Risk and associated risk factors of hospitalization for specific health problems over time in childhood cancer survivors: a medical record linkage study

Abstract

Childhood cancer survivors (CCS) experience higher hospitalization rates compared to the general population for neoplasms, circulatory diseases, endocrine/nutritional/metabolic diseases and eye disorders. We studied trends in hospitalization rates and associated patient and treatment‐specific risk factors for diagnosis subgroups among these four diseases. We performed medical record linkage of a ≥5‐year CCS cohort with national registers, and obtained a random reference sample matched on age, gender and calendar year per CCS. For each diagnosis subgroup we compared hospitalization rates and trends over time in CCS and the reference population. Further, we analyzed risk factors for hospitalizations within the four CCS diagnosis groups. We used multivariate Poisson regression for all models. We retrieved hospitalization data from 1382 CCS and 26,583 reference persons. CCS had increased hospitalization rates for almost all diagnosis subgroups examined. Hospitalization rates for endocrine/nutritional/metabolic diseases appeared to increase with longer time since primary cancer diagnosis up to 30 years after primary cancer diagnosis. Survivors initially treated with radiotherapy had increased hospitalization rates for neoplasms (P < 0.001), those initially treated with anthracyclines (2.5 [1.1–5.5]) and radiotherapy to thorax and/or abdomen (9.3 [2.4–36.6]) had increased hospitalization rates for diseases of the circulatory system, and those initially treated with radiotherapy to head and/or neck had increased hospitalization rates for endocrine/nutritional/metabolic diseases (6.7 [3.5–12.7]) and diseases of the eye (3.6 [1.5–8.9]). Our study highlights that long‐term health problems resulting in hospitalizations are still clinically relevant later in life of CCS. The identified treatment‐related risk factors associated with hospitalizations support targeted follow‐up care for these risk groups of CCS.

A detailed insight in the high risks of hospitalizations in long-term childhood cancer survivors—A Dutch LATER linkage study

“…We found that survivors experience significantly increased hospitalization rates, especially for endocrine conditions, and subsequent neoplasms. These results confirm previous studies, in which second neoplasms [13][14][15][16][24][25][26], endocrine conditions [14,15,24,26], conditions of the blood and blood forming organs [13,16,24,25] and cardiovascular conditions [14,15,26] were shown to lead to hospitalizations in CCS. We extended these previous hospitalization investigations by showing that CCS experienced higher hospitalization rates for nearly all underlying types of conditions, and by investigating the treatment related determinants for each type of diagnosis leading to hospitalization in CCS in detail.…”

“…These results add important insight to previous literature, in which only radiotherapy to the head/neck was found to be a determinant for hospitalizations for endocrine conditions. [26] For hospitalizations because of subsequent neoplasms we identified cranial, abdominopelvic, and lower extremity radiotherapy and treatment with epipodophyllotoxins (which include teniposide and etoposide) as determinants. Although epipodophyllotoxins have well-established leukemogenic properties [27,28]; they were not associated with risk of subsequent malignant neoplasms in previous analyses in our cohort.…”

The Dutch LATER physical outcomes set for self-reported data in survivors of childhood cancer

“…In long-term morbidity research in CCS, a broad variety of outcome assessment methods is used. Long-term morbidity outcomes can be assessed by self-reporting via questionnaires [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24], by medical evaluation during outpatient clinic visits [25][26][27][28][29][30][31][32][33][34] or by linkage with existing registries such as national hospital discharge registries [35][36][37][38][39]. Authors often include different types and different numbers of organ systems in their calculations of physical long-term morbidity .…”

Large variation in assessment and outcome definitions to describe the burden of long‐term morbidity in childhood cancer survivors: A systematic review

“…We decided not to focus on the burden of hospitalizations, because hospitalizations represent health conditions for which survivors need intensive medical care and thus important, less severe conditions managed in the outpatient setting might be missed. As a result, several important papers on hospitalizations in survivors, for example, from the Adult Life after Childhood Cancer in Scandinavia study and from the DCOG‐LATER study were not included 70‐72 . A future systematic review should investigate the methods featured in publications reporting hospitalizations in long‐term childhood cancer survivors.…”