EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a Canadian Pediatric Brain Tumor Consortium study.

BACKGROUND: The cure rate for childhood intracranial ependymoma is approximately 70% in the setting of a gross total resection followed by radiation, but management remains challenging in patients with residual disease. Therefore, robust biomarkers are needed to guide the development of new targeted therapy. The authors evaluated the expression of several biomarkers in pediatric intracranial ependymoma and observed that the expression of enhancer of zeste homolog 2 (EZH2), a polycomb complex protein involved in epigenetic regulation of gene expression, was independently associated with poor survival. METHODS: Tissue microarray immunostaining was performed on 180 ependymoma samples from 12 of 16 Canadian pediatric centers. Expression levels of EZH2, Ki-67, B lymphoma Moloney-murine leukemia virus insertion region 1 homolog, tumor protein 16 (P16), Y-box binding protein 1, phosphorylated protein kinase B (pAKT), and epidermal growth factor receptor were evaluated. Cox regression analyses were performed, and the Kaplan-Meier method was used to construct survival curves. RESULTS: EZH2 expressed in 16% of tumors was associated with inferior 5-year overall survival. Ki-67 and pAKT levels were associated with a poor outcome in patients with posterior fossa ependymoma, and the absence of P16 was associated with a poor outcome in patients with supratentorial ependymoma. Multivariate analysis revealed that younger age and EZH2 expression (95% confidence interval, 1.1-36.0) were independent markers of a poor prognosis. CONCLUSIONS: EZH2 is a novel, independent marker of a poor prognosis in patients with ependymoma, especially in those who have tumors located in the posterior fossa. EZH2, pAKT, and P16 are potential therapeutic targets, particularly for patients who have tumors in which standard gross total resection plus fractionated radiotherapy is not feasible.

Changes to memory structures in children treated for posterior fossa tumors.

Children treated for medulloblastoma (MB) exhibit long-term impairments in declarative memory, but the pathophysiology underlying this is unclear. Previous studies report declines in global white matter volume, but have failed to link this to declines in memory performance. We examined the effects of treatment on measures of global brain structure (i.e., total white and gray matter volume) and specific memory structures (i.e., hippocampus and uncinate fasciculus). We used volumetric MRI and diffusion tensor imaging in pediatric survivors of MB and one survivor of astrocytoma treated with cranial-spinal radiation (n = 20), and healthy controls (n = 13). Compared to controls, the survivor group exhibited reduced white matter volume, damage to the uncinate fasciculus, and a smaller right hippocampus. Critically, reduced hippocampal volume was not related to differences in brain volume, suggesting that the hippocampus may be especially vulnerable to treatment effects. A subset of the survivors (n = 10) also underwent memory testing using the Children's Memory Scale (CMS). Performance on the general index of the CMS was significantly correlated with measures of hippocampal volume and uncinate fasciculus. The examination of treatment effects on specific brain regions provides a better understanding of long-term cognitive outcome in children with brain tumors, particularly medulloblastoma.

Anthracycline induced cardiac toxicity in pediatric Ewing sarcoma: a longitudinal study.

BACKGROUND: Reports on incidence and factors associated with anthracycline cardiotoxicity in patients with Ewing sarcoma vary and few studies evaluate effect over time. Longitudinal trends in cardiac function and prognostic value of % decline in ejection fraction (EF) during therapy have not been previously described in Ewing sarcoma. PROCEDURE: A retrospective review of patients age <17 years, diagnosed with Ewing sarcoma during 1978-2006, treated at British Columbia Children's Hospital with anthracycline chemotherapy was undertaken. Echocardiograms performed pre-treatment, worst function during treatment, on therapy completion; worst function during surveillance and the most recent echocardiogram were reviewed. Cardiac toxicity was graded using Common Terminology Criteria for Adverse Events v 3.0 and 4.0. RESULTS: Among 71 eligible patients, median age at diagnosis 11.1 years, median cumulative dose of anthracycline was 365 mg/m2 . There were 397 echocardiograms with 153 (39%) abnormal. There were 21/71 patients with EF < 50%, 11 with EF < 40% and five cardiac deaths including 2/3 patients post-cardiac transplant. The median time to worst cardiac function was 51 months. Post-therapy completion 16/71 patients with progressive decline in cardiac function were noted. No patient with 10-15% decline in EF during therapy developed cardiotoxicity. Younger age (P = 0.004) and low BMI (P = 0.034) as continuous variables with anthracycline administration by IV push (P = 0.03) were risk factors for cardiotoxicity on univariate analysis but not significant within logistic regression models. CONCLUSIONS: The high incidence of cardiotoxicity associated with higher administered anthracycline dose, young age, bolus infusion, and EF decline warrants evaluation in a larger cohort.

Roadmap for the exposé of radiation flows (Xflows) experiment on NIF.

The goal of the Xflows experimental campaign is to study the radiation flow on the National Ignition Facility (NIF) reproducing the sensitivity of the temperature (±8 eV, ±23 µm) and density (±11 mg/cc) measurements of the COAX platform [Johns et al., High Energy Density Phys. 39, 100939 (2021); Fryer et al., High Energy Density Phys. 35, 100738 (2020); and Coffing et al., Phys. Plasmas 29, 083302 (2022)]. This new platform will enable future astrophysical experiments involving supernova shock breakout, such as Radishock (Johns et al., Laboratory for Laser Energetics Annual Report 338, 2020) on OMEGA-60 [Boehly et al., Rev. Sci. Instrum. 66, 508 (1995)], and stochastic media (such as XFOL on OMEGA). Greater energy and larger physical scale on NIF [Moses et al., Eur. Phys. J. D 44, 215 (2007)] will enable a greater travel distance of radiation flow, higher density, and more manufacturable foams and enable exploration of a greater range of radiation behavior than achievable in the prior OMEGA experiments. This publication will describe the baseline configuration for the Xflows experimental campaign and the roadmap to achieve its primary objectives.

Cerebello-thalamo-cerebral connections in pediatric brain tumor patients: impact on working memory.

Brain tumors are the leading cause of death and disability from childhood disease in developed countries. Pediatric posterior fossa tumors are often effectively controlled with a combination of surgery, radiation, and chemotherapy, depending on tumor type. White matter injury following resection of tumor and radiation treatment is associated with cognitive declines, including working memory deficits. We investigated how brain injury following treatment for posterior fossa tumors results in deficits in working memory. We used diffusion tensor imaging and probabilistic tractography to examine the structural integrity of cerebello-thalamo-cerebral tracts in patients and healthy children. We also compared working memory outcome in patients versus controls, and related this function to integrity of cerebello-thalamo-cerebral tracts. Bilateral cerebello-thalamo-cerebral tracts were delineated in all participants. Patients treated with a combination of surgery and radiation had lower mean anisotropy and higher mean radial diffusivity within the cerebellar regions of the cerebello-thalamo-cerebral tract compared to patients treated with surgery only and healthy controls. Poorer working memory scores were observed for the cranial radiation group relative to controls. Reduced anisotropy and higher radial diffusivity within the entire cerebello-thalamo-cerebral pathway predicted lower working memory. Our finding that working memory function is related to the integrity of cerebello-thalamo-cerebral connections is a novel contribution to the understanding of cerebral-cerebellar communication. Identifying differences in the structural integrity of white matter for specific pathways is an essential step in attempting to localize the effects of posterior fossa tumors and their treatment methods.

Late effects in childhood cancer survivors: a review with a framing effect bias?

Most publications report the adverse (negative) health issues in childhood cancer survivors. Presenting information to the newly diagnosed patient in a positive manner is advocated, while noting that recurrence is the most likely adverse event. Re-analysis of population-based studies on life-threatening toxicities from Nordic, Dutch, United Kingdom, French, Italian, and N. American publications shows that 5-year survivors have a near normal life expectancy, 75% have no severe or life-threatening treatment related toxicity and 87% remain free of a second malignancy. Children who received radiation or anthracycline >250-300 mg/m(2) are at greatest risk for treatment related life-threatening toxicities.

Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone.

BACKGROUND: Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease. METHODS: Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide. RESULTS: A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were randomly assigned to the standard-therapy group and 58 to the experimental-therapy group. There was no significant difference in five-year event-free survival between the treatment groups (P=0.81). Among the 398 patients with nonmetastatic disease, the mean (+/-SE) five-year event-free survival among the 198 patients in the experimental-therapy group was 69+/-3 percent, as compared with 54+/-4 percent among the 200 patients in the standard-therapy group (P=0.005). Overall survival was also significantly better among patients in the experimental-therapy group (72+/-3.4 percent vs. 61+/-3.6 percent in the standard-therapy group, P=0.01). CONCLUSIONS: The addition of ifosfamide and etoposide to a standard regimen does not affect the outcome for patients with metastatic disease, but it significantly improves the outcome for patients with nonmetastatic Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone.

Associating Physical Activity Levels with Motor Performance and Physical Function in Childhood Survivors of Acute Lymphoblastic Leukemia.

Purpose: This cross-sectional, observational study investigated whether physical activity (PA) levels are associated with motor performance and physical function in children after treatment for acute lymphoblastic leukemia (ALL). Method: Participants aged 8-13 years who had completed treatment for ALL (3-36 months post-treatment) were tested at their oncology long-term follow-up appointment at the British Columbia Children's Hospital. PA level was measured using the Physical Activity Questionnaire for Older Children (PAQ-C). Motor performance was measured using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, Short Form (BOT-2 SF), and physical function was measured using the 6-minute walk test (6MWT). Results: Thirteen children completed testing. PAQ-C scores were not associated with BOT-2 SF or 6MWT performance. Eleven children (85%) performed below the norm for the 6MWT. Children with elevated body mass index had poorer 6MWT but similar PAQ-C scores. Conclusion: PA was not found to be associated with motor performance and physical function. Participants who were overweight or obese had poorer 6MWT performance, which may indicate the need for closer monitoring of post-treatment weight status and physical function in the oncology follow-up setting.

Objectif : cette étude observationnelle à méthodologie transversale portait sur le lien potentiel entre le niveau d'activité physique (AP) et la capacité motrice et physique des enfants ayant reçu un traitement contre la leucémie lymphoblastique aiguë (LLA). Méthode : des participants âgés de 8 à 13 ans ayant reçu un traitement contre la LLA (de 3 à 36 mois après le traitement) ont été évalués lors de leur rendez-vous de suivi à long terme en oncologie au British Columbia Children's Hospital. Le niveau d'AP a été mesuré à l'aide du Questionnaire de mesure de l'activité physique chez les enfants (PAQ-C). La capacité motrice a été mesurée à l'aide du Bruininks-Oseretsky Test of Motor Proficiency, Deuxième édition, Formulaire court (BOT-2 SF) et la capacité physique a été mesurée à l'aide du test de marche de 6 minutes (6MWT). Résultats : treize enfants ont effectué les tests. Aucun lien n'a été observé entre les scores du PAQ-C et les résultats du BOT-2 SF ni ceux du 6MWT. Onze enfants (85 %) ont obtenu un résultat inférieur à la norme au 6MWT. Les enfants ayant un indice de masse corporelle élevé ont obtenu des résultats plus faibles au 6MWT, mais des résultats similaires au PAQ-C. Conclusion : le niveau d'AP ne semble pas avoir de lien avec la capacité motrice ou physique. Les participants en surpoids et obèses ont obtenu des résultats plus faibles au 6MWT, ce qui peut indiquer un besoin de surveillance plus étroit du poids et de la capacité physique après le traitement lors des rendez-vous de suivi en oncologie.

White matter and information processing speed following treatment with cranial-spinal radiation for pediatric brain tumor.

OBJECTIVE: We compared the structure of specific white matter tracts and information processing speed between children treated for posterior fossa tumors with cranial-spinal radiation (n = 30), or with surgery +/- focal radiation (n = 29), and healthy children (n = 37). METHOD: Probabilistic diffusion tensor imaging (DTI) tractography was used to delineate the inferior longitudinal fasciculi, optic radiation, inferior frontal occipital fasciculi, and uncinate fasciculi bilaterally. Information processing speed was measured using the coding and symbol search subtests of the Wechsler Intelligence Scales, and visual matching, pair cancellation, and rapid picture naming subtests of the Woodcock-Johnson Test of Cognitive Ability, 3rd revision. We examined group differences using repeated measures MANOVAs and path analyses were used to test the relations between treatment, white matter structure of the tracts, and information processing speed. RESULTS: DTI indices of the optic radiations, the inferior longitudinal fasciculi, and the inferior fronto-occipital fasciculi differed between children treated with cranial-spinal radiation and children treated with surgery +/- focal radiation, and healthy controls (p = .045). Children treated with cranial-spinal radiation also exhibited lower processing speed scores relative to healthy control subjects (p = .002). Notably, we observed that group differences in information processing speed were related to the structure of the right optic radiation (p = .002). CONCLUSION: We show that cranial-spinal radiation may have a negative impact on information processing speed via insult to the right optic radiations. (PsycINFO Database Record

Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer Group and Pediatric Oncology Group study.

PURPOSE: One hundred twenty patients with metastatic Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes. METHODS: Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m(2), cyclophosphamide 1,200 mg/m(2), and either doxorubicin 75 mg/m(2) or dactinomycin 1.25 mg/m(2). Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m(2)/d for 5 days and etoposide 100 mg/m(2)/d for 5 days. RESULTS: Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms. CONCLUSION: Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at diagnosis.

Influence of kinetic sorption and diffusion on pesticide movement through aggregated soils.

Laboratory studies were carried out to investigate solute leaching at different times from application in relation to temperature and initial soil moisture. Aggregates of a heavy clay soil were treated with a non-interactive solute (bromide) and the herbicides chlorotoluron, isoproturon and triasulfuron. The soil was incubated at 90% field capacity and either 5 or 15 degrees C. The influence of application to initially dry and initially wet aggregates on the behaviour of isoproturon was also investigated. At intervals, samples were either leached in small columns, centrifuged to characterise the fraction of chemical available in pore water under natural moisture conditions or extracted with organic solvents to assess total residues in soil. Bromide concentrations in leachate and in pore water extracted by centrifugation were constant with time. In contrast, availability for leaching and concentration in pore water of the herbicides decreased with increasing time from application in soil incubated at 15 degrees C. The effect of residence time was much smaller at 5 than at 15 degrees C. At the higher temperature, pesticide concentrations in leachate and pore water declined faster than would be expected from degradation alone, probably due to slow diffusion of the pesticides into soil aggregates where they are less available for leaching and/or slow sorption-desorption. The faster decline in availability for leaching at 15 than at 5 degrees C was attributed to faster degradation of the readily available fraction. There was no significant influence of initial soil moisture on either the leaching behaviour of isoproturon or its availability in soil water.

Lysimeter study to investigate the effect of rainfall patterns on leaching of isoproturon.

The influence of five rainfall treatments on water and solute leaching through two contrasting soil types was investigated. Undisturbed lysimeters (diameter 0.25 m, length 0.5 m) from a sandy loam (Wick series) and a moderately structured clay loam (Hodnet series) received autumn applications of the radio-labelled pesticide isoproturon and bromide tracer. Target rainfall plus irrigation from the end of November 1997 to May 1998 ranged from drier to wetter than average (235 to 414 mm); monthly rainfall was varied according to a pre-selected pattern or kept constant (triplicate lysimeters per regime). Leachate was collected at intervals and concentrations of the solutes were determined. Total flow (0.27-0.94 pore volumes) and losses of bromide (3-80% of applied) increased with increasing inputs of water and were larger from the Wick sandy loam than from the Hodnet clay loam soil. Matrix flow appeared to be the main mechanism for transport of isoproturon through the Wick soil whereas there was a greater influence of preferential flow for the Hodnet lysimeters. The total leached load of isoproturon from the Wick lysimeters was 0.02-0.26% of that applied. There was no clear variation in transport processes between the rainfall treatments investigated for this soil and there was an approximately linear relationship (r2 = 0.81) between leached load and total flow. Losses of isoproturon from the Hodnet soil were 0.03-0.39% of applied and there was evidence of enhanced preferential flow in the driest and wettest treatments. Leaching of isoproturon was best described by an exponential relationship between load and total flow (r2 = 0.62). A 45% increase in flow between the two wettest treatments gave a 100% increase in leaching of isoproturon from the Wick soil. For the Hodnet lysimeters, a 35% increase in flow between the same treatments increased herbicide loss by 325%.

Atypical teratoid rhabdoid tumors (ATRTs): the British Columbia's Children's Hospital's experience, 1986-2006.

As "atypical teratoid rhabdoid tumors" (ATRTs) may mimic "small round blue cell tumors" (SRBCT), we reexamined our ATRT experience focusing upon INI-1 immunohistochemistry (IHC). All high-grade pediatric brain tumors occurring from 1986-2006 at our institution underwent INI-1 IHC. Clinicopathologic data from each INI-1 immunonegative case were reviewed. Additional genetic, epigenetic and IHC analyses (including interrogation of INI-1 and CLDN6) were performed on a subset of the INI-1 immunonegative cases. Twelve INI-1 IHC negative tumors were identified retrospectively, of which only two previously carried the diagnosis of ATRT. Overall, the clinicopathologic and genetic data supported the assertion that all 12 cases represented ATRT. Unexpectedly, three long-term survivors (4.2, 7.0 and 8.5 years) were identified. As hypothesized, "teratoid" and "rhabdoid" histologic features were relatively infrequent despite gross total resections in some cases. Methylation specific polymer chain reaction (PCR) (MSP) revealed a uniform methylation pattern across all cases and gene promoters tested (ie, MGMT, HIC1, MLH3 and RASSF1); notably, all cases demonstrated unmethylated MGMT promoters. Our data demonstate that a primitive non-rhabdoid histophenotype is common among ATRTs and highlights the diagnostic importance of INI-1 IHC. Epigenetically, the MGMT promoter is usually unmethylated in ATRT, suggesting that potential temozolomide-based chemotherapy may be of limited efficacy.

Clinical and neuroanatomical predictors of cerebellar mutism syndrome.

Cerebellar mutism syndrome (CMS) is an important medical challenge in the management of pediatric posterior fossa brain tumors, because it occurs in a subset of children following tumor resection. A definitive clinical profile and neuroanatomical substrate associated with CMS remains unclear. We investigated the relationship between presurgical and clinical variables and the incidence of CMS, along with diffusion tensor imaging, to characterize the integrity of cerebello-thalamo-cerebral white matter pathways. Seventeen children with posterior fossa tumors and CMS, 34 children with posterior fossa tumors without CMS, and 28 healthy children were enrolled in this study. Bilateral cerebello-thalamo-cerebral pathways were delineated and segmented into anatomical regions. Mean integrity measures for each region were compared among children with CMS, children without CMS, and healthy children. Left-handedness, medulloblastoma histology, and larger tumor size distinguished between patients with CMS and patients without CMS (P < .04). Right cerebellar white matter within the cerebello-thalamo-cerebral pathway was compromised in children with CMS relative to children without CMS and healthy children (P < .02). We provide a potential schema for CMS risk among children treated for posterior fossa tumors. Left-handed children treated for medulloblastoma may be the most at risk for CMS, and unilateral, localized damage within the cerebello-thalamo-cerebral pathway at the level of the right cerebellum is implicated in the presentation of CMS. This disruption in communication between the right cerebellum and left frontal cortex may contribute to speech-language problems observed in children with CMS. Our findings may be relevant for surgical planning and speech-language therapy to mitigate symptoms of CMS.

Blast wave energy diagnostic.

The distance radiation waves that supersonically propagate in optically thick, diffusive media are energy sensitive. A blast wave can form in a material when the initially diffusive, supersonic radiation wave becomes transonic. Under specific conditions, the blast wave is visible with radiography as a density perturbation. [Peterson et al., Phys. Plasmas 13, 056901 (2006)] showed that the time-integrated drive energy can be measured using blast wave positions with uncertainties less than 10% at the Z Facility. In some cases, direct measurements of energy loss through diagnostic holes are not possible with bolometric and x-ray radiometric diagnostics. Thus, radiography of high compression blast waves can serve as a complementary technique that provides time-integrated energy loss through apertures. In this paper, we use blast waves to characterize the energy emerging through a 2.4 mm aperture and show experimental results in comparison to simulations.

Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: evaluation of increasing the dose intensity of chemotherapy--a report from the Children's Oncology Group.

BACKGROUND: The outcome for patients with Ewing sarcoma family of tumors (ESFTs) of bone with metastases at diagnosis remains poor despite new approaches to treatment. We evaluated whether a dose-intensity chemotherapy regimen improved survival for patients with ESFTs of bone with metastases at diagnosis. METHODS: We entered 60 patients with metastatic ESFTs of bone onto a single arm trial of a new intensive therapy. Treatment consisted of 51-weeks of chemotherapy and local control of the primary with radiation, surgery, or both. The chemotherapeutic protocol included two alternating blocks: one with vincristine (2 mg/m(2)), doxorubicin (90 mg/m(2)), and cyclophosphamide (2,200 mg/m(2)); and the second with ifosfamide (2,800 mg/m(2)/day x 5 days) and etoposide (100 mg/m(2)/day x 5 days). RESULTS: Of the 60 patients with metastatic ESFTs of bone enrolled onto this single arm trial, 12 had metastasis to lung only, 7 to bone marrow or bone only, 38 to multiple sites, 2 in other sites and 3 not specified. There were three toxic deaths. Six patients (6-year cumulative incidence: 9%) developed second malignant neoplasms and died. The 6-year overall event-free survival (EFS) was 28% (standard error (SE) 6%) and survival (S) was 29% (SE 6%). CONCLUSION: An intensified treatment regimen using higher doses of cyclophosphamide, ifosfamide, and doxorubicin increased toxicity and risk of second malignancy without improving EFS and S.

Local control in pelvic Ewing sarcoma: analysis from INT-0091--a report from the Children's Oncology Group.

PURPOSE: The impact of the modality used for local control of Ewing sarcoma is uncertain. We investigated the relationship between the type of local control modality, surgery, radiation (RT) or both (S + RT), and subsequent risk for local failure (LF) in patients with nonmetastatic pelvic Ewing sarcoma treated on INT-0091. PATIENTS AND METHODS: Patients < or = 30 years with Ewing sarcoma, primitive neuroectodermal tumor or primitive sarcoma of bone were randomly assigned to receive chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin, (VACA) or with these four drugs alternating with ifosfamide and etoposide (VACA-IE). The local control modality, surgery, RT or both was chosen by the treating physicians. The effect of local control modality was assessed after adjusting for the size of tumor (< 8 cm, > or = 8 cm) and chemotherapy type. RESULTS: Seventy-five patients with pelvic tumors and a median follow-up of 4.4 years (0.6 to 11.4 years) comprised the study population. Twelve underwent surgery, 44 received RT, and 19 received both. The 5-year event-free survival (EFS) and cumulative incidence of LF was 49% and 21% (16%, LF only; 5%, LF and distant failure). There was no significant difference in EFS or LF by tumor size (< 8 cm, > or = 8 cm), local control (LC) modality, or chemotherapy. However, VACA-IE seems to confer an LC benefit (11% v 30%; P = .06). CONCLUSION: There was no significant effect of local control modality (surgery, RT or S + RT) selected by the treating physicians on rates of local failure or EFS. However, VACA-IE improves LC (11%) compared with previously published results for pelvic Ewing sarcoma.

A pilot study of prophylactic ciprofloxacin during delayed intensification in children with acute lymphoblastic leukemia.

BACKGROUND: We hypothesized that prophylactic administration of an appropriate antibiotic following each delayed intensification (DI) in children with acute lymphoblastic leukemia (ALL) would reduce the episodes of fever and bacteremia associated with neutropenia, and hence reduce both the rate and duration of hospitalization. PROCEDURE: All patients in the study were treated according to a modified Medical Research Council United Kingdom ALL XI (MRC UKALL XI) protocol utilizing three DI courses. Between June and December 2000 patients received prophylactic ciprofloxacin following DI courses. The rates of hospitalization and bacteremias were compared to ALL patients who had received between one and three DI courses prior to June 2000. RESULTS: There were 69 patients who received a total of 194 DIs (controls 130; study group 64). The rate of hospitalization was 90% in the controls and 58% in the study group (P < 0.001). The median hospital stay was 10.1 days for controls and 6.0 for the study group (P < 0.001). Intensive care unit admissions were reduced from 12 to 1.5% (P = 0.02). The overall rate of proven bacteremia was reduced from 22 to 9% (P = 0.028). There were no Gram-negative bacteremias in the study group compared to 10 (7.7%) in the controls (P < 0.001). CONCLUSIONS: Compared to historical controls, patients in this study receiving prophylactic ciprofloxacin had a reduced rate and duration of hospitalization and incidence of Gram-negative bacteremia.