Balancing the benefits and harms of thyroid cancer surveillance in survivors of Childhood, adolescent and young adult cancer: Recommendations from the international Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium.

Radiation exposure to the thyroid gland during treatment of childhood, adolescent and young adult cancer (CAYAC) may cause differentiated thyroid cancer (DTC). Surveillance recommendations for DTC vary considerably, causing uncertainty about optimum screening practices. The International Late Effects of Childhood Cancer Guideline Harmonization Group, in collaboration with the PanCareSurFup Consortium, developed consensus recommendations for thyroid cancer surveillance in CAYAC survivors. These recommendations were developed by an international multidisciplinary panel that included 33 experts in relevant medical specialties who used a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. Of the two available surveillance strategies, thyroid ultrasound and neck palpation, neither was shown to be superior. Consequently, a decision aid was formulated to guide the health care provider in counseling the survivor. The recommendations highlight the need for shared decision making regarding whether to undergo surveillance for DTC and in the choice of surveillance modality.

Subsequent malignant neoplasms in pediatric cancer patients treated with and without hematopoietic SCT.

Pediatric cancer patients are at increased risk of subsequent malignant neoplasms (SMNs). However, little is known about the contribution of hematopoietic SCT (HSCT) to the development of SMNs. The objective of this study was to compare the incidence of SMNs in a population cohort of childhood cancer survivors treated with and without HSCT. A cohort of 7986 children (age 0-14 years) diagnosed with cancer in the province of Ontario, Canada between 1985 and 2009 was identified in POGONIS (Pediatric Oncology Group of Ontario Networked Information System), a population-based active cancer registry, and linked to a clinical HSCT database. Among this cohort, 796 patients had an HSCT as part of their primary treatment. Of the 375 allogeneic HSCT patients, 14 (3.7%) developed a SMN at a median follow-up of 12.3 years (range: 2.0-22.9 years). Of the 421 autologous HSCT patients, 8 (1.9%) developed a SMN at a median of 4.5 years (range: 1.3-14.3 years). Of the 7190 patients who did not receive an HSCT, 160 (2.2%) developed a SMN at a median follow-up of 6.8 years (range: 0.0-24.9 years). The 15-year cumulative incidence of SMN was 3.1% among the allogeneic HSCT group, 2.5% among the autologous group and 2.3% in the non-HSCT group. The cumulative incidence curves for the allogeneic HSCT and non-transplant groups only diverged after ~15 years from primary diagnosis. Our findings further corroborate the observation that children who undergo allogeneic HSCT are at a significantly increased risk of developing SMN compared with pediatric cancer survivors treated without HSCT.

Does the use of the revised psychosocial assessment tool (PATrev) result in improved quality of life and reduced psychosocial risk in Canadian families with a child newly diagnosed with cancer?

OBJECTIVES: Early psychosocial screening may guide interventions and ameliorate the adverse psychosocial effects of childhood cancer. The revised psychosocial assessment tool provides risk information - Universal (typical distress), Targeted (additional specific distress), and Clinical (severe distress) - about the child with cancer and his or her family. This pilot study investigated the benefits of providing a summary of family psychosocial risk information to the medical team treating the newly diagnosed child (Experimental Group, EG). METHOD: We conducted a pilot randomized control trial with a sample of 67 parents, comparing the EG to the control group (CG) on parental perception of family psychosocial difficulties (revised psychosocial assessment tool risk levels), child behavior (behavior assessment scale for children-2), pediatric quality of life (PedsQL), and parental anxiety (state-anxiety scale of the state-trait anxiety inventory ), 2-4 weeks after diagnosis (Time 1) and 6 months later (Time 2). RESULTS: Compared to the CG, participants in the EG had significantly reduced targeted and clinical risk (p < 0.001), and improved pain related PedsQL at Time 2 (p < 0.05). Scores for PedsQL total and nearly all subscales improved over time in both groups (p < 0.05 to p < 0.001). No changes in behavior scores were noted. CONCLUSION: Preliminary findings suggest that providing a summary of the Psychosocial Assessment Tool to the treating team shortly after diagnosis may help reduce family wide psychosocial risk 6 months later and improve quality of life related to pain for children who are undergoing treatment for cancer.

External validity and reliability of the Psychosocial Assessment Tool (PAT) among Canadian parents of children newly diagnosed with cancer.

BACKGROUND: The Psychosocial Screening Tool (PAT) was developed and validated with a sample of caregivers of children newly diagnosed with cancer in the United States. This study aimed to assess cultural adaptation (Phase 1) and validity and reliability of the revised PAT (PATrev) with a Canadian sample (Phase 2). PROCEDURE: In Phase 1, a convenience sample of seven parents of children who were treated for cancer and six pediatric oncology healthcare experts participated. In Phase 2, 67 parents of children newly diagnosed with cancer from 4 Canadian pediatric cancer centers participated. To assess reliability and validity of the PATrev, parents completed behavioral (BASC-2) and quality of life (PedsQL) instruments about the child and an anxiety inventory (STAI) about themselves. RESULTS: The PAT required minor changes to be culturally adapted for the Canadian population. The PATrev had strong inter-rater (0.77) test-retest (0.75), and internal consistency reliability (0.85), as well as moderate to strong validity comparing PATrev child's problems and PedsQL total (-0.49), PedsQL anxiety (-0.47), BASC-2 internalizing (0.64), behavioral (0.63), and adaptive scores (-0.56). PATrev discriminative validity was confirmed with BASC-2 scores (AUR scores of 0.70-0.74). PATrev parental stressors were strongly correlated to STAI scores (0.53). Finally, agreement between PATrev child's problems and parental anxiety scores was moderate (0.47). CONCLUSION: This study supports the original PAT, demonstrates PATrev is a reliable and valid psychosocial screening tool, and provides unique evidence regarding early psychosocial risk in the family, which have important implications for guiding psychosocial practice.

Late mortality after hematopoietic SCT for a childhood malignancy.

Hematopoietic SCT (HSCT) has been used as a curative therapy for pediatric malignancies. Survivors of HSCT are at risk for disease recurrence, late morbidity and mortality. We assessed late mortality (≥2 years post-HSCT) in a population-based cohort of children who underwent HSCT for a malignancy. Mortality outcomes were determined by linking a clinical transplant database with the Canadian province of Ontario's pediatric cancer mortality files. Seven hundred and fifty-four children underwent HSCT (371 allogeneic, 383 autologous). Of the 479 (63.5%) who were alive ≥2 years post HSCT, 98 (20.5%) suffered a late death. Late mortality in the allogeneic HSCT group was 14.9% (median follow-up 10.0 years; range: 2.0-25.6 years), mainly due to relapse of the primary malignancy (64.7%). Chronic GVHD and second malignancies were not major causes of late mortality. A total of 25.5% suffered a late death following autologous HSCT (median follow-up 6.7 years; range: 2.0-22.2 years). Recurrence of the primary malignancy accounted for 87.5% of these deaths. Recurrence of the primary malignancy is the predominant cause of late mortality after HSCT. In contrast to studies of adult patients, non-relapse mortality is less common in children, and death due to chronic GVHD and secondary malignancies is uncommon.

Prolonged neutropenia after irinotecan-based chemotherapy in a child with polymorphisms of UGT1A1 and SLCO1B1.

Genetic polymorphisms of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and SLCO1B1 coding organic anion-transporter polypeptide 1B1, are independent risk factors known to increase irinotecan toxicity in adults. Although combined occurrence of polymorphisms in these 2 genes is likely to influence susceptibility to irinotecan toxicity, data are scarce, especially in children. We report an 11-year-old female with severe and prolonged neutropenia after irinotecan-based chemotherapy. The patient's genotyping revealed polymorphisms in both UGT1A1 and SLCO1B1. To our knowledge, this is the first case report of combined genotyping of both UGT1A1 and SLCO1B1 in a child with severe irinotecan toxicity.

A Bayesian meta-analysis of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in children with cancer.

The purpose of this analysis was to examine the efficacy of prophylactic hematopoietic colony-stimulating factors (CSFs) in pediatric cancer and to describe how a Bayesian meta-analysis can be conducted and then modified to incorporate information not readily included in a frequentist meta-analysis. Three Bayesian models were developed. The simplest model used the same data as a published frequentist meta-analysis. The second model included data that could not easily be incorporated into the frequentist meta-analysis, including data from different courses of chemotherapy and continuous outcomes that did not report variance estimates. The third model examined the effect of CSF type (granulocyte CSF vs. granulocyte-macrophage CSF). Compared with the frequentist model, the Bayesian model with the most data suggested a greater benefit of CSFs, with a 3.2-day reduction in duration of parenteral antibiotics (95% credible interval: -7.1, 0.7) in the expanded Bayesian model compared with a 0.8-day (95% confidence interval: -2.3, 0.7) reduction in the frequentist model. Bayesian meta-analysis also suggested that, compared with granulocyte-macrophage CSF, granulocyte CSF was associated with a 4.8-day decrease in the duration of parenteral antibiotics. Bayesian meta-analysis can readily include information not easily incorporated in a frequentist meta-analysis. Some treatment effect estimates were larger by a clinically important amount when additional data contributed to the pooled estimate.

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.

Health status of young children during therapy for advanced neuroblastoma.

BACKGROUND: The purpose of this study was to describe the health status experienced by young children during various phases of therapy for advanced neuroblastoma. METHODS: Nineteen patients aged 2.00-4.99 years at the time of diagnosis of neuroblastoma (stages 3 or 4) who received active therapy between 1996 and 2000 were enrolled on the study. Their parents provided proxy assessments of their health status at a maximum of 10 assessment points during therapy using the Comprehensive Health Status Classification System for Pre-school Children (CHSCS-PS), which assesses level of function on 10 separate health domains. RESULTS: Eighty-six assessment questionnaires were completed. Maximum morbidity was reported immediately following diagnosis and in the 2-3 weeks following bone marrow transplantation. The greatest morbidity was observed in the pain, self-care, mobility, and emotion domains. CONCLUSIONS: In addition to facing a high risk of mortality, young children being treated for advanced neuroblastoma also experience considerable morbidity.

Inter-observer agreement of a comprehensive health status classification system for pre-school children among patients with Wilms' tumor or advanced neuroblastoma.

We assessed inter-observer agreement on a new comprehensive health status classification system for preschool children (CHSCS-PS). Prospective assessments of children aged 2-4.9 years at the time of diagnosis of neuroblastoma (stages 3-4, excluding 4S) or Wilms' tumor (stages II-V) were collected independently from a parent and nurse by self-report during therapy. Responses were used to determine functional status on 10 health domains, as well as an overall disability score. Inter-observer agreement was evaluated by a kappa statistic for agreement about levels within individual domains, and by an intraclass correlation coefficient (ICC) for agreement of overall disability scores. Twenty-four parent/nurse pairs of assessments were collected. Agreement was almost perfect for mobility and self-care, substantial for emotion and pain, and slight for speech. There was high percent agreement for vision, hearing, dexterity, learning and remembering, and thinking and problem solving, but insufficient variability in responses to calculate a kappa statistic. The ICC for overall disability scores between observers was 0.86, indicating strong agreement. Given the need for, and paucity of, instruments for the measurement of health-related quality of life in very young children, these results strongly support further evaluation of the CHSCS-PS.

Isochromosome (17)(q10) and translocation (4;12)(q12;p13) in a child with acute myeloid leukemia.

Isochromosome 17q is a commonly observed cytogenetic aberration in hematologic malignancies. Isolated isochromosome 17q usually presents as a marker of a chronic myeloid disorder, with a high propensity for transformation into acute nonlymphoblastic leukemia (ANLL). t(4;12)(q11-12;p13) is a recently described translocation, associated with ANLL, predominantly in adults. In this article, we present a case of acute myeloblastic leukemia (AML) in a 14-year-old female in which i(17q) and t(4;12)(q12;p13) were found in the leukemic clone at diagnosis. We briefly review the literature and hypothesize as to the significance of the coexistence of these cytogenetic changes.