Background: No studies have estimated the population-level burden of morbidity in individuals diagnosed with cancer as children (ages 0–19 years). We updated prevalence estimates of childhood cancer survivors as of 2011 and burden of morbidity in this population reflected by chronic conditions, neurocognitive dysfunction, compromised health-related quality of life, and health status (general health, mental health, functional impairment, functional limitations, pain, and fear/anxiety).

Methods: Surveillance, Epidemiology, and End Results (SEER) Program data from 1975 to 2011 were used to update the prevalence of survivors of childhood cancers in the United States. Childhood Cancer Survivor Study data were used to obtain estimates of morbidity burden indicators, which were then extrapolated to SEER data to obtain population-level estimates.

Results: There were an estimated 388,501 survivors of childhood cancer in the United States as of January 1, 2011, of whom 83.5% are ≥5 years after diagnosis. The prevalence of any chronic condition among ≥5-year survivors ranged from 66% (ages 5–19) to 88% (ages 40–49). Estimates for specific morbidities ranged from 12% (pain) to 35% (neurocognitive dysfunction). Generally, morbidities increased by age. However, mental health and anxiety remained fairly stable, and neurocognitive dysfunction exhibited initial decline and then remained stable by time since diagnosis.

Conclusions: The estimated prevalence of survivors of childhood cancer is increasing, as is the estimated prevalence of morbidity in those ≥5 years after diagnosis.

Impact: Efforts to understand how to effectively decrease morbidity burden and incorporate effective care coordination and rehabilitation models to optimize longevity and well-being in this population should be a priority. Cancer Epidemiol Biomarkers Prev; 24(4); 653–63. ©2015 AACR.

This article is featured in Highlights of This Issue, p. 635

Estimates of the overall 5-year survival rates for childhood cancers have steadily increased since the 1970s and are currently over 80% (1). Although increased survival rates are promising, the low specificity of curative treatments for childhood cancer often results in long-term and late effects due to their impact on normal healthy tissues (2). Thus, survivors of childhood cancer are at an increased risk of adverse health and quality of life outcomes compared with individuals without a cancer history (3). These include increased number and severity of chronic health conditions (4, 5), health limitations (6, 7), hospitalizations (8, 9), premature frailty (10), psychologic distress (11), neurocognitive dysfunction (11, 12), and reduced productivity (i.e., inability to work or limitation in amount/kind or work) due to health problems (6). Adult survivors of childhood cancers also report poorer overall health (6, 13) and physical health–related quality of life (HRQOL; ref. 11). Prevalence for most of these adverse outcomes is estimated from individual cohort studies with less known about the burden of morbidity in childhood cancer survivors at the population level. As the number of survivors is expected to continue to increase due to increased incidence (14) and advances in lifesaving treatments, defining the public health and healthcare implications of childhood cancer survivors is an important next step.

Although no U.S. population–based study of childhood cancer survivors exists, the Childhood Cancer Survivor Study (CCSS) provides rich, high-quality data on a range of potential adverse and late effects of cancer treatment (15–17). CCSS is a large, geographically, and socioeconomically diverse, retrospectively established cohort study that prospectively follows health and disease outcomes in individuals from 26 North American pediatric cancer hospitals who were diagnosed with cancer during childhood or adolescence and survived at least 5 years. Using statistical models, data relevant to morbidity can be extrapolated from CSSS and applied to population-level survivorship prevalence data from the Surveillance Epidemiology and End Results (SEER) program, a collection of population-based registries of cancer incidence and survival in the United States (http://seer.cancer.gov). Combining CCSS and SEER data can provide an estimation of the population-level burden of morbidity in absolute numbers of affected childhood cancer survivors rather than relying only on CCSS data.

The purpose of the present study is 2-fold: (i) to update previously published (16) prevalence estimates of childhood cancer survivors in the United States through 2011 using SEER and (ii) to estimate the burden of morbidity among ≥5-year survivors of childhood cancer in the United States.

Data sources

SEER data.

SEER (18) data on incidence and survival from cancers diagnosed in individuals ≤19 years of age from 1975 to 2011 in 9 SEER registries including the states of Connecticut, Hawaii, Iowa, New Mexico, and Utah and the metropolitan areas of Atlanta, Detroit, San Francisco-Oakland, and Seattle/Puget Sound were used to estimate prevalence. These registries represent approximately 10% of the U.S. population. Cancer sites considered for prevalence estimates are those identified by the International Classification for Childhood Cancer ICD-O3 codes consistent with other publications using these data (19, 20). To match CCSS and SEER data, cancer sites were restricted to those in the CCSS study: leukemia, brain and central nervous system tumors, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft tissue, and bone tumors. CCSS brain tumors that were either germ cells or benign/borderline were excluded from CCSS data to better align with the SEER histology data. We used population estimates from the U.S. Census Bureau in the SEER*stat software (21).

CCSS burden of morbidity data.

The CCSS cohort includes over 14,000 long-term survivors of childhood cancer diagnosed between 1970 and 1986. Since enrollment in 1994 to 1998, participants have been periodically surveyed to track health outcomes, healthcare use patterns, and health behaviors and practices. The CCSS cohort study design and methodology have been previously described (15–17). The prevalence of factors contributing to the morbidity burden in survivors of childhood cancer 5 or more years following diagnosis was estimated using self-reported CCSS cohort data. These factors include chronic health conditions, neurocognitive functioning, HRQOL, and health status indicators. Table 1 summarizes the measures, cutoff values, and assessment time points used to estimate morbidity burden in the present study. For the purposes of this study, only CCSS survivors diagnosed between 1970 and 1986, who were ages 0 to 19 at diagnosis, were included to provide as similar a population to that in SEER as possible. Survivors with germ cell tumors (n = 62) were excluded because these tumor types were only captured for central nervous system patients and brain in the CCSS cohort. Survivors with benign or borderline brain and central nervous system tumors were also removed (n = 35) because these data were not incorporated into SEER until 2004.

Table 1.

Measures, cutoff values, and time schedule of data collection for burden of morbidity outcomes in CCSS

Assessment time pointNumber of survivors with dataNumber of records in model
Morbidity outcomeMeasure descriptionCutoff value used to indicate compromised functioning, impairment or severityBaseline (1994–98)200020032007
Chronic conditions/second cancers (4) Self-reported or proxy-reported (if <18 years of age or deceased at the time of the questionnaire):
  • physical health conditions and age at condition onset

  • second cancer reports were verified by pathology report review

 
Severity determined by the Common Terminology for Adverse Events (version4.03; ref. 39):
  • Grade 1: Mild

  • Grade 2: Moderate

  • Grade 3: Severe

  • Grade 4: Life-threatening or disabling

  • – If condition not listed: categorized as “other, specify” according to organ system affected

  • – If not enough information to distinguish between grades, lower score selected

 
13,974 32,471 
Neurocognitive functioning: CCSS Neurocognitive Questionnaire (12, 40, 41) Assesses degree (never, sometimes, often) to which participants experience any of 25 problems over the past 6 months. Has 4 subscales:
  • Task efficiency

  • Emotional regulation

  • Organization

  • Memory

 
T score <10th percentile of sibling groups' norm (i.e., ≥63) on any subscale (12)    7,228 7,228 
HRQOL: SF-36 (42, 43) Assesses 8 health-related dimensions: physical functioning, physical limitations, pain, behavior disturbances due to emotional problems, mental capacity, perceptions of health, social functioning, and feelings of energy/fatigue. Yields 2 component measures:
  • Physical component score (PCS)

  • Mental component score (MCS)

 
Score ≤40 on either PCS or MCS subscales    7,228 7,228 
Health status indicators (24) 
 General health In general, would you say that your health is excellent, very good, good, fair, or poor? Report fair/poor health  11,634 20,994 
 Mental health Brief Symptom Inventory 18 (BSI-18) to assess psychologic symptoms on 3 symptom-specific subscales: depression, somatization, and anxiety T scores ≥63 on any of the 3 symptom-specific subscales (24)  11,634 20,994 
 Functional impairment Any impairment (yes/no) or health problems resulting in:
  • needing help with personal care needs, such as easting, bathing, dressing, or getting around your home

  • needing help in handling routine needs, such as everyday household chores, doing necessary business, shopping, or getting around for other purposes

  • keeping you from holding a job or attending school

 
Positive response to a, b, or c   10,946 15,569 
 Limitations in activity How long (≥3 months, <3 months, or not all), over the last 2 years, was your health limited in:
  • kinds or amounts of moderate activities you can do, such as moving a table, carrying groceries, or bowling

  • walking uphill or climbing a few flights of stairs

  • walking one block

 
Report limitation on a, b, or c for ≥3 months   10,946 15,569 
 Pain Do you currently have pain as a result of your cancer or its treatment? (yes/no) Reported medium to excruciating pain   11,111 16,401 
 Anxiety/fear Do you currently have anxiety/fears as a result of your cancer or its treatment? Reported medium to very many, extreme anxiety/fears  11,634 20,994 
Assessment time pointNumber of survivors with dataNumber of records in model
Morbidity outcomeMeasure descriptionCutoff value used to indicate compromised functioning, impairment or severityBaseline (1994–98)200020032007
Chronic conditions/second cancers (4) Self-reported or proxy-reported (if <18 years of age or deceased at the time of the questionnaire):
  • physical health conditions and age at condition onset

  • second cancer reports were verified by pathology report review

 
Severity determined by the Common Terminology for Adverse Events (version4.03; ref. 39):
  • Grade 1: Mild

  • Grade 2: Moderate

  • Grade 3: Severe

  • Grade 4: Life-threatening or disabling

  • – If condition not listed: categorized as “other, specify” according to organ system affected

  • – If not enough information to distinguish between grades, lower score selected

 
13,974 32,471 
Neurocognitive functioning: CCSS Neurocognitive Questionnaire (12, 40, 41) Assesses degree (never, sometimes, often) to which participants experience any of 25 problems over the past 6 months. Has 4 subscales:
  • Task efficiency

  • Emotional regulation

  • Organization

  • Memory

 
T score <10th percentile of sibling groups' norm (i.e., ≥63) on any subscale (12)    7,228 7,228 
HRQOL: SF-36 (42, 43) Assesses 8 health-related dimensions: physical functioning, physical limitations, pain, behavior disturbances due to emotional problems, mental capacity, perceptions of health, social functioning, and feelings of energy/fatigue. Yields 2 component measures:
  • Physical component score (PCS)

  • Mental component score (MCS)

 
Score ≤40 on either PCS or MCS subscales    7,228 7,228 
Health status indicators (24) 
 General health In general, would you say that your health is excellent, very good, good, fair, or poor? Report fair/poor health  11,634 20,994 
 Mental health Brief Symptom Inventory 18 (BSI-18) to assess psychologic symptoms on 3 symptom-specific subscales: depression, somatization, and anxiety T scores ≥63 on any of the 3 symptom-specific subscales (24)  11,634 20,994 
 Functional impairment Any impairment (yes/no) or health problems resulting in:
  • needing help with personal care needs, such as easting, bathing, dressing, or getting around your home

  • needing help in handling routine needs, such as everyday household chores, doing necessary business, shopping, or getting around for other purposes

  • keeping you from holding a job or attending school

 
Positive response to a, b, or c   10,946 15,569 
 Limitations in activity How long (≥3 months, <3 months, or not all), over the last 2 years, was your health limited in:
  • kinds or amounts of moderate activities you can do, such as moving a table, carrying groceries, or bowling

  • walking uphill or climbing a few flights of stairs

  • walking one block

 
Report limitation on a, b, or c for ≥3 months   10,946 15,569 
 Pain Do you currently have pain as a result of your cancer or its treatment? (yes/no) Reported medium to excruciating pain   11,111 16,401 
 Anxiety/fear Do you currently have anxiety/fears as a result of your cancer or its treatment? Reported medium to very many, extreme anxiety/fears  11,634 20,994 

Data analyses

Prevalence of childhood cancer survivors.

Data on incidence and survival from 1975 to 2011 from the SEER registries were used to update prevalence estimates of childhood cancer survivors by anatomic sites and all cancer sites, combined, in the United States through January 1, 2011. The number of people in the United States alive in 2011 and diagnosed with cancer between ages 0 and 19 years was calculated in 3 steps. First, the proportion of survivors alive in the SEER-9 areas diagnosed with childhood cancer at ages 0 to 19 years between the years 1975 and 2011 was calculated by cancer site, sex, race (white, black, other; where unknown race was grouped with white race), and age using the SEER*Stat software (21) and the counting method (22). Second, to estimate complete U.S. childhood cancer survivor prevalence, the site/sex/race/age-specific SEER cancer prevalence proportions were multiplied by the respective U.S. sex/race/age-specific populations. To obtain overall prevalence, these categories were summed. Third, complete prevalence of childhood cancer, which includes childhood cancers diagnosed before 1975 (i.e., with ≥36 years from prevalence date), was calculated using the CHILDPREV method (16, 23). Briefly, this method estimates the long-term childhood cancer survivors, diagnosed before 1975, using age and period parametric cancer site/sex-specific incidence and survival models fitted to SEER data. Prevalence was examined by sex, age at prevalence estimate (0–19, 20–29, 30–39, 40–49, 50–59, and ≥60 years), and cancer type (leukemia, acute lymphocytic leukemia, acute myelogenous leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, brain/central nervous system, neuroblastoma and other peripheral nervous cell tumor, renal tumors, malignant bone tumors, osteosarcoma, Ewing tumor and related sarcomas of bone, soft tissue and other extraosseous sarcomas, germ cell and trophoblastic tumors, and neoplasms of gonads).

Representativeness of CCSS.

To ensure that the CCSS data were representative of the larger U.S. population of childhood cancer survivors, prevalence of all cancers by age at diagnosis (0–4, 5–9, 10–14, and 15–19 years), sex and race (white/unknown, black or other), and each cancer type listed, above, were calculated and compared for the SEER population–based and CCSS samples.

Burden of morbidity.

To estimate the burden of morbidity of U.S. childhood cancer survivors, data on chronic conditions, neurocognitive dysfunction, HRQOL, and health status indicators were extrapolated from CCSS to U.S. prevalence data. Some adjustments were made to combine morbidity proportions from CCSS and SEER prevalence data to reflect the CCSS sample: (i) prevalence estimates were restricted to people who survived ≥5 years; (ii) complete prevalence up to 36 years duration was used instead of complete prevalence because this was the maximum length of follow-up for CCSS data; and (ii) only cancers considered in CCSS were included.

We used a logistic regression model to estimate prevalence of morbidities as the proportion of subjects who had experienced the binary outcome of interest as of a specified postdiagnosis period (or age). At-risk subjects were classified into prevalent cases versus noncases at each interval using reported age at onset (chronic conditions, assessed retrospectively) or age at assessment time point (all other variables). Given the follow-up time frame for the CCSS cohort, we were only able to estimate the burden of morbidity indicators up to 36 years after diagnosis for survivors 5 to 49 years of age. Binary outcome variables examined included presence of (a) any (grades 1–4) chronic conditions; (b) any grade 1 (mild) or grade 2 (moderate), and any grade 3 (severe) or grade 4 (life-threatening or disabling) chronic conditions; (c) multiple (≥2 and ≥3) grade 3 or 4 chronic conditions (4); (d) neurocognitive dysfunction; (e) compromised mental or physical HRQOL; and (f) moderate to extreme impairments in health status indicators (24), including general health, mental health, functional status, functional limitations, pain, and anxiety/fear.

Chronic conditions were assessed at multiple time points. Thus, a participant could contribute observations in more than one follow-up/age period. Survivors with the onset of the condition before a given time period were assumed to have the condition in subsequent periods. The remainder of the health outcomes were obtained from one or more questionnaire time points (see Table 1) and were evaluated at the time points after diagnosis at which they were assessed. If a survivor completed two questionnaires within the same age or time since diagnosis interval, data from the later questionnaire were used. Table 1 provides detailed information on the number of unique cases and number of records used in analyses for each morbidity indicator. As chronic conditions were the most frequently assessed morbidity indicator, the sample and record size was largest for these outcomes. Because the remaining morbidity outcomes were obtained at varying frequencies, the denominators for these outcomes differ. Estimates for health status indicators do not include the 5- to 19-year age group because the Brief Symptom Inventory (BSI) assessment was limited to those subjects ≥18 years of age. Neurocognitive functioning and HRQOL were only assessed at 2003 follow-up when all survivors were ≥14 years after diagnosis. Consequently, estimates for these factors were limited to survivors 15 to 36 years after diagnosis.

Logistic regression models were fit for each binary outcome, incorporating years after diagnosis and age at that observation time, controlling for impact of sex, as needed. Because most individuals contributed multiple records to the analysis via the multiple time point scenario developed for the morbidity indicators assessed at multiple time points, the analysis utilized generalized linear models, with generalized estimating equations and robust sandwich variance estimates to account for intraperson correlation (25). Predicted probability estimates from the models provided estimates of the prevalence of morbidity indicators, along with associated confidence intervals and P values for comparisons between groups defined by covariate levels. Once final models were obtained for U.S. cancer prevalence and CCSS morbidity prevalence, combined estimates of the burden of morbidity after cancer for this subset of the U.S. population were obtained by multiplying the CCSS morbidity prevalence by the relevant number of SEER cancer survivors within the equivalent age/follow-up periods.

SEER prevalence estimates

A total of 388,501 survivors of childhood cancer are estimated to be alive in the United States as of January 1, 2011 (Table 2). Of these, 83.5% had survived ≥5 years since their original diagnosis and 44.9% had survived ≥20 years. The cancer sites with the largest number of survivors were leukemia (75,677), brain (60,540), germ cell and trophoblastic tumors and neoplasms of gonads (38,439), and renal tumors (23,990). The proportion of long-term (≥20 years) survivors varied by cancer site. Sites with the largest proportions of longer-term survivors were as follows: germ cell, trophoblastic tumors, and neoplasms of gonads (58%); renal (58%); soft tissues (57%); and Hodgkin lymphoma (48%). Acute lymphocytic leukemia was the site with the smallest proportion of long-term survivors with only 23% surviving ≥20 years. Childhood cancer survivors ≥60 years represented 5% of all childhood cancer survivors. Germ cell, trophoblastic tumors and neoplasms of gonads (17.7%), and soft tissues (14.6%) cancer sites had the largest proportion of survivors ≥60 years of age.

Table 2.

SEER estimates of the number of people previously diagnosed with cancer as children (ages 0–19 years) in the United States and alive January 1, 2011, by International Classification of Childhood Cancer (ICCC) group, age, time since diagnosis, and gender

Complete prevalence counts by age at prevalenceTime since diagnosis (in years)
SiteGender/age0–1920–2930–3940–4950–5960+All ages<55–1010–<1515–<20≥20≥36
All sites Both 114,469 96,086 63,670 56,072 39,055 19,149 388,501 64,105 56,369 49,311 44,394 174,322 73,757 
 Male 61,300 50,413 31,574 25,285 16,475 9,976 195,023 33,865 30,060 25,669 22,928 82,501 32,774 
 Female 53,169 45,673 32,096 30,787 22,580 9,173 193,478 30,241 26,309 23,642 21,465 91,821 40,983 
Leukemia (I) Both 35,982 20,750 11,794 5,282 1,659 210 75,677 15,512 13,991 11,847 10,349 23,977 4,269 
 Male 19,822 10,941 6,006 2,737 766 92 40,364 8,401 7,946 6,368 5,498 12,151 1,924 
 Female 16,160 9,809 5,788 2,545 893 118 35,313 7,111 6,045 5,479 4,851 11,826 2,345 
Acute lymphocytic leukemia Both 30,395 16,935 9,972 4,732 564 62,601 12,299 11,277 10,063 8,626 20,335 3,265 
 Male 16,803 9,125 5,220 2,611 308 34,069 6,818 6,440 5,441 4,735 10,635 1,696 
 Female 13,592 7,810 4,752 2,121 256 28,532 5,481 4,838 4,622 3,891 9,700 1,569 
Acute myelogenous leukemia (Ib) Both 3,992 2,528 1,185 690 245 8,644 2,221 1,944 1,298 1,167 2,015 499 
 Male 2,075 1,183 498 321 137 4,217 1,028 1,099 694 515 881 265 
 Female 1,917 1,345 687 369 108 4,427 1,193 845 604 652 1,134 234 
Hodgkin lymphoma (IIa) Both 4,863 8,832 8,058 7,834 5,056 1,353 35,996 5,622 4,267 4,742 4,002 17,364 5,424 
 Male 2,693 4,544 4,009 3,829 2,504 702 18,281 2,994 2,246 2,249 1,844 8,948 2,910 
 Female 2,170 4,288 4,049 4,005 2,552 651 17,715 2,627 2,021 2,493 2,158 8,416 2,514 
Non-Hodgkin lymphoma (IIb,c,e) Both 6,654 6,888 4,353 2,908 1,759 1,146 23,708 4,949 4,190 3,446 2,837 8,285 3,441 
 Male 4,405 4,445 3,060 1,852 937 672 15,371 3,071 2,637 2,410 2,018 5,235 1,865 
 Female 2,249 2,443 1,293 1,056 822 474 8,337 1,879 1,553 1,036 818 3,050 1,576 
Brain/central nervous system (III) Both 20,913 15,272 9,006 8,615 5,044 1,690 60,540 10,660 9,349 8,185 7,230 25,116 10,996 
 Male 11,275 8,482 4,792 4,318 2,269 751 31,887 5,586 5,114 4,428 4,009 12,750 5,011 
 Female 9,638 6,790 4,214 4,297 2,775 939 28,653 5,074 4,235 3,757 3,221 12,366 5,985 
Neuroblastoma and other peripheral nervous cell tumor (IV) Both 9,632 3,883 2,119 1,741 1,446 830 19,651 3,096 2,971 2,222 2,464 8,899 3,991 
 Male 4,936 2,015 988 588 438 216 9,181 1,655 1,485 1,095 1,222 3,724 1,252 
 Female 4,696 1,868 1,131 1,153 1,008 614 10,470 1,441 1,486 1,127 1,241 5,176 2,739 
Renal tumors (VI) Both 7,787 4,702 3,809 4,280 2,554 858 23,990 2,439 2,336 2,711 2,610 13,894 7,904 
 Male 3,862 2,174 1,729 2,403 1,379 500 12,047 1,158 1,137 1,276 1,352 7,124 4,473 
 Female 3,925 2,528 2,080 1,877 1,175 358 11,943 1,282 1,199 1,434 1,257 6,771 3,431 
Malignant bone tumors (VIII) Both 3,567 4,417 3,167 2,568 2,417 907 17,043 3,110 2,421 1,871 2,051 7,591 3,570 
 Male 2,066 2,569 1,787 1,290 1,053 472 9,237 1,986 1,208 1,259 1,089 3,695 1,645 
 Female 1,501 1,848 1,380 1,278 1,364 435 7,806 1,123 1,213 612 962 3,896 1,925 
Osteosarcoma (VIIIa) Both 1,859 2,253 1,777 1,293 1,237 829 9,248 1,594 1,292 1,039 1,001 4,323 2,123 
 Male 1,002 1,265 1,014 657 499 396 4,833 965 601 685 495 2,087 965 
 Female 857 988 763 636 738 433 4,415 629 690 354 506 2,235 1,158 
Ewing tumor and related sarcomas of bone (VIIIc) Both 1,347 1,467 972 728 358 148 5,020 1,146 772 599 721 1,781 600 
 Male 819 872 487 336 197 43 2,754 747 387 436 386 798 248 
 Female 528 595 485 392 161 105 2,266 399 385 163 335 983 352 
Soft tissue and other extraosseous sarcomas (IX) Both 6,799 7,126 4,166 4,913 4,267 4,670 31,941 4,270 3,518 3,404 2,645 18,105 10,464 
 Male 3,724 3,812 2,131 2,424 1,995 2,608 16,694 2,225 2,005 1,755 1,401 9,309 5,344 
 Female 3,075 3,314 2,035 2,489 2,272 2,062 15,247 2,045 1,513 1,649 1,244 8,796 5,120 
Germ cell and trophoblastic tumors and neoplasms of gonads (X) Both 5,233 7,869 5,634 6,245 6,641 6,817 38,439 4,760 4,359 3,557 3,503 22,260 13,953 
 Male 2,749 5,143 3,461 3,322 3,301 3,136 21,112 2,985 2,822 2,236 2,086 10,983 6,605 
 Female 2,484 2,726 2,173 2,923 3,340 3,681 17,327 1,775 1,536 1,321 1,417 11,277 7,348 
Complete prevalence counts by age at prevalenceTime since diagnosis (in years)
SiteGender/age0–1920–2930–3940–4950–5960+All ages<55–1010–<1515–<20≥20≥36
All sites Both 114,469 96,086 63,670 56,072 39,055 19,149 388,501 64,105 56,369 49,311 44,394 174,322 73,757 
 Male 61,300 50,413 31,574 25,285 16,475 9,976 195,023 33,865 30,060 25,669 22,928 82,501 32,774 
 Female 53,169 45,673 32,096 30,787 22,580 9,173 193,478 30,241 26,309 23,642 21,465 91,821 40,983 
Leukemia (I) Both 35,982 20,750 11,794 5,282 1,659 210 75,677 15,512 13,991 11,847 10,349 23,977 4,269 
 Male 19,822 10,941 6,006 2,737 766 92 40,364 8,401 7,946 6,368 5,498 12,151 1,924 
 Female 16,160 9,809 5,788 2,545 893 118 35,313 7,111 6,045 5,479 4,851 11,826 2,345 
Acute lymphocytic leukemia Both 30,395 16,935 9,972 4,732 564 62,601 12,299 11,277 10,063 8,626 20,335 3,265 
 Male 16,803 9,125 5,220 2,611 308 34,069 6,818 6,440 5,441 4,735 10,635 1,696 
 Female 13,592 7,810 4,752 2,121 256 28,532 5,481 4,838 4,622 3,891 9,700 1,569 
Acute myelogenous leukemia (Ib) Both 3,992 2,528 1,185 690 245 8,644 2,221 1,944 1,298 1,167 2,015 499 
 Male 2,075 1,183 498 321 137 4,217 1,028 1,099 694 515 881 265 
 Female 1,917 1,345 687 369 108 4,427 1,193 845 604 652 1,134 234 
Hodgkin lymphoma (IIa) Both 4,863 8,832 8,058 7,834 5,056 1,353 35,996 5,622 4,267 4,742 4,002 17,364 5,424 
 Male 2,693 4,544 4,009 3,829 2,504 702 18,281 2,994 2,246 2,249 1,844 8,948 2,910 
 Female 2,170 4,288 4,049 4,005 2,552 651 17,715 2,627 2,021 2,493 2,158 8,416 2,514 
Non-Hodgkin lymphoma (IIb,c,e) Both 6,654 6,888 4,353 2,908 1,759 1,146 23,708 4,949 4,190 3,446 2,837 8,285 3,441 
 Male 4,405 4,445 3,060 1,852 937 672 15,371 3,071 2,637 2,410 2,018 5,235 1,865 
 Female 2,249 2,443 1,293 1,056 822 474 8,337 1,879 1,553 1,036 818 3,050 1,576 
Brain/central nervous system (III) Both 20,913 15,272 9,006 8,615 5,044 1,690 60,540 10,660 9,349 8,185 7,230 25,116 10,996 
 Male 11,275 8,482 4,792 4,318 2,269 751 31,887 5,586 5,114 4,428 4,009 12,750 5,011 
 Female 9,638 6,790 4,214 4,297 2,775 939 28,653 5,074 4,235 3,757 3,221 12,366 5,985 
Neuroblastoma and other peripheral nervous cell tumor (IV) Both 9,632 3,883 2,119 1,741 1,446 830 19,651 3,096 2,971 2,222 2,464 8,899 3,991 
 Male 4,936 2,015 988 588 438 216 9,181 1,655 1,485 1,095 1,222 3,724 1,252 
 Female 4,696 1,868 1,131 1,153 1,008 614 10,470 1,441 1,486 1,127 1,241 5,176 2,739 
Renal tumors (VI) Both 7,787 4,702 3,809 4,280 2,554 858 23,990 2,439 2,336 2,711 2,610 13,894 7,904 
 Male 3,862 2,174 1,729 2,403 1,379 500 12,047 1,158 1,137 1,276 1,352 7,124 4,473 
 Female 3,925 2,528 2,080 1,877 1,175 358 11,943 1,282 1,199 1,434 1,257 6,771 3,431 
Malignant bone tumors (VIII) Both 3,567 4,417 3,167 2,568 2,417 907 17,043 3,110 2,421 1,871 2,051 7,591 3,570 
 Male 2,066 2,569 1,787 1,290 1,053 472 9,237 1,986 1,208 1,259 1,089 3,695 1,645 
 Female 1,501 1,848 1,380 1,278 1,364 435 7,806 1,123 1,213 612 962 3,896 1,925 
Osteosarcoma (VIIIa) Both 1,859 2,253 1,777 1,293 1,237 829 9,248 1,594 1,292 1,039 1,001 4,323 2,123 
 Male 1,002 1,265 1,014 657 499 396 4,833 965 601 685 495 2,087 965 
 Female 857 988 763 636 738 433 4,415 629 690 354 506 2,235 1,158 
Ewing tumor and related sarcomas of bone (VIIIc) Both 1,347 1,467 972 728 358 148 5,020 1,146 772 599 721 1,781 600 
 Male 819 872 487 336 197 43 2,754 747 387 436 386 798 248 
 Female 528 595 485 392 161 105 2,266 399 385 163 335 983 352 
Soft tissue and other extraosseous sarcomas (IX) Both 6,799 7,126 4,166 4,913 4,267 4,670 31,941 4,270 3,518 3,404 2,645 18,105 10,464 
 Male 3,724 3,812 2,131 2,424 1,995 2,608 16,694 2,225 2,005 1,755 1,401 9,309 5,344 
 Female 3,075 3,314 2,035 2,489 2,272 2,062 15,247 2,045 1,513 1,649 1,244 8,796 5,120 
Germ cell and trophoblastic tumors and neoplasms of gonads (X) Both 5,233 7,869 5,634 6,245 6,641 6,817 38,439 4,760 4,359 3,557 3,503 22,260 13,953 
 Male 2,749 5,143 3,461 3,322 3,301 3,136 21,112 2,985 2,822 2,236 2,086 10,983 6,605 
 Female 2,484 2,726 2,173 2,923 3,340 3,681 17,327 1,775 1,536 1,321 1,417 11,277 7,348 

Representativeness of CCSS

CCSS participants were similar in terms of age at diagnosis, gender, race, and cancer type by time interval since diagnosis (see Table 3) to those reported in SEER, indicating CCSS was representative of the larger U.S. population of childhood cancer survivors to which the burden of morbidity data were extrapolated.

Table 3.

Demographic and disease characteristics of the CCSS sample compared with U.S. survivorsa diagnosed with childhood cancer by time since diagnosis

Times since diagnosis, years
5 to 1415 to 2425 to 36
CCSSU.S. populationaCCSSU.S. populationaCCSSU.S. populationa
Characteristic(N = 13,974)(N = 81,470)(N = 12,031)(N = 62,741)(N = 6,466)(N = 42,200)
Age at primary diagnosis (n, %), y 
 0–4 5,738 (41%) 29,298 (36%) 5,031 (42%) 23,963 (38%) 2,586 (40%) 15,286 (36%) 
 5–9 3,175 (23%) 16,767 (21%) 2,694 (22%) 13,033 (21%) 1,470 (23%) 9,021 (21%) 
 10–14 2,877 (21%) 16,819 (21%) 2,460 (20%) 11,429 (18%) 1,349 (21%) 8,779 (21%) 
 15–19 2,184 (16%) 18,586 (23%) 1,846 (15%) 14,316 (23%) 1,061 (16%) 9,115 (22%) 
Gender (n, %) 
 Male 7,514 (54%) 44,617 (55%) 6,339 (53%) 34,089 (54%) 3,354 (52%) 21,892 (52%) 
 Female 6,460 (46%) 36,853 (45%) 5,692 (47%) 28,651 (46%) 3,112 (48%) 20,309 (48%) 
Race (n, %) 
 White/unknown 12,392 (89%) 69,021 (85%) 10,770 (89%) 53,819 (86%) 5,948 (92%) 37,686 (89%) 
 Black 739 (5%) 8,731 (11%) 587 (5%) 6,348 (10%) 218 (4%) 3,288 (8%) 
 Other 843 (6%) 3,719 (5%) 674 (6%) 2,574 (4%) 300 (5%) 1,226 (3%) 
Cancer type (n, %) 
 Leukemia 4,808 (34%) 25,854 (32%) 4,084 (34%) 18,390 (29%) 2,115 (33%) 11,460 (27%) 
 Brain and central nervous system tumor 1,761 (13%) 17,538 (22%) 1,441 (12%) 13,243 (21%) 692 (11%) 7,493 (18%) 
 Hodgkin lymphomas (IIa) 1,779 (13%) 9,009 (11%) 1,553 (13%) 8,058 (13%) 910 (14%) 6,289 (15%) 
 Non-Hodgkin lymphomas (IIa) 1,059 (8%) 7,634 (9%) 925 (8%) 5,269 (8%) 503 (8%) 3,329 (8%) 
 Renal tumors (VI) 1,255 (9%) 5,047 (6%) 1,145 (10%) 4,826 (8%) 598 (9%) 3,740 (9%) 
 Neuroblastoma 953 (7%) 5,174 (6%) 863 (7%) 4,247 (7%) 474 (7%) 3,120 (7%) 
 Soft tissue 1,211 (9%) 6,921 (8%) 1,055 (9%) 5,164 (8%) 617 (10%) 4,583 (11%) 
 Bone tumors (VIII) 1,148 (8%) 4,294 (5%) 965 (8%) 3,543 (6%) 557 (9%) 2,187 (5%) 
Times since diagnosis, years
5 to 1415 to 2425 to 36
CCSSU.S. populationaCCSSU.S. populationaCCSSU.S. populationa
Characteristic(N = 13,974)(N = 81,470)(N = 12,031)(N = 62,741)(N = 6,466)(N = 42,200)
Age at primary diagnosis (n, %), y 
 0–4 5,738 (41%) 29,298 (36%) 5,031 (42%) 23,963 (38%) 2,586 (40%) 15,286 (36%) 
 5–9 3,175 (23%) 16,767 (21%) 2,694 (22%) 13,033 (21%) 1,470 (23%) 9,021 (21%) 
 10–14 2,877 (21%) 16,819 (21%) 2,460 (20%) 11,429 (18%) 1,349 (21%) 8,779 (21%) 
 15–19 2,184 (16%) 18,586 (23%) 1,846 (15%) 14,316 (23%) 1,061 (16%) 9,115 (22%) 
Gender (n, %) 
 Male 7,514 (54%) 44,617 (55%) 6,339 (53%) 34,089 (54%) 3,354 (52%) 21,892 (52%) 
 Female 6,460 (46%) 36,853 (45%) 5,692 (47%) 28,651 (46%) 3,112 (48%) 20,309 (48%) 
Race (n, %) 
 White/unknown 12,392 (89%) 69,021 (85%) 10,770 (89%) 53,819 (86%) 5,948 (92%) 37,686 (89%) 
 Black 739 (5%) 8,731 (11%) 587 (5%) 6,348 (10%) 218 (4%) 3,288 (8%) 
 Other 843 (6%) 3,719 (5%) 674 (6%) 2,574 (4%) 300 (5%) 1,226 (3%) 
Cancer type (n, %) 
 Leukemia 4,808 (34%) 25,854 (32%) 4,084 (34%) 18,390 (29%) 2,115 (33%) 11,460 (27%) 
 Brain and central nervous system tumor 1,761 (13%) 17,538 (22%) 1,441 (12%) 13,243 (21%) 692 (11%) 7,493 (18%) 
 Hodgkin lymphomas (IIa) 1,779 (13%) 9,009 (11%) 1,553 (13%) 8,058 (13%) 910 (14%) 6,289 (15%) 
 Non-Hodgkin lymphomas (IIa) 1,059 (8%) 7,634 (9%) 925 (8%) 5,269 (8%) 503 (8%) 3,329 (8%) 
 Renal tumors (VI) 1,255 (9%) 5,047 (6%) 1,145 (10%) 4,826 (8%) 598 (9%) 3,740 (9%) 
 Neuroblastoma 953 (7%) 5,174 (6%) 863 (7%) 4,247 (7%) 474 (7%) 3,120 (7%) 
 Soft tissue 1,211 (9%) 6,921 (8%) 1,055 (9%) 5,164 (8%) 617 (10%) 4,583 (11%) 
 Bone tumors (VIII) 1,148 (8%) 4,294 (5%) 965 (8%) 3,543 (6%) 557 (9%) 2,187 (5%) 

aU.S. survivors are estimated using the prevalence proportions of people diagnosed with cancer between 1975 and 2010 and ages 0 and 19 in the SEER-9 areas and applied to the respective U.S. population to generate U.S. counts.

Estimated burden of morbidity

Table 4 displays estimates of the number of prevalent cases for each morbidity indicator by age and time since diagnosis.

Table 4.

Estimates of the number of prevalent cases of chronic conditions, cognitive dysfunction, compromised HRQOL, and health status in childhood cancer survivors in the United States who survived a minimum of 5 years as of January 1, 2011

Number of prevalent cases
Years since diagnosis
5 to 1415 to 2425 to 36
Current ageTotal(n = 105,697)(n = 81,519)(n = 55,996)
Chronic conditions 
 Any grade 1–4 condition 5–19 (n = 61,882) 41,059 (66%) 35,208 5,851 N/A 
 20–29 (n = 84,589) 60,392 (71%) 30,406 25,592 4,394 
 30–39 (n = 61,461) 48,796 (79%) 5,822 24,891 18,083 
 40–49 (n = 35,280) 30,986 (88%) N/Aa 6,122 24,867 
 Total (N = 243,212) 181,236 (75%) 71,436 (68%) 62,456 (77%) 47,344 (85%) 
 Any grade 1–2 (mild/moderate) condition 5–19 (n = 61,882) 38,401 (62%) 32,780 5,621 N/A 
 20–29 (n = 84,589) 55,297 (66%) 27,644 24,087 4,196 
 30–39 (n = 61,461) 45,753 (74%) 5,271 23,303 17,179 
 40–49 (n = 35,280) 29,542 (84%) N/A 5,778 23,764 
 Total (N = 243,212) 169,263 (70%) 65,695 (62%) 58,789 (72%) 45,139 (81%) 
 Any grade 3–4 (severe/life-threatening or disabling) condition 5–19 (n = 61,882) 16,152 (26%) 13,787 2,365 N/A 
 20–29 (n = 84,589) 24,492 (29%) 12,109 10,572 1,811 
 30–39 (n = 61,461) 22,331 (36%) 2,565 11,434 8,332 
 40–49 (n = 35,280) 16,902 (48%) N/A 3,315 13,587 
 Total (N = 243,212) 79,877 (33%) 28,461 (27%) 27,686 (34%) 23,730 (42%) 
Multiple chronic health conditions 
 ≥2 grade 3–4 5–19 (n = 61,882) 4,528 (7%) 3,753 775 N/A 
 20–29 (n = 84,589) 7,090 (8%) 3,150 3,319 621 
 30–39 (n = 61,461) 7,585 (12%) 711 3,827 3,047 
 40–49 (n = 35,280) 7,057 (20%) N/A 1,291 5,766 
 Total (N = 243,212) 26,260 (11%) 7,614 (7%) 9,212 (11%) 9,434 (17%) 
 ≥3 grade 3–4 5–19 (n = 61,882) 1,511 (2%) 1212 299 N/A 
 20–29 (n = 84,589) 2,296 (3%) 911 1,148 237 
 30–39 (n = 61,461) 2,635 (4%) 200 1,296 1,139 
 40–49 (n = 35,280) 2,939 (8%) N/A 495 2,444 
 Total (N = 243,212) 9,381 (4%) 2,323 (2%) 3,238 (4%) 3,820 (7%) 
   Years since diagnosis 
   5 to 14 15 to 24 25 to 36 
 Current age Total (none) (n = 73,281) (n = 55,996) 
Impaired neurocognitive functioning 20–29 (n = 40,353) 15,946 (40%) N/Ab 13,522 2,424 
 30–39 (n = 53,644) 18,399 (34%) N/A 10,383 8,016 
 40–49 (n = 35,280) 11,518 (33%) N/A 2,137 9,381 
 Total (N = 129,277) 45,863 (35%) N/A 26,042 (36%) 19,821 (35%) 
HRQOL 
 Physical component score 20–29 (n = 40,353) 4,231 (10%) N/A 3,626 605 
 30–39 (n = 53,644) 8,788 (16%) N/A 5,134 3,654 
 40–49 (n = 35,280) 8,220 (23%) N/A 1,636 6,584 
 Total (N = 129,277) 21,239 (16%) N/A 10,396 (14%) 10,843 (19%) 
 Mental component score 20–29 (n = 40,353) 7,956 (20%) N/A 6,790 1,166 
 30–39 (n = 53,644) 9,897 (18%) N/A 5,708 4,189 
 40–49 (n = 35,280) 5,691 (16%) N/A 1,103 4,588 
 Total (N = 129,277) 23,544 (18%) N/A 13,601 (19%) 9,943 (18%) 
   Years since diagnosis 
   5 to 14 15 to 24 25 to 36 
 Current age Total (n = 52,053) (n = 73,281) (n = 55,996) 
Health status indicators 
 Poor/fair general health 20–29 (n = 84,589) 9,388 (11%) 4,685 4,007 696 
 30–39 (n = 61,461) 8,310 (14%) 961 4,222 3,127 
 40–49 (n = 35,280) 5,973 (17%) N/A 1,152 4,821 
 Total (N = 181,330) 23,671 (13%) 5,646 (11%) 9,381 (13%) 8,644 (15%) 
 Impaired mental health 20–29 (n = 84,589) 14,965 (18%) 7,969 6,125 871 
 30–39 (n = 61,461) 10,639 (17%) 1,445 5,719 3,475 
 40–49 (n = 35,280) 5,701 (16%) N/A 1,284 4,417 
 Total (N = 181,330) 31,305 (17%) 9,414 (18%) 13,128 (18%) 8,763 (16%) 
 Functional impairment 20–29 (n = 84,589) 10,612 (13%) 5071 4,617 924 
 30–39 (n = 61,461) 8,018 (13%) 825 3,874 3,319 
 40–49 (n = 35,280) 6,030 (17%) N/A 1,036 4,994 
 Total (N = 181,330) 24,660 (14%) 5,896 (11%) 9,527 (13%) 9,237 (16%) 
   Years since diagnosis 
   5 to 14 15 to 24 25 to 36 
 Current age Total (n = 52,053) (n = 73,281) (n = 55,996) 
 Limitations in activity 20–29 (n = 84,589) 10,182 (12%) 5369 4,066 747 
 30–39 (n = 61,461) 8,802 (14%) 1106 4,318 3,378 
 40–49 (n = 35,280) 7,249 (21%) N/A 1,343 5,906 
 Total (N = 181,330) 26,233 (14%) 6,475 (12%) 9,727 (13%) 10,031 (18%) 
 Pain (moderate to excruciating) 20–29 (n = 84,589) 8,149 (10%) 4,672 3,009 468 
 30–39 (n = 61,461) 7,533 (12%) 1,147 3,834 2,552 
 40–49 (n = 35,280) 5,336 (15%) N/A 1,117 4,219 
 Total (N = 181,330) 21,018 (12%) 5,819 (11%) 7,960 (11%) 7,239 (13%) 
 Anxiety/fear (medium to extreme) 20–29 (n = 84,589) 10,807 (13%) 6,027 4,134 646 
 30–39 (n = 61,461) 8,080 (13%) 1,171 4,143 2,766 
 40–49 (n = 35,280) 4,773 (14%) N/A 998 3,775 
 Total (N = 181,330) 23,660 (13%) 7,198 (14%) 9,275 (13%) 7,187 (13%) 
Number of prevalent cases
Years since diagnosis
5 to 1415 to 2425 to 36
Current ageTotal(n = 105,697)(n = 81,519)(n = 55,996)
Chronic conditions 
 Any grade 1–4 condition 5–19 (n = 61,882) 41,059 (66%) 35,208 5,851 N/A 
 20–29 (n = 84,589) 60,392 (71%) 30,406 25,592 4,394 
 30–39 (n = 61,461) 48,796 (79%) 5,822 24,891 18,083 
 40–49 (n = 35,280) 30,986 (88%) N/Aa 6,122 24,867 
 Total (N = 243,212) 181,236 (75%) 71,436 (68%) 62,456 (77%) 47,344 (85%) 
 Any grade 1–2 (mild/moderate) condition 5–19 (n = 61,882) 38,401 (62%) 32,780 5,621 N/A 
 20–29 (n = 84,589) 55,297 (66%) 27,644 24,087 4,196 
 30–39 (n = 61,461) 45,753 (74%) 5,271 23,303 17,179 
 40–49 (n = 35,280) 29,542 (84%) N/A 5,778 23,764 
 Total (N = 243,212) 169,263 (70%) 65,695 (62%) 58,789 (72%) 45,139 (81%) 
 Any grade 3–4 (severe/life-threatening or disabling) condition 5–19 (n = 61,882) 16,152 (26%) 13,787 2,365 N/A 
 20–29 (n = 84,589) 24,492 (29%) 12,109 10,572 1,811 
 30–39 (n = 61,461) 22,331 (36%) 2,565 11,434 8,332 
 40–49 (n = 35,280) 16,902 (48%) N/A 3,315 13,587 
 Total (N = 243,212) 79,877 (33%) 28,461 (27%) 27,686 (34%) 23,730 (42%) 
Multiple chronic health conditions 
 ≥2 grade 3–4 5–19 (n = 61,882) 4,528 (7%) 3,753 775 N/A 
 20–29 (n = 84,589) 7,090 (8%) 3,150 3,319 621 
 30–39 (n = 61,461) 7,585 (12%) 711 3,827 3,047 
 40–49 (n = 35,280) 7,057 (20%) N/A 1,291 5,766 
 Total (N = 243,212) 26,260 (11%) 7,614 (7%) 9,212 (11%) 9,434 (17%) 
 ≥3 grade 3–4 5–19 (n = 61,882) 1,511 (2%) 1212 299 N/A 
 20–29 (n = 84,589) 2,296 (3%) 911 1,148 237 
 30–39 (n = 61,461) 2,635 (4%) 200 1,296 1,139 
 40–49 (n = 35,280) 2,939 (8%) N/A 495 2,444 
 Total (N = 243,212) 9,381 (4%) 2,323 (2%) 3,238 (4%) 3,820 (7%) 
   Years since diagnosis 
   5 to 14 15 to 24 25 to 36 
 Current age Total (none) (n = 73,281) (n = 55,996) 
Impaired neurocognitive functioning 20–29 (n = 40,353) 15,946 (40%) N/Ab 13,522 2,424 
 30–39 (n = 53,644) 18,399 (34%) N/A 10,383 8,016 
 40–49 (n = 35,280) 11,518 (33%) N/A 2,137 9,381 
 Total (N = 129,277) 45,863 (35%) N/A 26,042 (36%) 19,821 (35%) 
HRQOL 
 Physical component score 20–29 (n = 40,353) 4,231 (10%) N/A 3,626 605 
 30–39 (n = 53,644) 8,788 (16%) N/A 5,134 3,654 
 40–49 (n = 35,280) 8,220 (23%) N/A 1,636 6,584 
 Total (N = 129,277) 21,239 (16%) N/A 10,396 (14%) 10,843 (19%) 
 Mental component score 20–29 (n = 40,353) 7,956 (20%) N/A 6,790 1,166 
 30–39 (n = 53,644) 9,897 (18%) N/A 5,708 4,189 
 40–49 (n = 35,280) 5,691 (16%) N/A 1,103 4,588 
 Total (N = 129,277) 23,544 (18%) N/A 13,601 (19%) 9,943 (18%) 
   Years since diagnosis 
   5 to 14 15 to 24 25 to 36 
 Current age Total (n = 52,053) (n = 73,281) (n = 55,996) 
Health status indicators 
 Poor/fair general health 20–29 (n = 84,589) 9,388 (11%) 4,685 4,007 696 
 30–39 (n = 61,461) 8,310 (14%) 961 4,222 3,127 
 40–49 (n = 35,280) 5,973 (17%) N/A 1,152 4,821 
 Total (N = 181,330) 23,671 (13%) 5,646 (11%) 9,381 (13%) 8,644 (15%) 
 Impaired mental health 20–29 (n = 84,589) 14,965 (18%) 7,969 6,125 871 
 30–39 (n = 61,461) 10,639 (17%) 1,445 5,719 3,475 
 40–49 (n = 35,280) 5,701 (16%) N/A 1,284 4,417 
 Total (N = 181,330) 31,305 (17%) 9,414 (18%) 13,128 (18%) 8,763 (16%) 
 Functional impairment 20–29 (n = 84,589) 10,612 (13%) 5071 4,617 924 
 30–39 (n = 61,461) 8,018 (13%) 825 3,874 3,319 
 40–49 (n = 35,280) 6,030 (17%) N/A 1,036 4,994 
 Total (N = 181,330) 24,660 (14%) 5,896 (11%) 9,527 (13%) 9,237 (16%) 
   Years since diagnosis 
   5 to 14 15 to 24 25 to 36 
 Current age Total (n = 52,053) (n = 73,281) (n = 55,996) 
 Limitations in activity 20–29 (n = 84,589) 10,182 (12%) 5369 4,066 747 
 30–39 (n = 61,461) 8,802 (14%) 1106 4,318 3,378 
 40–49 (n = 35,280) 7,249 (21%) N/A 1,343 5,906 
 Total (N = 181,330) 26,233 (14%) 6,475 (12%) 9,727 (13%) 10,031 (18%) 
 Pain (moderate to excruciating) 20–29 (n = 84,589) 8,149 (10%) 4,672 3,009 468 
 30–39 (n = 61,461) 7,533 (12%) 1,147 3,834 2,552 
 40–49 (n = 35,280) 5,336 (15%) N/A 1,117 4,219 
 Total (N = 181,330) 21,018 (12%) 5,819 (11%) 7,960 (11%) 7,239 (13%) 
 Anxiety/fear (medium to extreme) 20–29 (n = 84,589) 10,807 (13%) 6,027 4,134 646 
 30–39 (n = 61,461) 8,080 (13%) 1,171 4,143 2,766 
 40–49 (n = 35,280) 4,773 (14%) N/A 998 3,775 
 Total (N = 181,330) 23,660 (13%) 7,198 (14%) 9,275 (13%) 7,187 (13%) 

aAll participants were diagnosed between 1970 and 1986 at ages 0 to 19 years. Therefore, participants age 40 or older at completion of the questionnaires were at least 15 years after diagnosis (earliest questionnaire November 1992).

bEstimates for impaired neurocognitive dysfunction and HRQOL do not include survivors 5 to 14 years after diagnosis because at data collection (see Table 1), all participants in this category were at least 15 years after diagnosis.

Chronic conditions.

Approximately 70% of childhood cancer survivors were estimated to have a grade 1 or 2 (mild/moderate) chronic condition, and about one third (32%) were estimated to have a grade 3 or 4 (severe, disabling, or life-threatening) chronic condition. An estimated two thirds (68%) of childhood cancer survivors had any chronic condition 5 to 14 years after diagnosis with this number increasing to 77% and 85% at 15 to 24 and 25 to 36 years after diagnosis, respectively. Two thirds (66%) of childhood cancer survivors ages 5 to 19 years were projected to have any chronic condition (grades 1–4; see Fig. 1). This proportion increased with increasing age to 88% at ages 40 to 49 years (see Fig. 1), reflecting the consistent increase in the proportion of survivors with a grade 3 or 4 condition across age categories. Almost half (48%) of those ages 40 to 49 had a grade 3 or 4 chronic condition. An estimated 11% of survivors had two or more grade 3 or 4 conditions, over half of which (55%) occur in those ages 30 to 49. Finally, an estimated 4% of childhood cancer survivors had three or more grade 3 or 4 chronic conditions with just over half (57%) observed in those ages 30 to 49.

Figure 1.

A, estimates of the prevalence of chronic health conditions in childhood cancer survivors in the United States who survived a minimum of 5 years as of January 1, 2011, by age. B, estimates of the prevalence of chronic conditions in childhood cancer survivors in the United States who survived a minimum of 5 years as of January 1, 2011, by gender and age.

Figure 1.

A, estimates of the prevalence of chronic health conditions in childhood cancer survivors in the United States who survived a minimum of 5 years as of January 1, 2011, by age. B, estimates of the prevalence of chronic conditions in childhood cancer survivors in the United States who survived a minimum of 5 years as of January 1, 2011, by gender and age.

Close modal

Grade 1 or 2 condition prevalence estimates were similar for males and females across age categories ranging from 38% to 44% (see Fig. 1). Grade 3 and 4 conditions increased for both males and females with increasing age, but the proportion of women in each age category was higher (P value < 0.001).

Neurocognitive functioning.

An estimated 35% of childhood cancer survivors ages 20 to 49 had neurocognitive dysfunction. The estimated number of prevalent cases decreased by age category ranging from 40% to 33% (see Fig. 2) and was stable by time since diagnosis (36% and 35% at 15–24 and 25–36 years after diagnosis, respectively).

Figure 2.

Estimates of the prevalence of compromised neurocognitive function, compromised HRQOL, and health status in childhood cancer survivors in the United States who survived a minimum of 5 years by age as of January 1, 2011.

Figure 2.

Estimates of the prevalence of compromised neurocognitive function, compromised HRQOL, and health status in childhood cancer survivors in the United States who survived a minimum of 5 years by age as of January 1, 2011.

Close modal

HRQOL.

Estimated prevalence for compromised physical (PCS) and mental (MCS) HRQOL scores in survivors 20 to 49 years of age was 16% and 18%, respectively. The proportion of prevalent cases with compromised PCS scores increased across time since diagnosis and age categories from 14% to 19% and 10% to 23% (see Fig. 2), respectively. The proportion of survivors with MCS scores indicative of emotional problems was relatively consistent by time since diagnosis (18%–19%) and age category (16%–20%). In contrast with PCS, the prevalence of compromised MCS declined with increasing age (see Fig. 2).

Health status.

Prevalence estimates for self-reported poor or fair health (13%), functional impairment (14%), activity limitations (14%), impaired mental health (17%), pain (12%), and anxiety/fear (13%) were similar for childhood cancer survivors ages 20 to 49 years. The proportion of prevalent cases for impaired overall health status, activity limitations, and pain increased by age ranging from 11% to 17%, 12% to 21%, and 10% to 15%, respectively (see Fig. 2). Impaired overall health status and pain remained stable by time since diagnosis while activity limitation remained stable up to 24 years after diagnosis and then declined at 25 to 36 years after diagnosis (12% vs. 18%). Impaired mental health and anxiety estimates remained stable by age and time since diagnosis. Finally, functional impairment prevalence estimates remained stable for survivors <40 years of age (13%) and increased for those 40 to 49 years (17%), and increased by time since diagnosis interval from 11% to 16%.

It is estimated that there were 388,501 childhood cancer survivors alive in the United States as of January 1, 2011, an increase of 59,849 from the previous (2005) estimate (20). Findings of this analysis indicate that 83.5% of those diagnosed with childhood cancer survived ≥5 years after their cancer diagnosis, with almost 45% surviving ≥20 years. Moreover, 5% of childhood cancer survivors were ≥60 years of age. The increased prevalence of childhood cancer survivors through 2011 reflects ongoing treatment successes for a variety of childhood cancers. Moreover, by applying rates for selected adverse outcomes obtained from the CCSS cohort, we present the first population-level estimates of the number of survivors experiencing morbidity.

Our results further define the magnitude of the health challenges faced by childhood cancer survivors. Over two thirds of survivors exhibited at least one chronic health condition 5 to 14 years after diagnosis with almost half of survivors ages 40 to 49 years estimated to have a severe or life-threatening chronic condition. Following a similar trajectory, though with lower prevalence, population estimates suggest a significant plurality of childhood cancer survivors experiencing compromised physical HRQOL, poor or fair overall health, functional impairments, activity limitation, and pain. In contrast, emotional distress and anxiety prevalence remained relatively stable by age and time since diagnosis, whereas mental HRQOL and neurocognitive dysfunction demonstrated somewhat lower prevalence by age. From these projected trends, we begin to see the burden of morbidity faced by these survivors generally increased as they age and move further from time of diagnosis, a trend recently described by the CCSS (26).

Implications of findings

Harkening back to earlier warnings (27), a clear message emerges from these findings: a singular focus on curing cancer yields an incomplete picture of childhood cancer survivorship. The burden of chronic conditions in this population is profound, both in occurrence and severity. Because of their young age at diagnosis and their longevity, the consequences of these morbidities have implications for both survivors and the healthcare system. Survivors are likely challenged by the demand of managing multiple chronic conditions and the resulting limitations in their daily life, especially in the context of potential lack of awareness of their long-term health risks (28). These limitations in physical, cognitive, and mental functioning can disrupt typical development of personal relationships, education, and occupation, establishing independence, and negotiating family demands. Facing typical developmental milestones in the context of managing multiple morbidities is a challenge for which limited personal and healthcare system resource and support may exist. Childhood cancer survivors may also face challenges in their interactions with the healthcare system (3) as they may represent high service users requiring the management of multiple teams of specialists, appointments, medication regimens, and financial outlays. Typical population guidelines for preventive behaviors such as cancer screening may not apply to this group (29), further complicating clinical pathways of care. Moreover, the complex morbidity in these survivors challenges healthcare system communication, cost, and care coordination processes.

Given the emerging picture of significant chronic condition burden for these childhood cancer survivors occurring within the context of functional and cognitive limitations as well as psychosocial distress for a significant subset, the resulting challenges form the basis of key directions for suggested research.

Susceptibility to multiple chronic conditions.

Essential to improving our understanding of morbidity susceptibility is the question: what factors are associated with increased susceptibility? This question calls for examination from multiple perspectives in addition to oncology, including genomics, personalized medicine, treatment regimen–specific toxicities, behavioral medicine, psychology, cardiology, and endocrinology. A related question is the extent and mechanisms by which cancer treatments interact with the natural aging process. Although the high morbidity prevalence suggests childhood survivors' functional age may be older than their chronological age suggests (3), elucidating potential mechanisms underlying these processes is an important next step. In addition, further explication of morbidity trajectories, and determinants of these trajectories, is necessary. However, it is important to move beyond the description of a single chronic comorbidity (e.g., cardiac), and construct a picture of parallel and interactive trajectories, given our findings suggest that older survivors may be experiencing multiple, serious chronic conditions, and limitations.

Broadening the scope beyond chronic conditions to include other morbidity indicators (i.e., HRQOL, health status, and neurocognitive functioning), the question of susceptibility remains vital. What biomarkers or mechanistic processes are associated with decrements in cognitive functioning and health status? What are the susceptibilities for the consistent subset of patients experiencing impaired mental health? How do physical and psychologic factors interact to influence morbidity burden? Answering these questions could result in improved care via risk stratification and intervention development, but will require detailed longitudinal assessments to understand the pathophysiology of outcome-specific conditions.

Prevention of chronic diseases morbidity.

Our data illustrate an increased prevalence of poor health status including functional impairment and activity limitations in those ages 40 to 49 years. Approaches focused on preventing and ameliorating this health trajectory are essential. For example, physical activity, weight management, social support, and cognitive stimulation have been shown to be key components of healthy aging across disease prevention and management, cognition, and quality of life domains (30). Understanding the role of these factors in the prevention and trajectories of development of morbidity in childhood cancer survivors is essential. Current childhood cancer survivor screening guidelines recommend screening for second cancer and chronic conditions (29). However, these guidelines will need to be updated as cancer survivors age and could be expanded to include the additional endpoints explored in this study. Lastly, multiple studies have cited age-associated declines in cognitive abilities as a concern in the general population (31). Because approximately one third of childhood cancer survivors ≥15 years beyond diagnosis are estimated to experience neurocognitive dysfunction, investigation into possible prophylactic strategies and interventions warrants further investigation.

Care coordination.

Childhood cancer survivors need comprehensive follow-up care to address their complex healthcare needs (32, 33). Their needs do not end with cancer treatment. The burden of managing multiple chronic conditions and the accompanying need to coordinate care between multiple professionals and care teams becomes even more complicated for childhood cancer survivors and the healthcare system with the added need for incorporation of risk-based survivorship care. The emerging focus on survivorship care planning is in direct response to growing appreciation of the multiple chronic and late effects of cancer experienced by both childhood and adult cancer survivor populations and their care coordination needs (34–36). Much emphasis has been placed on documentation of treatments and toxicities, the transmission of screening schedules, and information on health behaviors. Although documentation of this information is important, it is imperative to move to more active survivorship care planning and coordination to simultaneously address the prevalence of chronic conditions, impairments, and limitations presented here, and the dynamic, complex active prevention, and treatment necessary for childhood cancer survivors.

Rehabilitation model focused on integrated care.

Determining the most effective and efficient clinical models of care for this population is an important next step (3, 37). Conceptualizing survivorship care through a rehabilitation model focused on optimization of function and quality of life and the coordination of complex care (38) offers rich opportunities for determining how best to address morbidity burden across the childhood cancer survivorship trajectory, especially since the significant chronic condition burden may be further complicated by compromised mental health and physical and cognitive dysfunction. Future research is needed to determine the feasibility and efficacy of this approach to address childhood cancer survivors' needs.

Limitations

Although study strengths include the use of multiple indicators of morbidity burden and extrapolation of these data to obtain population-level prevalence estimates, it is not without limitations. First, because the granularity and reliability of SEER data are limited in terms of secondary treatment and specific treatment agents and dosages, we were not able to directly link our findings to treatment data. Thus, we assumed treatment for childhood cancers was similar for the 1970 to 1986 CCSS treatment era as for the 1975 to 2005 diagnosis era used for SEER and are unable to comment on how these outcomes may differ based on treatment received. Most of our morbidity burden measures were based on self-report and thus are subject to possible under- and over-reporting. Our estimates of morbidity prevalence included only those who survived a minimum of 5 years and a maximum of 36 years and do not represent all childhood survivors. Future research is warranted to explore these relationships further by treatment and varying times since diagnosis to obtain a richer, more accurate picture of the burden of morbidity in this population and provide further insight into how morbidity may be prevented or delayed.

The estimated prevalence of childhood cancer survivors is increasing, as is the estimated morbidity prevalence in those ≥5 years beyond diagnosis. Taken together, these data paint a picture of a population experiencing co-occurring treatment benefits and morbidity. These findings call for future research focused not only on decreasing the morbidity burden, but also incorporating effective clinical models of care coordination and rehabilitation to reduce morbidity burden and optimize childhood cancer survivors' HRQOL, physical and neurocognitive functioning, and mental health.

No potential conflicts of interest were disclosed.

Conception and design: S.M. Phillips, L.S. Padgett, W.M. Leisenring, C.M. Alfano, J.S. de Moor, D.B. Hartigan, G.T. Armstrong, L.L. Robison, J.H. Rowland, K.C. Oeffinger, A.B. Mariotto

Development of methodology: S.M. Phillips, L.S. Padgett, W.M. Leisenring, K.R. Krull, C.M. Alfano, D.B. Hartigan, G.T. Armstrong, J.H. Rowland, K.C. Oeffinger, A.B. Mariotto

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): L.S. Padgett, G.T. Armstrong, L.L. Robison

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): S.M. Phillips, L.S. Padgett, W.M. Leisenring, K.K. Stratton, K. Bishop, K.R. Krull, C.M. Alfano, K.C. Oeffinger, A.B. Mariotto

Writing, review, and/or revision of the manuscript: S.M. Phillips, L.S. Padgett, W.M. Leisenring, K.K. Stratton, K.R. Krull, C.M. Alfano, T.M. Gibson, J.S. de Moor, D.B. Hartigan, G.T. Armstrong, L.L. Robison, J.H. Rowland, K.C. Oeffinger, A.B. Mariotto

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): W.M. Leisenring

Study supervision: S.M. Phillips, W.M. Leisenring, G.T. Armstrong, A.B. Mariotto

The CCSS is supported by a grant (U24-CA-55727; to G.T. Armstrong, Principal Investigator) from the NCI.

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Med Care
1993
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31
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247
263
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