Primary intramedullary extradural Ewing sarcoma.

Ewing sarcoma is the second most frequent primary bone tumour of childhood and adolescence. The aim of this report is to describe the imaging, pathology, clinical findings, and treatment of a primary intradural extramedullary Ewing sarcoma with a unique intracranial metastatic component in a pediatric patient. A 14-year-old girl with a history of mood disorders presented to the emergency department with a 3-week history of neck torticollis, cervical pain, paresis, and paresthesia of the upper and lower extremities on the left side. Initially, non-organic causes such as somatization or conversion disorder were suspected. She returned 3 months later when her symptoms worsened. MRI of the head and spine was performed, and demonstrated the presence of a suprasellar, retro-chiasmatic mass lesion. There was also diffuse leptomeningeal enhancement, another well-defined intradural extramedullary lesion the sacral region and several multifocal cauda equina soft tissue nodules. The patient first underwent surgery. The patient was also treated with a combination of chemotherapy (vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide (VDC/IE)) and radiation as per the Children's Oncology Group AEWS1221 protocol. Most recent imaging conducted 22 months after the initial mass discovery revealed improvement of the suprasellar mass lesion with residual stable appearance of the prominence and enhancement of the pituitary stalk and tuber cinereum. There was interval improvement of the spinal lesions with no convincing residual. Clinically, at almost three years since initial imaging findings, and 25 months since completing treatment, she is stable from an oncology perspective.

Successful Transjugular Portosystemic Shunt Treatment of Pediatric Sinusoidal Obstruction: Case Report and Review of Literature.

Background: In adults with medically refractory sinusoidal obstruction syndrome (SOS), a transjugular intrahepatic portosystemic shunt (TIPS) has been used successfully to improve portal hypertension and symptoms such as ascites. There is limited data on the use of TIPS for SOS in pediatric patients. Methods: The index case was reviewed retrospectively. PubMed and Medline databases were searched to identify other cases. Results: A 4-year-old male with high-risk neuroblastoma, developed SOS after tandem autologous stem cell transplant. He was medically managed with defibrotide, diuretics, and peritoneal drainage, but, due to refractoriness, he underwent TIPS day +54 following bone marrow transplant. Hepatic venous pressure gradient improved from 17 to 8 mm Hg following TIPS placement with significant improvement in the patient's clinical status and ascites. However, 15 months later, his shunt remained patent, and he remains clinically well with stable liver enzymes. A literature review identified 13 pediatric cases of TIPS for SOS due to varied causes. TIPS caused a median hepatic venous pressure gradient of 9 mmHg (range, 2-38 mm Hg). The mortality following the procedure was 15%, with 2 cases who died at 2- and 11-days post-TIPS. At the time of the last follow-up (range 8-25 months), 5 patients were alive, and 8 were lost to follow-up. Conclusion: We present here a pediatric case of SOS due to stem cell transplant treated successfully with TIPS with a review of the literature. A timely, individualized application of TIPS can be effective in treating children with medication-refractory SOS.

Vaginal Metastases of Wilms' Tumor in a Pediatric Patient: A Rare Case.

BACKGROUND: Wilms' tumor is the second most common pediatric abdominal cancer; however, it rarely involves the female reproductive tract. There are few cases reported in the literature describing uterine, ovarian, cervical, and vaginal involvement. CASE: We report the case of a 7-year-old girl presenting with a large renal mass with retroperitoneal nodal and lung metastases; she was diagnosed with stage 4 favorable histology Wilms' tumor. She was treated with surgery, chemotherapy, and radiation. She presented with vaginal bleeding 10 months after completing treatment; biopsy of a vaginal mass confirmed recurrence, and this was sent for molecular profiling, which did not identify an inherited cancer predisposition or targetable mutation. She was again treated with chemotherapy; examination redemonstrated a small vaginal mass, but re-biopsy of the lesion was negative for malignancy. Due to high risk of local relapse, ongoing chemotherapy and pelvic radiation ensued. End-of-treatment imaging and vaginoscopy showed no residual disease. SUMMARY AND CONCLUSION: Vaginal metastases of Wilms' tumor are very rare; this is the second reported case in the literature. Pediatric clinicians should have a strong suspicion for vaginal metastases in cancer patients presenting with vaginal bleeding, especially when their pubertal development does not suggest that bleeding would be secondary to menarche. Long-term gynecologic care for these patients is paramount to reduce morbidity from chemotherapy and pelvic radiation. Fertility preservation counselling should be made early, through referral to a specialist.

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study.

Background: Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored. To inform the development of new and existing care guidelines for CCS, the epidemiology and monitoring of CKD and hypertension in the early period following cancer therapy warrants further investigation. Objective: To describe the design and methods of the KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors study, which aims to evaluate the burden of late kidney and blood pressure outcomes in the first ~10 years after cancer therapy, the extent of appropriate screening and complications monitoring for CKD and hypertension, and whether patient, disease/treatment, or system factors are associated with these outcomes. Design: Two distinct, but related studies; a prospective cohort study and a retrospective cohort study. Setting: Five Ontario pediatric oncology centers. Patients: The prospective study will involve 500 CCS at high risk for these late effects due to cancer therapy, and the retrospective study involves 5,000 CCS ≤ 18 years old treated for cancer between January 2008 and December 2020. Measurements: Chronic kidney disease is defined as Estimated glomerular filtration rate <90 mL/min/1.73 m2 or albumin-to-creatinine ratio ≥ 3mg/mmol. Hypertension is defined by 2017 American Academy of Pediatrics guidelines. Methods: Prospective study: we aim to investigate CKD and hypertension prevalence and the extent to which they persist at 3- and 5-year follow-up in CCS after cancer therapy. We will collect detailed biologic and clinical data, calculate CKD and hypertension prevalence, and progression at 3- and 5-years post-therapy. Retrospective study: we aim to investigate CKD and hypertension monitoring using administrative and health record data. We will also investigate the validity of CKD and hypertension administrative definitions in this population and the incidence of CKD and hypertension in the first ~10 years post-cancer therapy. We will investigate whether patient-, disease/treatment-, or system-specific factors modify these associations in both studies. Limitations: Results from the prospective study may not be generalizable to non-high-risk CCS. The retrospective study is susceptible to surveillance bias. Conclusions: Our team and knowledge translation plan is engaging patient partners, researchers, knowledge users, and policy group representatives. Our work will address international priorities to improve CCS health, provide the evidence of new disease burden and practice gaps to improve CCS guidelines, implement and test revised guidelines, plan trials to reduce CKD and hypertension, and improve long-term CCS health.

Treatment of Sinusoidal Obstruction Syndrome With Defibrotide in Pediatric Cancer Patients Following Nontransplant-associated Chemotherapy: A Case Report and Review of the Literature.

Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer patients often presents as a complication of hematopoietic stem cell transplantation, and less commonly secondary to nontransplant-associated chemotherapy. Therapy with defibrotide is well-described as standard care for transplant-associated SOS/VOD, but the treatment of nontransplant-associated SOS/VOD is less clear. We report a 3-year-old with relapsed Wilms tumor and recurrent SOS/VOD, with successful use of defibrotide during chemotherapy. A review of pediatric cancer patients with nontransplant-associated SOS/VOD treated with defibrotide revealed 83 patients, and 66 were in remission. This review supports early treatment with defibrotide in patients with nontransplant-associated SOS/VOD.

Using a dyadic approach to explore parental support for physical activity among young cancer survivors.

BACKGROUND: Physical activity confers many physical and psychosocial benefits for adolescent and young adult cancer survivors, yet most are not active enough to accrue benefits. Parental support for physical activity may be important to consider when exploring factors that influence physical activity in this population. PURPOSE: Explore adolescent and young adult cancer survivors' experiences of parental support for physical activity received and their parents' experiences of support provided. METHODS: Ten adolescent and young adult cancer survivors (Mage = 17.4 ± 3.2 years; 70% male) and one of their parents (50% fathers) were interviewed separately. Data were analyzed thematically. RESULTS: Participants' experiences were summarized into three main themes: (1) the basics - instrumental, informational, and emotional support, (2) companionship support - doing it together, and (3) role modeling - a double-edged sword. In general, there was congruence between participants' perceptions of the types of support provided and received for physical activity. However, parents felt their role was to provide instrumental, informational, and emotional support, whereas adolescent and young adult cancer survivors emphasized the importance of companionship support. CONCLUSIONS: Findings underscore the complexity of parental support for physical activity among adolescent and young adult cancer survivors. Developing and testing resources to empower adolescent and young adult cancer survivors to ask for parental support and to enable parents to support their child's physical activity is imperative.Implications for RehabilitationMany adolescent and young adult cancer survivors do not participate in enough physical activity to acquire physical and psychosocial benefits.Parental support may represent a key factor that influences physical activity participation.Rehabilitation professionals should consider the influence parents may have on adolescent and young adult cancer survivors' physical well-being post-diagnosis.Promoting co-participation may be a viable strategy to enhance physical activity participation among adolescent and young adult cancer survivors.

A Newborn with Simmering Bleeding after Circumcision.

We present a case of a healthy male neonate born at term, circumcised on Day 1 of life. Facing ongoing bleeding at the incision site, the baby was transferred to a level III neonatal intensive care unit for further investigation and management. His family history was unremarkable for bleeding disorders. On arrival, the baby was hemodynamically stable with abnormal coagulation values. Further investigations revealed a diagnosis compatible with severe hemophilia A. He deteriorated on Day 2, developing acute severe anemia which required two red blood cell transfusions. This rare but potentially fatal event reminds clinicians to remain extremely vigilant with minor surgical procedures such as circumcision even in the absence of family history.

Extreme hepatic resections for the treatment of advanced hepatoblastoma: Are planned close margins an acceptable approach?

BACKGROUND: Orthotopic liver transplantation (OLT) is considered the standard for children with hepatoblastoma (HB) in whom complete surgical resection is not possible. However, OLT is not always available or feasible. OBJECTIVE: To describe the outcome of children with HB who were initially deemed unresectable and underwent complex hepatectomy with planned close margins, and ultimately avoided OLT. METHODS: Demographic data, surgical and pathologic details, and survival information were collected from children treated for HB between January 2010 to December 2015. RESULTS: Among six children (median age 12 months (3-41 months)), PRETEXT classification was III (n = 2), III/IV (n = 1), and IV (n = 3). Patients received a median of six cycles (range 4-7) of platinum-based induction chemotherapy; five received doxorubicin. Experienced pediatric surgeons performed extended right and left hepatectomy in five and one patients, respectively, with assistance of an experienced liver transplant surgeon (n = 4). Microscopic margins were positive (n = 2) and negative but close (n = 4; 2-5 mm). Two patients required vascular reconstruction of the vena cava. At median follow-up of 3.3 years (1.7-4.6 years), there was no evidence of local recurrence. One patient had recurrence of pulmonary disease 3 months after surgery. CONCLUSIONS: Patients with advanced HB treated with complex surgical resections with positive or close negative margins had good outcomes without OLT. We suggest that planned positive or close microscopic margins in highly selected HB patients may spare the morbidity of OLT and offer an alternative for those ineligible for OLT. Our experience illustrates the importance of a multidisciplinary team specialized in the management of liver tumors.

H3.1 K36M mutation in a congenital-onset soft tissue neoplasm.

We describe a patient who presented with a congenital soft tissue lesion initially diagnosed as infantile fibromatosis at 15 days of age. Unusually, the mass demonstrated malignant progression leading to death at 20 months of age. Biological progression to malignancy is not known to occur in fibromatosis, and fibrosarcoma is not known to progress from a benign lesion. Whole-exome sequencing of the tumor identified a driver mutation in histone H3.1 at lysine (K)36. Our findings support the link between oncohistones and infantile soft tissue tumors and provide additional evidence for the oncogenic effects of p.K36M in H3 variants.

Pediatric Oncology Clinic Care Model: Achieving Better Continuity of Care for Patients in a Medium-sized Program.

Providing the best care in both the inpatient and outpatient settings to pediatric oncology patients is all programs goal. Using continuous improvement methodologies, we changed from a solely team-based physician care model to a hybrid model. All patients were assigned a dedicated oncologist. There would then be 2 types of weeks of outpatient clinical service. A "Doc of the Day" week where each oncologist would have a specific day in clinic when their assigned patients would be scheduled, and then a "Doc of the Week" week where one physician would cover clinic for the week. Patient satisfaction surveys done before and 14 months after changing the model of care showed that patients were very satisfied with the care they received in both models. A questionnaire to staff 14 months after changing showed that the biggest effect was increased continuity of care, followed by more efficient clinic workflow and increased consistency of care. Staff felt it provided better planning and delivery of care. A hybrid model of care with a primary physician for each patient and assigned clinic days, alternating with weeks of single physician coverage is a feasible model of care for a medium-sized pediatric oncology program.

Occupational exposure to chemotherapy of pharmacy personnel at a single centre.

BACKGROUND: Cyclophosphamide is one of the most commonly used chemotherapy drugs worldwide. Data concerning environmental contamination and biological exposure of pharmacy personnel to this and other chemotherapy drugs are limited. OBJECTIVES: To determine whether pharmacy personnel involved in preparing and checking cyclophosphamide doses were more likely to have detectable levels of this drug in their urine than non-oncology pharmacy personnel with no known contact with the drug, and to compare the degree of surface contamination with cyclophosphamide, methotrexate, and ifosfamide in the oncology pharmacy of a tertiary care pediatric hospital, where chemotherapy doses were prepared, and the main (control) pharmacy in the same institution, where no chemotherapy was prepared. METHODS: Biological exposure to cyclophosphamide was compared between pharmacy personnel who did and did not handle this drug by determining whether participants had detectable amounts of cyclophosphamide in their urine. Environmental exposure to chemotherapy drugs was assessed by using surface wipes to determine the degree of surface contamination with various chemotherapy agents in the oncology pharmacy and the main (control) pharmacy. RESULTS: On initial testing, cyclophosphamide was detected in the urine of all pharmacy personnel (n = 7 oncology personnel, n = 5 control personnel). However, it was determined that all control personnel had been exposed to the oncology pharmacy on the day of testing. Repeat testing of these individuals revealed no positive samples among those not exposed to the oncology pharmacy on the day of repeat testing. The sole positive result on retesting of control personnel was for a participant who had been exposed to the oncology pharmacy on the retest day. Surface wipe testing revealed contamination of the oncology pharmacy with cyclophosphamide and methotrexate before and after cleaning, as well as contamination with ifosfamide after cleaning. The main (control) pharmacy showed no evidence of contamination with cyclophosphamide, methotrexate, or ifosfamide. CONCLUSIONS: The findings suggest that environmental contamination plays a role in biological exposure to cyclophosphamide. Measures to reduce environmental contamination from chemotherapy and biological exposure of pharmacy personnel when handling chemotherapy agents should be identified and implemented as a priority.

CONTEXTE: La cyclophosphamide est l'un des médicaments de chimiothérapie les plus couramment utilisés dans le monde. Or, il n'y a que très peu de données sur la contamination environnementale et l'exposition biologique du personnel de pharmacie à ces produits. OBJECTIFS: Déterminer si le personnel de pharmacie s'occupant de la préparation et de la vérification des doses de cyclophosphamide est plus susceptible de présenter des concentrations détectables de ce médicament dans leurs urines que le personnel de pharmacie ne travaillant pas en oncologie, donc sans contact connu avec ce médicament, et comparer le niveau de contamination de surface par la cyclophosphamide, le méthotrexate et l'ifosfamide dans la pharmacie d'oncologie d'un hôpital pédiatrique de soins tertiaires, où sont préparées les doses de chimiothérapie, à celui dans la pharmacie principale (témoin) du même établissement, où n'est préparée aucune chimiothérapie. MÉTHODES: L'on a comparé l'exposition biologique à la cyclophosphamide du personnel de pharmacie ayant manipulé ce médicament à celle de personnel ne l'ayant pas manipulé en examinant si les participants présentaient des concentrations détectables de cyclophosphamide dans leurs urines. L'exposition environnementale aux produits de chimiothérapie a été évaluée à l'aide de lingettes utilisées pour essuyer les surfaces de la pharmacie d'oncologie et de la pharmacie principale (témoin) afin d'en déterminer les niveaux de contamination par différents agents de chimiothérapie. RÉSULTATS: Lors de l'analyse initiale, des concentrations de cyclophosphamide ont été détectées dans les urines de l'ensemble du personnel de pharmacie (n = 7 dans l'équipe en oncologie et n = 5 dans le groupe témoin). Mais l'on a constaté que tout le personnel du groupe témoin avait été exposé à la pharmacie d'oncologie le jour de l'analyse. Une seconde analyse chez ces personnes s'est montrée négative pour celles n'ayant pas été exposées à la pharmacie d'oncologie le jour de cette seconde analyse. Le seul résultat positif observé au cours de la seconde analyse chez le personnel du groupe témoin concernait un participant ayant été exposé à la pharmacie d'oncologie le jour de la seconde analyse. L'analyse des lingettes a révélé une contamination des surfaces de la pharmacie d'oncologie par la cyclophosphamide et le méthotrexate avant et après nettoyage ainsi qu'une contamination par l'ifosfamide après nettoyage. La pharmacie principale (témoin) ne présentait quant à elle aucun signe de contamination par l'un ou l'autre des trois produits. CONCLUSIONS: D'après ces résultats, la contamination environnementale joue un rôle dans l'exposition biologique à la cyclophosphamide. Ainsi, trouver et mettre en place des mesures visant à réduire la contamination environnementale par les produits de chimiothérapie et l'exposition biologique du personnel de pharmacie lors de la manipulation de ces produits doit représenter une priorité.

Atypical fibrodysplasia ossificans progressiva diagnosed by whole-exome sequencing.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification of connective tissue that begins during the first decade of life. Our patient presented with intrauterine growth retardation, respiratory distress, neonatal onset soft tissue masses, bilateral hallux valgus, and congenital anomalies of the thyroid and uterus. She was initially diagnosed with atypical infantile myofibromatosis based on clinical and pathological findings. She underwent whole-exome sequencing (WES) as part of the FORGE study to identify the gene for infantile myofibromatosis; however a de novo dominant mutation in ACVR1 (NM_001105.4:c.617G>A) revised the diagnosis to FOP. This patient highlights the utility of WES as an early diagnostic tool in the investigation of patients with unusual presentations of rare diseases, thereby providing clinicians with accurate molecular diagnoses and the opportunity to tailor clinical management to improve patient care.

Is time of the essence? Delayed diagnosis of Ewing's sarcoma.

Rarely in modern medicine are we able to observe the natural history of a patient with a sarcoma. This unusual case provides that opportunity. A CT scan was performed on the leg of a 15-year-old boy with a tender soft tissue mass on the lateral aspect of his left calf. Despite showing a lesion consistent with a sarcoma, neither the patient nor his family was informed. Almost a year and a half later, the patient returned and was diagnosed with Ewing's sarcoma. A staging work up showed no metastatic disease. After undergoing chemotherapy and a complete surgical resection of the tumour, the patient remains disease-free 10 years later, indicating that the biology of Ewing's sarcoma may be more important than time to diagnosis in determining outcome.

Knowledge, attitudes, and practices related to pet contact by immunocompromised children with cancer and immunocompetent children with diabetes.

OBJECTIVE: To compare knowledge, attitudes, and risks related to pet contact in households with and without immunocompromised children. STUDY DESIGN: A questionnaire was distributed to parents of children diagnosed with cancer (immunocompromised; n=80) or diabetes (immunocompetent; n=251) receiving care at the Children's Hospital of Eastern Ontario. Information was collected on knowledge of pets as sources of disease, concerns regarding pet-derived pathogens, and pet ownership practices. Data were analyzed with multivariable logistic regression. RESULTS: The questionnaire was completed by 65% (214 of 331) of the individuals to whom it was given. Pet ownership was common; 45% of respondents had a household pet when their child was diagnosed, and many (households with a child with diabetes, 49%; households with a child with cancer, 20%) acquired a new pet after diagnosis. Most households that obtained a new pet had acquired a pet considered high risk for infectious disease based on species/age (diabetes, 73%; cancer, 77%). Parents of children with cancer were more likely than parents of children with diabetes to recall being asked by a physician/staff member if they owned a pet (OR, 5.9) or to recall receiving zoonotic disease information (OR, 5.3), yet these interactions were reported uncommonly (diabetes, ≤13%; cancer, ≤48%). Greater knowledge of pet-associated pathogens was associated with recalled receipt of previous education on this topic (OR, 3.9). Pet exposure outside the home was reported frequently for children in non-pet-owning households (diabetes, 48%; cancer, 25%). CONCLUSION: Improved zoonotic disease education is needed for pet-owning and non-pet-owning households with immunocompromised children, with ongoing provision of information while the children are at increased risk of disease. Additional efforts from pediatric and veterinary healthcare professionals are required.

Occupational exposure to cyclophosphamide in nurses at a single center.

OBJECTIVE: To evaluate biological and environmental exposure to cyclophosphamide in nurses at a single institution. METHODS: Biological exposure to cyclophosphamide in nurses administering cyclophosphamide compared with two control groups: nononcology nurses not administering cyclophosphamide and community members without recent hospital exposure. Environmental exposure to chemotherapy was measured using surface wipes taken from oncology and nononcology areas in the hospital. RESULTS: More than one third of all nurses and no community controls tested positive for urinary cyclophosphamide. Oncology and nurse controls tested positive in equal numbers. Surface wipes were positive only in the oncology ward. CONCLUSION: We have demonstrated elevated levels of cyclophosphamide in one third of all nurses and cyclophosphamide contamination of surfaces within the oncology patient environment. This suggests that environmental contamination plays a major role in biological exposure to cyclophosphamide.

Stress and physical activity in young adults treated for cancer: the moderating role of social support.

PURPOSE: The first objective of the current investigation was to explore the relationships between adolescents and young adults' (AYA) experiences of stress and social support resources (i.e., perceived social support and support group involvement) following treatment for cancer. The second objective was to examine the relationship between stress and physical activity behavior, and test if social support resources are moderators of this relationship. METHODS: AYAs (N = 64; mean age = 28.8 years, standard deviation (SD) = 5.5 years; mean time since diagnosis = 2.9, SD = 3.0 years) completed an online questionnaire. Data were analyzed using correlation and hierarchical multivariate linear regression analyses. RESULTS: Stress was negatively related to perceived social support, support group involvement, and physical activity behavior. Support group involvement, but not perceived social support, moderated the association between stress and physical activity behavior. CONCLUSIONS: Findings suggest establishing support groups, as part of psychosocial rehabilitation services, may help to reduce stress and promote an active lifestyle in AYAs treated for cancer.

Risk factors for hyperferritinemia secondary to red blood cell transfusions in pediatric cancer patients.

BACKGROUND: Transfusion of packed red blood cells is common in pediatric cancer patients who receive chemotherapy. This study was done to identify characteristics of pediatric cancer patients at risk of hyperferritinemia secondary to frequent transfusions. PROCEDURE: In this retrospective chart review, all pediatric cancer patients who completed chemotherapy from January 2007 to January 2012 and had an assessment of serum ferritin 6 months after the end of treatment were included. Variables included: age, sex, type of cancer diagnosis, weight and body surface area (BSA) at the time of diagnosis, number of transfusions, total transfused volume (TTV), total transfused volume per body weight (TVPBW), and weight and BSA change from the time of diagnosis to the time of ferritin check. RESULTS: Of 109 eligible patients, 85 (78%) received transfusions. Sixteen patients (14.7%) had ferritin levels > 200 µg/L and four (3.7%) had ferritin levels > 1,000 µg/L. Although age, weight and BSA at cancer diagnosis, number of transfusions and TVPBW were correlated with the level of ferritin, independent risk factors were TTV (range 1,961-30,090 ml in patients with hyperferritinemia, P < 0.001) and BSA change from the time of diagnosis to the time of ferritin check (range -0.15 to 0.31 m(2) in patients with hyperferritinemia, P < 0.001). Increase in BSA was correlated with reduction of hyperferritinemia in follow-up ferritin measurements (P = 0.049). CONCLUSIONS: In addition to TTV, change in BSA is an independent predictor for the degree and possibly persistence of hyperferritinemia in pediatric cancer patients and should be considered in decisions to initiate interventions.