Summary Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male ...pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.
Background
Childhood cancer survivors face late health problems; despite advances in research, details on risk remain unclear. We describe the methodological aspects of the Dutch Childhood Cancer ...Survivor Study (DCCSS) cross‐sectional clinical study (LATER 2 study).
Procedure
From the multi‐center DCCSS LATER cohort of 6165 five‐year survivors diagnosed during 1963–2001, we invited 4735 eligible survivors in 2016, as well as siblings and parents of survivors. Gaps in evidence identified during development of surveillance guidelines were translated into clinical research questions for 16 outcome‐specific subprojects. The regular care visit to the LATER outpatient clinic forms the backbone of outcome assessment complemented with research‐defined measurements (physical examination, clinical tests, questionnaires). Furthermore, blood/saliva samples were taken for deoxyribonucleic acid (DNA) extraction.
Results
In total, 2519 (53.2%) survivors participated in the LATER 2 study. When comparing participants with nonparticipants, we observed that males, CNS survivors, and those treated with surgery only were less likely to participate. Of the participating survivors, 49.3% were female. Median time since childhood cancer diagnosis was 26.9 years (range 14.8–54.7 years) and median attained age was 34.4 years (range 15.4–66.6 years).
Conclusions
The high‐quality data generated in the LATER 2 study will provide valuable insights into risks of and risk factors for clinical and physical and psychosocial health outcomes and factors for early recognition of those health outcomes in long‐term childhood cancer survivors. This will contribute to fill in important gaps in knowledge and improve the quality of life and care for childhood cancer survivors.
Background
The aim of this study is to evaluate how cumulative burden of clinically relevant, self‐reported outcomes in childhood cancer survivors (CCSs) compares to a sibling control group and to ...explore how the burden corresponds to levels of care proposed by existing risk stratifications.
Methods
The authors invited 5925 5‐year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete a questionnaire on health outcomes. Health outcomes were validated by self‐reported medication use or medical record review. Missing data on clinically relevant outcomes in CCSs for whom no questionnaire data were available were imputed with predictive mean matching. We calculated the mean cumulative count (MCC) for clinically relevant outcomes. Furthermore, we calculated 30‐year MCC for groups of CCSs based on primary cancer diagnosis and treatment, ranked 30‐year MCC, and compared the ranking to levels of care according to existing risk stratifications.
Results
At median 18.5 years after 5‐year survival, 46% of CCSs had at least one clinically relevant outcome. CCSs experienced 2.8 times more health conditions than siblings (30‐year MCC = 0.79; 95% confidence interval CI, 0.74–0.85 vs. 30‐year MCC = 0.29; 95% CI, 0.25–0.34). CCSs’ burden of clinically relevant outcomes consisted mainly of endocrine and vascular conditions and varied by primary cancer type. The ranking of the 30‐year MCC often did not correspond with levels of care in existing risk stratifications.
Conclusions
CCSs experience a high cumulative burden of clinically relevant outcomes that was not completely reflected by current risk stratifications. Choices for survivorship care should extend beyond primary tumor and treatment parameters, and should consider also including CCSs’ current morbidity.
Survivors of childhood cancer experience a high cumulative burden of clinically relevant outcomes. Choices for survivorship care should extend beyond primary tumor and treatment parameters and should also consider including the current morbidity of childhood cancer survivors.
Abstract
Context
Pituitary hormonal deficiencies in patients with craniopharyngioma may impair their bone health.
Objective
To investigate bone health in patients with craniopharyngioma.
Design
...Retrospective cross-sectional study.
Setting
Dutch and Swedish referral centers.
Patients
Patients with craniopharyngioma (n = 177) with available data on bone health after a median follow-up of 16 years (range, 1-62) were included (106 60% Dutch, 93 53% male, 84 48% childhood-onset disease).
Main outcome measures
Fractures, dual X-ray absorptiometry-derived bone mineral density (BMD), and final height were evaluated. Low BMD was defined as T- or Z-score ≤-1 and very low BMD as ≤-2.5 or ≤-2.0, respectively.
Results
Fractures occurred in 31 patients (18%) and were more frequent in men than in women (26% vs. 8%, P = .002). Mean BMD was normal (Z-score total body 0.1 range, -4.1 to 3.5) but T- or Z-score ≤-1 occurred in 47 (50%) patients and T-score ≤-2.5 or Z-score ≤-2.0 in 22 (24%) patients. Men received less often treatment for low BMD than women (7% vs. 18%, P = .02). Female sex (OR 0.3, P = .004) and surgery (odds ratio OR, 0.2; P = .01) were both independent protective factors for fractures, whereas antiepileptic medication was a risk factor (OR, 3.6; P = .03), whereas T-score ≤-2.5 or Z-score ≤-2.0 was not (OR, 2.1; P = .21). Mean final height was normal and did not differ between men and women, or adulthood and childhood-onset patients.
Conclusions
Men with craniopharyngioma are at higher risk than women for fractures. In patients with craniopharyngioma, a very low BMD (T-score ≤-2.5 or Z-score ≤-2.0) seems not to be a good predictor for fracture risk.
Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and ...electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure.
To describe the methodology of the Dutch LATER cardiology study (LATER CARD).
The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings.
The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure.
Summary
Childhood cancer survivors (CCS) are at increased risk to develop metabolic syndrome (MetS), diabetes, and cardiovascular disease. Common criteria underestimate adiposity and possibly ...underdiagnose MetS, particularly after abdominal radiotherapy. A systematic literature review and meta‐analysis on the diagnostic and predictive value of nine newer MetS related biomarkers (adiponectin, leptin, uric acid, hsCRP, TNF‐alpha, IL‐1, IL‐6, apolipoprotein B (apoB), and lipoprotein(a) lp(a)) in survivors and adult non‐cancer survivors was performed by searching PubMed and Embase. Evidence was summarized with GRADE after risk of bias evaluation (QUADAS‐2/QUIPS). Eligible studies on promising biomarkers were pooled. We identified 175 general population and five CCS studies. In the general population, valuable predictive biomarkers are uric acid, adiponectin, hsCRP and apoB (high level of evidence), and leptin (moderate level of evidence). Valuable diagnostic biomarkers are hsCRP, adiponectin, uric acid, and leptin (low, low, moderate, and high level of evidence, respectively). Meta‐analysis showed OR for hyperuricemia of 2.94 (age‐/sex‐adjusted), OR per unit uric acid increase of 1.086 (unadjusted), and AUC for hsCRP of 0.71 (unadjusted). Uric acid, adiponectin, hsCRP, leptin, and apoB can be alternative biomarkers in the screening setting for MetS in survivors, to enhance early identification of those at high risk of subsequent complications.
Purpose
Although quality of life (QoL) is improved in patients with acromegaly after disease control, QoL correlates only weakly with traditional biomarkers. Our objective is to investigate a ...potential relation between the new serum biomarker soluble Klotho (sKlotho), GH and insulin-like growth factor 1 (IGF-1) levels, and QoL.
Methods
In this prospective cohort study, we investigated 54 acromegaly patients biochemically well-controlled on combination treatment with first-generation somatostatin receptor ligands (SRLs) and pegvisomant (PEGV) at baseline and 9 months after switching to pasireotide LAR (PAS-LAR; either as monotherapy,
n
= 28; or in combination with PEGV,
n
= 26). QoL was measured by the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) and Acromegaly Quality of Life (AcroQoL) questionnaire.
Results
Switching to PAS-LAR treatment significantly improved QoL without altering IGF-1 levels. QoL did not correlate with GH or IGF-1 levels, but sKlotho correlated with the observed improvements in QoL by the AcroQoL global (
r
= −0.35,
p
= 0.012) and physical subdimension (
r
= −0.34,
p
= 0.017), and with PASQ headache (
r
= 0.28,
p
= 0.048), osteoarthralgia (
r
= 0.46,
p
= 0.00080) and soft tissue swelling score (
r
= 0.29,
p
= 0.041). Parallel changes in serum sKlotho and IGF-1 (
r
= 0.31,
p
= 0.023) suggest sKlotho and IGF-1 to be similarly dependent on GH. Comparing the PAS-LAR combination therapy and the monotherapy group we did not observe a significant difference in improvement of QoL.
Conclusions
Patients experienced improved QoL during PAS-LAR, either as monotherapy or in combination with PEGV. Soluble Klotho concentrations appear to be a useful marker of QoL in acromegaly patients but the underlying mechanisms remain to be investigated.
Small functional pituitary tumors can cause severely disabling symptoms and early death. The gold standard diagnostic approach includes laboratory tests and MRI, with or without inferior petrosal ...sinus sampling (IPSS). In up to 40% of patients, however, the source of excess hormone production remains unidentified or uncertain. This excludes patients from surgical, Gamma Knife, and CyberKnife therapy and adversely affects overall cure rates. We here assess the diagnostic yield of
-(2-
Ffluoroethyl)-l-tyrosine (
FFET) PET/MRI for detection of small functional pituitary tumors in these patients.
This retrospective analysis included patients with Cushing disease (CD) but prior negative or inconclusive MRI results who underwent
FFET PET/MRI between February 1, 2021, and December 1, 2022. PET/MR images and MR images alone were evaluated by experienced nuclear radiologists, neuroradiologists, or radiologists. Postoperative tissue analysis (when performed) was used as a reference standard to assess diagnostic metrics (i.e., sensitivity and positive predictive value). Results were also compared with previously obtained MR images, preceding IPSS, and clinical or biochemical follow-up.
Twenty-two patients (68% female; mean age ± SD, 48 ± 15 y; range, 24-68 y) were scanned. All patients showed a clear metabolic focus on
FFET PET, whereas reading of the MRI alone yielded a suspected lesion in only 50%. Fifteen patients underwent surgery directed at the
FFET-positive focus. Tissue analysis confirmed a pituitary adenoma/pituitary neuroendocrine tumor of the corticotroph cell type (TPIT lineage) in 10 of 15 and a pituicytoma in 1 of 15, rendering a sensitivity of 100% and a positive predictive value of 73%. Lateralization was more accurate with
FFET PET/MRI than with IPSS in 33%. Twelve of 16 (75%) patients who received surgical, Gamma Knife, or CyberKnife therapy after
FFET PET/MRI reached short-term remission.
FFET PET/MRI shows a high diagnostic yield for localizing small functional pituitary tumors. This multimodal imaging technique provides a welcome improvement for diagnosis, planning of surgery, and clinical outcome in patients with Cushing disease, particularly those with repeated negative or inconclusive MRI results with or without IPSS.
Background: Limited data are available on the risk factors of salivary gland dysfunction in long-term childhood cancer survivors (CCS). The objective of this cross-sectional study, part of the ...multidisciplinary multicenter Dutch CCS Study Late Effects 2 (DCCSS LATER 2), was to assess the prevalence of and risk factors for hyposalivation and xerostomia in CCS. Methods: From February 2016 until March 2020, 292 CCS were included. Data with regard to gender, age at study, diagnosis, age at diagnosis, and treatment characteristics were collected, as well as the unstimulated (UWS) and stimulated whole salivary flow rate (SWS). Xerostomia was assessed with the Xerostomia Inventory (XI) questionnaire. Multivariable Poisson regression analyses were used to evaluate the association between potential risk factors and the occurrence of hyposalivation. Results: The minimum time between diagnosis and study enrollment was 15 years. The prevalence of hyposalivation was 32% and the prevalence of xerostomia was 9.4%. Hyposalivation and xerostomia were not significantly correlated. Risk factors for hyposalivation were female gender and a higher dose of radiotherapy (>12 Gy) to the salivary gland region. Conclusion: Considering the importance of saliva for oral health, screening for hyposalivation in CCS is suggested in order to provide optimal oral supportive care aimed to improve oral health.
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