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Childhood Cancer Survivor Care

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Guidance for primary care clinicians assessing and managing children with a history of childhood cancer

Survivorship care is holistic, collaborative care that focuses on the health and well-being of the cancer survivor. Survivorship care should be individualized based on the patient’s age at diagnosis and therapy, as well as the therapies they received. It includes management of the physical, mental, emotional, social, and financial effects of cancer. Survivorship begins at the time of diagnosis and is life-long.

Ideally, survivorship care is led by specialists in survivorship medicine who understand the unique needs of cancer survivors. The team may include oncology, primary care, subspecialists (when appropriate), family, friends, and caregivers focused on a patient's health and wellness for a lifetime. Follow-up involves regular health and wellness checkups as well as managing the late effects of treatment, cancer recurrence, second cancers, and quality of life issues. It is imperative that children, adolescents, and young adults with cancer receive specialized care after they finish cancer therapy.

It can be difficult to stay up to date with the health risks associated with specific cancer therapies, much less with the recommendations for surveillance. However, the primary care clinician can play a pivotal role in the health and well-being of a childhood cancer survivor by delivering risk-based health care. This article is intended to assist the primary care clinician in this role.

Other Names

Late effects of cancer
Long-term follow-up of cancer survivors
Survivorship

Key Points

Survivorship care plan
The primary care clinician must understand what treatment each survivor received and for which complications the survivor is at risk; a Survivorship Care Plan outlines these risks. Every patient who completes cancer therapy should receive an SCP from the treatment team. If an SCP is not received, it can be requested. This document is integral to provide comprehensive care for the childhood cancer survivor.

Failure of surveillance for survivors
Evidence demonstrates that less than half of high-risk survivors receive the recommended secondary malignancy and cardiac disease screenings, which likely exposes them to preventable morbidity and mortality. Given the high rate of success for patients and the high need for education and services immediately following therapy, a better model would be that survivorship care that starts immediately following therapy, if not sooner. [Yan: 2020]

Role of the primary care clinician
The primary care clinician is integral in preventive and acute health care for childhood cancer survivors, particularly those in their young adult years. This high-risk population is relatively small but growing. [Mariotto: 2009]

Toxic therapy yields a high risk of late effects
Following chemotherapy, radiotherapy, and surgery, many survivors will experience chronic or late-occurring health problems, often not becoming clinically apparent until decades after therapy. Given the propensity of data demonstrating the cumulative morbidity and excess mortality that cancer and its treatment can have on a patient throughout a lifetime, survivorship is more important in cancer care than ever before. [Hudson: 1997] [Mertens: 2008] [Armstrong: 2016] [Oeffinger: 2006]

Identifying cancer predisposition
Cancer screening recommendations and risk reduction strategies are available for certain cancer predisposition syndromes. [Foulkes: 2017] [Schultz: 2017] [Kratz: 2017] Research has demonstrated that using these strategies significantly improves outcomes for at-risk populations. [Ballinger: 2017] [Villani: 2016]

Practice Guidelines

Children's Oncology Group.
Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers.
2018; 5. http://www.survivorshipguidelines.org/pdf/2018/cog_ltfu_guidelines_v5....

Assessment

Surveillance for primary cancer recurrence is greatest in the first 18-36 months and drops off precipitously after 5 years after completion of therapy. The primary oncology team is responsible for surveying for primary cancer recurrence during that period. This typically involves testing (usually blood tests and/or imaging) to monitor for relapse. Alternatively, it is the survivorship and primary care teams’ responsibility to educate, mitigate, screen, and treat health conditions caused by their treatment for the primary cancer. Testing and screening care is individualized, based on the patient’s age at diagnosis and therapy, as well as the therapies they received. The SCP is the roadmap for risks and screening measures.

Diagnostic Criteria & Classifications

  • Childhood cancer ages 0-14 years
  • Adolescent and Young Adult Cancer ages 15-39 years
  • Adult cancer more than 40 years old

Genetics & Inheritance

Germline mutations in cancer-predisposing genes have been identified in 8.5% of children and adolescents with cancer. [Zhang: 2016] [Parsons: 2016] In a study of 1,120 children and adolescents with cancer, the most commonly mutated genes found in affected patients were TP53, APC, BRCA2, NF1, PMS2, RB1, and RUNX1. [Zhang: 2016]
In the context of genetic counseling, several factors inform whether a survivor is likely to harbor a harmful germline mutation. These factors are the type of primary cancer, a previous diagnosis or presence of phenotypic characteristics of an underlying genetic syndrome, and a positive family history of cancer. However, family history alone cannot be relied upon to identify childhood cancer patients with germline mutations because most patients will not have a concerning family history. [Wang: 2018]
Identifying a cancer predisposition syndrome has significant clinical implications.
  1. Cancer screening recommendations and risk reduction strategies are available for certain cancer predisposition syndromes. [Foulkes: 2017] [Schultz: 2017] [Kratz: 2017]. Research has demonstrated that utilizing these strategies significantly improves outcomes among at-risk populations. [Ballinger: 2017] [Villani: 2016]
  2. For survivors who carry a cancer predisposition gene mutation, genetic information may provide valuable information about cancer risk for other family members and inform reproductive decisions in the future.

Prevalence

Cancer
Cancer remains the leading cause of death from disease among children. In the United States, in 2022, an estimated 10,470 new cases of cancer will be diagnosed among children from birth to 14 years. (About 89,000 young people (ages 15 to 39) are diagnosed with cancer each year in the United States.) The most common cancer diagnoses in children 0 to 14 years are leukemias, brain and other central nervous system (CNS) tumors, and lymphomas.
Cancer survival
More than 500,000 survivors of childhood cancer live in the US today. This is due to incredible improvements in cure rate of childhood cancer. This drastically differs from the mid-20th century when less than half of children diagnosed with malignancy achieved a 5-year survival. Today, children diagnosed with cancer have a 5-year survival greater than 85% and a 10-year survival rate greater than 80%. [Ries: 1983] [Armstrong: 2016] [Fidler: 2016]Contributions to this progress include collaborative trials, cancer pathobiology, novel therapeutics, diagnostic images, radiation technology, supportive care, and recognition of late effects.

Prognosis

It is important to differentiate between the prognosis as it pertains to the primary cancer and prognosis as it pertains to other conditions aside from the primary cancer, i.e., late effects such as secondary neoplasm, heart disease, kidney disease, etc.

Childhood cancer survivors are at significantly increased risk for serious health conditions largely as a result of adverse effects of the therapies that cured their primary malignancies. [Hudson: 2013] [Oeffinger: 2006] [Armstrong: 2014] Due to their long life expectancy, childhood cancer survivors are at a particular risk of long-term sequelae from the cancer itself or the therapies used to treat the cancer.

It has been shown that for survivors of childhood cancer at a mean age of 26 years, 62% had at least 1 chronic health condition, with about 25% having a severe, life-threatening, or disabling condition. [Oeffinger: 2006] Evidence demonstrates that these risks continue to compound as survivors age. Even with time, there seems to be no point where the morbidity and mortality seen in a noncancer population are equivalent to that of childhood cancer survivors.

Treatment & Management

Survivorship care includes educating about the risk for late effects and modifiable risk factors, identifying late effects early, and treating those conditions. The following is a systems-based guide to some of the most commonly affected body systems, exposures predisposing to later complications, and screens for complications. Refer to the survivor’s care plan for individualized risk assessment and monitoring.

Cardiovascular

Childhood cancer survivors are at significantly increased risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular dysfunction compared with sibling controls, as well as at risk of increased cardiovascular mortality. [Mulrooney: 2009] [Mertens: 2008]
Cardiovascular disease, the leading cause of death in the United States, contributes to early morbidity and mortality among cancer survivors.
Main exposures leading to increased risk:
  • Anthracylines (chemotherapy)
  • Radiation exposure (usually in the form of chest radiation)
Potential screening:
  • Physical exam, ECG, echocardiogram, cardiovascular laboratory tests

Hematology/Oncology

Subsequent malignant neoplasms (SMNs), defined as new primary malignancies after an initial cancer diagnosis, are the most frequent cause of nonrelapse late mortality, accounting for nearly half of nonrelapse deaths among 5-year survivors. [Armstrong: 2016] Radiation and SMN risk has been studied for many cancers and shows an exponential risk based on exposure dose. [Inskip: 2016]Chemotherapy is strongly associated with SMNs, including leukemias, gasto-intestinal, thyroid, lung, breast, bladder cancers, as well as sarcoma. [Travis: 2013]
Multiple primary cancers within an individual can occur in several cancer susceptibility syndromes. See Genetics (above) for more information. Despite surveillance recommendations, many primary care providers are unaware of, and many survivors are often nonadherent with recommended screenings. [Hawkins: 1992]
Main exposures leading to increased risk:
  • Alkylators, topoisomerase II inhibitors, anthracyclines, platinum (chemotherapy)
  • Radiation exposure: Dose and site dependent
  • Germline cancer predisposition syndrome
Potential screening:
  • Physical exam, skin exam, mammograms, breast MRIs, colonoscopy, thyroid U/S

Learning, Education, Schools

Neurocognitive dysfunction is demonstrated in up to 40% of childhood cancer survivors in 1 or more domains (e.g., processing speed, attention, memory. [Moleski: 2000] [Mulhern: 1991] This, in turn, can result in poor academic and vocational success, low self-esteem, and behavioral or emotional disorders.
Regular monitoring of neurocognitive outcomes has been recommended for children exposed to cranial irradiation or antimetabolite chemotherapy during pediatric cancer treatment. [Nathan: 2007] Ideally, all such children could undergo comprehensive neurocognitive evaluations to identify strengths and weaknesses, which could then be used to develop appropriate intervention plans. [Krull: 2008]
Children with neurocognitive dysfunction may need accommodations in school settings to promote their academic success and effective participation in the curriculum. See School Accommodations: IEPs & 504s for more information on how the primary care clinician can counsel and support families working with school districts on appropriate accommodations.
Main exposures leading to increased risk:
  • Metabolites (chemotherapy), intrathecal chemotherapy (chemotherapy)
  • Radiation exposure to brain
  • Surgery to brain
Potential screening
  • History, developmental screening, neurocognitive testing

Endocrine

Ovarian Insufficiency, Infertility, and Sexual Dysfunction in Female Survivors
Premature Ovarian Insufficiency
Cancer-directed therapies can accelerate the decline of ovarian follicles, resulting in menopause earlier than expected (premature ovarian insufficiency. [Chemaitilly: 2017]
Acute ovarian failure (menopause occurring within 5 years from diagnosis) occurs in about 6% of female survivors. Menopause after 5 years from diagnosis but before 40 years occurs in 8-9% of female survivors. [Sklar: 2006] [Thomas-Teinturier: 2013] [Chemaitilly: 2017]
Fertility preservation options in survivorship that were not available before starting therapy may exist , but those options might be physiologically time-sensitive. Proper counseling before starting therapy and survivorship care are critical.
Sexual dysfunction has been reported for 20-57% of female survivors of childhood cancer. [Zebrack: 2010] [Bjornard: 2020] [Hovén: 2021] This underscores the need for the routine assessment of sexual health in the follow-up care of survivors.
Main exposures leading to increased risk:
  • Alkylating agents (chemotherapy), platinum agents (chemotherapy), hematopoetic stem cell transplant (HSCT)
  • Radiation exposure to brain (hypopituitary axis) and gonads
  • Surgical resection of one or both gonads
Potential screening
  • History, labs, ovarian ultasound
Infertility, Testosterone Insufficiency, and Sexual Dysfunction in Male Survivors
Impaired spermatogenesis, testosterone insufficiency, and sexual dysfunction are all adverse reproductive outcomes experienced by men who are survivors of childhood, adolescent, and young adult cancer. These conditions can be the direct result of damage to reproductive organs by cancer-directed therapy or a consequence of physical and emotional effects of the cancer experience on a developing child, adolescent, or young adult. [Kenney: 2012] [Skinner: 2017]
Treatment of hypogonadal hypogonadism with testosterone replacement therapy (intramuscular, oral, or topical) should be offered to all pre- and peripubertal boys with delayed or arrested puberty. The treatment goals are the induction or continuation of an optimal pubertal-associated growth spurt, pubertal development with secondary physical development, accrual of bone mass, and psychological well-being. [Watson: 2014]
Sexual dysfunction has been reported for 20-35% of male survivors of childhood cancer. This underscores the need for routine assessment of sexual health in follow-up care of survivors.
[Zebrack: 2010] [Bjornard: 2020] [Hovén: 2021]
Posttherapy Infertility Men with a history of clinical infertility or ejaculatory oligo- or azoospermia who have not banked sperm should be offered evaluation by a reproductive urologist.
Main exposures leading to increased risk:
  • Alkylating agents (chemotherapy), platinum agents (chemotherapy), hematopoetic stem cell transplant (HSCT)
  • Radiation exposure to brain (hypopituitary axis) and gonads
  • Surgical resection of one or both gonads
Potential screening
  • History, physical exam, labs, sperm analysis

Financial Hardship in Survivorship

Financial hardship” (financial distress due to cancer diagnosis or treatment) and “financial toxicity” (adverse impact of financial hardship on health outcomes) are emerging concepts to describe financial issues faced by cancer populations. Depending on the study, 20-65% of childhood cancer survivors have reported financial hardship in adulthood. [Kent: 2013] [Kale: 2016] [Yabroff: 2016] [Huang: 2019]
The social and economic impact of the sequelae of childhood cancer (chronic health conditions, physical and neurocognitive deficits, symptom prevalence, etc.) is considerable; childhood cancer survivors are less likely to graduate from college, assume higher-skilled occupations, or earn a higher income than siblings. [Gurney: 2009] [Kirchhoff: 2011] [Kirchhoff: 2010]Socioeconomic factors and late effects (often associated with the intensity of therapy) are related to financial hardship, which in turn affects insurance affordability, retirement planning, and health outcomes. [Nipp: 2017]
Main exposures leading to increased risk:
  • Lower socioeconomic status
  • High intensity of therapy/ high burden of late effects/ chronic health conditions
Potential screening
  • Evaluate for challenges in job attainment, medical insurance coverage

Mental Health/Behavior

Transitions

Services & Referrals

ICD-10 Coding

Z85, Personal history of malignant neoplasm[DF1]

Z85.0, Personal history of malignant neoplasm of digestive organs

Z85.1, Personal history of malignant neoplasm of trachea, bronchus and lung

Z85.2, Personal history of malignant neoplasm of other respiratory and intrathoracic organs

Z85.3, Personal history of malignant neoplasm of breast

Z85.4, Personal history of malignant neoplasm of genital organs

Z85.5, Personal history of malignant neoplasm of urinary tract

Z85.6, Personal history of leukemia

Z85.7, Personal history of other malignant neoplasms of lymphoid, hematopoietic and related tissues

Z85.8, Personal history of malignant neoplasms of other organs and systems

Z85.9, Personal history of malignant neoplasm, unspecified

Resources

Information & Support

Related Portal Content
The Medical Home Portal provides related general diagnositic and management information, including:

Care Notebook may also be helpful for tracking medical history, test results, and records.

For Professionals

Guidelines for Adolescents and Young Adults with Cancer (NCCN)
More than 65 free books that help people with cancer talk with their doctors about the best treatment options for their disease. They are also available as a free app; National Comprehensive Cancer Network.

Childhood and AYA Cancer Survivorship Clinic at Primary Children’s Hospital
The Cancer Survivorship Program provides holistic care to support the health and wellbeing of survivors of childhood, adolescent, and young adult cancer.

Childhood Cancer Survivorship (Cancer.Net - American Society for Clinical Oncology)
Descriptions of childhood cancers, long-term effects of cancer treatment, and related resources.

Care for Childhood Cancer Survivors (National Institutes of Health and National Cancer Institute)
Follow-Up Care after Childhood Cancer Treatment, Long-Term and Late Effects of Childhood Cancer, and Questions to Ask Your Child's Cancer Treatment Team

Childhood Cancer Survivors: What to Expect After Treatment (healthychildren.org AAP (American Academy of Pediatrics))
Information about what to expect during follow-up care and some common questions families of childhood cancer survivors may have.

Follow-Up Care for Childhood Cancer Survivors (Leukemia and Lymphoma Society)
Includes links to Survivorship Workbook, Beyond Treatment, and additional guidelines.

For Parents and Patients

Survivorship Care for Cancer-Related Late and Long-Term Effects (NCCN Guidelines for Patients) (PDF Document 1.6 MB)
National Comprehensive Cancer Network guidelines to help with survivorship issues such as hormonal, cardiovascular, mental health, and other resources.

Survivorship Care for Healthy Living (NCCN Guidelines for Patients) (PDF Document 1.4 MB)
National Comprehensive Cancer Network guide with information about survivorship, physical activity, food and supplements, weight and metabolism, preventing infections, and other resources for cancer survivors.

Childhood and AYA Cancer Survivorship Clinic at Primary Children’s Hospital
The Cancer Survivorship Program provides holistic care to support the health and wellbeing of survivors of childhood, adolescent, and young adult cancer.

Survivorship: During and After Treatment (American Cancer Society)
Information and tips on staying active and healthy during and after cancer treatment. You can also get information on managing your health care as a cancer survivor.

Passport for Care
A free online resource that can provide childhood cancer survivors access to a comprehensive treatment summary, potential late effects of therapy, educational pages on survivorship issues, and a tailored and comprehensive long-term follow-up care plan based on the Children’s Oncology Group recommendations, which can be shared with health care providers.

American Society for Reproductive Medicine
ASRM is a multidisciplinary organization dedicated to the advancement of the science and practice of reproductive medicine. The Society accomplishes its mission through the pursuit of excellence in education and research and through advocacy on behalf of patients, physicians, and affiliated health care providers.

Alliance for Fertility Preservation
The Alliance for Fertility Preservation is a 501c3 charitable organization. The Alliance is made up of a team of professionals who have chosen to join together to advance the field of fertility preservation. Their members are recognized leaders with expertise in all aspects of fertility preservation including, oncology, reproductive endocrinology, urology, psychology, oncology nursing, and reproductive law.

Long-term Follow-up Care
Discusses survivorship care, including accessing a long-term follow-up healthcare provider, frequency of care, medical care between follow-up visits, treatment summary, and late effects.

Patient Education

Passport for Care
A free online resource that can provide childhood cancer survivors access to a comprehensive treatment summary, potential late effects of therapy, educational pages on survivorship issues, and a tailored and comprehensive long-term follow-up care plan based on the Children’s Oncology Group recommendations, which can be shared with health care providers.

Care Checklist: Early Ambulatory Stage/Childhood (Parent Project MD)
For use by parents and caregivers of individuals with Duchenne muscular dystrophy to help you manage your child’s care if they are showing signs of Duchenne, like a waddling type of walk, walking on their toes, or needing to support themselves with their hands when they get up from the floor.

Care Checklist: Late Ambulatory Stage (Parent Project MD)
For use by parents and caregivers of individuals with Duchenne muscular dystrophy to help you manage your child’s care if they are having more trouble walking, getting up from the floor, and climbing stairs.

Care Checklist: Early Non-Ambulatory Stage/Childhood (Parent Project MD)
For use by individuals with Duchenne muscular dystrophy or their caregivers, to help manage care if needing a wheelchair for mobility.

Care Checklist: Late Non-Ambulatory Stage (Parent Project MD)
For use by individuals with Duchenne muscular dystrophy to help manage care if there is reduced upper limb function and difficulty maintaining good posture.

Studies

Helpful Articles

Hewitt M, Weiner SL, Simone JV ed.
Childhood Cancer Survivorship: Improving Care and Quality of Life.
Washington, DC: National Academies Press; 2003. https://www.ncbi.nlm.nih.gov/books/NBK221742/

Authors & Reviewers

Initial publication: July 2023
Current Authors and Reviewers:
Authors: Jennifer Goldman, MD, MRP, FAAP
Douglas Fair, MD, MS

Page Bibliography

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Foulkes WD, Kamihara J, Evans DGR, Brugières L, Bourdeaut F, Molenaar JJ, Walsh MF, Brodeur GM, Diller L.
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Gurney JG, Krull KR, Kadan-Lottick N, Nicholson HS, Nathan PC, Zebrack B, Tersak JM, Ness KK.
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Hovén E, Fagerkvist K, Jahnukainen K, Ljungman L, Lähteenmäki PM, Axelsson O, Lampic C, Wettergren L.
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Kirchhoff AC, Leisenring W, Krull KR, Ness KK, Friedman DL, Armstrong GT, Stovall M, Park ER, Oeffinger KC, Hudson MM, Robison LL, Wickizer T.
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