Because little is known about long-term treatment-related nephrotoxicity, the aim was to determine risk factors for renal impairment long after childhood cancer treatment.
Data from 763 adult ...childhood cancer survivors (414 men) were obtained during regular visits at the late-effects clinic between 2003 and 2009. Median follow-up time was 18.3 years (range=5.0-58.2). Glomerular function was assessed by estimated GFR (using the Modification of Diet in Renal Disease formula), urinary albumin creatinine ratio, and tubular function by urinary β2-microglobulin creatinine ratio. The association with treatment factors was analyzed with covariance analysis for estimated GFR and logistic regression for urinary albumin and urinary β2-microglobulin creatinine ratios.
Survivors treated with nephrectomy and abdominal irradiation had significantly lower estimated GFR than survivors not treated with nephrectomy/abdominal irradiation (estimated mean=90 ml/min per 1.73 m(2) versus 106, P<0.001). Estimated GFR was significantly lower in survivors after treatment with high-dose ifosfamide (88 versus 98, P=0.02) and high-dose cisplatin (83 versus 101, P=0.004) compared with survivors not treated with these regimen. Nephrectomy combined with abdominal radiotherapy (odds ratio=3.14, 95% confidence interval=1.02; 9.69) and high-dose cisplatin (odds ratio=5.19, 95% confidence interval=1.21; 22.21) was associated with albuminuria. High-dose ifosfamide (odds ratio=6.19, 95% confidence interval=2.45; 15.67) was associated with increased urinary β2-microglobulin creatinine ratio. Hypertension was present in 23.4% of survivors and 31.4% of renal tumor survivors.
Treatment with unilateral nephrectomy, abdominal radiotherapy, cisplatin, and ifosfamide was associated with lower estimated GFR. Persisting tubular damage was related to ifosfamide treatment.
Obesity, represented by high body mass index (BMI), is a major complication after treatment for childhood cancer. However, it has been shown that high total fat percentage and low lean body mass are ...more reliable predictors of cardiovascular morbidity. In this study longitudinal changes of BMI and body composition, as well as the value of BMI and waist-hip ratio representing obesity, were evaluated in adult childhood cancer survivors.
Data from 410 survivors who had visited the late effects clinic twice were analyzed. Median follow-up time was 16 years (interquartile range 11-21) and time between visits was 3.2 years (2.9-3.6). BMI was measured and body composition was assessed by dual X-ray absorptiometry (DXA, Lunar Prodigy; available twice in 182 survivors). Data were compared with healthy Dutch references and calculated as standard deviation scores (SDS). BMI, waist-hip ratio and total fat percentage were evaluated cross-sectionally in 422 survivors, in who at least one DXA scan was assessed.
BMI was significantly higher in women, without significant change over time. In men BMI changed significantly with time (ΔSDS = 0.19, P<0.001). Percentage fat was significantly higher than references in all survivors, with the highest SDS after cranial radiotherapy (CRT) (mean SDS 1.73 in men, 1.48 in women, P<0.001). Only in men, increase in total fat percentage was significantly higher than references (ΔSDS = 0.22, P<0.001). Using total fat percentage as the gold standard, 65% of female and 42% of male survivors were misclassified as non-obese using BMI. Misclassification of obesity using waist-hip ratio was 40% in women and 24% in men.
Sixteen years after treatment for childhood cancer, the increase in BMI and total fat percentage was significantly greater than expected, especially after CRT. This is important as we could show that obesity was grossly underestimated using BMI and waist-hip ratio.
Abstract This study focuses on the effect of chemotherapy on endocrinopathies and the metabolic syndrome in adult survivors of childhood acute myeloid leukemia (AML). Endocrine function and metabolic ...syndrome were evaluated in 12 AML survivors, treated with chemotherapy, and in 9 survivors of myeloid leukemias treated with stem cell transplantation (SCT), after a median follow-up time of 20 years (range 9–31). In survivors treated with chemotherapy, no endocrinopathies or metabolic syndrome were present, although AMH and Inhibin B levels tended to be lower than in controls. In SCT survivors, pituitary deficiencies and metabolic syndrome were more frequent.
Extracorporeal membrane oxygenation is a supportive cardiopulmonary bypass technique for patients with acute reversible cardiovascular or respiratory failure. Favourable effects of haemofiltration ...during cardiopulmonary bypass instigated the use of this technique in infants on extracorporeal membrane oxygenation. The current study aimed at comparing clinical outcomes of newborns on extracorporeal membrane oxygenation with and without continuous haemofiltration.
Demographic data of newborns treated with haemofiltration during extracorporeal membrane oxygenation were compared with those of patients treated without haemofiltration in a retrospective 1:3 case-comparison study. Primary outcome parameters were time on extracorporeal membrane oxygenation, time until extubation after decannulation, mortality and potential cost reduction. Secondary outcome parameters were total and mean fluid balance, urine output in mL/kg/day, dose of vasopressors, blood products and fluid bolus infusions, serum creatinin, urea and albumin levels.
Fifteen patients with haemofiltration (HF group) were compared with 46 patients without haemofiltration (control group). Time on extracorporeal membrane oxygenation was significantly shorter in the HF group: 98 hours (interquartile range (IQR) = 48 to 187 hours) versus 126 hours (IQR = 24 to 403 hours) in the control group (P = 0.02). Time from decannulation until extubation was shorter as well: 2.5 days (IQR = 0 to 6.4 days) versus 4.8 days (IQR = 0 to 121.5 days; P = 0.04). The calculated cost reduction was euro5000 per extracorporeal membrane oxygenation run. There were no significant differences in mortality. Patients in the HF group needed fewer blood transfusions: 0.9 mL/kg/day (IQR = 0.2 to 2.7 mL/kg/day) versus 1.8 mL/kg/day (IQR = 0.8 to 2.9 mL/kg/day) in the control group (P< 0.001). Consequently the number of blood units used was significantly lower in the HF group (P< 0.001). There was no significant difference in inotropic support or other fluid resuscitation.
Adding continuous haemofiltration to the extracorporeal membrane oxygenation circuit in newborns improves outcome by significantly reducing time on extracorporeal membrane oxygenation and on mechanical ventilation, because of better fluid management and a possible reduction of capillary leakage syndrome. Fewer blood transfusions are needed. All in all, overall costs per extracorporeal membrane oxygenation run will be lower.
Fatigue, slowness, apathy and decrease in level of activity are common long-term complaints after a subarachnoid haemorrhage (SAH). They resemble the symptoms frequently found in patients with ...endocrine dysfunction. Pituitary dysfunction may be the result of SAH or its complications. We therefore hypothesized that it may explain some of the long-term complaints after SAH. We reviewed the literature to clarify the occurrence, pattern and severity of endocrine abnormalities and we attempted to identify risk factors for hypopituitarism after SAH. We also assessed the effect of hypopituitarism on long-term functional recovery after SAH.
In a MEDLINE search for studies published between 1995 and 2014, we used the term subarachnoid haemorrhage in combination with pituitary, hypopituitarism, growth hormone, gonadotropin, testosterone, cortisol function, thyroid function and diabetes insipidus. We selected all case-series and cohort studies reporting endocrine function at least 3 months after SAH and studied their reported prevalence, pathogenesis, risk factors, clinical course and outcome.
We identified 16 studies describing pituitary function in the long term after SAH. The reported prevalence of endocrine dysfunction varied from 0 to 55% and the affected pituitary axes differed between studies. Due to methodological issues no inferences on risk factors, course and outcome could be made.
Neuroendocrine dysfunction may be an important and modifiable determinant of poor functional outcome after SAH. There is an urgent need for well-designed prospective studies to more precisely assess its incidence, clinical course and effect on mood, behaviour and quality of life.
Abstract 4228
Survival of childhood acute myeloid leukemia (AML) has increased significantly over the past decades. Improved treatment strategies include intensive chemotherapy, by which stem cell ...transplantation (SCT) has been replaced in most of the current protocols for more than 80% of the cases. Limited data exist on endocrine late effects in AML survivors treated with chemotherapy only. The current study focuses on the effect of chemotherapy only on endocrine function and components of the metabolic syndrome (MetS) in adult survivors of childhood AML.
In this prospective study with a cross-sectionally recruited controlgroup, endocrine function and components of the MetS were assessed in 12 AML survivors (3 females), treated with chemotherapy only, and in 9 survivors of myeloid leukemias treated with SCT, including TBI as conditioning regimen, after a median follow up time of 20 years (range 9–31). Data were compared with those of 60 controls (23 females).
In survivors treated with chemotherapy only no endocrinopathies were observed, although AMH and Inhibin B levels tended to be lower than in controls. In chemo-only survivors, frequency of the components of the MetS was not different from controls. In transplanted AML survivors one subject was growth hormone deficient, five had thyroid dysfunction and all survivors had gonadal dysfunction. SCT survivors had a higher risk for components of the MetS, especially a significantly higher frequency of dyslipidemia than controls (63% vs. 6%, P<0.001).
At twenty years of follow up, survivors of AML treated with chemotherapy only did not show an increased risk at most endocrinopathies and metabolic syndrome as compared to healthy controls, which is in contrast to childhood AML survivors treated with SCT. Gonadal function should however be evaluated with care. Display omitted SCT: stem cell transplantation; Display omitted SCT: stem cell transplantation
No relevant conflicts of interest to declare.
Purpose: Osteopenia is a potential complication of childhood cancer treatment, but the magnitude of this problem in survivors is unknown. We examined (determinants of) bone mineral density (BMD) ...status in long-term survivors of adult childhood cancer (CCS).
Methods: This retrospective single-center cohort study included 346 subjects with the most common types of childhood cancer. Acute leukemia or lymphoma was diagnosed in 273 (81%) of the patients. All subjects had a median age at diagnosis of 7.0 years (range: 0.1-16.8 years) and a median follow-up time of 16.7 years (range 5.6-39.9 years). Total body BMD (BMDTB) and BMD of the lumbar spine (BMDLS) were measured by dual-X-ray absorptiometry. Osteopenia was defined as BMD standardized deviation score (SDS) below -1. Twelve candidate single nucleotide polymorphisms (SNPs) in 11 genes (COL1A1, TNFSF11, TNFRSF11, TNRFSA11B, VDR, ESR1,WLS, LRP5, MTHFR, MTRR, IL6) were investigated.
Results: Survivors had a lower BMDTB and BMDLS (mean SDS: -0.55, p<0.001; and -0.30, p<0.001, respectively) as compared to healthy peers. This was similar in cancer survivors of leukemia and lymphoma (mean SDS: -0.49, p<0.001; and -0.32, p<0.001, respectively). Osteopenia (BMDTB and/or BMDLS) was present in 45% of the survivors (46% of the leukemia and lymphoma survivors). Multivariate logistic regression analyses identified age at diagnosis <12 years, age >30 years at follow-up, male gender, underweight at follow-up, carriers of the minor allele of rs2504063 (LRP5), treatment with cranial-spinal radiotherapy and prednisone as independent prognostic factors for osteopenia. In survivors of leukemia and lymphoma, we identified low BMI at follow-up, carriers the minor allele of rs2504063 (LRP5), treatment with cranial-spinal radiotherapy and cyclophosphamide use as prognostic factors for osteopenia.
Conclusions: This large cohort of childhood cancer survivors with the long follow-up identified osteopenia in 45% of CCS. This indicates that greater awareness for low BMD is warranted, especially in survivors who are older than 30 years, male, have underweight, have a genetic predisposition, and who were treated with cranial-spinal radiotherapy and/or steroids.
No relevant conflicts of interest to declare.
Abstract Background Genetic variation that regulates insulin resistance, blood pressure and adiposity in the normal population might determine differential vulnerability for metabolic syndrome after ...treatment for childhood cancer. Objective To evaluate the contribution of candidate single nucleotide polymorphisms (SNPs) relevant for metabolic syndrome in our single centre cohort of adult long-term childhood cancer survivors. Methods In this retrospective study 532 survivors were analysed. Median age at diagnosis was 5.7 years (range 0.0–17.8 years), median follow-up time was 17.9 years (range 5.0–48.8) and median age at follow-up was 25.6 years (range 18.0–50.8). JAZF1 gene rs864745, THADA gene rs7578597, IRS1 gene rs2943641, TFAP2B gene rs987237, MSRA gene rs7826222, ATP2B1 gene rs2681472 and rs2681492 were genotyped. The association of genotypes with total cholesterol levels, blood pressure, body mass index, waist circumference and frequency of diabetes were assessed. Results Metabolic syndrome was more frequent in cranially (23.3%, P = 0.002) and abdominally (23.4%, P = 0.009) irradiated survivors as compared with non-irradiated survivors (10.0%). Association of allelic variants in rs2681472 and rs2681492 with hypertension, rs987237 and rs7826222 with waist circumference and rs864745, rs7578597 and rs2943641 with diabetes were not significant. None of the SNPs was associated with the metabolic syndrome. Adjusting for age, sex, follow-up time, cranial irradiation and abdominal irradiation did not change these results. Conclusions Treatment factors and not genetic variation determine hypertension, waist circumference, diabetes and metabolic syndrome in adult long-term survivors of childhood cancer.
Abstract 506▪FN2▪This icon denotes a clinically relevant abstract
Over the last decades childhood cancer survival rates have improved significantly. Currently, 70–80% of patients become long term ...cancer survivors. It has been estimated that 1 out of 640 young adults in the U.S. is a survivor of childhood cancer. Consequently, the incidence of late, treatment-related complications is increasing. Endocrine sequelae, such as the metabolic syndrome, osteopenia, sub fertility, thyroid dysfunction and growth hormone deficiency represent an important category of such late effects. Growth hormone deficiency (GHD) in childhood cancer survivors, mainly caused by cranial radiotherapy, is reflected by low levels of insulin like growth factor 1 (IGF-I). Whereas the value of IGF-I measurement for the diagnosis of GHD is controversial, low IGF-I levels are associated with high body mass index and high visceral fat percentage. However the clinical relevance of low IGF-I levels in long term childhood cancer survivors is not extensively studied. In this study we evaluated whether IGF-I is useful as a marker for altered body composition and growth hormone deficiency in this group.
We retrospectively analyzed data of 610 adult childhood cancer survivors, retrieved from the Rotterdam late effects clinic, which starts 5 years after cessation of therapy. Median age at diagnosis was 6 years (interquartile range (IQR) 3–11) and follow up time was 18 years (13–24). We assessed IGF-I Z-scores, anthropometrical measures, growth hormone stimulation tests in patients with clinical suspicion of GHD and measures of body composition (assessed by dual X-ray absorptiometry, Lunar Prodigy).
Cranial irradiated acute leukaemia survivors (25 Gy (24–25)) and locally irradiated brain tumour survivors (42 Gy (35–54)) had significantly lower IGF-I Z-scores (p<0.001), lower height SDS (p<0.001), higher body mass index (p=0.01), higher waist-hip ratio (p=0.001), higher visceral fat percentage (p<0.001), higher total fat percentage (p<0.001) and lower lean body mass (p<0.001), compared to non cranial irradiated survivors. IGF-I did not show a strong correlation with BMI (r=-0.12, p=0.04), waist hip ratio (r=-0.15, p=0.01), total fat percentage (r=-0.14, p=0.02) and lean body mass (r=0.15, p=0.01). In the patients with low IGF-I levels who had growth hormone stimulation, IGF-I Z-scores did not significantly differ between the patients with and without severe GHD (p = 0.39).
This study shows that there is a limited value of IGF-I as marker for alterations in body composition, and confirms the fact that low IGF-I levels are not predictive for GHD, in a large cohort of childhood cancer survivors. Therefore the use of IGF-I should not be encouraged in adult childhood cancer survivors.
No relevant conflicts of interest to declare.
Objective
Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim ...was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment.
Methods
Three hundred fifty‐one male CCS were included. Median age at diagnosis was 5.9 years (0‐17.8) and median age at follow‐up 25.6 years (18.0‐45.8). Total and non‐SHBG‐bound testosterone, sex hormone‐binding globulin, inhibin B, and follicle‐stimulating hormone (FSH) were studied. Potential determinants were BMI, waist circumference, waist–hip ratio, and body composition measures (dual energy X‐ray absorptiometry).
Results
Non‐SHBG‐bound testosterone was significantly decreased in survivors with BMI ≥ 30 kg/m2 (adjusted mean 9.1 nmol/L vs. 10.2 nmol/L, P = 0.015), high fat percentage (10.0 vs. 11.2, P = 0.004), and high waist circumference (>102 cm) (9.0 vs. 11.0, P = 0.020). Survivors with high fat percentage (≥25%) had significantly lower inhibin B/FSH ratios (inhibin B/FSH ratio: β −34%, P = 0.041).
Conclusion
Obesity is associated with gonadal dysfunction in male CCS, independent of the irreversible effect of previous cancer treatment. Randomized controlled trials are required to evaluate whether weight normalization could improve gonadal function, especially in obese survivors with potential other mechanisms than lifestyle causing their obesity.
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