Identifying symptoms using the drawings of 4-7 year olds with cancer.

PURPOSE: Symptom burden in children with cancer who are less than 8 years old is not well understood. Our research focuses on identifying how to structure a self-report instrument for younger children. Our aim was to describe how children with cancer, aged 4-7 years, express their symptoms through drawings. METHODS: Children were asked to make drawings of a day when they were "feeling bad or not good". Content of 18 children's drawings was analyzed. RESULTS: Four themes were established: physical symptoms, emotions, location and miscellaneous. Most of the drawings illustrated specific symptoms important to this age group, while also facilitating our understanding of how children with cancer view their symptoms. CONCLUSION: Having children draw pictures may help initiate communication regarding how they feel, and develop rapport between the interviewer and children.

Pharmacologic interventions for fatigue in cancer and transplantation: a meta-analysis.

Background: Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (hsct). Methods: For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, cinahl, and Psychinfo for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of hsct. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models. Results: In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins (n = 31), stimulants (n = 19), l-carnitine (n = 6), corticosteroids (n = 5), antidepressants (n = 5), appetite stimulants (n = 3), and other agents (n = 48). Fatigue was significantly reduced with erythropoietin [standardized mean difference (smd): -0.52; 95% confidence interval (ci): -0.89 to -0.14] and with methylphenidate (smd: -0.36; 95% ci: -0.56 to -0.15); modafinil (or armodafinil) and corticosteroids were not effective. Conclusions: Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of hsct. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects.

Olanzapine for prevention of chemotherapy-induced nausea and vomiting in children and adolescents: a multi-center, feasibility study.

CONTEXT: There are no prospective pediatric trials evaluating olanzapine for chemotherapy-induced nausea and vomiting (CINV) prevention. OBJECTIVE: This study evaluated the feasibility of a trial of olanzapine to evaluate the contribution of olanzapine to CINV control in pediatric oncology patients. METHODS: Patients < 18 years receiving CINV prophylaxis with ondansetron/granisetron/palonosetron ± dexamethasone ± aprepitant were eligible to participate in this prospective, single-arm, open-label study. All patients received olanzapine (0.14 mg/kg/dose; max 10 mg/dose) once daily orally starting before the first chemotherapy dose and continuing for up to four doses after the last chemotherapy administration. A future trial was considered feasible if mean time to enroll 15 patients was ≤ 12 months/site, ≥ 12/15 took at least half of the planned olanzapine doses, and ≤ 3/15 experienced significant sedation or dizziness despite dose reduction. The proportion of children who experienced complete CINV control (no nausea, vomiting, or retching) was described. RESULTS: Fifteen patients (range 4.1-17.4 years) participated; mean recruitment period was 9.3 months/site. All patients took at least half of the planned olanzapine doses. Six patients experienced sedation which resolved with olanzapine dose reduction (N = 5) or bedtime administration (N = 1). Olanzapine was stopped in one patient with blurry vision and in another with increased plasma GGT values. In both the acute and delayed phases, eight patients experienced complete control of vomiting but almost all (14/15) had nausea. CONCLUSION: A pediatric trial of olanzapine for CINV control is feasible. Our findings will inform the design of a future study.

The burden of chemotherapy-induced nausea and vomiting in children receiving hematopoietic stem cell transplantation conditioning: a prospective study.

This prospective study describes chemotherapy-induced nausea and vomiting (CINV) in children (4-18 years) receiving their first hematopoietic stem cell transplant. Emetic episodes, nausea severity (assessed using a validated, self-report nausea severity assessment tool) and antiemetic administration were documented from the start of conditioning until 24 h after the last conditioning agent was administered (acute) and for a further 7 days (delayed). Relationships between CINV control and parenteral nutrition (PN) use and acute gut GvHD (aGvHD) were explored. Fifty-nine children (4.6-17.4 years) were evaluable. Complete chemotherapy-induced vomiting (CIV; acute: 24%; delayed 22%) and chemotherapy-induced nausea (CIN; acute 7%; delayed 12%) control rates were low. Few children experienced complete CINV control (no vomiting/retching and no nausea) during the acute (5%) or delayed phases (12%). Children experiencing complete acute or delayed CIN control or complete delayed CIV control were more likely to have received: a lower proportion of their total energy requirement as PN at the end of the delayed phase (P<0.036) and PN for a shorter time (P<0.044). Low patient numbers did not permit evaluation of the association between gut aGvHD and CINV control. Effective and safe interventions aimed at improving CINV control in children are required.

Self-report of symptoms in children with cancer younger than 8 years of age: a systematic review.

OBJECTIVE: The study's objective was to summarize the psychometric evaluation of self-report symptom instruments used in children with cancer younger than 8 years of age. METHODS: We conducted electronic searches of Ovid Medline, EMBASE, PsycInfo, Science Citation, Social Science Citation (Web of Science), and CINAHL. We included studies of children with cancer in which their self-report symptoms had been quantified and in which results were described for those younger than 8 years of age. The search was restricted to publications in English. Two reviewers screened studies and abstracted all data in duplicate. Descriptive analysis of reliability and validity was performed. RESULTS: Thirteen studies were included. Only one study recruited children <8 years alone. Most studies described reliability and validity in a wider age range cohort in which most children were older than 8 years of age. Of the eight studies that evaluated reliability within the younger age group, six raised concerns about poor internal consistency with Cronbach's alpha <0.7 in at least one dimension. Concerns about test re-test reliability and inter-rater reliability were also observed. None of the studies evaluated validity. CONCLUSIONS: We failed to demonstrate that currently available instruments to measure self-report symptoms are reliable or valid specifically for children with cancer younger than 8 years of age. Development of psychometrically robust instruments for younger children should be a priority.

The importance of evidence-based supportive care practice guidelines in childhood cancer-a plea for their development and implementation.

As cure rates in pediatric oncology have improved substantially over the last decades, supportive care has become increasingly important to reduce morbidity and mortality and improve quality of life in children with cancer. Currently, large variations exist in pediatric oncology supportive care practice, which might negatively influence care. This plea underlines the importance of development and implementation of trustworthy supportive care clinical practice guidelines, which we believe is the essential next step towards better supportive care practice, and thus a higher quality of care. To facilitate international development and endorsement, the International Pediatric Oncology Guidelines in Supportive Care Network has been established.

Refinement of the symptom screening in pediatrics tool (SSPedi).

BACKGROUND: Objective was to evaluate and refine a new instrument for paediatric cancer symptom screening named the Symptom Screening in Pediatrics Tool (SSPedi). METHODS: Respondents were children 8-18 years of age undergoing active cancer treatment and parents of eligible children. Respondents completed SSPedi once and then responded to semi-structured questions. They rated how easy or difficult SSPedi was to complete. For items containing two concepts, we asked respondents whether concepts should remain together or be separated into two questions. We also asked about each item's importance and whether items were missing. Cognitive probing was conducted in children to evaluate their understanding of items and the response scale. After each group of 10 children and 10 parents, responses were reviewed to determine whether modifications were required. Recruitment ceased with the first group of 10 children in which modifications were not required. RESULTS: Thirty children and 20 parents were required to achieve a final version of SSPedi. Fifteen items remain in the final version; the score ranges from 0 to 60. CONCLUSIONS: Using opinions of children with cancer and parents of paediatric cancer patients, we successfully developed a symptom screening tool that is easy to complete, is understandable and demonstrates content validity.

Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation

To develop an evidence-based guideline for the empiric management of pediatric fever and neutropenia (FN). The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group composed of experts in pediatric oncology and infectious disease as well as a patient advocate. The Panel was convened for the purpose of creating this guideline. We followed previously validated procedures for creating evidence-based guidelines. Working groups focused on initial presentation, ongoing management, and empiric antifungal therapy. Each working group developed key clinical questions, conducted systematic reviews of the published literature, and compiled evidence summaries. The Grades of Recommendation Assessment, Development, and Evaluation approach was used to generate summaries, and evidence was classified as high, moderate, low, or very low based on methodologic considerations. Recommendations were made related to initial presentation (risk stratification, initial evaluation, and treatment), ongoing management (modification and cessation of empiric antibiotics), and empiric antifungal treatment (risk stratification, evaluation, and treatment) of pediatric FN. For each recommendation, the strength of the recommendation and level of evidence are presented. This guideline represents an evidence-based approach to FN specific to children with cancer. Although some recommendations are similar to adult-based guidelines, there are key distinctions in multiple areas. Implementation will require adaptation to the local context.

Outpatient and oral antibiotic management of low-risk febrile neutropenia are effective in children--a systematic review of prospective trials.

BACKGROUND: There is no consensus on whether therapeutic intensity can be reduced safely in children with low-risk febrile neutropenia (FN). Our primary objective was to determine whether there is a difference in efficacy between outpatient and inpatient management of children with low-risk FN. Our secondary objective was to compare oral and parenteral antibiotic therapy in this population. METHODS: We performed electronic searches of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials, and limited studies to prospective pediatric trials in low-risk FN. Percentages were used as the effect measure. RESULTS: From 7,281 reviewed articles, 16 were included in the meta-analysis. Treatment failure, including antibiotic modification, was less likely to occur in the outpatient setting compared with the inpatient setting (15 % versus 28 %, P = 0.04) but was not significantly different between oral and parenteral antibiotic regimens (20 % versus 22 %, P = 0.68). Of the 953 episodes treated in the outpatient setting and 676 episodes treated with oral antibiotics, none were associated with infection-related mortality. CONCLUSION: Based on the combination of results from all prospective studies to date, outpatient and oral antibiotic management of low-risk FN are effective in children and should be incorporated into clinical care where feasible.

Dismal response to high-dose methylprednisolone after failure to respond to standard dose in patients with acute GVHD.

Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD). Patients who are refractory to standard treatment (MP 2 mg/kg/day) may be treated with high-dose MP. This study evaluated the response to high-dose MP in children with aGVHD refractory to standard dose MP. Children who underwent hematopoietic SCT (HSCT) at our hospital between 1 June 2002 and 31 July 2006 and were treated with high-dose MP upon developing steroid-refractory aGVHD were included. Response to aGVHD therapy, adverse effects attributed to MP and overall outcomes were documented. Ten children received high-dose MP (≥ 20mg/kg/day) on 3-5 consecutive days followed by a tapering dose for steroid-refractory aGVHD, at a median of 12 days after starting standard treatment. Nine patients had ≥ grade III aGVHD. Only one patient with grade III aGVHD had a complete response. Two patients had a partial response but flared when MP was tapered. Complications included hypertension (100%), hyperglycemia requiring insulin therapy (33%) and four documented severe infections. Five children (50%) died (median follow-up: 5.9 years). Salvage therapy other than high-dose MP should be considered in children who fail to respond to MP 2 mg/kg/day.

Determination of initial i.v. CYA dosage to achieve target AUC values in pediatric hematopoietic stem cell transplant patients.

In solid organ transplantation, CYA dosing is based on the area under the concentration vs time curve (AUC(inf)). This study aimed to develop a guideline for the initial i.v. CYA dose for pediatric hematopoietic SCT (HSCT) patients to achieve the target AUC(inf) recommended in solid organ transplantation. Whole-blood CYA concentrations were determined in 24 patients (0.5-16.9 years) after the first i.v. dose given over 2 h, 1 day before HSCT. The i.v. CYA dose predicted to achieve an AUC(inf) of 4200 microg x h/l was calculated for each patient and expressed as a function of each patient's actual weight and body surface area (BSA). In patients 9 years of age, the mean i.v. CYA dose predicted to achieve the target AUC was 2.6+/-0.94 and 2.1+/-1.21 mg/kg, respectively. When these doses were expressed in terms of BSA, the mean dose was 65+/-23.1 and 68+/-35.0 mg/m(2) in children 9 years of age, respectively. In children 0.5-17 years of age undergoing HSCT, we recommend an initial i.v. CYA dose of 65 mg/m(2) infused over 2 h to achieve an AUC(inf) of approximately 4200 microg x h/l.

A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy: a Bayesian randomized serial N-of-1 trials design.

GOALS OF WORK: Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. PATIENTS AND METHODS: We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. MAIN RESULTS: Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1-11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32-6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15-3.14, probability of rate ratio<1=75%) and decreased parents' ratings of their child's distress. The drug was more effective during the delayed chemotherapy phase than the acute phase. No adverse events were attributed to metopimazine. CONCLUSIONS: Based on this pilot study, we believe that the high likelihood that metopimazine is an effective adjunct to ondansetron monotherapy suggests that this combination therapy is worthy of further study in children receiving emetogenic chemotherapy.

Outcomes of antiemetic prophylaxis in children undergoing bone marrow transplantation.

A prospective survey of the control of acute and delayed antineoplastic and radiation-induced nausea and vomiting was undertaken in children undergoing bone marrow transplantation (BMT) at The Hospital for Sick Children. Prior administration of antineoplastic agents or irradiation, presence of anticipatory nausea or vomiting prior to starting the conditioning regimen, antiemetic use within 24 h of conditioning, the prescribed antineoplastic and/or radiation ablative regimen, and prescribed antiemetic regimens were recorded. Emetic episodes, dietary intake, administration of conditioning agents and antiemetics, and adverse effects were monitored on each day of the conditioning regimen and for 96 h thereafter. Children older than 3 years of age assessed their nausea on each study day. Twenty-five children were followed for 258 patient days. Children did not vomit or retch on 73% and 43% of patient days, in the acute and delayed phases, respectively. Nausea data were evaluable for 21 children on 200 patient days. Nausea was absent on 55% and 26% of patient days in the acute and delayed phases, respectively. Five children never had an emetic episode during the entire study period. One child was completely free from nausea and vomiting throughout the study period. Antineoplastic and radiation-induced nausea and vomiting can be successfully prevented in the majority of children undergoing BMT. However, effective treatment strategies must be developed in the event of antiemetic failure and for effective prophylaxis in children who cannot tolerate dexamethasone.

Delayed nausea and vomiting in children receiving antineoplastics.

BACKGROUND: The nature and prevalence of delayed antineoplastic-induced nausea and vomiting have not been well-described in children. This study describes the extent of delayed nausea and vomiting in children receiving antineoplastic agents as well as the drug therapies initiated in an attempt to prevent or manage it. PROCEDURE: All children receiving antineoplastics were eligible for study entry. The date and time of each emetic episode were recorded on each day antineoplastics were given and for 3 days thereafter. Nausea was self-assessed daily by children who were older than 3 years and were not developmentally delayed. Diet was also assessed daily. The emetic response, median nausea rating and median diet achieved were described. RESULTS: The emetic response of 124 children who received 174 antineoplastic cycles was evaluated. Most cycles (137/174;79%) were not associated with delayed vomiting. Cycles which included cisplatin, carboplatin, or cyclophosphamide; involved antineoplastic therapy given over 2 or more consecutive days; or were accompanied by vomiting during the acute phase were associated with a significantly higher incidence of delayed vomiting. Moderate to severe nausea was reported on 58% (267/459) of study days. No antiemetics were given on most study days (412/522;79%); nevertheless, most of the study days (381/412;93%) which were unaccompanied by antiemetic support during the delayed phase were completely free from vomiting. Antiemetics were most often given as single agents (ondansetron: 54 study days; dimenhydrinate: 17 study days; dexamethasone: 6 study days). Diet was largely unaffected during the study period. CONCLUSIONS: Antineoplastic-induced delayed nausea and vomiting may be less prevalent in children than in adults. Routine antiemetic administration during the delayed phase may not be warranted in all patients. Med Pediatr Oncol 2001;37:115-121.

Practical vaccination guidelines for children with cancer.

The paediatrician or family physician usually provides primary care for children diagnosed with cancer. Immunizations are an important facet of this care, but guidelines for the immunization of these immunocom-promised children are difficult to locate and cumbersome to follow. The authors have developed immunization guidelines for children receiving chemotherapy for cancer that will hopefully facilitate the care of this group of children. Before initiating any immunizations in this group of children, communication with a cancer specialist is recommended. There is little evidence-based literature to support immunization guidelines in immunocompromised hosts; thus, the recommendations presented are derived from the available literature, existing guidelines and expert opinion.

Retrospective appraisal of busulfan dose adjustment in children.

This report describes and critically appraises our experience with busulfan dose adjustment in children undergoing bone marrow transplant between April 1997 and March 1999. All children received an initial busulfan dose of 40 mg/m2 p.o. or by nasogastric tube. Whole blood samples were obtained 1, 1.5 and 6 h later and analyzed for busulfan content by gas chromatography with electron capture detection. The area under the whole blood busulfan concentration vs time curve (AUC) and an individualized dose which would achieve an AUC of 1300 microM/min were calculated. Mean and median busulfan doses were calculated using actual, ideal and effective body weight and stratified according to age. The relationship between the busulfan concentration at hour 6 and AUC was determined using linear regression. Thirty-nine courses of busulfan were evaluated in 38 patients. A change from the initial busulfan dose was required to achieve the target AUC in 34 courses (87%). Most children >1 to 5 years old required dose increments while most children >5 years old required dose reductions. Obesity did not significantly affect busulfan dose requirements. Busulfan concentrations at 6 h only weakly predicted the AUC achieved (r2 = 0.496; P = 0.001). Based on these findings, we recommend that the initial busulfan dose be assigned according to patient age and actual body weight. We also recommend that busulfan AUC be calculated for children using a four-sample (1, 1.5, 4 and 6 h) limited sampling technique.