Pediatric Oncology Population Research Articles

Investigating the safety and feasibility of osteopathic manipulative medicine in hospitalized children and adolescent young adults with cancer.

Children and adolescents young adults (AYAs) undergoing treatment for oncologic diagnoses are frequently hospitalized and experience unwanted therapy-induced side effects that diminish quality of life. Osteopathic manipulative treatment (OMT) is a medical intervention that utilizes manual techniques to diagnose and treat body structures. Few studies have investigated the implementation of OMT in the pediatric oncology outpatient setting. To date, no studies have investigated the safety and feasibility of OMT in the pediatric oncology inpatient setting. The objective of this study is to investigate the safety and feasibility of OMT in the pediatric oncology inpatient setting. This is a prospective, single-institution pilot study evaluating children and AYAs aged≥2 years to≤30 years with a diagnosis of cancer hospitalized at Riley Hospital for Children (RH) from September 2022 to July 2023. Approval was obtained from the Indiana University Institutional Review Board (IRB). Patients were evaluated daily with a history and physical examination as part of routine inpatient management. Patients who reported chemotherapy side effects commonly encountered and managed in the inpatient setting, such as pain, headache, neuropathy, constipation, or nausea, were offered OMT. Patients provided written informed consent/assent prior to receiving OMT. OMT was provided by trained osteopathic medical students under the supervision of a board-certified osteopathic physician and included techniques commonly taught in first- and second-year osteopathic medical school curricula. Safety was assessed by a validated pain (FACES) scale immediately pre/post-OMT and by adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE) 24 h post-OMT. All data were summarized utilizing descriptive statistics. A total of 11 patients were screened for eligibility. All patients met the eligibility criteria and were enrolled in the study. The majority of patients were male (n=7, 63.6 %) with a median age of 18.2 years at time of enrollment (range, 10.2-29.8 years). Patients had a variety of hematologic malignancies including B-cell acute lymphoblastic leukemia (ALL) (n=5, 45.5 %), T-cell ALL (n=1, 9.1 %), acute myeloid leukemia (AML) (n=2, 18.2 %), non-Hodgkin's lymphoma (n=2, 18.2 %), and Hodgkin's lymphoma (n=1, 9.1 %). All patients were actively undergoing cancer-directed therapy at the time of enrollment. There were 40 unique reasons for OMT reported and treated across 37 encounters, including musculoskeletal pain (n=23, 57.5 %), edema (n=7, 17.5 %), headache (n=5, 12.5 %), peripheral neuropathy (n=2, 5.0 %), constipation (n=2, 5.0 %), and epigastric pain not otherwise specified (n=1, 2.5 %). Validated FACES pain scores were reported in 27 encounters. Of the 10 encounters for which FACES pain scores were not reported, 8 encounters addressed lower extremity edema, 1 encounter addressed peripheral neuropathy, and 1 encounter addressed constipation. The total time of OMT was documented for 33 of the 37 encounters and averaged 9.8 min (range, 3-20 min). Hospitalized children and AYAs with cancer received OMT safely with decreased pain in their reported somatic dysfunction(s). These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology inpatient setting and to a broader inpatient pediatric oncology population.

Factors influencing caregiver decisions to use complementary and integrative therapies in pediatric oncology settings: Findings from a qualitative analysis

PurposeComplementary and integrative medicine (CIM) therapies (i.e., non-conventional Western medicine interventions) may reduce side-effects associated with pediatric oncology treatment. CIM therapies may also improve caregiver psychological and physical health that is exacerbated during pediatric cancer treatment. Despite known benefits, these therapies are not widely used within pediatric oncology populations in the United States. To guide and promote CIM use among this population, the aim of this project was to qualitatively explore factors that contribute to caregivers' decision to include CIM use in their own and child's care. MethodsTwenty caregivers of children (ages 0.5–14 years) being treated for cancer participated in this study. Each completed a demographic form and the CIM use questionnaire. Qualitative interviews followed by a card sort task were used to assess barriers and facilitators of uptake for caregivers and their child with cancer. ResultsA number of predisposing (e.g., child age, beliefs) and needs factors (e.g., potential to treatment-related side-effects) provide insight into caregivers’ decisions to use CIM for their child. Analyses also revealed the importance of enabling factors (e.g., resources) for caregiver use. Caregivers also reported benefiting from additional information about risk/benefit analysis of these therapies, and current research for CIM use in caregivers and children being treated for cancer. ConclusionChildren may benefit from individually tailored complementary and integrative medicine consultations that explore patient history and specific needs factors to improve preference concordant care and uptake. Caregivers may benefit from support that improves enabling factors associated with care (e.g., improved accessibility).

Evaluation of a Quality Improvement Process for Health-System Retention of Long Acting Growth Factors Prescriptions in the Pediatric Oncology Population

OBJECTIVE Granulocyte-colony stimulating factor (GCSF) products are often used in pediatric patients with malignant diagnoses to reduce the time that the patient is neutropenic. Long-acting GCSF products have been shown to be non-inferior to daily dosing of GCSF products, and are becoming more desired by patients and families. Insurance companies often require a prior authorization prior to approving the use of the long-acting GCSF products. This process has proven challenging leading to treatment delays and missed doses. The purpose of this study is to evaluate a quality improvement process for the prescribing and dispensing of long-acting GCSF to better serve pediatric patients within a single health care system. METHODS This is a single-center, retrospective chart review with the purpose of collecting data to compare prescription retention before and after the improvement intervention. Study timeline includes all doses of long-acting GCSF prescribed for pediatric oncology patients between June 2020–June 2021 compared with July 2021–March 2022. On June 30, 2021, educational information was provided to the appropriate stakeholders regarding the change in practice. RESULTS A total of 31 patients were included in the review, with 22 patients prior to the intervention (115 prescriptions), and 9 patients after the intervention (43 prescriptions). There was a 37.8% increase in health system prescription retention (15.7% vs 53.5%). CONCLUSIONS Pharmacist directed long-acting GCSF prescription destination and a dedicated prior-authorization team led to an increase in prescription retention for patients regardless of payer mandated outpatient pharmacy.

Vitamin D Deficiency in Pediatric Oncology Patients: A Single-Center Experience in Saudi Arabia.

Background There is a lack of local studies on vitamin D deficiency in children with cancer. This study aims to estimate the prevalence of vitamin D deficiency in the pediatric oncology population at King Abdul-Aziz Medical City (KAMC) in Jeddah, addressing knowledge gaps for improved clinical practice and future research. Methods This retrospective observational studywas conducted from 2016 to 2021 at the pediatric oncology clinic in National Guard Hospital, Jeddah. The study focused on children aged 14 or younger at cancer diagnosis, data encompassed patient demographics, cancer details, and treatment information, including serum measurements of vitamin D (25(OH)D, calcium, phosphate, alkaline phosphatase). Vitamin D levels were categorized as deficient (<25 ng/ml), insufficient (25-49 ng/ml), sufficient (≥50- 125 ng/ml), or hypervitaminosis (>125 ng/ml), based on our center reference range and the validation of the assay. Results In this retrospective study of 155 pediatric oncology patients, the majority aged 0 to 10 years (78%), findings reveal a male preponderance (54.2%) and a more prevalent in patients with hematological malignancies (85%). Chemotherapy was administered to 98%, with 7% underwent radiotherapy, and 89% received steroids. Analysis of serum 25-OH vitamin D levels indicated an overall deficiency and insufficiency at diagnosis (63%) and post-therapy (43%). Age and gender had a significant influence on vitamin D levels at diagnosis, with older children and females exhibiting lower concentrations. However, these differences diminished by the end of therapy. Notably, hematological malignancy patients often presented insufficient vitamin D levels, while solid tumor patients frequently had sufficient levels. Clinical outcomes showed a high survival rate (90.7%), limited bone density assessments (18.1%), and a 14.2% prevalence of hypervitaminosis. Conclusion In summary, our study reveals that over two-thirds of pediatric oncology patients experience vitamin D deficiency and insufficiency at the time of diagnosis, particularly notable in females and older children. Notably, those with solid tumors exhibit higher baseline 25-OH vitamin D concentrations compared to counterparts with hematological malignancies. The findings underscore the importance of educating both patients and caregivers on supplementation and sun exposure to mitigate the prevalence of deficient and insufficient vitamin D levels in pediatric oncology cases.

Inherited Thrombophilia and Risk of Thrombosis in Children with Cancer: a Single-center Experience.

Thrombosis is an increasingly recognized complication of childhood malignancy and its treatment. The incidence and etiology of pediatric cancer-related thrombosis is still not well understood. The aim of this study was to evaluate the prevalence of common prothrombotic genetic conditions in children with cancer, the frequency of thrombosis, and the role of inherited thrombophilia in the development of thrombosis in a pediatric oncology population. Forty-seven children (36 treated for hematological malignancies and 11 for solid tumors) with a median age of 8.8. years (range 0.4 - 19.3 years) were included in the study. Genetic polymorphisms of Factor V Leiden (G1691A), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were determined by real-time polymerase chain reaction-based DNA analysis. Four (8.5%) patients were heterozygous for Factor V Leiden, 3 (6.4%) were heterozygous for prothrombin G20210A mutation, and 3 (6.4%) were homozygous for MTHFR C677T mutation. All patients had implanted central venous catheters. Four (8.5%) children had documented thrombosis, three of which were in the upper venous system. Two of the four patients with thrombosis had Factor V Leiden heterozygosity. Thrombosis is an important complication of childhood cancer. The risk of thrombosis may be increased in patients with Factor V Leiden. In the absence of consensus guidelines, our results support the recommendation for thrombophilia screening in children with cancer.

Management of a major varicella zoster exposure in a pediatric oncology population

Management of the exposure of pediatric oncology patients to varicella zoster virus (VZV) is controversial. We report the exposure of 56 patients to a single child with chicken pox at a pediatric cancer housing facility and describe our strategic approach for their management. We reviewed the immune and clinical status of 56 children with cancer receiving ongoing treatment at Memorial Sloan Kettering Cancer Center (MSK) who, while living at a pediatric cancer housing facility, were exposed to the index patient. The management of patients exposed included: (1) determination of immune status, (2) availability of vaccination history or VZV disease prophylaxis, (3) exposure status and subsequent isolation during the period of incubation, and (4) VZV disease prophylaxis. In addition to the 56 patients exposed to the index case, eight children with cancer treated at other facilities and 11 healthy siblings living in the facility were exposed. Of the 56 MSK patients, 21 were classified as immunosuppressed and received varicella zoster immune globulin (human), intravenous standard immune globulin, or acyclovir based on serostatus and immune function. The cohort was followed for 4 weeks after the exposure and no secondary infections were diagnosed. We performed a risk assessment and created a management plan to control and prevent further exposure and development of disease. No secondary cases developed. This strategic approach could serve as a model for the management of VZV exposure for other pediatric oncology centers.

The role of oral microbiota in the development of oral mucositis in pediatric oncology patients treated with antineoplastic drugs: a systematic review

BackgroundIn the pediatric oncology population, oral mucositis as a consequence of chemotherapy is a highly prevalent complication which strongly affects both the quality of life and treatment possibilities of the patients. Still, the etiopathological mechanisms carrying to its development are not fully understood, although a possible role of oral dysbiosis has been previously investigated with unclear conclusions. The aim of this systematic review was to assess the available evidence on the role of microbiota in the development of oral mucositis.MethodsA systematic literature search was performed following PRISMA guidelines. Three electronic databases were searched up until April 2023 and a following manual search included the reference lists of the included studies and reviews. Studies reporting microbiological and clinical data of pediatric patients treated by antineoplastic drugs were included.ResultsThirteen studies met the inclusion criteria, reporting an average mucositis prevalence of 57,6%. Candida albicans infections were frequently observed in studies performing microbiological analysis on oral lesions, in contrast with the low rate detection of the Herpes simplex viruses. Bacterial species such as coagulase-negative Staphylococci and Streptococcus viridans were detected more frequently on lesion sites. Studies reporting a quantitative analysis of the general flora did not show comparable results. Risk of bias assessment among studies was generally considered high or very high.ConclusionsWhile the specific role of certain microbiological agents, such as Candida albicans, was frequently reported among studies, data regarding the general dynamics of oral microbiota in the development of oral mucositis are lacking in the current literature. Thus, more studies are needed to provide the knowledge required in order to improve protocols for the prevention and treatment of this threatening complication.

Characterization of the Use and Efficacy of Isavuconazonium Sulfate in a Pediatric Oncology and Stem Cell Transplant Population: A Single Institution Retrospective Review.

Isavuconazonium sulfate (ISA) is a triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis in adults. This single-center, retrospective review of pediatric oncology and stem cell transplant patients receiving ISA for prophylaxis (n=20) or treatment (n=6) of invasive fungal disease (IFD) aims to characterize real-world clinical efficacy and toxicity of ISA in patients <18 years of age. Of 20 patients receiving ISA for prophylaxis, three patients had presumed breakthrough IFD (1 proven, 2 probable/possible). No adverse effects were attributed to ISA use or led to the discontinuation of therapy.

Families' experiences accessing care after genomic sequencing in the pediatric cancer context: "It's just been a big juggle".

Access to genomic sequencing (GS) and resulting recommendations have not been well described in pediatric oncology. GS results may provide a cancer predisposition syndrome (CPS) diagnosis that warrants screening and specialist visits beyond cancer treatment, including testing or surveillance for family members. The Texas KidsCanSeq (KCS) Study evaluated implementation of GS in a diverse pediatric oncology population. We conducted semi-structured interviews (n = 20) to explore experiences of KCS patients' families around learning about a CPS diagnosis and following up on recommended care. We used qualitative content analysis to develop themes and subthemes across families' descriptions of their experiences accessing care and to understand which factors presented barriers and/or facilitators. We found participants had difficulty differentiating which follow-up care recommendations were made for their child's current cancer treatment versus the CPS. In families' access to follow-up care for CPS, organizational factors were crucial: travel time and distance were common hardships, while coordination of care to streamline multiple appointments with different providers helped facilitate CPS care. Financial factors also impacted families' access to CPS-related follow-up care: having financial assistance and insurance were facilitators for families, while costs and lack of insurance posed as barriers for patients who lost coverage during transitions from pediatric to adult care, and for adult family members who had no coverage. Factors related to beliefs and perceptions, specifically perceiving the risk as less salient to them and feeling overwhelmed with the patient's cancer care, presented barriers to follow-up care primarily for family members. Regarding social factors, competing life priorities made it difficult for families to access follow-up care, though having community support alleviated these barriers. We suggest interventions to improve coordination of cancer treatment and CPS-related care and adherence to surveillance protocols for families as children age, such as care navigators and integrating longitudinal genetic counseling into hereditary cancer centers.

Correlating food and nutritional patterns with cancers in the pediatric oncology population at two specialized hospitals in Tanzania

BackgroundThis study of nutritional patterns in relation to cancers among pediatric oncology population in Tanzania was motivated by the lack of up-to-date information about the nutritional practices, the controversy around the importance of nutritional support and the lack of consistent nutritional criteria among pediatric oncology populations.MethodsA survey study in two cancer referral hospitals of children diagnosed with any cancers, aged between 1 and 17 years inclusive and being eligible for enteral feeding included 131 children. Their demographic, nutritional, feeding and cancer profiles were analyzed descriptively through mapping and other approaches as well as inferentially using multinomial regression models to understand different aspects of nutrition for children suffering from cancers.ResultsThe majority (15% or higher) of pediatric oncology population originated from the lake zone. Between 7 and 12% of pediatric oncology population originated from the Western zone. The top-three cancers with their percentages in the brackets were: Wilms Tumor (32%), Acute Lymphoblastic Leukemia (26%) and Retinoblastoma (13%). About 69% of the pediatric oncology population ate foods that are rich in energy but poor in protein such as rice (21.5%), porridge (19.3%), banana (11.7%) and potatoes (10.2%). On the other hand, only 17.5% ate foods that are generally protein-rich such as meat (8.0%), fish (5.3%) and chicken (4.2%); and 12.7% ate milk (4.2%), beans (3.4%), vegetables (2.7%), eggs (1.9%) and fruits (1.5%). Cancers impacted food intake in about 60% of all children with cancers and affected appetite in 18.3% of them. Cancers caused vomiting in 16% and diarrhea in 6.1% of children. The majority of children with cancers (61.8%) took at least one meal while 34.4% took just snacks (p < 0.001).ConclusionsThe majority of pediatric oncology population had erratic nutritional patterns and took foods high in energy and poor in proteins. There is a two-way interaction between cancers and nutrition in which cancers affect general nutritional intake which could affect the cancer treatment outcomes in return. Therefore, it is important to consider these interactions while managing pediatric oncology populations in this and similar settings.

Evaluations of NSAIDs and Opioids as Analgesics in Pediatric Oncology

As one of the leading causes of death in childhood, cancer also causes discomfort to pediatric patients. Even with guidelines for pain management, more than half of hospitalized children have intense and unrelieved pain. The present work aims to describe the intensity of pain and its pharmacological management in a pediatric oncology population. Patients aged 0 to 17 years old, diagnosed with cancer, who were admitted to a children’s oncology hospital and had well-documented data on pain management in their medical records were included. A total of 333 patients were included, mostly male (55.8%) with a mean age of 7.9 years. A substantial portion of the patient cohort (51.4%) initially reported experiencing pain of moderate intensity during the first assessment. Subsequently, following the pharmacological intervention, a significant proportion of patients (90.1%) reported complete alleviation of pain. The predominant pharmaceutical agents utilized for pain management encompassed metamizole (76.6%) and morphine (10.2%). All pharmacological interventions used were able to significantly reduce patients’ pain. This study underscores the utilization of different pharmacological classes to achieve notable reductions in pain intensity among patients grappling with severe pain.

Exploring Barriers to Pediatric Cancer Clinical Trials: The Role of a Networked, Just-in-Time Study Program

The Research to Accelerate Cures and Equity (RACE) for Children Act mandates that newly developed targeted oncology drugs be tested in children when molecular targets are relevant to pediatric cancers. In its first year, the RACE for Children Act was effective in creating novel drug development opportunities for children with cancer; however, significant barriers to clinical trial enrollment persist. Pediatric cancer clinical trials are impacted by challenges surrounding logistics, complexity, and access. As such, there is potential for a networked and centralized study approach to address these barriers. Here we discuss adapting a just-in-time clinical trial approach for adults to serve the pediatric oncology population. Through innovative patient matching solutions leveraging large, real-world datasets with high computational power, the Tempus Integrated Molecular Evaluation (TIME) for Kids Program aims to address barriers in the development of new therapies. This commentary explores the potential for reducing challenges in developing novel pediatric therapeutics, advancing equity in genomic biomarker testing for precision tailored treatment, and improving outcomes for pediatric oncology patients.

Evaluation of potential cost savings through chemotherapy and biotherapy dose-rounding at a pediatric institution.

Rapidly increasing costs of medication acquisition can pose a challenge for health-system pharmacy budgets. The impact of dose-rounding in a pediatric oncology population has not previously been well documented and a retrospective review was undertaken to quantify the potential cost benefits. A retrospective chart review of patients with an oncologic diagnosis was performed for cytotoxic agents, asparaginase products, and biotherapy administered between January 1, 2014, and December 31, 2017. In the analysis, orders that could be rounded down to the nearest vial size by 5 or 10% were included. Medication pricing information was based on wholesale acquisition cost (WAC) and was provided by the Department of Pharmacy. Cost savings per medication were determined by multiplying the WAC of the medication by the number of vials saved. Over a 4-year span, 347 patients were evaluated and 552 out of a possible 3110 orders (17.7%) met criteria for a theoretical cost savings of approximately $1,126,000 (∼$3200 per patient). Rounding down doses by up to 5% resulted in a potential savings of about $529,000. When rounding was extended to 5-10% of the originally ordered dose, an additional $597,000 of approximate cost savings could have been realized. The medications with the largest impact on cost savings were rituximab, pegaspargase, and erwinia asparaginase. For pediatric oncology patients, there exists a unique potential cost savings opportunity if doses are rounded down within 5 or 10% of the originally ordered weight-based or body surface area-calculated dose.

What is the role of neutropenia in pediatric cancer patients with pneumatosis intestinalis?

We aimed to identify prognostic indicators in pneumatosis intestinalis (PI) in a pediatric oncology population. We hypothesized that neutropenia would be an independent risk factor for adverse outcomes, including the need for abdominal operation to treat PI and for the development of recurrent PI. We performed a retrospective review of all patients treated for PI between 2009 and 2019 with a diagnosis of cancer or history of bone marrow transplant (BMT). Sixty-eight children were treated for their first episode of PI; 15 (22%) were not neutropenic at presentation; eight underwent urgent abdominal operation (12%). Patients with neutropenia were more likely to receive TPN, had a longer course of NPO, and received a longer course of antibiotics. Neutropenia at presentation was associated with a decreased risk of PI recurrence (40% vs 13%, p = 0.03). Children who required an abdominal operation were more likely to require vasopressors at diagnosis (50% vs 10%, p = 0.013). Among pediatric cancer patients, need for vasopressors at the time of PI is a marker of severe PI, with increased likelihood of requiring operative intervention. The presence of neutropenia is associated with lower rates of PI recurrence. Level III.

Indocyanine green fluorescence-guided lymphadenectomy with single site retroperitoneoscopy in children

Retroperitoneoscopic lymphadenectomy is an established surgical approach in adult urology, but rarely described in pediatric population. We develop retroperitoneoscopic surgical oncology in children, combining new technology innovations in pediatric surgery such as single site port retroperitoneoscopic in supine position and indocyanine green (ICG). The video describes a step-by-step approach from the ICG injection technique to the lymph-node retroperitoneoscopic harvesting. The video highlights anatomical landmarks and ICG intraoperative lymph nodes findings. Four consecutive surgical procedures were performed in children with paratesticular rhabdomyosarcoma who required staging template retroperitoneal lymph node dissection (RPLND) for staging. All patients were discharged the same day without 30-days postoperative complications. Retroperitoneoscopic approach with single port and indocyanine guided lymphatic mapping for template retroperitoneal lymph node dissection (RPLND) is a feasible minimally invasive procedure in children. Combining different technology innovations allows an effective lymph node harvesting with the possibility to offer an enhanced recovery after surgery in pediatric oncology population.

157 Association Between Structural Racism and Acuity of Illness at Initial Presentation in Pediatric Patients with Solid Tumors

OBJECTIVES/GOALS: Racial/ethnic minoritized children experience poorer cancer outcomes, which may be driven by structural racism. We apply an index that combines segregation and neighborhood vulnerability to a pediatric oncology population and assesses its association with acuity of illness at initial presentation. METHODS/STUDY POPULATION: A retrospective analysis will be performed in a cohort of pediatric patients diagnosed with solid tumors at Children’s Healthcare of Atlanta (CHOA) from 2010-2018 (N=1149). The sample will be linked to a structural racism index (SRI) that has been established in our prior work. We abstract data from medical records to quantify initial acuity of illness based on the need for ICU-level resources. Differences in sociodemographic characteristics will be analyzed by the SRI, using chi-squared, Student t-tests, and ANOVA where appropriate. Logistic regression models will be used to assess the association of the SRI with acuity of illness. RESULTS/ANTICIPATED RESULTS: We anticipate that relevant sociodemographic characteristics (e.g., race/ethnicity, insurance status) differ by the SRI. The CHOA Cancer Registry includes a racially and ethnically diverse group of patients: 63% of the cohort is White, 30% is Black,10% are Other, and 15% are Hispanic/Latino. Furthermore, we anticipate that pediatric patients with solid tumors living in counties with greater levels of structural racism as measured by the SRI experience an increased acuity of illness at initial presentation. DISCUSSION/SIGNIFICANCE: By applying a novel index quantifying structural racism, we will provide new information about the structural barriers patients and families face prior to a pediatric cancer diagnosis. This work will allow us to identify areas for potential interventions in this vulnerable young patient population.

The Impact of COVID-19 on Pediatric Malignancy Diagnosis and Treatment: Never the Same but Lessons Learned.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected the pediatric oncology population globally. Over the course of 2 years, increasing reports have been made to better understand this entity and its pathologic complications on these patients. The pandemic has allowed healthcare providers, hospital systems, and leading oncologic societies to quickly adapt and formulate new guidelines for the effective understanding, management, and treatment of patients with pediatric malignancy.

Development of a Therapeutic Drug Monitoring Strategy for the Optimization of Vincristine Treatment in Pediatric Oncology Populations in Africa

Recent studies have reported ethnic differences in vincristine exposure and outcomes such as toxicity. This resulted in the hypothesis of subtherapeutic dosing in African children. To optimize individual treatment, a strategy to identify subtherapeutic exposure using therapeutic drug monitoring is essential. The aim of the current study was to develop a strategy for therapeutic drug monitoring of vincristine in African children to meet the following criteria: (1) identify patients with low vincristine exposure with sufficient sensitivity (>70%), (2) determine vincristine exposure with a limited sampling strategy design of 3 samples, and (3) allow all samples to be collected within 4 hours after administration. An in silico simulation study was performed using a previously described population pharmacokinetic model and real-life demographic dataset of Kenyan and Malawian pediatric oncology patients. Two different therapeutic drug monitoring strategies were evaluated: (1) Bayesian approach and (2) pharmacometric nomogram. The sampling design was optimized using the constraints described above. Sensitivity analysis was performed to investigate the influence of missing samples, erroneous sampling times, and different boundaries on the nomogram weight bands. With the Bayesian approach, 43.3% of the estimated individual exposure values had a prediction error of ≥20% owing to extremely high shrinkage. The Bayesian approach did not improve with alternative sampling designs within sampling constraints. However, the pharmacometric nomogram could identify patients with low vincristine exposure with a sensitivity, specificity, and accuracy of 75.1%, 76.4%, and 75.9%, respectively. The pharmacometric nomogram performed similarly for different weight bands. The pharmacometric nomogram was able to identify patients with low vincristine exposure with high sensitivity, with 3 blood samples collected at 1, 1.5, and 4 hours after administration. Missing samples should be avoided, and the 3 scheduled samples should be collected within 15, 5, and 15 minutes of 1, 1.5, and 4 hours after administration, respectively.

Is higher physical fitness associated with better psychological health in young pediatric cancer survivors? Across-sectional study from the iBoneFIT project.

To examine the associations of self-perceived and objectively-measured physical fitness with psychological well-being and distress indicators in young pediatric cancer survivors. A total of 116 participants (12.1 ± 3.3 years, 56.9% boys) from the iBoneFIT project participated in this cross-sectional study. Objectively-measured physical fitness (muscular fitness) was obtained by handgrip strength and standing long jump tests for the upper and lower body, respectively. Self-perceived physical fitness was obtained by the International Fitness Scale (IFIS). Positive and negative affect were assessed by the positive affect schedule for children (PANAS-C), happiness by Subjective Happiness Scale (SHS), optimism by Life Orientation Test-Revised (LOT-R), self-esteem by the Rosenberg Self-Esteem Scale (RSE), anxiety by State-Trait Anxiety Inventory for Children (STAIC-R), and depression by Children Depression Inventory (CDI). Multiple linear regressions adjusted by key covariates were performed to analyze associations. No associations were found between objectively-measured muscular fitness and any of the psychological well-being and distress indicators (p > 0.05). Self-perceived overall fitness and flexibility were positively associated with positive affect (β ≥ 0.258, p < 0.05). Self-perceived cardiorespiratory fitness, speed/agility, and flexibility were negatively associated with depression (β ≥ -0.222, p < 0.05). Finally, self-perceived cardiorespiratory fitness was also negatively associated with anxiety and negative affect (β ≥ -0.264, p < 0.05). Perceived physical fitness, but not objectively physical fitness, seems to be inversely related to psychological distress variables and to less extent positively related to psychological well-being. The findings from this study highlight the importance of promoting self-perceived fitness in the pediatric oncology population.

Applying a risk prediction model for bloodstream infection in a febrile, nonseverely neutropenic cohort of pediatric stem cell transplant patients.

The optimal management of febrile stem cell transplant (SCT) patients presenting without severe neutropenia (absolute neutrophil count [ANC]≥500/µL) is unclear. The authors have developed iterative risk prediction models (Esbenshade Vanderbilt [EsVan] models) that reliably predict bloodstream infections (BSIs) in the febrile general pediatric oncology population without severe neutropenia, but SCT-specific data are limited. All SCTs occurring from May 2005 to November 2019 at a single institution were identified. Episodes of fever with a central venous catheter and ANC values ≥ 500/µL were abstracted. All previous versions of the EsVan model were applied to the SCT data, and c-statistics were generated. The models were additionally applied to each type of transplant (autologous/allogeneic), and a new allogeneic model that further adjusted for metrics of immunosuppression, Esbenshade Vanderbilt Allogeneic SCT Model(EsVanAlloSCT), was developed and internally validated. For 429 SCT episodes (221 autologous and 208 allogeneic), the BSI incidence was 19.6% (84 of 429), and it was higher in allogeneic transplant patients (25.5%) than autologous transplant patients (14.0%; p< .01). All versions of the EsVan model performed well for the overall SCT cohort (c-statistics, 0.759-0.795). The EsVan models performed better for the autologous episodes (c-statistics, 0.869-0.881) than the allogeneic SCT episodes (c-statistics, 0.678-0.717). The new allogeneic transplant-specific model, EsVanAlloSCT, which added an adjustment for the extent of immunosuppression, yielded a c-statistic of 0.792 (bootstrap-corrected, 0.750). The EsVan models work exceptionally well when they are applied to autologous SCT, but they work less well for allogeneic SCT. EsVanAlloSCT appears to improve the predictive ability in allogeneic SCT, but it will need additional external validation.