Pediatric Cancers

Question 1

What is the epidemiology of childhood and adolescent cancers?

Answer 1

• Cancers affect approximately 20,000 children and young adults annually in the United States
  
  • Although relative 5-yr survival rates have continued to improve over the past several decades, malignant neoplasms remain the leading cause of disease-related related mortality in children

Question 2

How do pediatric cancers differ from adult malignancies?

Answer 2

• Pediatric cancers differ significantly from adult malignancies in both prognosis and distribution by histology and tumor site
• Broadly, 40% of all childhood cancers are of lymphohematopoietic origin (i.e., acute lymphoblastic leukemia, lymphomas), 30% are central nervous system tumors, 10% are embryonal tumors and 10% are sarcomas
• Common adult epithelial tumors of the lung, colon, breast and prostate are rarely seen in children
• Unlike adult cancers, where cancer incidence increases with age, pediatric cancers present throughout the age spectrum
  
  • ​There is a peak in early childhood and a second peak in adolescence
  • Tumors of developmental origin such as neuroblastoma, nephroblastoma (Wilm’s tumor) and hepatoblastoma occur more commonly in younger children
  • As the normal developmental processes slow down, they become less common in older children and adolescents
  • Adolescence and young adulthood is a transitional period between the common early childhood malignancies and characteristic carcinomas of adulthood
• Most pediatric cancers are sporadic with no identifiable cause
  
  • Efforts at identifying environmental, exposure or infectious causes have been inconclusive thus far
  • The varying incidence patterns of specific childhood cancers globally imply additional genetic and epidemiologic risk factors that are yet to be elucidated

Question 3

What are the genetic conditions related to childhood cancers?

Answer 3

• An underlying genetic predisposition syndrome affects approximately 5% of all children with cancer
• Genetic conditions that impart susceptibility to childhood cancer are:
  
  • neurofibromatosis types 1 and 2
  • Down syndrome
  • Beckwith-Wiedemann syndrome
  • tuberous sclerosis
  • von Hippel-Lindau disease
  • xeroderma pigmentosum
  • ataxia-telangiectasia
  • nevus basal cell carcinoma syndrome
  • Li-Fraumeni (p53) syndrome

Question 4

What are the common signs and symptoms of childhood cancer? How is childhood cancer more challenging that adult cancers?

Answer 4

• The symptoms and signs of cancer in pediatric patients are variable, nonspecific and often overlap with benign illnesses
• Age related challenges in diagnosis include the fact that infants and young children cannot localize or express their symptoms well
  
  • Additionally, late adolescents and young adults are more hesitant to seek medical care
  • The physiology and biology of growth and development during childhood is variable, further contributing to the difficulty in making a diagnosis of cancer early
• In children, dissemination of disease at diagnosis is more common than in adults, and presenting symptoms or signs are often caused by systemic involvement
• Pain is the single most common presentation of childhood cancer
• Mass screening strategies to improve early detection of pediatric cancers are not practical
• However, children with cancer predisposition syndromes require an individualized plan for cancer screening

Question 5

What are the adverse effects of treatment of childhood cancers?

Answer 5

• Curative therapy with chemotherapy, radiation, and/or surgery commonly adversely affects a child’s development and results in serious long-term medical and psychosocial effects throughout the lifespan
• These include:
  
  • second malignancies
  • early death
  • infertility
  • impaired growth
  • pulmonary fibrosis
  • cardiomyopathy
  • neurocognitive impairments
  • mental health disorders
  • altered social functioning
• Therefore, contemporary cancer therapy is focused on maximizing cure while minimizing potential adverse late effects

Question 6

What are the treatment modalities of childhood cancers?

Answer 6

• Treatment for childhood cancer requires a multi-disciplinary and multi-modal approach
• As a general principle, chemotherapy is used more widely in children than in adults; malignant tumors in children are more responsive to chemotherapy and children tolerate the acute adverse effects much better than adults
  
  • Radiation therapy is used sparingly in children because they are significantly more vulnerable than adults to its late adverse effects
  • Biologic and molecularly targeted agents are increasing in popularity and are currently considered part of first line therapy for some childhood malignancies
• Every effort is made to deliver a majority of therapy as an outpatient to maximize time at home and in school

Question 7

What are the common pediatric solid tumors?

Answer 7

• Primary tumors of the central nervous system (CNS) tumors are a group of heterogeneous diseases and together are the second most common malignancy in children and young adults
• Overall survival for all patients with newly diagnosed CNS tumors is near 75% at five years
  
  • However, CNS tumors are the largest contributor to cancer-related mortality in children
  • Further patients often have significant morbidity from both the tumor and subsequent treatment
• Pediatric CNS tumors require expert, multidisciplinary care
  
  • Surgery with complete resection, if feasible, is the foundation, with radiation therapy and chemotherapy utilized according to the diagnosis, patient age, and other factors
  • Outcomes have slowly improved over time with innovations in neurosurgery and radiation therapy as well as introduction of conventional and targeted chemotherapy

Question 8

What is the management and prognosis of neuroblastoma?

Answer 8

• Neuroblastomas are embryonal cancers of the peripheral sympathetic nervous system which most commonly affect younger children
  
  • These tumors are associated with heterogeneous clinical presentation and course, ranging from tumors that undergo spontaneous regression to very aggressive tumors unresponsive to very intensive multimodal therapy
• Most cases are sporadic and patients with low risk disease have excellent outcomes
• In contrast, patients with high risk neuroblastoma have inferior outcomes and require aggressive multimodal therapy including surgery, chemotherapy, autologous stem cell transplantation and radiation therapy

Question 9

What are the most common childhood tumors and how are they managed?

Answer 9

• A vast majority (90%) of all tumors of the kidney in children are nephroblastoma (Wilm’s tumor)
  
  • Through cooperative group efforts, the cure rate for this disease jumped significantly from 30% in the 1980’s to approximately 95% in the current era
• Ongoing work is attempting to limit long term toxicities of chemotherapy in this patient population
• Other tumors of the kidney including malignant rhabdoid tumor, clear cell sarcoma of the kidney and renal cell carcinoma are rare and have poor outcomes

Question 10

What is the management and prognosis of childhood cancers?

Answer 10

• Sarcomas of the bone and soft tissue affect children throughout the age spectrum, but have an incidence peak in adolescence and young adulthood
  
  • They can occur in virtually any anatomic site
  • Rhabdomyosarcoma is the most common pediatric soft tissues sarcoma
• Tumors of the bone include osteosarcoma and Ewing’s Sarcoma (characterized by a specific chromosomal translocation t(11;22))
  
  • For all histologies, localized disease that is amenable to surgical resection has the most favorable outcomes
• Metastatic disease (most often to the lung) confers a very poor prognosis, despite improved understanding of tumor biology

Question 11

What are some rare pediatric cancers and conditions?

Answer 11

• Retinoblastoma is an embryonal cancer of the retina and can be either sporadic or hereditary
  
  • Hereditary cases are typically diagnosed at a younger age with multifocal and bilateral tumors
  • They are associated with a germline mutation or deletion in the retinoblastoma (RB1) gene
  • Outcomes in developing countries are excellent, but 50% of patients with retinoblastoma worldwide will progress to metastatic disease and die
• Childhood histiocytoses are a diverse group of disorders cared for by pediatric oncologist
  
  • Though histiocytoses technically are not malignant condition, they may be severe in their clinical expression
  • Histiocytic disorders are characterized by a prominent proliferation or accumulation of cells of the monocyte-macrophage system of bone marrow origin

Question 12

What is Children’s Oncology Group?

Answer 12

• The Children’s Oncology Group is a multi-institutional research consortium that facilitates cooperative clinical, biologic, and epidemiologic research in more than 200 affiliated institutions in the United States, Canada, and other countries
• Given the relative rarity of specific types of childhood cancer and the technology and expertise required for diagnosis, treatment, and monitoring of late effects, all children with cancer should be treated on clinical protocols in pediatric clinical research settings if possible
  
  • Coordinated participation in such trials has been the single greatest factor in the increased survival for many children with cancer
  • These ongoing efforts are critical to understand the etiology of childhood cancers, improve survival and maximize quality of life for survivors