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Infections lead to substantial morbidity during treatment of acute lymphoblastic leukemia (ALL) in which the adaptive immune system gets severely affected, leading to declining serum immunoglobulin levels. The aim of this trial was to investigate whether intravenous immunoglobulin (IVIG) prophylaxis in pediatric patients with ALL prevents admissions for fever. This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study. Patients aged 1-19 years with medium risk (MR) ALL were randomized into two groups receiving either IVIG prophylaxis (0.7 g/kg IVIG given every three weeks, starting day 22 after diagnosis) or well defined standard of care (control group). Between October 2012 until March 2019, 91 (51%) patients were randomly assigned to IVIG prophylaxis and 86 (49%) to the control arm. In the IVIG prophylaxis group there were 206 admissions for fever versus 271 in the control group (p=0.011). IVIG prophylaxis was not associated with bacteremia. However, IVIG prophylaxis was associated with significantly less admissions for fever with negative blood cultures compared to the control group (N=113 versus 200, p.
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PURPOSE: Splenectomy might be a risk factor for valvular heart disease (VHD) in adult Hodgkin lymphoma survivors. As this risk is still unclear for childhood cancer survivors (CCS), the aim of this study is to evaluate the association between treatments affecting splenic function (splenectomy and radiotherapy involving the spleen) and VHD in CCS. METHODS: CCS were enrolled from the DCCSS-LATER cohort, consisting of 6,165 five-year CCS diagnosed between 1963 and 2002. Symptomatic VHD, defined as symptoms combined with a diagnostic test indicating VHD, was assessed from questionnaires and validated using medical records. Differences in the cumulative incidence of VHD between CCS who received treatments affecting splenic function and CCS who did not were assessed using the Gray test. Risk factors were analyzed in a multivariable Cox proportional hazards model. RESULTS: The study population consisted of 5,286 CCS, with a median follow-up of 22 years (5-50 years), of whom 59 (1.1%) had a splenectomy and 489 (9.2%) radiotherapy involving the spleen. VHD was present in 21 CCS (0.4%). The cumulative incidence of VHD at the age of 40 years was significantly higher in CCS who received treatments affecting splenic function (2.7%, 95% confidence interval (CI) 0.4%-4.9%) compared with CCS without (0.4%, 95% CI 0.1%-0.7%) (Gray's test, p = 0.003). Splenectomy was significantly associated with VHD in a multivariable analysis (hazard ratio 8.6, 95% CI 3.1-24.1). CONCLUSIONS AND IMPLICATIONS: Splenectomy was associated with VHD. Future research is needed to determine if CCS who had a splenectomy as part of cancer treatment might benefit from screening for VHD.
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The trajectory of hematopoietic stem cell transplantation (HSCT) is often accompanied by physically disabling complications that impair physical performance of pediatric patients. However, knowledge about when impairments in physical performance arise and the factors contributing to these impairments is limited. Therefore, we conducted a retrospective analysis of physical performance 100 days post-HSCT in patients aged 3-18 years. Additionally, we aim to elucidate the relationship between pre- and post-HSCT physical performance and to unravel the impact of intensive HSCT procedures on post-HSCT physical performance. To explore associations between physical performance outcomes post-HSCT and covariates, linear regression models were estimated. Seventy-seven patients were included with a median age of 11.8 years (interquartile range: 5.9, 14.8). Patients had lower hip flexion muscle strength and appendicular skeletal muscle mass and a slower rising from the floor time 100 days post-HSCT compared to average values of the normal population. Pre-HSCT physical performance was positively associated with physical performance post-HSCT, independent of age, the cumulative glucocorticoids dosage administered and the total duration of hospitalization during the HSCT trajectory. This explorative study highlights the potential role of prehabilitation in enhancing physical performance of pediatric HSCT patients.
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PURPOSE: To optimize recognition and management of nausea in children with cancer using patient reported outcome measures (PROMs) and to identify preferences of children with cancer regarding two validated tools: the Baxter Retching Faces (BARF) scale and the Pediatric Nausea Assessment Tool (PeNAT). DESIGN AND METHODS: This quantitative descriptive cross-sectional study (n = 34) used bespoke questionnaires to measure feasibility and face validity of the BARF and the PeNAT. Feasibility included the items: understanding, ease of use, and communication. Face validity was studied in terms of the degree in which the faces of both PROMs corresponded with children's feelings of nausea. A descriptive and comparative analysis of the data was performed. RESULTS: Both the BARF and the PeNAT were rated by the children as feasible, and no significant differences were found. However, regarding the item communication, the PeNAT did not reach the cut-off value (≥80% of all children scored neutral, agree or totally agree on the Likert scale). Regarding face validity, only the BARF reached the cut-off value and corresponded significantly better with children's feelings of nausea than the PeNAT. CONCLUSION: According to children with cancer, only the BARF is both feasible and meets criteria for face validity. Therefore, the BARF is recommended as a PROM for reporting nausea in children with cancer. However, possible differences between age groups should be taken into account for future research. PRACTICE IMPLICATIONS: This study will help health care professionals in making a patient-centered and informed choice when using a PROM for measuring nausea in children with cancer.
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PURPOSE: Investigate the association between presence, number and type of clinically relevant health conditions and a range of psychosocial outcomes (emotional, social, cognitive, physical) in survivors of childhood cancer (CCS). METHODS: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed between 1963-2001, attained age ≥ 18, diagnosed < 18, ≥ 5 years since diagnosis) completed a questionnaire on health conditions (2013-2014), and questionnaires on psychosocial outcomes (2017-2020): Hospital Anxiety and Depression Scale, Short form 36, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and the Self-Rating Scale for Post-Traumatic Stress Disorder. Associations among health conditions and psychosocial outcomes were assessed with regression analysis, adjusting for attained age, sex, and time since diagnosis, and adjusting for multiple testing (p < 0.004). RESULTS: A total of 1437 CCS, mean age 36.3 years, 51.1% female, ≥ 15 years since diagnosis, completed questionnaires on health and psychosocial outcomes. CCS with a clinically relevant health condition, and those with more conditions had worse emotional, social, and physical outcomes; regression coefficients were small to moderate. CCS with gastro-intestinal conditions, endocrine, nervous systems, eye, or ear conditions, and especially those with secondary malignant neoplasms, reported worse psychosocial functioning; regression coefficients were small/moderate to large. CONCLUSION AND IMPLICATIONS: Health care professionals should be aware of the increased risk for psychosocial problems among CCS with health conditions, especially for survivors with secondary malignant neoplasms, gastro-intestinal, endocrine, nervous system, eye, and ear conditions. CCS may benefit from psychological interventions to develop coping strategies to manage health conditions and psychosocial consequences of the cancer trajectory.
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PURPOSE: In current clinical practice, recommendations regarding restrictions in daily life for children with cancer are often lacking or not evidence-based. Critically reviewing the evidence and formulating recommendations are therefore of great importance as social restrictions (e.g., swimming, school attendance, sports) can impair the quality of life of these children severely. Therefore, our aim was to develop a clinical practice guideline for clinicians, children, and their parents regarding social restrictions in children with cancer. METHODS: A comprehensive multidisciplinary panel was assembled, comprising 21 professionals and patient representatives. A systematic literature review was performed, including dual appraisal of all citations. The GRADE methodology was used to extract, summarize, and assess the evidence. Multiple in-person meetings were held to rank outcomes, discuss evidence, complete evidence-to-decision frameworks, and formulate recommendations. Final recommendations were unanimously supported by all panel members. RESULTS: Six studies, including 758 children, formed the evidence base for the recommendations. Given the scarcity of the available evidence and various designs of studies in children with cancer, additional evidence was extracted from adult oncology guidelines, and shared expert opinions were utilized. In total, 14 recommendations were formulated of which multiple result in changes in current policy and standard of practice in the Netherlands. Topics covered in this guideline are swimming, having pets, visiting the zoo or farm, performing sports or high-velocity events, attending school or kindergarten, and use of public transport. This guideline is not intended to provide recommendations for patients after end of treatment, for palliative care settings, or for children undergoing a stem cell transplantation. CONCLUSIONS: In this clinical practice guideline, we provide recommendations regarding restrictions in daily life in children with cancer. These include evidence-based recommendations and, in the absence of sufficient evidence, recommendations based on expert evidence. With these recommendations, we provide guidance for clinicians, children, and parents and contribute to improving quality of life for children with cancer.
Subject(s)
Neoplasms , Quality of Life , Humans , Child , Neoplasms/therapy , Activities of Daily Living , NetherlandsABSTRACT
In current clinical practice, recommendations regarding restrictions in daily life for children with cancer are often lacking or not evidence-based. Critically reviewing the evidence and formulating recommendations are therefore of great importance as social restrictions (e.g., swimming, school attendance, sports) can impair the quality of life of these children severely. Therefore, our aim was to develop a clinical practice guideline for clinicians, children, and their parents regarding social restrictions in children with cancer. A comprehensive multidisciplinary panel was assembled, comprising 21 professionals and patient representatives. A systematic literature review was performed, including dual appraisal of all citations. The GRADE methodology was used to extract, summarize, and assess the evidence. Multiple in-person meetings were held to rank outcomes, discuss evidence, complete evidence-to-decision frameworks, and formulate recommendations. Final recommendations were unanimously supported by all panel members. Six studies, including 758 children, formed the evidence base for the recommendations. Given the scarcity of the available evidence and various designs of studies in children with cancer, additional evidence was extracted from adult oncology guidelines, and shared expert opinions were utilized. In total, 14 recommendations were formulated of which multiple result in changes in current policy and standard of practice in the Netherlands. Topics covered in this guideline are swimming, having pets, visiting the zoo or farm, performing sports or high-velocity events, attending school or kindergarten, and use of public transport. This guideline is not intended to provide recommendations for patients after end of treatment, for palliative care settings, or for children undergoing a stem cell transplantation. In this clinical practice guideline, we provide recommendations regarding restrictions in daily life in children with cancer. These include evidence-based recommendations and, in the absence of sufcient evidence, recommendations based on expert evidence. With these recommendations, we provide guidance for clinicians, children, and parents and contribute to improving quality of life for children with cancer.
Subject(s)
Humans , Child , Quality of Life , Cancer SurvivorsABSTRACT
Background: Childhood cancer survivors at risk for heart failure undergo lifelong echocardiographic surveillance. Previous studies reported the limited diagnostic accuracy of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in detecting left ventricular (LV) dysfunction. However, potential enhanced diagnostic accuracy through the combination of biomarkers and clinical characteristics has been suggested. Objectives: The aim of this study was to develop and internally validate a diagnostic model that combines cardiac biomarkers with clinical characteristics for effectively ruling in or ruling out LV dysfunction in childhood cancer survivors. Methods: A multicenter cross-sectional study included 1,334 survivors (median age 34.2 years) and 278 siblings (median age 36.8 years). Logistic regression models were developed and validated through bootstrapping, combining biomarkers with clinical characteristics. Results: Abnormal NT-proBNP levels were observed in 22.1% of survivors compared with 5.4% of siblings, whereas hs-cTnT levels exceeding 10 ng/L were uncommon in both survivors (5.9%) and siblings (5.0%). The diagnostic models demonstrated improvement upon the addition of NT-proBNP and hs-cTnT to clinical characteristics, resulting in an increased C statistic from 0.69 to 0.73 for LV ejection fraction (LVEF) <50% and a more accurate prediction of more severe LV dysfunction, with the C statistic increasing from 0.80 to 0.86 for LVEF <45%. For LVEF <50% (prevalence 10.9%), 16.9% of survivors could be effectively ruled out with high sensitivity (95.4%; 95% CI: 90.4%-99.3%) and negative predictive value (97.5%; 95% CI: 94.6%-99.7%). Similarly, for LVEF <45% (prevalence 3.4%), 53.0% of survivors could be ruled out with moderate to high sensitivity (91.1%; 95% CI: 79.2%-100%) and high negative predictive value (99.4%; 95% CI: 98.7%-100%). Conclusions: The biomarker-based diagnostic model proves effective in ruling out LV dysfunction, offering the potential to minimize unnecessary surveillance echocardiography in childhood cancer survivors. External validation is essential to confirm these findings. (Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors; A DCOG LATER Study; https://onderzoekmetmensen.nl/nl/trial/23641).
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OBJECTIVE: To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. DESIGN: Genome-wide association study. SETTING: Not applicable. PATIENTS: A discovery cohort of adult female childhood cancer survivors from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nervous system or total body irradiation, or stem cell transplantation. Replication was attempted in the US-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years). EXPOSURE: Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the interindividual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions, and cyclophosphamide equivalent doses were used to quantify alkylation agent exposure. MAIN OUTCOME MEASURE: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function, and the findings were combined in a meta-analysis. RESULTS: Three genome-wide significant (<5.0 × 10-8) and 16 genome-wide suggestive (<5.0 × 10-6) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. On the basis of the effect allele frequency (EAF) (>0.01 if not genome-wide significant), and biologic relevance, 15 single nucleotide polymorphisms were selected for replication. None of the single nucleotide polymorphisms were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated with borderline genome-wide statistical significance (reference/effect allele: C/T; effect allele frequency: 0.04, beta (SE): -0.484 (0.091). CONCLUSION: This study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment because the findings of this genome-wide association study were not statistically significant replicated in the replication cohort. Suggestive evidence for the potential importance of 1 variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. Because the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity as well as fertility preservation options for childhood cancer survivors.
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INTRODUCTION: The aim of the current study was to investigate whether subtypes of chronic fatigue (CF) can be identified in childhood cancer survivors (CCS), and if so, to determine the characteristics of participants with a specific subtype. METHODS: Participants were included from the nationwide DCCSS LATER cohort. The Checklist Individual Strength (CIS) was completed to assess fatigue. Participants with CF (scored ≥35 on the fatigue severity subscale and indicated to suffer from fatigue for ≥6 months) were divided into subgroups using two-step cluster analysis based on the CIS concentration, motivation, and physical activity subscales. Differences between groups on demographics, psychosocial, lifestyle, and treatment-related variables were determined using ANOVA and chi-square analyses (univariable) and multinomial regression analysis (multivariable). RESULTS: A total of 1910 participants participated in the current study (n = 450 with CF; n = 1460 without CF). Three CF subgroups were identified: Subgroup 1 (n = 133, 29% of participants) had CF with problems in physical activity; Subgroup 2 (n = 111, 25% of participants) had CF with difficulty concentrating; and Subgroup 3 (n = 206, 46% of participants) had multi-dimensional CF. Compared to Subgroup 1, Subgroup 2 more often reported sleep problems, limitations in social functioning, and less often have more than two comorbidities. Subgroup 3 more often reported depression, sleep problems, a lower self-esteem, and limitations in social functioning and a lower educational level compared to Subgroup 1. CONCLUSION: Different subgroups of CCS with CF can be identified based on fatigue dimensions physical activity, motivation and concentration. Results suggest that different intervention strategies, tailored for each subgroup, might be beneficial.
Subject(s)
Cancer Survivors , Neoplasms , Humans , Male , Female , Cancer Survivors/psychology , Child , Adolescent , Neoplasms/complications , Neoplasms/psychology , Fatigue/etiology , Adult , Fatigue Syndrome, Chronic/psychology , Fatigue Syndrome, Chronic/etiology , Quality of Life , Follow-Up Studies , Young Adult , Child, PreschoolABSTRACT
BACKGROUND: The objective of this study was to examine the prevalence of unhealthy lifestyle behaviors, overweight, and obesity in Dutch childhood cancer survivors (CCSs) compared with sibling controls and the Dutch general population. Other aims were to assess associated factors of unhealthy lifestyle behaviors, overweight, and obesity and to identify subgroups of CCSs at risk for these unhealthy statuses. METHODS: The authors included 2253 CCSs and 906 siblings from the Dutch Childhood Cancer Survivor Study-Late Effects After Childhood Cancer cohort, part 1, and added data from the Dutch general population. Questionnaire data were collected on overweight and obesity (body mass index >25.0 kg/m2), meeting physical activity guidelines (>150 minutes per week of moderate or vigorous exercises), excessive alcohol consumption (>14 and >21 alcoholic consumptions per week for women and men, respectively), daily smoking, and monthly drug use. Multivariable logistic regression analyses and two-step cluster analyses were performed to examine sociodemographic-related, health-related, cancer-related, and treatment-related associated factors of unhealthy lifestyle behaviors and to identify subgroups of CCSs at risk for multiple unhealthy behaviors. RESULTS: CCSs more often did not meet physical activity guidelines than their siblings (30.0% vs. 19.3%; p < .001). Married as marital status, lower education level, nonstudent status, and comorbidities were common associated factors for a body mass index ≥25.0 kg/m2 and insufficient physical activity, whereas male sex and lower education were shared associated factors for excessive alcohol consumption, daily smoking, and monthly drug use. A subgroup of CCSs was identified as excessive alcohol consumers, daily smokers, and monthly drug users. CONCLUSIONS: The current results emphasize the factors associated with unhealthy behaviors and the potential identification of CCSs who exhibit multiple unhealthy lifestyle behaviors.
Subject(s)
Cancer Survivors , Exercise , Life Style , Obesity , Overweight , Humans , Male , Cancer Survivors/statistics & numerical data , Female , Netherlands/epidemiology , Overweight/epidemiology , Adult , Obesity/epidemiology , Child , Neoplasms/epidemiology , Health Behavior , Alcohol Drinking/epidemiology , Alcohol Drinking/adverse effects , Adolescent , Body Mass Index , Young Adult , Smoking/epidemiology , Smoking/adverse effects , Prevalence , Middle AgedABSTRACT
BACKGROUND: We assessed the prevalence and diagnostic value of ECG abnormalities for cardiomyopathy surveillance in childhood cancer survivors. METHODS: In this cross-sectional study, 1381 survivors (≥5 years) from the Dutch Childhood Cancer Survivor Study part 2 and 272 siblings underwent a long-term follow-up ECG and echocardiography. We compared ECG abnormality prevalences using the Minnesota Code between survivors and siblings, and within biplane left ventricular ejection fraction (LVEF) categories. Among 880 survivors who received anthracycline, mitoxantrone or heart radiotherapy, logistic regression models using least absolute shrinkage and selection operator identified ECG abnormalities associated with three abnormal LVEF categories (<52% in male/<54% in female, <50% and <45%). We assessed the overall contribution of these ECG abnormalities to clinical regression models predicting abnormal LVEF, assuming an absence of systolic dysfunction with a <1% threshold probability. RESULTS: 16% of survivors (52% female, mean age 34.7 years) and 14% of siblings had major ECG abnormalities. ECG abnormalities increased with decreasing LVEF. Integrating selected ECG data into the baseline model significantly improved prediction of sex-specific abnormal LVEF (c-statistic 0.66 vs 0.71), LVEF <50% (0.66 vs 0.76) and LVEF <45% (0.80 vs 0.86). While no survivor met the preset probability threshold in the first two models, the third model used five ECG variables to predict LVEF <45% and was applicable for ruling out (sensitivity 93%, specificity 56%, negative predictive value 99.6%). Calibration and internal validation tests performed well. CONCLUSION: A clinical prediction model with ECG data (left bundle branch block, left atrial enlargement, left heart axis, Cornell's criteria for left ventricular hypertrophy and heart rate) may aid in ruling out LVEF <45%.
Subject(s)
Cancer Survivors , Electrocardiography , Stroke Volume , Humans , Female , Male , Cross-Sectional Studies , Adult , Stroke Volume/physiology , Neoplasms/complications , Cardiomyopathies/physiopathology , Cardiomyopathies/diagnosis , Cardiomyopathies/etiology , Cardiomyopathies/epidemiology , Child , Netherlands/epidemiology , Echocardiography , Ventricular Function, Left/physiology , Prevalence , Adolescent , Young Adult , Child, Preschool , Predictive Value of TestsABSTRACT
PURPOSE: The primary objective of this randomized study was to determine whether a continuous dosing schedule (without the asparaginase-free interval) would result in less hypersensitivity reactions to PEGasparaginase (PEGasp) compared with the standard noncontinuous dosing schedule. METHODS: Eight hundred eighteen patients (age 1-18 years) with ALL were enrolled in the Dutch Childhood Oncology Group-ALL11 protocol and received PEGasp. Three hundred twelve patients stratified in the medium-risk arm were randomly assigned to receive 14 individualized PEGasp doses once every two weeks in either a noncontinuous or continuous schedule after the first three doses in induction (EudraCT: 2012-000067-25). Hypersensitivity reactions were defined as allergies, allergic-like reactions, and silent inactivation. Secondary end points were other asparaginase-related toxicities, asparaginase activity and antibody levels, and outcome. RESULTS: During induction, 27 of 818 patients (3.3%) experienced hypersensitivity reactions. After random assignment, 4 of 155 (2.6%) in the continuous treatment arm versus 17 of 157 (10.8%) patients in the noncontinuous treatment arm had hypersensitivity reactions (P < .01), of which two (1.3%) versus 13 (8.3%) were inactivating reactions (P < .01). The occurrence of inactivating hypersensitivity reactions was seven times lower in the continuous arm (odds ratio, 0.15 [0.032-0.653]). In addition, antibody levels were significantly lower in the continuous arm (P < .01). With exception of a lower incidence of increased amylase in the continuous arm, there were no significant differences in total number of asparaginase-associated toxicities between arms. However, the timing of the toxicities was associated with the timing of the asparaginase administrations. No difference in 5-year cumulative incidence of relapse, death, or disease-free survival was found between both treatment arms. CONCLUSION: A continuous dosing schedule of PEGasp is an effective approach to prevent antibody formation and inactivating hypersensitivity reactions. The continuous PEGasp schedule did not increase toxicity and did not affect the efficacy of the therapy.
Subject(s)
Asparaginase , Drug Hypersensitivity , Polyethylene Glycols , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Asparaginase/administration & dosage , Asparaginase/adverse effects , Child , Child, Preschool , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Female , Male , Adolescent , Drug Hypersensitivity/etiology , Infant , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Drug Administration Schedule , Netherlands , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosageABSTRACT
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.
Subject(s)
Cancer Survivors , Neoplasms , Pregnancy , Female , Child , Male , Humans , Neoplasms/therapy , Cohort Studies , Survivors , Patient Acceptance of Health CareABSTRACT
Smell and taste changes are bothersome treatment symptoms interfering with food intake. It remains unclear how and when children with cancer experience such changes during chemotherapy, and if the symptoms resolve after treatment. In this longitudinal study, we measured smell and taste function of 94 childhood cancer patients treated for hematological, solid, or brain malignancies. Smell and taste function were assessed using commercial Sniffin' Sticks and Taste Strips, respectively. For both tests, normative values were used to identify the presence of smell and taste abnormalities. Self-reported chemosensory and appetite changes were assessed using a questionnaire. Measurements were taken approximately 6 weeks (T0), 3 months (T1), 6 months after starting chemotherapy (T2), and 3 months after termination of chemotherapy or maintenance phase for children with acute lymphoblastic leukemia (ALL) (T3). We found that smell and taste scores did not change during active treatment (T0-2). However, approximately 20% of the patients suffered from decreased taste function according to normative values, particularly children with lymphoma or solid tumors. Changes in smell were predominantly characterized as increased rather than decreased. Self-reported changes were much more common than objectively measured, with smell changes ranging from 26 to 53% and taste changes up to 80% during treatment. After active treatment, odor threshold scores decreased in children with ALL during maintenance phase, whereas total taste scores increased in all children at T3. In summary, objectively measured smell and taste function remained stable during active treatment, while at the individual level a fairly large number of children suffered from chemosensory distortions which comprised either increased or decreased sensitivity. Individual dietary advice and coping strategies are warranted to prevent detrimental effects on food intake in children with cancer.
Subject(s)
Neoplasms , Smell , Child , Humans , Taste , Longitudinal Studies , Neoplasms/drug therapy , Dysgeusia , Taste DisordersABSTRACT
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.
Subject(s)
Cancer Survivors , Neoplasms , Child , Humans , Neoplasms/epidemiology , Neoplasms/therapy , Neoplasms/pathology , Self Report , Survivorship , SurvivorsABSTRACT
BACKGROUND: The authors developed a pain monitoring app offering educational information, and real-time health care professional feedback on clinically significant pain (>4 numeric rating scale [NRS]-11) for children with cancer to reduce pain at home. METHODS: This monocenter, nonblinded randomized controlled trial enrolled Dutch children (0-18 years old) receiving cancer treatment (≥3 months after diagnosis, ≥2 months treatment remaining). Children were randomly assigned to use the app or receive usual care (two parallel groups). We assessed whether use of the app yielded less clinically significant pain (aim 1) and whether it affected pain severity, duration, interference, pain management strategies, and parental emotional well-being (aim 2). The app was also evaluated by families (aim 3). RESULTS: A total of 94 children were randomized to use the app (15 drop-outs), and 90 were to receive care as usual (11 drop-outs). The app group (n = 79, mean age: 7.5 [5.1] years, 48% girls, 63% hemato-oncology diagnosis) reported significantly less clinically significant pain compared to usual care (n = 79, mean age: 7.5 [5.4] years, 52% girls, 65% hemato-oncology diagnosis) (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.198-0.734]) (aim 1), as well as significantly lower pain severity (ß = -0.27; 95% CI, -0.407 to -0.142). No differences were found for duration, interference, or management strategies. Parents in the app group reported significantly less distress compared to usual care (ß = -0.84; 95% CI, -1.61 to -0.03]) (aim 2). Families generally evaluated the app positively (aim 3). CONCLUSIONS: Use of the app resulted in less clinically significant pain at home. The exact working mechanisms of the app should be further elucidated.
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Background: Children treated for a malignancy are at risk to develop serious illness from a COVID-19 infection. Pegylated E. coli asparaginase (PEG-asparaginase) is used in the treatment of acute lymphoblastic leukemia. Allergy to this drug is common and both asparaginase and polyethylene glycol (PEG) are identified as possible antigens. The mRNA-based vaccines against COVID-19 contain PEG as a stabilizing component. Methods: We developed a protocol to be able to safely vaccinate children with a PEG-asparaginase allergy. All patients with a history of allergy to PEG-asparaginase have been included and skin prick testing for various PEGs was performed before vaccination with the mRNA Pfizer-BioNTech COVID-19 vaccine. Results: Twelve children between six and 16 years old were vaccinated, without allergic reaction. None of them got a positive skin prick test for PEG. Ten patients had pre-existing IgG or IgM antibodies against PEG. Conclusion: Children with a PEG-asparaginase allergy can be safely vaccinated against COVID-19 with mRNA vaccines containing PEG irrespective of IgG/IgM antibodies to PEG-asparaginase. Routine skin prick testing in patients with PEG-asparaginase allergy does not seem to be of added value.
ABSTRACT
OBJECTIVES: Health-related quality of life (HRQoL) is impaired in paediatric patients with acute lymphoblastic leukaemia (ALL). Over the past decades, ALL treatment has successfully been adjusted to the risk of relapse, which is now reflected by the stratification of patients into three risk groups who receive treatment of differing intensities. This study is the first to evaluate the longitudinal course of HRQoL in light of these adjustments and identify determinants of HRQoL. DESIGN: Two prospective, national cohort studies (add-on studies within the two most recent treatment protocols for children with ALL (ALL-10 and ALL-11)). SETTING: Dutch paediatric oncology hospitals between October 2006 and October 2009 (ALL-10) and between August 2013 and July 2017 (ALL-11). PARTICIPANTS: Patients with ALL (2-18 years) are treated according to the ALL-10 or ALL-11 treatment protocol. Patients treated according to the ALL-10 protocol only completed a cancer-specific QoL measure and patients treated according to the ALL-11 protocol completed both a cancer-specific and generic QoL measure (see below). OUTCOME MEASURES: HRQoL, assessed with parent-proxy questionnaires (PedsQL Generic and Cancer module) within the first 5 months (T0), at 1 year (T1), 2 years (T2) and 3 years (T3) after diagnosis. The proportion of patients with clinically relevant generic HRQoL impairment was compared with healthy norm values. Multivariable mixed model analyses were used to evaluate the development of HRQoL over time and its medical and sociodemographic determinants (collected on enrolment). RESULTS: Of the ALL-10 cohort, 132 families participated and of the ALL-11 cohort, 136 families participated (268 total). Thus, cancer-specific HRQoL assessments were available for 268 patients (median age 5.3 years (IQR 6.15), 56.0% boys, 69.0% medium-risk ALL), and generic HRQoL assessments for 136 patients (median age 4.8 years (IQR 6.13), 60.3% boys, 75.0% medium-risk ALL). Generic HRQoL improved between timepoints T0 and T3 (total score B 16.1, 95% CI 12.2 to 20.1, p<0.001), but did not restore to normal 1 year after the end of treatment: 28.0% of children remained impaired compared with 16% in the general population (p=0.003). Cancer-specific HRQoL generally improved from T0 to T2 (Pain B 11.3, 95% CI 7.1 to 15.5; Nausea B 11.7, 8.4 to 15.1; Procedural Anxiety B 19.1, 14.8 to 23.4; Treatment Anxiety B 12.8, 9.5 to 16.0; Worry B 3.5, 0.6 to 6.3; Communication B 8.5, 5.0 to 11.9; all p<0.001 except for Worry (p=0.02)), while Physical Appearance and Cognitive Functioning remained stable. Higher treatment intensity and experiencing pain or simultaneous chronic illness were associated with lower HRQoL over time for multiple subscales. CONCLUSIONS: HRQoL impairment is prevalent during and after ALL treatment. Patients with standard-risk ALL and reduced treatment intensity have better HRQoL than patients in higher risk groups. Systematic monitoring of HRQoL is of utmost importance in order to provide timely psychosocial interventions and supportive care.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Quality of Life , Male , Humans , Child , Child, Preschool , Female , Prospective Studies , Longitudinal Studies , Netherlands , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Pain , Surveys and QuestionnairesABSTRACT
Background: Childhood cancer survivors (CCS) who received radiotherapy involving the spleen or total body irradiation (TBI) might be at risk for splenic dysfunction. A comprehensive screening test for examining splenic dysfunction is lacking. Objective: We investigated whether IgM memory B-cells could be used to assess splenic dysfunction in CCS who received a splenectomy, radiotherapy involving the spleen, or TBI. Methods: All CCS were enrolled from the DCCSS-LATER cohort. We analyzed differences in IgM memory B-cells and Howell-Jolly bodies (HJB) in CCS who had a splenectomy (n = 9), received radiotherapy involving the spleen (n = 36), or TBI (n = 15). IgM memory B-cells < 9 cells/µL was defined as abnormal. Results: We observed a higher median number of IgM memory B-cells in CCS who received radiotherapy involving the spleen (31 cells/µL, p=0.06) or TBI (55 cells/µL, p = 0.03) compared to CCS who received splenectomy (20 cells/µL). However, only two CCS had IgM memory B-cells below the lower limit of normal. No difference in IgM memory B-cells was observed between CCS with HJB present and absent (35 cells/µL vs. 44 cells/µL). Conclusion: Although the number of IgM memory B-cells differed between splenectomized CCS and CCS who received radiotherapy involving the spleen or TBI, only two CCS showed abnormal values. Therefore, this assessment cannot be used to screen for splenic dysfunction.