Table 2.
The burden of chronic conditions among adolescent and young adult cancer survivors by tumor group (n = 34).
| Reference | Cancer Type | Number of AYA Participants | Outcome Ascertainment | Results |
|---|---|---|---|---|
| Mixed-cancer cohort | ||||
| Bradley, 2010 [50] | Any primary malignancy | 252 | Hospital records | In the 15–19 age group, there were 63 hospitalized survivors and 252 non-hospitalized survivors. OR for risk of hospitalization was 0.69 (95% CI 0.42–1.14) compared to the reference group, which was children aged 0–4. |
| Deyell, 2013 [51] | Any primary malignancy | 1237 | PharmaNet, the administrative database that captures all outpatient prescriptions in British Columbia | Adjusted OR of ever using a prescription antidepressant medication among the 15–20 age group was 1.89 (95% CI = 1.04–3.45) and among 20–25 age group was 1.78 95% CI = 0.88–3.5). Reference group was children diagnosed before 5 years. |
| Zhang, 2014 [47] | Any primary malignancy | 902 | Hospital records containing morbidity data | 455 survivors (50%) had at least one type of late morbidity leading to hospitalization, corresponding to a rate ratio (RR) of 1.37 (95% CI 1.22–1.54) relative to the general population. The highest risks were found for hospitalization due to blood disease (RR = 4.2, 95% CI 1.98–8.78) and neoplasm (RR = 4.3, 95% CI 3.41–5.33). |
| Brewster, 2014 [52] | Any primary malignancy | 3053 | National linked database that includes acute hospital discharge records, psychiatric hospital records, and Scottish cancer registration and mortality records | Among people in the AYA age group who were 5-year survivors, the standardized bed day ratio (SBDR) for acute hospitalizations was 3.5 (95% CI 3.4, 3.6) for the 15–19 age group and 2.4 (95% CI 2.4, 2.5) for the 20–24 age group. The SBDR for psychiatric hospitalizations was 0.3 for both the 15–19 and 20–24 age groups 95% CI 0.2–0.3 and 0.3–0.3, respectively, compared to the general population. |
| Kero, 2014 [49] | Any primary malignancy | 9401 | Finnish hospital discharge registry | Compared to their siblings, cancer survivors aged 20–34 had a higher risk of cardiovascular events: cardiomyopathy/cardiac insufficiency (HR = 3.6, 95% CI 2.8–4.6), atherosclerosis/brain vascular thrombosis (HR = 1.7, 95% CI 1.4–2.0), myocardial infarction/cardiac ischemia (HR = 1.8, 95% CI 1.5–2.1), and cardiac arrhythmia (HR = 1.4, 95% CI 1.2–1.7). |
| Kirchoff, 2014 [53] | Any primary malignancy | 597 | Records from the Utah Department of Health statewide inpatient hospitalization claims data | Among 597 AYA cancer survivors captured in this cohort, 292 did not have a hospitalization during the follow-up and 305 did have a hospitalization during follow-up. |
| Rugbjerg, 2014 [48] | Any primary malignancy | 43,153 | Danish Patient Register, containing data on hospital admissions | 24.5% of survivors were discharged from the hospital with CVD during follow-up (HRR = 1.30, 95% CI 1.28–1.33). AER was 393 (95% CI 359–427) per 100,000 person-years compared to a cohort of age- and sex-matched subjects. Venous and lymphatic disease was the leading reason for hospitalization (AER = 133 per 100,000 person-years). |
| van Laar, 2014 [54] | Any primary malignancy except skin carcinomas and melanomas | 1880 | Hospital admissions data | The rate of hospitalization in the YA cohort was not significantly higher than the general population (HRR = 1.2, 95% CI 0.9–1.5). However, there was a significant increase in the hospitalization rate for pericardial disease (HRR = 4.0, 95% CI 1.8–8.8), cardiomyopathy and heart failure (HRR = 3.8, 95% CI 2.2–6.6), pulmonary heart disease (HRR = 3.5, 95% CI 2.0–6.4), conduction disorders (HRR = 2.0, 95% CI 1.2–3.2), and hypertension (HRR = 1.8, 95% CI 1.3–2.5). |
| Ahomaki, 2015 [55] | Any First primary Malignant Neoplasm. Excluded those with SMN | 9543 | Finnish hospital discharge registry | Compared to siblings, YA survivors had higher risk of organic memory/brain disorders (HR = 2.1; 95% CI 1.4–3.1) and mood disorders (HR = 1.3; 95% CI 1.1–1.5). Females had significantly increased risk for neurotic/anxiety disorders (HR = 1.6, 95% CI 1.2–2.1) compared to their siblings, whereas males did not. Radiotherapy did not explain the differences in psychiatric effects. |
| Asdahl, 2016 [56] | Any primary malignancy | 9921 | National patient registries containing hospital admissions data | Survivors had 50% excess gastrointestinal or liver diseases compared to the general population (RR = 1.5, 95% CI 1.4–1.6). |
| Kero, 2016 [57] | Any primary malignancy | 2184 | Drug Purchase Registry | Higher HR for purchasing anti-hypertensives (HR 1.5, 95% CI 1.3–1.8), diabetes drugs (HR 1.6, 95% CI 1.1–2.2), and lipid-lowering drugs (HR = 1.6, 95% CI 1.0–2.5) in YA cancer survivors compared to siblings. Among specific cancer diagnosis groups, highest HR values for anti-hypertensives were found in YA ALL (HR 4.8, 95% CI 3.1–7.0) and myeloid leukemia (HR 3.4, 95% CI 2.2–5.1) patients. YA ALL patients showed strongest likelihood of purchasing diabetes drugs compared to siblings (HR 3.7, 95% CI 1.2–9.5) |
| Chao, 2016 [58] | Any primary malignancy | 5673 | Kaiser Permanente Southern California electronic health records with linkage across clinical databases | For cancer survivors, incidence rate ratio for developing CVD was 2.4 (95% CI 1.9–2.9) compared to patients without cancer. Highest risk in leukemia (IRR = 4.2, 95% CI 1.7–10.3) and breast cancer (IRR = 3.6, 95% CI 2.4–5.5) survivors. Of the three cardiovascular risk factors examined, having diabetes (IRR = 3.2, 95% CI 1.9–5.5) or hypertension (IRR = 3.7, 95% CI 2.4.–5.7) generally imposed a greater risk for CVD than dyslipidemia (IRR = 1.8, 95% CI 1.1–2.9). |
| Rugbjerg, 2016 [40] | Any primary malignancy except non-melanoma skin cancer | 33,555 | Danish National Patient Register containing hospital admissions data | 53,052 hospitalizations occurred over the follow-up. RR 1.4 (95% CI 1.37–1.39) for survivors compared to controls. The highest risks of hospitalization were for diseases of the blood and blood-forming organs (hospitalization rate ratio [RR] = 2.0, 95% CI 1.87–2.14), infectious and parasitic diseases (RR = 1.69, 95% CI 1.61–1.77), and new malignant neoplasms (RR = 1.63, 95% CI 1.59–1.68). Overall AER was 2803 (95% CI 2712–2893) per 100,000 person-years. |
| Bright, 2017 [45] | Any primary malignancy | 178,962 | Hospital Episode Statistics database | 2782 AYA cancer survivors were hospitalized for at least one cerebrovascular event—standardized hospitalization ratio (SHR), 1.40 (95% CI 1.3–1.4). AYA cancer survivors are at 2-fold, 1.5-fold, and 1.4-fold risk of cerebral hemorrhage, cerebral infarction, and other cerebrovascular events, respectively. |
| Jensen, 2018 [59] | Any primary malignancy | 32,584 | Danish Patient Register, containing data on hospital admissions | 6.5% of survivors had at least one hospital contact for an endocrine disease, while 3.8% were expected (RR 1.7 95% CI 1.7–1.871; AER 236.6 per 100,000 person-years). Hospitalization rate ratios (RR) were highest for testicular hypofunction (RR = 75.1, 95% CI 46.0–122.7), ovarian hypofunction (RR = 14.7, 95% CI 8.3–25.9), and pituitary hypofunction (RR = 11.1, 95% CI 8.1–15.3). Leading reasons for hospital contacts: thyroid disease (38%), testicular dysfunction (17%), and diabetes (14%). |
| Keegan, 2018 [46] | 14 first primary AYA cancers | 79,176 | California Cancer Registry linked to California Office of Statewide Health Planning and Development hospital discharge data | 2.8% of survivors developed CVD. |
| Krawczuk-Rybak, 2018 [60] | Any primary malignancy | 197 | Self-report data verified by physicians and medical records and entered into an online registry | Of 197 survivors that were 15–18 at diagnosis, organ/system toxicities were most frequent for the skin (38%), male gonads (36%), circulatory system (29%), and female gonads (23%). |
| Nathan, 2018 [61] | Any primary malignancy | 537 | Administrative health databases (Registered Persons Database, the Ontario Health Insurance Plan Claims Database, the National Ambulatory Care Reporting System, the Canadian Institutes of Health Information Discharge Abstract Database the Ontario Mental Health Reporting System, and the Ontario Cancer Registry) | In multivariable regression models controlling for age, sex, and income quintile, the relative risk of mental health care visit rates in survivors of AYA (age 15–18) cancer was 1.81 (95% CI 1.2–2.8) relative to the 0–4 age group (p = 0.008). In a similar model predicting severe psychiatric events, the relative risk was 0.66 (95% CI 04–1.0; p = 0.072). |
| Ahomaki, 2019 [62] | Any primary malignancy | 4598 | Drug Purchase Registry | HR for antidepressant purchases was 4.5 (95% CI 3.9–5.3) among AYA cancer survivors compared to siblings. |
| Smith, 2019 [43] | Any primary malignancy excluding skin carcinomas and melanomas | 2627 | Hospital Episode Statistics database | Respiratory admission rates were 74% higher in AYA cancer survivors than the general population (Hospital Rate Ratio 1.74, 95% CI 1.6–1.9). For asthma, pneumonia, and chronic lower respiratory disease, admission rates were 49%, 285%, and 266% higher than the general population, respectively. |
| de Fine Licht, 2019 [44] | Any primary malignancy | 11,822 | Drug Purchase Registry | Compared to the population-based comparison cohort, AYA cancer survivors had increased risks for hospital contact and prescriptions for diabetes, hyperlipidemia, and hypertension. |
| Anderson, 2020 [41] | Any primary malignancy | 6330 | Hospital discharge data from the Utah Department of Health | Higher risk of hospitalization among AYA cancer survivors compared to matched population (HR = 1.9, 95% CI 1.8–2.1). Rate of hospitalizations was also increased among survivors relative to the comparison cohort (RR = 2.05, 95% CI 1.95–2.14). |
| Bhandari, 2020 [63] | Solid tumors or non-hematologic malignancy | 54 | Electronic medical records | The risk of acute kidney/chronic kidney disease in AYA was similar to those diagnosed at age younger than 15 years (OR: 1.30, 95% CI: 0.5–3.4) |
| Chao, 2020 [64] | Any primary malignancy | 6778 | Kaiser Permanente Southern California electronic health records with linkage across clinical databases | Incidence rate ratio was significantly increased for nearly all comorbidities. IRRs ranged up to 8.3 (95% CI 4.6–14.9) for avascular necrosis. Survivors had a 2- to 3-fold increase for diseases such as cardiomyopathy, stroke, premature ovarian failure, chronic liver disease, and renal failure. Compared to those without cancer, higher percentage of survivors had 2+ comorbidities at 10 years after index date (40% vs. 20% respectively). Adjusted IRR of developing 2+ incident comorbidities: 1.6 (95% CI 1.5–1.8). |
| Yu, 2020 [65] | Any malignancy | 7 | Medical records | Among survivors diagnosed at 15–18 years of age, none developed abnormal puberty. Gonadal dysfunction was observed in 2.6% males (1 out of 3), while none was observed among females. |
| Suh, 2020 [42] | Leukemia, CNS malignancy, HL, NHL, Wilms tumor, Neuroblastoma, Soft-tissue sarcoma, and Bone cancer | 4082 | Self-report by participants | Early adolescent and YA cancer survivors had HR of 4.2 (95% CI 3.7–4.8) for developing severe and disabling, life-threatening, or fatal health conditions compared to siblings of the same age. |
| Hodgkin lymphoma cohort | ||||
| van Nimwegen, 2015 [66] | HL | 1864 | Medical records | Compared to the general population, AYA survivors aged 18–24, 25–29, and 30–39 had a 5.4-fold (95% CI 4.5–6.5), 4.1-fold (95% CI 3.3–5.1), and 2.8-fold (95% CI 2.4–3.3) greater risk of developing coronary heart disease (CHD), respectively, and a 18.7-fold (95% CI 14.5–23.6), 10.4-fold (95% CI 7.5–14.2), and 5.7-fold (95% CI 4.4–7.2) greater risk of developing heart failure (HF), respectively. |
| Keegan, 2018 [67] | HL | 5085 | California Cancer Registry linked to hospital data from the Office of Statewide Health Planning and Development | 39% of AYAs had a hospital admission more than 2 years post-diagnosis. 26% of AYAs had at least one medical condition and 15% had two or more. Ten-year cumulative incidence of disease was highest for endocrine conditions, but estimates varied by race/ethnicity: lowest for non-Hispanic Whites (CI = 12.2, 95% CI 11.0–13.6) and highest for non-Hispanic Blacks (CI = 21.5, 95% CI 16.7–26.7). |
| Other tumor-specific cohort | ||||
| Bhuller, 2016 [32] | First primary malignancy: HL. SMN: Any cancer based on ICDO-3 with behavior code 3 or higher | 281 | British Columbia Cancer Registry | Survivors had an almost 1.5-fold increased risk of developing morbidity resulting in hospitalization compared to the general population. Higher proportion of survivors experienced two or more types of morbidity resulting in hospitalization compared to controls (26% vs. 15%, respectively). Most common disease groups requiring hospitalization: SMN (n = 45; 16%), digestive disease (n = 38; 14%), injury and poisoning (n = 35; 12%), genitourinary system (n = 28; 10%), circulatory disease (n = 24; 9%), and respiratory disease (n = 22; 8%). |
| Gunn, 2015 [68] | Brain tumors | 315 | Finnish Cancer Registry and Hospital Discharge Registry | Compared to siblings, survivors had the most increased risk for diseases of the nervous system (HR = 9.6, 95% CI 6.6–14.0), diseases of the kidney (HR = 5.9, 2.5–14.1), and diseases of the circulatory system (HR = 4.9, 95% CI 2.9–8.1;) and the least increased risk for disorders of vision or hearing loss (HR = 3.6, 95% CI 1.5–8.5), late endocrine diseases (HR = 2.9, 1.1–8.0), and psychiatric disorders (HR = 2.0, 95% CI 1.2–3.2). Cumulative prevalence for most diagnoses remained increased even 20 years after diagnosis. |
| Abrahao, 2020 [37] | NHL | 4392 HIV-uninfected and 425 HIV-infected | California Cancer Registry linked to hospital data from the Office of Statewide Health Planning and Development | Highest 10-year cumulative incidence of disease among HIV-uninfected patients: endocrine (18.5%, 95% CI 17.2–19.9%), cardiovascular (11.7%, 95% CI 10.6–12.8%), respiratory (5.0%, 95% CI 4.3–5.8%), renal (2.2%, 95% CI 1.8–2.8%), and neurologic (2.2%, 95% CI 1.7–2.7%), liver/pancreatic (2.0%, 95% CI 1.5–2.5%), and avascular necrosis (1.2%, 95% CI 0.9–1.7%). |
| Gingrich, 2020 [38] | Cutaneous melanoma | 8259 | California Cancer Registry linked to hospital data from the Office of Statewide Health Planning and Development | 8.4% of patients had regional disease. The most commonly diagnosed conditions were hematologic disorders (9.1%), cardiac disease (7.7%), and subsequent cancers (6.4%). |
| Muffly, 2020 [39] | ALL | 1069 | California Cancer Registry linked to hospital data from the Office of Statewide Health Planning and Development | The 10-year cumulative incidence of late effects was highest for endocrine disease (28.7, 95% CI 25.8–31.6) and cardiac diseases (17.0, 95% CI 14.6–19.5), and lowest for second cancers (1.4, 95% CI 0.7–2.4) and renal disease (3.1, 95% CI 2.1–4.4). All late effects increased over time. |
| Perisa, 2020 [69] | Ewing Sarcoma | 45 | Paper and electronic medical records | Treatment-related complications presented in AYA: Neuropathy (87.5%); cardiotoxicity (26.2%); transfections (Median number: 9, 95% CI: 0–72); admissions for fever and neutropenia (median number: 2.95% CI: 0–11). The differences were not significant compared to the pediatric group except for median number of admissions for fever and neutropenia. |
Abbreviations: AER, absolute excess risk; ALL, acute lymphoblastic leukemia; AYA, adolescent and young adult; CI, confidence interval; CNS, central nervous system; CVD, cardiovascular disease; HIV, human immunodeficiency virus; HL, Hodgkin lymphoma; HR, hazard ratio; IRR, incidence rate ratio; NHL, non-Hodgkin lymphoma; RR, rate ratio; SBDR, standardized bed day ratio; SEER, National Cancer Institute’s Surveillance, Epidemiology and End Results Program; SHR, standardized hospitalization ratio; SIR, standardized incidence ratio; SMN, subsequent malignant neoplasm; SPN, second primary neoplasm; YA, young adult.