Endocrine Health in Childhood Cancer Survivors.

2020

1171-1186

2020 Dec

1557-8240

<p>Endocrine late effects, including reproductive disorders and secondary thyroid cancer, have been reported in up to 50 %childhood cancer survivors (CCS) more than&nbsp;5&nbsp;years after treatment. Most endocrine disorders are amenable to treatment; awareness of symptoms is therefore of great importance. Recognition of these symptoms may be delayed however because many are nonspecific. Timely treatment of endocrine disorders improves quality of life in CCS and prevents possible consequences, such as short stature, bone and cardiovascular disorders, and depression. At-risk CCS must therefore be regularly and systematically monitored. This article provides a summary of the most commonly reported endocrine late effects in CCS.</p>

10.1016/j.pcl.2020.08.002

Pediatr Clin North Am

33131540

Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus.

2019

2019 Jul 22

1460-2105

<p><strong>BACKGROUND: </strong>Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus but the association between risk and radiation dose and volume is unclear.</p>

<p><strong>METHODS: </strong>Participants included 20,762 five-year survivors of childhood cancer (4,568 exposed to abdRT) and 4,853 siblings. For abdRT, we estimated maximum dose to abdomen, mean doses for whole pancreas, pancreatic head, body, tail, and percent pancreas volume receiving ≥10, ≥20, and ≥30Gy. Relative risks (RRs) were estimated with a Poisson model using generalized estimating equations, adjusted for attained age. All statistical tests were two-sided.</p>

<p><strong>RESULTS: </strong>Survivors exposed to abdRT (median age=31.6 years, range=10.2-58.3) were 2.92-fold more likely than siblings (95% confidence interval [CI]=2.02 to 4.23) and 1.60-times more likely than survivors not exposed to abdRT (95%CI=1.24 to 2.05) to develop diabetes. Among survivors treated with abdRT, greater attained age (RR(per 10 years)=2.11, 95%CI=1.70 to 2.62), higher body mass index (RR(BMI 30+)=5.00, 95%CI=3.19 to 7.83 with reference(BMI 18.5-24.9)), and increasing pancreatic tail dose were associated with increased diabetes risk in a multivariable model; an interaction was identified between younger age at cancer diagnosis and pancreatic tail dose with much higher diabetes risk associated with increasing pancreatic tail dose among those diagnosed at the youngest ages (p&lt;.001). Radiation dose and volume to other regions of the pancreas were not statistically significantly associated with risk.</p>

<p><strong>CONCLUSIONS: </strong>Among survivors treated with abdRT, diabetes risk was associated with higher pancreatic tail dose, especially at younger ages. Targeted interventions are needed to improve cardiometabolic health among those at highest risk.</p>

10.1093/jnci/djz152

J. Natl. Cancer Inst.

31329225

Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970-99: a report from the Childhood Cancer Survivor Study cohort.

2018

2018 Nov 08

1474-5488

<p><strong>BACKGROUND: </strong>Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment.</p>

<p><strong>METHODS: </strong>We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk.</p>

<p><strong>FINDINGS: </strong>Among 23 601 survivors with a median follow-up of 21 years (IQR 15-25), the 20-year cumulative incidence of at least one grade 3-5 chronic condition decreased significantly from 33·2% (95% CI 32·0-34·3) in those diagnosed 1970-79 to 29·3% (28·4-30·2; p&lt;0·0001) in 1980-89, and 27·5% (26·4-28·6; p=0·012 vs 1980-89) in 1990-99. By comparison, the 20-year cumulative incidence of at least one grade 3-5 condition in 5051 siblings was 4·6% (95% CI 3·9-5·2). The 15-year cumulative incidence of at least one grade 3-5 condition was lower for survivors diagnosed 1990-99 compared with those diagnosed 1970-79 for Hodgkin lymphoma (17·7% [95% CI 15·0-20·5] vs 26·4% [23·8-29·1]; p&lt;0·0001), non-Hodgkin lymphoma (16·9% [14·0-19·7] vs 23·8% [19·9-27·7]; p=0.0053), astrocytoma (30·5% [27·8-33·2] vs 47·3% [42·9-51·7]; p&lt;0·0001), Wilms tumour (11·9% [9·5-14·3] vs 17·6% [14·3-20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5-33·1] vs 36·5% [31·5-41·4]; p=0·021), and osteosarcoma (65·6% [60·6-70·6] vs 87·5% [84·1-91·0]; p&lt;0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3-5 condition was higher (1990-99 vs 1970-79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4-63·3] vs 42·9% [34·9-50·9]; p=0·00060), and neuroblastoma (25·0% [21·8-28·2] vs 18·0% [14·5-21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3-5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64-0·92; HR with treatment in the model=0·89, 95% CI 0·72-1·11; p=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65-0·85; HR with treatment=0·91, 95% CI 0·73-1·12; p=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970-79 to survivors diagnosed 1990-99 were noted for endocrinopathies (5·9% [5·3-6·4] vs 2·8% [2·5-3·2]; p&lt;0·0001), subsequent malignant neoplasms (2·7% [2·3-3·1] vs 1·9% [1·6-2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2-6·4] vs 3·3% [2·9-3·6]; p&lt;0·0001), and gastrointestinal conditions (2·3% [2·0-2·7] vs 1·5% [1·3-1·8]; p=0·00037), while hearing loss increased (3·0% [2·6-3·5] vs 5·7% [5·2-6·1]; p&lt;0·0001).</p>

<p><strong>INTERPRETATION: </strong>Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population.</p>

<p><strong>FUNDING: </strong>National Cancer Institute and the American Lebanese-Syrian Associated Charities.</p>

10.1016/S1470-2045(18)30537-0

Lancet Oncol.

30416076