Medicine:Childhood cancer

From HandWiki
Childhood cancer
Other namesPediatric cancer
Trying out hats to wear after chemotherapy - cropped.jpg
A girl trying out hats to wear after chemotherapy against a Wilms' tumor[1]
SpecialtyPediatrics, oncology

Childhood cancer is cancer in a child. About 80% of childhood cancer cases can be successfully treated thanks to modern medical treatments and optimal patient care.[2] However, only about 10% of children diagnosed with cancer reside in high-income countries where the necessary treatments and care is available.[3][4] Childhood cancer represents only about 1% of all types of cancers diagnosed in children and adults.[citation needed] For this reason, childhood cancer is often ignored in control planning, contributing to the burden of missed opportunities for its diagnoses and management in countries that are low- and mid-income.[5]

In the United States, an arbitrarily adopted standard of the ages used are 0–14 years inclusive, that is, up to 14 years 11.9 months of age.[6][7] However, the definition of childhood cancer sometimes includes adolescents between 15 and 19 years old.[7] Pediatric oncology is the branch of medicine concerned with the diagnosis and treatment of cancer in children.

Signs and symptoms

Leukemia

This is the most common type of cancer during childhood, and acute lymphoblastic leukemia (ALL) is most common in children. ALL usually develops in children between the ages of 1 and 10 (it could occur at any age). This type of cancer is more prevalent in males and in whites.[8]

Signs & Symptoms:

Frequent delayed diagnosis (early symptoms are nonspecific)

  • Generalized malaise
  • Loss of appetite
  • Low-grade fever
  • Pallor
  • Petechiae  
  • Ecchymoses
  • Bone pain
  • Significant, unintended, and sudden weight loss

Physical examination:

Important: It is recommended that a complete blood count is obtained (CBC) if any suspicious finding arise.

Central nervous system tumors

This is the second most common malignancy diagnosed during childhood.[9]

Signs and Symptoms

  • Ataxia
  • Other gait disturbances (hydrocephalus due to aqueduct compression)
  • Cranial nerve abnormalities as a result of brainstem compression

Hodgkin's disease

The likelihood of developing Hodgkin's disease increases during childhood and it peaks in adolescence.[8][10]

Hodgkin's disease

Signs and Symptoms

  • Painless mass in the neck
  • Persistent cough secondary to a mediastinal mass
  • Less commonly: splenomegaly or enlarged axillary or inguinal lymph nodes
  • Intermittent fever
  • Drenching night sweats
  • Loss of greater than 10 percent of total body weight.
  • Anorexia
  • Fatigue
  • Pruritus
  • Persistent painless mass

Non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma is more common in older children, and it is less prevalent than Hodgkin's disease.[11]

Signs and Symptoms

If abdomen is affected

If mediastinum is affected

  • Severe dyspnea
  • Superior vena cava syndrome[12]

If head and neck masses are affected

  • Palpable mass
  • Cranial nerve palsies
  • Nasal obstruction

Neuroblastoma

This cancer is an extracranial solid tumor commonly diagnosed in childhood.  

Signs and Symptoms

  • Dysfunction of the location of the primary tumor
  • Anorexia
  • Abdominal pain
  • Distention.

Wilms' tumor

Main page: Medicine:Wilms' tumor

This malignancy presents as an abdominal mass in a child.[13]

Signs and Symptoms

Malignancies of the musculoskeletal system

A tumor that arises in the musculoskeletal system often presents as a mass, a painful extremity or, occasionally, a pathologic fracture.[8]

Signs and Symptoms

  • Pain awakens a child at night
  • Significant extremity dysfunction (when trauma is not involved)

Genetic syndromes associated with cancer

The cause of cancer is not yet well understood. Several chromosomal disorders and constitutional syndromes are associated with it.[8][14]

Learning problems

This cognitive problem is known as post-chemotherapy cognitive impairment (PCCI) or "chemo brain." This term is commonly use by cancer survivors who describe having thinking and memory problems after cancer treatment.[15] Researchers are unsure what exactly causes chemo brain, however, they say it is likely to be linked to either the cancer itself, the cancer treatment, or be an emotional reaction to both.[15]

This cognitive impairment is commonly noticed a few years after a child endures cancer treatment. When a childhood cancer survivor goes back to school, they might experience lower test scores, problems with memory, attention, and behavior, as well as poor hand-eye coordination and slowed development over time.[16] Children with cancer should be monitored and assessed for these neuropsychological deficits during and after treatment.[17] Patients with brain tumors can have cognitive impairments before treatment [18] and radiation therapy is associated with increased risk of cognitive impairment.[19] Parents can apply their children for special educational services at school if their cognitive learning disability affects their educational success.[20]

Risk factors

Risk factors are any genetic or environmental exposure that increase the chances of developing a pathological condition. Some examples are age, family history, environmental factors, genetics, and economic status among others.[21]

Demographic risk factors

  • Childhood cancer varies by age, sex, ethnicity, and race.[22] Its incidence peaks in infancy with about 240 cases/million/year.
  • This rate decreases to 128 cases per million from 5–9 years of age, and it rises again to 220 cases/million.
  • Slight male dominance for most childhood cancers.

Environmental factors

  • High dose ionizing radiation and prior chemotherapy are accepted causes of childhood cancer, each raising risk several fold (4-7).[23]

Genetic factors

Identified Cancer Predisposition Syndromes[24]

  • Li-Fraumeni syndrome (TP53)
  • Hereditary breast or ovarian cancer (BRCA ​1⁄2)
  • Colorectal cancer/polyposis syndromes
  • Familial retinoblastoma (RB1)
  • Familial and genetic factors are identified in 5-15% of childhood cancer cases. In <5-10% of cases, there are known environmental exposures and exogenous factors, such as prenatal exposure to tobacco, X-rays, or certain medications.[25] For the remaining 75-90% of cases, however, the individual causes remain unknown.[25] In most cases, as in carcinogenesis in general, the cancers are assumed to involve multiple risk factors and variables.[26]

Aspects that make the risk factors of childhood cancer different from those seen in adult cancers include:[27]

  • Different, and sometimes unique, exposures to environmental hazards. Children must often rely on adults to protect them from toxic environmental agents.
  • Immature physiological systems to clear or metabolize environmental substances
  • The growth and development of children in phases known as "developmental windows" result in certain "critical windows of vulnerability".

Also, a longer life expectancy in children avails for a longer time to manifest cancer processes with long latency periods, increasing the risk of developing some cancer types later in life.[27]

Advanced parental age has been associated with increased risk of childhood cancer in the offspring.[28] There are preventable causes of childhood malignancy, such as delivery overuse and misuse of ionizing radiation through computed tomography scans when the test is not indicated or when adult protocols are used.[29][30]

Diagnosis

Types

Two girls with acute lymphocytic leukemia demonstrating intravenous access for chemotherapy.

The most common cancers in children are (childhood) leukemia (32%), brain tumors (18%), and lymphomas (11%).[31][32] In 2005, 4.1 of every 100,000 young people under 20 years of age in the U.S. were diagnosed with leukemia, and 0.8 per 100,000 died from it.[33] The number of new cases was highest among the 1–4 age group, but the number of deaths was highest among the 10–14 age group.[33]

In 2005, 2.9 of every 100,000 people 0–19 years of age were found to have cancer of the brain or central nervous system, and 0.7 per 100,000 died from it.[33] These cancers were found most often in children between 1 and 4 years of age, but the most deaths occurred among those aged 5–9.[33] The main subtypes of brain and central nervous system tumors in children are: astrocytoma, brain stem glioma, craniopharyngioma, desmoplastic infantile ganglioglioma, ependymoma, high-grade glioma, medulloblastoma and atypical teratoid rhabdoid tumor.[34]

Other, less common childhood cancer types are:[34][32]

Medical specialties

Overall, treating childhood cancer requires a multidisciplinary team of doctors, nurses, social workers, therapists, and other members of the community. Here is a brief list of doctors that can treat childhood cancer:[35]

  • Pediatric oncologist: These doctors specialize in treating childhood cancers.
  • Pediatric hematology-oncologist: These doctors specialize in treating blood diseases in children.
  • Pediatric surgeon: These doctors specialize in performing surgery on children.
  • Adolescent and young adult oncology (AYA): AYA is a branch of medicine that deals with the prevention, diagnosis, and treatment of cancer in adolescents and young adults, often defined as those aged 13–30. Studies have continuously shown that while pediatric cancer survival rates have gone up, the survival rate for adolescents and young adults has remained stagnant. Additionally, AYA helps patients with college concerns, fertility, and sense of aloneness. Studies have often shown that treating young adults with the same protocols used in pediatrics is more effective than adult-oriented treatments.

Other specialties that can assist in the treatment process include radiology, neurosurgery, orthopedic surgery, psychiatry, and endocrinology.

Treatment

Childhood cancer treatment is individualized and varies based on the severity & type of cancer.[36] In general, treatment can include surgical resection,[37] chemotherapy,[38] radiation therapy,[39] or immunotherapy.[40]

Recent medical advances have improved our understanding of the genetic basis of childhood cancers. Treatment options are expanding, and precision medicine for childhood cancers is a rapidly growing area of research.[41]

The side effects of chemotherapy can result in immediate and long-term treatment-related comorbidities.[42] For children undergoing treatment for high-risk cancer, more than 80% experience life-threatening or fatal toxicity as a result of their treatment.[43]

Psychosocial care of children with cancer is also important during the cancer journey, but the implementation of evidence-based interventions need to be further spread across pediatric cancer centers.[44] In general, psychosocial care can include therapy with a psychologist or psychiatrist, referral to a social worker, or referral to a pastoral counselor.[35] Family-centered psychosocial care is one approach that can be used to not only support the patient's psychosocial well-being but also support the parents and any caregivers of the patient.[45]

Prognosis

Since adult survivors of childhood cancer are living longer, these individuals may experience long-term complications that are associated with their cancer treatment.[46] This can include problems with organ function, growth and development, neurocognitive function and academic achievement, and risk for additional cancers.[46][47]

Premature heart disease is one example of a major long-term consequence seen in adult survivors of childhood cancer.[48] These individuals are eight times more likely to die of heart disease than other people, and more than half of the children treated for cancer develop some type of cardiac abnormality, although this may be asymptomatic or too mild to qualify for a clinical diagnosis of heart disease.[48]

Childhood cancer survivors are also at risk of sustaining adverse effects on the kidneys [49] and the liver.[50] Specific cancer treatments such as cisplatin, carboplatin, and radiotherapy are known to cause kidney damage.[49] The risk of liver damage is increased in those who have had radiotherapy to the liver and in those with other risk factors, such as a higher body mass index or chronic viral hepatitis.[50] Certain treatments and liver surgery may also increase the risk of adverse liver effects in childhood cancer survivors.[50]

To help monitor for these long-term consequences, a set of guidelines have been created to facilitate long term follow up for childhood, adolescent, and young adult cancer survivors.[47] This provides guidance for healthcare professionals on how to provide high quality follow-up care and appropriate monitoring. These guidelines also help healthcare providers collaborate with oncology specialists, in order to create recommendations specific to an individual patient.[47]

Quality of Life in survivors

Usually, Quality of Life improves with time since diagnosis, especially for children with solid tumors and hematological malignancies. Children with a CNS tumors, on the other hand, show little or no improvement over time.[51] Quality of Life is often measured both during and after treatment, but international comparisons of both outcomes and predictors are hindered by the use of a large number of different measurements.[52] Recently, a first step for a joint international consensus statement for measuring Quality of Life in survivors of childhood cancer has been established.[53]

Epidemiology

Epidemiology is the study of the distribution and determinants of disease frequency in the human population and the study of how to control health problems.[54] Internationally, the greatest variation in childhood cancer incidence occurs when comparing high-income countries to low-income ones.[55] This may result from differences in being able to diagnose cancer, differences in risk among different ethnic or racial population subgroups, as well as differences in risk factors.[55] An example of differing risk factors is in cases of pediatric Burkitt lymphoma, a form of non-Hodgkin lymphoma that sickens 6 to 7 children out of every 100,000 annually in parts of sub-Saharan Africa, where it is associated with a history of infection by both Epstein-Barr virus and malaria.[55][56][57] In industrialized countries, Burkitt lymphoma is not associated with these infectious diseases.[55] Non-Hispanic white children often have a better chance of survival compared to other racial and ethnic groups. Where an individual lives is one of the biggest determinants of health in the world, as illness and healthcare options can vary by an individual's postal code.[citation needed]

United States

In the United States, cancer is the second most common cause of death among children between the ages of 1 and 14 years, exceeded only by unintentional injuries such as injuries sustained in a car wreck.[33][58] More than 16 out of every 100,000 children and teens in the U.S. were diagnosed with cancer, and nearly 3 of every 100,000 died from the disease.[33] In the United States in 2012, it was estimated that there was an incidence of 12,000 new cases, and 1,300 deaths, from cancer among children 0 to 14 years of age.[59] Cancer is the second leading cause of death in males and fourth in women under the age of 20 in the United States. The survival rate of children with cancer has improved since the late 1960s which is due to improved treatment and public health measures. The estimated proportion surviving 5 years from diagnosis increased from 77.8 percent to 82.7 percent to 85.4 percent for those diagnosed in the 1990s, 2000s, and 2010–2016.[60]

Statistics from the 2014 American Cancer Society report:

Ages birth to 14[61]
Sex Incidence Mortality Observed Survival %
Boys 178.0 23.3 81.3
Girls 160.1 21.1 82.0
Ages 15 to 19[61]
Sex Incidence Mortality Observed Survival %
Boys 237.7 34.5 80.0
Girls 235.5 24.7 85.4

Note: Incidence and mortality rates are per 1,000,000 and age-adjusted to the 2000 US standard population. Observed survival percentage is based on data from 2003 to 2009.

Sub-Saharan Africa

A large number of children in Africa live in low- and middle-income countries where there is limited access to prevention or treatment of cancer. The under-five mortality rate (U5MR), a robust indicator of child health, is at 109 per 1,000 live births.[62] The proportion of childhood cancer is higher in Africa than in developed countries, at 4.8%.[63] Kids with cancer are disadvantaged compared to kids in developed countries; therefore their statistic for childhood cancer is higher.[clarification needed] In sub-Saharan Africa, 10% of children die before their 5th birthday, yet it is not due to cancer; communicable diseases such as malaria, cholera, and other infections are the leading cause of death.[64] Children with cancer are often exposed to these preventable infections and diseases. Tumor registries only cover 11% of the African population, and there is a significant absence in death registration, making the mortality database unreliable. Overall, there is a lack of reliable data, as there is limited funding and many diseases are largely unknown to this population.

United Kingdom

Cancer in children is rare in the UK, with an average of 1,800 diagnoses every year but contributing to less than 1% of all cancer-related deaths.[65] Age is not a confounding factor in mortality from the disease in the UK. From 2014 to 2016, approximately 230 children died from cancer, with brain/CNS cancers being the most commonly fatal type.

Foundations and fundraising

Part of the proceeds from the sale of yellow silage wrappings goes to childhood cancer research, Brastad, Sweden

Currently, there are various organizations whose main focus is fighting childhood cancer. Organizations focused on childhood cancer through cancer research and/or support programs include: Childhood Cancer Canada, Young Lives vs Cancer and the Children's Cancer and Leukaemia Group (in United Kingdom ), Child Cancer Foundation (in New Zealand), Children's Cancer Recovery Foundation (in United States ),[66] American Childhood Cancer Organization (in United States ),[67] Childhood Cancer Support (Australia) and the Hayim Association (in Israel).[68] Alex's Lemonade Stand Foundation allows people across the US to raise money for pediatric cancer research by organizing lemonade stands.[69] The National Pediatric Cancer Foundation focuses on finding less toxic and more effective treatments for pediatric cancers. This foundation works with 24 different hospitals across the US in search of treatments effective in practice.[70] Childhood Cancer International is the largest global pediatric cancer foundation. It focuses on early access to care for childhood cancers, focusing on patient support and patient advocacy.[71]

According to estimates by experts in the field of pediatric cancer, by 2020, cancer will cost $158 million annually for both research and treatment which marks a 27% increase since 2010.[72] Ways in which the foundations are helped by people include writing checks, collecting spare coins, bake/lemonade sales, donating portions of purchases from stores or restaurants, or Paid Time Off donations[73] as well as auctions, bike rides, dance-a-thons. Additionally, many of the major foundations have donation buttons on their respective websites.

In addition to advancing research focusing on cancer, the foundations also offer support to families whose children are affected by the disease. The estimated total cost for one child with cancer (medical costs and lost parental wages) is $833,000.[74] Organizations such as the National Children's Cancer Society and the Leukemia and Lymphoma Society can provide financial assistance for the costs associated with childhood cancer like medical care, home care, child care, and transportation.

Importance of family support

The emotional challenges that a parent may encounter can disrupt their child's treatment, parenting and support for the child who is ill and their siblings, and impact overall family stability.[45] Therefore, having a support network during this time is important. Different foundations fund support groups within hospitals and online for parents and families to aid in the coping process.[75] Targeted support for siblings of children with cancer is also warranted. Resources that account for family context, age, and gender can help siblings process cancer-related emotional reactions.[76] These targeted resources help promote family activities and normal family functioning, while enhancing family adjustment over time.[76][77][78]

The foundations for pediatric cancer all fall under the 501(c)3 designation which means that they are non-profit organizations that are tax-exempt.[79] The "International Childhood Cancer Day" occurs annually on February 15.[80][81]

References

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  2. ↑ "Long-term survival and cure fraction estimates for childhood cancer in Europe (EUROCARE-6): results from a population-based study". The Lancet. Oncology 23 (12): 1525–1536. December 2022. doi:10.1016/s1470-2045(22)00637-4. PMID 36400102. 
  3. ↑ "Toward the Cure of All Children With Cancer Through Collaborative Efforts: Pediatric Oncology As a Global Challenge". Journal of Clinical Oncology 33 (27): 3065–3073. September 2015. doi:10.1200/JCO.2014.60.6376. PMID 26304881. 
  4. ↑ Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995. 1999. doi:10.1037/e407432005-001. http://dx.doi.org/10.1037/e407432005-001. Retrieved 2022-09-17. 
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  8. ↑ 8.0 8.1 8.2 8.3 "Translocation (11;15;19): a highly specific chromosome rearrangement associated with poorly differentiated thymic carcinoma in young patients". American Journal of Clinical Oncology 26 (3): 300–306. June 2003. doi:10.1097/00000421-200306000-00019. PMID 12796605. 
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  11. ↑ "Non-Hodgkin's lymphoma". Mayo Clinica. https://www.mayoclinic.org/diseases-conditions/non-hodgkins-lymphoma/symptoms-causes/syc-20375680. 
  12. ↑ "Superior Vena Cava Syndrome". StatPearls [Internet].. Treasure Island (FL): StatPearls Publishing. 26 September 2022. https://www.ncbi.nlm.nih.gov/books/NBK441981/. 
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  29. ↑ "Radiology Safety - What can I do?". Alliance for Radiation Safety in Pediatric Imaging. http://www.imagegently.org/Procedures/Interventional-Radiology/Protocols. 
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  33. ↑ 33.0 33.1 33.2 33.3 33.4 33.5 "Cancer in Children". Centers for Disease Control and Prevention. 30 July 2009. https://www.cdc.gov/features/dscancerinchildren/index.html. 
  34. ↑ 34.0 34.1 "Childhood Cancer overview". American Society of Clinical Oncology (ASCO). http://www.cancer.net/cancer-types/childhood-cancer. 
  35. ↑ 35.0 35.1 "Who Treats Children with Cancer?" (in en). https://www.cancer.org/treatment/children-and-cancer/when-your-child-has-cancer/finding-treatment/cancer-care-team.html. 
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  37. ↑ "Cancer Surgery". National Cancer Institute. U.S. Department of Health and Human Services, National Institutes of Health. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/surgery.html. 
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  39. ↑ "Radiation Therapy". National Cancer Institute. U.S. Department of Health and Human Services, National Institutes of Health. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/radiation.html. 
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  42. ↑ "Immune-Based Approaches for the Treatment of Pediatric Malignancies". Annual Review of Cancer Biology 4 (1): 353–370. March 2020. doi:10.1146/annurev-cancerbio-030419-033436. PMID 34113750. 
  43. ↑ "Improving the outcome for children with cancer: Development of targeted new agents". CA 65 (3): 212–220. 2015. doi:10.3322/caac.21273. PMID 25754421. 
  44. ↑ "Advances in pediatric psychooncology". Current Opinion in Pediatrics 32 (1): 41–47. February 2020. doi:10.1097/MOP.0000000000000851. PMID 31790025. 
  45. ↑ 45.0 45.1 "Standards of Psychosocial Care for Parents of Children With Cancer". Pediatric Blood & Cancer 62 (S5): S632–S683. December 2015. doi:10.1002/pbc.25761. PMID 26700921. 
  46. ↑ 46.0 46.1 "The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE)". Lancet 390 (10112): 2569–2582. December 2017. doi:10.1016/S0140-6736(17)31610-0. PMID 28890157. 
  47. ↑ 47.0 47.1 47.2 "Long-term Follow-up Care for Childhood, Adolescent, and Young Adult Cancer Survivors". Pediatrics 148 (3): e2021053127. September 2021. doi:10.1542/peds.2021-053127. PMID 34462344. 
  48. ↑ 48.0 48.1 "Cardiovascular disease in adult survivors of childhood cancer". Annual Review of Medicine 66 (1): 161–176. January 2015. doi:10.1146/annurev-med-070213-054849. PMID 25587648. 
  49. ↑ 49.0 49.1 "Early and late adverse renal effects after potentially nephrotoxic treatment for childhood cancer". The Cochrane Database of Systematic Reviews 2019 (3): CD008944. March 2019. doi:10.1002/14651858.cd008944.pub3. PMID 30855726. 
  50. ↑ 50.0 50.1 50.2 "Hepatic late adverse effects after antineoplastic treatment for childhood cancer". The Cochrane Database of Systematic Reviews 4 (4): CD008205. April 2019. doi:10.1002/14651858.cd008205.pub3. PMID 30985922. 
  51. ↑ "The course of health-related quality of life after the diagnosis of childhood cancer: a national cohort study". BMC Cancer 23 (1): 855. September 2023. doi:10.1186/s12885-023-11379-z. PMID 37697253. 
  52. ↑ "A systematic review of health-related quality of life in children and adolescents during treatment for cancer". EJC Paediatric Oncology 2: 100134. December 2023. doi:10.1016/j.ejcped.2023.100134. ISSN 2772-610X. https://doi.org/10.1016/j.ejcped.2023.100134. 
  53. ↑ "A joint international consensus statement for measuring quality of survival for patients with childhood cancer". Nature Medicine 29 (6): 1340–1348. June 2023. doi:10.1038/s41591-023-02339-y. PMID 37322119. 
  54. ↑ Essentials of Epidemiology in Public Health. Burlington, MA: Jones & Bartlett Learning. 2020. pp. 237–266. 
  55. ↑ 55.0 55.1 55.2 55.3 "Children and Cancer". Children's Health and the Environment. A WHO Training Package for the Health Sector, World Health Organization. https://www.who.int/ceh/capacity/cancer.pdf.  In turn citing: "Childhood cancer epidemiology in low-income countries". Cancer 112 (3): 461–72. February 2008. doi:10.1002/cncr.23205. PMID 18072274. 
  56. ↑ "Viral Cancers: Epstein-Barr virus". World Health Organization Initiative for Vaccine Research. https://www.who.int/vaccine_research/diseases/viral_cancers/en/index1.html. 
  57. ↑ "The company malaria keeps: how co-infection with Epstein-Barr virus leads to endemic Burkitt lymphoma". Current Opinion in Infectious Diseases 24 (5): 435–441. October 2011. doi:10.1097/QCO.0b013e328349ac4f. PMID 21885920. 
  58. ↑ "WISQARS Leading Causes of Death Reports". https://wisqars.cdc.gov/fatal-leading. 
  59. ↑ "Cancer Facts & Figures". American Cancer Society. 2011. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-029771.pdf. 
  60. ↑ "Epidemiology of Childhood Cancer in the United States". Childhood Cancer and Functional Impacts Across the Care Continuum. Washington, DC: National Academies Press (US). 9 December 2020. ISBN 978-0-309-68352-4. https://www.ncbi.nlm.nih.gov/books/NBK569403/. 
  61. ↑ 61.0 61.1 "Childhood and adolescent cancer statistics, 2014". CA 64 (2): 83–103. Mar–Apr 2014. doi:10.3322/caac.21219. PMID 24488779. 
  62. ↑ "Paediatric cancer in low-income and middle-income countries". The Lancet. Oncology 14 (3): e104–e116. March 2013. doi:10.1016/s1470-2045(13)70008-1. PMID 23434340. 
  63. ↑ "Paediatric cancer in low-income and middle-income countries". The Lancet. Oncology 14 (3): e104–e116. March 2013. doi:10.1016/S1470-2045(13)70008-1. PMID 23434340. 
  64. ↑ Committing to childhood survival: A promise renewed. Progress Report (Report). 2013. http://www.unicef.org/publications/files/APR_Progress_Report_2013_9_Sept_2013.pdf. 
  65. ↑ "Childhood cancer statistics". http://www.cancerresearchuk.org/cancer-info/cancerstats/childhoodcancer/. 
  66. ↑ "Children's Cancer Recovery Foundation". http://childrenscancerrecovery.org/. 
  67. ↑ "Homepage". American Childhood Cancer Organization. http://www.acco.org/. 
  68. ↑ "Hayim Association". http://www.hayim.org/. 
  69. ↑ "About ALSF". https://www.alexslemonade.org/. 
  70. ↑ "About NPCF". https://nationalpcf.org/. 
  71. ↑ "Who We Are". 2015-09-16. http://childhoodcancerinternational.org/. 
  72. ↑ "Cancer costs projected to reach at least $158 billion in 2020". U.S. Department of Health and Human Services. 2015-07-23. https://www.nih.gov/news-events/news-releases/cancer-costs-projected-reach-least-158-billion-2020. 
  73. ↑ "Fundraising Ideas". https://curechildhoodcancer.org/fundraising-ideas/. 
  74. ↑ U.S. Environmental Protection Agency. (2017). NIEHS/EPA Children's Environmental Health and Disease Prevention Research Centers Impact Report: Protecting children's health where they live, learn, and play. EPA Publication No. EPA/600/R-17/407.
  75. ↑ "PSYCHOLOGICAL AND EMOTIONAL SUPPORT". 2014-11-18. https://www.acco.org/psychological-and-emotional/. 
  76. ↑ 76.0 76.1 "Siblings Dealing with Pediatric Cancer: A Family- and Context-oriented Approach". Journal of Pediatric Oncology Nursing 38 (3): 166–175. May 2021. doi:10.1177/1043454221992303. PMID 33792425. https://biblio.ugent.be/publication/8680415. 
  77. ↑ "Support for families at home during childhood cancer treatment: a pilot study with Mr.V the Spaceman, a family-based activities tool". Supportive Care in Cancer 29 (8): 4875–4884. August 2021. doi:10.1007/s00520-021-05995-3. PMID 33550470. 
  78. ↑ "Family Adjustment When Facing Pediatric Cancer: The Role of Parental Psychological Flexibility, Dyadic Coping, and Network Support". Frontiers in Psychology 10: 2740. 2019. doi:10.3389/fpsyg.2019.02740. PMID 31920799. 
  79. ↑ "Exemption Requirements - 501(c)(3) Organizations". https://www.irs.gov/charities-non-profits/charitable-organizations/exemption-requirements-section-501c3-organizations. 
  80. ↑ "International Childhood Cancer Day". educationscotland.gov.uk. 15 February 2013. http://www.educationscotland.gov.uk/resources/i/internationalchildhoodcancerday.asp. 
  81. ↑ "February 15th is International Childhood Cancer Awareness Day!!!". The Foundation for Children with Cancer (FCC). http://www.childrenwithcancer.org/links/february-15th-is-world-childhood-cancer-awareness-day/. 

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