TY - JOUR

T1 - Endocrine Late Effects in Survivors of Cancer in Adolescence and Young Adulthood

T2 - A Danish Population-Based Cohort Study

AU - Jensen, Mette Vestergaard

AU - Rugbjerg, Kathrine

AU - de Fine Licht, Sofie

AU - Johansen, Christoffer

AU - Schmiegelow, Kjeld

AU - Andersen, Klaus Kaae

AU - Winther, Jeanette Falck

PY - 2018

Y1 - 2018

N2 - Importance: As survival rates from cancer have improved dramatically over the last decades, there is a need to explore the long-term consequences. Adolescents and young adults with cancer are at risk for several therapy-related late effects; however, these have not been studied extensively.Objective: To investigate the lifetime risks of endocrine late effects of cancer and cancer treatment in adolescent and young adult cancer survivors.Design, Setting, and Participants: This Danish, nationwide, population-based cohort study was conducted from January 1, 1976, through December 31, 2009, and included follow-up from January 1, 1977, through December 31, 2010. A total of 32 548 one-year cancer survivors diagnosed at ages 15 to 39 years were identified using the Danish Cancer Registry and 188 728 cancer-free comparison participants matched by year of birth and sex were randomly chosen from the Danish Civil Registration system. Analyses were performed from July 3, 2015, to February 27, 2018.Exposures: Individuals in the survivor cohort were diagnosed with a first primary cancer at ages 15 to 39 years and received treatment according to recommendations and guidelines at time of diagnosis.Main Outcomes and Measures: By linkage to the National Patient Register, all hospital contacts for endocrine diseases were identified, and standardized hospitalization rate ratios (RRs) and absolute excess risks (AERs) were calculated.Results: A total of 32 548 adolescent and young adult 1-year cancer survivors (14 021 [43.1%] male) in the Danish Patient Registry were followed up for 379 157 person-years (median [range]: 10 [0-34] years) and 188 728 cancer-free participants (82 669 [43.8%] male) for comparison were followed up for 2 958 994 person-years (median [range]: 15 [0-34] years). A total of 2129 survivors (6.5%) had at least 1 hospital contact for an endocrine disease, while 1232.0 (3.8%) were expected, yielding a statistically significant increased RR of 1.73 (95% CI, 1.65-1.81). The RRs were highest for testicular hypofunction (75.12; 95% CI, 45.99-122.70), ovarian hypofunction (14.65; 95% CI, 8.29-25.86), and pituitary hypofunction (11.14; 95% CI, 8.09-15.34). The leading reasons for hospital contacts were thyroid disease (38.0% of total AER), testicular dysfunction (17.1% of total AER), and diabetes (14.4% of total AER). Leukemia survivors were at a high risk for any endocrine disease (RR, 3.97; 95% CI, 3.10-5.09), while Hodgkin lymphoma survivors (RR, 3.06; 95% CI, 2.62-3.57) had the highest disease-specific excess risk for hypothyroidism (AER, 362 per 100 000 person-years; 95% CI, 280-443 per 100 000 person-years).Conclusions and Relevance: The increased risk for endocrine diseases in adolescent and young adult cancer survivors indicates the need for counseling and follow-up, and could guide future preventive measures and surveillance strategies. Additional studies are required to determine exact associations between treatment regimens and endocrine diseases.

AB - Importance: As survival rates from cancer have improved dramatically over the last decades, there is a need to explore the long-term consequences. Adolescents and young adults with cancer are at risk for several therapy-related late effects; however, these have not been studied extensively.Objective: To investigate the lifetime risks of endocrine late effects of cancer and cancer treatment in adolescent and young adult cancer survivors.Design, Setting, and Participants: This Danish, nationwide, population-based cohort study was conducted from January 1, 1976, through December 31, 2009, and included follow-up from January 1, 1977, through December 31, 2010. A total of 32 548 one-year cancer survivors diagnosed at ages 15 to 39 years were identified using the Danish Cancer Registry and 188 728 cancer-free comparison participants matched by year of birth and sex were randomly chosen from the Danish Civil Registration system. Analyses were performed from July 3, 2015, to February 27, 2018.Exposures: Individuals in the survivor cohort were diagnosed with a first primary cancer at ages 15 to 39 years and received treatment according to recommendations and guidelines at time of diagnosis.Main Outcomes and Measures: By linkage to the National Patient Register, all hospital contacts for endocrine diseases were identified, and standardized hospitalization rate ratios (RRs) and absolute excess risks (AERs) were calculated.Results: A total of 32 548 adolescent and young adult 1-year cancer survivors (14 021 [43.1%] male) in the Danish Patient Registry were followed up for 379 157 person-years (median [range]: 10 [0-34] years) and 188 728 cancer-free participants (82 669 [43.8%] male) for comparison were followed up for 2 958 994 person-years (median [range]: 15 [0-34] years). A total of 2129 survivors (6.5%) had at least 1 hospital contact for an endocrine disease, while 1232.0 (3.8%) were expected, yielding a statistically significant increased RR of 1.73 (95% CI, 1.65-1.81). The RRs were highest for testicular hypofunction (75.12; 95% CI, 45.99-122.70), ovarian hypofunction (14.65; 95% CI, 8.29-25.86), and pituitary hypofunction (11.14; 95% CI, 8.09-15.34). The leading reasons for hospital contacts were thyroid disease (38.0% of total AER), testicular dysfunction (17.1% of total AER), and diabetes (14.4% of total AER). Leukemia survivors were at a high risk for any endocrine disease (RR, 3.97; 95% CI, 3.10-5.09), while Hodgkin lymphoma survivors (RR, 3.06; 95% CI, 2.62-3.57) had the highest disease-specific excess risk for hypothyroidism (AER, 362 per 100 000 person-years; 95% CI, 280-443 per 100 000 person-years).Conclusions and Relevance: The increased risk for endocrine diseases in adolescent and young adult cancer survivors indicates the need for counseling and follow-up, and could guide future preventive measures and surveillance strategies. Additional studies are required to determine exact associations between treatment regimens and endocrine diseases.

U2 - 10.1001/jamanetworkopen.2018.0349

DO - 10.1001/jamanetworkopen.2018.0349

M3 - Journal article

C2 - 30646084

VL - 1

SP - 1

EP - 12

JO - JAMA network open

JF - JAMA network open

SN - 2574-3805

IS - 2

M1 - e180349

ER -