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Introduction: Among childhood cancer survivors, the cumulative incidence rate of differentiated thyroid carcinomas (DTCs) is estimated to be 8-11%. Although the association of DTC with prior radiotherapy is well-studied, the association with chemotherapy remains less understood. Most studies focused on young adults, leaving a knowledge gap on subsequent DTC occurring in childhood and adolescence. Methods: In this retrospective cohort study, we analyzed DTCs in children and adolescents under 18 years of age who were registered with the national multicenter Malignant Endocrine Tumor studies in Germany (1997-2023). We compared patients with first primary DTC to those with subsequent DTC that developed after a history of childhood cancer or hematopoietic stem cell transplantation (HSCT). In the subsequent DTC subgroup, we compared DTCs following chemotherapy only to those following chemo- and radiotherapy. Results: Of 505 patients with DTCs, 66 (13.1%) (38 male, 28 female) were subsequent DTCs. The median age at subsequent DTC diagnosis was 12.7 years (range, 5.1-17.9), with a median latency of 7.3 years (range, 2.2-15.6) from the first malignancy or HSCT. The 5-year overall survival (OS) and thyroid-related adverse event-free survival (EFS) estimates from the diagnoses of a subsequent DTC were 100.0% and 82.5%, respectively. Prior treatment included chemotherapy in 64 patients, with 18 receiving chemotherapy alone. In all, 46 subsequent DTC patients had a history of external radiotherapy, including 2 treated with radiotherapy only and 14 with total body irradiation. Two patients received 131 I-metaiodobenzylguanidine treatment. Subsequent DTCs versus first DTCs were smaller in size but more frequently multifocal. Subsequent DTCs following chemotherapy only, compared with chemo- and radiotherapy, developed after a shorter latency (median 6.2 vs. 7.8 years), and were larger (median 1.86 vs. 1.18 cm). Patients with subsequent DTCs following chemotherapy only were younger at diagnosis (median 11.5 vs. 13.7 years). No differences were observed for OS and EFS. Conclusions: Presenting features of subsequent DTCs differ from primary counterparts, although the prognosis is not significantly different. Subsequent DTCs following chemotherapy only versus chemo- and radiotherapy DTCs were larger and diagnosed in younger patients after a shorter latency. More research is needed to identify risk factors and mechanisms potentially contributing to thyroid tumorigenesis post-chemotherapy.

Introduction: The increasing incidence of differentiated thyroid carcinoma (DTC) in children and adolescents has become a growing concern. This study provides the first extensive assessment of incidence patterns and temporal trends of pediatric DTC in Germany, using the best available data from the German Malignant Endocrine Tumor (MET) Registry and the German Childhood Cancer Registry (GCCR) covering a period of 25 years. Patients and Methods: We conducted a register-based incidence and time series analysis, identifying all children and adolescents diagnosed with DTC at ages 0-17 years between 1997 and 2021 in Germany, as recorded in the German MET Registry and/or the GCCR. Age-specific and age-standardized incidence rates (ASR) over time, average annual percentage changes (AAPC), and cross-tabulations were used to evaluate incidence and temporal patterns. Results: We identified 469 DTC cases, including 85.7% papillary thyroid cancer and 9.4% follicular thyroid cancer. The average ASR for the period 1997-2021 was 1.16 per million, with higher rates in females compared with males (1.64 vs. 0.72 per million, respectively). Incidence rates increased with increasing age. The overall ASR increased from 0.84 per million in 1997-2001 to 1.48 per million in 2017-2021, with an AAPC of 3.46% [confidence interval or CI: 2.12-4.83]. The increase was most pronounced in adolescents aged 15-17 years (AAPC: 6.79% [CI: 4.43-9.19]). The proportion of incidentalomas rose from 5% in 1997-2001 to 26% in 2017-2021, yet we observed no marked shift in tumor size between symptomatic and incidental cases. Conclusions: Our study revealed a significant increase in pediatric DTC incidence in Germany, most pronounced among adolescents. The observation of an increasing incidence mirrors global trends and presents a complex public health challenge. While improved detection likely contributes to this trend, the stable tumor size distribution suggests that other factors are also in play. The rising detection of incidentalomas suggests enhanced diagnostic practices unrelated to symptoms of thyroid neoplasia. These findings highlight the need to carefully evaluate diagnostic and screening practices in pediatric populations.

Purpose: The COVID-19 pandemic was associated with severe disruptions in healthcare worldwide. Cancer patients are at particular risk of adverse consequences from delays in diagnosis and treatment. To evaluate the available data on the impact of the pandemic on cancer diagnoses, oncological care and patient well-being in Germany, the German Society for Epidemiology (DGEpi) in collaboration with the Epidemiological Cancer Registry of Lower Saxony invited to a workshop on "COVID & Cancer" (held on 26-27 October 2023 in Hanover, Germany). This report provides a summary of the scientific presentations, highlights methodological challenges, and recognises essential evidence gaps., Methods: Twelve studies addressing various aspects in relation to cancer diagnoses, oncological care and patient well-being during the COVID-19 pandemic in Germany and two talks sharing experiences from the UK and the Netherlands were presented at the workshop., Results and Conclusions: Results from German cancer registries consistently showed lower number of incident cancer diagnoses among adults during the first months of the pandemic compared to the respective months of the years before the pandemic. Data from the cancer registries of Baden-Württemberg and Lower Saxony found especially for breast cancer a notable drop (by approximately one third) in the numbers of diagnoses during the first restriction period (April-May 2020), during which the nationwide mammography screening programme in Germany was temporarily suspended. Overall, the extent and ways, in which the pandemic had adversely affected cancer diagnoses, oncological care and created service backlogs, is still not adequately understood. The long-term consequences are yet to be determined., (© 2024. The Author(s).)

Objectives: The aim of this billing data analysis was to examine the implementation of the second opinion directive in Germany and to investigate how often informing patients about their right to a second opinion (SO) and obtaining a SO are documented., Methods: To examine the frequency of "informing about SO" and "obtaining an SO", insured patients who received an indication for tonsillectomy, tonsillotomy or hysterectomy in 2019 or 2020 were included, as well as insured patients who received an indication for shoulder arthroscopy in Q2-Q3 2020. Data were analyzed descriptively., Results: During the study period, 5307 surgeries were reported for the above-mentioned indications. "Informing about SO" was documented for 121 patients with surgery and "obtaining an SO" was documented for 12 patients with surgery. The proportion of documented "informing about SO" compared to the number of surgeries was highest for tonsillectomy/tonsillotomy<18 years (4%) and lowest for shoulder arthroscopy (0.6%). In total, no patient was documented for both "informing about SO" and "obtaining an SO"., Conclusions: The present billing data analysis shows that information about the right to an SO according to the directive as well as the obtaining of such an SO has not yet been implemented in standard care as required by law., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Tumors of the central nervous system (CNS) are the second most common type of pediatric cancer in Germany. We aimed to describe registration practice, incidence, and survival patterns for childhood CNS tumors in Germany for the past 40 years., Procedure: Including all CNS tumor cases in children diagnosed at ages 0-14 years registered at the German Childhood Cancer Registry (GCCR) in 1980-2019 (for survival analysis 1980-2016), we calculated age-specific and age-standardized incidence rates (ASIR) over time, average annual percentage changes (AAPC), and 1- and 5-year overall survival., Results: While we observed a pronounced increase in ASIR after the establishment of the GCCR during the 1980s, ASIR for all pediatric CNS tumors combined continued to increase markedly from 28.6 per million in 1990-1999 to 43.3 in 2010-2019 (AAPC = 2.7% in 1991-2010, AAPC = 0.3% in 2010-2019). The 5-year overall survival from CNS tumors improved from 63% in the 1980s, 70% in the 1990s to 79% in 2010-2016. These improvements have occurred across all age groups. Children diagnosed with ependymomas and choroid plexus tumors experienced the strongest increase (from 54% to 81%)., Conclusions: Observed increases in incidence rates for pediatric CNS tumors are likely only partially caused by actual increasing case numbers. The majority is a function of improved registration and, to a minor extent, improvements in diagnostics. Survival from pediatric CNS tumors has, by and large, improved consistently, leading to a growing population of childhood cancer survivors with diverse health biographies and risk of lifelong adverse impact on health and wellbeing., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Primary lung malignancies are a heterogeneous group of cancers that occur very rarely in childhood. Due to limited knowledge of their epidemiologic and clinical features, these tumors present a challenge to the treating physicians. This study aimed to increase the knowledge about the occurrence of primary lung malignancies in childhood in Germany., Materials and Methods: Pseudonymized data of cases recorded at the German Center for Cancer Registry Data (ZfKD) between 1990 and 2017 were retrieved. Primary lung malignancies were identified using the ICD- and ICD-O classification. Numbers were compared to those reported to the German Childhood Cancer Registry (GCCR). Crude incidence rates were calculated using the ZfKD database., Results: A total of 168 patients diagnosed with primary lung malignancies in the age below 19 years were identified from the ZfKD. The median age at diagnosis was 13 years. The most common tumor entities were lung carcinoids (n = 49), lung carcinoma (n = 36), and pleuropulmonary blastoma (n = 14). An unexpected accumulation of lung cancer cases was noted in the first year of life without a clearly specified histopathological diagnosis. A substantial discrepancy in the numbers of primary lung malignancies between ZfKD and GCCR was found., Conclusions: We present population-based data on the occurrence of primary childhood lung malignancies in Germany, which were more frequent than previously anticipated but likely remained underreported. For better understanding and optimal treatment of these entities, cancer registration needs to be improved through mandatory reporting to the GCCR and regular data sharing between GCCR, population-based and clinical cancer registries., (© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Very rare pediatric tumors (VRTs) pose a challenge for treating physicians as little is known about the best diagnostic assessment and therapeutic decision-making in these malignancies. A large proportion of these cancers occur in adolescence. Therefore, the established structures of pediatric oncology including cancer registration may partly be circumvented. This may lead to an underregistration in clinical cancer registries of yet unclear extent. The aim of this study is to increase the knowledge on the occurrence of VRTs in pediatric patients in Germany. Pseudonymized data of cases recorded in the Bavarian Cancer Registry (BCR) between 2002 and 2014 were retrieved. VRTs according to the definition of the European Cooperative Study Group for Pediatric Rare Tumors were identified using the ICD and ICD-O classification. The numbers of registered patients were compared to those reported to the German Childhood Cancer Registry (GCCR). 6.3% (n = 290) of all malignancies (n = 4615) in the age below 18 years were classified as VRTs. Median age at diagnosis was 15 years (range 0-17 years). The most common tumor types included malignant melanoma, skin carcinoma, and gonadal tumors. During the same period, 49 pediatric patients from Bavaria with matchable VRTs were reported to the GCCR, accounting for 17% of cases reported to the BCR., Conclusions: The frequency of VRTs in Germany is underestimated in the national GCCR. With this study, we present population-based data on the incidence of VRTs in Germany for the first time. In order to gain additional knowledge about these malignancies, registration of VRTs must be improved through enhanced data exchange between the GCCR, the public cancer registries, and the clinical Registry for Rare Pediatric Tumors (STEP)., What Is Known: • Rare pediatric tumors pose a challenge for treating physicians as limited knowledge is available on these malignancies for diagnostic and therapeutic decision-making. • Little is known about the frequency of these rare tumors in pediatric patients., What Is New: • The frequency of rare pediatric tumors in Germany is distinctly underestimated in the German Childhood Cancer Registry. • We present population-based data on the incidence of these rare pediatric cancers for the first time., (© 2022. The Author(s).)

Purpose: Fanconi anemia (FA) and ataxia-telangiectasia (AT) are rare inherited syndromes characterized by abnormal DNA damage response and caused by pathogenic variants in key DNA repair proteins that are also relevant in the pathogenesis of breast cancer and other cancer types. The risk of cancer in children with these diseases is poorly understood and has never been assessed in a population-based cohort before., Methods: We identified 421 patients with FA and 160 patients with AT diagnosed between 1973 and 2020 through German DNA repair disorder reference laboratories. We linked patients' laboratory data with childhood cancer data from the German Childhood Cancer Registry., Results: Among 421 patients with FA, we observed 33 cases of childhood cancer (15 cases of myelodysplastic syndrome; seven cases of acute myeloid leukemia; two cases of lymphoma, carcinoma, medulloblastoma, and nephroblastoma, respectively; and one case of rhabdomyosarcoma, acute lymphoblastic leukemia, and glioma, respectively) versus 0.74 expected (on the basis of population-based incidence rates in Germany). This corresponds to a 39-fold increased risk (standardized incidence ratio [SIR] = 39; 95% CI, 26 to 56). For all FA subgroups combined, the cancer-specific SIR for myeloid neoplasms was 445 (95% CI, 272 to 687). Among the 160 patients with AT, we observed 19 cases of childhood cancer (15 cases of lymphoma, three cases of leukemia, and one case of medulloblastoma) versus 0.32 expected. This corresponds to a 56-fold increased risk (SIR = 56; 95% CI, 33 to 88). The cancer-specific SIR for Hodgkin lymphoma was 215 (95% CI, 58 to 549) and for non-Hodgkin lymphoma 470 (95% CI, 225 to 865)., Conclusion: Approximately 11% of patients with FA and 14% of patients with AT develop cancer by age 18 years.

The growing population of long-term childhood cancer survivors is at increased risk for severe, therapy-related late effects and premature mortality. The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS) study is a cohort of patients from Germany diagnosed with a neoplasia prior to 15 years of age in the time period 1980 to 1990. Late mortality was evaluated in a total of 4505 individuals who survived 5 years or more after the initial diagnosis (5-year survivors). Survivors with a second primary tumor were excluded. Standardized mortality ratios (SMRs) were calculated. By December 2014, 400 patients had died. Available cause of death information from 188 individuals was used to estimate cause-specific mortality for all deceased persons. Compared to the population of (former) West Germany, we observed an excess overall mortality risk (SMR = 9.53, 95% confidence interval [CI] = 8.62-10.51). After correcting for missing cause of death information, an increased cancer mortality (SMR = 43.50, 95% CI = 25.79-73.50) in the 5-year survivors was detected. Cardiac death was ascertained in 14 individuals, resulting in an SMR of 10.85 (95% CI = 2.80-32.02) after correcting for missing values. In conclusion, childhood cancer survivors diagnosed in Germany in 1980 to 1990 have a higher mortality risk overall and an elevated risk of dying from cancer and cardiac causes in particular. The results are consistent with those of international cohort studies. However, the reported results are based on few cases and individuals with secondary cancers were excluded., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Neuroblastoma screening aims to reduce neuroblastoma-related mortality. A controlled trial showed no reduction in stage 4 disease incidence and preliminary mortality data. This article presents epidemiologic and clinical data 20 years after cessation of the screening program., Methods: The patients with detected disease in the screening area were compared with the clinically diagnosed patients in the control area and in the prestudy and poststudy cohorts. All statistical tests were 2-sided., Results: The cumulative incidence for children aged 1 to 6 years in the birth study cohorts (1994-1999) in the screening arm was 13.4 cases per 100 000 births (95% confidence interval [CI] = 12.2 to 14.6) based on 61.2% of screening participants and 38.8% of nonparticipants. Screening participants had a cumulative incidence of 15.7 (95% CI = 14.0 to 17.4) per 100 000 births. The cumulative incidence in the contemporary control cohort was 9.3 (95% CI = 8.2 to 10.3) per 100 000 births, 7.6 (95% CI = 6.8 to 8.4) in the prestudy cohort, and 8.1 (95% CI = 7.4 to 8.9) in the poststudy cohort from 2000 to 2004 ( P  <   .001 each). The increased incidence in the screening cohort was restricted to stages 1 through 3, while stage 4 incidence was not reduced. The cumulative mortality for deaths within 10 years from diagnosis and per 100 000 births remained unchanged. Patients with stage 4 disease detected by screening had better biological characteristics and an improved outcome compared with those stage 4 cases not detected by screening., Conclusions: Neuroblastoma screening at 1 year of age reduced neither stage 4 incidence nor neuroblastoma mortality and was affected by overdiagnosis, leading to unnecessary treatment. A few screening-detected stage 4 cases represent a biologically interesting subgroup but do not change the recommendation to close the "catecholamine-based neuroblastoma screening book.", (© The Author(s) 2021. Published by Oxford University Press.)

Background: Successive multicenter studies for pediatric low-grade glioma (LGG) in Germany were accompanied by a doubling of annual recruitment over 2 decades. We investigated whether this increase conveyed a change of epidemiologic characteristics or survival., Methods and Results: Participating centers reported 4634 patients with the radiologic/histologic diagnosis of LGG (1996-2018), rising from 109 to 278/year. Relating these numbers to all pediatric CNS tumors registered at the German Childhood Cancer Registry, the LGG fraction and annual crude incidence rates increased (32% to 51%; 0.94 to 2.12/100,000 children/adolescents<15 years). The consecutive LGG studies recruited 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004), and 1836 (LGG-registry) patients with similar distribution of tumor-sites, histology, and dissemination. 5-year overall survival was 96%-98% at median observation time of 8.1 years. Acknowledging unequal follow-up periods, 589/899 (66%), 1089/1582 (69%), and 1387/1836 (76%) patients remained under observation, while 1252/4317 received adjuvant treatment with decreasing frequency of front-line radiotherapy from 16% to 5%., Conclusion: Pediatric LGG incidence rates in Germany are now comparable to other European countries. The rise in patient numbers followed implementation of standard-of-care treatment protocols, but did not result in relevant changes of epidemiologic or clinical parameters or survival. Shifts in patient distribution between treatment arms reflect growing acceptance of the LGG therapy algorithm., Hintergrund: In den vergangenen 20 Jahren hat sich die jährliche Patientenrekrutierung in den aufeinanderfolgenden multizentrischen Studien für pädiatrische niedrig-gradige Gliome (LGG) in Deutschland verdoppelt. Wir haben untersucht, ob sich mit dieser Zunahme auch epidemiologische Merkmale oder das Überleben verändert haben., Methodik Und Ergebnisse: Zwischen 1996 und 2018 meldeten die teilnehmenden Zentren insgesamt 4634 Patienten mit der radiologischen/histologischen Diagnose eines LGG. Die Zahl stieg von anfangs 109 bis 278 Patienten pro Jahr. Gleichzeitig stieg der Anteil der LGGs an allen am Deutschen Kinderkrebsregister gemeldeten pädiatrischen Hirntumoren von 32 auf 51%, die jährliche Inzidenz erhöhte sich von 0,94 auf 2,12/100 000 Kinder/Jugendliche<15 Jahre. Die aufeinanderfolgenden LGG-Studien rekrutierten 899 (HIT-LGG 1996), 1592 (SIOP-LGG 2004) und 1836 (LGG-Register) Patienten mit vergleichbarer Verteilung von Tumorsitz, Histologie und Disseminierung. Das 5-Jahres-Überleben lag bei einer medianen Nachbeobachtungszeit von 8,1 Jahren zwischen 96 und 98%. Unter Berücksichtigung der ungleich langen Follow-up-Zeit wurden 589/899 (65,5%), 1089/1582 (68,8%) und 1387/1836 (75,5%) Patienten bislang beobachtet, während 1252/4317 eine adjuvante Therapie erhielten. Dabei sank der Anteil der primären Radiotherapie von 16 auf 5%., Schlussfolgerung: Die Rekrutierung pädiatrischer LGG ist dank Implementierung verbindlicher Therapiestandards in Deutschland gestiegen, ohne zu relevanten Veränderungen epidemiologischer oder klinischer Merkmale oder des Überlebens zu führen. Die Inzidenz ist mit anderen europäischen Ländern vergleichbar. Verschiebungen der Patientenzuteilung zwischen den Therapiearmen spiegeln die zunehmende Akzeptanz des LGG-Therapie-Algorithmus wider., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)