Background
Cancer‐related fatigue is a debilitating late effect after treatment for childhood cancer. The prevalence of fatigue in childhood cancer survivors (CCSs) and associated factors for fatigue ...has varied widely in previous studies. Two important aspects of cancer‐related fatigue, its severity and chronicity, are often not assessed. This study investigated the prevalence of, and risk factors for, severe chronic fatigue (CF) in a national cohort of Dutch CCSs.
Methods
In this study, 2810 CCSs (5‐year survivors of all childhood malignancies diagnosed between 1963 and 2001 with a current age of 12‐65 years) and 1040 sibling controls were included. CF was assessed with the Short Fatigue Questionnaire and was defined as a score ≥ 18 and persistence of fatigue for ≥6 months. Cancer‐ and treatment‐related characteristics, current health problems, and demographic and lifestyle variables were assessed as potential risk factors for CF via multivariable logistic regression analyses.
Results
In adult CCSs and sibling controls (≥18 years old), the prevalence of CF was 26.1% and 14.1%, respectively (P < .001). In adolescent CCSs and sibling controls (<18 years old), the prevalence of CF was 10.9% and 3.2%, respectively. Female gender (odds ratio OR, 2.13; 95% confidence interval CI, 1.73‐2.62), unemployment (OR, 2.18; 95% CI, 1.67‐2.85), having 1 or more health problems (OR for 1‐2, 1.48; 95% CI, 1.18‐1.87; OR for >2, 2.20; 95% CI, 1.50‐3.21), and a central nervous system diagnosis (OR, 1.74; 95% CI, 1.17‐2.60) were significantly associated with CF in adult CCSs.
Conclusions
This study shows that CCSs, regardless of their cancer diagnosis, report CF more often than sibling controls. This study provides new evidence for the prevalence of fatigue in CCSs.
One in 4 childhood cancer survivors reports chronic fatigue. Current health problems increase the risk of reporting chronic fatigue.
Background
The aim was to evaluate self‐reported reproductive characteristics and markers of ovarian function in a nationwide cohort of female survivors of childhood acute lymphoblastic leukemia ...(ALL), because prior investigations have produced conflicting data.
Procedure
Self‐reported reproductive characteristics were assessed by questionnaire among 357 adult 5‐year survivors, treated between 1964 and 2002, and 836 controls. Ovarian function was assessed by serum levels of anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), and inhibin B and by antral follicle count (AFC). Differences between controls and (subgroups of) survivors (total group, chemotherapy CT‐only group, CT and radiotherapy RT group) were analyzed.
Results
Survivors treated with CT only do not differ from controls regarding timing of menarche, virginity status, desire for children, or pregnancy rates. Compared to controls, the CT+RT group was at significantly increased risk of a younger age at menarche (P < .01), virginity, an absent desire for children, and lower pregnancy rates (odds ratio OR 95% CI: 0.3 CI 0.1‐0.6, 0.5 0.3‐0.9, and 0.4 0.2‐0.9, respectively). Survivors in the CT‐only group were significantly younger at the birth of their first child. Pregnancy outcomes were not significantly different between any (sub)groups. Survivors treated with total body irradiation (TBI) or hematopoietic stem cell transplantation (HSCT) are at increased risk of abnormal markers of ovarian function.
Conclusion
Reproductive function of ALL survivors treated with CT only does not differ from controls. However, survivors additionally treated with RT seem to be at an increased risk of certain adverse reproductive outcomes. Providing personalized counseling about (future) reproductive health risks in this group is imperative.
Background
This study compares a comprehensive range of psychosocial outcomes of adult childhood cancer survivors (CCS) to general population‐based references and identifies sociodemographic and ...medical risk factors.
Methods
CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)‐LATER cohort (diagnosed 1963–2001) part 2 (attained age ≥18 years, diagnosed <18 years, ≥5 years since diagnosis) completed the Rosenberg Self‐Esteem Scale, Hospital Anxiety and Depression Scale, Distress Thermometer, Self‐Rating Scale for Post‐Traumatic Stress Disorder, and the Short Form‐36 (Health Related Quality of Life). CCS’ scores were compared with references using analysis of variances and logistic regression analysis, controlling for age and sex (p < .05). Risk factors for worse psychosocial outcomes were assessed with regression analyses (p < .05).
Results
CCS, N = 1797, mean age 35.4 years, 49.0% female, all ≥15 years since diagnosis, participated. Three percent reported posttraumatic stress disorder because of childhood cancer and 36.6% experienced clinical distress. CCS did not differ from references on self‐esteem and anxiety but were less depressed (d = −.25), and scored poorer on all health‐related quality of life scales, except for bodily pain (.01 ≤ d ≥ −.36). Female sex, lower educational attainment, not being in a relationship, and being unemployed were negatively associated with almost all psychosocial outcomes. Except for a central nervous system tumor diagnosis, few medical characteristics were associated with psychosocial outcomes.
Conclusion
CCS appear resilient regarding mental health but have slightly poorer health‐related quality of life than references. Sociodemographic characteristics and central nervous system tumors were related to most psychosocial outcomes, but no clear pattern was observed for other medical factors. Future studies should address additional factors in explaining CCS’ psychosocial functioning, such as coping, social support, and physical late effects.
Adult childhood cancer survivors appear resilient regarding mental health but have slightly poorer health‐related quality of life than reference patients. Sociodemographic characteristics and central nervous system tumors were related to most psychosocial outcomes, but no clear pattern was observed for other medical factors.
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.
Background
The objective of this study was to compare the health‐related quality of life (HRQOL) of Dutch adult male and female childhood cancer survivors (CCSs) to general population references and ...to study medical determinants.
Methods
CCSs from the Dutch Childhood Cancer Survivor Study LATER cohort (1963‐2001) part 2, who were 18 years old or older (time since diagnosis ≥ 5 years), were invited to complete the TNO‐AZL Questionnaire for Adult Health‐Related Quality of Life. Domain scores and proportions of CCSs with impaired HRQOL (score < 25th percentile of the reference scores) were compared with references via Mann‐Whitney U tests and logistic regression analyses corrected for age and sex (P < .004). Interactions of group with sex were included if they were significant (P < .05). Moreover, medical determinants were analyzed with multivariable logistic regression analyses.
Results
HRQOL scores for 1766 CCSs (mean age, 35.9 years standard deviation, 9.4 years; male, 51%; response rate, 71%) differed from references on most domains with small effect sizes. Both male and female CCSs were more often impaired in gross and fine motor functioning, cognitive functioning, sleep, and vitality with odds ratios (ORs) > 1.4. In addition, female CCSs were more often impaired in daily activities, pain, and sexuality (ORs, 1.4‐1.9) and were less often aggressive (OR, 0.6). CCCs of central nervous system (CNS) tumors, bone tumors, and retinoblastoma and those with cranial, abdominopelvic, or lower extremity radiotherapy were at increased risk of impairment in 1 or more domains.
Conclusions
Dutch adult CCSs, especially females, have impaired HRQOL in several domains; this is most pronounced in cognitive functioning. The vulnerabilities of subgroups at risk, such as CCSs of CNS tumors, were confirmed. Surveillance of HRQOL and multidisciplinary survivor care are recommended.
Lay Summary
The health‐related quality of life in a Dutch nationwide cohort of 1766 survivors of childhood cancer was studied.
Survivors of childhood cancer were found to have lower health‐related quality of life in several domains (eg, motor functioning and vitality) in comparison with the general population.
They most often reported low cognitive functioning (eg, memory and attention).
Females had low health‐related quality of life in more domains than males.
Survivors of brain tumors had low health‐related quality of life in most domains.
Monitoring health‐related quality of life regularly and collaborating between disciplines in survivor care is recommended.
Dutch adult survivors of childhood cancer, especially females and central nervous system tumor survivors, have impaired health‐related quality of life in several domains; this is most pronounced in cognitive functioning. Surveillance of health‐related quality of life and multidisciplinary survivor care are recommended.
Severe fatigue after treatment for childhood cancer van Deuren, Sylvia; Boonstra, Amilie; van Dulmen‐den Broeder, Eline ...
Cochrane database of systematic reviews,
03/2020, Letnik:
2020, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background
Treatment strategies for childhood cancer are improving, resulting in higher survival rates. However, the consequences of childhood cancer do not end with the successful completion of ...cancer treatment. Most patients will develop late effects after cessation of treatment. Severe fatigue is seen as a common and debilitating late effect in cancer survivors. Although most research on fatigue has been performed in patients after adult‐onset cancer, our review focuses on fatigue after childhood cancer.
Objectives
To estimate the prevalence of severe fatigue after treatment for childhood cancer. Secondary objectives are to describe the course of severe fatigue following cancer treatment and to examine risk factors for fatigue, or factors associated with it.
Search methods
We searched the Cochrane Central Register of Controlled Trials (the Cochrane Library 2019; issue 8 March 2019), MEDLINE/PubMed (from 1945 to 8 March 2019), Embase/Ovid (from 1947 to 8 March 2019), reference lists of included articles and several conference proceedings from 2011 to 2018.
Selection criteria
Observational studies, randomised controlled trials and controlled clinical trials reporting on fatigue in participants after treatment for childhood cancer. Case series and case reports were not eligible for inclusion.
Data collection and analysis
Two review authors independently extracted data and assessed risks of bias. If the publication did not present the prevalence of severe fatigue, we contacted study authors for additional information.
Main results
We included 30 studies (18,682 participants in total). Eighteen studies contributed to the main objective and 22 studies contributed to the secondary objectives. We found substantial differences between studies in cancer diagnosis, cancer treatment, age of participants, questionnaires used to assess fatigue, and sample size. All included studies scored at least one 'Risk of bias' item as unclear or high risk.
We identified both clinical and statistical heterogeneity and therefore could not pool results, so we present them descriptively. Eighteen studies (describing 14,573 survivors) reported the prevalence of severe fatigue, which ranged from 0% to 61.7%. In a subgroup of three studies including children aged up to 18 years at fatigue assessment (268 survivors), prevalence rates ranged from 6.7% to 12.5%. In comparison, in a subgroup of 12 studies including participants aged 16 and over (13,952 survivors), prevalence rates ranged from 4.4% to 61.7%. The prevalence of severe fatigue in a subgroup of survivors of haematological cancer was presented in seven studies and ranged from 1.8% to 35.9% (1907 survivors). Prevalence of severe fatigue in brain cancer survivors was presented in two studies (252 survivors) and was 14.6% and 21.1% respectively. One study presented a prevalence for bone cancer survivors of 0.0% (17 survivors). Four studies provided prevalence rates of severe fatigue in control groups of siblings or population‐based controls, which ranged from 3.1% to 10.3%. In these four studies, survivors were more often fatigued than controls, but this difference was statistically significant in only two studies.
Studies assessing risk and associated factors for fatigue were heterogeneous, and definitions of the factors under study were often inconsistent, with results therefore presented descriptively. They found that depression might be associated with fatigue. In contrast, age at diagnosis and education level did not seem to be associated with fatigue. We were unable to calculate any overall risk estimate for any of the reported risks and associated factors, because we could not conduct meta‐analysis.
One study provided information about the course of fatigue over time, and found that over the course of 2.7 years, 32 of the 102 participants (31.4%) reported persistent severe fatigue.
Authors' conclusions
It is unclear how many childhood cancer survivors suffer from severe fatigue. This review encountered several difficulties. We found statistical and clinical heterogeneity and great variation in the reporting of possible risk and associated factors. The evidence in this review is therefore weak, and the exact prevalence of severe fatigue after treatment for childhood cancer remains to be determined. This is also the case for the course of severe fatigue following treatment and the strength of the relationship between fatigue and associated and risk factors. Despite these limitations, our review does provide a comprehensive overview of the existing literature about severe fatigue after treatment for childhood cancer.
Background
Treatment‐related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes ...and reproductive health care utilization among male CCSs compared with male siblings.
Methods
A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study.
Results
Fewer CCSs had biological children compared with siblings (65% vs. 88%; p < .001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p = .86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p < .001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p = .001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p = .001).
Conclusions
More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists.
This study showed that two‐thirds of male survivors of childhood cancer who had a desire for children fathered a biological child and that children of 90% of male survivors were conceived spontaneously. Compared with male siblings, more male survivors consulted a reproductive specialist because of not siring a pregnancy; however, both the application of and birth rates after assisted reproductive techniques in survivors were lower.
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
Knowledge of the desire for children among childhood cancer survivors (CCSs) is scarce. This study evaluated the desire for children in male CCSs in comparison with male siblings.
Methods
...A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor Study LATER study: 1317 male CCSs and 407 male sibling controls completed a questionnaire addressing the desire for children. Logistic regression analyses were used to explore the independent association between survivorship status and the desire for children. Furthermore, additional analyses were performed to identify which cancer‐related factors were associated with the desire for children in male CCSs.
Results
After adjustments for the age at assessment, the percentage of men who had a desire for children was significantly lower among CCSs compared with the siblings (74% vs. 82%; odds ratio OR, 0.61; 95% CI, 0.46–0.82; p = .001). The association between survivorship status and the desire for children was attenuated after adjustments for marital status, level of education, and employment status (OR, 0.83; 95% CI, 0.61–1.14; p = .250). The percentage of men who had an unfulfilled desire for children remained significantly higher among CCSs compared with the siblings after adjustments for sociodemographic factors (25% vs. 7%; OR, 5.14; 95% CI, 2.48–10.64; p < .001).
Conclusions
The majority of male CCSs have a desire for children. The likelihood of having to deal with an unfulfilled desire for children is 5 times higher among CCSs compared with their siblings. This insight is important for understanding the needs and experienced problems of CCSs regarding family planning and fertility issues.
Male survivors of childhood cancer report a lower desire for children in comparison with male siblings, and this can be explained by differences in marital status, level of education, and employment status. The likelihood of having to deal with an unfulfilled desire is 5 times higher among male survivors compared with siblings, and cancer diagnosis, allogeneic hematopoietic stem cell transplantation, and cancer treatment are associated with an unfulfilled desire for children.
Background
Improvements in diagnostics and treatment for paediatric malignancies resulted in a major increase in survival. However, childhood cancer survivors (CCS) are at risk of developing adverse ...effects caused by multimodal treatment for their malignancy. Nephrotoxicity is a known side effect of several treatments, including cisplatin, carboplatin, ifosfamide, radiotherapy and nephrectomy, and can cause glomerular filtration rate (GFR) impairment, proteinuria, tubulopathy, and hypertension. Evidence about the long‐term effects of these treatments on renal function remains inconclusive. It is important to know the risk of, and risk factors for, early and late adverse renal effects, so that ultimately treatment and screening protocols can be adjusted. This review is an update of a previously published Cochrane Review.
Objectives
To evaluate existing evidence on the effects of potentially nephrotoxic treatment modalities on the prevalence of renal dysfunction in survivors treated for childhood cancer with a median or mean survival of at least one year after cessation of treatment, where possible in comparison with the general population or CCS treated without potentially nephrotoxic treatment. In addition, to evaluate evidence on associated risk factors, such as follow‐up duration, age at time of diagnosis and treatment combinations, as well as the effect of doses.
Search methods
On 31 March 2017 we searched the following electronic databases: CENTRAL, MEDLINE and Embase. In addition, we screened reference lists of relevant studies and we searched the congress proceedings of the International Society of Pediatric Oncology (SIOP) and The American Society of Pediatric Hematology/Oncology (ASPHO) from 2010 to 2016/2017.
Selection criteria
Except for case reports, case series and studies including fewer than 20 participants, we included studies with all study designs that reported on renal function (one year or longer after cessation of treatment), in CCS treated before the age of 21 years with cisplatin, carboplatin, ifosfamide, radiation involving the kidney region, a nephrectomy, or a combination of two or more of these treatments. When not all treatment modalities were described or the study group of interest was unclear, a study was not eligible for the evaluation of prevalence. We still included it for the assessment of risk factors if it had performed a multivariable analysis.
Data collection and analysis
Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction using standardised data collection forms. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
Main results
Apart from the remaining 37 studies included from the original review, the search resulted in the inclusion of 24 new studies. In total, we included 61 studies; 46 for prevalence, six for both prevalence and risk factors, and nine not meeting the inclusion criteria, but assessing risk factors. The 52 studies evaluating the prevalence of renal dysfunction included 13,327 participants of interest, of whom at least 4499 underwent renal function testing. The prevalence of adverse renal effects ranged from 0% to 84%. This variation may be due to diversity of included malignancies, received treatments, reported outcome measures, follow‐up duration and the methodological quality of available evidence.
Seven out of 52 studies, including 244 participants, reported the prevalence of chronic kidney disease, which ranged from 2.4% to 32%.
Of these 52 studies, 36 studied a decreased (estimated) GFR, including at least 432 CCS, and found it was present in 0% to 73.7% of participants. One eligible study reported an increased risk of glomerular dysfunction after concomitant treatment with aminoglycosides and vancomycin in CCS receiving total body irradiation (TBI). Four non‐eligible studies assessing a total cohort of CCS, found nephrectomy and (high‐dose (HD)) ifosfamide as risk factors for decreased GFR. The majority also reported cisplatin as a risk factor. In addition, two non‐eligible studies showed an association of a longer follow‐up period with glomerular dysfunction.
Twenty‐two out of 52 studies, including 851 participants, studied proteinuria, which was present in 3.5% to 84% of participants. Risk factors, analysed by three non‐eligible studies, included HD cisplatin, (HD) ifosfamide, TBI, and a combination of nephrectomy and abdominal radiotherapy. However, studies were contradictory and incomparable.
Eleven out of 52 studies assessed hypophosphataemia or tubular phosphate reabsorption (TPR), or both. Prevalence ranged between 0% and 36.8% for hypophosphataemia in 287 participants, and from 0% to 62.5% for impaired TPR in 246 participants. One non‐eligible study investigated risk factors for hypophosphataemia, but could not find any association.
Four out of 52 studies, including 128 CCS, assessed the prevalence of hypomagnesaemia, which ranged between 13.2% and 28.6%. Both non‐eligible studies investigating risk factors identified cisplatin as a risk factor. Carboplatin, nephrectomy and follow‐up time were other reported risk factors.
The prevalence of hypertension ranged from 0% to 50% in 2464 participants (30/52 studies). Risk factors reported by one eligible study were older age at screening and abdominal radiotherapy. A non‐eligible study also found long follow‐up time as risk factor. Three non‐eligible studies showed that a higher body mass index increased the risk of hypertension. Treatment‐related risk factors were abdominal radiotherapy and TBI, but studies were inconsistent.
Because of the profound heterogeneity of the studies, it was not possible to perform meta‐analyses. Risk of bias was present in all studies.
Authors' conclusions
The prevalence of adverse renal effects after treatment with cisplatin, carboplatin, ifosfamide, radiation therapy involving the kidney region, nephrectomy, or any combination of these, ranged from 0% to 84% depending on the study population, received treatment combination, reported outcome measure, follow‐up duration and methodological quality. With currently available evidence, it was not possible to draw solid conclusions regarding the prevalence of, and treatment‐related risk factors for, specific adverse renal effects. Future studies should focus on adequate study designs and reporting, including large prospective cohort studies with adequate control groups when possible. In addition, these studies should deploy multivariable risk factor analyses to correct for possible confounding. Next to research concerning known nephrotoxic therapies, exploring nephrotoxicity after new therapeutic agents is advised for future studies. Until more evidence becomes available, CCS should preferably be enrolled into long‐term follow‐up programmes to monitor their renal function and blood pressure.
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