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Amsterdam UMC, Emma’s Children’s Hospital, Amsterdam, The Netherlands
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Many long-term childhood cancer survivors suffer from treatment-related late effects, which may occur in any organ and include a wide spectrum of conditions. Long-term follow-up (LTFU) is recommended to facilitate early diagnosis and to ensure better health outcomes. Due to the heterogeneity of these sequelae, different specialists work together in the diagnosis and treatment of these conditions. Experts from both pediatric and internal medicine are involved in age-appropriate care by providing a transition process. Hence, LTFU of childhood cancer survivors is a prototypic example of multidisciplinary care for patients with complex needs treated in a specialized setting. International collaborations of healthcare professionals and scientists involved in LTFU of childhood cancer survivors, such as the International Guideline Harmonization Group, compile surveillance recommendations that can be clinically adopted all over the world. These global networks of clinicians and researchers make a joint effort to address gaps in knowledge, increase visibility and awareness of cancer survivorship and provide an excellent example of how progress in clinical care and scientific research may be achieved by international and multidisciplinary collaboration.
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Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
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Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
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Department of Pediatric Oncology/Hematology, Amsterdam University Medical Center, location VU University Medical Center, Amsterdam, The Netherlands
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Department of Pediatrics, Emma Children’s Hospital, Amsterdam University Medical Center, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Objective
The incidence of cranial radiotherapy (cRT)–induced central hypothyroidism (TSHD) in childhood brain tumor survivors (CBTS) is reported to be low. However, TSHD may be more frequent than currently suspected, as its diagnosis is challenging due to broad reference ranges for free thyroxine (FT4) concentrations. TSHD is more likely to be present when FT4 levels progressively decline over time. Therefore, we determined the incidence and latency time of TSHD and changes of FT4 levels over time in irradiated CBTS.
Design
Nationwide, 10-year retrospective study of irradiated CBTS.
Methods
TSHD was defined as ‘diagnosed’ when FT4 concentrations were below the reference range with low, normal or mildly elevated thyrotropin levels, and as ‘presumed’ when FT4 declined ≥ 20% within the reference range. Longitudinal FT4 concentrations over time were determined in growth hormone deficient (GHD) CBTS with and without diagnosed TSHD from cRT to last follow-up (paired t-test).
Results
Of 207 included CBTS, the 5-year cumulative incidence of diagnosed TSHD was 20.3%, which occurred in 50% (25/50) of CBTS with GHD by 3.4 years (range, 0.9–9.7) after cRT. Presumed TSHD was present in 20 additional CBTS. The median FT4 decline in GH-deficient CBTS was 41.3% (P < 0.01) to diagnosis of TSHD and 12.4% (P = 0.02) in GH-deficient CBTS without diagnosed TSHD.
Conclusions
FT4 concentrations in CBTS significantly decline over time after cRT, also in those not diagnosed with TSHD, suggesting that TSHD occurs more frequently and earlier than currently reported. The clinical relevance of cRT-induced FT4 decline over time should be investigated in future studies.
