Survival rates and extra-regional migration patterns of children and adolescents with cancer in Italy: The 30-year experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP) with the Italian hospital-based registry of pediatric cancer (Mod. 1.01).

Since the 1970s, Italian pediatric oncologists have collaborated through the Italian Association for Pediatric Hematology Oncology (AIEOP) network using a common centralized system for the registration of childhood cancer, known as Model 1.01 (Mod. 1.01). In this study, we report on recruitment trends, extra-regional migration and changes in outcome over time in the Italian population of children (0-14 years) and adolescents (15-19 years) registered and treated within the national AIEOP network in the period between 1989 and 2017. In almost 30 years, a cohort of 43,564 patients with a neoplasia diagnosis was registered in Mod. 1.01. The analysis of national extra-regional migration showed that patients tend to migrate from the South to the North and, to a lesser extent, to the Center of the country. During the study period, migration apparently decreased, especially for lymphohematopoietic diseases, whereas it remained substantial for solid tumors. Our data showed a progressive and significant increase in the cumulative survival 5 years after diagnosis since the 1990s, reaching almost 84% for all patients diagnosed in the last decade. Survival rates of Mod. 1.01 patients are similar to those provided by the main national and international reports showing childhood cancer surveillance estimates. The AIEOP Mod 1.01 has proved to be an invaluable tool from both an epidemiological and a health policy point of view, allowing us, in this study, to examine the survival experience of the largest cohort of Italian pediatric cancer patients with a very long follow-up.

An application of the Toronto Childhood Cancer Stage Guidelines in three population-based cancer registries: The case of central nervous tumors.

BACKGROUND: Cancer stage is a determinant of survival of childhood central nervous system (CNS) cancers and could help the interpretation of survival variability among countries. Consensus guidelines to stage childhood malignancies in population cancer registries ("Toronto Childhood Cancer Stage Guidelines") have been recently proposed with the goal of data comparability. Indeed, stage is not systematically recorded in all registries and, when it is, different classification systems are used. We applied the Toronto Childhood Cancer Stage Guidelines to CNS cancer cases of three population-based cancer registries with the aim of evaluating the feasibility of staging this type of cancer and the critical points in the classification of CNS tumors. PROCEDURES: The Toronto Childhood Cancer Stage Guidelines were applied to 175 CNS patients, diagnosed from January 1, 2002 to December 31, 2014 in three cancer registries in Italy, and the percentage of cases that could be staged was assessed. RESULTS: One hundred eight of 126 (86%) medulloblastomas and other embryonal CNS cancers and 22 of 49 (45%) ependymomas were staged. Using these guidelines, survival of children with localized tumors could be discriminated from that of children with metastatic disease. CONCLUSIONS: The use of the Toronto Childhood Cancer Stage Guidelines is feasible for staging medulloblastoma in Italian population-based cancer registries, whereas it is more difficult for ependymomas. In Italy, cerebrospinal fluid examination, one of the decisive tests to stage CNS tumors, is not routinely performed as a first-line diagnosis procedure in ependymoma pediatric patients. A similar exercise by a larger number of cancer registries in different countries could suggest improvements in the childhood cancer staging system.

Association between maternal education and survival after childhood cancer.

BACKGROUND: Several nonbiological factors, including socioeconomic status indicators and other family characteristics, influence survival from childhood cancers. Our study explores the association between parental education and childhood cancer survival. METHODS: The specialized Childhood Cancer Registry of the Piedmont region in Italy provided data on all the cases (aged 0-14) diagnosed with cancer in the period 1976-2011 who resided in the city of Turin (capital of the Piedmont region) at least once since 1971. Information on parental education was extracted from the Turin Longitudinal Study by record linkage. The association between parental educational level and survival was estimated using Cox regression. RESULTS: The study included 949 children. We observed a disadvantage in the overall survival for children of less educated mothers. No such effect was observed for paternal education. The effect of maternal education was particularly strong for central nervous system tumors (hazard ratios, 2.9; 95% confidence interval, 1.1-8.0). A similar effect, though smaller in magnitude, was observed for leukemia and embryonal tumors, whereas the estimates for lymphoma were imprecise. CONCLUSIONS: Our study shows an association between maternal educational level and survival in children with central nervous system tumors, a diagnosis that often requires long-lasting treatment and special care. Giving support to the families of affected children to provide them the optimal care has the potential to improve children's cancer treatment outcomes.

Adolescents with Cancer in Italy: Improving Access to National Cooperative Pediatric Oncology Group (AIEOP) Centers.

This analysis compared the numbers of patients treated at Italian pediatric oncology group (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]) centers with the numbers of cases predicted according to the population-based registry. It considered 32,431 patients registered in the AIEOP database (1989-2012). The ratio of observed (O) to expected (E) cases was 0.79 for children (0-14 years old) and 0.15 for adolescents (15-19 years old). The proportion of adolescents increased significantly over the years, however, from 0.05 in the earliest period to 0.10, 0.18, and then 0.28 in the latest period of observation, suggesting a greater efficacy of local/national programs dedicated to adolescents.

The economic burden of caregiving on families of children and adolescents with cancer: a population-based assessment.

BACKGROUND: Childhood cancer represents a relevant economic burden on families. The preferred tool to investigate family expenditure is the retrospective questionnaire, which is subject to recall errors and selection bias. Therefore, in the present study the economic burden of caregiving on families of children and adolescents (0-19 years of age) with cancer was analysed using administrative data as an alternative to retrospective questionnaires. PROCEDURE: Incident cases of cancer diagnosed in children and adolescents in 2000-2005 (N = 917) were identified from the Piedmont Childhood Cancer Registry and linked to available administrative databases to identify episodes of care during the 3 years after diagnosis (N = 13,433). The opportunity cost of informal caregiving was estimated as the value of the time spent by one of the parents, and was assumed to be equal to the number of days during which the child received inpatient care, day-care or outpatient radiotherapy. Factors affecting the level of economic burden of caregiving on families were analysed in a multivariable model. RESULTS: The economic burden of caregiving increased when care was supplied at the Regional Referral Centre, or when treatment complexity was high. Families with younger children had a higher level of economic burden of caregiving. Leukaemia required a higher family commitment than any other cancer considered. CONCLUSIONS: Estimates of the economic burden of caregiving on families of children and adolescents with cancer derived from administrative data should be considered a minimum burden. The estimated effect of the covariates is informative for healthcare decision-makers in planning support programmes.

Evolving Services for Adolescents with Cancer in Italy: Access to Pediatric Oncology Centers and Dedicated Projects.

Purpose: To describe how the provision of services for adolescents with cancer has evolved in Italy, the study evaluated access to pediatric oncology centers affiliated to the national cooperative group Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), and the development of dedicated local projects. Methods: We calculated the observed/expected (O/E) ratio of adolescent patients (15-19 years old) admitted to AIEOP centers during the years 2013-2017. Observed cases were obtained from the AIEOP database (model 1.01). Expected cases were calculated on the incidence rates derived from the population-based registries. In addition, a questionnaire investigated the presence of any formal upper age limits for admitting patients, and to the development of local projects. Results: In the years 2013-2017, 9534 cases of cancer were registered in the AIEOP database, that is, 8031 children (0-14 years) and 1503 adolescents (15-19 years). The overall O/E ratio was 0.81, that is, 1.06 for children, and 0.37 for adolescents, and differed according the different tumor types. Concerning the questionnaire, 26% of centers reported age limits <18 years. Nineteen centers reported to have local projects dedicated to adolescents. Conclusions: The study shows an improvement in the services for adolescents in Italy, with an increase percentage of cases treated at AIEOP centers (from 10% of previous study, to 37%), the decrease of centers with admission age limits <18 years (from 44% 10 years ago, to 26%), and the development of many specific local projects. Effective cooperation with adult oncology societies and government recognition remain goals to be achieved.

Health-related quality of life of long-term childhood cancer survivors: a population-based study from the Childhood Cancer Registry of Piedmont, Italy.

AIM OF THE STUDY: To determine the Health Related Quality of Life (HRQL) in a population-based cohort of long-term survivors of childhood cancer in Piedmont, northwestern Italy. PATIENTS AND METHODS: During 2003, a 15-item Health Utilities Index questionnaire was mailed to 1005 5-year survivors, identified from the population-based Childhood Cancer Registry of Piedmont, to derive scores for overall HRQL and for eight single attributes of health. Score differences were estimated as adjusted prevalence odds ratios. RESULTS: A large majority of long-term survivors had moderately high scores for overall HRQL and for each of the single attributes. Males reported better overall HRQL and less morbidity with respect to dexterity, emotion and pain than females. Survivors diagnosed when they were 10-14 years of age had better overall HRQL and less morbidity with respect to emotion, cognition and pain than younger persons. Long-term survivors of central nervous system (CNS) tumours, retinoblastoma and bone tumours had greater impairment of overall HRQL, vision, ambulation, dexterity, cognition and pain than survivors of other forms of cancer. CONCLUSION: Many survivors of childhood cancer in Piedmont had fairly good overall HRQL. Greater probability of impaired HRQL was seen for females, survivors of CNS tumours, retinoblastoma and bone tumours, and persons diagnosed before 10 years of age.

Expected number of childhood cancers in Italy from 2001 to 2015.

The total number of children with incident cancer in Italy has never been specifically estimated. Specialized population-based Childhood Cancer Registries have only been operating in Piedmont (CCRP) and in the Marche region, while general population cancer registries cover about 20% of the Italian population. The number of expected cases of childhood cancer (0-14 years) in Italy in the period 2001-2015 has been estimated using CCRP incidence rates and annual percentage changes. The expected number of cases of all cancer types were 8,132, 8,672 and 8,944 in the periods 2001-2005, 2006-2010 and 2011-2015 respectively. These figures help evaluate the allocation of resources for the care of child cancer patients in Italy, and to estimate the number of cases expected to enter clinical trials.

Analysis of nonresponse in the assessment of health-related quality of life of childhood cancer survivors.

The aim of this study was to compare the characteristics of respondents and nonrespondents in a survey of childhood cancer survivors recorded in the Childhood Cancer Registry of Piedmont and their current primary care general practitioners. Eligible subjects were identified from the Childhood Cancer Registry of Piedmont and the referring general practitioners were traced through the National Health Service. A postal questionnaire was sent both to childhood cancer survivors and to their general practitioners. Prevalence odds ratios were estimated for demographic and clinical characteristics in survivors and for demographic characteristics in general practitioners. A total of 1005 childhood cancer survivors and 857 general practitioners (132 of them had two or more cancer survivors in care) were included in the study. Completed questionnaires were obtained from 691 survivors (69%) and 615 general practitioners (72%). For survivors, the only associations with nonresponse were for age 35-44 years [prevalence odds ratio: 0.53 (95% confidence interval: 0.33-0.85)], being married [prevalence odds ratio: 1.45 (95% confidence interval: 0.96-2.18)] and diagnosis after 1977 [prevalence odds ratio: 0.66 (95% confidence interval: 0.42-1.03)]. For general practitioners, the only associations were for male sex [prevalence odds ratio: 1.62 (95% confidence interval: 1.13-2.32)] and place of work outside of the city of Turin [prevalence odds ratio: 1.93 (95% confidence interval: 1.07-3.47)]; furthermore associations were relatively weak. An association was also found between nonresponse in survivors and nonresponse in their general practitioners [prevalence odds ratio: 3.40 (95% confidence interval: 2.54-4.56)]. In conclusion, apart from age, marital status and period of diagnosis, there were little differences between respondent and nonrespondents, for the considered clinical and demographical characteristics. Participation of survivors and their general practitioners correlated, suggesting that involvement of the general practitioners in the study may be a method to increase participation of survivors of childhood cancers.

Avoided deaths as an indicator of improvement of childhood cancer treatment.

The aim of this study was to estimate how many deaths have been avoided because of the substantial improvement in childhood cancer survival both in Piedmont (2769 incident cases) and in Italy during 1970-1999. For each time period of diagnosis, the number of avoided deaths within 5 years after diagnosis was estimated as the difference between the observed number of deaths and the number of deaths that would have been observed if the patients had experienced the same mortality as in the reference period of 1970-1974. The national estimate of the number of avoided deaths was calculated by applying Piedmont cumulative mortality to the expected number of incident cases in Italy. An increase in the number of avoided deaths from 103 (95% confidence interval: 65-140) in 1975-1979 to 239 (95% confidence interval: 209-268) in 1995-1999 was observed in Piedmont. In Italy, the number of avoided deaths was 3880 in 1995-1999, with respect to 1970-1974. Results of these analyses provide an effective way to quantify the improvement in the quality of care for children with childhood cancer.

Comment on Piscitelli et al. Hospitalizations in Pediatric and Adult Patients for All Cancer Type in Italy: The EPIKIT Study under the E.U. COHEIRS Project on Environment and Health. Int. J. Environ. Res. Public Health 2017, 14, 495.

In the "Epikit study" [1], P. Piscitelli with 27 co-authors from 20 scientific institutions estimated the absolute number of hospital admissions for newly diagnosed cancer in people aged 0-19 in Italian provinces and regions in 2007-2011.[...].

Cancer incidence rates and trends among children and adolescents in Piedmont, 1967-2011.

In the past, increases in childhood cancer incidence were reported in Europe and North America. The aim of this study is to show updated patterns of temporal behavior using data of the Childhood Cancer Registry of Piedmont (CCRP), a region with approximately 4.5 million inhabitants in North-West Italy. CCRP has been recording incident cases in children (0-14 years) since 1967 and in adolescents (15-19) since 2000. Time trends were estimated as annual percent change (APC) over the 1976-2011 period for children, and over 2000-2011 for both children and adolescents. CCRP registered 5020 incident cases from 1967 to 2011. Incidence rates were 157 per million person-years for children (1967-2011) and 282 for adolescents (2000-2011). From 1976-2011, increasing trends were observed in children for all neoplasms (APC 1.1, 95%CI: 0.8; 1.5) and for both embryonal and non-embryonal tumors: 1.1%, (0.5; 1.6) and 1.2%, (0.7; 1.6), respectively. Increases were observed in several tumor types, including leukemia, lymphoma, central nervous system tumors and neuroblastoma. In 2000-2011, incidence rates showed mostly non statistically significant variations and large variability. The observation of trends over a long period shows that the incidence of most tumors has increased, and this is only partially explained by diagnostic changes. Large rate variability hampers interpretation of trend patterns in short periods. Given that no satisfying explanation for the increases observed in the past was ever found, efforts must be made to understand and interpret this peculiar and still ununderstood pattern of childhood cancer incidence.

Late deaths among five-year survivors of childhood cancer. A population-based study in Piedmont Region, Italy.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze late mortality among 5-year survivors of childhood cancer, in Piedmont (Italy), in terms of risk factors and causes of death. DESIGN AND METHODS: From 1967 to 1999, the Childhood Cancer Registry of Piedmont recorded 3164 incident cases. Patients identified only by a death certificate (n = 59), lost to follow-up (n = 32), alive with a period of observation shorter than 5 years at the end of follow-up (n = 65) and records corresponding to a second malignant tumor during childhood (n = 9) were excluded from the analyses. RESULTS: Within 5 years after diagnosis, 1301 children died, and among the 1698 5- year survivors, 144 children subsequently died. Among 5-year survivors, cumulative mortality percentages increased from 5.1% (95% CI 4.0-6.2) at 10 years after diagnosis to 16.0% (12.2-19.8) at 35 years. Period of diagnosis (p = 0.006), age at diagnosis (p = 0.002), and tumor type (p = 0.003) were associated with late mortality. Most deaths were related to cancer recurrence (62.2%) and treatment-related sequelae (22.4%), including second malignant neoplasms, cardiac diseases and other late effects. Compared to the general population, children included in this study had a 9-fold increased risk of overall mortality, and experienced an absolute excess of 4.4 deaths per 1000 person-years. INTERPRETATION AND CONCLUSIONS: Among 5-year survivors, patients treated more recently (after 1979) had a statistically significant lower risk of late death than those treated earlier. However, long-term survivors still experienced higher mortality rates than those in the general population, and recurrence or progression of the primary tumor was the first cause of death.

Population-based survival after childhood cancer diagnosed during 1970-98: a report from the Childhood Cancer Registry of Piedmont, Italy.

BACKGROUND AND OBJECTIVES: Survival after childhood cancer has shown a steady improvement from the late 1970s in most developed countries. Since 1967 the Childhood Cancer Registry of Piedmont has been collecting cases of malignant tumor, diagnosed in children aged 0-14 years, living in Piedmont. This work aims to update survival rates to 31.12.2000. DESIGN AND METHODS: This study includes 2,678 children diagnosed between 1970-98. Vital status was assessed at the Registry Office of the town of residence. One thousand four-hundred ninety cases were reported to be alive, 1170 dead and for 18 the status was unknown. Thirty-three cases registered with a death certificate only were excluded. Completeness of follow-up was 99.3%. All tumor types were classified according to the Birch-Marsden classification. Histologic verification was available for 94.4% of cases. RESULTS: Survival at 5 years increased over the period 1970-98 for all tumor types with a statistically significant trend over time (p<0.0001). The 5 year survival rate for acute lymphoblastic leukemia (ALL) increased steadily from 24.7% (95%CI 15.0-34.3) to 87.6% (80.9-94.3), for acute non-lymphoblastic leukemia (ANLL) from 0.0% to 38.1% (17.3-58.9), and for non-Hodgkin's lymphomas from 25.2% (0.6-49.8) to 79.7% (61.9-97.5). Five year survival rates of children with central nervous system tumors increased from 33.4% in 1970-74 to 78.5% in 1990-94 and decreased in 1995-98 to 70.9%. Age <1 year and >50,000x10(6) cells/L at diagnosis were negative prognostic factors for ALL. Age <1 year was a favorable prognostic factor for neuroblastoma. INTERPRETATION AND CONCLUSIONS: Survival of children with all types of tumors improved in Piedmont. This improved survival is comparable to that reported by other European and North American population-based cancer registries.

Time trends and prognostic factors for survival from childhood cancer: a report from the Childhood Cancer Registry of Piedmont (Italy).

Survival after childhood cancer has been improving since the late 1970s in most developed countries. The Childhood Cancer Registry of Piedmont has been recording malignant tumors in children (0-14 years) throughout Piedmont since 1967. The present paper is based on the records of the 2,970 children diagnosed during the period 1970-2001; survival rates are estimated up to June 30, 2004. Based on records from the Registrar Offices of the relevant towns of residence, 1,698 children were reported to be alive, 1,252 deceased, and 20 were of unknown vital status. Over the period 1970-2001, 5-year survival rates for all tumor types combined showed a statistically significant increasing trend (p<0.0001). For acute lymphocytic leukemia, the survival rate increased steadily from 24.7% (95% CI 15.0-34.3) in 1970-1974 to 87.8% (82.1-93.6) in 1995-1999. Five-year survival rates for central nervous system tumors increased from 32.8% (21.0-44.6) in 1970-1974 to 80.3% (72.6-88.0) in 1990-1994 and decreased thereafter. Age of less than 1 year at time of diagnosis was a favorable prognostic factor for neuroblastoma and ganglioneuroblastoma. The extent of disease at diagnosis was related to prognosis for neuroblastoma and ganglioneuroblastoma and other selected solid tumors. A white blood cell count greater than 50,000 x 10(6) cells/l was associated with decreased survival in children with acute lymphocytic leukemia and acute non-lymphocytic leukemia. We have found positive trends in survival for all tumor types in Piedmont, similar to those reported by other population-based cancer registries. Age, extent of disease, and white blood cell count at diagnosis are prognostic factors for selected cancer sites.

Increasing incidence of childhood leukemia in Northwest Italy, 1975-98.

Although some childhood cancer registries reported increasing incidence, the evidence and magnitude of time trends in the incidence of childhood leukemia are debated and the scientific evidence is conflicting. Only limited data have so far been supplied from Southern European countries. We present an analysis of the incidence trend of childhood leukemia in Piedmont (NW Italy) in 1975-98, based on data from the population-based childhood cancer registry. The Childhood Cancer Registry of Piedmont has been recording cases of childhood neoplasms since 1967. Procedures have been uniform and are based on an active search for cases and relevant information. Only cases with confirmed residence in Piedmont at diagnosis are included. Eight hundred cases of leukemia (622 acute lymphoblastic [ALL], 133 acute nonlymphoblastic [AnLL], 45 other and unspecified) were recorded in the period 1975-98 considered in our study. Incidence trends were analyzed using piecewise regression and Poisson regression, based on annual incidence rates. As results from the 2 analyses were similar, only the former were reported. In the age group 1-4 years, a statistically significant annual 2.6% increase in incidence rate of ALL (adjusted by age and gender; 95% confidence interval [CI] 1.13-4.13) was estimated. There was no evidence of increase in other age groups. During 1980-98, a statistically significant 4.4% annual increase (95% CI 1.86-6.90) was seen for pre-B-All in the age group 1-4 years. An increase was also seen for T-ALL that was not statistically significant. Sensitivity analyses were conducted, with no relevant differences from the main results. Our data suggest an increasing trend in ALL incidence for children between the ages of 1 and 4 years. These results are unlikely to be explained by changes in quality of data or exhaustiveness in reporting in the study period. The results were not changed in the sensitivity analyses we conducted. Possible causes to be investigated include environmental factors, changes in family size and parental age, socioeconomic conditions and geographical distribution of cases.

Early deaths from childhood cancer. A report from the Childhood Cancer Registry of Piedmont, Italy, 1967-1998.

UNLABELLED: The population-based Childhood Cancer Registry of Piedmont (CCRP) has collected data on incidence since 1967. The occurrence of early death (i.e. within 30 days of diagnosis) was investigated in 3006 cases of childhood cancer diagnosed during the period 1967-1998. The proportion of early deaths (178 of the 3006 cases) was analysed by period of diagnosis (three decennial periods), age group, major diagnostic group and hospital category, with univariate statistics and logistic regression. The proportion of children with cancer who died within 1 month of diagnosis was 10.8%, 5.3% and 1.8% for cases diagnosed during 1967-1978, 1979-1988 and 1989-1998, respectively. This trend may reflect earlier diagnosis, improved diagnosis, more effective therapy or more frequent referral to specialised centres. The risk factors for early death were: age <1 year and diffuse disease at diagnosis, diagnosis during 1967-1978, a diagnosis of acute non lymphocytic leukaemia, non-Hodgkin lymphoma, central nervous system tumour or hepatic tumour. Early death was not related to the sex of the child. Care in an extra-regional specialised centre was associated with lower risk of early death. CONCLUSION: No temporal changes in early mortality were found among children with acute non lymphocytic leukaemia diagnosed in the first, second or third decade of activity of the CCRP, the percentages of children dying within 1 month being 12.8%, 10.7% and 12.8%, respectively. This pattern clearly differed from the corresponding trend for acute lymphoid leukaemia (6.4%, 2.0%, 0.4%).