Germ Cell Tumor

The book aims to provide an overview of current knowledge regarding germ cell tumors. It deals with the clinical presentations, treatment modalities, the biology and genetics of germ cell tumors in children and adults. Most chapters are focused on testicular germ cell tumors whose incidence has been increasing in young males. Included are reviews on the pathogenesis, risk factors, diagnosis and treatment regimens applied to precursor, pre-invasive lesions as well as to seminomatous and non-seminomatous germ cell tumors of the testes. In addition, a review is included on the diagnosis and current management options for intracranial germ cell tumors in children. Authors have also contributed articles on the genetics and epigenetics of germ cell tumor development in humans and in the mouse model system. This book will be of interest to scientists, physicians and lay readers wishing to review recent developments in the field of germ cell cancers

Treatment and survival of malignant extracranial germ cell tumours in the paediatric population: a systematic review and meta-analysis

Simple Summary Germ cell tumours are a heterogeneous group of neoplasms and are predominantly midline tumours occurring from birth to late adulthood. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis or platinum-resistant disease. The aim of our systematic review was to explore survival rates internationally over the past two decades in order to better define future practice and treatment strategies and also to define specific subgroups with inferior outcomes. The results of our systematic review describe the heterogeneous nature of germ cell tumours in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, subpopulations can be defined which have an inferior survival and where future research and more individualised treatment would help to improve survival. Objective: This systematic review and meta-analysis was performed to explore overall survival (OS) and event free survival (EFS) rates internationally over the past two decades and to define specific subgroups with inferior outcomes which may demand different treatment strategies. Methods: The search focused on malignant extracranial germ cell tumours (GCTs) in the paediatric population. The initial database search identified 12,556 articles; 32 articles were finally included in this review, comprising a total of 5095 patients. Results: The studies were heterogeneous, varying from single institution reports to large prospective trials. Older studies, describing eras where non-platinum-based chemotherapy regimens were used, showed clearly worse outcomes. Survival for stage I-II gonadal disease is excellent. On the other hand, patients with an initial alpha-fetoprotein (AFP) > 10,000 ng/mL or kU/L, age > 11 years and stage IV disease confer a survival disadvantage. For testicular disease in particular, lymphovascular invasion and certain histopathological subtypes, such as embryonal carcinoma (EC) and mixed malignant GCTs, survival is poorer. Survival data for sacrococcygeal and mediastinal GCTs show a heterogeneous distribution across studies in this review, independent of year of publication. Patients > 12 years presenting with a mediastinal GCT pose a subpopulation which fares worse than GCTs in other locations or age groups. This is independent of AFP levels, stage of disease or treatment protocol, and these patients may demand a different treatment strategy. Conclusions: This review describes the heterogeneous nature of GCTs in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, in line with the current developmental biology-based classification system, subpopulations can be defined which have an inferior EFS and OS and where future research and more individualised treatment would help to improve survival.Development and application of statistical models for medical scientific researc

Treatment and Survival of Malignant Extracranial Germ Cell Tumours in the Paediatric Population: A Systematic Review and Meta-Analysis

OBJECTIVE: This systematic review and meta-analysis was performed to explore overall survival (OS) and event free survival (EFS) rates internationally over the past two decades and to define specific subgroups with inferior outcomes which may demand different treatment strategies. METHODS: The search focused on malignant extracranial germ cell tumours (GCTs) in the paediatric population. The initial database search identified 12,556 articles; 32 articles were finally included in this review, comprising a total of 5095 patients. RESULTS: The studies were heterogeneous, varying from single institution reports to large prospective trials. Older studies, describing eras where non-platinum-based chemotherapy regimens were used, showed clearly worse outcomes. Survival for stage I-II gonadal disease is excellent. On the other hand, patients with an initial alpha-fetoprotein (AFP) > 10,000 ng/mL or kU/L, age > 11 years and stage IV disease confer a survival disadvantage. For testicular disease in particular, lymphovascular invasion and certain histopathological subtypes, such as embryonal carcinoma (EC) and mixed malignant GCTs, survival is poorer. Survival data for sacrococcygeal and mediastinal GCTs show a heterogeneous distribution across studies in this review, independent of year of publication. Patients > 12 years presenting with a mediastinal GCT pose a subpopulation which fares worse than GCTs in other locations or age groups. This is independent of AFP levels, stage of disease or treatment protocol, and these patients may demand a different treatment strategy. CONCLUSIONS: This review describes the heterogeneous nature of GCTs in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, in line with the current developmental biology-based classification system, subpopulations can be defined which have an inferior EFS and OS and where future research and more individualised treatment would help to improve survival

Treatment and Survival of Malignant Extracranial Germ Cell Tumours in the Paediatric Population: A Systematic Review and Meta-Analysis

OBJECTIVE: This systematic review and meta-analysis was performed to explore overall survival (OS) and event free survival (EFS) rates internationally over the past two decades and to define specific subgroups with inferior outcomes which may demand different treatment strategies. METHODS: The search focused on malignant extracranial germ cell tumours (GCTs) in the paediatric population. The initial database search identified 12,556 articles; 32 articles were finally included in this review, comprising a total of 5095 patients. RESULTS: The studies were heterogeneous, varying from single institution reports to large prospective trials. Older studies, describing eras where non-platinum-based chemotherapy regimens were used, showed clearly worse outcomes. Survival for stage I-II gonadal disease is excellent. On the other hand, patients with an initial alpha-fetoprotein (AFP) > 10,000 ng/mL or kU/L, age > 11 years and stage IV disease confer a survival disadvantage. For testicular disease in particular, lymphovascular invasion and certain histopathological subtypes, such as embryonal carcinoma (EC) and mixed malignant GCTs, survival is poorer. Survival data for sacrococcygeal and mediastinal GCTs show a heterogeneous distribution across studies in this review, independent of year of publication. Patients > 12 years presenting with a mediastinal GCT pose a subpopulation which fares worse than GCTs in other locations or age groups. This is independent of AFP levels, stage of disease or treatment protocol, and these patients may demand a different treatment strategy. CONCLUSIONS: This review describes the heterogeneous nature of GCTs in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, in line with the current developmental biology-based classification system, subpopulations can be defined which have an inferior EFS and OS and where future research and more individualised treatment would help to improve survival

Clinical Profile of Children with Extra Cranial Germ Cell Tumors

INTRODUCTION: Germ cell tumors (GCTs) are a rare group of benign and malignant tumors which can occur at many different sites. These can be both gonadal and extragonadal. They occur in the para-axial locations like sacrococcygeal area, gonads, retroperitoneum, mediastinum, neck and pineal gland in order of frequency, due to the arrest or abnormal migration of primitive germ cells. These tumors represent about 1-3% of all childhood tumors, and about 8-10% of all paediatric solid tumors. There is large spectrum of these tumors from the mature teratoma to the highly malignant embryonal carcinoma. Benign teratomas are the commonest although upto 30% malignancy has been described in various series. AIM/OBJECTIVES: To assess the clinico-pathological profile and the long term effects of treatment in children, with extracranial germ cell tumors (GCTs). MATERIALS AND METHODS: All children below the age of 16 years who presented to the department of Paediatric Surgery with GCTs between January 2003 and December 2012 were included in this study. This was a retrospective study looking at the patient data base. All eligible patients were informed by mail and phone by the investigator and requested to attend the outpatient department for follow up. Data was analyzed using descriptive statistical methods for continuous and categorical variables. Binary logistic regression was used to look at risk factors, and Kaplan Meier curves for overall survival and event free survival. RESULTS: 107 children with GCTs were studied for the period between 2003 to 2012, 64% were female and 36% were male, 56% were below 5 years of age. A majority were found to have ovarian GCTs (28%) followed by sacrococcygeal (23%) and testicular (15%) tumors. Malignancy was found in 46%, the commonest being yolk sac tumor. Elevated Alpha feto protein was found in all children with malignancy. Surgery alone or in combination with chemotherapy was used to treat these tumors. Overall survival and event free survival for malignant GCTs was 85.2% and 75.9% respectively. Median survival was 44 months. CONCLUSIONS: GCTs are rare tumors which occur at many different sites. They are more common in females and have different age peaks for different sites. Non gonadal sites predominate in early childhood, while gonadal GCTs are more common during the later part of childhood and adolescence. Benign tumors are more common. Malignancy can occur, with Yolk Sac tumors being the commonest. Multimodality treatment with surgery and chemotherapy has excellent results in malignant tumors. Long term follow up is advisable for all patients who have GCTs