Time trends of cancer incidence in childhood in Campania region: 25 years of observation

Background Childhood cancer is relatively uncommon and the European age-standardized rate was 164 new case per million per year among children 0 to 14 years of age (95 % CI 158-170). Aims of our study are to evaluate the cases of these malignant diseases observed between 0 and 15 years of age in the Campania region between 1990 and 2014, the ration between observed and expected cases by disease and province of residence. Also we studied the percentage of extra-regional migration over the time by disease and province of residence. Methods In this study we reported the patients with malignant disease observed in 25 years (1990–2014) based on the specialized registry, the Mod. 1.01 of the AIEOP (Association Italian Pediatric Hematology-Oncology). The size of the monitored population also allowed us to systematically examine five time trends: 1990–94: 1995–99; 2000–04; 2005–09; and 2010–14. Results Between 1990 and 2014 a total of 3655 malignant neoplasms were reported: Napoli province (2059 cases), Salerno province (625), Caserta province (589), Avellino province (229), and Benevento province (153). Epidemiological data suggested that about 4100 cases could be expected in Campania region during the same period. The overall ratio between observed (O) and expected (E) numbers of cases in the five periods considered rose gradually from 0.69 in the first period to 0.76, then 0.82, 0.91, and 0.94, in the other periods considered. The extra-regional migration involved 1029 cases (28.1 %), showing a reduction from 33.7 % of the first period to 20.3 % of the last period considered. Considering single province of residence we observed the lowest rate of migration in Napoli and Caserta province, whereas higher levels were observed in the other provinces. For all provinces, except Salerno, the extra-regional migration declined significantly over time. Conclusions The present findings showed an increase over time of O/E ratio, probably due to improvement in the organization of centers and greater trust of families in local centers. It is possible to further improve the efficiency of healthcare system of Campania region and migration can be reduced with a more rational use of hospitals throughout region.


Background
Childhood cancer is relatively uncommon and actually the European age-standardized rate was about 164 new case per million per year among children 0 to 14 years of age (95 % CI 158-170) [1,2]. Between 1988 and 2008 a total of 5,709 malignant neoplasms were reported in children aged 0-14 years. Incidence rates in children for all malignant cancer peaked in 1997 (211 cases/million boys and 175 cases/million girls per year), followed by a decline, non statistically significant [1,2]. Instead, the annual incidence rate in adolescents (15-19 years) was 269 per million (95 % CI 256-283) [3,4]. The ranking of cancer types as defined by the ICCC-3 (International Classification for Childhood Cancer) classification shows that leukemias are the most frequent neoplasms (33 % of all malignant cancers), followed by lymphomas (16 %), malignant tumours of Central Nervous System (CNS) (13 %), which increase to 18 % when including non-malignant tumours), followed by neoplasms of the peripheral nervous system (8 %), and the soft tissue cancers (7 %). The remaining neoplasms, more rare, account for no more than 5 % each and 23 % altogether [5,6]. Aims of our study are to evaluate the incidence of these malignant diseases observed between 0 and 15 years of age in the Campania region, the ration between observed and expected cases by disease and province of residence. Also we studied the percentage of extra-regional migration over the time by disease and province of residence. A minor objective was to evaluate an eventually increase of incidence of cancer in Napoli and Caserta provinces, called "Ground of fires", from involuntuary exposure to environmental pollutants. However, it is worth remembering that a correlation between pollution and cancer requires several types of evidence and a systematic approach following well-defined criteria and methods that make it a specialized activity.

Methods
For this report we selected all cancer cases diagnosed in the 0-15 years age group. The age specific rates were computed dividing the number of newly diagnosed cases in a period in this group of age of population by the corresponding population in the same period. The rates defines the mean number of diagnoses in one year and is referred to 1,000,000 subjects of the specific age group. The European age-standardized rate was 164 new cases per million children per year (95 % CI 158-170) [5] In this study we reported the number of patients with malignant disease diagnosed before their 15th birthday and observed in 25 years , based on the specialized registry, the Mod. 1.01 of the AIEOP (Association Italian Pediatric Hematology-Oncology). This centralized archive, called Model (Mod.) 1.01, has been in use since 01.01.1989 and records essential standardized information on all cases of childhood cancer for ages 0-19 years, diagnosed and/or treated in the AIEOP centers. For this reason we started our analysis since 1990. We recognize the limits of the Mod. 1.01 as a potential cancer registry. An study was estimated for the period 1989-1998, as a total and by tumour type, comparing the recruitment vs the expected numbers based on the incidence rates measured by the Childhood Cancer Registry of Piedmont. Results showed good correspondence [7]. Actually the AIEOP database to include in Italy about the 90 % of children aged 0-15 years affected by cancer. The size of the monitored population also allowed us to systematically

Global analysis
During the study period 3655 cancer patients aged 0-15 years old were registered in the AIEOP database, 2036 males (55.7 %) and 1619 females (44.2 %). Epidemiological data suggest that about 4.100 cases in Campania Region and 37,000 cases in Italy could be expected during the same period. Table 1 shows all cases registered by diagnosis and   Table 4 shows the O/E ratios in the five diagnostic periods considered. The overall O/E ratio rose gradually from the first period to the last period considered, with the exception of Benevento province. This improvement was statistically significant for Napoli and Caserta provinces, as trend across diagnostic periods. In the Caserta and Salerno provinces the O/E ratio was particularly high (>1) in the last 5-year time.

Extra-regional migration by period of observation and type of disease
Analyzing the 3655 cases who were diagnosed in the period 1990-2014, extra-regional migration involved 1029 (28.1 %) cases. Table 5 shows the global extraregional migration for all cases, by disease. Table 6 shows in detail the variation in the five diagnostic periods considered of all malignat neoplasms observed. The analysis over time proves a progressive improvement for more frequent pediatric neoplasms. In detail, we observed for acute/hybrid lymphoblastic leukemias a progressive reduction of extra-regional migration from 18.5 % of the first period examined to 10.1 % of the last 5-year time (2010-2014), as for acute non lymphoblastic leukemia from 38.4 % to 12.2 %, Also, we observed a very good reduction of migration over time for lymphomas, neuroblastoma and kidney cancer, with a reduction from  Different is the problem related to the retinoblastoma, probably due to the more specific diagnostic and therapeutic approach. In fact, we observed a progressive extra-regional migration over time from a 12.5 % of the period 1990-1994 to 100 % of the 2010-2014 (Table 6). Table 5 shows the extra-regional migration of the patients by province of residence. In Table 7 was evident the reduction of migration over time in the five provinces of Campania region even if with different results.

Extra-regional migration by province of residence
Better results were registered for Napoli and Caserta whereas in the last 5-year time considered in the other three provinces more cases opted for the diagnosis and/ or treatment in centers of a different region: Salerno (36.7 %); Avellino (26.6 %), and Benevento (25.9 %).

Discussion
The present findings update descriptive cancer epidemiology in children (0-15 years) in Campania in the period 1990-2014 (25 years of observation) based on data provided by specialized clinical Mod.1.01 from AIEOP centers. The cases of cancer expected in Campania in this period, calculated using the last AIRTUM's site-specific incidence rates by age group (0-15 years), were about 4,100 cases (11.5 %), of which 29.7 % were leukemias, 14.5 % were lymphomas, 20.4 % were CNS tumours, and 35.4 % were solid neoplasms non CNS. These percentages bring about a number of expected cases per year of 51 cases of leukemia, 25 cases of lymphoma, 35 cases of  These results probably are due to substantial improvements in non-invasive diagnostic techniques but also to better collaboration between pediatric and neurosurgery oncologists. These data were calculated using the Italian Network of Cancer Registries (AIRTUM) that includes 32 general cancer registries and five specialized which two dedicated to childhood (0-14 years), including about 4,000,000 of children. According to the province of residence in Campania in our study the overall O/E ratio rose gradually from the first time to last 5-year time and in 2010-2014 this ratio was particularly high (>1) for cancer observed in province of Caserta and Salerno. Conversely, the lowest O/E ratios were seen in province of Benevento. The analysis of extra-regional migration shows a progressive improvement of reduction over time, particularly for emo-lymphoproliferative diseases, neuroblastoma, and kidney cancer (under 20 % in the last period). Actually, there is still a relevant elective migration (more of 30 %) for CNS tumours, Ewing/PNET sarcomas, liver and rare tumours. This situation is motivated by organizational shortcomings which have created a historically rooted distrust toward health centers in their home region. This is particularly true for retinoblastoma were the rarity of neoplasm and specific local diagnostic and therapeutic approach makes migration toward another region obligatory. Our data are according to AIRTUM registry where the extra-regional migration of Campania Better results (20.3 %) were registered in our region in the last period considered [5,6]. The evaluation of migration by province of residence describes a progressive reduction over time in the different provinces even if the better results were registered for Napoli and Caserta. Minor results have been registered for Benevento and Avellino, while the lowest rate of reduction was observed in Salerno with a decrease of 9 % at last period respect to the percentage of the first period 1990-1994. In a 2005 Censis study on the reason behind patient migration, two third of respondents declared their primary reason was search for quality, the desire to make use of higher quality hospital facilities and medical personnel [5]. These reasons explain the importance to make a Network Campania of Pediatric Oncology (NETCOP) in order to do more efficacy the collaboration between the regional centers of pediatric oncology (Hub centers) and pediatric hospitals present in the five province of Campania region (Spoke centers). In the next future other problem is the recruitment of immigrant children that underwent a progressive, steady increase over the years, growing from 30 cases (2 % of the total number) in 1999 to 130 cases (8 % of the total number) in 2008 [8][9][10]. Actually, AIEOP centers in Campania treated 2.4 % of immigrant children [5].

Conclusions
The present findings update descriptive cancer epidemiology in children (0-15 years old) in Campania based on data provided by specialized clinical Mod.1.01 from AIEOP centers and showed an increase over time of O/E ratio, probably due to improvement in the organization of centers and greater trust of families in local centers. Findings derived from this analysis suggest that it is possible to further improve the efficiency of healthcare system of Campania region and migration, problem actually still relevant for the specific cancers that can be reduced with a more rational use of hospitals throughout region.