Outcome of patients with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcomas enrolled in phase 2 cooperative group clinical trials: A report from the Children's Oncology Group.

BACKGROUND: The aim of this study was to estimate the event-free survival (EFS) of children and young adults with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) treated in nonrandomized phase 2 studies conducted by the Children's Oncology Group (COG) and predecessor groups to establish a benchmark EFS for future phase 2 NRSTS trials evaluating the activity of novel agents. METHODS: A retrospective analysis of patients with recurrent or refractory NRSTS prospectively enrolled in nonrandomized phase 2 COG and predecessor group trials between 1994 and 2015 was conducted. EFS was defined as disease progression/relapse or death and calculated via the Kaplan-Meier method. The log-rank test and relative risk regression were used to compare EFS distribution by age at enrollment, sex, race, NRSTS histology, prior lines of therapy, calendar year of trial, and type of radiographic response. RESULTS: In total, 137 patients were enrolled in 13 phase 2 trials. All trials used radiographic response rate as a primary outcome, and none of the agents used were considered active on the basis of trial-specified thresholds. The estimated median EFS and 6-month EFS of the entire study cohort was 1.5 months (95% confidence interval [CI], 1.3-1.8 months) and 19.4% (95% CI, 12.7%-26%), respectively. No difference in EFS was observed by age at enrollment, sex, race, NRSTS histology subtype, prior lines of therapies, and trial initiation year. EFS significantly differed by radiographic response. CONCLUSIONS: The EFS for children and young adults with relapsed or refractory NRSTS remains suboptimal. Established EFS can be referenced as a benchmark for future single-agent phase 2 trials incorporating potentially active novel agents in this population.

Roadmap for the next generation of Children's Oncology Group rhabdomyosarcoma trials.

Clinical trials conducted by the Intergroup Rhabdomyosarcoma (RMS) Study Group and the Children's Oncology Group have been pivotal to establishing current standards for diagnosis and therapy for RMS. Recent advancements in understanding the biology and clinical behavior of RMS have led to more nuanced approaches to diagnosis, risk stratification, and treatment. The complexities introduced by these advancements, coupled with the rarity of RMS, pose challenges to conducting large-scale phase 3 clinical trials to evaluate new treatment strategies for RMS. Given these challenges, systematic planning of future clinical trials in RMS is paramount to address pertinent questions regarding the therapeutic efficacy of drugs, biomarkers of response, treatment-related toxicity, and patient quality of life. Herein, the authors outline the proposed strategic approach of the Children's Oncology Group Soft Tissue Sarcoma Committee to the next generation of RMS clinical trials, focusing on five themes: improved novel agent identification and preclinical to clinical translation, more efficient trial development and implementation, expanded opportunities for knowledge generation during trials, therapeutic toxicity reduction and quality of life, and patient engagement.

Event-free survival in relapsed and refractory rhabdomyosarcoma treated on cooperative group phase II trials: A report from the Children's Oncology Group.

BACKGROUND: Novel therapies are needed for relapsed and refractory rhabdomyosarcoma (RRMS). Phase II clinical trials in RRMS have typically utilized radiologic response as the primary activity endpoint, an approach that poses several limitations in RRMS. In this analysis, we aimed to estimate an event-free survival (EFS) endpoint for RRMS that could be used as a benchmark for future studies. PROCEDURE: We performed a retrospective study of patients with RRMS enrolling on 13 single-agent phase II Children's Oncology Group and legacy group trials from 1997 to 2016. All included trials used radiographic response as their primary activity endpoint. Six-month EFS was estimated from time of trial enrollment with 95% confidence intervals. Clinical characteristics, including trial of enrollment, sex, age, race, histology, number of prior chemotherapies, and radiographic response were evaluated for their impact on 6-month EFS. RESULTS: We identified 175 patients across 13 trials. The 6-month EFS was 16.8% (11.6%-22.8%). No differences were seen in 6-month EFS based on age, sex, race, or histology. There were nonsignificant trends toward improved 6-month EFS for patients with less than or equal to two prior lines of therapy versus higher than two, for patients enrolled on trials that achieved their primary radiographic response endpoint versus trials that did not, and for patients who achieved complete or partial response compared to those achieving stable disease. CONCLUSIONS: The prognosis of RRMS enrolled on single-agent phase II trials is poor. This pooled 6-month EFS of RRMS on single-agent trials may be used as a RRMS-specific benchmark for future single-agent phase II trials.

Cannabinoids for symptom management in children with cancer: A systematic review and meta-analysis.

BACKGROUND: Despite the widespread use of medical cannabis, little is known regarding the safety, efficacy, and dosing of cannabis products in children with cancer. The objective of this study was to systematically appraise the existing published literature for the use of cannabis products in children with cancer. METHODS: This systematic review, registered with the International Prospective Register of Systematic Reviews (CRD42020187433), searched four databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library. Abstracts and full texts were screened in duplicate. Data on types of cannabis products, doses, formulations, frequencies, routes of administration, indications, and clinical and demographic details as well as reported efficacy outcomes were extracted. Data on cannabinoid-related adverse events were also summarized. RESULTS: Out of 34,611 identified citations, 19 unique studies with a total of 1927 participants with cancer were included: eight retrospective chart reviews, seven randomized controlled trials, two open-label studies, and two case reports. The included studies reported the use of various cannabis products for the management of symptoms. Cannabinoids were commonly used for the management of chemotherapy-induced nausea and vomiting (11 of 19 [58%]). In controlled studies, somnolence, dizziness, dry mouth, and withdrawal due to adverse events were more commonly associated with the use of cannabinoids. Across all included studies, no serious cannabis-related adverse events were reported. CONCLUSIONS: Although there is evidence to support the use of cannabis for symptom management, in children with cancer, there is a lack of rigorous evidence to inform the dosing, safety, and efficacy of cannabinoids. Because of the increasing interest in using cannabis, there is an urgent need for more research on medical cannabis in children with cancer.

Common queries in managing rhabdomyosarcoma in low- and middle-income countries: An Indo-North American collaboration.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma among children and adolescents. The management of RMS involves risk stratification of the patients based on various clinicopathological characteristics. The multimodality treatment approach requires chemotherapy, surgery, and/or radiation. The treatment of RMS necessitates the involvement of multiple disciplines, such as pathology, pediatric oncology, surgery, and radiation oncology. The disease heterogeneity, molecular testing, evolving treatment regimens, and limited resources are some of the challenges faced by clinicians while treating a patient with RMS in low- and middle-income countries (LMICs). In this review, we endeavor to bring experts from varying fields to address clinicians' common questions while managing a child or adolescent with RMS in LMICs. This review is most applicable to level 2 centers in LMICs as per the levels of services described by the Adapted Treatment Regimens Working Group of the Pediatric Oncology in Developing Countries committee of the International Society of Pediatric Oncology.

Feasibility of combining temsirolimus to vincristine, dactinomycin, cyclophosphamide, and vincristine and irinotecan chemotherapy for children with intermediate-risk rhabdomyosarcoma: A report from Children's Oncology Group.

BACKGROUND: Temsirolimus has shown in vivo activity against rhabdomyosarcoma (RMS). We aimed to determine the feasibility of incorporating temsirolimus within the standard Children's Oncology Group (COG) chemotherapy backbone of vincristine, actinomycin-D, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) in children with intermediate-risk (IR) RMS. METHODS: The feasibility phase of the COG IR-RMS trial, ARST1431 (NCT02567435), assigned 10 patients to receive 15 mg/m2 /dose (dose level 1) of temsirolimus on days 1, 8, and 15 of each of three weekly VAC and VI cycles for the first 12 weeks of induction chemotherapy. The primary endpoint of the feasibility phase was to establish the safe dose and safety of combining temsirolimus with VAC/VI. The combination regimen was deemed feasible if less than 40% of patients developed a priori defined nonhematological dose-limiting toxicities (DLTs). RESULTS: Ten patients (seven males and three females; median age = 4.5 years [range: 0.2-14.4 years]) with IR-RMS were enrolled and received dose level 1 of temsirolimus. Eight patients had FOXO1-negative disease, while two had FOXO1-positive disease. Two patients had metastatic disease. Of 10 patients, two developed DLTs: grade 3 oral mucositis and pneumonitis. Four patients (40%) had grade 4 neutropenia. No treatment-related mortality occurred. The median duration of the completion of the feasibility phase was 12.1 weeks (range: 11.7-15 weeks). CONCLUSIONS: Weekly temsirolimus at 15 mg/m2 /dose during VAC/VI chemotherapy was feasible and well tolerated. The efficacy of this regimen is currently being tested in a phase III randomized trial against VAC/VI chemotherapy alone in the ARST1431 trial.

Children's Oncology Group's 2023 blueprint for research: Soft tissue sarcomas.

In the United States, approximately 850-900 children and adolescents each year are diagnosed with soft tissue sarcomas (STS). STS are divided into rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma STS (NRSTS). RMS and NRSTS are risk stratified into low-, intermediate-, and high-risk categories, with 5-year survival rates of approximately 90%, 50%-70%, and 20%, respectively. Recent key achievements from the Children's Oncology Group (COG) STS Committee include the identification of new molecular prognostic factors for RMS, development and validation of a novel risk stratification system for NRSTS, successful completion of a collaborative NRSTS clinical trial with adult oncology consortia, and collaborative development of the INternational Soft Tissue SaRcoma ConsorTium (INSTRuCT). Current COG trials for RMS are prospectively evaluating a new risk stratification system that incorporates molecular findings, de-intensification of therapy for a very low-risk subgroup, and augmented therapy approaches for intermediate- and high-risk RMS. Trials for NRSTS exploring novel targets and local control modalities are in development.

Trimodality Treatment of Extremity Soft Tissue Sarcoma: Where Do We Go Now?

OPINION STATEMENT: Extremity soft tissue sarcoma (ESTS) constitutes the majority of patients with soft tissue sarcoma (STS). Patients with localized high-grade ESTS > 5 cm in size carry a substantial risk of developing distant metastasis on follow-up. A neoadjuvant chemoradiotherapy approach can enhance local control by facilitating resection of the large and deep locally advanced tumors while trying to address distant spread by treating the micrometastasis for these high-risk ESTS. Preoperative chemoradiotherapy and adjuvant chemotherapy are often used for children with intermediate- or high-risk non-rhabdomyosarcoma soft tissue tumors in North America and Europe. In adults, the cumulative evidence supporting preoperative chemoradiotherapy or adjuvant chemotherapy remains controversial. However, some studies support a possible benefit of 10% in overall survival (OS) for high-risk localized ESTS, especially for those with a probability of 10-year OS < 60% using validated nomograms. Opponents of neoadjuvant chemotherapy argue that it delays curative surgery, compromises local control, and increases the rate of wound complications and treatment-related mortality; however, the published trials do not support these arguments. Most treatment-related side effects can be managed with adequate supportive care. A coordinated multidisciplinary approach involving sarcoma expertise in surgery, radiation, and chemotherapy is required to achieve better outcomes for ESTS. The next generation of clinical trials will shed light on how comprehensive molecular characterization, targeted agents and/or immunotherapy can be integrated into the upfront trimodality treatment to improve outcomes. To that end, every effort should be made to enroll these patients on clinical trials, when available.

Outcomes of Coronavirus Disease 2019 Infection in Children and Adolescents With Cancer in Canada: Population-based Study and Systematic Review.

Published outcomes for children with cancer with coronavirus disease 2019 (COVID-19) have varied. Outcome data for pediatric oncology patients in Canada, outside of Quebec, have not been reported. This retrospective study captured patient, disease, and COVID-19-related infectious episode characteristics and outcome data for children, 0 to 18 years, diagnosed with a first COVID-19 infection between January 2020 to December 2021 at 12 Canadian pediatric oncology centers. A systematic review of pediatric oncology COVID-19 cases in high-income countries was also undertaken. Eighty-six children were eligible for study inclusion. Thirty-six (41.9%) were hospitalized within 4 weeks of COVID-19; only 10 (11.6%) had hospitalization attributed to the virus, with 8 being for febrile neutropenia. Two patients required intensive care unit admission within 30 days of COVID-19 infection, neither for COVID-19 management. There were no deaths attributed to the virus. Of those scheduled to receive cancer-directed therapy, within 2 weeks of COVID-19, 20 (29.4%) experienced treatment delays. Sixteen studies were included in the systematic review with highly variable outcomes identified. Our findings compared favorably with other high-income country's pediatric oncology studies. No serious outcomes, intensive care unit admissions, or deaths, in our cohort, were directly attributable to COVID-19. These findings support the minimization of chemotherapy interruption after COVID-19 infection.

Mental Disorders Among Mothers of Children Born Preterm: A Population-Based Cohort Study in Canada.

BACKGROUND: Our aim was to examine the association between preterm delivery and incident maternal mental disorders using a population-based cohort of mothers in Canada. METHODS: Retrospective matched cohort study using Manitoba Centre for Health Policy (MCHP) administrative data in Manitoba. Mothers who delivered preterm babies (<37 weeks gestational age) between 1998 and 2013 were matched 1:5 to mothers of term babies using socio-demographic variables. Primary outcome was any incident mental disorder within 5 years of delivery defined as any of (a) mood and anxiety disorders, (b) psychotic disorders, (c) substance use disorders, and (d) suicide or suicide attempts. Multivariable Poisson regression model was used to estimate the 5-year adjusted incidence rate ratios (IRRs). RESULTS: Mothers of preterm children (N = 5,361) had similar incidence rates of any mental disorder (17.4% vs. 16.6%, IRR = 0.99, 95% CI, 0.91 to 1.07) compared to mothers of term children (N = 24,932). Mothers of term children had a higher rate of any mental disorder in the first year while mothers of preterm children had higher rates from 2 to 5 years. Being the mother of a child born <28 week (IRR = 1.5, 95% CI, 1.14 to 2.04), but not 28-33 weeks (IRR = 1.03, 95% CI, 0.86 to 1.19) or 34-36 weeks (IRR = 0.96, 95% CI, 0.88 to 1.05), was associated with any mental disorder. INTERPRETATION: Mothers of preterm and term children had similar rates of incident mental disorders within 5-years post-delivery. Extreme prematurity was a risk factor for any mental disorder. Targeted screening and support of this latter group may be beneficial.

Psychological distress and experiences of Adolescents and Young Adults with cancer during the COVID-19 pandemic: A cross-sectional survey.

BACKGROUND: This study investigated prevalence of psychological distress, factors associated with distress, and experiences of Adolescents and Young Adults (AYAs) with cancer during the COVID-19 pandemic. It also compared distress in this group to previously surveyed Canadian AYAs with cancer in 2018 by the Young Adults with Cancer in their Prime (YACPRIME) study. METHODS: A cross-sectional, online, self-administered survey of AYAs diagnosed with cancer between 15 and 39 years of age was conducted. Psychological distress was measured by the Kessler Psychological Distress Scale (K10). Associations between variables and high psychological distress (K10 ≥ 25), and comparison of prevalence of psychological distress with the YACPRIME study were done using multivariable logistic regression. Summative qualitative content analysis analyzed participant experiences during this pandemic. RESULTS: We included 805 participants. High psychological distress was present in over two-thirds of the group (68.0%; 95% CI, 64.7%-71.2%). Employment impact during pandemic (AOR (adjusted odds ratio), 2.16; 95% CI, 1.41-3.31) and hematologic malignancy (AOR, 1.76; 95% CI 1.08-2.97) were associated with higher psychological distress, while older age [AOR, 0.95; 95% CI, 0.92-0.99] and personal income < $40,000 (AOR, 0.38; 95% CI, 0.24-0.58) were associated with lower distress. Adjusted odds of experiencing psychological distress among AYAs with cancer during pandemic compared to pre-pandemic years was 1.85 (95% CI: 1.36-2.53). Overarching themes of pandemic experiences included: inferior quality of life, impairment of cancer care, COVID-19 related concerns and extreme social isolation. CONCLUSION: AYAs diagnosed with cancer are experiencing high psychological distress during this pandemic. Distress screening and evidence-based interventions to alleviate distress are essential.

Diagnostic and treatment intervals are not associated with survival in rhabdomyosarcoma: A Cancer in Young People in Canada study.

BACKGROUND: Delay in diagnosis and treatment initiation can be associated with adverse outcomes in children with cancer. Diagnostic interval (DI) is defined as the time between the date of first health care contact for symptoms related to cancer to the date of cancer diagnosis, and treatment interval (TI) is defined as interval between the definitive cancer diagnosis and cancer treatment initiation. We aimed to determine the predictors of DI and TI in children with rhabdomyosarcoma (RMS) and their association with event-free survival (EFS) and overall survival (OS). METHODS: Using the Cancer in Young People in Canada (CYP-C) national population-based database, we conducted a retrospective cohort study of children (0-14.99 years) newly diagnosed with RMS between 2001 and 2015 in Canada. Quantile regression was used to assess the predictors of DI and TI, and Cox regression was used to determine if these intervals were associated with EFS and OS. RESULTS: Median DI and TI were 16.5 days (interquartile range [IQR] 6.0-38.0) and 5 days (IQR 0-12), respectively. DI and TI were not significantly associated with age at diagnosis, sex, race, tumor site, stage or histology, treatment region, distance from treatment center, income quintile or diagnosis year (all p > .05). DI and TI were not associated with EFS (DI: hazard ratio [HR] 1.00, 95% CI 0.96-1.05, p = .871; TI: HR 1.03, 95% CI 1.00-1.05, p = .053) or OS (DI: HR 0.99, 95% CI 0.94-1.05, p = .797; TI: HR 1.02, 95% CI 0.99-1.05, p = .155). CONCLUSIONS: In the publicly funded Canadian health care system, DI and TI did not affect the survival of children with RMS.

Loneliness among adolescents and young adults with cancer during the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: Adolescents and young adults (AYAs) diagnosed with cancer are at an increased risk of experiencing social isolation and loneliness secondary to their cancer and its treatment. The physical distancing measures implemented during the COVID-19 pandemic may have further increased loneliness among this group. This study examined the prevalence of loneliness and factors associated with loneliness among AYAs with cancer during this pandemic. METHODS: We conducted a self-administered, online, cross-sectional survey of Canadian AYAs diagnosed with cancer between 15 and 39 between January and February 2021. Loneliness was measured using the 3-item UCLA Loneliness Scale. Factors associated with higher levels of loneliness were identified using multiple logistic regression. RESULTS: The analysis included 805 AYAs. The prevalence of loneliness was 52.2% [N = 419, 95% CI (confidence interval) 48.7 to 55.6%]. Individuals who were 18-25 years old [AOR (adjusted odds ratio)1.60, CI 1.03-2.47, p = 0.035], currently undergoing cancer therapy (AOR 1.46, 95% CI 1.03-2.07, p = 0.035), who self-disclosed the presence of a pre-pandemic mental health condition (AOR 2.09, 95% CI = 1.22-3.58, p = 0.007), or were not in a relationship (AOR 2.22, 95% CI 1.57-3.14, p < 0.001) were more likely to report loneliness than others. Participants that lived in rural or remote locations were less likely to experience loneliness (AOR 0.59, 95%CI 0.40-0.87, p = 0.008). CONCLUSION: One in two AYAs with cancer are feeling lonely during the COVID-19 pandemic. Future studies for developing interventions to target loneliness, particularly for those at greater risk, are necessary to improve the health and quality of life of AYAs with cancer.

Precursor B-Cell Acute Lymphoblastic Leukemia With MYC and BCL2 Rearrangements Presenting as Extensive Extranodal Disease in an Adolescent.

Combined rearrangements of MYC and BCL2 are rare in precursor B-cell acute lymphoblastic leukemia (B-ALL). A 14-year-old boy presented with swelling of the knee and face. Imaging revealed diffuse infiltration of lacrimal glands, parotid glands along with the extensive epidural disease. Morphology and immunophenotype of knee joint aspirate were consistent with precursor B-ALL. Fluorescent in situ hybridization identified rearrangements of MYC and BCL2 genes. The disease was refractory to intensive treatment. The patient died of progressive disease. Precursor B-ALL with combined MYC and BCL2 rearrangements is rare, characterized by an aggressive clinical course, and has an inadequate response to standard therapeutic approaches.

Medical cannabis in pediatric oncology: a survey of patients and caregivers.

BACKGROUND: There are minimal data regarding the safety and efficacy of cannabis used as an anti-cancer agent or for symptom management in pediatric oncology. We aimed to characterize the prevalence and factors associated with the use of cannabis for the treatment of cancer and management of cancer-related symptoms in children during or after cancer treatment. METHODS: An anonymous 40 question paper survey was offered to patients/caregivers of children with cancer attending a pediatric oncology clinic in a provincially mandated cancer agency between October 2019 and March 2020. RESULTS: There were 64 respondents included in the analysis. Fourteen participants (N=14/64; 22%) reported use of cannabis, of which half used cannabis for either cancer treatment or symptom management, or both. Leukemia (n=9/14; 64%) was the most frequent diagnosis in children whose caregivers reported using cannabis and the majority of them were still receiving active cancer treatment (N= 5/9; 56%). All of the respondents using cannabis (14/14, 100%) experienced symptom improvement. Most of the caregivers procured cannabis from their friends (N=5/14; 36%), and oil was the most commonly used formulation (N=12/14; 86%). Cannabis-related information was received from another parent (N=4/14; 29%) or from a doctor (N=4/14; 29%). The reported monthly expenditure on cannabis varied widely from less than $50 CAD (N=4/14; 29%) to more than $500 CAD (N=3/14; 21%). CONCLUSIONS: Our survey shows that cannabis, mostly oil products, was used by one-fifth of children with cancer during or after the completion of cancer treatment. These findings require validation in a larger nationwide survey.

Invasive Fungal Disease in Pediatric Acute Leukemia in the Nontransplant Setting: 8 Years' Experience From a Tertiary Care Center in North India.

BACKGROUND/AIM: The aim of this article is to study the spectrum, changing prevalence, and predictors for mortality of invasive fungal disease (IFD) in pediatric leukemia in a resource-limited setting. OBSERVATIONS: Prevalence was 7% (proven, 69%; probable, 16.4%; possible, 14.6%) and did not differ between acute lymphoblastic leukemia and acute myeloid leukemia. Lungs were frequently involved (46%). Aspergillus was the commonest fungus (47%). Visceral abscesses were frequent with candidiasis as compared with invasive molds (P=0.016). IFD resulted in a prolonged admission (mean, 12.6±2 d; P=0.014) and death (44%) (Aspergillus, 50%; Candida, 50%; Mucor, 34%). Diagnosis of acute myeloid leukemia predicted mortality (P=0.03). CONCLUSIONS: IFD was an important cause of treatment related mortality in pediatric leukemia (odds ratio, 8.39). Protocolled use of computed tomography-chest and galactomannan-assay aided diagnosis (P<0.05).

Validation of risk stratification for children with febrile neutropenia in a pediatric oncology unit in India.

PURPOSE: The study aims to validate a score predicting risk of complications in pediatric patients with chemotherapy-related febrile neutropenia (FN) and evaluate the performance of previously published models for risk stratification. PATIENTS AND METHODS: Children diagnosed with cancer and presenting with FN were evaluated in a prospective single-center study. A score predicting the risk of complications, previously derived in the unit, was validated on a prospective cohort. Performance of six predictive models published from geographically distinct settings was assessed on the same cohort. RESULTS: Complications were observed in 109 (26.3%) of 414 episodes of FN over 15 months. A risk score based on undernutrition (two points), time from last chemotherapy (<7 days = two points), presence of a nonupper respiratory focus of infection (two points), C-reactive protein (>60 mg/l = five points), and absolute neutrophil count (<100 per µl = two points) was used to stratify patients into "low risk" (score <7, n = 208) and assessed using the following parameters: overall performance (Nagelkerke R2 = 34.4%), calibration (calibration slope = 0.39; P = 0.25 in Hosmer-Lemeshow test), discrimination (c-statistic = 0.81), overall sensitivity (86%), negative predictive value (93%), and clinical net benefit (0.43). Six previously published rules demonstrated inferior performance in this cohort. CONCLUSION: An indigenous decision rule using five simple predefined variables was successful in identifying children at risk for complications. Prediction models derived in developed nations may not be appropriate for low-middle-income settings and need to be validated before use.

Can complications in febrile neutropenia be predicted? Report from a developing country.

PURPOSE: Febrile neutropenia (FN) is an important cause of morbidity and mortality in children with acute lymphoblastic leukemia (ALL). We aimed to look at complications in febrile neutropenia and to derive a risk model for developing complications from the variables predicting complications. METHODS: Children on treatment for ALL, presenting with FN, were prospectively enrolled over a period of 1 year. Their clinical presentation, course during hospital stay, and outcomes were recorded. Complications recorded included septic shock, pneumonia requiring invasive or non-invasive ventilation, renal failure, neutropenic enterocolitis, encephalopathy, congestive heart failure, and bleeding manifestations. RESULTS: There were 320 episodes of FN among 176 patients. Complications occurred during 73 (22.8%) episodes. Time since last chemotherapy ≤7 days [OR 2.2 (1-4.5)], clinical focus of infection [OR 2.7 (1.3-5.5)], undernutrition [OR 2.5 (1.1-5.5)], absolute neutrophil count (ANC) ≤ 100/µL [OR 2.8 (1.3-5.9)], and C-reactive protein (CRP) > 60 mg/L at admission [OR 13.3 (5.2-33.8)] were independent predictors of complications. A risk model (total score = 13) was developed based on these predictors. Children with score of ≥7 had 17.2 (7.7-38.6) odds of developing complications as compared to those with score <7. Score of <7 predicted children at lower risk of complications [sensitivity 88% (78.2-93.8%), specificity 72.5% (65.7-78.4%), PPV 53.6% (44.3-62.6%), NPV 94.4% (89.3-97.1%)]. CONCLUSIONS: Complications during febrile neutropenia are high in a developing country setup. A risk score model based on identified risk factors can possibly help in recognizing low-risk febrile neutropenic children at admission.

Function and size of the residual kidney after treatment of Wilms tumor.

Long-term damage to the residual kidney is of concern in the survivors of Wilms tumor. Our objective was to evaluate the long-term glomerular function and size of the residual kidney in these patients. Twenty-nine survivors of Wilms tumor diagnosed between July 1999 and June 2004 were enrolled. The glomerular function was assessed by creatinine clearance, 99mTc DTPA radionuclide scintigraphy and 24-hour urinary protein. Renal size was evaluated by ultrasonography. Median age at diagnosis and at enrollment were 2.87 ± 1.8 (range: 0.5-7.5) and 7.9 ± 3.8 years (range: 2.5-18). Median duration of follow-up was 4.78 ± 2.6 years (range: 1-8.8). Evidence of renal dysfunction in the form of either function or size was identified in eight (27.6%) children. Six children had subnormal glomerular filtration rate and one had proteinuria. Subnormal size of the residual kidney was observed in one child. Age at diagnosis, stage, and duration elapsed after nephrectomy had no association with renal dysfunction (P >.05). Long-term follow up is crucial to identify clinical nephrotoxicity among survivors of Wilms tumor.

Medication errors on oral chemotherapy in children with acute lymphoblastic leukemia in a developing country.

BACKGROUND: Medication errors occur universally. Inappropriate administration of chemotherapy drugs can have adverse effects in cancer patients. Our objective was to assess the rate and type of medication errors in children with acute lymphoblastic leukemia (ALL) receiving oral chemotherapy in outpatient setting. PROCEDURE: Prescription and administration of oral chemotherapy drugs in children with ALL were evaluated prospectively to determine rate and type of medication errors. Errors were defined as prescription (physician) level or administration (patient) level errors. RESULTS: Two hundred eighty-nine drugs were prescribed to 121 patients. Medication errors occurred in 36 (12.5%) prescriptions; 21(7.3%) were administration errors, 13 (4.5%) were prescribing errors, and two errors occurred at both levels. Mercaptopurine (6-MP) was significantly associated with higher rates of errors (Odds ratio [OR] = 2.1, 95% CI [confidence interval] 1-4.1) whereas lapses were less with dexamethasone (OR = 0.25, 95% CI 0.09-0.67). As a result of medication errors 28 (23.1%) patients received inappropriate doses. Twenty five (21%) patients received sub-optimal doses whereas three got higher doses of chemotherapy. On univariate analysis, socioeconomic status, education status of the caregiver, 6-MP and methotrexate were significantly associated with errors (P ≤ 0.05). On multivariate analysis, ≤ primary school education of the caregiver and prescription of methotrexate were independent predictors of errors. CONCLUSIONS: Medication errors affected nearly one fourth of the children receiving oral chemotherapy. Future studies are needed to look at effective interventions to avoid chemotherapy associated errors especially amongst the lower strata of society.