During the past five decades, dramatic progress has been made in the development of curative therapy for pediatric malignancies. Long-term survival into adulthood is the expectation for more than 80% of children with access to contemporary therapies for pediatric malignancies.[1,2] The therapy responsible for this survival can also produce adverse long-term health-related outcomes, referred to as late effects, which manifest months to years after completion of cancer treatment.
A variety of approaches have been used to advance knowledge about the very long-term morbidity associated with childhood cancer and its contribution to early mortality. These initiatives have utilized a spectrum of resources including investigation of data from the following:
- Population-based registries.[3-5]
- Self-reported outcomes (provided through large-scale cohort studies).[6,7]
- Medical assessments.[8,9]
Studies reporting outcomes in survivors who have been well characterized in regards to clinical status and treatment exposures, and comprehensively ascertained for specific effects through medical assessments, typically provide the highest quality of data to establish the occurrence and risk profiles for late cancer treatment–related toxicity. Regardless of study methodology, it is important to consider selection and participation bias of the cohort studies in the context of the findings reported.
Prevalence of Late Effects in Childhood Cancer Survivors
Late effects are commonly experienced by adults who have survived childhood cancer; the prevalence of late effects increases as time from cancer diagnosis elapses. Population-based studies support excess hospital-related morbidity among childhood and young adult cancer survivors compared with age- and sex-matched controls.[3-5,10-12]
Research has demonstrated that among adults treated for cancer during childhood, late effects contribute to a high burden of morbidity, including the following:[6,8,9,13-15]
- 60% to more than 90% develop one or more chronic health conditions.
- 20% to 80% experience severe or life-threatening complications during adulthood.
Using the cumulative burden metric—which incorporates multiple health conditions and recurrent events into a single metric that takes into account competing risks—by age 50 years, survivors in the St. Jude Lifetime Cohort experienced an average of 17.1 chronic health conditions, 4.7 of which were severe/disabling, life threatening, or fatal. This is in contrast to the cumulative burden in matched community controls who experienced 9.2 chronic health conditions, 2.3 of which were severe/disabling, life threatening, or fatal (refer to Figure 1).
Figure 1. Figure shows distribution of cumulative burden by age among childhood cancer survivors of specific pediatric cancer subtypes and community controls participating in St. Jude Lifetime Cohort Study. The cumulative burden at age 30 years and rate of cumulative burden growth is variable across cancer subtypes and organ systems. Reprinted from The LancetExit Disclaimer, Volume 390, Issue 10112, Bhakta N, Liu Q, Ness KK, Baassiri M, Eissa H, Yeo F, Chemaitilly W, Ehrhardt MJ, Bass J, Bishop MW, Shelton K, Lu L, Huang S, Li Z, Caron E, Lanctot J, Howell C, Folse T, Joshi V, Green DM, Mulrooney DA, Armstrong GT, Krull KR, Brinkman TM, Khan RB, Srivastava DK, Hudson MM, Yasui Y, Robison LL, The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE), Pages 2569–2582, Copyright (2017), with permission from Elsevier.
The variability in prevalence is related to differences in the following:
- Age and follow-up time of the cohorts studied.
- Methods and consistency of assessment (e.g., self-reported vs. risk-based medical evaluations).
- Treatment intensity and treatment era.
Childhood Cancer Survivor Study (CCSS) investigators demonstrated that the elevated risk of morbidity and mortality among aging survivors in the cohort increases beyond the fourth decade of life. By age 50 years, the cumulative incidence of a self-reported severe, disabling, life-threatening, or fatal health condition was 53.6% among survivors, compared with 19.8% among a sibling control group. Among survivors who reached age 35 years without a previous severe, disabling, life-threatening, or fatal health condition, 25.9% experienced a new grade 3 to grade 5 health condition within 10 years, compared with 6.0% of healthy siblings (refer to Figure 2).
The presence of serious, disabling, and life-threatening chronic health conditions adversely affects the health status of aging survivors, with the greatest impact on functional impairment and activity limitations. Predictably, chronic health conditions have been reported to contribute to a higher prevalence of emotional distress symptoms in adult survivors than in population controls. Female survivors demonstrate a steeper trajectory of age-dependent decline in health status than do male survivors. The even-higher prevalence of late effects among clinically ascertained cohorts is related to the subclinical and undiagnosed conditions detected by screening and surveillance measures.
Figure 2. Cumulative incidence of chronic health conditions for (A) grades 3 to 5 chronic health conditions, (B) multiple grade 3 to 5 conditions in survivors, (C) multiple grade 3 to 5 conditions in siblings, (D) conditioned based on no previous grade 3 to 5 conditions among survivors by ages 25, 35, or 45, and (E) conditioned based on no previous grade 3 to 5 conditions among siblings by ages 25, 35, or 45. Gregory T. Armstrong, Toana Kawashima, Wendy Leisenring, Kayla Stratton, Marilyn Stovall, Melissa M. Hudson, Charles A. Sklar, Leslie L Robison, Kevin C. Oeffinger; Aging and Risk of Severe, Disabling, Life-Threatening, and Fatal Events in the Childhood Cancer Survivor Study; Journal of Clinical Oncology, volume 32, issue 12, pages 1218-1227. Reprinted with permission. © (2014) American Society of Clinical Oncology. All rights reserved.
CCSS investigators also evaluated the impact of race and ethnicity on late outcomes by comparing late mortality, subsequent neoplasms, and chronic health conditions in Hispanic (n = 750) and non-Hispanic black (n = 694) participants with non-Hispanic white participants (n = 12,397). The following results were observed:
- Cancer treatment did not account for disparities in mortality, chronic health conditions, or subsequent neoplasms observed among the groups.
- Differences in socioeconomic status and cardiovascular risk factors affected risk. All-cause mortality was higher among non-Hispanic black participants than among other groups, but this difference disappeared after adjustment for socioeconomic status.
- Risk of developing diabetes was elevated among racial/ethnic minority groups even after adjustment for socioeconomic status and obesity.
- Non-Hispanic blacks had a higher likelihood of reporting cardiac conditions, but this risk diminished after adjusting for cardiovascular risk factors.
- Nonmelanoma skin cancer was not reported by non-Hispanic blacks, a finding that has been replicated by others, and Hispanic participants had a lower risk than did non-Hispanic white participants.
Recognition of late effects, concurrent with advances in cancer biology, radiological sciences, and supportive care, has resulted in a change in the prevalence and spectrum of treatment effects. In an effort to reduce and prevent late effects, contemporary therapy for most pediatric malignancies has evolved to a risk-adapted approach that is assigned based on a variety of clinical, biological, and sometimes genetic factors. The CCSS reported that with decreased cumulative dose and frequency of therapeutic radiation use over treatment decades from 1970 to 1999, survivors have experienced a significant decrease in risk of subsequent neoplasms. With the exception of survivors requiring intensive multimodality therapy, sometimes including hematopoietic cell transplantation, for aggressive or refractory/relapsed malignancies, life-threatening treatment effects are relatively uncommon after contemporary therapy in early follow-up (up to 10 years after diagnosis). However, survivors still frequently experience life-altering morbidity related to effects of cancer treatment on endocrine, reproductive, musculoskeletal, and neurologic function.
Late effects also contribute to an excess risk of premature death among long-term survivors of childhood cancer as observed in the following:
- Several studies of very large cohorts of survivors have reported early mortality among individuals treated for childhood cancer compared with age- and sex-matched general population controls. Relapsed/refractory primary cancer remains the most frequent cause of death, followed by excess cause-specific mortality from subsequent primary cancers, and cardiac and pulmonary toxicity.[21-27]
- An analysis of the CCSS and Surveillance, Epidemiology, and End Results (SEER) that evaluated conditional survival demonstrated a subsequent 5-year survival rate of 92% or higher among most diagnoses at 5 years, 10 years, 15 years, and 20 years. Among those who had survived at least 5 years from diagnosis, the probability of all-cause mortality in the next 10 years was 8.8% in the CCSS and 10.6% in the SEER study, with neoplasms accounting for cause of death in approximately 75% of survivors.
Despite high premature morbidity rates, overall mortality has decreased over time.[21,29-31] This reduction is related to a decrease in deaths from the primary cancer without an associated increase in mortality from subsequent cancers or treatment-related toxicities. The former reflects improvements in therapeutic efficacy, and the latter reflects changes in therapy made subsequent to studying the causes of late effects. The expectation that mortality rates in survivors will continue to exceed those in the general population is based on the long-term sequelae that are likely to increase with attained age. If patients treated on therapeutic protocols are followed up for long periods into adulthood, it will be possible to evaluate the excess lifetime mortality in relation to specific therapeutic interventions.
Monitoring for Late Effects
Recognition of both acute and late modality–specific toxicity has motivated investigations evaluating the pathophysiology and prognostic factors for cancer treatment–related effects. The results of these studies have played an important role in the following areas:[21,29]
- Changing pediatric cancer therapeutic approaches to reduce treatment-related mortality among survivors treated in more recent eras.
- The development of risk counseling and health screening recommendations for long-term survivors by identifying the clinical and treatment characteristics of those at highest risk of treatment complications.
The common late effects of pediatric cancer encompass several broad domains, including the following:
- Growth and development.
- Organ function.
- Reproductive capacity and health of offspring.
- Secondary carcinogenesis.
- Psychosocial sequelae related to the primary cancer, its treatment, or maladjustment associated with the cancer experience.
Late sequelae of therapy for childhood cancer can be anticipated based on therapeutic exposures, but the magnitude of risk and the manifestations in an individual patient are influenced by numerous factors. Factors that should be considered in the risk assessment for a given late effect include the following:
- Tumor location.
- Direct tissue effects.
- Tumor-induced organ dysfunction.
- Mechanical effects.
- Radiation therapy: Total dose, fraction size, organ or tissue volume, type of machine energy.
- Chemotherapy: Agent type, dose-intensity, cumulative dose, schedule.
- Surgery: Technique, site.
- Hematopoietic cell transplantation.
- Use of combined modality therapy.
- Blood product transfusion.
- Management of chronic graft-versus-host disease.
- Genetic predisposition.
- Premorbid health state.
- Developmental status.
- Age at diagnosis.
- Time from diagnosis/therapy.
- Inherent tissue sensitivities and capacity for normal tissue repair.
- Hormonal milieu.
- Function of organs not affected by cancer treatment.
- Socioeconomic status.
- Health habits.
Resources to Support Survivor Care
The need for long-term follow-up for childhood cancer survivors is supported by the American Society of Pediatric Hematology/Oncology, the International Society of Pediatric Oncology, the American Academy of Pediatrics, the Children’s Oncology Group (COG), and the Institute of Medicine. A risk-based medical follow-up is recommended, which includes a systematic plan for lifelong screening, surveillance, and prevention that incorporates risk estimates based on the following:
- Previous cancer.
- Cancer therapy.
- Genetic predisposition.
- Lifestyle behaviors.
- Comorbid conditions.
Part of long-term follow-up is also focused on appropriate screening of educational and vocational progress. Specific treatments for childhood cancer, especially those that directly impact nervous system structures, may result in sensory, motor, and neurocognitive deficits that may have adverse consequences on functional status, educational attainment, and future vocational opportunities. In support of this, a CCSS investigation observed the following:
- Treatment with cranial radiation doses of 25 Gy or higher was associated with higher odds of unemployment (health related: odds ratio [OR], 3.47; 95% confidence interval [CI], 2.54–4.74; seeking work: OR, 1.77; 95% CI, 1.15–2.71).
- Unemployed survivors reported higher levels of poor physical functioning than employed survivors, had lower education and income, and were more likely to be publicly insured than unemployed siblings.
These data emphasize the importance of facilitating survivor access to remedial services, which has been demonstrated to have a positive impact on education achievement, which may in turn enhance vocational opportunities.
In addition to risk-based screening for medical late effects, the impact of health behaviors on cancer-related health risks is also emphasized. Health-promoting behaviors are stressed for survivors of childhood cancer. Targeted educational efforts appear to be worthwhile in the following areas:
- Abstinence from smoking, excess alcohol use, and illicit drug use to reduce the risk of organ toxicity and, potentially, subsequent neoplasms.
- Healthy dietary practices and active lifestyle to reduce treatment-related metabolic and cardiovascular complications.
Proactively addressing unhealthy and risky behaviors is pertinent, as several research investigations confirm that long-term survivors use tobacco and alcohol and have inactive lifestyles at higher rates than is ideal given their increased risk of cardiac, pulmonary, and metabolic late effects.[36-38]
Access to risk-based survivor care
Most childhood cancer survivors do not receive recommended risk-based care. The CCSS observed the following:
- 88.8% of survivors reported receiving some form of medical care.
- 31.5% reported receiving care that focused on their previous cancer (survivor-focused care).
- 17.8% reported receiving survivor-focused care that included advice about risk reduction and discussion or ordering of screening tests.
- Surveillance for new cases of cancer was very low in survivors at the highest risk of colon, breast, or skin cancer, suggesting that survivors and their physicians need education about the risk of subsequent neoplasms and recommended surveillance.
- Sociodemographic factors have been linked to declining rates of follow-up care over time from diagnosis. CCSS participants who were male, had a household income of less than $20,000 per year, and had lower educational attainment (high school education or less) were more likely to report no care at their most recent follow-up survey. This trend is of concern because the prevalence of chronic health conditions increases with longer elapsed time from cancer diagnosis in adults treated for cancer during childhood.
Access to health insurance appears to play an important role in risk-based survivor care.[42,43] Lack of access to health insurance affects the following:
- Cancer-related visits. In the CCSS, uninsured survivors were less likely than those privately insured to report a cancer-related visit (adjusted relative risk [RR], 0.83; 95% CI, 0.75–0.91) or a cancer center visit (adjusted RR, 0.83; 95% CI, 0.71–0.98). Uninsured survivors had lower levels of utilization in all measures of care than privately insured survivors. In contrast, publicly insured survivors were more likely to report a cancer-related visit (adjusted RR, 1.22; 95% CI, 1.11–1.35) or a cancer center visit (adjusted RR, 1.41; 95% CI, 1.18–1.70) than were privately insured survivors.
- Health outcomes. In a study comparing health care outcomes for long-term survivors of adolescent and young adult (AYA) cancer with young adults who have no cancer history, the proportion of uninsured survivors did not differ between the two groups.
- Financial burden. Subgroups of AYA survivors may be at additional risk of facing health care barriers. Younger survivors (aged 20–29 years), females, nonwhites, and survivors reporting poorer health faced more cost barriers, which may inhibit the early detection of late effects.
Overall, lack of health insurance remains a significant concern for survivors of childhood cancer because of health issues, unemployment, and other societal factors.[45,46] Legislation, including the Health Insurance Portability and Accountability Act (HIPAA),[47,48] has improved access and retention of health insurance among survivors, although the quality and limitations associated with these policies have not been well studied.
Transition to Survivor Care
Long-term follow-up programs
Transition of care from the pediatric to adult health care setting is necessary for most childhood cancer survivors in the United States.
When available, multidisciplinary long-term follow-up programs in the pediatric cancer center work collaboratively with community physicians to provide care for childhood cancer survivors. This type of shared care has been proposed as the optimal model to facilitate coordination between the cancer center oncology team and community physician groups providing survivor care.
An essential service of long-term follow-up programs is the organization of an individualized survivorship care plan that includes the following:
- Details about therapeutic interventions undertaken for childhood cancer and their potential health risks (e.g., chemotherapy type and cumulative dose, radiation treatment fields and dose, surgical procedures, blood product transfusions, and hematopoietic cell transplantation).
- Personalized health screening recommendations.
- Information about lifestyle factors that modify risks.
For survivors who have not been provided with this information, the COG offers a template that can be used by survivors to organize a personal treatment summary (refer to the COG Survivorship Guidelines, Appendix 1Exit Disclaimer).
COG Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers
To facilitate survivor and provider access to succinct information to guide risk-based care, COG investigators have organized a compendium of exposure- and risk-based health surveillance recommendations, with the goal of standardizing the care of childhood cancer survivors.
The compendium of resources includes the following:
- Long-Term Follow-Up Guidelines. COG Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult CancersExit Disclaimer are appropriate for asymptomatic survivors presenting for routine exposure-based medical evaluation 2 or more years after completion of therapy.
- Health Links. Patient education materials called Health Links provide detailed information on guideline-specific topics to enhance health maintenance and promotion among this population of cancer survivors.
- Comprehensive reviews. Multidisciplinary system-based (e.g., cardiovascular, neurocognitive, and reproductive) task forces who are responsible for monitoring the literature, evaluating guideline content, and providing recommendations for guideline revisions as new information becomes available have published several comprehensive reviews that address specific late effects of childhood cancer.[52-64] Information concerning late effects is summarized in tables throughout this summary.
Several groups have undertaken research to evaluate the yield from risk-based screening as recommended by the COG and other pediatric oncology cooperative groups.[9,65,66] Pertinent considerations in interpreting the results of these studies include:
- Variability in the cohort’s age at treatment.
- Age at screening.
- Time from cancer treatment.
- Participation bias.
Collectively, these studies demonstrate that screening identifies a substantial proportion of individuals with previously unrecognized, treatment-related health complications of varying degrees of severity. Study results have also identified low-yield evaluations that have encouraged revisions of screening recommendations. Ongoing research is evaluating cost effectiveness of screening in the context of consideration of benefits, risks, and harms.
- Jemal A, Siegel R, Xu J, et al.: Cancer statistics, 2010. CA Cancer J Clin 60 (5): 277-300, 2010 Sep-Oct. [PUBMED Abstract]
- Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2010. Bethesda, Md: National Cancer Institute, 2013. Also available online. Last accessed January 31, 2018.
- Lorenzi MF, Xie L, Rogers PC, et al.: Hospital-related morbidity among childhood cancer survivors in British Columbia, Canada: report of the childhood, adolescent, young adult cancer survivors (CAYACS) program. Int J Cancer 128 (7): 1624-31, 2011. [PUBMED Abstract]
- Mols F, Helfenrath KA, Vingerhoets AJ, et al.: Increased health care utilization among long-term cancer survivors compared to the average Dutch population: a population-based study. Int J Cancer 121 (4): 871-7, 2007. [PUBMED Abstract]
- Rebholz CE, Reulen RC, Toogood AA, et al.: Health care use of long-term survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol 29 (31): 4181-8, 2011. [PUBMED Abstract]
- Armstrong GT, Kawashima T, Leisenring W, et al.: Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol 32 (12): 1218-27, 2014. [PUBMED Abstract]
- Oeffinger KC, Mertens AC, Sklar CA, et al.: Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355 (15): 1572-82, 2006. [PUBMED Abstract]
- Geenen MM, Cardous-Ubbink MC, Kremer LC, et al.: Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. JAMA 297 (24): 2705-15, 2007. [PUBMED Abstract]
- Hudson MM, Ness KK, Gurney JG, et al.: Clinical ascertainment of health outcomes among adults treated for childhood cancer. JAMA 309 (22): 2371-81, 2013. [PUBMED Abstract]
- Sun CL, Francisco L, Kawashima T, et al.: Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. Blood 116 (17): 3129-39; quiz 3377, 2010. [PUBMED Abstract]
- Kurt BA, Nolan VG, Ness KK, et al.: Hospitalization rates among survivors of childhood cancer in the Childhood Cancer Survivor Study cohort. Pediatr Blood Cancer 59 (1): 126-32, 2012. [PUBMED Abstract]
- Zhang Y, Lorenzi MF, Goddard K, et al.: Late morbidity leading to hospitalization among 5-year survivors of young adult cancer: a report of the childhood, adolescent and young adult cancer survivors research program. Int J Cancer 134 (5): 1174-82, 2014. [PUBMED Abstract]
- Berbis J, Michel G, Chastagner P, et al.: A French cohort of childhood leukemia survivors: impact of hematopoietic stem cell transplantation on health status and quality of life. Biol Blood Marrow Transplant 19 (7): 1065-72, 2013. [PUBMED Abstract]
- Phillips SM, Padgett LS, Leisenring WM, et al.: Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer Epidemiol Biomarkers Prev 24 (4): 653-63, 2015. [PUBMED Abstract]
- Bhakta N, Liu Q, Ness KK, et al.: The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE). Lancet 390 (10112): 2569-2582, 2017. [PUBMED Abstract]
- Vuotto SC, Krull KR, Li C, et al.: Impact of chronic disease on emotional distress in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer 123 (3): 521-528, 2017. [PUBMED Abstract]
- Hudson MM, Oeffinger KC, Jones K, et al.: Age-dependent changes in health status in the Childhood Cancer Survivor cohort. J Clin Oncol 33 (5): 479-91, 2015. [PUBMED Abstract]
- Liu Q, Leisenring WM, Ness KK, et al.: Racial/Ethnic Differences in Adverse Outcomes Among Childhood Cancer Survivors: The Childhood Cancer Survivor Study. J Clin Oncol 34 (14): 1634-43, 2016. [PUBMED Abstract]
- Ehrhardt MJ, Bhakta N, Liu Q, et al.: Absence of Basal Cell Carcinoma in Irradiated Childhood Cancer Survivors of Black Race: A Report from the St. Jude Lifetime Cohort Study. Cancer Epidemiol Biomarkers Prev 25 (9): 1356-60, 2016. [PUBMED Abstract]
- Turcotte LM, Liu Q, Yasui Y, et al.: Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015. JAMA 317 (8): 814-824, 2017. [PUBMED Abstract]
- Armstrong GT, Pan Z, Ness KK, et al.: Temporal trends in cause-specific late mortality among 5-year survivors of childhood cancer. J Clin Oncol 28 (7): 1224-31, 2010. [PUBMED Abstract]
- Bhatia S, Robison LL, Francisco L, et al.: Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. Blood 105 (11): 4215-22, 2005. [PUBMED Abstract]
- MacArthur AC, Spinelli JJ, Rogers PC, et al.: Mortality among 5-year survivors of cancer diagnosed during childhood or adolescence in British Columbia, Canada. Pediatr Blood Cancer 48 (4): 460-7, 2007. [PUBMED Abstract]
- Tukenova M, Guibout C, Hawkins M, et al.: Radiation therapy and late mortality from second sarcoma, carcinoma, and hematological malignancies after a solid cancer in childhood. Int J Radiat Oncol Biol Phys 80 (2): 339-46, 2011. [PUBMED Abstract]
- Prasad PK, Signorello LB, Friedman DL, et al.: Long-term non-cancer mortality in pediatric and young adult cancer survivors in Finland. Pediatr Blood Cancer 58 (3): 421-7, 2012. [PUBMED Abstract]
- Youn P, Milano MT, Constine LS, et al.: Long-term cause-specific mortality in survivors of adolescent and young adult bone and soft tissue sarcoma: a population-based study of 28,844 patients. Cancer 120 (15): 2334-42, 2014. [PUBMED Abstract]
- Reulen RC, Winter DL, Frobisher C, et al.: Long-term cause-specific mortality among survivors of childhood cancer. JAMA 304 (2): 172-9, 2010. [PUBMED Abstract]
- Mertens AC, Yong J, Dietz AC, et al.: Conditional survival in pediatric malignancies: analysis of data from the Childhood Cancer Survivor Study and the Surveillance, Epidemiology, and End Results Program. Cancer 121 (7): 1108-17, 2015. [PUBMED Abstract]
- Yeh JM, Nekhlyudov L, Goldie SJ, et al.: A model-based estimate of cumulative excess mortality in survivors of childhood cancer. Ann Intern Med 152 (7): 409-17, W131-8, 2010. [PUBMED Abstract]
- Armstrong GT, Chen Y, Yasui Y, et al.: Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer. N Engl J Med 374 (9): 833-42, 2016. [PUBMED Abstract]
- Fidler MM, Reulen RC, Winter DL, et al.: Long term cause specific mortality among 34 489 five year survivors of childhood cancer in Great Britain: population based cohort study. BMJ 354: i4351, 2016. [PUBMED Abstract]
- McCabe MS, Partridge AH, Grunfeld E, et al.: Risk-based health care, the cancer survivor, the oncologist, and the primary care physician. Semin Oncol 40 (6): 804-12, 2013. [PUBMED Abstract]
- Hudson MM, Mulrooney DA, Bowers DC, et al.: High-risk populations identified in Childhood Cancer Survivor Study investigations: implications for risk-based surveillance. J Clin Oncol 27 (14): 2405-14, 2009. [PUBMED Abstract]
- Kirchhoff AC, Leisenring W, Krull KR, et al.: Unemployment among adult survivors of childhood cancer: a report from the childhood cancer survivor study. Med Care 48 (11): 1015-25, 2010. [PUBMED Abstract]
- Mitby PA, Robison LL, Whitton JA, et al.: Utilization of special education services and educational attainment among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Cancer 97 (4): 1115-26, 2003. [PUBMED Abstract]
- Nathan PC, Ford JS, Henderson TO, et al.: Health behaviors, medical care, and interventions to promote healthy living in the Childhood Cancer Survivor Study cohort. J Clin Oncol 27 (14): 2363-73, 2009. [PUBMED Abstract]
- Schultz KA, Chen L, Chen Z, et al.: Health and risk behaviors in survivors of childhood acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer 55 (1): 157-64, 2010. [PUBMED Abstract]
- Tercyak KP, Donze JR, Prahlad S, et al.: Multiple behavioral risk factors among adolescent survivors of childhood cancer in the Survivor Health and Resilience Education (SHARE) program. Pediatr Blood Cancer 47 (6): 825-30, 2006. [PUBMED Abstract]
- Nathan PC, Greenberg ML, Ness KK, et al.: Medical care in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 26 (27): 4401-9, 2008. [PUBMED Abstract]
- Nathan PC, Ness KK, Mahoney MC, et al.: Screening and surveillance for second malignant neoplasms in adult survivors of childhood cancer: a report from the childhood cancer survivor study. Ann Intern Med 153 (7): 442-51, 2010. [PUBMED Abstract]
- Casillas J, Oeffinger KC, Hudson MM, et al.: Identifying Predictors of Longitudinal Decline in the Level of Medical Care Received by Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study. Health Serv Res 50 (4): 1021-42, 2015. [PUBMED Abstract]
- Casillas J, Castellino SM, Hudson MM, et al.: Impact of insurance type on survivor-focused and general preventive health care utilization in adult survivors of childhood cancer: the Childhood Cancer Survivor Study (CCSS). Cancer 117 (9): 1966-75, 2011. [PUBMED Abstract]
- Keegan TH, Tao L, DeRouen MC, et al.: Medical care in adolescents and young adult cancer survivors: what are the biggest access-related barriers? J Cancer Surviv 8 (2): 282-92, 2014. [PUBMED Abstract]
- Kirchhoff AC, Lyles CR, Fluchel M, et al.: Limitations in health care access and utilization among long-term survivors of adolescent and young adult cancer. Cancer 118 (23): 5964-72, 2012. [PUBMED Abstract]
- Crom DB, Lensing SY, Rai SN, et al.: Marriage, employment, and health insurance in adult survivors of childhood cancer. J Cancer Surviv 1 (3): 237-45, 2007. [PUBMED Abstract]
- Pui CH, Cheng C, Leung W, et al.: Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med 349 (7): 640-9, 2003. [PUBMED Abstract]
- Park ER, Kirchhoff AC, Zallen JP, et al.: Childhood Cancer Survivor Study participants' perceptions and knowledge of health insurance coverage: implications for the Affordable Care Act. J Cancer Surviv 6 (3): 251-9, 2012. [PUBMED Abstract]
- Warner EL, Park ER, Stroup A, et al.: Childhood cancer survivors' familiarity with and opinions of the Patient Protection and Affordable Care Act. J Oncol Pract 9 (5): 246-50, 2013. [PUBMED Abstract]
- Oeffinger KC, McCabe MS: Models for delivering survivorship care. J Clin Oncol 24 (32): 5117-24, 2006. [PUBMED Abstract]
- Landier W, Bhatia S, Eshelman DA, et al.: Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol 22 (24): 4979-90, 2004. [PUBMED Abstract]
- Eshelman D, Landier W, Sweeney T, et al.: Facilitating care for childhood cancer survivors: integrating children's oncology group long-term follow-up guidelines and health links in clinical practice. J Pediatr Oncol Nurs 21 (5): 271-80, 2004 Sep-Oct. [PUBMED Abstract]
- Castellino S, Muir A, Shah A, et al.: Hepato-biliary late effects in survivors of childhood and adolescent cancer: a report from the Children's Oncology Group. Pediatr Blood Cancer 54 (5): 663-9, 2010. [PUBMED Abstract]
- Henderson TO, Amsterdam A, Bhatia S, et al.: Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med 152 (7): 444-55; W144-54, 2010. [PUBMED Abstract]
- Jones DP, Spunt SL, Green D, et al.: Renal late effects in patients treated for cancer in childhood: a report from the Children's Oncology Group. Pediatr Blood Cancer 51 (6): 724-31, 2008. [PUBMED Abstract]
- Liles A, Blatt J, Morris D, et al.: Monitoring pulmonary complications in long-term childhood cancer survivors: guidelines for the primary care physician. Cleve Clin J Med 75 (7): 531-9, 2008. [PUBMED Abstract]
- Nandagopal R, Laverdière C, Mulrooney D, et al.: Endocrine late effects of childhood cancer therapy: a report from the Children's Oncology Group. Horm Res 69 (2): 65-74, 2008. [PUBMED Abstract]
- Nathan PC, Patel SK, Dilley K, et al.: Guidelines for identification of, advocacy for, and intervention in neurocognitive problems in survivors of childhood cancer: a report from the Children's Oncology Group. Arch Pediatr Adolesc Med 161 (8): 798-806, 2007. [PUBMED Abstract]
- Ritchey M, Ferrer F, Shearer P, et al.: Late effects on the urinary bladder in patients treated for cancer in childhood: a report from the Children's Oncology Group. Pediatr Blood Cancer 52 (4): 439-46, 2009. [PUBMED Abstract]
- Shankar SM, Marina N, Hudson MM, et al.: Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children's Oncology Group. Pediatrics 121 (2): e387-96, 2008. [PUBMED Abstract]
- Wasilewski-Masker K, Kaste SC, Hudson MM, et al.: Bone mineral density deficits in survivors of childhood cancer: long-term follow-up guidelines and review of the literature. Pediatrics 121 (3): e705-13, 2008. [PUBMED Abstract]
- Metzger ML, Meacham LR, Patterson B, et al.: Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications. J Clin Oncol 31 (9): 1239-47, 2013. [PUBMED Abstract]
- Kenney LB, Cohen LE, Shnorhavorian M, et al.: Male reproductive health after childhood, adolescent, and young adult cancers: a report from the Children's Oncology Group. J Clin Oncol 30 (27): 3408-16, 2012. [PUBMED Abstract]
- Effinger KE, Migliorati CA, Hudson MM, et al.: Oral and dental late effects in survivors of childhood cancer: a Children's Oncology Group report. Support Care Cancer 22 (7): 2009-19, 2014. [PUBMED Abstract]
- Bass JK, Knight KR, Yock TI, et al.: Evaluation and Management of Hearing Loss in Survivors of Childhood and Adolescent Cancers: A Report From the Children's Oncology Group. Pediatr Blood Cancer 63 (7): 1152-62, 2016. [PUBMED Abstract]
- Landier W, Armenian SH, Lee J, et al.: Yield of screening for long-term complications using the children's oncology group long-term follow-up guidelines. J Clin Oncol 30 (35): 4401-8, 2012. [PUBMED Abstract]
- Wasilewski-Masker K, Mertens AC, Patterson B, et al.: Severity of health conditions identified in a pediatric cancer survivor program. Pediatr Blood Cancer 54 (7): 976-82, 2010. [PUBMED Abstract]
Retrieved from https://www.cancer.gov/types/childhood-cancers/late-effects-hp-pdq on October 27, 2018.