Publications by authors named "Cecilia Follin"

23 Publications

  • Page 1 of 1

Cognitive interference processing in adult survivors of childhood acute lymphoblastic leukemia using functional magnetic resonance imaging.

Acta Oncol 2021 Oct 12:1-8. Epub 2021 Oct 12.

Department of Oncology, Skåne University Hospital, Lund, Sweden.

Background: Childhood acute lymphoblastic leukemia (ALL) is associated with cognitive impairment in adulthood. Cognitive interference processing and its correlated functional magnetic resonance imaging (fMRI) activity in the brain have not yet been studied in this patient group.

Material: Twenty-six adult childhood ALL survivors (median [interquartile range {IQR}] age, 40.0 [37.0-42.3] years) were investigated at median age (IQR), 35.0 (32.0-37.0) years after treatment with intrathecal and intravenous chemotherapy as well as cranial radiotherapy (24 Gy) and compared with 26 matched controls (median [IQR] age, 37.5 [33.0-41.5] years).

Methods: Cognitive interference processing was investigated in terms of behavioral performance (response times [ms] and accuracy performance [%]) and fMRI activity in the cingulo-fronto-parietal (CFP) attention network as well as other parts of the brain using the multisource interference task (MSIT).

Results: ALL survivors had longer response times and reduced accuracy performance during cognitive interference processing (median [IQR] interference effect, 371.9 [314.7-453.3] ms and 6.7 [4.2-14.7]%, respectively) comparedwith controls (303.7 [275.0-376.7] ms and 2.3 [1.6-4.3]%, respectively), but did not exhibit altered fMRI activity in the CFP attention network or elsewhere in the brain.

Conclusion: Adult childhood ALL survivors demonstrated impaired behavioral performance but no altered fMRI activity when performing cognitive interference processing when compared with controls. The results can be used to better characterize this patient group and to optimize follow-up care and support for these individuals.
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http://dx.doi.org/10.1080/0284186X.2021.1987514DOI Listing
October 2021

European PanCareFollowUp Recommendations for surveillance of late effects of childhood, adolescent, and young adult cancer.

Eur J Cancer 2021 Sep 29;154:316-328. Epub 2021 Jul 29.

Princess Máxima Centre for Paediatric Oncology, Heidelberglaan 25, Utrecht, 3584 CS, the Netherlands.

Background: Long-term follow-up (LTFU) care for childhood, adolescent, and young adult (CAYA) cancer survivors is essential to preserve health and quality of life (QoL). Evidence-based guidelines are needed to inform optimal surveillance strategies, but many topics are yet to be addressed by the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG). Therefore, the PanCareFollowUp Recommendations Working Group collaborated with stakeholders to develop European harmonised recommendations in anticipation of evidence-based IGHG guidelines.

Methods: The PanCareFollowUp Recommendations Working Group, consisting of 23 late effects specialists, researchers, and survivor representatives from nine countries, collaborated in the first Europe-wide effort to provide unified recommendations in anticipation of evidence-based guidelines. A pragmatic methodology was used to define recommendations for topics where no evidence-based IGHG recommendations exist. The objective was to describe the surveillance requirements for high-quality care while balancing the different infrastructures and resources across European health care systems. The process included two face-to-face meetings and an external consultation round involving 18 experts from 14 countries.

Results: Twenty-five harmonised recommendations for LTFU care were developed collaboratively and address topics requiring awareness only (n = 6), awareness, history and/or physical examination (n = 9), or additional surveillance tests (n = 10).

Conclusions: The PanCareFollowUp Recommendations, representing a unique agreement across European stakeholders, emphasise awareness among survivors and health care providers in addition to tailored clinical evaluation and/or surveillance tests. They include existing IGHG guidelines and additional recommendations developed by a pragmatic methodology and will be used in the Horizon 2020-funded PanCareFollowUp project to improve health and QoL of CAYA cancer survivors.
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http://dx.doi.org/10.1016/j.ejca.2021.06.004DOI Listing
September 2021

Cognitive interference processing in adults with childhood craniopharyngioma using functional magnetic resonance imaging.

Endocrine 2021 Jul 22. Epub 2021 Jul 22.

Department of Endocrinology, Skåne University Hospital, Lund, Sweden.

Purpose: To assess cognitive interference processing in adults with childhood craniopharyngioma (CP), with and without hypothalamic injury, respectively, in terms of behavioral performance and functional magnetic resonance imaging (fMRI) activity, using the multi-source interference task (MSIT).

Methods: Twenty-eight CP patients (median age 34.5 [29.0-39.5] years) were investigated at median 20.5 (16.3-28.8) years after treatment with surgical resection and in some cases additional radiotherapy (n = 10) and compared to 29 matched controls (median age 37.0 [32.5-42.0] years). The subjects performed the MSIT during fMRI acquisition and behavioral performance in terms of response times (ms) and accuracy performance (%) were recorded.

Results: The MSIT activated the cingulo-fronto-parietal (CFP) attention network in both CP patients and controls. No differences were found in behavioral performance nor fMRI activity between CP patients (interference effect 333.9 [287.3-367.1] ms and 3.1 [1.6-5.6]%, respectively) and controls (309.1 [276.4-361.0] ms and 2.6 [1.6-4.9]%). No differences were found in behavioral performance nor fMRI activity between the two subgroups with (332.0 [283.6-353.4] ms and 4.2 [2.3-5.7]%, respectively) and without hypothalamic injury (355.7 [293.7-388.7] ms and 2.1 [1.0-5.2]%, respectively), respectively, and controls.

Conclusion: Adults with childhood CP performed cognitive interference processing equally well as controls and demonstrated no compensatory fMRI activity in the CFP attention network compared to controls. This was also true for the two subgroups with and without hypothalamic injury. The results can be useful to better characterize this condition, and to optimize treatment and support for these individuals.
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http://dx.doi.org/10.1007/s12020-021-02824-9DOI Listing
July 2021

The European multistakeholder PanCareFollowUp project: novel, person-centred survivorship care to improve care quality, effectiveness, cost-effectiveness and accessibility for cancer survivors and caregivers.

Eur J Cancer 2021 Aug 18;153:74-85. Epub 2021 Jun 18.

Princess Máxima Centre for Paediatric Oncology, Heidelberglaan 25, Utrecht, 3584 CS, the Netherlands.

Background: The majority of childhood cancer survivors are at risk of treatment-related adverse health outcomes. Survivorship care to mitigate these late effects is endorsed, but it is not available for many adult survivors of childhood cancer in Europe. The PanCareFollowUp project was initiated to improve their health and quality of life (QoL) by facilitating person-centred survivorship care.

Methods: The PanCareFollowUp consortium was established in 2018, consisting of 14 project partners from ten European countries, including survivor representatives. The consortium will develop two PanCareFollowUp Interventions, including a person-centred guideline-based model of care (Care Intervention) and eHealth lifestyle coaching (Lifestyle Intervention). Their development will be informed by several qualitative studies and systematic reviews on barriers and facilitators for implementation and needs and preferences of healthcare providers (HCPs) and survivors. Implementation of the PanCareFollowUp Care Intervention as usual care will be evaluated prospectively among 800 survivors from Belgium, Czech Republic, Italy and Sweden for survivor empowerment, detection of adverse health conditions, satisfaction among survivors and HCPs, cost-effectiveness and feasibility. The feasibility of the PanCareFollowUp Lifestyle Intervention will be evaluated in the Netherlands among 60 survivors.

Results: Replication manuals, allowing for replication of the PanCareFollowUp Care and Lifestyle Intervention, will be published and made freely available after the project. Moreover, results of the corresponding studies are expected within the next five years.

Conclusions: The PanCareFollowUp project is a novel European collaboration aiming to improve the health and QoL of all survivors across Europe by developing and prospectively evaluating the person-centred PanCareFollowUp Care and Lifestyle Interventions.
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http://dx.doi.org/10.1016/j.ejca.2021.05.030DOI Listing
August 2021

Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis.

Pituitary 2021 Oct 25;24(5):797-809. Epub 2021 May 25.

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.

Purpose: Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development.

Data Sources: Systematic literature search in four databases.

Study Selection: Observational studies reporting the prevalence of NS after BA in adult patients with CD.

Data Extraction: Data extraction and risk of bias assessment were performed by three independent investigators.

Data Synthesis: Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)].

Conclusions: Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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http://dx.doi.org/10.1007/s11102-021-01158-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416875PMC
October 2021

Mixed methods assessment of impact on health awareness in adult childhood cancer survivors after viewing their personalized digital treatment summary and follow-up recommendations.

BMC Cancer 2021 Apr 1;21(1):347. Epub 2021 Apr 1.

Department of Clinical Sciences Lund, Oncology, Skane University Hospital, Lund University, Lund, Sweden.

Background: The survival rate after childhood cancer has improved to 80%. The majority of childhood cancer survivors (CCS) will experience late complications which require follow up care, including access to their individual cancer treatment summary. The need to understand CCS needs and preferences in terms of ways to receive information e.g. digitally, becomes important. This study aims to through a mixed methods approach a) examine how CCS' health awareness was impacted by viewing their personalized digital treatment summary and follow-up recommendations, b) explore E health literacy, and c) determine self-reported survivorship experiences and health care usage.

Methods: Survivors with a recent visit to the Late effects clinic were eligible for the study (n = 70). A representative sample of primary diagnoses were invited (n = 28). 16 CCS were enrolled. Recent medical visits, e health literacy and impressions of the digital treatment summary were assessed by a survey in conjunction with viewing their digital treatment summary on a computer screen. Their experience of reading and understanding their digital treatment summary in the context of their health related survivorship experiences were assessed in focus groups. The transcribed data was analyzed with conventional qualitative content analysis.

Results: The self-reported medical problems largely reflected that, only 6,3% reported no cancer-related reasons for seeking medical attention. Of the medical specialists, the primary care physician was the most frequently visited specialist (68.8%). High E health literacy was not associated with treatment features but with educational level (p = 0.003, CI: 3.9-14.6) and sex (p = 0.022, CI: - 13.6- -1.3). All survivors graded the digital treatment summary above average in terms of being valuable, agreeable and comprehensive. The focus group interviews identified three themes: 1) The significance of information, 2) The impact of awareness; and 3) Empowerment.

Conclusions: Reading the treatment summaries furthered the survivors understanding of their health situation and consequently aided empowerment. A digital treatment summary, provided by knowledgeable health care professionals, may increase the self-managed care and adherence to follow-up recommendations. Further insights into e health literacy in larger samples of CCS may determine to what extent health-related information can be communicated via digital resources to this at risk population.
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http://dx.doi.org/10.1186/s12885-021-08051-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017604PMC
April 2021

Brain white matter lesions are associated with reduced hypothalamic volume and cranial radiotherapy in childhood-onset craniopharyngioma.

Clin Endocrinol (Oxf) 2021 01 17;94(1):48-57. Epub 2020 Nov 17.

Department of Endocrinology, Skåne University Hospital, Malmö, Sweden.

Context: White matter lesions (WML) are caused by obstruction of small cerebral vessels associated with stroke risk. Craniopharyngioma (CP) patients suffer from increased cerebrovascular mortality.

Objective: To investigate the effect of reduced HT volume and cranial radiotherapy (CRT) on WML in childhood-onset CP patients.

Design: A cross-sectional study of 41 patients (24 women) surgically treated childhood-onset CP in comparison to controls.

Setting: The South Medical Region of Sweden (2.5 million inhabitants).

Methods: With magnetic resonance imaging (MRI), we analysed qualitative measurement of WML based on the visual rating scale of Fazekas and quantitative automated segmentation of WML lesion. Also, measurement HT volume and of cardiovascular risk factors were analysed.

Results: Patients had a significant increase in WML volume (mL) (P = .001) compared to controls. Treatment with cranial radiotherapy (CRT) vs no CRT was associated with increased WML volume (P = .02) as well as higher Fazekas score (P = .001). WML volume increased with years after CRT (r = 0.39; P = .02), even after adjustment for fat mass and age. A reduced HT volume was associated with increased WML volume (r = -0.61, P < .001) and explained 26% of the variation (r  = 0.26). Altogether, 47% of the WML volume was explained by age at investigation, HT volume and CRT. Patients with more WML also had higher cardiovascular risk.

Conclusions: CRT may be associated directly with increased WML volume or indirectly with reduced HT volume associated with higher cardiovascular risk. Risk factors should be carefully monitored in these patients.
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http://dx.doi.org/10.1111/cen.14307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839677PMC
January 2021

Excess Morbidity Persists in Patients With Cushing's Disease During Long-term Remission: A Swedish Nationwide Study.

J Clin Endocrinol Metab 2020 08;105(8)

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.

Objective: To investigate comorbidities in patients with CD.

Design, Setting, And Patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.

Main Outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.

Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.

Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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http://dx.doi.org/10.1210/clinem/dgaa291DOI Listing
August 2020

The incidence of Cushing's disease: a nationwide Swedish study.

Pituitary 2019 Apr;22(2):179-186

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, and The Department of Endocrinology, Sahlgrenska University Hospital, Gröna Stråket 8, 413 45, Gothenburg, Sweden.

Background: Studies on the incidence of Cushing's disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.

Methods: Patients registered with a diagnostic code for Cushing's syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.

Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4-1.8) cases per million. 1987-1995, 1996-2004, and 2005-2013, the mean annual incidence was 1.5 (1.1-1.8), 1.4 (1.0-1.7) and 2.0 (1.7-2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).

Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987-2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
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http://dx.doi.org/10.1007/s11102-019-00951-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418061PMC
April 2019

Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy - a diffusional kurtosis study.

Acta Oncol 2019 Jul 12;58(7):1021-1028. Epub 2019 Feb 12.

e Department of Endocrinology , Skåne University hospital , Lund , Sweden.

Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Thirty-eight (21 women) ALL survivors, median age 38 (27-46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention ( < .001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all  < .05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum ( < .05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory ( = -0.40,  < .04). The left and right uncinate fasciculus ( = 0.6,  < .001), ( = -0.5,  < .02) as well as the right ventral cingulum ( = 0.5,  < .007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus ( = 0.3,  = 0.05,  = .02), and ventral cingulum ( = 0.3,  = .02) were associated with impaired results of episodic visual memory. ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.
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http://dx.doi.org/10.1080/0284186X.2019.1571279DOI Listing
July 2019

Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study.

J Clin Endocrinol Metab 2019 06;104(6):2375-2384

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.

Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable.

Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD.

Design, Patients, And Methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality.

Results: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome.

Conclusion: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
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http://dx.doi.org/10.1210/jc.2018-02524DOI Listing
June 2019

Hypothalamic-Pituitary and Growth Disorders in Survivors of Childhood Cancer: An Endocrine Society Clinical Practice Guideline.

J Clin Endocrinol Metab 2018 08;103(8):2761-2784

Mayo Clinic Evidence-Based Practice Center, Rochester, Minnesota.

Objective: To formulate clinical practice guidelines for the endocrine treatment of hypothalamic-pituitary and growth disorders in survivors of childhood cancer.

Participants: An Endocrine Society-appointed guideline writing committee of six medical experts and a methodologist.

Conclusions: Due to remarkable improvements in childhood cancer treatment and supportive care during the past several decades, 5-year survival rates for childhood cancer currently are >80%. However, by virtue of their disease and its treatments, childhood cancer survivors are at increased risk for a wide range of serious health conditions, including disorders of the endocrine system. Recent data indicate that 40% to 50% of survivors will develop an endocrine disorder during their lifetime. Risk factors for endocrine complications include both host (e.g., age, sex) and treatment factors (e.g., radiation). Radiation exposure to key endocrine organs (e.g., hypothalamus, pituitary, thyroid, and gonads) places cancer survivors at the highest risk of developing an endocrine abnormality over time; these endocrinopathies can develop decades following cancer treatment, underscoring the importance of lifelong surveillance. The following guideline addresses the diagnosis and treatment of hypothalamic-pituitary and growth disorders commonly encountered in childhood cancer survivors.
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http://dx.doi.org/10.1210/jc.2018-01175DOI Listing
August 2018

Microstructure alterations in the hypothalamus in cranially radiated childhood leukaemia survivors but not in craniopharyngioma patients unaffected by hypothalamic damage.

Clin Endocrinol (Oxf) 2017 Oct 19;87(4):359-366. Epub 2017 Jun 19.

Department of Endocrinology, Skåne University Hospital, Lund, Sweden.

Objective: Metabolic complications are frequent in childhood leukaemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors.

Design: Case-control study.

Patients: Three groups were included: (i) 27 CRT treated ALL survivors on hormone supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without HT involvement and (iii) 27 matched controls.

Measurements: DTI parameters of the HT were measured and body composition.

Results: Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥25 than with BMI <25. Compared to controls, ALL survivors had reduced FA (P=.04), increased MD (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT, ALL survivors with a BMI ≥25 showed elevated MD (P=.03) and AD (P=.02) compared to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between CP survivors and controls.

Conclusions: Long-term follow-up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT.
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http://dx.doi.org/10.1111/cen.13373DOI Listing
October 2017

Childhood leukaemia survivors' experiences of long-term follow-ups in an endocrine clinic - A focus-group study.

Eur J Oncol Nurs 2017 Feb 19;26:19-26. Epub 2016 Nov 19.

Department of Endocrinology, Skåne University Hospital, Institution of Clinical Sciences, Lund, Sweden. Electronic address:

The survival rate after childhood cancer has improved markedly and today more than 80% of patients will survive. Many childhood cancer survivors suffer from late complications due to radiotherapy and chemotherapy. Survivors of Acute Lymphoblastic Leukaemia (ALL), treated with cranial radiotherapy, are at a particularly high risk of having endocrine complications.

Purpose: To illuminate childhood ALL survivors' experiences of a long-term follow-up in an endocrine clinic.

Method: Data collection carried out using semi-structured focus-group interviews. Fifteen ALL survivors were included in the study, divided into 4 groups. Data was analysed with conventional qualitative content analysis.

Results: The survivors' experiences were captured in the theme: "The need for understanding and support in order to manage daily life". An understanding of their situation, as well as support for managing daily life was fundamental. Lack of understanding and support from the community was connected with a fear for the future. The follow-up at the endocrine clinic was shown to be crucial for increasing the survivors' understanding of late complications. The past feeling of being out of control was replaced with an increased self-confidence.

Conclusion: Many leukaemia survivors experienced their daily lives as a struggle and as a complicated issue to cope with. The theme "understanding and support to manage daily life" mirrors how the survivors are in need of knowledge and support in order to handle and understand their complex situation after surviving leukaemia. Offering understanding and support with a holistic approach, may be a way in which to strengthen the survivors' health.
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http://dx.doi.org/10.1016/j.ejon.2016.10.006DOI Listing
February 2017

Impaired brain metabolism and neurocognitive function in childhood leukemia survivors despite complete hormone supplementation in adulthood.

Psychoneuroendocrinology 2016 11 1;73:157-165. Epub 2016 Aug 1.

Department of Diagnostic Radiology, Skåne University Hospital and Clinical Sciences, Lund University, Sweden; Lund University Bioimaging Centre (LBIC), Lund University, Sweden.

Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27-46) years. All were treated with a CRT dose of 24Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p<0.001), memory (p<0.001), learning capacity (p<0.001), spatial ability (p<0.001), executive functions and attention (p<0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536cm, p<0.001) and grey matter (GM) volumes (525 vs 555cm, p=0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p=0.004), WM NAA+NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p<0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p=0.001) and GM NAA+NAAG/Cr (1.28 vs 1.34, p=0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p=0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA+NAAG/Cr (r=-0.4, p=0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group.
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http://dx.doi.org/10.1016/j.psyneuen.2016.07.222DOI Listing
November 2016

Long-Term Effect of Cranial Radiotherapy on Pituitary-Hypothalamus Area in Childhood Acute Lymphoblastic Leukemia Survivors.

Curr Treat Options Oncol 2016 09;17(9):50

Department of Endocrinology, Skåne University hospital and IKVL, Lund University, Lund, Sweden.

Opinion Statement: Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT <50 Gy, the primary site of radiation damage is the hypothalamus and this usually causes isolated GH deficiency (GHD). Higher doses (>50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70-80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.
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http://dx.doi.org/10.1007/s11864-016-0426-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967419PMC
September 2016

Attitudes and preferences in patients with acromegaly on long-term treatment with somatostatin analogues.

Endocr Connect 2016 Jul 25;5(4):167-73. Epub 2016 Jul 25.

Department of EndocrinologySkåne University Hospital, Lund, Sweden.

Introduction: Patients with acromegaly can be treated with surgery, medical therapy and/or radiation therapy. For the patients not being cured with surgery, treatment with somatostatin analogues (SSAs) is the primary therapy. SSA can be taken by self- or partner-administered injections in addition to being given by a nurse at a clinic. The aim was to assess if patients with acromegaly prefer self-injections and to investigate their attitudes towards long-term medical therapy.

Method: All patients in the southern medical region of Sweden with a diagnosis of acromegaly and treated with SSA were eligible for the study (n = 24). The study is based on a questionnaire asking about the patients' attitudes and preferences for injections with SSA, including their attitudes towards self-injection with SSA.

Results: The patients' (23 included) median age was 68.5 years and the patients had been treated with SSA for 13 (1-38) years. One patient was currently self-injecting. All of the other patients were receiving injections from a nurse at a clinic. Three patients preferred self-injections, one preferred partner injections and 19 patients did not prefer self- or partner injections. The most frequent arguments to not preferring self-injections were 'feeling more secure with an educated nurse' and 'preferring regular contact with a specialised nurse'.

Conclusion: Patients with acromegaly prefer regular contact with the endocrine team to the independence offered by self-injections. These findings might mirror the patients' desires for continuity and safety. We need to address patients' concerns regarding injections with SSA and support them in their choices.
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http://dx.doi.org/10.1530/EC-16-0038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308196PMC
July 2016

Associations between Metabolic Risk Factors and the Hypothalamic Volume in Childhood Leukemia Survivors Treated with Cranial Radiotherapy.

PLoS One 2016 29;11(1):e0147575. Epub 2016 Jan 29.

Department of Endocrinology, Skåne University hospital and IKVL, Lund University, Lund, Sweden.

Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 31 matched controls. We performed analyses of fat mass, fat free mass, plasma (p)-glucose, p-insulin, Homa-Index (a measure of insulin resistance), serum (s)-leptin, s-ghrelin and of the hypothalamic volume in scans obtained by magnetic resonance imaging (MRI) at 3 Tesla. Serum leptin/kg fat mass (r = -0.4, P = 0.04) and fat mass (r = -0.4, P = 0.01) were negatively correlated with the HT volume among ALL survivors, but not among controls. We also detected significantly higher BMI, waist, fat mass, p-insulin, Homa-Index, leptin/kg fat mass and s-ghrelin and significantly lower fat free mass specifically among female ALL survivors (all P<0.01). Interestingly, s-ghrelin levels increased with time since diagnosis and with low age at diagnosis for childhood ALL. Our results showed that leptin/kg fat mass and fat mass were associated with a reduced HT volume 34 years after ALL diagnosis and that women treated with CRT after ALL are at high risk of metabolic abnormalities. Taken together our data suggest that the hypothalamus is involved in the metabolic consequences after CRT in ALL survivors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732818PMC
July 2016

Prolactin insufficiency but normal thyroid hormone levels after cranial radiotherapy in long-term survivors of childhood leukaemia.

Clin Endocrinol (Oxf) 2013 Jul 27;79(1):71-8. Epub 2013 Apr 27.

Department of Endocrinology, Skåne University Hospital, Lund, Sweden.

Background: Acute lymphoblastic leukaemia (ALL) patients treated with cranial radiotherapy (CRT) have an increased risk of GH deficiency (GHD). Little is known about insufficiencies of prolactin (PRL) and TSH, but also lactation failure has been reported in this population.

Objective: To study the long-term outcome of CRT on PRL and thyroid hormone levels in GHD ALL patients and the prevalence of lactation failure.

Design: Case-control study.

Patients: We examined 40 GHD and 4 GH insufficient ALL patients, in median 20 years (range: 8-27) after ALL diagnosis and 44 matched population controls.

Measurements: PRL secretion (area under the curve; AUC) after GHRH-arginine test in all patients and matched controls, and PRL and TSH AUC after a TRH-test in 13 patients and 13 controls. And basal PRL and thyroid hormone levels after 5 years with GH therapy and 8 years without GH therapy.

Results: Compared with controls, ALL patients had significantly lower basal and AUC PRL after GHRH-Arginine (P = 0·03, P = 0·02), and AUC PRL after TRH (P = 0·001). After 5 and 8 years, PRL levels decreased further (P = 0·01, P = 0·03), but thyroid hormones remained normal at baseline and at follow-up. PRL insufficiency was significantly associated with increased levels of BMI and insulin. Six out of seven pregnant ALL women reported lactation failure.

Conclusions: Long-term ALL survivors treated with CRT have GHD and PRL insufficiency, and a high prevalence of lactation failure, but thyroid hormones remained normal. PRL insufficiency was associated with cardiovascular risk.
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http://dx.doi.org/10.1111/cen.12111DOI Listing
July 2013

Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma.

Eur J Endocrinol 2011 Jul 18;165(1):25-31. Epub 2011 Apr 18.

Department of Internal Medicine, Central Hospital, SE 291 85 Kristianstad, Sweden.

Context: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment.

Objective: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures.

Design And Participants: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls.

Results: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (P=0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels ≤-2.0 s.d. Furthermore, 75% of those with a Z-score ≤-2.0 s.d. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only.

Conclusions: Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.
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http://dx.doi.org/10.1530/EJE-11-0229DOI Listing
July 2011

Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy.

Eur J Endocrinol 2011 May 4;164(5):695-703. Epub 2011 Mar 4.

Department of Endocrinology, Skåne University Hospital, Lund, Sweden.

Objective: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with GH deficiency (GHD), with and without GH therapy.

Design: Case-control study.

Methods: We examined 44 (21 women) GHD patients (median 25 years) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls for BMD with dual-energy X-ray absorptiometry. For 5 and 8 years, two subgroups with (0.5 mg/day) (n=16) and without GH therapy (n=13) and matched controls were followed respectively.

Results: At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all P>0.3). After another 8 years with GHD, the Z-scores at femoral neck had significantly decreased compared with baseline (0.0 to -0.5; P<0.03) and became lower at the femoral neck (P=0.05), and at L2-L4 (P<0.03), compared with controls. After 5 years of GH therapy, only female ALL patients had a significantly lower femoral neck Z-scores (P=0.03). The female ALL patients reached an IGF1 level of -0.7 s.d. and male patients reached the level of +0.05 s.d.

Conclusions: On average, 25 years after diagnosis, GH-deficient ALL patients experienced a significant decrease in Z-scores at femoral neck, and if Z-scores continue to decrease, there could be a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.
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http://dx.doi.org/10.1530/EJE-10-1075DOI Listing
May 2011

Cardiovascular risk, cardiac function, physical activity, and quality of life with and without long-term growth hormone therapy in adult survivors of childhood acute lymphoblastic leukemia.

J Clin Endocrinol Metab 2010 Aug 19;95(8):3726-35. Epub 2010 May 19.

Department of Endocrinology, Lund and Malmö University Hospital, Lund University, SE-221 85 Lund, Sweden.

Context: Long-term data are missing in GH-treated acute lymphoblastic leukemia (ALL) patients. GH therapy may result in poorer outcome regarding cardiovascular (CV) and particularly cardiac effects than in patients with hypothalamic-pituitary disease.

Objective: Our objective was to evaluate GH therapy on CV risk, cardiac function, physical activity, and quality of life in ALL patients treated with cranial radiotherapy (18-24 Gy) and chemotherapy (anthracycline dose 120 mg/m2).

Design And Setting: We conducted a 5- and 8-yr open nonrandomized prospective study in a university hospital clinic.

Study Participants: Two groups of GH-deficient ALL patients (aged 25 yr; range 19-32 yr) and matched population controls participated.

Interventions: One ALL group (n=16) received GH for 5 yr, and the other ALL group (n=13) did not receive GH therapy.

Main Outcome Measures: We evaluated the prevalence of CV risk factors and metabolic syndrome (International Diabetes Federation consensus), cardiac function (echocardiography), and quality of life and physical activity questionnaires.

Results: In comparison with 8 yr without, 5 yr with GH therapy resulted in significant positive changes in plasma glucose (-0.5 vs. 0.6 mmol/liter, P=0.002), apolipoprotein B/apolipoprotein A1 ratio (-0.1 vs. 0.0, P=0.03), and high-density lipoprotein-cholesterol (0.20 vs.-0.01 mmol/liter, P=0.008) and a significant reduction in the prevalence of metabolic syndrome (P=0.008). No significant difference in the left-ventricular systolic function or in physical activity and quality of life was recorded before and after 5 or 8 yr, respectively (all P>0.3).

Conclusion: GH therapy reduced the CV risk in this young ALL population but resulted in no clear benefit or deterioration in cardiac function.
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http://dx.doi.org/10.1210/jc.2010-0117DOI Listing
August 2010

Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after two years of growth hormone (GH) treatment in GH-deficient adult survivors of childhood-onset acute lymphoblastic leukemia.

J Clin Endocrinol Metab 2006 May 7;91(5):1872-5. Epub 2006 Mar 7.

Department of Endocrinology, Lund University Hospital, SE-221 85 Lund, Sweden.

Context: Survivors of childhood-onset (CO) acute lymphoblastic leukemia (ALL) treated with prophylactic cranial radiotherapy often exhibit GH deficiency (GHD), which is associated with increased prevalence of cardiovascular risk factors and cardiac dysfunction.

Objective: The objective of the study was to evaluate the effect of GH replacement on cardiovascular risk factors and cardiac function in former CO ALL patients.

Design: Eighteen former CO ALL patients (aged 19-32 yr) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and with confirmed GHD were studied at baseline and after 12 (n = 18) and 24 months (n = 13) of GH treatment (median 0.5 mg/d). A group of 18 age- and sex-matched subjects served as controls.

Results: After 12 months of GH treatment, a significant decrease in serum leptin (P = 0.002), leptin per kilogram fat mass (FM) (P = 0.01), plasma glucose (P = 0.004), FM (P = 0.002), and hip (P = 0.04) and waist (P = 0.02) circumference and increased muscle mass (P = 0.004) were recorded in the patients. Before GH treatment six patients had a metabolic syndrome, but after 12 months only one had it and after 24 months none. After 24 months of GH treatment, an increase in left ventricular mass index (P = 0.06) and significant improvements in cardiac systolic function, measured as fractional shortening (P = 0.03) and ejection fraction (P = 0.03), were recorded.

Conclusions: Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome were recorded after 2 yr of GH replacement in former CO ALL patients with GHD. Long-term follow-up is highly warranted.
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http://dx.doi.org/10.1210/jc.2005-2298DOI Listing
May 2006
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