Assessment of proxy-reported responses as predictors of motor and sensory peripheral neuropathy in children with B-lymphoblastic leukemia.

Chemotherapy-induced peripheral neuropathy (CIPN), a common condition in children with acute lymphoblastic leukemia, can be challenging to diagnose. Using data from Children's Oncology Group AALL0932 physical function study, we sought to determine if parent/guardian proxy-reported responses from the Pediatric Outcomes Data Collection Instrument could identify children with motor or sensory CIPN diagnosed by physical/occupational therapists (PT/OT). Four variables moderately discriminated between children with and without motor CIPN (c-index 0.76, 95% confidence interval [CI]: 0.64-0.84), but sensory and optimism-corrected models had weak discrimination (c-index sensory models 0.65, 95% CI: 0.54-0.74). New proxy-report measures are needed to identify children with PT/OT diagnosed CIPN.

Physical activity and physical fitness assessments in adolescents and young adults diagnosed with cancer: a scoping review.

PURPOSE: This scoping review describes the assessment methodologies for physical activity (PA) and physical fitness assessments used in studies focusing on adolescents and young adults (AYAs) diagnosed with cancer. METHODS: A search of the literature was conducted in PubMed, CINAHL, Web of Science, and Cochrane Library following the PRISMA-ScR statement. A total of 34 studies were included in this review. RESULTS: PA was primarily assessed via self-reported questionnaires (30/34) either completed in-person (n = 17) or online (n = 13) at different time points and different stages along the cancer trajectory (i.e., from diagnosis onward). A total of 9 studies conducted a physical fitness assessment. CONCLUSIONS: PA and physical fitness measurements are key when trying to describe outcomes, assess for associations, track changes, measure intervention adherence, and test intervention efficacy and effectiveness. Considerable heterogeneity across studies was reported limiting the generation of formal recommendations or guidance for researchers, healthcare providers, and policy makers.

Recommendations for the surveillance of mental health problems in childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Survivors of childhood, adolescent, and young adult (diagnosed when <25 years of age) cancer are at risk of mental health problems. The aim of this clinical practice guideline is to harmonise international recommendations for mental health surveillance in survivors of childhood, adolescent, and young adult cancer. This guideline was developed by a multidisciplinary panel of experts under the sponsorship of the International Guideline Harmonization Group. We evaluated concordance among existing survivorship clinical practice guidelines and conducted a systematic review following evidence-based methods. Of 7249 studies identified, 76 articles from 12 countries met the inclusion criteria. Recommendations were formulated on the basis of identified evidence in combination with clinical considerations. This international clinical practice guideline strongly recommends mental health surveillance for all survivors of childhood, adolescent, and young adult cancers at every follow-up visit and prompt referral to mental health specialists when problems are identified. Overall, the recommendations reflect the necessity of mental health surveillance as part of comprehensive survivor-focused health care.

Newly identified chemotherapy-induced peripheral neuropathy in a childhood cancer survivorship clinic.

Chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect of pediatric cancer therapy, can be challenging to diagnose. We estimated the prevalence of newly identified and previously diagnosed CIPN in the regional HEROS Childhood Cancer Survivorship Clinic. From 2016 to 2018, 148 survivors (45.3% female, age 17.1 [SD 7.7] years, 81.8% in ongoing routine oncology follow-up) had their initial survivorship evaluation at an average of 7.4 (SD 6.6) years from diagnosis. Fifty-six survivors (37.8%) had CIPN, of these 46 (82.1%) were newly identified. Our findings demonstrate CIPN may be missed in routine oncology care, and new methods are needed to screen for CIPN.

A Case of Pheochromocytoma as a Subsequent Neoplasm in a Survivor of Childhood Embryonal Rhabdomyosarcoma.

Childhood cancer survivors are at risk for subsequent neoplasms. We describe the clinical presentation and genetic testing of a 29-year-old woman diagnosed with a pheochromocytoma 22 years post-treatment for childhood embryonal rhabdomyosarcoma of the bladder. Genetic testing for cancer predisposition revealed a pathogenic variant in BRCA2 and a variant of uncertain significance in MSH2. Pathogenic variants associated with deafness were also identified in GJB2. This article reports a novel subsequent neoplasm following childhood embryonal rhabdomyosarcoma, and discusses the potential contribution of genetic cancer predisposition to this case as well as the clinical implications of genetic testing.

Ultrasound-assisted Lumbar Puncture for Obese Pediatric Oncology Patients: A Feasibility Study.

Lumbar punctures (LPs) are performed frequently on children with leukemia and lymphoma as part of the standard of care. They are typically performed by pediatric oncology providers for both diagnostic and therapeutic interventions with the aid of moderate or deep sedation. Point-of-Care Ultrasound (POCUS) has emerged as a promising strategy to aid in LP procedures and has been found to be associated with lower number of attempts, and higher success rates. We describe our experience using POCUS to assist with LPs in a subgroup of pediatric oncology patients identified to be procedurally difficult secondary to obesity. This collaboration was well received and resulted in successful LPs in most (8/9) cases. This is a promising modality to improve the delivery of care and LP success in pediatric oncology patients.

The association of health status and cancer history of young adult survivors of childhood cancer with parental accompaniment to survivorship clinic visits.

PURPOSE: Adult childhood cancer survivors are frequently accompanied by a parent to survivorship clinic. From clinical evaluations among young adult survivors of childhood cancer we aimed to (1) investigate the association between accompaniment and the survivors' health complexity; and (2) determine whether accompaniment is associated with adherence to recommended surveillance tests and follow-up in clinic. METHODS: This was a cross-sectional study of all patients ≥ 18 years old at their first visit to the regional Yale Childhood Cancer Survivorship Clinic from 2003 to 2018. Patients underwent standardized evaluations for medical, neurocognitive, and emotional late effects of therapy; individuals accompanying patients were documented. RESULTS: The 168 patients were a median of 12.0 (range: 0-17.9) years at diagnosis and 22.7 (range: 18.1-39.9) years at evaluation, and 45.8% were accompanied by a parent. In multivariable analyses, 18.0-24.99 years vs. 25.0-39.99 years at visit (OR = 3.43, p = 0.022) and central nervous system (CNS) tumor diagnosis (OR = 6.09 vs. leukemia/lymphoma diagnosis, p = 0.010) were significantly associated with parental accompaniment. Accompaniment was not associated with number and severity of medical late effects, neurocognitive impairment, or emotional distress. Accompaniment was not associated with completed surveillance tests or a clinic follow-up within 2 years. CONCLUSION: Forty-six percent of survivors were accompanied by a parent, and accompaniment was not associated with survivor health status. Accompaniment was not associated with adherence to recommended surveillance tests or clinic follow-up.

Severity of reduced bone mineral density and risk of fractures in long-term survivors of childhood leukemia and lymphoma undergoing guideline-recommended surveillance for bone health.

BACKGROUND: Survivors of childhood leukemia/lymphoma are at increased risk for reduced bone mineral density (BMD). The authors sought to determine the frequency of reduced BMD detected by off-therapy surveillance, factors associated with reduced BMD, and the association of reduced BMD with fractures. METHODS: This cross-sectional study included childhood leukemia/lymphoma survivors attending 2 survivorship clinics who received guideline-recommended BMD surveillance ≥2 years post-therapy with dual-energy x-ray absorptiometry (from January 1, 2004 to August 31, 2016). Lumbar spine BMD z-scores were height-for-age-adjusted. Low and very low BMD were >1 SD and >2 SDs below norms, respectively. Treatment, chronic conditions, and fractures were abstracted from medical records. Logistic regression was used to examine the association of low BMD with patient/treatment factors and fractures. RESULTS: In total, 542 patients (51.5% female) with a mean age of 15.5 years (range, 4.4-52.2 years) who were 6 years post-therapy (range, 2.0-35.1 years) were evaluated, including 116 who reported post-therapy fractures. Lumbar spine low BMD was identified in 17.2% of survivors, and very low BMD was identified in 3.5% of survivors, but frequencies varied considerably between subgroups; 10.8% of survivors aged 15 to 19 years at diagnosis had very low BMD. In multivariable analyses, older age at diagnosis, white race, and being underweight were significantly associated with low BMD. Survivors with low BMD had greater odds of nondigit fractures (odds ratio, 2.2; 95% CI, 1.3-3.7) and specifically long-bone fractures (odds ratio, 2.7; 95% CI, 1.5-4.7). CONCLUSIONS: In this study of childhood leukemia/lymphoma survivors undergoing guideline-recommended dual-energy x-ray absorptiometry surveillance, patients who were older at diagnosis, white, and underweight were at the highest risk for lumbar spine low BMD. Low BMD was associated with a greater risk of fractures, emphasizing the clinical importance of surveillance.

Longitudinal analysis of quality-of-life outcomes in children during treatment for acute lymphoblastic leukemia: A report from the Children's Oncology Group AALL0932 trial.

BACKGROUND: Children with average-risk acute lymphoblastic leukemia (AR-ALL) face many challenges that can adversely affect their quality of life (QOL). However, to the authors' knowledge, patterns and predictors of QOL impairment during therapy have not been well characterized to date. METHODS: Patients with AR-ALL who were enrolled on the Children's Oncology Group AALL0932 trial were offered participation in this prospective cohort study if they were aged ≥4 years at the time of diagnosis and had an English-speaking parent. At approximately 2 months, 8 months, 17 months, 26 months, and 38 months (boys only) after diagnosis, parents completed the Pediatric Quality of Life Inventory Generic Core Scales Version 4.0 (PedsQL4.0) and McMaster Family Assessment Device instruments for QOL (physical, emotional, and social functioning) and family functioning, respectively. The proportions of individuals scoring in the impaired range (2 standard deviations below the population mean) were calculated at each time point. Longitudinal impairment patterns and predictors were examined. RESULTS: A total of 594 participants with AR-ALL were diagnosed at a mean age of 6.0 years (standard deviation, 1.6 years). At 2 months, a substantial proportion of participants had impaired scores for physical (36.5%; 95% confidence interval [95% CI], 32.3%-40.8%) and emotional (26.2%; 95% CI, 22.5%-30.2%) functioning compared with population norms of 2.3%. These elevations persisted at 26 months. Emotional impairment at 2 months (odds ratio, 3.4; 95% CI, 1.5-7.7) was found to significantly predict emotional impairment at 26 months. In repeated measures analysis with multivariate modeling, unhealthy family functioning (odds ratio, 1.5; 95% CI, 1.1-2.1) significantly predicted emotional impairment controlling for age and sex. QOL outcomes were similar between sexes at the end of therapy (26 months for girls and 38 months for boys). CONCLUSIONS: Many children with AR-ALL experience physical and emotional functioning impairment that begins early in treatment and persists. Early screening may identify high-risk patients who might benefit from family-based interventions. Cancer 2018;124:571-9. © 2017 American Cancer Society.

Long-term psychological and educational outcomes for survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Neuroblastoma survivors may be at elevated risk for psychological impairments because of their young age at diagnosis and neurotoxic treatment, but this is not well described. METHODS: A total of 859 ≥5-year survivors of neuroblastoma younger than 18 years (diagnosed in 1970-1999), who had a median age at diagnosis of 0.8 years (range: 0.0-7.3 years) and a median follow-up of 13.3 years (range: 8.0-17.9 years), were compared with 872 siblings of childhood cancer survivors who were younger than 18 years with the parent-reported Behavior Problem Index (BPI) for psychological functioning. Age- and sex-adjusted multivariate log-binomial models were used to identify factors associated with impairment in BPI domains (scores worse than the sibling 10th percentile). The impact of psychological impairment on educational outcomes was examined among survivors. RESULTS: Compared with siblings, neuroblastoma survivors had an increased prevalence of impairment in the domains of anxiety/depression (19% vs 14%; P = .003), headstrong behavior (19% vs 13%; P < .001), attention deficits (21% vs 13%; P < .001), peer conflict/social withdrawal (26% vs 17%; P < .001), and antisocial behavior (16% vs 12%; P = .01). Common treatment exposures (vincristine, cisplatin, and retinoic acid) were not associated with impairment. Having 2 or more chronic health conditions predicted impairment in 4 domains (P < .001). Specifically, pulmonary disease predicted impairment in all 5 domains (P ≤ .004). Endocrine disease (P ≤ .004) and peripheral neuropathy (P ≤ .02) each predicted impairment in 3 domains. Psychological impairment was associated with special education service usage and educational attainment less than college. CONCLUSIONS: Neuroblastoma survivors are at elevated risk for psychological impairment, which is associated with special education service usage and lower adult educational attainment. Those with chronic health conditions may represent a high-risk group for targeted screening and intervention. Cancer 2018. © 2018 American Cancer Society.

Parental perception of child vulnerability in childhood cancer survivors.

BACKGROUND: Parents' perception of their children's vulnerability to illness following cancer treatment is largely unknown, but is important to understand given known challenges of transitioning survivors to postcancer care. We investigated the frequency of and factors associated with perceived vulnerability by parents of childhood cancer survivors attending a regional survivorship clinic. PROCEDURE: This cohort study was offered to all parents of pediatric patients (currently ≤18 years) attending the Yale childhood cancer survivorship clinic January 2010 to October 2016 who were ≥1 year postcurative cancer therapy. Participating parents (one per patient) completed the standardized Child Vulnerability Scale at the beginning of the clinic visit (cutoff score ≥10 for perceived vulnerability). Patient sociodemographics, cancer history, and posttherapy complications were abstracted from medical records. RESULTS: Overall, 116 parents participated (98% participation rate) consisting of 89% mothers; survivors were 46% female, had a current mean age of 12.7 ± 3.9 years, and were a mean of 6.4 ± 3.8 years posttherapy. Twenty-eight percent (n = 33) of parents perceived their children as vulnerable. Survivor sociodemographics (age, sex, race/ethnicity, family income, insurance, parental marital status, number of siblings), cancer diagnosis, years off-therapy, survivorship visit number, treatment intensity, and late complications (number, type, severity) were not associated with perception of vulnerability. CONCLUSIONS: A sizeable proportion of parents continue to perceive their children as vulnerable even years after cancer therapy completion independent of current health status or past cancer history. Our data suggest the need to educate all parents of childhood cancer survivors regarding health risk, including those at lower risk for late complications.

Randomized web-based physical activity intervention in adolescent survivors of childhood cancer.

BACKGROUND: Healthy lifestyle choices, including participation in regular physical activity, may improve health outcomes in survivors of childhood cancer. We aimed to evaluate the efficacy of a web-delivered physical activity intervention among adolescent survivors to increase moderate to vigorous physical activity (MVPA) and improve fitness and neurocognitive and health-related quality of life (HRQoL) over 24 weeks. PROCEDURE: This randomized controlled trial was conducted among survivors (aged ≥11 to <15 years) treated at a single institution. Participants were randomized to either a physical activity intervention delivered over the internet or a control group. The intervention group received educational materials, an activity monitor, and access to an interactive website designed to motivate increased physical activity via rewards; the control group received an activity monitor and educational materials. Physical activity, fitness, and neurocognitive and HRQoL outcomes were assessed at baseline and at 24 weeks. Mean changes were compared between groups using paired t-tests. RESULTS: Of the 97 survivors enrolled, 78 completed the study; the mean age was 12.7 (standard deviation 1.1), 80% were White, and 55.1% were female. Fifty-three survivors were assigned to the intervention and 25 to the control group. While survivors in the intervention group increased, and those in the control group decreased (4.7 ± 119.9 vs. -24.3 ± 89.7 min) weekly MVPA, this difference was not significant (P = 0.30). However, hand grip strength, number of sit-ups and pushups, neurocognitive function, and HRQoL outcomes improved in the intervention, but not in the control group. CONCLUSIONS: An interactive, rewards-based intervention designed to increase MVPA is feasible in adolescent survivors of childhood cancer.

Physical activity barriers, preferences, and beliefs in childhood cancer patients.

PURPOSE: Childhood cancer patients report low physical activity levels despite the risk for long-term complications that may benefit from exercise. Research is lacking regarding exercise barriers, preferences, and beliefs among patients (1) on- and off-therapy and (2) across the age spectrum. METHODS: Cross-sectional study in the Yale Pediatric Hematology-Oncology Clinic (October 2013-October 2014). Participants were ≥ 4 years old, > 1 month after cancer diagnosis at < 20 years, not acutely ill, expected to live > 6 months, and received chemotherapy and/or radiation. Participants (or parents if < 13 years) completed a survey. RESULTS: The 162 patients (99% participated) were 34% children (4.0-12.9 years), 31% adolescents (13.0-17.9 years), and 35% adults (≥ 18 years). Most had leukemia/lymphoma (66%); 32% were on-therapy. On-therapy patients were more likely than off-therapy patients (73 vs. 48%; p = 0.003) to report ≥ 1 barrier related to physical complaints, such as "just too tired" (46 vs. 28%; p = 0.021) or "afraid" of injury (22 vs. 9%; p = 0.027). The majority preferred walking (73%), exercising at home (91%), exercising in the afternoon (79%), and a maximum travel time of 10-20 min (54%); preferences did not vary significantly by therapy status or age. Most respondents (94%) recognized the benefits of exercise after cancer, but 50% of on- vs. 12% of off-therapy patients believed "their cancer diagnosis made it unsafe to exercise regularly" (p < 0.001). CONCLUSIONS: Physical activity barriers pertaining to physical complaints and safety concerns were more pronounced in on-therapy childhood cancer patients but persisted off-therapy. Preferences and beliefs were relatively consistent. Our data can inform interventions in different patient subgroups.

Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis.

Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with 5-year survival rates of ∼90% even after largely eliminating cranial radiation. This meta-analysis assesses the long-term neurocognitive functioning after chemotherapy-only regimens among survivors of childhood ALL. We conducted a systematic review to identify studies that evaluated long-term neurocognitive functioning following treatment of ALL by searching MEDLINE/PubMed, Database of Abstracts of Reviews of Effects, and secondary sources. Studies were included if ALL survivors were in continuous first remission, did not receive any radiation, were at least ≥2 years off therapy or ≥5 years since diagnosis, and were compared with a healthy control group. Weighted mean differences with 95% confidence intervals (CIs) were calculated. Ten nonexperimental studies met all eligibility criteria and included 509 patients and 555 controls. Meta-analysis demonstrated statistically significant moderate impairment across multiple neurocognitive domains evaluated, with intelligence most affected. Significant differences in standard deviation (SD) scores were found for Full Scale intelligence quotient (IQ) (-0.52 SD; 95% CI, -0.68 to -0.37), Verbal IQ (-0.54 SD; 95% CI, -0.69 to -0.40), and Performance IQ (-0.41 SD; 95% CI, -0.56 to -0.27); these SD scores correspond to changes in IQ of 6 to 8 points. Working memory, information processing speed, and fine motor domains were moderately, but statistically significantly, impaired. Meta-analysis of ALL survivors treated without cranial radiation demonstrated significant impairment in IQ and other neurocognitive domains. Patients and their families should be informed about these potential negative effects to encourage surveillance and educational planning. Both preventive and intervention strategies are needed.

A home-based physical activity intervention using activity trackers in survivors of childhood cancer: A pilot study.

BACKGROUND: Over 70% of childhood cancer survivors develop late complications from therapy, many of which can be mitigated by physical activity. Survivors engage in exercise at similar or lower rates than their sedentary healthy peers. We piloted a novel home-based exercise intervention with a motivational activity tracker. We evaluated (i) feasibility, (ii) impact on activity levels and physical fitness, and (iii) barriers, preferences, and beliefs regarding physical activity. METHODS: Childhood cancer survivors currently 15 years or older and not meeting the Centers for Disease Control and Prevention physical activity guidelines were enrolled and instructed to wear the Fitbit One, a 4.8 cm × 1.8 cm motivational activity tracker, daily for 6 months. Baseline and follow-up evaluations included self-report surveys, an Actigraph accelerometer for 7 days, and a VO2 maximum test by cardiac stress test. RESULTS: Nineteen participants were enrolled (13.4% participation rate) with a mean age of 24.3 ± 5.8 years (range 15-35). Four participants withdrew with a 79% retention rate. Participants wore the Fitbit an average of 19.0 ± 4.7 days per month during months 1-3 and 15.0 ± 7.9 days per month during months 4-6. Total weekly moderate to vigorous physical activity increased from 265.6 ± 117.0 to 301.4 ± 135.4 min and VO2 maximum increased from 25.7 ± 7.7 to 27.2 ± 7.4 ml/kg/min. These changes were not statistically significant (P = 0.47 and 0.30, respectively). Survey responses indicated no change in barriers, preferences, and beliefs regarding physical activity. CONCLUSIONS: This pilot study of a motivational activity tracker demonstrated feasibility as measured by participant retention, receptivity, and belief of utility. Future studies with a large sample size are needed to demonstrate the efficacy and sustainability of this intervention.

The Behavior Rating Inventory of Executive Function (BRIEF) to Identify Pediatric Acute Lymphoblastic Leukemia (ALL) Survivors At Risk for Neurocognitive Impairment.

Neurocognitive problems, including executive dysfunction, are potential late effects of pediatric acute lymphoblastic leukemia treatment. Surveillance for neurocognitive impairment in a timely and efficient manner is imperative to ongoing clinical care. We sought to determine if the Behavior Rating Inventory of Executive Function (BRIEF) Parent Form identified leukemia survivors with cognitive impairment. In this 28-site cross-sectional study, parents of 256 children, a mean of 8.9±2.2 years after treatment for standard-risk precursor-B acute lymphoblastic leukemia and in first remission, completed the BRIEF. We used a multivariate logistic regression to calculate the association between elevated scores on 3 composite BRIEF indices (Behavioral Regulation Index, Metacognition Index, Global Executive Composite [GEC]) and special education and attention-deficit/hyperactivity disorder (ADHD) outcomes. All BRIEF index scores were significantly associated with receipt of special education services or ADHD. The BRI was most strongly associated with ADHD (odds ratios=4.33; 95% confidence interval, 1.72-10.9). The GEC was most strongly associated with ADHD (odds ratios=4.46; 95% confidence interval, 1.77-11.22). Elevated scores on the BRIEF GEC were associated with low sensitivity (24.1 to 39.1) for detecting the outcomes but better specificity (range, 87.7 to 89.3). These results suggest that the parent-completed BRIEF is associated with clinical outcomes but is not a sensitive tool to identify leukemia survivors that require a comprehensive neuropsychological assessment.

Experiences with the survivorship care plan in primary care providers of childhood cancer survivors: a mixed methods approach.

PURPOSE: Focusing on primary care providers (PCPs) of known childhood cancer survivors, we used a mixed methods approach to understand providers' experiences with the survivorship care plan (SCP), as well as preferences and barriers regarding survivorship care. METHODS: The SCP was sent to 202 eligible PCPs of patients attending a regional survivorship clinic. The PCPs then completed quantitative postal surveys. Sixteen PCPs underwent an additional qualitative interview. Provider characteristics were examined as potential predictors of experiences, preferences, and barriers regarding survivorship care. Grounded theory was utilized to analyze the qualitative data. RESULTS: Respondents (n=134) included 55% pediatricians, 23% internists, 20% family practitioners, and 2% obstetricians/gynecologists. Only 8% of PCPs preferred to have primary responsibility for survivorship care; 46% favored a specialized clinic. A minority of PCPs reported that they felt "very comfortable" using the SCP to guide surveillance (31%) or deliver all survivorship care (3%). Endorsed barriers included lack of knowledge/training (74%), not recalling or understanding the contents of the SCP (69%), and uncertainty about who is responsible for providing care (58%). Two distinct themes emerged from the qualitative interviews: a preference not to be responsible for survivorship care, and uncertain utility of the SCP. CONCLUSIONS: Our study suggests that PCPs of childhood cancer survivors generally felt uncomfortable using the SCP and providing survivorship care. Even with the availability of the SCP, the biggest barrier was lack of knowledge. Our data suggests that including PCPs in survivorship care will require additional educational opportunities and evaluation of more collaborative models of care delivery.

Prospective, longitudinal assessment of quality of life in children from diagnosis to 3 months off treatment for standard risk acute lymphoblastic leukemia: Results of Children's Oncology Group study AALL0331.

Standard risk acute lymphoblastic leukemia (SR-ALL) has high cure rates, but requires 2-3 years of therapy. We aimed to (i) prospectively evaluate health-related quality of life (HRQOL) during and after SR-ALL therapy, and (ii) identify associated predictors. Parents of 160 SR-ALL patients enrolled on Children's Oncology Group (COG) therapeutic trial AALL0331 at 31 sites completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (physical, emotional and social functioning) and Family Assessment Device-General Functioning (FAD-GF) at 1, 6 and 12 months after diagnosis, and 3 months post-therapy. Mean PedsQL scores in physical, emotional and social functioning were impaired 1 month after diagnosis but steadily improved. Three months post-therapy, impaired physical and social functioning was observed in 27.8 and 25.8% of patients, respectively. In repeated-measures analysis, problematic family functioning predicted emotional (OR = 1.85, 95% CI 1.03-3.34) and social (OR = 1.99, 95% CI 1.21-3.27) impairment. Larger household size was associated with social impairment (OR = 1.21, 95% CI 1.02-1.45). Adverse neurological event(s) during therapy predicted post-therapy physical (OR = 5.17, 95% CI 1.61-16.63) and social (OR = 8.17, 95% CI 1.19-56.16) impairment. HRQOL 1 month after diagnosis was not predictive of HRQOL 3 months after therapy completion. In conclusion, children with SR-ALL experience considerable impairment in HRQOL at the end of induction, but rapidly improve. However, many still experience physical and social impairment 3 months post-therapy, suggesting a role for continued family and physical functioning support. Longer follow-up is needed to determine if post-therapy deficits change over time.

Prevalence and predictors of anxiety and depression after completion of chemotherapy for childhood acute lymphoblastic leukemia: A prospective longitudinal study.

BACKGROUND: The months immediately after the completion of treatment for childhood acute lymphoblastic leukemia (ALL) are often regarded as a stressful time for children and families. In this prospective, longitudinal study, the prevalence and predictors of anxiety and depressive symptoms after the completion of treatment were examined. METHODS: Participants included 160 children aged 2 to 9 years with standard-risk ALL who were enrolled on Children's Oncology Group protocol AALL0331. Parents completed standardized rating scales of their children's emotional-behavioral functioning and measures of coping and family functioning at approximately 1 month, 6 months, and 12 months after diagnosis and again 3 months after the completion of chemotherapy. RESULTS: At 3 months off therapy, approximately 24% of survivors had at-risk/clinically elevated anxiety scores and 28% had elevated depression scores, which are significantly higher than the expected 15% in the general population (P = .028 and .001, respectively). Patients with elevated anxiety 1 month after diagnosis were at greater risk of off-therapy anxiety (odds ratio, 4.1; 95% confidence interval, 1.31-12.73 [P = .022]) and those with elevated depressive symptoms 6 months after diagnosis were at greater risk of off-therapy depression (odds ratio, 7.88; 95% confidence interval, 2.61-23.81 [P = .0002]). In adjusted longitudinal analyses, unhealthy family functioning (P = .008) and less reliance on social support coping (P = .009) were found to be associated with risk of emotional distress. Children from Spanish-speaking families (P = .05) also were found to be at a greater risk of distress. CONCLUSIONS: A significant percentage of children experience emotional distress during and after therapy for ALL. These data provide a compelling rationale for targeted early screening and psychosocial interventions to support family functioning and coping skills. Cancer 2016;122:1608-17. © 2015 American Cancer Society.

Anxiety, pain, and nausea during the treatment of standard-risk childhood acute lymphoblastic leukemia: A prospective, longitudinal study from the Children's Oncology Group.

BACKGROUND: This prospective study describes the procedure-related anxiety, treatment-related anxiety, pain, and nausea experienced by children with standard-risk acute lymphoblastic leukemia (ALL) during the first year of treatment. METHODS: This study was undertaken at 31 Children's Oncology Group (COG) sites. Eligible children who were 2 to 9.99 years old were enrolled in a COG trial for patients with newly diagnosed standard-risk ALL from 2005 to 2009. Parents completed a demographic survey at the baseline and the Pediatric Quality of Life Inventory 3.0 Cancer Module (proxy version) and the General Functioning Scale of the Family Assessment Device 1, 6, and 12 months after the diagnosis. The association between patient-related (age, sex, ethnicity, and treatment), parent-related (marital status and education), and family-related factors (functioning, income, and size) and symptom scores was evaluated. RESULTS: The mean scores for procedure-related anxiety, treatment-related anxiety, and pain improved during the first year of treatment (P < .0389). The mean nausea score was poorer 6 months after the diagnosis in comparison with the other assessments (P = .0085). A younger age at diagnosis was associated with significantly worse procedure-related anxiety (P = .004). An older age (P = .0002) and assignment to the intensified consolidation study arm (P = .02) were associated with significantly worse nausea. CONCLUSIONS: Children with ALL experienced decreasing treatment-related anxiety, procedure-related anxiety, and pain during the first year of treatment. In comparison with scores at 1 and 12 months, nausea was worse 6 months after the diagnosis. Minimization of procedure-related anxiety in younger children and improved nausea control in older children and those receiving more intensified treatment should be prioritized.