German cancer registry

https://onlinelibrary.wiley.com/doi/epdf/10.1002/pbc.24997 Rare Malignant Pediatric Tumors Registered in the German Childhood Cancer Registry 2001–2010 Background. The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trialsandreferencecenters.Procedure.Aretrospectiveanalysisofall rare extracranial solid tumors reported to the GCCR 2001–2010(age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/ yearandregisteredmalignancy).Results.Accordingtothisdefinition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not includedin preexisting GPOH studies/registries. Within 10 years, the number of registered nonGPOH-trial patients with a rare tumor increased. Conclusions. Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medicalcare in these patients. Pediatr Blood Cancer 2014;61:1202–1209. Approximately 2,000 children and adolescents diagnosed with a malignant disease are registered within the German Childhood Cancer Registry (GCCR) annually [1]. During the last 40 years pediatric oncologists in Germany have managed to build a close network within the German Society for Pediatric Oncology and Hematology (GPOH). By promoting multicenter and interdisciplinary, national, and international cooperation risk-adapted treatment protocolshavebeendeveloped,resultinginanimpressive improvementincurerates [2]. Aclosecooperation betweenclinical studies, reference centers, the GCCR, research groups and treating hospitals was established. Currently, more than 90% of all German children and adolescents under the age of 15 years with malignant diseases are enrolled into therapeutic trials and clinical registries andreportedtotheGCCR[3,4].Thisclinicalandtranslationalwork led to an increasing understanding of pediatric tumors. In contrast, it is assumed that a substantial proportion of patients with rare pediatric tumors are insufficiently captured by the presently available structures so far. Even though many German patients affected by rare pediatric tumors have already been registered with and treated according to guidelines of therapy optimization trials (Table I), it is estimated that still about 8–15% of patients with rare tumors are not treated according to standardized cooperativetreatment protocols and may not evenbe consulted by a pediatric oncologist [5–8]. Therefore, these patients are excluded from the well-developed network of the GPOH. As a result, no clinical or scientific structures have been developed to ensure accurate diagnosis and evidence based treatment, research projects appear to be impossible due to the rarity of these entities, and the interest of the pharmaceutical industry to develop and evaluate new drugs for these entities is rather limited [9,10]. Thus several European pediatric oncology groups have founded registries and study groupsfocusingon previously unregistered rare pediatric tumors [9,11,12]. The German Pediatric Rare Tumor Group (STEP) was founded in 2006, and registrationfor the entities not considered in the existing GPOH-trials within a consultation network was started in 2008 [13]. In the same year the existing national groups within Europe formed a new cooperative group (EXPeRT—European Cooperative Study Group for Pediatric Rare Tumors) [12]. These initiatives led to increased awareness of Background. The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trialsandreferencecenters.Procedure.Aretrospectiveanalysisofall rare extracranial solid tumors reported to the GCCR 2001–2010(age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/ yearandregisteredmalignancy).Results.Accordingtothisdefinition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not includedin preexisting GPOH studies/registries. Within 10 years, the number of registered nonGPOH-trial patients with a rare tumor increased. Conclusions. Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medicalcare in these patients. Pediatr Blood Cancer 2014;61:1202–1209. # 2014 Wiley Periodicals, Inc. Key words: cancer registry; epidemiology; orphan disease; pediatric oncology; rare tumors; sarcomas pediatric rare tumors, and a competence network could be built in a short time providing support for clinical management of patients with rare tumors and fostering research in the field. This manuscript describes the specific structures for rare pediatric tumors within Germany, and gives a broad overview of all rare solid pediatric tumors outside the CNS differentiating between entities enrolled in the existing clinical trials or registries and those which lie in the focus of the recently founded rare pediatric study groups. METHODS The German Childhood Cancer Registry (GCCR) is a population based registry. Since its initiation in 1980, all children <15 years with malignant diseases and residency in the Federal Republic of Germany at the time of diagnosis have been included. Patients 15and<18yearsweresporadicallyreportedbefore2009 and systematically since then. In 1991 the registry was extended to the area of the former German Democratic Republic (GDR). The completeness of registration is estimated to be 95% for patients until the age of 15 years [14]. Patients and/or their guardians have given their consent to registration. The families are committed to the goals of the registry and therefore only about 1% do not give their consent, another about 1% are missing for other reasons [14]. In case of missing permission, cases are registered anonymously with some minimum information in order to be able to calculate incidencerates.ClosecooperationwithGPOH,itsclinicaltrialsand the treating hospitals allows for high data quality, exact diagnosis confirmed by reference pathology and additional registration of clinical data such as grading and immunological subtypes. Over 90% of the patients registered are included in clinical trials of the GPOH [1,14]. Classification of the pediatric malignancies registered with the GCCR is based on the International Classification of Childhood Cancer 3rd edition (ICCC-3) [15]. We present an overview of all rare extracranial solid tumors reported to the GCCR between 2001 and 2010 (age <18 years). All extracranial solid tumors accounting for less than 0.3% of all malignant diseases were defined as rare (not more than six cases per year and registered malignancy on average). We chose this cut-off point for the purpose of the article as we found this to be the threshold just including all entities generally considered as rare pediatric tumors. We were especially interested to understand, which other entities (not included in the group of rare pediatric tumors in the closer sense so far) appear to have the same incidence by drawing this line. These tumors have been registered in pediatric clinical trials in Germany for years and therefore do not fall into the definition of rare pediatric tumors mentioned above. As the specific spectrum of rare cancers in children is not well described through one of the existingclassification systems,a combination of the third version of the ICCC-3 [15] and the International Classification of Diseases-Oncology (ICD-O) [16] was used to identify cases Total and relative numbers, age distribution, two time periods of registration (2001–2005, 2006–2010) and registration into a GPOH trial or registry are reported. In addition, total numbers and age distribution of entities, which are typically not registered within a GPOH study or registry, but should consequently be registered with the recently founded German Pediatric Rare Tumor Registry (STEP), are shown. These cases are termed non-GPOHtrial patients. RESULTS Between 2001 and 2010, the GCCR registered 20,974 malignancies in children <18 years. Among these, 6,532 patients (31.1% of all malignancies) were diagnosed with solid tumors outside the central nervous system. According to the above mentioned definition of rarity (<0.3% of all malignancies), 1,189 rare tumors were identified (5.7% of all malignancies; 18.2% of all malignant extracranial solid tumors). The distribution within the ICCC-3-groups was as follows: 69 rare extracranial solid tumors were identified within the ICCC-3-group IV Neuroblastoma and other peripheral and intraspinal neoplasms, 53 within ICCC-3group VI Renal tumors, 48 within ICCC-3-group VII Hepatic tumors,101withinICCC-3-groupVIIIMalignantbonetumors,359 TABLE I. Overview of Study Groups Prospectively Registering Rare Pediatric Extracranial Tumors within the Society of Pediatric Oncology and Hematology Rare tumor entities Clinical trial center/Registry Rare soft tissue sarcomas and bone tumors SoTiSar Registry of the German CWS, COSS, and EICESS study groups (Prof. Dr. E. Koscielniak, Prof. Dr. T. Klingebiel, Prof. Dr. S. Bielack, Prof. Dr. H. Ju ¨rgens) Rare gonadal tumors German MAKEI study group (Dr. G. Calaminus, Prof. Dr. D. Schneider) Endocrine tumors MET Registry (Prof. Dr. P. Vorwerk) Rare liver tumors German Cooperative Pediatric Liver Tumor Study Group (Prof. Dr. D. v. Schweinitz) Esthesioneuroblastoma German Neuroblastoma Study Group (Prof. Dr. med. F. Berthold) Gastrointestinal stromal tumors SoTiSar Registry (PD Dr. M. Benesch) Nasopharyngeal carcinoma German NPC study group (Prof. Dr. R. Mertens) Rare renal tumors SIOP/GPOH Nephroblastoma Study Group (Prof. Dr. N. Graf) Rhabdoid tumors EU-RHAB Registry (Prof. Dr. M. Fru ¨hwald) Pleuropulmonary blastoma SoTiSar Registry (Dr. S. Kirsch) SoTiSar, registry for soft tissue sarcoma and other soft tissue tumors in children, adolescents, and young adults; CWS, Cooperative Weichteilsarkom Studiengruppe; COSS, Cooperative Osteosarcoma Study Group; EICESS, European Intergroup Cooperative Ewing Sarcoma Studies; MAKEI, GermanPediatric GermCell Tumor StudyGroup; MET, Registry for Malignant Endocrine Tumorsin Children and Adolescents; NPC, German Nasopharyngeal Carcinoma Study Group; SIOP, International Society of Pediatric Oncology; GPOH, German Society of Pediatric Oncology and Hematology; EU-RHAB, European Registry for Rhabdoid Tumors. Pediatr Blood Cancer DOI 10.1002/pbc Rare Pediatric Tumors in Germany 1203 within ICCC-3-group IX Soft tissue and other extraosseous sarcomas, 276 within ICCC-3-group X Germ cell tumors, trophoblastic tumors, and neoplasms of gonads, 262 within ICCC-3-group XI Other malignant epithelial neoplasms and malignant melanomas, and 21 within ICCC-3-group XII Other and unspecified malignant neoplasms (Fig. 1). Not registered within a trial or registry of the GPOH were 249 (20.9%) out of these 1,189 rare tumors. These tumors would now qualify for registration in the recently founded STEP Registry (so called non-GPOH-trial patients). This accounts for 1.2% of all malignancies or 3.8% of all malignant extracranial tumors registered within the GCCR. Figure 2 gives an overview of these entities. Following the ICCC-3, most non-GPOH-trial patients can be classified as XI(d) Malignant Melanomas (n¼55) and XI(f) Other and Unspecified Carcinomas (n¼120). The age distribution of non-GPOH-trial patients demonstrated a predominance of adolescents older than 9 years (see Table II and Fig. 3). Over a period of 10 years, no incidence trend is seen. Within the time periods 2001–2005 and 2006–2010 a total of 10,549 and 10,425 patients with malignant diseases were registered, respectively. The number of registered patients with extracranial solid tumors remained also unchanged (2001–2005: 3,322 cases; 2006–2010: 3,210cases).Atthesametimethenumberofregisterednon-GPOHtrial patients with a rare tumor increased. Between years 2001 and 2005 106 non-GPOH trial patients were reported to the GCCR, while for the time period between 2006 and 2010 143 were identified. This increase of registrations within the last 5 years can be explained by a higher number of reported melanomas (2001– 2005:n¼13;2006–2010:n¼42)andsalivaryglandtumors(2001– 2005: n¼4; 2006–2010: n¼19). Out of the latter 31 cases (26%) Total and relative numbers, age distribution, two time periods of registration (2001–2005, 2006–2010) and registration into a GPOH trial or registry are reported. In addition, total numbers and age distribution of entities, which are typically not registered within a GPOH study or registry, but should consequently be registered with the recently founded German Pediatric Rare Tumor Registry (STEP), are shown. These cases are termed non-GPOHtrial patients. RESULTS Between 2001 and 2010, the GCCR registered 20,974 malignancies in children <18 years. Among these, 6,532 patients (31.1% of all malignancies) were diagnosed with solid tumors outside the central nervous system. According to the above mentioned definition of rarity (<0.3% of all malignancies), 1,189 rare tumors were identified (5.7% of all malignancies; 18.2% of all malignant extracranial solid tumors). The distribution within the ICCC-3-groups was as follows: 69 rare extracranial solid tumors were identified within the ICCC-3-group IV Neuroblastoma and other peripheral and intraspinal neoplasms, 53 within ICCC-3group VI Renal tumors, 48 within ICCC-3-group VII Hepatic tumors,101withinICCC-3-groupVIIIMalignantbonetumors,359 TABLE I. Overview of Study Groups Prospectively Registering Rare Pediatric Extracranial Tumors within the Society of Pediatric Oncology and Hematology Rare tumor entities Clinical trial center/Registry Rare soft tissue sarcomas and bone tumors SoTiSar Registry of the German CWS, COSS, and EICESS study groups (Prof. Dr. E. Koscielniak, Prof. Dr. T. Klingebiel, Prof. Dr. S. Bielack, Prof. Dr. H. Ju ¨rgens) Rare gonadal tumors German MAKEI study group (Dr. G. Calaminus, Prof. Dr. D. Schneider) Endocrine tumors MET Registry (Prof. Dr. P. Vorwerk) Rare liver tumors German Cooperative Pediatric Liver Tumor Study Group (Prof. Dr. D. v. Schweinitz) Esthesioneuroblastoma German Neuroblastoma Study Group (Prof. Dr. med. F. Berthold) Gastrointestinal stromal tumors SoTiSar Registry (PD Dr. M. Benesch) Nasopharyngeal carcinoma German NPC study group (Prof. Dr. R. Mertens) Rare renal tumors SIOP/GPOH Nephroblastoma Study Group (Prof. Dr. N. Graf) Rhabdoid tumors EU-RHAB Registry (Prof. Dr. M. Fru ¨hwald) Pleuropulmonary blastoma SoTiSar Registry (Dr. S. Kirsch) SoTiSar, registry for soft tissue sarcoma and other soft tissue tumors in children, adolescents, and young adults; CWS, Cooperative Weichteilsarkom Studiengruppe; COSS, Cooperative Osteosarcoma Study Group; EICESS, European Intergroup Cooperative Ewing Sarcoma Studies; MAKEI, GermanPediatric GermCell Tumor StudyGroup; MET, Registry for Malignant Endocrine Tumorsin Children and Adolescents; NPC, German Nasopharyngeal Carcinoma Study Group; SIOP, International Society of Pediatric Oncology; GPOH, German Society of Pediatric Oncology and Hematology; EU-RHAB, European Registry for Rhabdoid Tumors. Pediatr Blood Cancer DOI 10.1002/pbc Rare Pediatric Tumors in Germany 1203 within ICCC-3-group IX Soft tissue and other extraosseous sarcomas, 276 within ICCC-3-group X Germ cell tumors, trophoblastic tumors, and neoplasms of gonads, 262 within ICCC-3-group XI Other malignant epithelial neoplasms and malignant melanomas, and 21 within ICCC-3-group XII Other and unspecified malignant neoplasms (Fig. 1). Not registered within a trial or registry of the GPOH were 249 (20.9%) out of these 1,189 rare tumors. These tumors would now qualify for registration in the recently founded STEP Registry (so called non-GPOH-trial patients). This accounts for 1.2% of all malignancies or 3.8% of all malignant extracranial tumors registered within the GCCR. Figure 2 gives an overview of these entities. Following the ICCC-3, most non-GPOH-trial patients can be classified as XI(d) Malignant Melanomas (n¼55) and XI(f) Other and Unspecified Carcinomas (n¼120). The age distribution of non-GPOH-trial patients demonstrated a predominance of adolescents older than 9 years (see Table II and Fig. 3). Over a period of 10 years, no incidence trend is seen. Within the time periods 2001–2005 and 2006–2010 a total of 10,549 and 10,425 patients with malignant diseases were registered, respectively. The number of registered patients with extracranial solid tumors remained also unchanged (2001–2005: 3,322 cases; 2006–2010: 3,210cases).Atthesametimethenumberofregisterednon-GPOHtrial patients with a rare tumor increased. Between years 2001 and 2005 106 non-GPOH trial patients were reported to the GCCR, while for the time period between 2006 and 2010 143 were identified. This increase of registrations within the last 5 years can be explained by a higher number of reported melanomas (2001– 2005:n¼13;2006–2010:n¼42)andsalivaryglandtumors(2001– 2005: n¼4; 2006–2010: n¼19). Out of the latter 31 cases (26%)