Overcoming barriers to establishing autopsy procurement programs in pediatric patients with central nervous system tumors: a call to develop regional centers.

BACKGROUND: While autopsy-repository programs with a variety of pediatric central nervous system (CNS) tumor types are a critical resource for preclinical neuro-oncology research, few exist and there is no published guidance on how to develop one. The goal of this prospective Pediatric Brain Tumor Repository (PBTR) study was to develop such a program at Cincinnati Children's Hospital Medical Center (CCHMC) and then publish the quantitative and experiential data as a guide to support the development of similar programs. METHODS: Protocols and infrastructure were established-to educate oncologists and families, establish eligibility, obtain consent, address pre- and post-autopsy logistics (e.g., patient and tissue transportation), process and authenticate tissue samples, and collect and analyze data. RESULTS: Of the 129 pediatric CNS tumor patients at CCHMC who died between 2013 and 2018, 109 were eligible for our study. Of these, 74% (81 of 109) were approached for PBTR donation, and 68% (55 of 81) consented. In the final year of the study, approach and consent rates were 93% and 85%, respectively. Median time from death to autopsy (postmortem interval, PMI) was 10 h (range, 1.5-30). In the outpatient setting, PMI increased with distance (from the hospice/home where the patient died to CCHMC). In all patients, PMI appeared to be lower, when consent was obtained more than 24 h before death. CONCLUSIONS: Procurement of autopsy specimens need not be a barrier in neuro-oncology research. Regional centers, strict timing-of-consent, patient education, and dedicated staff are all needed to minimize PMI and, thereby, increase the value of the procured tissue for an array of basic and translational research applications.

Building capacity through integration of advanced practice nurses in research.

BACKGROUND: Advanced practice nurses (APNs) are well-positioned to function in research settings, however barriers to their engagement persist. Capacity-building through multisite research opportunities is an important strategy to overcome these barriers. PURPOSE: To describe the benefits and challenges of incorporating APNs in research and discuss opportunities for building capacity for nursing research. METHOD: Grounded in the experience of a nurse-led multisite longitudinal observational descriptive symptom study, field notes representing the research continuum were reviewed and categorized into themes reflecting benefits and challenges. FINDINGS: Uniform benefits of acquiring research knowledge and skills, participating in research activities, and engaging in professional development were experienced among APNs. Limited support for regulatory and research activities, inadequate financial infrastructure, and a perceived lack of value for APNs' professional growth were commonly encountered challenges. DISCUSSION: Establishment of an infrastructure that elevates benefits and mitigates challenges is necessary to effectively incorporate APNs in a research environment, build capacity, and advance nursing science.

Impact of a Vitamin D Replacement Algorithm in Children and Young Adults With Acute Lymphoblastic Leukemia.

BACKGROUND: Pediatric cancer patients have a high prevalence of vitamin D deficiency. Children and young adults with acute lymphoblastic leukemia are at high risk for associated poor bone outcomes due to contributing effects of chemotherapy and supportive care. Evidence-based vitamin D guidelines are lacking in this population. MATERIALS AND METHODS: This is a retrospective study following the implementation of an institutional guideline for standardized monitoring and supplementing vitamin D based on 25-hydroxyvitamin D levels and patient age. Goal 25-hydroxyvitamin D level was defined as ≥30 ng/mL and levels were checked every 3 months. RESULTS: Over a period of 22 months, 69 patients (median age, 6.7 y) were included. At diagnosis, 42 patients (60.8%) were insufficient. Among insufficient patients at diagnosis, 83.3% became sufficient at first repeat level following supplementation. At completion of the study 95.6% of patients were sufficient. Insufficiency was more common in winter than summer at baseline (74.3% vs. 47.1%, P=0.03), though the impact of seasonality was overcome following the algorithm. Throughout the study 4 patients had supratherapeutic but nontoxic levels. CONCLUSIONS: Vitamin D replacement guidelines implemented in the pediatric and young adult acute lymphoblastic leukemia population markedly increased the percentage of vitamin D sufficient patients in a short period of time.

Comparison of child self-report and parent proxy-report of symptoms: Results from a longitudinal symptom assessment study of children with advanced cancer.

PURPOSE: This report represents a subanalysis of data from a primary study and addresses a gap in understanding the similarities and differences of symptom reporting between children with advanced cancer and their parents. The objectives of this subanalysis were to (1) compare reports of symptom prevalence, symptom burden, and symptom frequency, severity, and distress between groups of children and adolescents and their parents, and (2) describe concordance of symptom reports within individual child-parent dyads. DESIGN AND METHODS: Forty-six children with relapsed, refractory, or progressive cancer and their parents from five pediatric cancer centers prospectively reported symptoms every 2 weeks for up to 61 weeks. The abbreviated Pediatric Quality of Life and Evaluation of Symptoms Technology-Memorial Symptom Assessment Scales were used to measure symptom prevalence, frequency, severity, and distress. RESULTS: Children and parents reported pain, fatigue, nausea, and sleeping difficulties as the most frequently occurring symptoms. With the exception of shortness of breath, parents reported symptom prevalence more often than children. The differences in parent reports were statistically significant for fatigue, nausea, lack of appetite, feeling nervous, and sadness. Parents reported higher symptom burden scores compared to children for all individual symptoms except shortness of breath. Children reported higher scores for 19 of 32 possible symptom frequency, severity, and distress ratings. Children's scores were higher for frequency and severity, while parents' scores were higher for distress. Sleeping difficulties, pain, nausea, and diarrhea demonstrated the highest concordance, while feeling nervous, sadness, irritability, and fatigue yielded the lowest concordance between children's and parents' symptom reports. PRACTICE IMPLICATIONS: Eliciting the symptom experience from the child, when appropriate, rather than a parent proxy is best practice given evidence supporting the overestimation of symptom prevalence by parents and underestimation of symptom frequency and severity for some symptoms. When proxy raters must be used, pediatric nurses should educate proxy raters regarding symptom assessment, and assess and tend to symptoms that may not exhibit visual cues. Pediatric nurses should conduct a comprehensive symptom assessment and evaluate beyond the presence of symptoms and include an assessment of frequency, severity, and distress for physical and psychological symptoms to optimize symptom management strategies.

Electronic Symptom Assessment in Children and Adolescents With Advanced Cancer Undergoing Hematopoietic Stem Cell Transplantation.

Background/Purpose: Effective symptom assessment and management for children with advanced cancer undergoing hematopoietic stem cell transplantation (HSCT) is critical to minimize suffering. The purpose of this subanalysis was to compare feasibility of electronic data collection data and symptom prevalence, frequency, severity, and distress from children with advanced cancer undergoing HSCT with a non-HSCT cohort. Method: An abbreviated Pediatric Quality of Life and Evaluation of Symptoms Technology Memorial Symptom Assessment Scale was electronically administered every 2 weeks to children with advanced cancer. A subanalysis was conducted for the cohort of children who received autologous or allogeneic HSCT. Results: Forty-six participants completed 563 symptom assessments during the study. However, 11 of these 46 children received HSCT and completed 201 symptom assessments. The median age in the HSCT cohort was 12.7 years, 73% were female, and most children had a hematologic (45%) or solid tumor (45%) malignancy. Pain (35%), nausea (30%), sleeping difficulty (29%), and fatigue (22%) were the most commonly reported symptoms in children receiving HSCT. Children in the HSCT cohort had similar total, subscale, and individual symptom scores compared with children who did not receive HSCT. Certain domains of gastrointestinal symptoms (nausea, lack of appetite, and diarrhea) were higher for children receiving HSCT compared with children with advanced cancer not receiving HSCT (p < .05). Conclusion: Elicitation of patient-reported symptom experiences using electronic methods improves nurses' understanding of the symptom experience for children with advanced cancer undergoing HSCT and may promote timely assessment and treatment of distressing symptoms.

Using Patient-Reported Outcomes to Measure Symptoms in Children With Advanced Cancer.

BACKGROUND: Children with advanced cancer experience symptoms despite access to quality care. Symptom research has previously relied upon retrospective designs and parent proxy rather than prospective measurement with self-report. OBJECTIVE: This study evaluated the feasibility of electronic data collection in children with advanced cancer using self-report of symptom frequency, severity, and distress. METHODS: A multisite prospective cohort design was used for this study. Children who were 7 to 18 years of age and English-speaking and had a diagnosis of advanced cancer were included. Symptom frequency, severity, and level of distress were measured every 2 weeks. RESULTS: Forty-six children completed 563 of 622 (91%) administered electronic symptom assessments. Pain, fatigue, nausea, and sleeping difficulties were the most reported symptoms across all assessments and during the last 12 weeks of life. Symptoms with the highest composite scores included pain, fatigue, nausea, and sleeping difficulties. During the last 12 weeks of life, pain, fatigue, diarrhea, and sleeping difficulties had the highest composite scores. When the domains of frequency, severity, and distress were compared between groups, children reported significantly higher frequency of pain and eating difficulty during the last 12 weeks of life. CONCLUSIONS: Electronic data collection is a feasible way to evaluate the constellation of symptoms. Children with advanced cancer continue to experience physical and psychological symptoms, especially during the last 12 weeks of life despite quality care. IMPLICATIONS FOR PRACTICE: Assessment of symptom domains, including frequency, severity, and distress when symptoms are present may allow clinicians to better understand and manage symptoms of most concern to the patient.

Intellectual and functional outcome of children 3 years old or younger who have CNS malignancies.

PURPOSE: To evaluate the impact of tumor location, clinical parameters, and therapy on neurocognitive, neuroendocrine, and functional outcomes in children < or = 3 years old with intracranial CNS malignancies who survived at least 2 years after diagnosis. PATIENTS AND METHODS: Records were retrospectively reviewed for 194 children diagnosed from 1985 to 1999 at St Jude Children's Research Hospital (Memphis, TN). RESULTS: The median age at diagnosis was 1.8 years (range, 0.1 to 3.5 years). Median follow-up was 7.64 years (2.0 to 19.4 years). Tumors were infratentorial (102), diencephalic (53), and hemispheric (39); 47% required ventriculoperitoneal shunts, 36% developed seizure disorders, and 20% developed severe ototoxicity. Therapy included no radiation therapy (RT) in 57 (30%), local RT in 87 (45%), and craniospinal irradiation (CSI) in 49 (25%). Overall survival at 10 years was 78 +/- 4%. In a longitudinal analysis of 126 patients with at least one neurocognitive evaluation (NE), the mean rate of intelligence quotient (IQ) change for patients who received CSI (-1.34 points per year) and local RT (-0.51 points per year) was significantly different from the no RT group (0.91 points per year; P = .005 and P = .036, respectively). Patients with hemispheric tumors had a significantly greater IQ decline (-1.52 points per year) than those with midline tumors (0.59 points per year; P = .038). Among those with NE > or = 5 years after diagnosis, 71.4% of CSI recipients compared with 23% of local RT recipients had IQ less than 70 (P = .021). Patients undergoing CSI were more likely to develop endocrinopathies (P < .0001) and to require special education (P = .0007). CONCLUSION: In young children with CNS tumors, CSI and hemispheric location are associated with significant declines in IQ scores.

Transitioning survivors of central nervous system tumors: challenges for patients, families, and health care providers.

Survivors of central nervous system tumors (SCNST) are a growing group of cancer survivors who require risk-based, long-term health care due to the chemotherapy, surgery, and radiation they have received.Although treatment strategies are being developed to reduce morbidity and mortality, ultimately this subgroup of pediatric cancer survivors often faces moderate to severe late effects of their treatment.As a result, they will need lifelong health care that includes risk-based health care due to cancer treatment exposures as well as primary adult health care, including primary and secondary preventative care. The best way to accomplish lifelong health care for SCNST as they enter adulthood is not clearly defined. In this article, the authors plan to (1) present an overview of the complexities of health care problems that make transition challenging for SCNST; (2) review the evolving transition literature; (3) explore the barriers to successful transition; (4) discuss methods to facilitate transition; (5) describe approaches, strategies, and models for survivorship care in SCNST; (6) present issues for consideration when transitioning SCNST; and (7) provide information on transition-related resources.

High-dose chemotherapy with autologous stem cell rescue for children with recurrent malignant brain tumors.

BACKGROUND: High-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been reported to be effective in treating children with recurrent central nervous system (CNS) malignancies. METHODS: To evaluate the efficacy and toxicities of HDCT and ASCR, the medical records of 27 children with recurrent CNS malignancies who received such therapy at St. Jude Children's Research Hospital between 1989 and 2004 were reviewed. RESULTS: The median age at diagnosis was 4.5 years (range, 0.4-16.6 years) and that at ASCR was 6.7 years (range, 1.1-18.5 years). Diagnoses included medulloblastoma (13 patients), primitive neuroectodermal tumor (3 patients), pineoblastoma (2 patients), atypical teratoid rhabdoid tumor (2 patients), ependymoma (3 patients), anaplastic astrocytoma (2 patients), and glioblastoma multiforme (2 patients). The 5-year overall and progression-free survival (PFS) rates were 28.2% and 18.5%, respectively. The 5-year PFS rate for patients aged<3 years at diagnosis (57.1%) was significantly better than older patients (5.0%) (P=.019). Among the 6 long-term survivors (5 with M0 disease and 1 with M3 disease at diagnosis), 5 received both radiotherapy and HDCT as part of their salvage regimen; 4 were aged<3 years at diagnosis and had received chemotherapy only as part of frontline therapy. Two patients died of transplant-related toxicities; 44% experienced grade 3 or 4 transplant-related toxicities (toxicities were graded according to the National Cancer Institute Common Toxicity Criteria). CONCLUSIONS: HDCT with ASCR is not an effective salvage strategy for older children with recurrent CNS malignancies. The significantly better outcome in the younger cohort was most likely related to the use of radiotherapy as part of the salvage strategy.

Osteosarcoma nursing care guidelines: a tool to enhance the nursing care of children and adolescents enrolled on a medical research protocol.

Clinical trials dominate the therapeutic approaches used in pediatric oncology with the majority of pediatric oncology patients receiving treatment on medical research protocols. These protocols detail the medical treatment that enrolled patients will receive. Nursing care is not described in these documents. However, nursing care must complement the medical care as written in the medical research protocol. Administering treatments safely, assessing treatment responses, educating patients and families, and communicating with the entire health care team are some of the essential nursing responsibilities that must be carefully orchestrated. Nursing care guidelines, as described here, were created to provide the careful balance between the medical research protocol and associated nursing care. These guidelines describe the nursing actions and considerations involved in caring for pediatric oncology patients enrolled on a particular medical research protocol. The purpose of this article is to describe the process used to create and evaluate nursing care guidelines.

Clear cell ependymoma: a clinicopathologic and radiographic analysis of 10 patients.

BACKGROUND: Clear cell ependymoma (CCE) is an uncommon central nervous system tumor with a predilection for the supratentorial region in children. Histologically, it may mimic oligodendroglioma, central neurocytoma, hemangioblastoma, and renal cell carcinoma. METHODS: The authors reviewed the clinical, radiographic, and pathologic features, therapy, and outcome in 10 children with CCE who were treated at St. Jude Children's Research Hospital (1984-2003). Fluorescence in situ hybridization (FISH) was performed using 1p/1q, 19p/19q, CEP18/DAL1, and bcr/NF2 probe pairs. RESULTS: The median patient age at diagnosis was 7.5 years (range, 1-19 years). Tumors occurred supratentorially in 9 of 10 patients. All tumors had rounded nuclei with surrounding, clear halos and at least focal perivascular pseudorosettes. Seven tumors had anaplastic features. No deletions involving 1p, 19q, or NF2 were detected. The tumors from 5 of 7 patients, all with anaplasia, had losses of both CEP18 and DAL-1. Radiographically, all tumors were enhanced, and 9 tumors had associated cysts with enhancing walls. Seven patients underwent gross total resection, which was near total in one patient and subtotal in two patients. Five patients received immediate postoperative local radiotherapy. Three patients were diagnosed initially with pilocytic astrocytoma (one patient) and oligodendroglioma (two patients) and were observed. The progression-free survival and overall survival rates at 5 years were 34% +/- 20% and 75% +/- 19%, respectively. The median follow-up was 37 months (range, 5-239 months). Five patients developed local recurrence within a median of 9 months after diagnosis. Two patients developed extracranial soft tissue and lymph node metastases. CONCLUSIONS: CCEs were found to have a predilection for extraneural metastases and early recurrence and demonstrate characteristic radiographic features, anaplastic histologic features, and chromosome 18 losses. The authors recommend resection followed by local radiotherapy as the treatment of choice in children.