Development and pilot testing of PROACTIVE: A pediatric onco-critical care capacity and quality assessment tool for resource-limited settings.

BACKGROUND: Nearly 90% children with cancer reside in low- and middle-income countries, which face multiple challenges delivering high-quality pediatric onco-critical care (POCC). We recently identified POCC quality and capacity indicators for PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), a tool that evaluates strengths and limitations in POCC services. This study describes pilot testing of PROACTIVE, development of center-specific reports, and identification of common POCC challenges. METHODS: The original 119 consensus-derived PROACTIVE indicators were converted into 182 questions divided between 2 electronic surveys for intensivists and oncologists managing critically ill pediatric cancer patients. Alpha-testing was conducted to confirm face-validity with four pediatric intensivists. Eleven centers representing diverse geographic regions, income levels, and POCC services conducted beta-testing to evaluate usability, feasibility, and applicability of PROACTIVE. Centers' responses were scored and indicators with mean scores ≤75% in availability/performance were classified as common POCC challenges. RESULTS: Alpha-testing ensured face-validity and beta-testing demonstrated feasibility and usability of PROACTIVE (October 2020-June 2021). Twenty-two surveys (response rate 99.4%) were used to develop center-specific reports. Adjustments to PROACTIVE were made based on focus group feedback and surveys, resulting in 200 questions. Aggregated data across centers identified common POCC challenges: (1) lack of pediatric intensivists, (2) absence of abstinence and withdrawal symptoms monitoring, (3) shortage of supportive care resources, and (4) limited POCC training for physicians and nurses. CONCLUSIONS: PROACTIVE is a feasible and contextually appropriate tool to help clinicians and organizations identify challenges in POCC services across a wide range of resource-levels. Widespread use of PROACTIVE can help prioritize and develop tailored interventions to strengthen POCC services and outcomes globally.

"Money was the problem": Caregivers' self-reported reasons for abandoning their children's cancer treatment in southwest Uganda.

INTRODUCTION: Treatment abandonment contributes significantly to poor survival of children with cancer in low- and middle-income countries (LMIC). In order to inform an approach to this problem, we investigated why caregivers withdraw their children from treatment. METHODS: In a qualitative study, carried out in October and November 2020, in-depth interviews were conducted with caregivers of children who had abandoned cancer treatment at the Pediatric Cancer Unit of Mbarara Regional Referral Hospital in south-western Uganda. Recorded in-depth interviews were transcribed and analyzed to identify themes of caregivers' self-reported reasons for treatment abandonment. The study was approved by the Review and Ethics Committee of Mbarara University of Science and Technology. RESULTS: Seventy-seven out of 343 (22.4%) children diagnosed with cancer abandoned treatment during the study period; 20 contactable and consenting caregivers participated in the study. The median age of the caregivers was 37 years and most (65%) were mothers. At the time of this study, eight (40%) children were alive and five (62.5%) were males; with a median age of 6.5 years. Financial difficulty, other obligations, the child falsely appearing cured, preference for alternative treatments, belief that cancer was incurable, fear that the child's death was imminent and chemotherapy side effects were the caregivers' reasons for treatment abandonment. CONCLUSIONS AND RECOMMENDATION: Seeking cancer treatment for children in Uganda is an expensive venture and treatment abandonment is mainly caused by caregivers' difficult socio-economic circumstances. This problem needs to be approached with empathy and support rather than blame.

Pediatric Solid Tumors in Resource-Constrained Settings: A Review of Available Evidence on Management, Outcomes, and Barriers to Care.

International disparities in outcomes from pediatric solid tumors remain striking. Herein, we review the current literature regarding management, outcomes, and barriers to care for pediatric solid tumors in low- and middle-income countries (LMICs). In sub-Saharan Africa, Wilms Tumor represents the most commonly encountered solid tumor of childhood and has been the primary target of recent efforts to improve outcomes in low-resource settings. Aggressive and treatment-resistant tumor biology may play a role in poor outcomes within certain populations, but socioeconomic barriers remain the principal drivers of preventable mortality. Management protocols that include measures to address socioeconomic barriers have demonstrated early success in reducing abandonment of therapy. Further work is required to improve infrastructure and general pediatric care to address disparities.

Risk factors for abandonment of Wilms tumor therapy in Kenya.

BACKGROUND: Survival from Wilms tumor (WT) in sub-Saharan Africa remains dismal as a result of on-therapy mortality and treatment abandonment. Review of patients diagnosed from 2008 to 2011 in our Kenyan Wilms Tumor Registry showed a loss to follow up (LTFU) rate approaching 50%. The purpose of this study was to trace those LTFU, estimate the survival rate, and identify risk factors for treatment abandonment. PROCEDURE: We administered a comprehensive survey to parents of patients with WT at the two largest referral hospitals in Kenya to identify barriers to care. We also telephoned families who had abandoned care to determine vital status and identify risk factors for treatment abandonment. RESULTS: Of 136 registered patients, 77 were confirmed dead (56.7%), 38 remained alive (27.9%), and the vital status of 21 patients remains unknown (15.4%). After contacting 33 of the patients who either abandoned curative treatment (n = 34) or did not attend off-therapy visits (n = 20), the best estimate of 2-year overall survival of patients with WT in Kenya approaches 36%. Sixty-three percent of parents misunderstood treatment plans and 55% encountered financial barriers. When asked how to increase comfort with the child's treatment, 27% of parents volunteered improving inefficient services and 26% volunteered reducing drug-unavailability. CONCLUSIONS: Treatment abandonment remains a significant problem contributing to increased mortality from WT in developing countries. This multi-center survey identified the barriers to treatment completion from the parental perspective to be lack of education about WT and treatment, financial constraints, need for quality improvement, and drug-unavailability. Pediatr Blood Cancer 2015;62:252-256. © 2014 Wiley Periodicals, Inc.

Race disparities in peptide profiles of North American and Kenyan Wilms tumor specimens.

BACKGROUND: Wilms tumor (WT) is the most common childhood kidney cancer worldwide and arises in children of black African ancestry with greater frequency and severity than other race groups. A biologic basis for this pediatric cancer disparity has not been previously determined. We hypothesized that unique molecular fingerprints might underlie the variable incidence and distinct disease characteristics of WT observed between race groups. STUDY DESIGN: To evaluate molecular disparities between WTs of different race groups, the Children's Oncology Group provided 80 favorable histology specimens divided evenly between black and white patients and matched for disease characteristics. As a surrogate of black sub-Saharan African patients, we also analyzed 18 Kenyan WT specimens. Tissues were probed for peptide profiles using matrix-assisted laser desorption ionization time of flight imaging mass spectrometry. To control for histologic variability within and between specimens, cellular regions were analyzed separately as triphasic (containing blastema, epithelia, and stroma), blastema only, and stroma only. Data were queried using ClinProTools and statistically analyzed. RESULTS: Peptide profiles, detected in triphasic WT regions, recognized race with good accuracy, which increased for blastema- or stroma-only regions. Peptide profiles from North American WTs differed between black and white race groups but were far more similar in composition than Kenyan specimens. Individual peptides were identified that also associated with WT patient and disease characteristics (eg, treatment failure and stage). Statistically significant peptide fragments were used to sequence proteins, revealing specific cellular signaling pathways and candidate drug targets. CONCLUSIONS: Wilms tumor specimens arising among different race groups show unique molecular fingerprints that could explain disparate incidences and biologic behavior and that could reveal novel therapeutic targets.