Management in Health, Vol 16, No 1 (2012)

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NEUROBLASTOMA IN ROMANIA, WHERE WE STAND AND WHAT

NEUROBLASTOMA IN ROMANIA, WHERE WE STAND AND WHAT

SHOULD WE DO

 

POPOIU M. C.1, DAVID V.L.2, BOERIU E.1, POPOIU A.V.1, ARGHIRESCU S1, VLADESCU C.3, CHIRIAC N.D.3, MUSAT I.3, BOIA E.S.1

 

 

1 University of Medicine and Pharmacy Victor Babes Timisoara, Romania

 

2 Emergency Childrens Hospital Louis Turcanu Timisoara, Romania

 

3 National School of Public Health, Management and Professional Development, Bucharest, Romania

 

ABSTRACT:

BACKGROUND: Neuroblastoma (NB) is the most common solid extra-cranial malignancy of childhood and is responsible for approximately 15% of all pediatric cancer deaths.

AIM: The purpose of this report is to provide and analyze specific epidemiologic data regarding the frequency, demographics, age and stage of the disease at diagnostic, treatment methods and outcomes of the treatment of NB in Romania over a 3 years period.

MATERIAL AND METHODS: In this purpose, we inquired the database of the National School of Public Health, Management and Professional Development using specific principal diagnosis codes, for NB tumors.

RESULTS: 623 cases with NB were reported in Romania in a 3 years period (2007-2009). The sex ratio of M: F 1.1: 1. In the majority of the cases (67%), the tumor origin was the adrenal gland. Only in 31 patients a surgical procedure was recorded.

CONCLUSIONS: NB is an aggressive tumor with high incidence in the 1-6 years age group and with equal sex distribution. Currently there is a high rate of hospital admission/ patient with a median hospital stay of 5 days. Only in approximately 10% of the patients, the tumor is resected, meaning a complete cure of the disease. We consider that the current medical system for diagnosis and treatment of NB must be improved and, is our believe the way for this is to concentrate the resources in fewer but more specialized medical centers for diagnosis and treatment of NB.

 

Keywords: neuroblastoma, epidemiology, treatment methods, outcomes

 

 

BACKGROUND

Neuroblastoma (NB) is an embryonal tumor of the sympathetic nervous system with origin in the primordial neural crest cells (1). NB is the most common solid extracranial malignancy of childhood (1). In the United States its incidence is 1/ 100,000 children and represents 7% to 10% of all malignancies diagnosed in pediatric patients younger than 15 years of age (2). NB is responsible for approximately 15% of all pediatric cancer deaths (2). In approximately 40% of cases, the diagnostic is made by age 1 year, 75% by 7 years, and 98% by 10 years (3). Nearly half of newly diagnosed NB occurs between ages 1 and 4 years (4). In the majority of cases (75%), the tumor is located in the retroperitoneum, in either the adrenal medulla (50%) or the paraspinal ganglia (25%). In 20% of cases, the primary tumor is in the posterior mediastinum. Less than 5% of tumors are located in the neck or pelvis or intracranial (5). NB exhibits extreme heterogeneity and is stratified into three risk categories, low, intermediate and high, considering age, tumor biology and staging of the disease (6). The staging system is based on clinical and pathologic criteria and an international NB staging system was adopted since 1993 (7). The treatment of the disease is a combined modality of surgery, chemotherapy, and radiotherapy based on disease stage and patient age at presentation. Low and intermediate risk NBs are successfully treated in the majority of the cases by a combination of the three therapeutic methods. High-risk NB remains a therapeutic challenge even in United States. The survival rate is 90% for low-risk cases, 75% for intermediate-risk cases, and 25% for high-risk cases (5). Overall, there is a 50% survival at 3 years.

Until now, there is no systematic report regarding the epidemiology of NB in Romania. The purpose of this report is to provide and analyze specific epidemiologic data regarding the frequency, demographics, age and stage of the disease at diagnostic, treatment methods and outcomes of the treatment of NB in Romania over a 3 years period. The purpose of our study is also, to assess the treatment results, and to establish other parameters like the gender ratio, age related NB repartition, county repartition, the location of the tumor and the type of surgical procedures applied and to optimize child care with NB.

 

MATERIAL AND METHODS

We inquired the database of the National School of Public Health, Management and Professional Development, using specific diagnosis codes, recorded as principal diagnosis at discharge, for malignant tumors having the following localizations: adrenal medulla, adrenal cortex, posterior mediastinum, peripheral nervous system and autonomous nervous system, nonspecific malignant tumor of the adrenal gland, adrenal gland tumors with unpredictable evolution. The ICD10-ICD10 AM for principal diagnosis were: C38.2, C47.8-9, C74.0,.1.9

We reviewed the abstract charts of NB patients in 2007-2009 periods. The analysis then followed the subsequent parameters: number of cases, number of admission for each patient, age, gender and hospital stays period/each patient, surgical or medical procedures.

 

RESULTS

623 cases having NB were reported in Romania (Table 1) in a 3 years period (2007-2009). The sex ratio M: F was 1.1: 1. In the majority of the cases (67%), the tumor origin was the adrenal gland (Table 2). Only in 31 patients a surgical procedure was recorded (Table 3).

 

Tabelul nr. 1. Numărul de pacienţi, sex şi grupa de vrstă. Sursa datelor: baza de date DRGNaţional.

 

 

Pacienţi

Externaţi

Feminin

Masculin

Vrsta (ani)

< 1

1- 6

7- 14

15-18

2007

89

213

87

126

0

108

87

8

2008

84

207

108

99

6

127

57

17

2009

84

203

74

109

8

133

56

6

 

 

Tabelul nr. 2. Frecvenţa cazurilor de NB, după localizarea tumorii. Sursa datelor: baza de date DRGNaţional.

 

Localizare

2007

2008

2009

Tumora malignă a mediastinului posterior

24

27

34

Tumora malignă a sitemului nervos periferic şi sistemului nervos autonom

16

13

6

Tumoră malignă care depăşeşte sistemul nervos periferic şi sistemul nervos autonom

34

25

17

Tumoră malignă medulosuprarenală

23

9

43

Tumoră malignă corticosuprarenală

5

10

3

Tumoră malignă nespecifică a glandei suprarenale

109

117

85

Tumoră malignă a glandei suprarenale cu evoluţie imprevizibilă

2

6

7

Total

213

207

203

 

 

 

Tabelul nr. 3. Procedurile chirurgicale efectuate cazurilor care au NB. Sursa datelor: baza de date DRGNaţional.

 

 

 

Proceduri chirurgicale

2007

2008

2009

Excizia unilaterală a glandei suprarenale

1

3

1

Excizia tumorii neuroendocrine retroperitoneale

1

5

2

Excizia tumorii neuroendocrine retroperitoneale cu disecţie retroperitoneală

2

 

 

Excizia tumorii glandei suprarenale

4

 

 

Excizia neuroblastomului intraabdominal

2

1

1

Excizia neuroblastomului intratoracic

 

2

 

Excizia tumorii mediastinale

 

2

3

Toracotomia

 

 

1

Total

10

13

8

 

 

DISCUSSIONS

To our knowledge, there is no systematic and comprehensive statistical report regarding the epidemiology of NB in Romania in the past decades. Before any attempt to improve the quality of the treatment, we should have first a clear image about the epidemiology of the disease, about the status of the treatment. Our data indicated a mean of 85 new cases of NB each year. The total number of children between 0 and 15 years of age in Romania is approximately 3.3 million (8). This means that the incidence of NB in Romania is approximately 3/ 100000 children, 3 times higher than in US (2). It is not the intention of this paper to analyze the causes leading to such a high incidence of this particular malignancy in children, but to stimulate the medical community for further research in this area.

Compared with other countries, especially US (2) the incidence of NB is three times higher in our country (3/ 100000). The survival rate is less than 22% in our country compared with the western countries where the overall survival rate is more than 50% (5). These differences could indicate a low capacity of the Romanian health system to manage such complex diseases. From the high number of hospital inpatient cases (about 200/year) for NB, only 10% results in surgical intervention with curative purpose. One can speculate that the remaining 12% of the survivals are treated outside Romania.

Without having any consistent data, nowadays a common situation is represented by NB patients treated in other EU countries. This could mean that the medical care for NB in Romanian hospitals should be much improved. The underlying cause for these results is the pediatric medical assistance. There is need for improving the diagnosis and staging system on one hand and, on the other hand, the sequence and the methods of treatment need to be standardized.

The low number of cases in low risk category revealed by our study reflects a poor detection of pathology rather than a different pattern of malign conditions.

An important issue highlighted by our study is that there is no recorded data over the results of the pathological exam, the staging of the tumor or the therapy methods (bone marrow transplantation and specific chemotherapy). The current system of patient level data collection and coding does not include specific coding for the staging of the tumor, neither data on the type of chemotherapy.

The lack of data makes impossible a detailed study and might indicate the need for a national register for tumors,

eventually with subsections for solid tumors in children. This register should collect specific data of each patient and may be the base for extensive clinical studies with huge impact on the results of the treatment. Although, the balance between the costs implied by the development of such a registry and the economic and social benefit induced by a nationwide evidence of the patients with NB should be carefully considered.

We propose as solution for improvement a more judiciously repartition of the cases in 2-3 major centers from Romania, with excellent medical expertise, resources, experience and good possibilities for treatment. In this way, the resources are not scattered, facts that correspond with EU policies to create poles of excellence in certain domains.

 

 

CONCLUSIONS

NB is an aggressive tumor with high incidence in the 1-6 years age group and with equal sex distribution. Currently there is a high rate of hospital admission/ patient with a median hospital stay of 5 days. Only in approximately 10% of the patients, the tumor is resected, meaning a complete cure of the disease. In order to cover the need for treatment, the current medical system for diagnosis and treatment of NB must be improved and, it is our believe the way for this is to concentrate the resources in fewer but more specialized medical centers for diagnosis and treatment of NB. In these centers the latest biomolecular, genetic, imagistic diagnosis methods may combined with the modern medical and surgical therapy, according to the international practice guidelines. In addition, the creation of a national register for tumors with specific subsection for solid tumors in children could lead to better outcome, through early diagnostics, good need assessment, better planning of services, better monitoring of the cases. Finally, all of these would improve the well-being of the little patients with malignancies.

 

 

References

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BRODEUR, G.M.-Neuroblastoma: Biological insights into a clinical enigma. Nat Rev Cancer;3:203-216, 2003,

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BRODEUR, G.M., PRITCHARD, J., BERTHOLD, F., et al.-Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment., J Clin Oncol;11:146677, 1993,

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