annual report 2014 - 2015 Swiss Childhood Cancer Registry Annual Report 2014 /2015 For the Swiss Childhood Cancer Registry Verena Pfeiffer Shelagh Redmond Rahel Kuonen Grit Sommer Ben Spycher Matthias Schindler Parvinder Singh Gisela Michel Claudia Kuehni For the Swiss Paediatric Oncology Group Felix Niggli Heinz Hengartner Maja Beck Popovic Nicolas von der Weid Isabelle Lamontagne - Müller Bern, June 2016 Publisher: Swiss Childhood Cancer Registry Claudia E. Kuehni Address: Institute of Social and Preventive Medicine University of Bern Finkenhubelweg 11 CH - 3012 Bern Switzerland Tel. +41 (0)31 631 56 70 Tel. +41 (0)31 631 38 99 E - mail: kinderkrebsregister@ispm.unibe.ch www.childhoodcancerregistry.ch www.kinderkrebsregister.ch www.registretumeursenfants.ch www.registrotumouripediatrici.ch Bern, Swiss Childhood Cancer Registry 4 Table of contents 1. Introduction 7 2. Organisation of the Swiss Childhood Cancer Registry 9 2.1 Institute of Social and Preventive Medicine (ISPM), University of Bern 9 2.2 Swiss Paediatric Oncology Group (SPOG) 10 2.3 General information 11 3. Routine Analyses 13 3.1 Overview 13 3.2 All cases registered in the SCCR (N = 9353) 13 3.3 Swiss residents aged 0 - 14 years at diagnosis (N = 6604) 15 3.4 Swiss residents aged 15 - 20 years at diagnosis (N = 501) 21 4. Research on childhood cancer 23 4.1 Aetiology of childhood cancer 25 4.2 Long - term outcomes 26 4.3 International collaborations 28 4.4 Psychosocial outcomes and follow-up care 30 5. Publications of the Swiss Childhood Cancer Registry 31 5.1 Original articles (Peer reviewed journals) 31 5.2 Editorials, commentaries and author replies (Peer reviewed journals) 34 5.3 Reviews (Peer reviewed journals) 34 5.4 Publications (other journals) 35 5.5 Reports 36 6. Appendix: Classification of cancer diagnoses 37 5 6 1. Introduction The Swiss Childhood Cancer Registry (SCCR) is the national population - based cancer registry for children and adolescents in Switzerland. New cancer diagnoses, clinical information, details on treatment and long - term follow - up (survival, second primary neoplasms and late effects) have been registered in the SCCR since 1976. This year, 2016, the SCCR celebrates its 40th birthday! With many associated research projects and through close collaboration with clinicians it contributes to understanding the causes of cancer in children, improving follow - up care and reducing late effects. The SCCR is located at the Institute of Social and Preventive Medicine (ISPM) at the University of Bern. It is operated jointly by the Swiss Paediatric Oncology Group (SPOG) and the University of Bern. Since 1976, all nine Swiss paediatric haematology - oncology centres report newly diagnosed cases to the registry and send annual updates on clinical follow - up. Since 2007, the SCCR also collects supplementary data from other sources, including cantonal cancer registries, other hospitals, pathology laboratories and the Swiss Federal Statistical Office (SFSO). As of 31st December 2014, data from 9353 cases (diagnosed in 9225 patients) have been registered. The SCCR is authorized to collect non - anonymised data. The permission has been issued in 2007 by the Federal Commission of Experts for Professional Secrecy in Medical Research (Eidgenössische Expertenkommission für das Berufsgeheimnis in der medizinischen Forschung). Since 2014 the new act on human research is in place. The SCCR got a new authorization issued by the ethics committee of the canton of Bern in July 2014. This seventh report covers the routine analyses of all children diagnosed between 1st January 1976 and 31st December 2014. Activities, research and publications of the SCCR are described for the years 2014 to 2016. The report contains: • An overview of the organisation and team of the SCCR, SPOG and the participating paediatric haematology oncology centres (Chapter 2) • A summary of the data collected in the registry up to 31st December 2014 (Chapter 3) • A summary of current research of the SCCR (Chapter 4) • A list of publications (Chapter 5) Our website (www.childhoodcancerregistry.ch) contains further information, including past annual reports and scientific publications. We would like to thank all the children and their families, and all adolescent and adult childhood cancer survivors, for allowing us to collect their data. We also thank the physicians and clinical research coordinators of the Swiss Paediatric Oncology Group for their excellent collaboration. Our thanks also go to the cantonal cancer registries, the National Institute for Cancer Epidemiology and Registration (NICER), the Swiss Federal Statistical Office (SFSO), the Federal Office of Public Health (FOPH) and the pathology laboratories for their cooperation. Finally, we thank our supporters for their generous contributions. The SCCR is an associated member of the National Institute for Cancer Epidemiology and Registration (NICER), of the European Network of Cancer Registries (ENCR) and of the International Association of Cancer Registries (IACR), and collaborates with childhood cancer registries throughout Europe. What did the Swiss Childhood Cancer Registry achieve in 40 years? • Performed national childhood cancer monitoring of high quality • Provided reliable statistical routine data • Established a competitive research platform • Gave competent ad hoc answers to health-, environmental-, socio- , political- related questions • Cooperated closely with all paediatric oncologists, • Established a strong network with Swiss parents organisations Swiss Childhood Cancer Registry Annual Report 2014/2015 lntroduction 7 8 2. Organisation of the Swiss Childhood Cancer Registry The Swiss Childhood Cancer Registry (SCCR) is a member of the Swiss Paediatric Oncology Group (SPOG) and is organised as a joint operation of the Institute of Social and Preventive Medicine (ISPM) at the University of Bern and the SPOG. 2.1 Institute of Social and Preventive Medicine (ISPM), University of Bern Swiss Childhood Cancer Registry Institute of Social and Preventive Medicine Finkenhubelweg 11 CH - 3012 Bern Switzerland Tel. +41 (0)31 631 56 70 www.childhoodcancerregistry.ch Direction Claudia Kuehni, Prof MD Head of SCCR claudia.kuehni@ispm.unibe.ch Gisela Michel, Prof PhD Vice head of SCCR gisela.michel@unilu.ch Swiss Childhood Cancer Registry Verena Pfeiffer, PhD Project coordinator SCCR verena.pfeiffer@ispm.unibe.ch Katharina Flandera Administration katharina.flandera@ispm.unibe.ch Shelagh Redmond, PhD Diagnostic coding, data quality Parvinder Singh Statistics Meltem Altun Data management Erika Brantschen Data management Trust Centre Christina Krenger Data management Informatics and database support Priska Wölfli Database support Research projects Ben Spycher, PhD Senior research fellow, Project manager Grit Sommer, PhD Senior research fellow, Project manager Rahel Kuonen, MSc Senior research fellow, Project manager Christian Kreis, PhD Senior research fellow Fabien Belle, MSc PhD student Konstantinoudis Garyfallos, MSc PhD student Rahel Kasteler, MD PhD student Matthias Schindler, MSc PhD student Annette Weiss, MSc PhD student Swiss Childhood Cancer Registry Annual Report 2014/2015 Organisation of the Swiss Childhood Cancer Registry 9 2.2 Swiss Paediatric Oncology Group (SPOG) SPOG Office Effingerstrasse 33, 3008 Bern Tel.: +41 (0)31 508 42 33 www.spog.ch SPOG Executive Board Felix Niggli, Prof MD President Heinz Hengartner, MD Vice president Maja Beck Popovic, Prof MD Committee Member SPOG Office in Bern Isabelle Lamontagne - Müller, MSc Managing director Marlise Rohrer Director’s assistant Barbara Böttcher, PhD Head Quality assurance Julia Ruckstuhl, MSc Head Regulatory affairs Tu- My Diep Lai, PhD Regulatory affairs Martina Peluso, MSc Regulatory affairs Silvia Wirth, PhD Quality assurance Regulatory affairs isabelle.lamontagne@spog.ch Participating centres (paediatric haematology - oncology) Head of Division Clinical Research Coordinator Aarau Kinderklinik, Kantonsspital Aarau R. Angst, MD C. Anderegg, MSc Basel Universitäts - Kinderspital beider Basel [UKBB] N. von der Weid, Prof MD V. Stahel M. Imbach Bern Universitätsklinik für Kinderheilkunde, Inselspital K. Leibundgut, Prof MD F. Julmy N. Beusch Genève Hôpital des Enfants, Hôpitaux Universitaires de Genève [HUG] M. Ansari, Prof MD R. Lo Piccolo V. Mattiello, MD Lausanne Service de Pédiatrie, Centre Hospitalier M. Beck Popovic, Prof MD R. - E. Garcia, MD Universitaire Vaudois [CHUV] E. Lemmel Bellinzona Reparto di Pediatria, Ospedale S. Giovanni, Bellinzona P. Brazzola, MD P. Brazzola, MD P. Balestra Luzern Kinderspital, Kantonsspital Luzern J. Rischewski, PD MD N. Lanz St.Gallen Ostschweizer Kinderspital J. Greiner - Lang, MD F. Hochreutener A. Schiltknecht F. Niggli, Prof MD M. Grotzer, Prof MD H. Markiewicz A. Reinberg R. Siegenthaler C. Althaus, MD Zürich Universitäts - Kinderspital, Zürich 10 2.3 General information Aims The Swiss Childhood Cancer Registry collects information on the diagnosis, treatment and follow-up of children and adolescents with cancer in Switzerland, and provides data for national and international statistics and research projects. It aims: • To collect representative, population- based data on cancer in children and adolescents in Switzerland (cancer incidence, prevalence, time trends, regional distribution and survival rates) • To document diagnostic evaluations, treatment and participation in clinical trials • To describe short- term and long- term prognosis (mortality, morbidity and quality of life) after cancer in childhood and adolescence • To provide a research platform for clinical, epidemiological and basic research It thus contributes to: • Research into the aetiology of cancer in children and adolescents • Planning of health services • Continuous improvement of treatment • Identifying possible late effects of therapy, with the aim to diagnose and treat them early and prevent them in the future Inclusion criteria The SCCR registers all children and adolescents aged 0 to 20 years, resident or treated in Switzerland, diagnosed with: • Acute and chronic leukaemias, including myelodysplastic syndrome • Lymphomas • Malignant solid tumours • Central nervous system tumours (CNS), malignant and benign tumours • Langerhans cell histiocytosis (LCH), Hemophagocytic lymphohistiocytosis (HLH) Since 2014 it also registers children and adolescents diagnosed with: • • • • • Aggressive fibromatosis (ICD - O - 3M code 8821 /1) Benign /mature teratoma (ICD - O - 3M code 9080 /0) Mesoblastic nephroma (ICD - O - 3M code 8960 /1) Severe aplastic anaemia (ICD - 10 D61.9) Neoplasms of the liver, histologically proven, but no malformations Children and adolescents who are not Swiss residents but are diagnosed or treated in Switzerland are registered, but they are excluded from analyses of incidence and survival. Swiss Childhood Cancer Registry Annual Report 2014/2015 Sources of data Data on children and adolescents with cancer are collected from several sources, including: • The nine Swiss centres for paediatric oncology and haematology (Chapter 2.2) • Other hospitals • Cantonal cancer registries, represented by the National Institute for Cancer Epidemiology and Registration (NICER) • Clinical and epidemiological registries (e.g. brain tumour registry, bone tumour registry, Swiss growth registry etc.) • The Swiss Federal Statistical Office (SFSO; Swiss mortality statistics) • Pathology laboratories Most children are reported by one of the nine Swiss centres for paediatric oncology and haematology. Local clinical research coordinators complete forms for all newly diagnosed patients. Basic information on diagnosis is later completed with information on treatments, remissions, relapses, transplantations and health outcomes. These forms are sent to the SCCR and information is entered into the database. Important medical documents (e.g. pathology reports) are scanned and stored electronically using a pseudonym. Paper copies are destroyed. Information on Swiss residency is validated through municipal population registers. For the first five to ten years after diagnosis follow- up data is extracted annually from patients’ hospital records by the local clinical research coordinators in all paediatric oncology and haematology centres (Chapter 3.3). To assess outcomes after the children have left the clinic, patients are contacted directly with a questionnaire and data is linked to mortality records (SFSO) and to records from cantonal cancer registries (Chapter 4.2). Life status update is assessed through community registries. For children not treated in a paediatric oncology and haematology centre, clinical follow- up from hospitals is often not available, but long- term epidemiological follow- up is done via questionnaires and by assessment of second primary neoplasms and mortality as for the other patients and life status update via community registries (Chapter 3.3). Clinical database The current SCCR database was set up in 2007. The following information is routinely collected: • Tumour diagnosis, date of diagnosis, morphology, topography, stage, metastases • Other diagnoses (cancer- relevant pre- existing conditions) • Relevant laboratory and clinical data • Treatment (clinical trial participation, chemotherapy, radiotherapy, surgical intervention, bone marrow transplantation) and treatment centres involved • Follow- up data (changes of treatment, remissions, relapses, survival /death and cause of death) • Late adverse outcomes (e.g. cardiovascular diseases, second primary neoplasms and endocrine disorders) Organisation of the Swiss Childhood Cancer Registry 11 Trust centre Data protection Since 2010, personal information (name and address) is stored in a separate database in the trust centre. The trust centre validates addresses, residence status, nationality, and vital status via community registers. This personal information is separated strictly from clinical information of the SCCR database. The following data is collected: In 2004, the SCCR received a special authorisation (Sonderbewilligung) from the Swiss Federal Commission of Experts for Professional Secrecy in Medical Research. Starting from June 2007, a general authorization (Registerbewilligung) ) permitted the data collection from paediatric cancer patients (children and adolescents) throughout Switzerland after obtaining written, oral or silent consent. • Patient name, address of residence at time of diagnosis, current address of residence • Date of birth, sex, first language • Country of residence and nationality at time of diagnosis • Vital status and date of death • Parental profession, parental date of birth Tumour coding All tumours are coded according to the following international classification systems (see appendix): • International Classification of Childhood Cancer, third edition (ICCC - 3) • International Classification of Diseases for Oncology, third edition (ICD - O - 3) • International Classification of Diseases and Related Health Problems, tenth revision (ICD - 10) In the annual report, the main diagnostic groups of the ICCC - 3 are used: I. Leukaemias, myeloproliferative diseases, and myelodysplastic diseases II. Lymphomas and reticuloendothelial neoplasms III. CNS and miscellaneous intracranial and intraspinal neoplasms IV. Neuroblastoma and other peripheral nervous cell tumours V. Retinoblastoma VI. Renal tumours VII. Hepatic tumours VIII. Malignant bone tumours IX. Soft tissue and other extraosseous sarcomas X. Germ cell tumours, trophoblastic tumours, and neoplasms of gonads XI. Other malignant epithelial neoplasms and malignant melanomas XII. Other specified and unspecified malignant neoplasms Langerhans cell histiocytosis (LCH), which is not included in ICCC - 3, is reported separately. 12 Since January 2014 the new Human Research Act and its three ordinances are in place. Out of those three ordinances, the ordinance on Human Research with the exception of Clinical Trials provides the new framework for the SCCR. Instead of the Swiss Federal Commission of Experts for Professional Secrecy in Medical Research, data collection and storage by SCCR now require an authorisation by the ethics committee of the canton of Bern. The general authorization (Registerbewilligung) has been replaced in July 2014 by an approval from the ethics committee of the canton of Bern. Funding The SCCR thanks the following supporters for their financial contributions towards the daily operation and the continuous development of the registry. Supporters of scientific research of the SCCR are listed in Chapter 4. Main funding sources 2014 /2015 • Schweizerische Konferenz der kantonalen Gesundheitsdirektoren und - direktorinnen (GDK) • Schweizerische Pädiatrische Onkologie Gruppe (SPOG) • Universität Bern, Institut für Sozial- und Präventivmedizin (ISPM) • Krebsforschung Schweiz • Kinderkrebshilfe Schweiz Other funding sources 2014 /2015 • National Institute for Cancer Epidemiology and Registration (NICER) • Federal Office of Health (FOH) • AXA- Winterthur • Celgene GmbH (through Förderverein Schweizer Kinderkrebsregister) • Amgen Switzerland AG (through Förderverein Schweizer Kinderkrebsregister) • Helsana Versicherungen AG (through Förderverein Schweizer Kinderkrebsregister) 3. Routine Analyses 3.1 Overview 3.2 All cases registered in the SCCR (N = 9353) The SCCR registers all tumours diagnosed and treated in Switzerland, classified according to the ICCC - 3 and Langerhans cell histiocytosis (LCH) in patients aged 0 to 20 years at time of diagnosis. This annual report covers the time period from 1st January 1976 until 31st December 2014. The additional disorders, which are registered since 2014 (see inclusion criteria under paragraph 2.3), have not been included in the following analyses. Incidence rates are calculated based on the number of primary neoplasms (cases). The number of cases slightly exceeds the number of patients because patients with more than one primary tumour diagnosed before age 20 years are counted separately for each new tumour. This chapter describes data from all cases diagnosed 1976 - 2014, resident in Switzerland or abroad, diagnosed or treated in Switzerland (N = 9353). The section on routine analyses includes three chapters: Chapter 3.2 presents data on all cases registered in the SCCR. This includes cases resident in Switzerland or abroad, who were diagnosed or treated in Switzerland. Chapter 3.3 presents data on cases resident in Switzerland, aged 0 to 14 years at diagnosis. This correspondents to the age group usually covered in international publications. Therefore, tables and figures can be compared with data from other countries. Because registration in Switzerland is more than 95% complete for this age range with estimated incidence and survival rates close to their true value. Chapter 3.4 presents data on cases resident in Switzerland, aged 15 to 20 years at diagnosis. Patients of this age group are treated in a large number and variety of clinics and therefore registration is less complete. Ultimately, incidence rates cannot be calculated for this age group. Up to 31st December 2014, a total of 9353 cases classifiable according to the ICCC-3, or Langerhans cell histiocytosis (LCH), have been registered in the SCCR. These tumours were diagnosed in 9225 patients. Among these, 9099 patients had only one primary neoplasm, 124 patients had two primary neoplasms and 2 patients had three primary neoplasms at age 0 - 20 years. The SCCR started in 1976. Initially, only patients aged 0 to 15 years who participated in clinical trials were registered. Non- trial patients have been included since 1982, resulting in a significant increase in the number registered. In the early 1990s, the introduction of the first electronic database further increased case registration. Since then, annual registration has remained constant (Figure 1). In the last five years (2010 - 2014), a total of 1461 newly diagnosed cases were registered; among them 1278 cases in Swiss residents (Table 1). Swiss residents account for 8317 (89%) of all cases and foreign residents for 1036 (11%) cases (Table 2). Swiss residents make up 38% (168 /447) of all retinoblastoma patients, while foreign residents make up 62% (279 /447) of these patients. This is due to the international reputation of the Jules Gonin Hospital in Lausanne, which is the national centre for retinoblastoma treatment but also attracts many patients from abroad. Figure 1 Annual number of registered cases over time Swiss and foreign residents, age at diagnosis 0 - 14 years; period of diagnosis 1976 - 2014; all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 7504 Annual number of cases 250 200 150 100 50 0 1976 1982 1988 Year of childhood cancer diagnosis Swiss Childhood Cancer Registry Annual Report 2014/2015 Routine Analyses 1994 2000 2006 2012 Total Swiss residents 13 Year of diagnosis All patients residents Swiss residents Foreign Age at diagnosis (years) Age at diagnosis (years) Age at diagnosis (years) 0 - 14 Table 1 Total number of cases registered in the SCCR, by period of diagnosis 15 - 20 0 - 14 15 - 20 0 - 14 15 - 20 1976 - 1984 1151 267 1024 243 127 24 1985 - 1989 864 231 730 213 134 18 1990 - 1994 1080 253 934 231 146 22 1995 - 1999 1043 294 930 268 113 26 2000 - 2004 1072 279 999 257 73 22 2005 - 2009 1061 297 931 279 130 18 2010 - 2014 1233 228 1056 222 177 6 7504 1849 6604 1713 900 136 Swiss and foreign residents, age at diagnosis 0 - 20 years; period of diagnosis 1976 - 2014; all diagnoses (ICCC - 3 or Langer hans cell histiocytosis); N = 9353 Age at diagnosis (years) All ages (0 -20) n Switzerland 8317 88,9 6604 88,0 1713 92,6 Foreign countries 1036 11,1 900 12,0 136 7,4 726 7,8 645 8,6 81 4,4 • Neighbouring countries % n % 405 4,3 351 4,7 54 2,9 - Austria 10 0,1 10 0,1 0 0,0 - France 141 1,5 110 1,5 31 1,7 79 0,8 74 1,0 5 0,3 174 1,9 156 2,1 18 1,0 1 0,0 1 0,0 0 0,0 - Germany - Italy - Liechtenstein • Other European countries 321 3,4 294 3,9 27 1,5 Middle East 34 0,4 29 0,4 5 0,3 North Africa 152 1,6 122 1,6 30 1,6 48 0,5 41 0,5 7 0,4 Other African countries Table 2 Total number of cases registered in the SCCR, by country of residence n Adolescents (15 -20) Country of residence Europe % Children (0 -14) All other countries 59 0,6 51 0,7 8 0,4 Abroad 17 0,2 12 0,2 5 0,3 TOTAL 9353 100,0 7504 100,0 1849 100,0 Swiss and foreign residents, age at diagnosis 0 - 20 years; period of diagnosis 1976 - 2013; all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 9353 14 3.3 Swiss residents aged 0 -14 years at diagnosis (N = 6604) ral tissue, nephroblastoma (5%) from renal tissue, hepatoblastoma (1%) in the liver, germ cell tumours (3%), and retinoblastoma (3%). This chapter reports on cases aged 0 - 14 years and resident in Switzerland at diagnosis with a tumour coded according to ICCC - 3 or a Langerhans cell histiocytosis. Results for this age group can be compared directly to data from other countries. Germ cell tumours may arise in the gonads (ovaries and testes), or in other sites, such as the brain (intracranial germ cell tumours). Soft tissue sarcomas (7%), and malignant bone tumours (4%) arise from abnormal connective tissue. Occasionally, children also develop carcinomas such as melanomas or other rare tumours (3%). Langerhans cell histiocytosis (3%) is officially not counted as a malignant disease. But as children with this disease are treated similarly to those with cancer and in rare cases also die, they are recorded in the Swiss Childhood Cancer Registry. The relative frequency of the different tumour types varies with age (Table 3 and Figure 2). Diagnoses The International Classification of Childhood Cancer (ICCC -3) distinguishes 12 groups of cancers (Table 3). The most common are leukaemias (33% of all cancers), followed by tumours of the central nervous system (20%; especially brain tumours); and lymphomas (12%). Other cancers arise from embryonic tissue. These include neuroblastoma (7%) from primitive neu- Table 3 Main diagnostic groups according to ICCC - 3, by age at diagnosis All children Diagnosis I Leukaemias, myeoloproliferative diseases and myelodysplastic diseases II Lymphomas and reticuloendothelial neoplasms III Central nervous system neoplasms n % n <1 % By age at diagnosis (years) 1 -4 5 -9 n % n % 10 - 14 n % 2167 32,8 87 13,7 1039 45,0 605 34,2 436 23,1 814 12,3 22 3,5 130 5,6 228 12,9 434 23,0 1318 20,0 73 11,5 375 16,2 488 27,6 382 20,2 IV Neuroblastoma and other peripheral nervous cell tumours 432 6,5 185 29,1 194 8,4 34 1,9 19 1,0 V 167 2,5 78 12,3 80 3,5 8 0,5 1 0,1 339 5,1 48 7,5 196 8,5 83 4,7 12 0,6 Retinoblastoma VI Renal tumours VII Hepatic tumours 62 0,9 20 3,1 25 1,1 7 0,4 10 0,5 VIII Malignant bone tumours 285 4,3 0 0,0 19 0,8 86 4,9 180 9,5 IX Soft tissue and other extraosseous sarcomas 443 6,7 47 7,4 127 5,5 111 6,3 158 8,4 179 2,7 36 5,7 42 1,8 25 1,4 76 4,0 184 2,8 4 0,6 8 0,3 40 2,3 132 7,0 X Germ cell tumours, trophoblastic tumours and neoplasms of gonads XI Other malignant epithelial neoplasms and malignant melanomas XII Other specified and unspecified malignant neoplasms Langerhans cell histiocytosis Total 14 0,2 2 0,3 4 0,2 1 0,1 7 0,4 200 3,0 34 5,3 71 3,1 54 3,1 41 2,2 6604 100,0 636 100,0 2310 100,0 1770 100,0 1888 100,0 Swiss residents; age at diagnosis 0 - 14 years; period of diagnosis 1976 - 2014; all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 6604 Swiss Childhood Cancer Registry Annual Report 2014/2015 Routine Analyses 15 Figure 2 Main diagnostic groups according to ICCC - 3, by age at diagnosis 100% 90% I. Leukaemias II. Lymphomas III. CNS neoplasms 80% IV. Neuroblastoma 70% V. Retinoblastoma VI. Renal tumours 60% VII. Hepatic tumours 50% VIII. Malignant bone tumours IX. Soft tissue sarcomas 40% X. Germ cell tumours 30% XI. Other malignant epithelial neoplasms 20% XII. Other specified and unspecified malignant neoplasms 10% 0% Langerhans cell histiocytosis <1 1-4 5-9 Age at diagnosis (years) 10-14 Swiss residents; age at diagnosis 0 - 14 years; period of diagnosis 1976 - 2014; all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 6604 Follow-up information The SCCR collects follow- up information for patients in several ways: 1. Clinical follow- up is any contact the patient has with the paediatric oncology and haematology centre. Annual clinical follow- up care in paediatric centres usually ends 5 - 10 years after diagnosis. Then the patient is officially discharged or referred to an adult oncology centre. Alternatively clinical follow- up also ends as soon as the patient dies. 2. Long- term epidemiological follow- up for vital status, subsequent neoplasms and current health employs four complementary approaches: • Vital status and current address and place of birth are updated by contacting municipal population registers. Vital status is known for most cases: among the 6541 patients, 1636 (25%) have died, and 4905 (75%) are still alive (Table 4). Among these, most (4608) have been followed- up during the past 5 years, 165 (3%) have last been followed up between 2004 and 2008, and only 132 (3%) before 2004. Among the latter, 93 (32 between 2004 - 2008 and 61 before 2004) are lost to follow- up, because they moved abroad. • Causes of death are retrieved from Swiss mortality statistics by record linkage. • Second primary neoplasms are notified via paediatric oncology and haematology centres, detected by regular comparison with cantonal (regional) cancer registries in Switzerland, or self- reported by survivors and then validated with pathology reports. • Morbidity and quality of life are assessed by paper questionnaires to survivors in the Swiss Childhood Cancer Survivor Study and Childhood Cancer Follow- up Study (Chapter 4.2). Table 4 Follow- up information available in the SCCR n % Alive 4905 75.0 Last clinical follow- up after 2008 4608 93.9 Last clinical follow- up 2004 - 2008 165 3.4 Last clinical follow- up before 2004 132 2.7 Deceased 1636 25.0 TOTAL 6541 100.0 Swiss residents; age at diagnosis 0 - 14 years; period of diagnosis 1976 - 2014; all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 6541 patients (6604 cases) 16 Survival Long- term survival has improved significantly over the last decades (Figure 3). Ten- year survival increased from 58% in children diagnosed between 1976 and 1984, to 71% in children diagnosed between 1985 and 1994, 80% in children diagnosed between 1995 and 2004, and 87% in children diagnosed within the last decade (2005 - 2014). Survival varied widely between diagnostic groups. Figure 4 presents survival by diagnostic group according to ICCC - 3 in children diagnosed between 1995 and 2014. Of 3916 children, 705 (18%) have died. The following numbers describe five- year survival for each main diagnostic group: 99% for Langerhans cell histiocytosis; 96% for germ cell tumours; 95% for renal tumours; 94% for lymphoma; 94% for retinoblastoma; 85% for children with leukaemia; 83% for malignant bone tumours; 78% for neuroblastoma; 76% for hepatic tumours; 75% for soft tissue sarcomas and 74% for central nervous system neoplasms. 100% 90% 80% 70% 60% 50% Figure 3 Survival of patients in the SCCR, by period of diagnosis Swiss residents; age at diagnosis 0 - 14 years; period of diagnosis 1976 - 2014; all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 6604; adjusted for age. 40% Period of diagnosis 30% 2005 - 2014 1995 - 2004 20% 1985 - 1994 10% 1976 - 1984 0% 0 5 10 Years since diagnosis 15 20 25 30 35 40 100% 90% 80% 70% 60% 50% 40% LHC Lymphoma Other malignant tumours Malignant bone tumours CNS tumours 30% Figure 4 Survival of patients by diagnostic groups according to ICCC - 3 20% Swiss residents; age at diagnosis 0 - 14 years; period of diagnosis 1995 - 2014 all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 3916; adjusted for age. 0% 10% 0 5 Years since diagnosis Swiss Childhood Cancer Registry Annual Report 2014/2015 20 Routine Analyses Retinoblastoma Renal tumours Leukemias Soft-tissue sarcoma Neuroblastoma 15 20 17 Cancer incidence (2005 -2014) in Switzerland, for children aged 0 -14 years at diagnosis Table 5 describes the tumours registered in the SCCR during the last ten years (2005-2014). Diagnoses are coded according to ICCC-3, most tumours were more common in boys than in girls. The age- standardised incidence (according to the European standard population) of any childhood cancer (not including Langerhans cell histiocytosis) was 16.1 per 100,000 person- years. Incidence was highest among children aged 2 years with 24.9 cases per 100,000 person- years (boys 28.0, girls 21.6). Incidence was lowest in 9 year olds with 8.6 cases per 100,000 person- years (boys 9.1, girls 8.0) (Figure 5 shows crude incidence rates in Swiss residents; age at diagnosis 0 - 14 years; period of diagnosis 1995 - 2014; all diagnoses (ICCC - 3 but not including Langerhans cell histiocytosis); Figure 6 shows age- and sex- specific incidence rates for age 0 - 14). Table 5 Childhood cancer diagnosed in Switzerland 2005 - 2014: number of cases, relative frequency, sex ratio, median age at diagnosis and incidence standardised according to the European standard population, by diagnostic groups according to ICCC - 3 n Relative frequency Leukaemias, myeloproliferative diseases and myelodysplastic diseases 648 33,6 1,6 4,8 5,4 a. Lymphoid leukaemias 522 80,6 1,5 4,7 4,4 78 12,0 1,9 4,7 0,7 9 1,4 3,5 10,0 0,1 32 4,9 3,0 6,3 0,3 7 1,1 0,8 5,5 0,1 215 11,2 1,8 10,9 1,8 96 44,7 0,9 12,7 0,8 Diagnosis I b. Acute myeloid leukaemias c. Chronic myeloproliferative diseases d. Myelodysplastic syndrome and other myeloproliferative diseases e. Unspecified and other specified leukaemias II Lymphomas and reticuloendothelial neoplasms a. Hodgkin lymphomas b. Non- Hodgkin lymphomas (except Burkitt lymphoma) 58 27,0 2,9 8,9 0,5 c. Burkitt lymphoma 56 26,0 7,0 7,3 0,5 d. Miscellaneous lymphoreticular neoplasms 5 2,3 0,3 1,3 0,0 e. Unspecified lymphomas 0 NA NA NA NA 442 22,9 1,2 6,8 3,7 48 10,9 1,3 2,7 0,4 186 42,1 1,1 7,0 1,6 80 18,1 1,4 6,5 0,7 III CNS and miscellaneous intracranial and intraspinal neoplasms a. Ependymomas and choroid plexus tumour b. Astrocytomas c. Intracranial and intraspinal embryonal tumours d. Other gliomas 52 11,8 1,3 6,5 0,4 e. Other specified intracranial and intraspinal neoplasms 67 15,2 1,2 10,8 0,6 f. Unspecified intracranial and intraspinal neoplasms IV Neuroblastoma and other peripheral nervous cell tumours a. Neuroblastoma and ganglioneuroblastoma b. Other peripheral nervous cell tumours V Retinoblastoma VI Renal tumours a. Nephroblastoma and other nonepithelial renal tumours b. Renal carcinomas c. Unspecified malignant renal tumours VII Hepatic tumours a. Hepatoblastoma 18 Sex ratio Age at Dx (male:female) (Median) Incidence* 9 2,0 0,8 8,6 0,1 118 6,1 1,1 1,5 1,0 118 100,0 1,1 1,5 1,0 0 NA NA NA NA 42 2,2 0,8 1,0 0,4 98 5,1 0,8 3,3 0,8 93 94,9 0,8 3,2 0,8 5 5,1 0,7 12,8 0,0 0 NA NA NA NA 15 0,8 2,0 2,1 0,1 14 93,3 1,8 1,9 0,1 b. Hepatic carcinomas 1 6,7 0,0 14,1 0,0 c. Unspecified malignant hepatic tumours 0 NA NA NA NA Table 5 Continued Diagnosis VIII Malignant bone tumours a. Osteosarcomas b. Chondrosarcomas c. Ewing tumour and related sarcomas of bone Sex ratio Age at Dx (male:female) (Median) Incidence* 79 4,1 0,9 11,2 0,7 38 48,1 0,9 11,7 0,3 1 1,3 0,0 14,4 0,0 39 49,4 1,0 10,9 0,3 d. Other specified malignant bone tumours 0 NA NA NA NA e. Unspecified malignant bone tumours 1 1,3 0,0 14,7 0,0 139 7,2 1,4 7,8 1,2 78 56,1 1,4 5,5 0,7 b. Fibrosarcomas, peripheral nerve sheath tumours, and other fibrous neoplasms 10 7,2 2,3 10,9 0,1 c. Kaposi sarcoma 0 NA NA NA NA d. Other specified soft tissue sarcomas 40 28,8 0,9 11,1 0,3 e. Unspecified soft tissue sarcomas 11 7,9 4,5 2,8 0,1 Germ cell tumours, trophoblastic tumours, and neoplasms of gonads 58 3,0 1,1 6,4 0,5 a. Intracranial and intraspinal germ cell tumours 15 25,9 2,0 12,1 0,1 IX Soft tissue and other extraosseous sarcomas a. Rhabdomyosarcomas X Relative frequency n b. Malignant extracranial and extragonadal germ cell tumours 18 31,0 0,6 0,2 0,2 c. Malignant gonadal germ cell tumours 24 41,4 1,2 11,5 0,2 d. Gonadal carcinomas 0 NA NA NA NA e. Other and unspecified malignant gonadal tumour 1 1,7 0,0 0,8 0,0 71 3,7 0,6 12,2 0,6 2 2,8 1,0 6,4 0,0 14 19,7 0,3 13,5 0,1 2 2,8 1,0 13,6 0,0 15 21,1 0,5 10,4 0,1 7 9,9 1,3 7,0 0,1 31 43,7 0,6 12,0 0,3 3 0,2 2,0 0,0 0,0 a. Other specified malignant tumours 2 66,7 1,0 1,8 0,0 b. Other unspecified malignant tumours 1 33,3 0,0 0,0 0,0 1928 100,0 1,3 6,2 16,1 59 3,0 1,4 5,2 0,5 1987 100,0 1,3 6,2 16,6 XI Other malignant epithelial neoplasms and malignant melanomas a. Adrenocortical carcinomas b. Thyroid carcinomas c. Nasopharyngeal carcinomas d. Malignant melanomas e. Skin carcinomas f. Other and unspecified carcinoma XII Other and unspecified malignant neoplasms Total (not including Langerhans cell histiocytosis) Langerhans cell histiocytosis Total (including Langerhans cell histiocytosis) * Incidence: newly diagnosed tumours in a one year time period per 100,000 persons (person - years) Swiss residents; age at diagnosis 0 - 14 years, period of diagnosis 2005 - 2014, all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 1987 Swiss Childhood Cancer Registry Annual Report 2014/2015 Routine Analyses 19 20.0 Figure 5 Crude incidence rate (per 100,000 person - years) in Switzerland, by sex and year of diagnosis for the last 20 years (1995 - 2014) Incidence rate 15.0 10.0 Total Boys Girls 5.0 Swiss residents; age at diagnosis 0 - 14 years; period of diagnosis 1995 - 2014; all diagnoses (ICCC - 3 but not including Langerhans cell histiocytosis); N = 3916 0.0 2000 1995 Year of childhood cancer diagnosis 2005 2010 2014 30 Boys Girls 25 20 15 10 Figure 6 Age- and sex- specific incidence rates (per 100,000 person- years) in Switzerland for the last 10 years Swiss residents; age at diagnosis 0 - 14 years; period of diagnosis 2005 - 2014; all diagnoses (ICCC - 3 but not including Langerhans cell histiocytosis); N = 1928 20 5 0 1 2 3 0 Age at diagnosis 4 5 6 7 8 9 10 11 12 13 14 3.4 Swiss residents aged 15 -20 years at diagnosis (N = 501) Table 6 describes the tumours registered in the last ten years (2005 - 2014) diagnosed in adolescent patients (aged 15 - 20 years at diagnosis, N = 501). Because data on adolescents are currently not complete within the SCCR, we do not present incidence rates. In adolescents the sex ratio is closer to 1 than in those aged 0 - 14 years at diagnosis. Table 6 Adolescent cancer diagnosed in Switzerland 2005 - 2014: number of cases, relative frequency, sex ratio, median age at diagnosis I Diagnosis n Relative frequency Sex ratio (male:female) Age at Dx (Median) Leukaemias, myeloproliferative diseases and myelodysplastic diseases 61 12,2 1,4 16,4 a. Lymphoid leukaemias 31 50,8 2,1 15,9 b. Acute myeloid leukaemias 16 26,2 0,8 16,8 c. Chronic myeloproliferative diseases 8 13,1 1,0 18,1 d. Myelodysplastic syndrome and other myeloproliferative diseases 6 9,8 2,0 16,7 e. Unspecified and other specified leukaemias II 0 NA NA NA 131 26,3 0,8 16,7 a. Hodgkin lymphomas 93 71,0 0,8 16,7 b. Non - Hodgkin lymphomas (except Burkitt lymphoma) 32 24,4 1,0 17,0 c. Burkitt lymphoma 5 3,8 1,5 17,9 d. Miscellaneous lymphoreticular neoplasms 1 0,8 0,0 16,6 Lymphomas and reticuloendothelial neoplasms e. Unspecified lymphomas III CNS and miscellaneous intracranial and intraspinal neoplasms a. Ependymomas and choroid plexus tumour b. Astrocytomas NA NA NA 16,8 1,2 16,7 6 7,1 1,0 18,3 26 31,0 0,7 16,7 c. Intracranial and intraspinal embryonal tumours 16 19,0 1,7 16,5 d. Other gliomas 10 11,9 1,0 16,8 e. Other specified intracranial and intraspinal neoplasms 25 29,8 1,5 16,5 1 1,2 0,0 15,4 0 NA NA NA 0 NA NA NA f. Unspecified intracranial and intraspinal neoplasms IV Neuroblastoma and other peripheral nervous cell tumours a. Neuroblastoma and ganglioneuroblastoma V 0 84 b. Other peripheral nervous cell tumours 0 NA NA NA Retinoblastoma 0 NA NA NA VI Renal tumours 7 1,4 2,5 16,6 a. Nephroblastoma and other nonepithelial renal tumours 2 28,6 0,0 16,0 b. Renal carcinomas 5 71,4 1,5 17,4 c. Unspecified malignant renal tumours 0 NA NA NA VII Hepatic tumours 2 0,4 0,0 17,4 a. Hepatoblastoma 0 NA NA NA b. Hepatic carcinomas 2 100,0 0,0 17,4 c. Unspecified malignant hepatic tumours 0 NA NA NA 48 9,6 1,5 16,2 33 68,8 1,8 16,3 VIII Malignant bone tumours a. Osteosarcomas b. Chondrosarcomas 1 2,1 0,0 15,1 12 25,0 1,0 16,0 d. Other specified malignant bone tumours 2 4,2 1,0 16,7 e. Unspecified malignant bone tumours 0 NA NA NA c. Ewing tumour and related sarcomas of bone Swiss Childhood Cancer Registry Annual Report 2014/2015 Routine Analyses 21 Table 6 Continued Diagnosis IX Soft tissue and other extraosseous sarcomas a. Rhabdomyosarcomas b. Fibrosarcomas, peripheral nerve sheath tumours, and other fibrous neoplasms c. Kaposi sarcoma d. Other specified soft tissue sarcomas e. Unspecified soft tissue sarcomas X n Relative frequency Sex ratio (male:female) Age at Dx (Median) 33 6,6 0,9 16,7 13 39,4 0,9 16,1 3 9,1 0,0 15,8 0 NA NA NA 13 39,4 0,4 17,4 4 12,1 3,0 16,8 38 7,6 8,5 17,8 a. Intracranial and intraspinal germ cell tumours 3 7,9 0,0 17,2 b. Malignant extracranial and extragonadal germ cell tumours 0 NA NA NA 33 86,8 15,5 18,0 2 5,3 0,0 15,7 Germ cell tumours, trophoblastic tumours, and neoplasms of gonads c. Malignant gonadal germ cell tumours d. Gonadal carcinomas e. Other and unspecified malignant gonadal tumour XI Other malignant epithelial neoplasms and malignant melanomas a. Adrenocortical carcinomas b. Thyroid carcinomas c. Nasopharyngeal carcinomas d. Malignant melanomas e. Skin carcinomas f. Other and unspecified carcinoma XII Other and unspecified malignant neoplasms a. Other specified malignant tumours b. Other unspecified malignant tumours Total (not including Langerhans cell histiocytosis) Langerhans cell histiocytosis Total (including Langerhans cell histiocytosis) 0 0,0 NA NA 93 18,6 0,7 18,1 1 1,1 0,0 17,0 25 26,9 0,1 18,0 3 3,2 2,0 18,7 29 31,2 0,9 18,6 9 9,7 0,8 18,4 26 28,0 1,4 17,7 2 0,4 0,0 16,3 2 100,0 0,0 16,3 0 NA NA NA 499 100,0 1,1 16,8 2 0,4 1,0 16,4 501 100,0 1,1 16,8 Age at diagnosis 15 - 20 years, period of diagnosis 2005 - 2014, all diagnoses (ICCC - 3 or Langerhans cell histiocytosis); N = 501 22 4. Research on childhood cancer The research of the childhood cancer registry focusses on three main topics: Aetiology of childhood cancer, long- term outcomes, and follow -up care after childhood cancer or young adult cancer. These topics are described with their background, aims, methods, recent findings, ongoing studies, and contacts in the remainder of Chapter 4. Additional information is avail- able from the investigators and our website (www.childhoodcancerregistry.ch). Further, we thank the supporters for their generous contributions towards the research projects. All ongoing studies, their funding sources and the senior investigator are summarized in Table 7. Table 7 Research grants of the SCCR, summary No Project name Senior investigator Funding sources Study period 1 Spatial and spatio - temporal clustering of childhood cancer: The role of infections and environmental hazards Spycher BD Swiss Cancer Research (KFS - 3515 - 08 - 2014) 01.2014 - 12.2016 2 The spatial epidemiology of childhood cancer in Switzerland Spycher BD Swiss National Science Foundation (PZ00P3_147987) 09.2013 - 08.2016 3 The role of population mixing and exposure to infections in Spycher BD the aetiology of childhood leukaemia: A national cohort study Swiss Cancer Research (KFS - 3049 - 08 - 2012) 01.2013 - 12.2014 4 Childhood cancer and geographically defined exposures in Switzerland: A census - based nationwide cohort study Federal Office of Public Health (12.008357) 03.2013 - 11.2013 5 Childhood cancer and vicinity of residence to petrol stations Kuehni CE and roads: A census -based nationwide cohort study (PETROL) Federal Office of Public Health (10.002946) 06.2010 - 02.2013 6 Childhood cancer and nuclear power plants in Switzerland: A census - based cohort study Swiss Cancer League (02224 - 03 - 2008); Federal Office of Public Health (08.001616) 09.2008 - 02.2011 Kuehni CE, Angst R Kuehni CE, Bergstraesser E Kuehni CE Von der Weid NX, Kuehni CE Von der Weid NX, Kuehni CE Kuehni CE Cancer League Aarau Cancer League Zurich 01.2012 - 12.2012 08.2010 - 07.2011 Cancer League Bern Swiss Cancer League (KLS - 2215 - 02 - 2008) Swiss Cancer League (KLS - 1605 - 10 - 2004) Kinderkrebshilfe Schweiz 04.2009 - 03.2010 07.2008 - 06.2010 Kuehni CE Swiss Cancer League (KLS - 3412 - 02 - 2014) EU (FP7 - HEALTH - F2 - 2013 602030; project no. 602030) 07.2014 - 06.2017 Aetiology of childhood cancer Spycher BD Kuehni CE Outcome research (Long - term outcomes, follow - up care, international collaboration) 1 Swiss Childhood Cancer Survivor Study (SCCSS) 2 PanCare Studies in Fertility and Ototoxicity to improve Quality of Life after Cancer during Childhood, Adolescence and Young Adulthood (PanCareLIFE) Kuehni CE 01.2006 - 10.2008 since 2006 11.2013 - 10.2018 3 Dietary habits, nutrition and risk of late effects after childhood cancer Bochud M, Kuehni CE Swiss Cancer League (KLS - 3644 - 02 - 2015) 07.2015 - 06.2018 4 Psychological late effects in long - term childhood cancer survivors – Development of guidelines for follow - up care Michel G Krebsliga Zentralschweiz 11.2015 - 10.2017 5 PanCare childhood and adolescent cancer survivor care and follow - up studies (PanCareSurFup) Kuehni CE Swiss Cancer Research (KFS - 02783 - 02 - 2011) EU (FP7 - HEALTH - F2 - 2010 257505; project no. 257505) 08.2011 - 07.2014 Kuehni CE 6 Mortality after cancer in childhood and adolescence Kuehni CE Kuehni CE 02.2011 - 01.2017 Swiss National Science 08.2012 - 08.2015 Foundation (PDFMP3_141775) Swiss Bridge 7 Follow - up care after childhood and young adult cancer (CCFU) Michel G Swiss National Science Foundation (PZ00P3_121682 and PZ00P3_141722) 08.2009 - 08.2014 8 Effectiveness of transition from paediatric to adult care after childhood cancer Michel G Swiss Cancer League (KFS - 02631 - 08 - 2010) 04.2011 - 04.2014 Research projects on childhood cancer 23 Swiss Childhood Cancer Registry Annual Report 2014/2015 No Project name (continued) Senior investigator Funding sources 9 Parents of long-term childhood cancer survivors Michel G Swiss National Science Foundation (100019_153268 /1) Kinderkrebshilfe Schweiz since 2013 10 Fertility after Chemo- and Radiotherapy in Childhood and Adolescence, FeCt – Multicentre Michel G Kinderkrebshilfe Schweiz since 2012 11 Risk of cancer and long-term mortality in children treated with growth hormone: Swiss participation in the EU FP7 project (SAGhE) Mullis P, Kuehni CE Swiss Cancer League (KLS-2948-02-2012) EU (FP-HEALTH-F2-2009223497) Swiss Cancer League (KLS-02586-02-2010) 07.2012-12.2013 Mullis P Mullis P, Kuehni CE 24 Study period 04.2011-03.2014 07.2010-12.2012 4.1 Aetiology of childhood cancer Background The aetiology of childhood cancers remains largely unknown. For leukaemia, the most frequent childhood cancer, known risk factors include trisomy 21, certain rare genetic syndromes, some common germline genetic variants, high birthweight, and high parental age at birth. Regarding environmental exposures, only ionising radiation at medium to high doses is an established risk factor – both for leukaemia and CNS tumours. Numerous other environmental factors are being discussed as potential risk factors. These include: low dose ionising radiation (e.g. natural background radiation and diagnostic radiation), traffic related air pollution, electromagnetic fields (e.g. from power lines, radio and TV transmitters, or mobile phones) pesticides, and infections. Aims The broad aims of the research group are to investigate whether: • Cancer risks in children are associated with environmental exposures, such as ionising and non- ionising radiation, air pollution and exposure to infectious diseases, as well as parents workplace exposures; • Cancer risks in children are associated with socio economic, family or perinatal exposures; • Cases of cancer tend to cluster in space and /or in space and time and, if yes, to elicit aetiological clues from the pattern of clustering. Methods Clinical and residential information on diagnosed cases are obtained from the SCCR. Data on the population at risk are obtained from the Swiss National Cohort (SNC) which includes the entire Swiss resident population at census time points (1990, 2000, and annually from 2010 onward). Record linkage between the two datasets allows investigating cancer incidence on a nationwide scale with a cohort design. The SCCR collects geocoded address histories from birth to diagnosis allowing to distinguish different exposure time windows. Geocoded places of residence are also available for the entire population from the SNC. This allows calculating geographically determined exposures such as distance to highways or NO2 concentration levels (based on spatial pollution models) for the entire population at risk. The SNC also provides demographic, socioeconomic and perinatal data for the entire population. The availability of precise geocodes of residence allows assessing spatial and spatio- temporal clustering using methods for point pattern data rather than methods for less precise regional count data (e.g. aggregated at municipality level). Swiss Childhood Cancer Registry Annual Report 2014/2015 Current status A, Recent findings: A summary of our recent research and findings is given in [Lupatsch - 2016a]. We found evidence of increased risks of childhood leukaemia and CNS tumours among children exposed to higher levels of natural background radiation (terrestrial gamma and cosmic radiation) [Spycher - 2015a, 2015b, 2015c]. Young children living in the immediate proximity (<100m) of highways were found to have an increased leukaemia risk [Spycher - 2015d]. We found little evidence of associations between childhood leukaemia and commonly used measures of population mixing [Lupatsch - 2015b, c] or for associations between leukaemia risk and socioeconomic status [Adam - 2015]. However, we did find evidence of a temporal association between childhood leukaemia and periods of rapid population growth in Swiss municipalities [Lupatsch - 2016d]. We found evidence for spatio- temporal clustering of leukaemia around the time of birth, but not around the time of diagnosis [Kreis - 2016]. B, Ongoing studies: In ongoing studies we are investigating whether: i) Childhood cancer is associated with increased air concentrations of benzene and NO2; ii) Childhood leukaemia is associated with perinatal characteristics (including parental age, birth order, age difference to next older sibling, and birth weight); iii) Cases of childhood leukaemia born close in time and space to another case (clustered cases) differ from non- clustered cases with respect to diagnostic, socio economic characteristics and environmental exposures; and iv) whether there is evidence for spatial clustering in Switzerland. Furthermore, we are v) collaborating in an international case control study on the association between childhood cancer and proximity to power lines. Contact The research team consists of Ben Spycher, Claudia Kuehni, Christian Kreis and Garyfallos Konstantinoudis. Research projects on childhood cancer 25 4.2 Long-term outcomes Background Cancer is the most common disease-related cause of death during childhood in the Western world. Thanks to therapeutic improvements in the recent decades, survival rates for childhood cancer now exceed 80%, leading to a growing population of long- term survivors. However, cancer and its treatment can cause adverse late effects, such as second primary malignancies, cardiovascular disease, hearing loss and infertility. These adverse late effects may affect survivors’ health, health behaviour and quality of life, and may lead to premature death. Comprehensive data on the burden of late effects of childhood cancer including premature mortality and their risk factors are scarce. The SCCR has a broad research program focusing on long- term outcomes that includes the national Swiss Childhood Cancer Survivor Study (SCCSS) and a study on cause- specific long- term mortality. Aims The research group aims: • To investigate prevalence, incidence and spectrum of somatic and psychosocial outcomes including second primary neoplasms, somatic health, mental health, educational and social outcomes, health- related quality of life, and cause- specific long- term mortality. • To determine sociodemographic, cancer- and treatment related predictors associated with long- term outcomes. • To describe health behaviours in long- term survivors. Methods This prospective cohort study is based on children and adolescents registered in the SCCR. Study population: All individuals who are at least 5-year survivors, who were diagnosed with cancer at age < 21 years, and were Swiss residents at time of diagnosis are eligible. Collected data: A detailed questionnaire is sent to childhood cancer survivors and their parents to obtain data about somatic, psychosocial, and mental health outcomes. For comparison, a similar questionnaire is sent to siblings of survivors. Questionnaire data are complemented with phone interviews to patients and are validated with information from general practitioners and hospital records, e.g. audiometric or lung function tests to validate hearing problems or lung diseases. Furthermore, we collect data from municipal population registries to obtain vital statistics including dates of death, and Swiss mortality statistics to obtain causes of death. For some studies, we also collect saliva samples for genetic analyses. These broad data make it possible to investigate prevalence and incidence of adverse late effects and to identify their predictors in Swiss survivors. Response rate: For the SCCSS questionnaire survey, we contacted 2930 five- years survivors aged 0 to 16 years at diagnosis, 2235 (76%) completed our questionnaire. Among 598 contacted survivors aged 16 - 20 years at diagnosis whom we contacted, 320 (57%) participated. We also contacted 1522 siblings, of whom 866 (57%) participated. 26 Current status A, Recent findings This study offers the first national-level data on adverse late effects, health behaviour, survival and long-term mortality after cancer in childhood and adolescence in Switzerland. The study is ongoing and we are currently contacting new 5 - year survivors diagnosed between 2005 - 2010. We obtained causes of death of 3965 of the 5 - year survivors who subsequently died. We analyse and publish our findings continuously. Previous publications have included topics like health-related quality of life, education, cognitive problems, partnership, income, physical activity, nutrition, survival, and mortality. Our findings will help to identify patients who are at increased risk for late effects, to adjust therapies and to develop tailored follow- up programs for survivors. Health- related quality of life (HRQoL): We found that the overall HRQoL of young survivors (8 - 16 years) was comparable to population norms for most parent- reported dimensions and higher for most self- reported dimensions [Wengenroth - 2015]. However, older survivors (>16 years) had lower HRQoL than their siblings, and among survivors, those with chronic health problems had the lowest health- related quality of life [Rueegg2013]. Survivors of acute lymphoblastic leukemia reported good HRQoL, even after a relapse [Essig - 2012]. Educational and social outcomes: We also showed that survivors achieved educational levels similar to the general population [Kuehni - 2012]. Survivors younger than 20 years were more likely than their siblings to report cognitive problems [Wengenroth - 2015]. We found lower personal income in survivors than in siblings [Wengenroth - 2016]. However, survivors’ personal income may increase later because treatment can push back education and carreer training and cause survivors to start working later than their peers. Survivors are less likely than peers to be married or in a life partnership [Wengenroth - 2014]. This might be because survivors take longer to reach their final educational achievement, which might in turn encourage them to delay marriage. Physical activity: We found that daily physical activity and sport levels in survivors were similar to the general population. Physical activity was mainly determined by socio- demographic and cultural factors [Rueegg - 2012a]. However, we found that survivors are at high risk of suffering from performance limitations in sports and in daily living activities and that these limitations differed strongly between diagnostic groups [Rueegg - 2012b]. Despite these physical performance limitations, many survivors maintained healthy activity levels [Rueegg -2013]. Nutrition: We showed that the adherence to dietary recommendations among survivors was similar to their siblings and the general population, but poor overall [Belle - submitted]. Hearing loss: We found that the burden of hearing loss as a late effect after ototoxic cancer treatment has stabilized in recently treated survivors, which suggests that survivors have benefited from new treatment regimens that use less ototoxic radiation and more carefully dosed platinum compounds [Weiss - accepted]. Mortality: We found that the mortality of five- year survivors of childhood cancers is elevated compared to the general population, with recurrence and progression of the original cancer as the most common causes of death up to 24 years after diagnosis [Schindler - 2016]. B, Ongoing studies Ongoing studies focus on different somatic health problems and health behaviours: i) diseases; ii) cardiac diseases; iii) hearing loss; and iv) dietary habits and excess weight. We are also collaborating with international studies (see International collaborations). Contact The research team consists of Claudia Kuehni, Fabiën Belle, Rahel Kasteler, Rahel Kuonen, Matthias Schindler, Grit Sommer, Annette Weiss, Gisela Michel and Nicolas von der Weid. Swiss Childhood Cancer Registry Annual Report 2014/2015 Research projects on childhood cancer 27 4.3 International collaborations Background Late effects of childhood cancer and its treatment are common, but numbers in individual countries are low. Therefore, pooling of data into large international cohorts is essential to identify risk factors for late effects using observational data and genetic tools. Survivors can benefit from personalized, evidence- based care based on their individual risk; and future patients may benefit from adapted treatment, that cause less severe side effects. International studies on childhood cancer often also include systematic reviews that summarize the evidence on risk factors of late effects. These provide the basis for creating new guidelines for the clinical long- term follow- up of survivors of cancer diagnosed at a young age. The SCCR collaborates with other childhood cancer cohorts [Bhatia - 2015, Winther - 2015], participates in European studies to investigate late effects, and is involved in the development of international guidelines for clinical long- term follow- up of childhood and adolescent cancer survivors. Aims Within the international collaborations, we aim to investigate: • Prevalence and incidence of late effects of childhood and adolescent cancer and its treatment • Risk factors for these late effects We also aim to develop guidelines to improve the health and quality of life of current and future survivors of childhood cancer. Methods Swiss patients of childhood and adolescence cancer are part of a Pan- European cohort. Researchers within this European collaboration can then select patients with late effects, for example patients with a second primary cancer, cardiac or hearing problems, for nested case- control or case- cohort studies. Within these studies, researchers can identify non- genetic and genetic risk factors of late effects. Experts and the International Guideline Harmonization Group (IGHG, http: / /www.ighg.org /) write up systematic reviews to develop evidence- based, standardised guidelines for clinical follow- up of survivors. 28 Current status A, Ongoing studies: Swiss patients of childhood and adolescence cancer are part of Pan- European cohorts. Researchers within this European collaboration can then select patients with late effects, for example patients with a second primary cancer, cardiac or hearing problems, for nested case- control or case- cohort studies. Within these studies, researchers can identify non- genetic and genetic risk factors of late effects. Currently, we are collaborating in two ongoing studies: PanCareSurFup (PanCare childhood and adolescent cancer survivor care and follow- up studies; http: / /www.pancaresurfup.eu /) This project investigates the burden and risk factors of the most severe and life threatening late effects, namely second primary neoplasms, cardiovascular disease and premature death. We contributed with 4719 Swiss 5 - year survivors to the Pan- European cohort and with detailed treatment data from medical records of 139 Swiss survivors to the European nestedcase control studies. Recent findings: A new method to facilitate valid and consistent grading of cardiac events in childhood cancer survivors has been published [Feijen - 2014] and several other publications are in preparation. PanCareLIFE (PanCare Studies in Fertility and Ototoxicity to Improve Quality of Life after Cancer during Childhood, Adolescence and Young Adulthood; http: / /www.pancarelife.eu /) This project investigates hearing loss, infertility and quality of life. We identified survivors at risk for hearing loss and collected their audiograms. We will contribute questionnaire data on hearing loss, fertility and quality of life from the SCCSS. We will be responsible, together with the University of Münster in Germany, for the statistical analysis of quality of life data from eight European countries. B, Development of guidelines In close collaboration with European and American experts and the International Guideline Harmonization Group (IGHG, http: / /www.ighg.org /), we write systematic reviews do develop evidence- based, standardized guidelines for clinical follow- up of survivors. We are currently involved as chairs, work group (WG) leaders and group members in the development of the following guidelines: Hearing loss (ototoxicity) • Chairs: Wendy Landier (USA), Richard Cohn (AUS) • WG leaders: Claudia Kuehni (CH), Thorsten Langer (DE) l Pulmonary dysfunction • Chairs and WG leaders: Claudia Kuehni (CH), Andrew Dietz (USA) l Fatigue, mental health and psychosocial problems • Chairs: Gisela Michel (CH), Jordan Gilleland Marchak (USA) • Fatigue WG leaders: Kathrin Scheinemann (CH), Gisela Michel (CH) • Mental Health WG leaders: Janine Vetsch (CH), Jordan Gilleland Marchak (USA) l Once the guidelines will be available, all centres of the Swiss Paediatric Oncology Group will implement these guidelines in Switzerland. Recent findings: A survey among paediatric oncology /haematology clinics from 44 European countries found that many clinics have insufficient or lack programmes for long- term follow- up into adulthood for survivors of childhood cancer [Brown - 2015]. This study showed that available guidelines are not universally used throughout Europe and we need to further develop and disseminate Pan- European long- term follow- up guidelines. Contact The research team consists of Claudia Kuehni, Rahel Kasteler, Rahel Kuonen, Grit Sommer, Annette Weiss, Gisela Michel and Nicolas von der Weid. Swiss Childhood Cancer Registry Annual Report 2014/2015 Research projects on childhood cancer 29 4.4 Psychosocial outcomes and follow-up care Background Treatment for cancer in children and young adults has greatly improved and most patients can be cured today. However, more than 50% of survivors of childhood cancer suffer from late effects. Similarly, parents might suffer long after their child has been cured. To detect and treat late effects as early as possible, most survivors should continue to attend follow- up care long after their cancer has been cured. Follow- up care needs to be constantly updated to meet the current status of research. International guidelines summarising the care needed after different cancers and treatment are necessary. Additionally, while various models of follow- up care have been described, so far none has been implemented in Switzerland. A successful model must not only take clinical aspect into account but also survivors’ preferences and needs. Aims The research group aims to: • Describe follow- up care models available across Europe, and preferences for a follow- up model among Swiss childhood and young adult cancer survivors, parents and physicians (oncologists and general practitioners) • Evaluate the transition / transfer from paediatric to adult care in survivors of childhood cancer • Describe psychological and socio- demographic outcomes, as well as needs in parents of long- term childhood cancer survivors Methods To describe follow- up care models in Europe, we invited 198 clinics and follow- up programmes in Europe to complete a questionnaire survey describing the follow- up care available at their institution. To assess preferences for different models of follow- up care, a questionnaire survey assessed opinions and perspectives on both currently used and desired optimal follow- up care among survivors, parents, paediatric and adult oncologists / haematologists and family practitioners. We evaluated the transition from paediatric to adults among childhood cancer survivors using medical records. Finally, we will contact parents in a questionnaire survey to assess positive and negative psychological, familial, and social outcomes [Mader - 2016]. These outcomes will be compared to the Swiss general population. 30 Current status A, Recent Findings: Follow- up care: Our survey among European paediatric oncology /haematology clinics found that many still lacked programmes for long- term follow- up into adulthood [Essig - 2012, Brown - 2015]. Additionally, a large proportion of Swiss survivors do not attend regular follow- up care [Michel - 2011, Rebholz - 2011, Lupatsch - 2016e]. Survivors and their parents desire precise information on late effects and follow- up care [Gianinazzi - 2014a, Vetsch - 2015]. Most survivors and parents reported preferences for care by a specialist (oncologist) [Vetsch - 2016, Christen - 2016]. Psychological late effects: We found that survivors are at increased risk for psychological distress [Michel - 2010, Gianinazzi 2013, Gianinazzi - 2014b, Michel - 2015, Gianinazzi - 2016] or other negative psychosocial outcomes [Wengenroth - 2014, 2015a, 2015b, Kuehni - 2012a, Rebholz - 2012]. Transition: In Switzerland, there is no specialised transition programme for survivors of childhood cancer from paediatric to adult care. We investigated if patients are receiving e.g. follow- up information after release from the paediatric oncology clinic [Gianinazzi - 2015]. Patient- adapted information on diagnosis, treatment and future follow- up, provided at the time of discharge, was rarely found. B, Ongoing studies: The study on parents of childhood cancer survivors will be the first population- based study among parents of long- term survivors of childhood cancer and will shed light on their psychological well- being, social outcomes and the needs they have for their children and themselves. Contact The research team consists of Gisela Michel, Katharina Roser, Luzius Mader, Julia Bänziger, Janine Vetsch, Salome Christen, Claudia Kuehni, and Nicolas von der Weid. 5. Publications of the Swiss Childhood Cancer Registry All articles published using SCCR data from January 2007 – June 2016 are reported below. Additional publications related to the SCCR or SPOG can be found on the SCCR and SPOG websites: www.childhoodcancerregistry.ch and www.spog.ch. 5.1 Original articles (Peer reviewed journals) 2016 1. Adam M, Rueegg CS, Schmidlin K, Spoerri A, Niggli F, Grotzer M, von der Weid NX, Egger M, Probst -Hensch N, Zwahlen M, Kuehni CE. Socioeconomic disparities in childhood cancer survival in Switzerland. Int J Cancer. 2016; 138(12):2856 -66. 2. Christen S, Vetsch J, Mader L, Dehler S, Korol D, Kuehni CE, Rueegg CS, Michel G. Preferences for the organization of long -term follow -up in adolescent and young adult cancer survivors. Support Care Cancer. 2016; 24(8):3425 -36. 3. Essig S, Steiner C, Kuehni CE, Weber H, Kiss A. Improving Communication in Adolescent Cancer Care: A Multiperspective Study. Pediatr Blood Cancer. 2016; 63(8):1423 -30. 4. Gianinazzi ME, Rueegg CS, Vetsch J, Luer S, Kuehni CE, Michel G, Swiss Pediatric Oncology G. Cancer’s positive flip side: posttraumatic growth after childhood cancer. Support Care Cancer. 2016; 24(1):195 -203. 5. Kreis C, Grotzer M, Hengartner H, Daniel Spycher B, Swiss Paediatric Oncology G, the Swiss National Cohort Study G. Space -time clustering of childhood cancers in Switzerland: A nationwide study. Int J Cancer. 2016; 138(9):2127 -35. 6. Lupatsch JE, Kreis C, Zwahlen M, Niggli F, Ammann RA, Kuehni CE, Spycher BD, Swiss Paediatric Oncology G, Swiss National Cohort Study G. Temporal association between childhood leukaemia and population growth in Swiss municipalities. Eur J Epidemiol. 2016d. 7. Lupatsch JE, Wengenroth L, Rueegg CS, Teuffel O, Gumy -Pause F, Kuehni CE, Michel G, Swiss Paediatric Oncology G. Follow -Up Care of Adolescent Survivors of Childhood Cancer: The Role of Health Beliefs. Pediatr Blood Cancer. 2016e; 63(2):318 -25. 8. Mader L, Rueegg CS, Vetsch J, Rischewski J, Ansari M, Kuehni CE, Michel G, Swiss Paediatric Oncology G. Employment Situation of Parents of Long -Term Childhood Cancer Survivors. Plos ONE. 2016; 11(3):e0151966. 9. Mulder RL, van der Pal HJ, Levitt GA, Skinner R, Kremer LC, Brown MC, Bardi E, Windsor R, Michel G, Frey E. Transition guidelines: An important step in the future care for childhood cancer survivors. A comprehensive definition as groundwork. Eur J Cancer. 2016; 54:64 -8. 10. Schindler M, Spycher BD, Ammann RA, Ansari M, Michel G, Kuehni CE, Swiss Paediatric Oncology G, Swiss Paediatric Oncology Group S. Cause -Specific Long -Term Mortality in Survivors of Childhood Cancer in Switzerland: A Population Based Study. Int J Cancer. 2016; 139(2):322 -33. 11. Vetsch J, Rueegg CS, Mader L, Bergstraesser E, Rischewski J, Kuehni CE, Michel G, Swiss Paediatric Oncology G. Follow -up care of young childhood cancer survivors: attendance and parental involvement. Support Care Cancer. 2016; 24(7):3127 -38. Swiss Childhood Cancer Registry Annual Report 2014/2015 12. Vienneau D, Infanger D, Feychting M, Schuz J, Schmidt LS, Poulsen AH, Tettamanti G, Klaeboe L, Kuehni CE, Tynes T, Von der Weid N, Lannering B, Roosli M. A multinational case -control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data. Cancer Epidemiol. 2016; 40:52 -59. 13. Wengenroth L, Sommer G, Schindler M, Spycher BD, von der Weid NX, Stutz -Grunder E, Michel G, Kuehni CE, Swiss Paediatric Oncology G. Income in Adult Survivors of Childhood Cancer. Plos ONE. 2016; 11(5):e0155546. 2015 14. Adam M, Kuehni CE, Spoerri A, Schmidlin K, Gumy -Pause F, Brazzola P, Probst -Hensch N, Zwahlen M. Socioeconomic Status and Childhood Leukemia Incidence in Switzerland. Front Oncol. 2015; 5:139. 15. Adel Fahmideh M, Lavebratt C, Schuz J, Roosli M, Tynes T, Grotzer MA, Johansen C, Kuehni CE, Lannering B, Prochazka M, Schmidt LS, Feychting M. CCDC26, CDKN2BAS, RTEL1, and TERT Polymorphisms in Pediatric Brain Tumor Susceptibility. Carcinogenesis. 2015; 36(8):876 -82. 16. Brown MC, Levitt GA, Frey E, Bardi E, Haupt R, Hjorth L, Kremer L, Kuehni CE, Lettner C, Mulder RL, Michel G, Skinner R, on behalf of the PanCareSurFup C. The views of European clinicians on guidelines for long -term follow -up of childhood cancer survivors. Pediatr Blood Cancer. 2015; 62:322 -328. 17. Gianinazzi ME, Rueegg CS, Zimmerman K, Kuehni CE, Michel G, Swiss Paediatric Oncology G. Intra -Rater and Inter -Rater Reliability of a Medical Record Abstraction Study on Transition of Care after Childhood Cancer. Plos ONE. 2015; 10(5):e0124290. 18. Hjorth L, Haupt R, Skinner R, Grabow D, Byrne J, Karner S, Levitt G, Michel G, van der Pal H, Bárdi E, Beck J, de Vathaire F, Essig S, Frey E, Garwicz S, Hawkins M, Jakab Z, Jankovic M, Kazanowska B, Kepak T, Kremer L, Lackner H, Sugden E, Terenziani M, Zadravec Zaletel L, Kaatsch P on behalf of the PanCare Network. Survivorship after childhood cancer: PanCare: A European network to promote optimal long term care. European Journal of Cancer.2015; 51(19), 1203–1211. 19. Lupatsch JE, Kuehni CE, Niggli F, Ammann RA, Egger M, Spycher BD. Population mixing and the risk of childhood leukaemia in Switzerland: a census -based cohort study. Eur J Epidemiol. 2015b; 30(12):1287 -98. 20. Magi T, Kuehni CE, Torchetti L, Wengenroth L, Luer S, Frei -Erb M. Use of Complementary and Alternative Medicine in Children with Cancer: A Study at a Swiss University Hospital. Plos ONE. 2015; 10(12):e0145787. 21. Michel G, Vetsch J. Screening for psychological late effects in childhood, adolescent and young adult cancer survivors: a systematic review. Current Opinion in Oncology. 2015; 7(4), 297 -305. 22. Schindler M, Mitter V, Bergstraesser E, Gumy -Pause F, Michel G, Kuehni CE. Death certificate notifications in the Swiss Childhood Cancer Registry: assessing completeness and registration procedures. Swiss Med Wkly. 2015; 145:w14225. Publications 31 23. Spycher BD, Feller M, Roosli M, Ammann RA, Diezi M, Egger M, Kuehni CE. Childhood cancer and residential exposure to highways: a nationwide cohort study. Eur J Epidemiol. 2015d; 30(12):1263 -75. 24. Spycher BD, Lupatsch JE, Zwahlen M, Roosli M, Niggli F, Grotzer MA, Rischewski J, Egger M, Kuehni CE, Swiss Pediatric Oncology G, Swiss National Cohort Study G. Background ionizing radiation and the risk of childhood cancer: a census -based nationwide cohort study. Environ Health Perspect. 2015a; 123(6):622 -8. 25. Swerdlow AJ, Cooke R, Albertsson -Wikland K, Borgstrom B, Butler G, Cianfarani S, Clayton P, Coste J, Deodati A, Ecosse E, Gausche R, Giacomozzi C, Kiess W, Hokken -Koelega AC, Kuehni CE, Landier F, Maes M, Mullis PE, Pfaffle R, Savendahl L, Sommer G, Thomas M, Tollerfield S, Zandwijken GR, Carel JC. Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone. Horm Res Paediatr. 2015; 84(3):172 -83. 26. Vetsch J, Rueegg CS, Gianinazzi ME, von der Weid NX, Michel G. Information provision and information needs in parents of long -term childhood cancer survivors. Pediatr Blood & Cancer. 2015; 62 (5), 859 -866. 27. Wengenroth L, Gianinazzi ME, Rueegg CS, Luer S, Bergstraesser E, Kuehni CE, Michel G. Health -related quality of life in young survivors of childhood cancer. Qual Life Res. 2015a; 24(9):2151 -61. 28. Wengenroth L, Rueegg CS, Michel G, Gianinazzi ME, Essig S, von der Weid NX, Grotzer M, Kuehni CE, Swiss Paediatric Oncology Group S. Concentration, working speed and memory: Cognitive problems in young childhood cancer survivors and their siblings. Pediatr Blood Cancer. 2015b; 62(5):875 -82. 2014 29. Essig S, Li Q, Chen Y, Hitzler J, Leisenring W, Greenberg M, Sklar C, Hudson MM, Armstrong GT, Krull KR, Neglia JP, Oeffinger KC, Robison LL, Kuehni CE, Yasui Y, Nathan PC. Risk of late effects of treatment in children newly diagnosed with standard -risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 2014; 15(8):841 -51. 30. Feijen EL, van der Pal HJ, van Dalen EC, Mulder RL, Bardi E, Kuehni C, Tissing WJ, Kremer LC. A new method to facilitate valid and consistent grading cardiac events in childhood cancer survivors using medical records. Plos ONE. 2014; 9(7):e100432. 31. Gianinazzi ME, Rueegg CS, von der Weid NX, Niggli FK, Kuehni CE, Michel G, Swiss Paediatric Oncology G. Mental health -care utilization in survivors of childhood cancer and siblings: the Swiss childhood cancer survivor study. Support Care Cancer. 2014b; 22(2):339 -49. 32. Gianinazzi ME, Essig S, Rueegg CS, von der Weid NX, Brazzola P, Kuehni CE, Michel G, Swiss Paediatric Oncology G. Information provision and information needs in adult survivors of childhood cancer. Pediatr Blood Cancer. 2014a; 61(2):312 -8. 32 33. Hauri DD, Spycher B, Huss A, Zimmermann F, Grotzer M, von der Weid N, Spoerri A, Kuehni CE, Roosli M, Swiss National C, the Swiss Paediatric Oncology G. Exposure to Radio -Frequency Electromagnetic Fields From Broadcast Transmitters and Risk of Childhood Cancer: A Census -based Cohort Study. Am J Epidemiol. 2014; 179(7):843 -51. 34. Shu X, Prochazka M, Lannering B, Schuz J, Roosli M, Tynes T, Kuehni CE, Andersen TV, Infanger D, Schmidt LS, Poulsen AH, Klaeboe L, Eggen T, Feychting M. Atopic conditions and brain tumor risk in children and adolescents - an international case -control study (CEFALO). Ann Oncol. 2014; 25(4):902 -8. 35. Terenziani M, Spinelli M, Jankovic D, Bardi E, Hjorth L, Haupt R, Michel G and Byrne J, on behalf of the PanCare Network. Practices of pediatric oncology and hematology providers regarding fertility issues: A European Survey. Pediatric Blood & Cancer. 2014; 61(11), 2054–2058. 36. Wengenroth L, Rueegg CS, Michel G, Essig S, Ammann RA, Bergstraesser E, Kuehni CE, Swiss Paediatric Oncology G. Life partnerships in childhood cancer survivors, their siblings, and the general population. Pediatr Blood Cancer. 2014; 61(3):538 -45. 2013 37. Andersen TV, Schmidt LS, Poulsen AH, Feychting M, Roosli M, Tynes T, Aydin D, Prochazka M, Lannering B, Klaeboe L, Eggen T, Kuehni CE, Schmiegelow K, Schuz J. Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents: an International Case -Control Study (CEFALO). Br J Cancer. 2013; 108(11):2346 -53. 38. Gianinazzi ME, Rueegg CS, Wengenroth L, Bergstraesser E, Rischewski J, Ammann RA, Kuehni CE, Michel G, for Swiss Pediatric Oncology G. Adolescent survivors of childhood cancer: are they vulnerable for psychological distress? Psychooncology. 2013c; 22(9):2051 -8. 39. Hauri D, Spycher B, Huss A, Zimmermann F, Grotzer M, von der Weid N, Weber D, Spoerri A, Kuehni CE, Roosli M, Swiss National C, Swiss Paediatric Oncology G. Domestic radon exposure and risk of childhood cancer: a prospective census -based cohort study. Environ Health Perspect. 2013; 121(10):1239 -44. 40. Hauri DD, Huss A, Zimmermann F, Kuehni CE, Roosli M, Swiss National C. Prediction of residential radon exposure of the whole Swiss population: comparison of model -based predictions with measurement -based predictions. Indoor Air. 2013; 23(5):406 -16. 41. Rueegg CS, Gianinazzi ME, Michel G, von der Weid NX, Bergstraesser E, Kuehni CE, Swiss Paediatric Oncology G. Do childhood cancer survivors with physical performance limitations reach healthy activity levels? Pediatr Blood Cancer. 2013a; 60(10):1714 -20. 42. Rueegg CS, Gianinazzi ME, Rischewski J, Beck Popovic M, von der Weid NX, Michel G, Kuehni CE. Health -related quality of life in survivors of childhood cancer: the role of chronic health problems. J Cancer Surviv. 2013b; 7(4):511 -22. 43. Satgé D, Stiller C, Rutkowski S, Bueren A, Lacour B, Sommelet D, Nishi M, Massimino M, Garré M, Moreno F, Hasle H, Jakab Z, Greenberg M, Weid N, Kuehni CE, Zurriaga O, Vicente M -L, Peris -Bonet R, Benesch M, Vekemans M, Sullivan S, Rickert C. A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries. J Neurooncol. 2013; 112(1):107 -14. 44. Singer S, Gianinazzi ME, Hohn A, Kuehni CE, Michel G. General practitioner involvement in follow -up of childhood cancer survivors: a systematic review. Pediatr Blood Cancer. 2013; 60(10):1565 -73. 45. Zimmermann K, Ammann RA, Kuehni CE, De Geest S, Cignacco E. Malnutrition in pediatric patients with cancer at diagnosis and throughout therapy: A multicenter cohort study. Pediatr Blood Cancer. 2013; 60(4):642 -9. 2012 46. Aydin D, Feychting M, Schuz J, Roosli M, team Cs. Childhood brain tumours and use of mobile phones: comparison of a case - control study with incidence data. Collaborators: Tynes T, Andersen TV, Schmidt LS, Poulsen AH, Johansen C, Prochazka M, Lannering B, Klæboe L, Eggen T, Jenni D, Grotzer M, Von der Weid N, Kuehni CE. Environ Health. 2012; 11:35. 47. Christensen JS, Mortensen LH, Roosli M, Feychting M, Tynes T, Andersen TV, Schmidt LS, Poulsen AH, Aydin D, Kuehni CE, Prochazka M, Lannering B, Klaeboe L, Eggen T, Schuz J. Brain tumors in children and adolescents and exposure to animals and farm life: a multicenter case -control study (CEFALO). Cancer Causes Control. 2012; 23(9). 48. Essig S, von der Weid NX, Strippoli MPF, Rebholz CE, Michel G, Rueegg CS, Niggli FK, Kuehni CE. Health -related quality of life in long -term survivors of relapsed childhood acute lymphoblastic leukemia: The Swiss Childhood Cancer Survivor Study. Plos ONE. 2012; 7(5):e38015. 49. Essig S, Skinner R, von der Weid NX, Kuehni CE, Michel G. Follow -up programs for childhood cancer survivors in Europe: a questionnaire survey. Plos ONE. 2012; 7(12):e53201. 50. Hauri DD, Huss A, Zimmermann F, Kuehni CE, Roosli M. A prediction model for assessing residential radon concentration in Switzerland. J Environ Radioact. 2012; 112:83 -9. 51. Kuehni CE, Strippoli MP, Rueegg CS, Rebholz CE, Bergstraesser E, Grotzer M, von der Weid NX, Michel G. Educational achievement in Swiss childhood cancer survivors compared with the general population. Cancer. 2012a; 118(5):1439 -49. 52. Rebholz CE, Spycher BD, Rueegg CS, Michel G, Ammann R, von der Weid NX, Kuehni CE. Clustering of health behaviours in adult survivors of childhood cancer and the general population. Brit J Cancer. 2012; 107(2):234 -42. 53. Rebholz CE, Kuehni CE, Strippoli MPF, Rueegg CS, Michel G, Hengartner H, Bergstraesser E, von der Weid NX. Alcohol consumption and binge drinking in young adult childhood cancer survivors: A report from the Swiss Childhood Cancer Survivor Study. Pediatric Blood Cancer. 2012; 58:256 -64. 54. Rueegg CS, Michel G, Wengenroth L, von der Weid NX, Bergstraesser E, Kuehni CE. Physical performance limitations in adolescent and adult survivors of childhood cancer and their siblings. Plos ONE. 2012a; 7(10):e47944. Swiss Childhood Cancer Registry Annual Report 2014/2015 55. Rueegg CS, Rebholz CE, Michel G, Grotzer M, von der Weid NX, Kuehni CE. Daily physical activity and sport of adult survivors of childhood cancer and healthy control. Plos ONE. 2012b; 7(4):e34930. 2011 56. Aydin D, Feychting M, Schuz J, Andersen TV, Poulsen AH, Prochazka M, Klaeboe L, Kuehni CE, Tynes T, Roosli M. Predictors and overestimation of recalled mobile phone use among children and adolescents. Prog Biophys Mol Biol. 2011; 107(3):356 -61. Epub 2011 /09 /13. 57. Aydin D, Feychting M, Schüz J, Andersen TV, Poulsen AH, Prochazka M, Klaebo L, Kuehni CE, Tynes T, Roeoesli M. Impact of random and systematic recall errors and of selection bias in case -control studies on mobile phone use and brain tumors in adolescents (CEFALO study). Bioelectromagnetics. 2011; 32:396 -407. 58. Aydin D, Feychting M, Schüz J, Tynes T, Andersen TV, Schmidt LS, Poulsen AH, Johansen C, Prochazka M, Lannering B, Klaeboe L, Eggen T, Jenni D, Grotzer M, Von der Weid NX, Kuehni CE, Roeoesli M. Mobile phone use and brain tumors in children and adolescents: a multicenter case -control study. J Natl Cancer Inst. 2011; 1264 -76. 59. Marquis A, Strippoli MPF, Spycher BD, Rebholz CE, von der Weid NX, Kuehni CE. Paracetamol, NSAIDS and risk of asthma in adult survivors of childhood cancer. J Allergy Clin Immunol. 2011; 127:270 -2. 60. Michel G, Kuehni CE, Rebholz CE, Zimmermann K, Eiser C, Rueegg CS, von der Weid NX. Can health beliefs help explaining attendance to follow -up care? The Swiss Childhood Cancer Survivor Study. Psychooncology. 2011; 20:1034 -43. 61. Rebholz CE, Reulen RC, Toogood A, Frobisher C, Lancashire ER, Winter DL, Kuehni CE, Hawkins M. Health care utilization of long -term survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol. 2011; 29:4181 -8. 62. Rebholz CE, von der Weid NX, Michel G, Niggli F, Kuehni CE. Follow -up care among long -term childhood cancer survivors: a report from the Swiss childhood cancer survivor study. Eur J Cancer. 2011; 41:221 -9. 63. Spycher BD, Feller M, Zwahlen M, Röösli M, von der Weid NX, Hengartner H, Egger M, Kuehni CE. Childhood cancer and nuclear power plants in Switzerland: a census -based cohort study. Int J Epidemiol. 2011; 40:1247 -60. 2010 64. Adam M, von der Weid NX, Michel G, Zwahlen M, Lutz JM, Probst -Hensch N, Niggli F, Kuehni CE. Access to specialized pediatric cancer care in Switzerland. Pediatr Blood Cancer. 2010; 54:721 -7. 65. Feller M*, Adam M*, Zwahlen M, Brazzola P, Niggli F, Kuehni CE. Family characteristics as risk factors for childhood acute lymphoblastic leukemia. *joint first authorship. PLo One. 2010; 5; e13156. 66. Marquis, A, Kuehni CE*, Strippoli MPF, Kühne T, Brazzola P, for the Swiss Pediatric Oncology Group (SPOG). Sperm analysis of patients after successful treatment of childhood acute lymphoblastic leukemia with chemotherapy only. *corresponding author. Pediatr Blood Cancer. 2010; 55:208 -10. Publications 33 67. Michel G, Rebholz CE, von der Weid NX, Bergstraesser E, Kuehni CE. Psychological distress in adult survivors of childhood cancer: the Swiss Childhood Cancer Survivor Study. J Clin Oncol. 2010; 28:1740 -8. 2009 68. Spycher BD, Minder CE, Kuehni CE. Multivariate modelling of responses to conditional items: New possibilities for latent class analysis. Stat Med. 2009; 28:1927 -39. 2008 69. Michel G, von der Weid N, Zwahlen M, Redmond S, Strippoli MPF, Kuehni CE. Incidence of childhood cancer in Switzerland: the Swiss Childhood Cancer Registry. Pediatr Blood Cancer. 2008; 50:46 -51. 2007 70. Michel G, von der Weid N, Zwahlen M, Adam M, Rebholz CE, Kuehni CE. The Swiss Childhood Cancer Registry: rationale, organisation and results for the years 2001 -2005. Swiss Med Wkly. 2007; 137:502 -9. 71. Röösli M, Michel G, Kuehni CE, Spoerri A. Cellular telephone use and time trends in brain tumour mortality in Switzerland from 1969 to 2002. Eur J Cancer Prev. 2007; 16:77 -82. 5.2 Editorials, commentaries and author replies (Peer reviewed journals) 2015 72. Lupatsch JE, Egger M, Kuehni CE, Spycher BD. The authors’ reply: Population mixing and childhood leukaemia. Eur J Epidemiol. 2015c; 30(12):1333 -4. 73. Spycher BD, Roosli M, Egger M, Kuehni CE. “Author’s Comment on ‘Background Ionizing Radiation and the Risk of Childhood Cancer: A Census -Based Nationwide Cohort Study’”. Environ Health Perspect. 2015b; 123(8):A198 -9. 74. Spycher BD, Roosli M, Egger M, Kuehni CE. Response to “Comment on ‘Background Ionizing Radiation and the Risk of Childhood Cancer: A Census -Based Nationwide Cohort Study’”. Environ Health Perspect. 2015c; 123(8):A200 -1. 2012 75. Spycher BD, Kuehni CE, Zwahlen M, Egger M on behalf of the Swiss National Cohort Study Group and the Swiss Paediatric Oncology Group. Authors’ response to: Childhood cancer and nuclear power plants in Switzerland: a census -based cohort study. Int J Epidemiol. 2012; 41: 321 -322. 2006 76. Kuehni CE, Zwahlen M. Commentary: Numerous, heterogeneous and often poor – the studies on childhood leukaemia and socioeconomic status. Int J Epidemiol. 2006; 35:384 -5. 34 5.3 Reviews (Peer reviewed journals) 2015 77. Bhatia S, Armenian SH, Armstrong GT, van Dulmen -den Broeder E, Hawkins MM, Kremer LC, Kuehni CE, Olsen JH, Robison LL, Hudson MM. Collaborative Research in Childhood Cancer Survivorship: The Current Landscape. J Clin Oncol. 2015; 33(27):3055 -64. 78. Winther JF, Kenborg L, Byrne J, Hjorth L, Kaatsch P, Kremer LC, Kuehni CE, Auquier P, Michel G, de Vathaire F, Haupt R, Skinner R, Madanat -Harjuoja LM, Tryggvadottir L, Wesenberg F, Reulen RC, Grabow D, Ronckers CM, van Dulmen -den Broeder E, van den Heuvel -Eibrink MM, Schindler M, Berbis J, Holmqvist AS, Gudmundsdottir T, de Fine Licht S, Bonnesen TG, Asdahl PH, Bautz A, Kristoffersen AK, Himmerslev L, Hasle H, Olsen JH, Hawkins MM. Childhood cancer survivor cohorts in Europe. Acta Oncol. 2015; 54(5):655 -68. 2014 79. Kuehni C, Spycher BD. Nuclear power plants and childhood leukaemia: lessons from the past and future directions. Swiss Med Wkly. 2014; 144:w13912. 80. Laurier D, Grosche B, Auvinen A, Clavel J, Cobaleda C, Dehos A, Hornhardt S, Jacob S, Kaatsch P, Kosti O, Kuehni C, Lightfoot T, Spycher B, Van Nieuwenhuyse A, Wakeford R, Ziegelberger G. Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research. J Radiol Prot. 2014; 34(3):R53 -68. 2012 81. Kuehni CE, Rueegg CS, Michel G, Rebholz CE, Strippoli MP, Niggli FK, Egger M, von der Weid NX. Cohort Profile: The Swiss Childhood Cancer Survivor Study. Int J Epidemiol. 2012b; 41(6):1553 -64. Epub 2012 /06 /28. 2008 82. Adam M, Rebholz C, Egger M, Zwahlen M, Kuehni CE. Childhood Leukaemia and Socioeconomic Status: what is the evidence? Radiat Prot Dosim. 2008; 132:246 -54. 5.4 Publications (other journals) Schweizer Krebsbulletin Other 2016 83. Lupatsch JE, Kreis C, Niggli F, Kuehni CE, Spycher B. 2016. Ursachen von Krebs bei Kindern: Was verrät der Wohnort? Schweizer Krebsbulletin 2016a; 36(01): 29 -33. 2013 93. Mitter V, Michel G. Krebs bei Kindern. Ein Überblick aus dem Schweizer Kinderkrebsregister. Onkologiepflege 1; 5 -8. 94. Ruegg CS, Gianinazzi ME, Michel G. Psychosoziale Spätfolgen nach Kinderkrebs – Eine Langzeitstudie des Schweizer Kinderkrebsregisters. Newsletter Schweizerische Gesellschaft für Psychoonkologie. 21; 5 -8. 95. Kuehni CE, Michel G, Egger M, Zwahlen M, Beck Popovic M, Nigglie F, von der Weid NX. Das Schweizer Kinderkrebsregister: Erfahrungen als nationales Krebsregister. Schweizerische Ärztezeitung 2013; 94: 327. 96. Kuehni CE, Niggli FK. Endlich ein nationales Krebsregistrierungsgesetz für Kinder und Erwachsene. Schweizerische Ärztezeitung 2013; 94: 160. 2014 84. Wengenroth L, Schindler M, Kuonen R, Kuehni CE. Krebs als Kind oder Teenager: das Leben danach. Schweizer Krebsbulletin 2014; 4: 292 -295. 85. Michel G, von der Weid NX. Nachsorge nach Krebs im Kindesalter – Pläne für die Schweiz. Schweizer Krebsbulletin 2014; 4: 296 -298 2013 86. Kuehni CE, Mitter V, Niggli F, von der Weid NX. Die Rolle des Kinderkrebsregisters unter dem geplanten Krebsregistrierungsgesetz: Chancen und Risiken. Schweizer Krebsbulletin 2013; 3:213 -216. 2012 87. Niggli F, Kuehni CE, Lamontagne -Müller S. Seltene Krebserkrankungen – das tägliche Brot der pädiatrischen Onkologie. Schweizer Krebsbulletin. 2012; 4. 309 -10. 88. Michel G. Nachsorge nach Krebs im Kindesalter. Schweizer Krebsbulletin. 2012; 3: 212 -213. 2010 89. Kuehni CE. The Swiss Childhood Cancer Registry: from causes to outcomes. Schweizer Krebsbulletin. 2010; 2:129 -130. 2009 90. Kuehni CE, Feller M, Egger M. Response to: Sufficient statistical power for CANUPIS? Bulletin suisse du cancer. 2009; 4.09:301. 2008 91. Kuehni CE, von der Weid NX, Hengartner H, Niggli F, Röösli M, Huss A, Feller M, Egger M. CANUPIS – Childhood Cancer and Nuclear Power Plants in Switzerland. Schweizer Krebsbulletin. 2008; 28: 264 -266. 92. von der Weid NX, Kuehni CE. Le Registre Suisse du Cancer de l’Enfant: premier Registre du Cancer national. Information de la communauté médicale quant à la nouvelle situation concernant la protection des données. Bulletin des médecins suisses. 2008; 89:117 -9. Swiss Childhood Cancer Registry Annual Report 2014/2015 2008 97. Michel G. Nachsorge nach Krebs im Kindesalter – ein neues Feld für Pflege?. Onkologiepflege 2011; 3: 20 -23. 98. Kuehni CE, von der Weid NX. Das Schweizer Kinderkrebsregister als erstes nationales Krebsregister: Information der Ärzteschaft zur neuen Datenschutzsituation. Schweizerische Aerztezeitung. 2008; 89:117 -9. 99. Kuehni CE, von der Weid NX. Das Schweizer Kinderkrebsregister als erstes nationales Krebsregister: Information der Ärzteschaft zur neuen Datenschutzsituation. Paediatrica. 2008; 19:53 -5. 100. von der Weid NX, Kuehni CE. Le Registre Suisse du Cancer de l’Enfant: premier Registre du Cancer national. Information de la communauté médicale quant à la nouvelle situation concernant la protection des données. Paediatrica. 2008; 19:50 -2. 2007 101. Kuehni CE. Children’s health and the environment. A global perspective (Book review). Paediatrica 2007; 15:13 -28. Publications 35 5.5 Reports Annual Reports SCCR Other Reports 2015 102. Schindler M, Mitter V, Pfeiffer V, Redmond S, Wölfli P, Kuonen R, Sommer G, Spring M, Singh P, Michel G, Kuehni CE, The Swiss Childhood Cancer Registry. Annual Report 2013 /2014. Berne: Dept. of Social and Preventive Medicine, University of Bern; March 2015. 2016 108. Arndt V, Feller A, Hauri D, Heusser R, Junker C, Kuehni CE, Lorenz M, Pfeiffer V, Roy E, Schindler M. Schweizerischer Krebsbericht 2015 – Stand der Entwicklungen. Bundesamt für Statistik (BFS); Neuchâtel 2016. 2013 103. Mitter V, Michel G, Wölfli P, Gianinazzi M, Ruegg CS, Sommer G, Hau E, Kuehni CE, The Swiss Childhood Cancer Registry. Annual Report 2011 /2012. Berne: Dept. of Social and Preventive Medicine, University of Bern; Feb 2013. 2011 104. Mitter V, Michel G, Strippoli MPF, Rebholz CE, Rueegg CS, Viehmann G, Reck M, Niggli F, Hengartner H, von der Weid NX, Kuehni CE. The Swiss Childhood Cancer Registry. Annual Report 2009 /2010. Bern: Dept. of Social and Preventive Medicine, University of Bern; April 2011. 2009 105. Kuehni CE, Michel G, Pyrlic M, Strippoli MP, Adam M, Rebholz C, Rueegg C, Viehmann G, Reck M, Niggli F, Hengartern H, von der Weid N. The Swiss Childhood Cancer Registry. Annual Report 2007 /2008. Berne: Dept. of Social and Preventive Medicine, University of Bern; June 2009. 2007 106. Michel G, von der Weid NX, Adam M, Rebholz G, Zwahlen M, Kuehni CE. The Swiss Childhood Cancer Registry. Annual Report 2005 /2006. Berne: Dept. Of Social and Preventive Medicine, University of Bern; May 2007. 2005 107. Kuehni CE, Michel G, Sturdy M, Redmond S, Zwahlen M, von der Weid N. The Swiss Childhood Cancer Registry. Annual Report 2004. Bern: Dept. of Social and Preventive Medicine, University of Bern; December 2005. 36 2011 109. Wyss N, Pury P, Strippoli MPF, Lutz JM, Bouchardy C, Kuehni CE, Junker C. Krebs in der Schweiz – Stand und Entwicklung von 1983 bis 2007. Bundesamt für Statistik (BFS); Neuchâtel 2011. 2005 110. Michel G, Sturdy M, Zwahlen M, Strippoli MPF, von der Weid N, Kuehni CE. Validating date and cause of death information in the Swiss Childhood Cancer Registry against death certificate information from the Swiss Federal Office of Statistics. Bern: Dept. of Social and Preventive Medicine, University of Bern; December 2005. 6. Appendix: Classification of cancer diagnoses International Classification of Childhood Cancer ICCC -3 The third edition of the International Classification of Childhood Cancer (ICCC - 3) represents the standard for presentation of international data on childhood cancer incidence and survival. It applies the rules, nomenclature and codes (morphology, topography and behaviour) of the ICD - O - 3. ICCC - 3 categories are defined in conformity with international classifications of the pathology and genetics of childhood cancers. In the ICCC - 3, three hierarchical levels have been developed: level one consists of 12 main diagnostic groups and level two of 47 diagnostic subgroups. These two levels of the ICCC - 3 allow standardised comparison of the broad categories of childhood tumours. Level three, an optional «extended» classification, comprises two to eleven divisions of selected diagnostic subgroups. The division of some diagnostic subgroups, e.g. leukaemia and Non - Hodgkin lymphomas, reflects the availability of detailed cytogenetic or molecular information that permits homogeneous groups of tumours to be distinguished within them and thus allows their separate study. The Swiss childhood cancer registry (SCCR) uses level one to three. Only malignant neoplasms are classified in ICCC - 3, with the exception of non - malignant intracranial and intraspinal tumours. Tumours known to occur only rarely in young patients are also included in ICCC - 3. The ICCC - 3 is used if data are compared with other childhood cancer registries. characters for topography (based on the malignant neoplasm section of ICD - 10). The topography code remains the same for all neoplasms of that site. The behaviour code is incorporated as the fifth digit in the morphology field. It identifies whether the tumour is malignant, benign, of uncertain or unknown behaviour, in situ, presumed to be primary or secondary. For all tumours diagnosed since 1st January 2014 the SCCR uses the 2011 updates to ICD - O - 3 which include new terms, codes and behaviour combinations. This allows e.g. B lymphoblastic leukaemias to be further classified according to their exact cytogenetic and molecular characteristics, which are relevant for disease prognosis. ICD - O - 3 is used to compare data with general cancer registries. International Statistical Classification of Diseases and Related Health Problems - ICD -10 The third edition of the International Statistical Classification of Diseases for Oncology (ICD - O - 3) has been developed by a working group hosted by the International Association of Research in Cancer (IARC) and WHO. The morphology code for neoplasm has been revised, especially for lymphomas and leukaemia. In contrast to the International Classification of Diseases, 10th revision (ICD - 10), ICD - O - 3 uses only one set of four The International Statistical Classification of Diseases and Related Health Problems (ICD) permits the systematic recording, analysis, interpretation and comparison of mortality and morbidity data collected in different regions and at different time periods. The ICD has become the international standard diagnostic classification for all general epidemiological purposes. The ICD - 10 classification comprises three volumes: Volume 1 contains the main classifications; Volume 2 provides guidance for users of the ICD; and Volume 3 is the alphabetical index to the classification. Classification is divided into 21 chapters. The first character of the ICD code is a letter. Each letter is associated with a particular chapter, e.g. the letter D is used in both chapter II «Neoplasms» and chapter III «Diseases of the blood and blood - forming organs and certain disorders involving the immune mechanism». The topography code in Volume 3 describes the site and the behaviour of the neoplasm: malignant, secondary or metastatic, in situ, benign or of unknown behaviour. The morphology codes listed in Volume 1 are the same as those used in the special adaptation of the ICD for oncology, the ICD - O97. Swiss Childhood Cancer Registry Annual Report 2014/2015 Appendix: Classification of cancer diagnoses International Statistical Classification of Diseases for Oncology - ICD -O -3 37 38 © 2016 Swiss Childhood Cancer Registry Logo: Elsbeth Kuehni, Bern Layout: HP Hauser, Bern