Longitudinal use of patient reported outcomes in pediatric leukemia and lymphoma reveals clinically relevant symptomatic adverse events.

BACKGROUND: Leukemia and lymphoma (LL) are the most common cancer diagnoses of childhood with high survival rates, but not without impact on the child's functioning and quality of life. This study aimed to use patient-reported data to describe the symptomatic adverse event (AE) experiences among children with LL diagnoses. METHODS: Two hundred and fifty seven children and adolescents aged 7-18 years with a first LL diagnosis completed the Pediatric Patient-Reported version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) and Patient-Reported Outcome Measurement Information System (PROMIS) Pediatric measures before starting a treatment course (T1) and after the treatment (T2). RESULTS: Fatigue was the most severe AE (68.1% at T1; 67% at T2) and caused the most interference over time. Gastrointestinal AEs were also quite common (e.g., nausea 46.3% at T1 and 48.9% at T2; abdominal pain 42.4% at T1; 46.5% at T2). In general, symptoms were present both at T1 and T2 and did not change significantly in severity or interference. The prevalence of AEs varied by LL disease group (e.g., nausea was most common in acute lymphoblastic leukemia (ALL), fatigue was most severe in ALL and Hodgkin Lymphoma (HL), acute myeloid leukemia had the fewest AEs). CONCLUSION: Despite current supportive care regimens, many children with LL continue to report fatigue, pain, insomnia, and gastrointestinal symptoms as the most frequent or severe symptoms during therapy.

Patients, caregivers, and clinicians differ in performance status ratings: Implications for pediatric cancer clinical trials.

BACKGROUND: The Lansky Play-Performance Scale (LPPS) is often used to determine a child's performance status for cancer clinical trial eligibility. Differences between clinician and caregiver LPPS ratings and their associations with child-reported functioning have not been evaluated. METHODS: Children aged 7 to 18 years who were receiving cancer treatment and their caregivers were recruited from 9 pediatric cancer centers. Caregivers and clinicians reported LPPS scores, and children completed Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric functioning and symptom measures before treatment (time 1 [T1]) and after treatment (time 2 [T2]). t tests and mixed-linear models were used to assess differences in caregiver and clinician LPPS scores; polyserial correlations quantified associations between PROMIS and LPPS scores. RESULTS: Of 482 children, 281 had matched caregiver- and clinician-reported LPPS T1/T2 scores. Caregivers rated children significantly worse on the LPPS than clinicians at both T1 (mean, 73.3 vs 87.4; P < .01) and T2 (mean, 67.9 vs 83.1; P < .01). These differences were not related to a child's age (P = .89), diagnosis (P = .17), or sex (P = .64) or to the time point (P = .45). Small to moderate associations existed between caregiver- and clinician-reported LPPS ratings and child-reported PROMIS scores for mobility (caregiver T1/T2 r = 0.51/0.45; P < .01; clinician T1/T2 r = 0.40/0.35; P < .01), fatigue (caregiver T1/T2 r = -0.46/-0.37; P < .01; clinician T1/T2 r = -0.26/-0.27; P < .01), and pain interference (caregiver T1/T2 r = -0.32/-0.30; P < .01; clinician T1/T2 r = -0.17/-0.31; P < .01). Caregivers and clinicians assigned significantly lower LPPS scores at T2 (caregiver Δ = -5.37; P < .01; clinician Δ = -4.20; P < .01), whereas child-reported PROMIS scores were clinically stable. CONCLUSIONS: Significant differences between clinician and caregiver LPPS ratings of child performance were sustained over time; their associations with child reports were predominantly small to moderate. These data suggest that clinician-reported LPPS ratings by themselves are inadequate for determining clinical trial eligibility and should be supplemented by appropriate measures of a child's functional status reflecting the child and caregiver perspectives.

Validation of the caregiver Pediatric Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events measure.

BACKGROUND: Despite improvements in survival rates, cancer treatments have significant side effects that affect the quality of life of children and their families. When an ill child cannot self-report symptoms (eg, he or she is too ill), caregiver (parent) reporting becomes critical. This study evaluates the validity and reliability of the caregiver-reported Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE [Caregiver]) measure. METHODS: A diverse sample of caregivers with children receiving treatment at 9 oncology centers completed the Ped-PRO-CTCAE [Caregiver] measure, the Patient-Reported Outcomes Measurement Information System® (PROMIS® ) Parent Proxy measures, the Lansky Play-Performance Scale (PPS), medication use questions, and Global Impressions of Change (GIC). Construct validity (including convergent, discriminant, and known groups validity and responsiveness over time) and reliability (stability) were examined. RESULTS: A majority of the 473 caregivers were female (85%), non-Hispanic White (61%), and married (75%). Symptoms assessed with the Ped-PRO-CTCAE [Caregiver] and PROMIS Parent Proxy measures were strongly correlated (e.g., r for pain = 0.78; r for fatigue = 0.78; and r for depression = 0.83). Most of the Ped-PRO-CTCAE [Caregiver] item mean scores distinguished among PPS function levels and between children who did take medications for symptom control and children who did not. Changes in Ped-PRO-CTCAE [Caregiver] item mean scores were responsive to GIC over time. Test-retest evaluation found moderate to high agreement (57.8%-93.3%) over time. CONCLUSIONS: This study found strong evidence for the convergent and discriminant validity, known groups validity, responsiveness, and stability of the Ped-PRO-CTCAE [Caregiver] measure in a large and diverse sample of caregivers. The caregiver perspective provides a valuable and unique insight into the experiences of children and adolescents undergoing cancer treatment. LAY SUMMARY: Despite advances in cancer treatments, children and adolescents continue to suffer from treatment side effects, including pain, nausea, fatigue, and emotional distress, that can adversely affect quality of life for children and their families. Although it is best for children to report how they are feeling, there are times when a child may be too young or too ill to self-report. This study provides critical evidence for a new type of questionnaire that allows the caregiver or parent to report accurately what the child is experiencing. This measure can be used to improve adverse event reporting and child cancer care.

Pilot study of combined aerobic and resistance exercise on fatigue for patients with head and neck cancer: Inflammatory and epigenetic changes.

This pilot study examined whether a combined aerobic resistance exercise program reduced fatigue and the potential inflammatory and epigenetic mechanisms in patients with head and neck cancer (HNC) receiving intensity-modulated radiotherapy. The exercise group (N = 12) received a 3-month supervised aerobic resistance exercise intervention that was initiated before a 6-week radiotherapy regimen; the control group (N = 14) received standard care. Fatigue was measured using Multidimensional Fatigue Inventory-20; physical function measures included a 6-minute walk distance (6MWD), chair stands, bicep curls, and hand grip strength. Inflammatory markers and DNA methylation data were acquired using standardized protocol. Patients were mostly white (93%) and male (81%) with a mean age of 57 years. At the end of the intervention, the exercise group had a marginal decrease in fatigue compared with the control (-5.0 vs. 4.9; P = 0.10). The exercise group had a significantly greater improvement in 6MWD (29.8 vs. -55.5 m; P = 0.04), and a marginally smaller decline in hand grip (-0.3 vs. -5.8 lbs; P = 0.05) at the end of the intervention than the control. No significant difference in inflammatory markers was observed between groups. Lower plasma interleukin (IL) 6, IL1 receptor antagonist, tumor necrosis factor α (TNFα), soluble TNF receptor II and C-reactive protein were significantly associated with increased 6MWD, chair stand, and bicep curl at the end of the intervention (p < 0.05). Among the 1152 differentially methylated sites (DMS) after intervention (p < 0.001), 163 DMS were located in gene promoter regions. Enrichment analysis suggested that the top 10 upstream regulators were associated with tumor (HNF4A, RPP38, HOXA9, SAHM1, CDK7, NDN, RPS15) and inflammation (IRF7, CRKL, ONECUT1). The top 5 diseases or functions annotations of the 62 hypermethylated DMS indicated anti-tumor and anti-inflammatory effects that might be linked to exercise. These findings suggest that exercise may improve physical performance and reduce fatigue, which could be further linked to decreased inflammation, during active radiotherapy for HNC patients. Larger studies are warranted.

Expanding construct validity of established and new PROMIS Pediatric measures for children and adolescents receiving cancer treatment.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric measures were designed to assess symptoms and functioning in children and adolescents. The study goal was to evaluate the validity and responsiveness of the PROMIS Pediatric measures in a diverse cohort of children with cancer. METHODS: Children (7-18 years) from nine pediatric oncology hospitals completed surveys at 72 hours preceding treatment initiation (T1) and at follow-up (T2) approximately 7 to 17 days later for chemotherapy, and 4+ weeks later for radiation. Children completed PROMIS Pediatric measures (Mobility, Pain Interference, Fatigue, Depressive Symptoms, Anxiety, Psychological Stress), Memorial Symptom Assessment Scale (MSAS), and global impressions of change (GIC) questions on their symptoms and functioning at T2 reflecting on T1. Parents completed the Lansky Play-Performance Status (PPS) scale and medication list for their child. RESULTS: The children (n = 482) were average age 12.9 years, 46% female, 60% Caucasian, and had diverse cancers and treatments. There were moderate to strong correlations between PROMIS Pediatric and MSAS, supporting convergent validity. In support for known-groups validity, the PROMIS Pediatric average scores were statistically different (P < 0.05) for most domains by PPS and if the child was on a medication (or not) for controlling a symptom. The PROMIS Pediatric measures were responsive over time in association with the GIC. CONCLUSIONS: In a large, diverse sample of children and adolescents with cancer, there was strong evidence for the construct validity and responsiveness of the PROMIS Pediatric measures. This evidence supports PROMIS Pediatric measure use in pediatric oncology trials.

The association of age, literacy, and race on completing patient-reported outcome measures in pediatric oncology.

PURPOSE: Age is often used to determine when children can begin completing patient-reported outcome (PRO) instruments or transition to adult instruments. This study's purpose was to determine relationships between literacy, age, and race and their influence on a child's ability to understand and complete a PRO instrument. METHODS: The Wide Range Achievement Test was used to evaluate literacy in children and young adults with cancer, participating in a cognitive interview for the Pediatric PRO-CTCAE instrument. 140 participants (7-20 years) were recruited from 8 sites. Logistic regression and multivariable liner regression were used to examine relationships among key variables. RESULTS: Higher literacy scores were significantly associated with fewer PRO-CTCAE items being identified as "hard to understand" (p = 0.017). Literacy scores increased with age, but older participants were more likely to fall behind expected reading levels compared with US norms. A 1-year increase in age was associated with a 19% increase in the likelihood for being below the expected WRAT word reading score (OR 1.19; 95% CI 1.06-1.33, p = 0.003). No associations were found between race and literacy. CONCLUSIONS: Wide variations in literacy were noted across age groups. All participants were able to complete the Pediatric PRO-CTCAE, although most 7 year olds (63%) required reading assistance. Those with lower literacy skills were able to understand items suggesting that multiple factors may be involved in comprehension (developmental stage, concentration, vocabulary, or prior health experiences). Risk for falling below expected literacy levels increased with age implying a need for literacy consideration for cancer patients.

Child and adolescent self-report symptom measurement in pediatric oncology research: a systematic literature review.

OBJECTIVE: Previous work in pediatric oncology has found that clinicians and parents tend to under-report the frequency and severity of treatment-related symptoms compared to child self-report. As such, there is a need to identify high-quality self-report instruments to be used in pediatric oncology research studies. This study's objective was to conduct a systematic literature review of existing English language instruments used to measure self-reported symptoms in children and adolescents undergoing cancer treatment. METHODS: A comprehensive literature search was conducted in MEDLINE/PubMed, EMBASE, CINAHL, and PsycINFO to identify relevant articles published through November 10, 2016. Using pre-specified inclusion/exclusion criteria, six trained reviewers carefully screened abstracts and full-text articles for eligibility. RESULTS: There were 7738 non-duplicate articles identified in the literature search. Forty articles met our eligibility criteria, and within these articles, there were 38 self-report English symptom instruments. Most studies evaluated only cross-sectional psychometric properties, such as reliability or validity. Ten studies assessed an instrument's responsiveness or ability to detect changes in symptoms over time. Eight instruments met our criteria for use in future longitudinal pediatric oncology studies. CONCLUSIONS: This systematic review aids pediatric oncology researchers in identifying and selecting appropriate symptom measures with strong psychometric evidence for their studies. Enhancing the child's voice in pediatric oncology research studies allows us to better understand the impact of cancer and its treatment on the lives of children.

The Why Behind the Questions: Question-asking in Parents of Children Newly Diagnosed With Cancer - A Report From the Children's Oncology Group.

PURPOSE: For parents of children newly diagnosed with cancer, the exchange of information during initial educational processes is critical. This focused analysis was completed to describe parent question-asking during the new childhood cancer diagnosis timeframe. DESIGN & METHODS: In previous research of new diagnosis education experiences, parents spoke extensively about asking questions. These data, captured in first level coding, were incorporated across higher level codes to describe how parents processed information after their child's cancer diagnosis. Using constant comparative analysis, we returned to our data to complete a focused analysis of our first level code, Asking Questions. Team members independently coded Asking Questions data from 20 parent interviews, followed by team discussions and consensus agreement for code assignment. RESULTS: Parents asked questions to learn, fill an unmet need, or clarify information. Clinicians asked questions to assess parent learning. CONCLUSION: Question-asking is a technique used by parents and clinicians to communicate new information, assess understanding of provided content, and/or to confirm previously provided information. PRACTICE IMPLICATIONS: Clinicians can benefit from carefully listening to patients/parents and reflecting on the type of questions asked in an effort to understand the reason behind the question. This can be used to guide further education.

Factor VIII gene variants and inhibitor risk in African American hemophilia A patients.

African American hemophilia A (HA) patients experience a higher incidence of neutralizing anti-factor VIII (FVIII) antibodies ("inhibitors") vis-à-vis white patients. Nonsynonymous single-nucleotide polymorphisms (ns-SNPs) in the F8 gene encoding FVIII-H484, FVIII-E1241, and FVIII-V2238 are more prevalent in African Americans. This study tested the hypothesis that immune responses to these sites provoke inhibitors. Blood samples were obtained from 174 African American and 198 white HA subjects and their F8 gene sequences determined. Major histocompatibility complex class II binding and T-cell recognition of polymorphic sequences were evaluated using quantitative binding assays and HLA-DRB1 tetramers. Peptides corresponding to 4 common ns-SNPs showed limited binding to 11 HLA-DRB1 proteins. CD4 T cells from 22 subjects treated with FVIII products having sequences at residues FVIII-484, 1241, and 2238 differing from those of putative proteins encoded by their F8 genes did not show high-avidity tetramer binding, whereas positive-control staining of tetanus-specific CD4 T cells was routinely successful. African Americans with an intron-22 inversion mutation showed a 2-3 times-higher inhibitor incidence than whites with the same mutation (odds ratio = 2.3 [1.1-5.0, P = .04]), but this did not correlate with any of the ns-SNPs. We conclude that immune responses to "sequence-mismatched" FVIII products are unlikely to contribute appreciably to the inhibitor incidence in African Americans.

Eliciting the child's voice in adverse event reporting in oncology trials: Cognitive interview findings from the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events initiative.

BACKGROUND: Adverse event (AE) reporting in oncology trials is required, but current practice does not directly integrate the child's voice. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being developed to assess symptomatic AEs via child/adolescent self-report or proxy-report. This qualitative study evaluates the child's/adolescent's understanding and ability to provide valid responses to the PRO-CTCAE to inform questionnaire refinements and confirm content validity. PROCEDURE: From seven pediatric research hospitals, children/adolescents ages 7-15 years who were diagnosed with cancer and receiving treatment were eligible, along with their parent-proxies. The Pediatric PRO-CTCAE includes 130 questions that assess 62 symptomatic AEs capturing symptom frequency, severity, interference, or presence. Cognitive interviews with retrospective probing were completed with children in the age groups of 7-8, 9-12, and 13-15 years. The children/adolescents and proxies were interviewed independently. RESULTS: Two rounds of interviews involved 81 children and adolescents and 74 parent-proxies. Fifteen of the 62 AE terms were revised after Round 1, including refinements to the questions assessing symptom severity. Most participants rated the PRO-CTCAE AE items as "very easy" or "somewhat easy" and were able to read, understand, and provide valid responses to questions. A few AE items assessing rare events were challenging to understand. CONCLUSIONS: The Pediatric and Proxy PRO-CTCAE performed well among children and adolescents and their proxies, supporting its content validity. Data from PRO-CTCAE may improve symptomatic AE reporting in clinical trials and enhance the quality of care that children receive.

Operational Failures Detected by Frontline Acute Care Nurses.

Frontline nurses encounter operational failures (OFs), or breakdowns in system processes, that hinder care, erode quality, and threaten patient safety. Previous research has relied on external observers to identify OFs; nurses have been passive participants in the identification of system failures that impede their ability to deliver safe and effective care. To better understand frontline nurses' direct experiences with OFs in hospitals, we conducted a multi-site study within a national research network to describe the rate and categories of OFs detected by nurses as they provided direct patient care. Data were collected by 774 nurses working in 67 adult and pediatric medical-surgical units in 23 hospitals. Nurses systematically recorded data about OFs encountered during 10 work shifts over a 20-day period. In total, nurses reported 27,298 OFs over 4,497 shifts, a rate of 6.07 OFs per shift. The highest rate of failures occurred in the category of Equipment/Supplies, and the lowest rate occurred in the category of Physical Unit/Layout. No differences in OF rate were detected based on hospital size, teaching status, or unit type. Given the scale of this study, we conclude that OFs are frequent and varied across system processes, and that organizations may readily obtain crucial information about OFs from frontline nurses. Nurses' detection of OFs could provide organizations with rich, real-time information about system operations to improve organizational reliability. © 2017 Wiley Periodicals, Inc.

Concept-elicitation phase for the development of the pediatric patient-reported outcome version of the Common Terminology Criteria for Adverse Events.

BACKGROUND: Symptoms arising from disease or treatment are subjective experiences. Insight into pediatric oncology treatment side effects or symptoms is ideally obtained from direct inquiry to the ill child. A concept-elicitation phase in a patient-reported outcome (PRO) instrument design provides an opportunity to elicit children's voices to shape cancer symptom selection and terminology. METHODS: Through semistructured, one-on-one, voice-recorded interviews, symptom data were collected from 96 children with cancer between the ages of 7 and 20 years who were undergoing oncologic treatment at 7 pediatric oncology sites in the United States and Canada. RESULTS: The mean number of symptoms reported per child over the prior 7 days was 1.49 (range, 0-7; median, 1; standard deviation, 1.56). The most common symptoms across all age groups were tiredness or fatigue, nausea or vomiting, aches or pains, and weakness. There was not a statistically significant correlation between self-reported wellness and the number of reported symptoms (r = -0.156, n = 65, P = .215) or the number of symptoms reported by age group or diagnosis type. Forty participants reported experiencing a change in their body in the past week, with one-third of these changes unanticipated. Only through direct questions about feelings were emotional symptoms revealed because 90.6% of interviewees who discussed feelings (48 of 53) did so only in the context of direct questioning on feelings. Adolescents were more likely than younger children to discuss feelings as part of the interview. CONCLUSIONS: Concept elicitation from children and adolescents has the potential to enable researchers to develop age-appropriate, accurately representative PRO measures.

Use of a Fitness Tracker to Promote Physical Activity in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Children with cancer identify fatigue as a pervasive symptom, which increases during the corticosteroid pulse in acute lymphoblastic leukemia (ALL) maintenance. The FitBit is a fitness tracker that downloads activity measurements to the Internet in real time. In this feasibility study, we explored if children who received daily FitBit coaching for 2 weeks before a maintenance steroid pulse had an increase in steps per day and determined the relationship between steps per day prepulse and fatigue postpulse. PROCEDURE: Seventeen children in ALL maintenance, aged 6-15, wore the FitBit for 3 days to establish a baseline. A tailored weekly step goal was then set with the child and parent. Daily emails with feedback and FitBit screenshots were sent over the 2-week intervention. Self-report of fatigue was measured at baseline, after 2 weeks (i.e. before the steroid pulse), and after 5 days of steroids. RESULTS: There was a trend toward increased steps per day from weeks 1-2 (P = 0.079); fatigue was low and did not increase during the corticosteroid pulse. A significant correlation (r = -0.66, P = 0.005) was found between the steps per day during week 2 and fatigue after the steroid pulse with higher steps associated with lower fatigue. CONCLUSIONS: The intervention was feasible in this small sample. The average steps each time period (week 1, week 2, and during steroids) was over 10,000, demonstrating that children with ALL can be active during treatment. Physical activity may be protective of fatigue during a corticosteroid pulse.

Weight change during childhood acute lymphoblastic leukemia induction therapy predicts obesity: a report from the Children's Oncology Group.

BACKGROUND: Obesity is a well documented problem associated with childhood acute lymphoblastic leukemia (ALL) with increasing body mass index often observed during therapy. This study aims to evaluate if weight gain, early in therapy, is predictive of obesity at the end of treatment. PROCEDURE: In this secondary analysis, data from 1,017 high-risk ALL patients previously treated on a Children's Oncology Group protocol (CCG study 1961) were reviewed. Logistic regression was used to examine whether change in BMI z-score at Induction or Delayed Intensification (DI) 1 were predictive of obesity at the end of therapy. RESULTS: The BMI z-score at the beginning of Induction and the change in BMI z-score during Induction were both significant predictors of obesity at the end of therapy. The change in BMI z-score during cycle 1 of DI was not found to be associated with obesity. CONCLUSIONS: It is well know that obesity at the beginning of therapy is predictive of obesity at the end of ALL therapy. The new, and more important, finding from this study is that even after adjusting for baseline weight, the increase in BMI z-scores during induction was an independent predictor of obesity at the end of therapy. Most researchers agree that prevention is the best form of treatment for obesity as it is difficult to reverse once it is present. This study suggests that monitoring weight trends during Induction may be useful in guiding healthcare practitioners in identifying which patients are at highest risk for obesity development so that early intervention may occur.

A Case for Caution: Patient Use of Artificial Intelligence.

Artificial intelligence use is increasing exponentially, including by patients in medical decision- making. Because of the limitations of chatbots and the possibility of receiving erroneous or incomplete information, patient.

Review of the microbiome and metabolic pathways associated with psychoneurological symptoms in children with cancer.

Children with cancer often endure a range of psychoneurological symptoms (PNS), including pain, fatigue, cognitive impairment, anxiety, depressive symptoms, and sleep disturbance. Despite their prevalence, the underlying pathophysiology of PNS remains unclear. Hypotheses suggest an interplay between the gut microbiome and the functional metabolome, given the immune, neurological, and inflammatory influences these processes exert. This mini-review aims to provide a synopsis of the literature that examines the relationship between microbiome-metabolome pathways and PNS in children with cancer, drawing insights from the adult population when applicable. While there is limited microbiome research in the pediatric population, promising results in adult cancer patients include an association between lower microbial diversity and compositional changes, including decreased abundance of the beneficial microbes Fusicatenibacter, Ruminococcus, and Odoribacter, and more PNS. In pediatric patients, associations between peptide, tryptophan, carnitine shuttle, and gut microbial metabolism pathways and PNS outcomes were found. Utilizing multi-omics methods that combine microbiome and metabolome analyses provide insights into the functional capacity of microbiomes and their associated microbial metabolites. In children with cancer receiving chemotherapy, increased abundances of Intestinibacter and Megasphaera correlated with six metabolic pathways, notably carnitine shuttle and tryptophan metabolism. Interventions that target the underlying microbiome-metabolome pathway may be effective in reducing PNS, including the use of pre- and probiotics, fecal microbiome transplantation, dietary modifications, and increased physical activity. Future multi-omics research is needed to corroborate the associations between the microbiome, metabolome, and PNS outcomes in the pediatric oncology population.

A Quality Approach to Blinatumomab Delivery in Pediatric Oncology: A Children's Oncology Group Study.

Background: Blinatumomab is a promising immunotherapy agent that has been shown to improve survival outcomes in children diagnosed with relapsed B-lineage acute lymphoblastic leukemia. Expanded use of blinatumomab in the treatment of childhood cancer is expected; however, clinician perspectives regarding administering this agent in healthcare and home settings have not been explored. Method: Semistructured interviews were conducted with clinicians (N = 13) from pediatric institutions across the United States and Canada. Qualitative data were analyzed using a constant comparative analysis three-stage method. Results: Participants were primarily nurses (92%), female (77%), and had greater than 10 years of pediatric oncology experience. The selective code and overarching theme identified was "A quality approach to blinatumomab delivery in pediatric oncology." Clinicians described detailed processes that were created and implemented to promote a common goal of safe blinatumomab administration across the continuum of care. Clinicians shared how they engaged in planning activities and considered a variety of factors prior to and during blinatumomab administration. Clinicians also expressed a need to reflect and evaluate on previous patient experiences to create new or revise existing processes and workflows. Communication was also central to clinicians' work. Clinicians provided recommendations to assist others with blinatumomab administration and offered suggestions for items that could help with implementing future clinical trials containing similar agents. Discussion: Findings suggest nurses are pivotal to establishing processes which support safe administration of immunotherapies, such as blinatumomab, while also considering patient-specific needs and promoting quality of life.

PROMIS pediatric measures in pediatric oncology: valid and clinically feasible indicators of patient-reported outcomes.

BACKGROUND: Establishing the ability of children and adolescents with cancer to complete the NIH-sponsored PROMIS pediatric measures electronically and the preliminary validity estimates of the measures (both full item banks and short forms) in pediatric oncology will contribute to our knowledge of the impact of cancer treatment on these young patients. PROCEDURES: A total of 203 8- to 17-year olds were administered eight PROMIS pediatric measures in a cross-sectional study design to establish known-group validity. Of the 200 who completed all or most of the items, a slight majority were male (55.5%) and white (54%). Patients were either undergoing treatment for cancer (n = 93) or in survivorship following treatment for cancer (n = 107). Measures were completed using computer interface during an in-person interaction with researchers. RESULTS: Only 3 of 203 participants did not complete the PROMIS pediatric measures. As hypothesized, participants in treatment were significantly different (worse) on parent-reported clinical indicators (blood counts, fatigue, and appetite) and on seven self-reported measures (depression, anxiety, peer relationships, pain interference, fatigue, upper extremity function, and mobility) from participants in survivorship. Females reported worse fatigue, anger, and pain interference than males. Worse patient-reported outcomes for patients in active treatment persisted after adjusting for potential confounding variables. CONCLUSIONS: Children and adolescents in treatment for cancer or in survivorship and ranging from 8 to 17 years of age can complete multiple PROMIS pediatric measures using a computer interface during an outpatient clinic visit or inpatient admission. Findings establish known-group validity for PROMIS pediatric measures in pediatric oncology.

The first step to integrating the child's voice in adverse event reporting in oncology trials: a content validation study among pediatric oncology clinicians.

PURPOSE: Children with cancer experience significant toxicities while undergoing treatment. Documentation of adverse events (AEs) in clinical trials is mandated by federal agencies. Although many AEs are subjective, the current standard is clinician reporting. Our long-term goal is to create and validate a self-report measure of subjective AEs for children aged 7 years and older that will inform AE reporting for the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). This content validation study aimed to identify which of the AEs in the current CTCAE should be included in a pediatric self-report measure. METHODS: We sought expert panel review and consensus among 187 pediatric clinicians from seven Children's Oncology Group institutions to determine which of the 790 AEs are amenable to child self-report. Two survey iterations were used to identify suitable AEs, and clinician agreement estimated by the content-validity ratio (CVR) was assessed. RESULTS: Response rates for surveys 1 and 2 were 72% and 67%, respectively. After the surveys, 64 CTCAE terms met the criteria of being subjective, relevant for use in pediatric cancer trials, and amenable to self-report by a child. The most frequent reasons for removal of CTCAE terms were that they relied on laboratory or clinical measures or were not applicable to children. CONCLUSION: The 64 CTCAE terms will be translated into child-friendly terms as the basis of the child-report toxicity measure. Ultimately, systematic collection of these data will improve care by enhancing the accuracy and completeness of treatment toxicity reports for childhood cancer.

Delivery of Care for Pediatric Patients Receiving Blinatumomab: A Children's Oncology Group Study.

BACKGROUND: Blinatumomab is an immunotherapy agent used in pediatric oncology for the treatment of B-lineage acute lymphoblastic leukemia. Administration of blinatumomab, via continuous 28-day infusion cycles, can present multiple decision points and challenges related to patient care. Nurses are at the forefront of coordinating and delivering care for patients receiving blinatumomab. OBJECTIVE: To describe the current state of practice across Children's Oncology Group (COG) member institutions regarding blinatumomab administration in both inpatient and home/outpatient settings. METHODS: Between August and December 2021, a cross-sectional survey was used to determine current institutional practices related to blinatumomab administration. A single targeted respondent who was actively engaged in coordinating blinatumomab administration completed the survey on behalf of each COG institution. RESULTS: Survey participation rate was 78% (150/192). During the first 28-day blinatumomab cycle, 71 institutions (53%) reported patient hospital stays between 73 hours and 7 days; 42 (31%) reported hospital stays ≤72 hours, and only 12 (9%) reported hospitalization for the full 28-day infusion. Small- to medium-size institutions were more likely to report longer hospitalizations (P = .03). Most blinatumomab administration occurred in the outpatient setting, with low rates of unplanned clinic/emergency room visits. CONCLUSIONS: The majority of COG institutions have navigated the complex coordination of care required for children to receive blinatumomab at home. Wide variations in practice were noted across institutions. IMPLICATIONS FOR PRACTICE: This study describes current institutional practices surrounding administration of 28-day blinatumomab infusions in children with leukemia and offers a starting point for institutional benchmarking and standardization of practice.