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  • 1
    In: Pediatric Blood & Cancer, Wiley, Vol. 65, No. 4 ( 2018-04)
    Abstract: Impairment of health‐related physical fitness (HRPF) in survivors of acute lymphoblastic leukemia has been shown. However, evidence of impairment in survivors of other pediatric malignancies and possible risk factors is limited. Participants and Methods HRPF of 17 survivors of pediatric acute myeloid leukemia (AML), 26 survivors of neuroblastoma (NBL), 28 survivors of Wilms tumor (WT) (median age 28.8 [18.8–62.6] years) after a median follow‐up time of 24.5 (6.5–43.6) years, and 74 healthy controls (median age 26.9 [17.9–61.7] years). Risk factors were investigated. Testing included submaximal cardiovascular endurance (6‐Minute Walk Test (6 MWT), flexibility, and muscle strength. Results Results are expressed as mean (standard error). Survivors scored significantly lower than controls on the 6 MWT (588 ± 6.1 m vs. controls 611 ± 6.0 m; P  = 0.008), on side flexion of the trunk (20.1 ± 0.4 cm vs. controls 22.4 ±0.4 cm; P   〈  0.001), and on vertical jump (39.7 ± 0.8 cm vs. controls 43.8 ± 0.8 cm; P   〈  0.001). Survivors of AML had lower scores on the 6 MWT (563 ± 12.4 m) than survivors of NBL (585 ± 9.9 m) and survivors of WT (606 ± 9.6 m), P  = 0.046. Being a survivor, higher body mass index (BMI) and no participation in sports were independently associated with lower scores on the 6 MWT. Conclusion Survivors of NBL, WT, and especially AML have impaired HRPF. Higher BMI and physical inactivity at adult age appeared prominent risk factors for impaired HRPF in these survivors.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 2
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 506-506
    Abstract: Abstract 506FN2 Introduction 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. Methods 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). Results 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). Conclusion 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. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Journal of Pediatric Hematology/Oncology, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. 7 ( 2013-10), p. 525-529
    Type of Medium: Online Resource
    ISSN: 1077-4114
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2047125-7
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  • 4
    In: Cancer Treatment Reviews, Elsevier BV, Vol. 35, No. 7 ( 2009-11), p. 616-632
    Type of Medium: Online Resource
    ISSN: 0305-7372
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 2002084-3
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  • 5
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5215-5215
    Abstract: Abstract 5215 Introduction. Currently, the 5-year survival for childhood NHL is ∼80%. Because of this high survival rate and since treatment is administered in a growing and developing individual, long-term side effects are an important issue. Studies on endocrine long-term effects in survivors of childhood non-Hodgkin lymphoma (NHL) are scarce and often limited by small sample sizes, or by the fact that data of NHL survivors have been combined with that of survivors of other malignancies. Aim of this study was to investigate the long-term endocrine effects of treatment for childhood NHL. Methods. A single centre cohort of 84 survivors (22 females) was included in this retrospective study. Median age was 21 yrs (9–40 yrs) and time after cessation of therapy 12 yrs (4–30 yrs). Height, weight, percentage fat, lean body mass (LBM), bone mineral content (BMC), bone mineral density of total body (BMDTB) and lumbar spine (BMDLS) were measured. Bone mineral apparent density of the lumbar spine (BMADLS) was calculated to correct for bone size. Thyroid stimulating hormone (TSH), free thyroxin (fT4), insulin-like growth factor-1 (IGF-1), Inhibin-B and anti-müllerian hormone (AMH) levels were measured. Results were compared with Dutch controls. Results. Height was lower in survivors at follow-up (mean SDS −0.36, P=0.002), but further analysis showed that shorter stature was already present at diagnosis (mean SDS −0.28, P=0.023). BMI, percentage fat, BMC, BMDTB, BMDLS and BMADLS were not different from controls. LBM was lower in survivors (mean SDS −0.47, P=0.008). TSH, fT4 and IGF-1 were normal in all survivors. Three out of 20 adult females had low AMH levels and 55% (23/42) of adult males had low Inhibin-B levels. Conclusion. Twelve years after cessation of therapy, survivors of NHL did not develope adiposity, osteopenia or osteoporosis or thyroid disease. Male NHL survivors seem to be at risk for infertility. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 922-923
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2065-2065
    Abstract: Abstract 2065 Background: Significant improvements in childhood cancer survival rates over recent decades have increased the importance of long-term treatment effects. Gonadal toxicity is a major complication in survivors of childhood cancer, which can especially occur in Hodgkin Lymphoma survivors, since they have been treated with alkylating agents. Inhibin B levels reflect gonadal function in men, and therefore this marker can be used to identify subgroups of childhood cancer survivors at risk for impaired gonadal function. Hitherto in male childhood cancer survivors, follow-up studies of gonadal function are lacking. Objective: To evaluate possible recovery of gonadal dysfunction over time in adult male survivors. Methods: In this retrospective study, adult male long-term childhood cancer survivors (n=201) of whom 24 (12%) were survivors of Hodgkin lymphoma were included. Serum inhibin B levels were used as a surrogate marker for gonadal function. Results: Median age at diagnosis was 6.0 years (range 0.0–17.5) and discontinuation of treatment was reached at a median age of 8.3 years (range 0.0–20.8). Inhibin B levels were first measured after a median follow-up time of 15.7 years (range 3.0–37.0). Median interval between the first (T1) and second measurement (T2) was 3.3 years (range 0.7–11.3). Median inhibin B level was 127 ng/L (range 5–366) at T1 and 156 ng/L (range 10–507) at T2. Survivors with an inhibin B level at first assessment≥105 ng/L have 50% chance to reach normal inhibin B levels, while this probability of recovery is negligible when the first inhibin B level is below 60 ng/L. The latter group consists of survivors of Hodgkin lymphoma treated with alkylating agents and survivors with an AAD score≥3. Conclusions: Our results suggest that recovery of gonadal function is possible even long after discontinuation of treatment. However, this recovery does not seem to occur in survivors who already reached critically low inhibin B levels after discontinuation of treatment, such as in survivors of a Hodgkin lymphoma treated with alkylating agents. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 20 ( 2017-07-10), p. 2288-2298
    Abstract: Childhood cancer survivors (CCSs) are at increased risk for subsequent malignant neoplasms (SMNs). We evaluated the long-term risk of SMNs in a well-characterized cohort of 5-year CCSs, with a particular focus on individual chemotherapeutic agents and solid cancer risk. Methods The Dutch Childhood Cancer Oncology Group–Long-Term Effects After Childhood Cancer cohort includes 6,165 5-year CCSs diagnosed between 1963 and 2001 in the Netherlands. SMNs were identified by linkages with the Netherlands Cancer Registry, the Dutch Pathology Registry, and medical chart review. We calculated standardized incidence ratios, excess absolute risks, and cumulative incidences. Multivariable Cox proportional hazard regression analyses were used to evaluate treatment-associated risks for breast cancer, sarcoma, and all solid cancers. Results After a median follow-up of 20.7 years (range, 5.0 to 49.8 years) since first diagnosis, 291 SMNs were ascertained in 261 CCSs (standardized incidence ratio, 5.2; 95% CI, 4.6 to 5.8; excess absolute risk, 20.3/10,000 person-years). Cumulative SMN incidence at 25 years after first diagnosis was 3.9% (95% CI, 3.4% to 4.6%) and did not change noticeably among CCSs treated in the 1990s compared with those treated earlier. We found dose-dependent doxorubicin-related increased risks of all solid cancers ( P trend 〈 .001) and breast cancer ( P trend 〈 .001). The doxorubicin-breast cancer dose response was stronger in survivors of Li-Fraumeni syndrome–associated childhood cancers (leukemia, CNS, and non-Ewing sarcoma) versus survivors of other cancers ( P difference = .008). In addition, cyclophosphamide was found to increase sarcoma risk in a dose-dependent manner ( P trend = .01). Conclusion The results strongly suggest that doxorubicin exposure in CCSs increases the risk of subsequent solid cancers and breast cancer, whereas cyclophosphamide exposure increases the risk of subsequent sarcomas. These results may inform future childhood cancer treatment protocols and SMN surveillance guidelines for CCSs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    S. Karger AG ; 2016
    In:  Neuroendocrinology Vol. 103, No. 1 ( 2016), p. 59-65
    In: Neuroendocrinology, S. Karger AG, Vol. 103, No. 1 ( 2016), p. 59-65
    Abstract: Historically, medical treatment of acromegaly has mainly been used as an adjuvant therapy after surgery. In the last decades, an increased range of medical therapy options has been available. Somatostatin analogues have become the cornerstones of medical treatment in acromegaly and are even seen as a primary treatment in a selected group of acromegaly patients. The most recent medical treatment available for acromegaly patients is pegvisomant, a growth hormone receptor antagonist. To date, it is the most effective medical treatment, but it is costly. Pegvisomant is used as monotherapy and combined with somatostatin analogues. In this article, we review clinical studies and cohorts that have documented the efficacy of pegvisomant monotherapy and combined therapy and give a concise overview of associated side effects.
    Type of Medium: Online Resource
    ISSN: 0028-3835 , 1423-0194
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
    detail.hit.zdb_id: 1483028-0
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  • 10
    In: JCSM Clinical Reports, Wiley, Vol. 6, No. 1 ( 2021-01), p. 3-10
    Abstract: Several simultaneous impairments in physical ability may be an indication of frailty in adult survivors of childhood cancer (CCS). The aim of our study was to assess the occurrence of frailty and to explore potential determinants in a selected Dutch cohort of long‐term adult CCS. Methods In this cross‐sectional study, we used data of 70 very long‐term CCS [median age 28.8 years (interquartile range: 23.9–34.6)] of acute myeloid leukaemia (AML) ( n  = 17), neuroblastoma (NBL) ( n  = 25), and Wilms' tumour (WT) ( n  = 28). Prefrailty and frailty were defined as having, respectively, 2 and ≥3 of the five following components: low relative lean body mass (by dual‐energy X‐ray absorptiometry less than −1.5 standard deviation, SD), self‐reported exhaustion (fatigue, exhaustion, or exertion related complaints), low energy expenditure (men: 〈 383 kcal/week, and women: 〈 270 kcal/week), slow walking speed (less than −2.0 SD on the 6‐min walk test), and weakness (hand grip strength less than −2.0 SD). Potential determinants of prefrailty and frailty (≥2 components), including treatment components, sociodemographic, and lifestyle factors, were evaluated using logistic regression analysis. Results Respectively, 6.3% and 28.1% women and 5.3% and 26.3% men were classified as frail and prefrail. Six per cent of the AML, 8% of the NBL, and 3.6% of the WT CCS were frail. Forty‐one per cent of the AML, 28% of the NBL, and 17.9% of the WT CCS were prefrail. No significant associations were found between any of the investigated determinants and frailty or prefrailty. Conclusion Our results confirm previous reports that CCS, in particular intensively treated, have a potential risk of (pre)frailty.
    Type of Medium: Online Resource
    ISSN: 2521-3555 , 2521-3555
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 3009848-8
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