suffered three relapses, is also the one which presents more serious sequelae.

[Improved survival in children with neuroblastoma]. / Forbedret overlevelse hos børn med neuroblastom.

INTRODUCTION: The aims of the present study were to analyze whether changes in incidence and mortality rates have taken place in Denmark during the period 1981-2005, and whether the distribution of known prognostic factors has changed during this period. MATERIAL AND METHODS: A total of 206 children below 15 years of age with neuroblastoma or ganglioneuroblastoma who were diagnosed in Denmark between 1981 and 2005. RESULTS: The incidence was 8.68 per million children below 15 years of age (world standard 9.6) and 43.5 per million children below 12 months of age and these incidences have remained unchanged since 1970. The mortality rate has decreased steadily during the study period. The prognostic factors age, stage and site of primary tumour did not change during the study period and were not different from those reported by others. 32% of the children were below 12 months of age at diagnosis. 53% of the children had metastatic disease. The overall 5-year survival increased over the study period from 38% in 1981-1985 to 69% in 2001-2005. A significant increase in the survival of children > 12 months of age with stage 4 disease was also observed. Relapse/disease progression more than three years from diagnosis occurred in only 2% of patients. The median time from relapse to death was three months. CONCLUSION: The survival of children with neuroblastoma in Denmark has increased significantly over the last 25 years.

Renal and adrenal tumours in children.

The differential diagnosis of renal and supra-renal masses firstly depends on the age of the child. Neuroblastoma (NBL) may be seen antenatally or in the newborn period; this tumour has a good prognosis unlike NBL seen in older children (particularly NBL in those aged 2-4 years). Benign renal masses predominate in early infancy but beyond the first year of life Wilms' tumour is the most common renal malignancy, until adolescence when renal cell carcinoma has similar or increased frequency as children get older. Adrenal adenomas and carcinomas also occur in childhood; these tumours are indistinguishable on imaging but criteria for the diagnosis of adrenal carcinoma include size larger than 5 cm, a tendency to invade the inferior vena cava and to metastasise. The most topical dilemmas in the radiological assessment of renal and adrenal tumours are presented. Topics covered include a proposed revision to the staging of NBL, the problems inherent in distinguishing nephrogenic rests from Wilms' tumour and the current recently altered approach regarding small lung nodules in children with Wilms' tumour.

Neuroblastoma: changing incidence and survival in young people aged 0-24 years. A report from the North of England Young Persons' Malignant Disease Registry.

BACKGROUND AND PROCEDURE: Population based data for neuroblastoma in children and young adults under 25 years at diagnosis were ascertained from the Northern Region Young Persons' Malignant Disease Registry for the period 1968-1995. Age-standardised incidence rates were calculated (ASR) and changes in incidence and survival were investigated. Over the study period 144 patients were registered, of these 136 were children under 15 years at diagnosis (median age: 2.2 years, ASR: 8.6 cases per million children per year), and 8 were 15-24 years (ASR 0.6). RESULTS AND CONCLUSIONS: Incidence of childhood neuroblastoma in the North of England increased significantly over time; ASRs were 5.8 for 1968-1981 and 9.5 for 1982-1995 (rate ratio: 1.6, 95%; CI 1.2-2.3). The increase in incidence was seen in both infants and older children, and in both low stage and advanced disease. Overall 5 year survival was 15% for 1968-1981 and 40% for 1982-1995 (P < 0.0001). Significant improvements in survival were documented across different stage and age-groups, including those over 1 with stage 4 disease (0% versus 18%, P < 0.0001). Further research is needed to investigate the reasons for the increasing incidence of neuroblastoma.

Incidence and mortality of neuroblastoma in Canada compared with other childhood cancers.

The incidence and mortality of neuroblastoma was reviewed in the general context of childhood cancer in Canada for the periods 1982-86 and 1987-91. This was done to complement the preliminary work of the Quebec Neuroblastoma Screening Project that is studying the impact of screening North American infants for the preclinical detection of neuroblastoma on population-based mortality. Annual age-standardized incidence rates for all childhood cancer in Canada appear to have declined slightly (nonsignificantly) from 155.1 to 150.8 per million, between 1982-86 and 1987-91; the rates for neuroblastoma were stable between the two five-year periods (11.8 per million in 1982-86 and 11.4 per million in 1987-91). With respect to mortality, the age-standardized rates for childhood cancer in Canada have shown a declining trend between the first and second halves of the decade, from 43.4 to 34.7 per million, while the rates for neuroblastoma have not changed (4.4 and 4.2 per million). The age-specific distributions of incident cancers indicate that neuroblastoma accounts for the greatest proportion of all cancers in children less than one year of age. Similarly, neuroblastoma is the leading cause of cancer deaths in children aged one to four years. Theoretically, infants less than one year of age could benefit most from effective preventive interventions, treatment, and research.

[Histopathologic differentiation of tumors derived from neuroblastic cells in children depending on age]. / Zróznicowanie histologiczne guzów grupy neuroblastoma u dzieci w zaleznosci od wieku.

The histopathology of 224 tumours of neuroblastic origin was analysed in relation to the age of patients. Maturing neuroblastomas (NBS) dominated in infants, where as in the most numerous group of children 1-5 years of age, prevalence of neuroblastomas without any signs of maturation was noted. In children over 5 years of age a high incidence of tumours with evident maturation was noted (ganglioneuroblastomas and ganglioneuromas). The prevalence of maturing neuroblastomas in infants correlate well with an advantageous clinical course of neuroblastomas at this age.

Observation of untreated patients with neuroblastoma detected by mass screening: a "wait and see" pilot study.

BACKGROUND: Recent studies have indicated that mass screening for neuroblastoma detects tumors that otherwise would have regressed spontaneously without recognition. Therefore, we started an observation program for these patients to determine how frequently spontaneous regression occurs. PROCEDURE: Eighteen patients were detected by mass screening between June 1994 and December 1996. Eight of these cases matched the following criteria and entered the observation program: Stage I or II, less than 5 cm in diameter; no involvement of large vessels or organs; not difficult to resect; informed consent. If there were an increase in tumor size, an elevation of tumor markers, or evidence of metastasis, the tumor would be immediately resected. RESULTS: Five of the eight cases showed spontaneous regression. Although the remaining three tumors were resected 6-10 months after diagnosis, all patients survived without evidence of recurrence. CONCLUSIONS: At least 60% of neuroblastoma cases who entered our observation program regressed spontaneously.