Saskia M.F. Pluijm

Prediction of Methotrexate Intolerance in Juvenile Idiopathic Arthritis: a prospective, observational cohort study

BackgroundMethotrexate (MTX) is an effective and safe drug in the treatment of juvenile idiopathic arthritis (JIA). Despite its safety, MTX-related gastrointestinal adverse effects before and after MTX administration, termed MTX intolerance, occur frequently, leading to non-compliance and potentially premature MTX termination. The aim of this study was to construct a risk model to predict MTX intolerance.MethodsIn a prospective JIA cohort, clinical variables and single nucleotide polymorphisms were determined at MTX start. The Methotrexate Intolerance Severity Score was employed to measure MTX intolerance in the first year of treatment. MTX intolerance was most prevalent at 6 or 12xa0months after MTX start, which was defined as the outcome for the prediction model. The model was developed in 152 patients using multivariable logistic regression analysis and subsequently internally validated using bootstrapping.ResultsThe prediction model included the following predictors: JIA category, antinuclear antibody, parent/patient assessment of pain, Juvenile Arthritis Disease Activity Score-27, thrombocytes, alanine aminotransferase and creatinine. The model classified 77.5% of patients correctly, and 66.7% of patients after internal validation by bootstrapping. The lowest predicted risk of MTX intolerance was 18.9% and the highest predicted risk was 85.9%. The prediction model was transformed into a risk score (range 0–17). At a cut-off of ≥6, sensitivity was 82.0%, specificity 56.1%, positive predictive value was 58.7% and negative predictive value 80.4%.ConclusionsThis clinical prediction model showed moderate predictive power to detect MTX intolerance. To develop into a clinically usable tool, it should be validated in an independent cohort and updated with new predictors. Such an easy-to-use tool could then assist clinicians in identifying patients at risk to develop MTX intolerance, and in turn to monitor them closely and intervene timely in order to prevent the development of MTX intolerance.Trial registrationISRCTN register, www.isrctn.com, ISRCTN13524271

The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia

Body mass index and change in body mass index during treatment may influence treatment outcome of pediatric patients with acute lymphoblastic leukemia. However, previous studies in pediatric acute lymphoblastic leukemia reported contradictory results. We prospectively collected data on body composition from a cohort of newly diagnosed Dutch pediatric patients with acute lymphoblastic leukemia (n=762, age 2–17 years). Patients were treated from 1997–2004 and the median follow-up was 9 years (range, 0–10). Body mass index at diagnosis was expressed as age- and gender-matched standard deviation scores and on the basis of these scores the patients were categorized as being underweight, of normal weight or overweight. Multivariate analyses showed that patients who were underweight (8%) had a higher risk of relapse [hazard ratio: 1.88, 95% confidence interval (1.13–3.13)], but similar overall survival and event-free survival as patients who had a normal weight or who were overweight. Patients with loss of body mass index during the first 32 weeks of treatment had a similar risk of relapse and event-free survival, but decreased overall survival [hazard ratio: 2.10, 95% confidence interval (1.14–3.87)] compared to patients without a loss of body mass index. In addition, dual X-ray absorptiometry scans were performed in a nested, single-center cohort. Data from these scans revealed that a loss of body mass consisted mainly of a loss of lean body mass, while there was a gain in the percentage of fat. In conclusion, being underweight at diagnosis is a risk factor for relapse, and a decrease in body mass index early during treatment is associated with decreased survival. In addition, loss of body mass during treatment seems to consist mainly of a loss of lean body mass. This study was approved by the Medical Ethical Committee in 1996 (trial number NTR460/SNWLK-ALL-9).

Talking about Death with Children with Incurable Cancer: Perspectives from Parents.

OBJECTIVEnTo investigate the rationale and consequences associated with a parents decision to discuss death with a child with incurable cancer.nnnSTUDY DESIGNnWe present data from a larger retrospective study involving bereaved parents of a child who died of cancer. Parents were asked whether they had discussed the impending death with their child, whether they reflected on this discussion positively, their reasons for not discussing death with their child, and the manner in which the conversation regarding death occurred. The data were analyzed qualitatively using a framework approach.nnnRESULTSnOf the 86 parents of 56 children who answered the questions regarding discussing death with their child, 55 parents of 35 children did not discuss the impending death with their child. The following themes were identified: the parents inability to discuss the impending death; the parents desire to protect their child; views regarding talking with children; parents views of child characteristics; the childs unwillingness to discuss the subject; lack of opportunity to talk; and the childs disability. The parents who did discuss death with their child generally used symbolic and/or religious narratives, or they had brief, direct conversations regarding death. The majority of parents felt positive regarding their decision about whether to talk with their child about his/her impending death.nnnCONCLUSIONnMost parents in this study cited several reasons for not discussing death with their child. Our findings highlight the sensitive and complex issues surrounding these conversations, indicating that there may be a role for clinicians in supporting parents.

Home-Based Palliative Care for Children With Incurable Cancer: Long-term Perspectives of and Impact on General Practitioners

CONTEXTnAlthough a large percentage of children with advanced-stage cancer die at home, remarkably little information is available regarding the experience of general practitioners (GPs) with respect to providing home-based palliative care to children with incurable cancer.nnnOBJECTIVESnThe objective of this study was to explore the perspectives of GPs who care for children with advanced-stage cancer in a home-based setting.nnnMETHODSnIn this cross-sectional study, 144 GPs who provided home-based palliative care to 150 children with incurable cancer from 2001 through 2010 were invited to complete a questionnaire addressing their perspectives regarding: 1) symptom management, 2) collaboration with other health care professionals, 3) the childs death and care after death, and 4) impact of having provided palliative care, scored on distress thermometer (range 0-10).nnnRESULTSnA total of 112 GPs (78%) responded, and 91 GPs completed the questionnaire for 93 patients. The median interval between the childs death and completing the questionnaire was sevenxa0years. The most prevalent symptoms reported in the patients were fatigue (67%) and pain (61%). Difficulties with communicating with (14%), coordinating with (11%), collaborating with (11%), and contacting (2%) fellow members of the multidisciplinary treatment team were rare. Hectic (7%) and shocking (5%) situations and panic (2%) around the childs death were rare. GPs reported feelings of sadness (61%) and/or powerlessness (43%) around the time of the patients death, and they rated their own distress level as relatively high during the terminal phase (median score 6, range 0-9.5). The majority of GPs (94%) reported that they ultimately came to terms with the childs death.nnnCONCLUSIONnIn general, GPs appear to be satisfied with the quality of home-based palliative care that they provide pediatric patients with incurable cancer. Communication among health care professionals is generally positive and is considered important. Finally, although the death of a pediatric patient has a profound impact on the GP, the majority of GPs eventually come to terms with the childs death.

Health-related fitness in very long-term survivors of childhood cancer: A cross-sectional study

Impairment of health‐related physical fitness (HRPF) in survivors of acute lymphoblastic leukemia has been shown. However, evidence of impairment in survivors of other pediatric malignancies and possible risk factors is limited.

Genetic variation and bone mineral density in long-term adult survivors of childhood cancer.

Despite similarities in upfront treatment of childhood cancer, not every adult survivor of childhood cancer (CCS) has an impaired bone mineral density (BMD). No data are available on the role of genetic variation on impairment of BMD in CCS.

Obesity independently influences gonadal function in very long-term adult male survivors of childhood cancer.

Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment.

The distress thermometer provides a simple screening tool for selecting distressed childhood cancer survivors

We investigated the value of the distress thermometer, a one‐item screening tool, in childhood cancer survivors.

Genetic Biomarkers to Identify the Risk of Osteonecrosis in Children with Acute Lymphoblastic Leukemia.

Osteonecrosis is a disabling complication of treatment for pediatric acute lymphoblastic leukemia, and much effort has been made to predict which patients are prone to develop this disease. Multiple clinical and genetic factors have already been identified as being associated with osteonecrosis; however, a prediction model that combines pretreatment genetic biomarkers and clinical factors has not yet been designed. Such a prediction model can only be developed with continuing international collaborations and research efforts, including large genome-wide association studies.

Final height and IGF1 in adult survivors of Wilms tumour

OBJECTIVEnOne-sided nephrectomy is followed by increased levels of IGF1, associated with linear growth during childhood. The aim was to evaluate final height and IGF1 levels in nephrectomized Wilms tumour survivors when compared with healthy Dutch references and survivors of other cancer types.nnnDESIGNnCross-sectional retrospective study.nnnMETHODSnData of 575 adult childhood cancer survivors were analysed. median follow-up time was 17.8 (range 5.048.8) years. Analysis of (co)variance was performed to evaluate differences between subgroups: nephrectomized Wilms survivors treated with or without abdominal irradiation (n=41 and n=36) and survivors of other cancer types treated with or without irradiation involving the cranium, abdomen or total body (n=149 and n=349). Main outcome measures were IGF1 and height, expressed as SDS.nnnRESULTSnAfter adjustment for age at diagnosis, former corticosteroid treatment and renal impairment, height SDS in non-irradiated nephrectomized Wilms survivors was significantly higher than that in non-irradiated survivors of other cancer types (estimated mean SDS -0.09 vs -0.49, P=0.044), abdominal irradiated survivors (SDS -0.70, P=0.015) and other irradiated survivors (SDS -1.47, P<0.001). Non-irradiated nephrectomized Wilms tumour survivors had significantly higher IGF1 SDS than other irradiated survivors (estimated mean SDS -0.05 vs -1.36, P<0.001 and 0.11 vs 1.37, P<0.001), while there was no significant difference with the other two subgroups.nnnCONCLUSIONSnAdult survivors of Wilms tumour showed better attainment of final height and relatively higher IGF1 levels than those of other cancer types who had significantly shorter stature and lower IGF1 levels than Dutch references.