Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study.

BACKGROUND: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. METHODS: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. RESULTS: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. DISCUSSION: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.

Risk of subsequent primary lymphoma in a cohort of 69,460 five-year survivors of childhood and adolescent cancer in Europe: The PanCareSurFup study.

BACKGROUND: Survivors of Hodgkin lymphoma (HL) are at risk of developing non-Hodgkin lymphoma (NHL) after treatment; however, the risks of developing subsequent primary lymphomas (SPLs), including HL and NHL, after different types of childhood cancer are unknown. The authors quantified the risk of SPLs using the largest cohort of childhood cancer survivors worldwide. METHODS: The Pan-European Network for Care of Survivors After Childhood and Adolescent Cancer (PanCare) Survivor Care and Follow-Up Studies (PanCareSurFup) cohort includes 69,460 five-year survivors of childhood cancer, diagnosed during 1940 through 2008, from 12 European countries. Risks of SPLs were quantified by standardized incidence ratios (SIRs) and relative risks (RRs) using multivariable Poisson regression. RESULTS: Overall, 140 SPLs, including 104 NHLs and 36 HLs, were identified. Survivors were at 60% increased risk of an SPL compared with the general population (SIR, 1.6; 95% confidence interval [CI], 1.4-1.9). Survivors were twice as likely to develop NHL (SIR, 2.3; 95% CI, 1.9-2.8), with the greatest risks among survivors of HL (SIR, 7.1; 95% CI, 5.1-10.0), Wilms tumor (SIR, 3.1; 95% CI, 1.7-5.7), leukemia (SIR, 2.8; 95% CI, 1.8-4.4), and bone sarcoma (SIR, 2.7; 95% CI, 1.4-5.4). Treatment with chemotherapy for any cancer doubled the RR of NHL (RR, 2.1; 95% CI, 1.2-3.9), but treatment with radiotherapy did not (RR, 1.2; 95% CI, 0.7-2.0). Survivors were at similar risk of developing a subsequent HL as the general population (SIR, 1.1; 95% CI, 0.8-1.5). CONCLUSIONS: In addition to HL, the authors show here for the first time that survivors of Wilms tumor, leukemia, and bone sarcoma are at risk of NHL. Survivors and health care professionals should be aware of the risk of NHL in these survivors and in any survivors treated with chemotherapy.

Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study.

BACKGROUND: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide. METHODS: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. RESULTS: 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN-comparable to the risk among members of the general population with at least two first-degree relatives affected. CONCLUSIONS: Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.

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.

[Seroprevalence of anti-SARS-CoV-2 IgG/IgM antibodies in Borgosesia (Piedmont Region, Northern Italy) population: a surveillance strategy in post-lockdown period?] / La prevalenza della risposta immunitaria a SARS-CoV-2 nella popolazione di Borgosesia (VC): una strategia di sorveglianza in fase post-lockdown?

BACKGROUND: to avoid a new spread of the SARS-CoV-2 infection, the post lockdown period requires the implementation of effective strategies for the case finding and contact tracing. The presence of asymptomatic subjects in the population, that are responsible for about 30% of the new infections, may complicate this phase. Serological tests for the measurement of immune response could represent an effective tool for the rapid monitoring of the population with asymptomatic infections and for estimating the proportion of immune in a territory, too. OBJECTIVES: to describe the distribution of the immune response to SARS-CoV-2 infection in the population of the Municipality of Borgosesia (Piedmont Region, Northern Italy) and to estimate the efficacy of this strategy for the identification of asymptomatic cases. DESIGN: Cross-sectional study with administration of a rapid test to assess the seroprevalence of anti-SARS-CoV-2 IgG/IgM antibodies. SETTING AND PARTICIPANTS: all subjects resident in Borgosesia over the age of 18, where invited to participate. A rapid serological test was administered to enrolled participants to detect the presence of SARS-CoV-2 IgG and IgM antibodies on peripheral blood. Subjects with IgG or IgM positivity were offered to perform a swab test for viral RNA research. MAIN OUTCOME MEASURES: the prevalence of IgM and IgG, and the relative risks of having positive swab test and of having symptoms similar to those of COVID-19 in the recent past has been estimated. RESULTS: 4,987 subjects participated to study, 44.5% of the adult population of Borgosesia. The average age was 55 years. There was a greater participation of women (54.4%), of people with a higher education level (37.3%) and of people without specific previous symptoms (95.1%). 245 people had a positive test for IgM or IgG, and the estimated prevalence was of 4.9%. 209 out of 245 subjects who were positive to the rapid test underwent to the RT-PCR test and this allowed to isolate 24 positive subjects. CONCLUSIONS: the seroprevalence values ​​estimated for subjects residing in the city of Borgosesia which underwent the rapid test for the detection of type M and type G antibodies on peripheral blood, confirmed the population-based estimates reported in literature, in particular with the results of the Italian survey of seroprevalence. Furthermore, the implementation of this test allowed the identification and isolation of completely asymptomatic subjects, that could have been identified only through screening with tests for viral RNA.

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.

The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer: a cohort from 12 European countries.

Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.

Evaluation of the risk of SARS-CoV-2 infection and hospitalization in vaccinated and previously infected subjects based on real world data.

The objective of our study was to determine the joint protective effect of a previous SARS-CoV-2 infection and vaccination on the risk of a new infection and hospitalization. Two case-control studies nested in a cohort of COVID-19 patients cared for by the Local Health Unit (LHU) of Vercelli, Italy, were performed, one to estimate the risk of infection and the second to estimate the risk of hospitalization. Each new infection and hospitalization was matched with up to 4 disease-free subjects who were the same age, sex and index date (i.e., controls). Study subjects were followed up from cohort entry date to disease outcome, end of follow-up or emigration. Vaccination was associated with a 36% (OR 0.64; 95%CI 0.62-0.66) and 90% (OR 0.10; 95%CI 0.07-0.14) reduction in the risk of infection and hospitalization, respectively. Prior infection was associated with a 65% (OR 0.35; 95%CI 0.30-0.40) and 90% (OR 0.10; 95%CI 0.07-0.14) reduction in the risk of infection and hospitalization, respectively. Vaccinated and recovered subjects showed a 63% (OR 0.37; 95%CI 0.34-0.14) and 98% (OR 0.02; 95%CI 0-0.13) reduction in the risk of infection and hospitalization, respectively. Vaccination remains an essential public health tool for preventing severe forms of COVID-19. Our study shows that vaccination or previous infection has a strong protective effect against Sars-CoV-2 hospitalization. The protective role against infection appears to be present although with a lower efficacy rate than that presented in the RCTs.

Risk Factors for Primary Bone Cancer After Childhood Cancer: A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study.

PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy. METHODS: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship. RESULTS: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.

The Dedalo Project, a Community-based Prevention Program for the Promotion of Healthy Behaviors in Adult Population: Model Description and Target Population Assessment.

Noncommunicable diseases (NCDs) are the leading global cause of death. The Italian National Prevention Plan (INPP) highlights the importance of health promotion and NCD prevention while avoiding health inequalities. In line with the INPP guidelines, we initiated a multicomponent community-based intervention program, named the Dedalo project, to promote healthy and active aging among population living around the Vercelli's municipality, Italy. A cross-sectional analysis, that used the baseline data of a longitudinal study of the project, evaluated the program's ability to enroll participants participants who represent the socioeconomic conditions present in the municipality. To this end, we compared the main social characteristics and behaviors of 40-74-year-old subjects (n = 155), who had attended at least one Dedalo activity, to those of same age individuals (n = 124) randomly extracted from the general population. We found that most participants were women (81.3%) and had a higher SES compared to the general population. Furthermore, they were healthier-OR 0.52, 95% CI 0.31-0.87 for self-reported diseases-and displayed healthier behaviors-OR 0.20, 95% CI 0.08-0.46 for smokers; 0.32 95%, CI 0.16-0.64 for fruit/vegetable consumers; and 0.36 95% CI 0.20-0.64 for sweet beverages consumers. Overall, our initial evaluation indicates that the Dedalo project has so far struggled to enroll individuals with low SES, men with any SES, and subjects displaying unhealthy behaviors, thereby failing to meet the INPP goal of preventing NCDs while avoiding health disparities. Thus, efforts should be made to ensure that this community-based intervention program can effectively reach all the target population, in particular those individuals most exposed to behavioral risk factors.

High Seroprevalence of SARS-CoV-2 among Healthcare Workers in a North Italy Hospital.

BACKGROUND: Healthcare workers (HCWs) have been the key players in the fight against the coronavirus disease 2019 (COVID-19) pandemic. The aim of our study was to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG anti-bodies. METHODS: We conducted a cross-sectional study among workers of two hospitals and Territorial Medical and Administrative services in Northern Italy. From 8 May to 3 June 2020, 2252 subjects were tested. Seroprevalence and 95% confidence interval (CI) were calculated for all individuals who were stratified by job title, COVID-19 risk of exposure, direct contact with patients, unit ward, and intensity of care. RESULTS: Median age was 50 years, and 72% of subjects were female. The overall seroprevalence was 17.11% [95% CI 15.55-18.67]. Around 20% of healthcare assistants were seropositive, followed by physicians and nurses (16.89% and 15.84%, respectively). HCWs with high risk of exposure to COVID-19 were more frequently seropositive (28.52%) with respect to those with medium and low risks (16.71% and 12.76%, respectively). Moreover, personnel in direct contact had higher prevalence (18.32%) compared to those who did not (10.66%). Furthermore, the IgG were more frequently detected among personnel of one hospital (19.43%). CONCLUSION: The high seroprevalence observed can be partially explained by the timing and the population seroprevalence; the study was conducted in an area with huge spread of the infection.

Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study.

OBJECTIVE: In this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study. METHODS: Eight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3-5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors. RESULTS: Overall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis: 23.0 years). The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14-30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)). CONCLUSIONS: In this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.

Risk of subsequent primary leukaemias among 69,460 five-year survivors of childhood cancer diagnosed from 1940 to 2008 in Europe: A cohort study within PanCareSurFup.

BACKGROUND: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors. METHODS: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. RESULTS: One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs. CONCLUSIONS: We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL.

Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe.

Background: Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer. Methods: We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. Results: Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma. Conclusions: For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.

The PanCareSurFup consortium: research and guidelines to improve lives for survivors of childhood cancer.

BACKGROUND: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. METHODS: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. RESULTS: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case-control studies of subsequent malignancies and cardiac disease in 5-year survivors. CONCLUSIONS: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health.

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.

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.

Surviving a childhood cancer: impact on education and employment.

Long-term consequences of childhood cancer encompass adverse psychosocial effects that may severely limit the opportunity to live a satisfying and productive life. We assessed the social integration of adults cured of a cancer in their first 14 years of life by record linkage between the population-based Childhood Cancer Registry of Piedmont and the Turin Longitudinal Study. We compared education and employment outcomes within the cohort of survivors and between the cohort of survivors and their peers in the general population through logistic regression. Individuals cured of a childhood tumour have a higher risk of not obtaining educational qualifications [odds ratio (OR) 0.67 (95% confidence interval 0.40-1.11) for compulsory school, OR 0.81 (0.61-1.07) for higher education] or employment, OR 0.66 (0.45-0.98), than the general population. This problem is particularly severe for individuals cured of a central nervous system neoplasm: OR 0.56 (0.31-1.01) for higher education and OR 0.28 (0.13-0.58) for employment. Within-cohort comparisons show that men are less likely to obtain educational goals than women, OR 0.72 (0.40-1.29), but more likely to be employed, OR 2.18 (0.90-5.28); parental education (university qualifications) is positively associated with the success of the child's education, OR 9.54 (2.60-35.02), but not with their employment status, OR 1.02 (0.21-4.85). Strategies should be put in place to mitigate the risk of adverse psychosocial effects from the beginning of treatment to cure and beyond to offer those suffering a cancer at a young age the possibility of full integration into society.

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.