[show abstract][hide abstract] ABSTRACT: OBJECTIVE. The purpose of this article is to assess the feasibility and utility of PET/CT in distinguishing benign from malignant pulmonary nodules in patients with solid childhood malignancies. SUBJECTS AND METHODS. This prospective study was conducted between March 2008 and August 2010. We enrolled 25 subjects 21 years old or younger with solid childhood malignancies and at least one pulmonary nodule measuring 0.5-3.0 cm. PET/CT was performed within 3 weeks of diagnostic chest CT. Three panels of three reviewers each reviewed diagnostic CT only (panel 1), PET/CT only (panel 2), or diagnostic CT and PET/CT concurrently (panel 3) and predicted each nodule's histologic diagnosis as benign, malignant, or indeterminate. Interreviewer agreement was assessed with the kappa statistic. Using nodule biopsy or clinical follow-up as reference standards, the sensitivity, specificity, and accuracy for each panel was assessed. Logistic regression was used to assess the nodule's maximum standardized uptake value (SUVmax) association with its histologic diagnosis. RESULTS. There were 75 nodules with a median size of 0.74 cm (range, 0.18-2.38 cm); 48 nodules were malignant. Sensitivity was 85% (41/48) for panel 1, 60% (29/48) for panel 2, and 67% (32/48) for panel 3. All panels had poor specificities. Interreviewer agreement was moderate for panel 1 (0.43) and poor for panels 2 (0.22) and 3 (0.33). SUVmax was a significant predictor of histologic diagnosis (p = 0.004). CONCLUSION. PET/CT assessment of pulmonary nodules is feasible in children with solid malignancies but may not reliably improve our ability to predict a nodule's histologic diagnosis. The SUVmax may improve the performance of PET/CT in this setting.
American Journal of Roentgenology 12/2013; 201(6):W900-W905. · 2.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: This case series depicts dental anomalies that may develop in children who have undergone bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL). The most common finding in these patients was root stunting; other abnormalities included microdontia, hypodontia, taurodontia, caries, enamel pearls, and pulpal calcification. Recognition of these adverse effects of BMT on odontogenesis, as demonstrated on panoramic radiograph images, will allow healthcare providers to explain to parents and patients the possible dental outcomes associated with BMT and to optimize their dental health regimen.
[show abstract][hide abstract] ABSTRACT: To investigate the safety, dose-limiting toxicities, and pharmacokinetics of the smoothened inhibitor vismodegib in children with refractory or relapsed medulloblastoma.
Initially, vismodegib was administered daily at 85 mg/m2 and escalated to 170 mg/m2. The study was then revised to investigate a flat-dosing schedule of 150 mg for patients with small body surface area (BSA, 0.67-1.32 m2) or 300 mg for those who were larger (BSA, 1.33-2.20 m2). Pharmacokinetics were performed during the first course of therapy, and the right knees of all patients were imaged to monitor bone toxicity. Immunohistochemical analysis was done to identify patients with SHH-subtype medulloblastoma.
Thirteen eligible patients were enrolled on the initial study: 6 received 85 mg/m2 vismodegib, and 7 received 170 mg/m2. Twenty eligible patients were enrolled on the flat-dosing part of the study: 10 at each dosage level. Three dose-limiting toxicities were observed, but no drug-related bone toxicity was documented. The median (range) vismodegib penetration in the cerebrospinal fluid (CSF) was 0.53 (0.26-0.78), when expressed as a ratio of the concentration of vismodegib in the CSF to that of the unbound drug in plasma. Antitumor activity was seen in 1 of 3 patients with SHH-subtype disease whose tumors were evaluable and in none of the patients in the other subgroups.
Vismodegib was well tolerated in children with recurrent or refractory medulloblastoma; only 2 dose-limiting toxicities were observed with flat dosing. The recommended Phase-II study dose is 150 mg or 300 mg, depending on the patient's BSA.
Clinical Cancer Research 09/2013; · 7.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: Testing of promising drug combinations is crucial in the treatment of diffuse intrinsic pontine glioma (DIPG). Since the VEGF and PDGF pathways are critical in gliomas, we evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of vandetanib, a VEGFR-2 inhibitor, combined with dasatinib, a potent PDGFR inhibitor, during and after radiotherapy in children with newly diagnosed DIPG. EXPERIMENTAL DESIGN: Dasatinib was started concurrently with radiotherapy. Vandetanib was started 8 days later. We tested increasing doses of vandetanib (65 and 85 mg/m2 once daily) and dasatinib (65 and 85 mg/m2 twice daily). Dose-limiting toxicities were evaluated during the first six weeks of therapy. Plasma pharmacokinetics was obtained on days 8 and 42±3 in all patients and concomitantly with cerebrospinal fluid (CSF) when possible. Inhibition of targets of dasatinib in peripheral blood mononuclear cells (PBMCs) was evaluated. RESULTS: Twenty-five patients were treated. Treatment was well tolerated. The median duration of treatment was 184 days. Diarrhea was the most significant toxicity. Three patients experienced substantial myelosuppression. The steady-state plasma pharmacokinetics of vandetanib was comparable to previous studies. Although the plasma exposure to dasatinib decreased from days 8 to 42, it remained similar to adult studies. CSF to plasma exposure of vandetanib and dasatinib were approximately 2% in 2 patients. Phosphorylated 70S6K decreased during therapy in PBMCs. CONCLUSIONS: The MTD of vandetanib and dasatinib in combination was 65 mg/m2 for each drug. Other studies are underway to test dasatinib and other PDGFR inhibitors alone or in combination for this deadly cancer.
Clinical Cancer Research 03/2013; · 7.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: To evaluate the growing skeleton for potential altered skeletalgenesis associated with antiangiogenesis therapy. PATIENTS AND METHODS: Knee radiographs and magnetic resonance imaging (MRI) were prospectively obtained on patients enrolled on two consecutive clinical trials using vandetanib, a potent oral (VEGF receptor 2) VEGFR-2 inhibitor alone or combined with dasatinib, a multiple tyrosine kinase inhibitor, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). RESULTS: Fifty-nine patients (32 females) underwent 119 MRIs; 51 patients underwent 89 radiographs of the knees. The median age at enrollment was 6.2 years (range, 2.4-17.6 years). The dose of vandetanib ranged from 50 to 145 mg/m(2) /day. The median treatment duration was 205 days. Only two patients have not experienced disease progression after 18 and 60 months from diagnosis. MRI identified clinically significant premature physeal fusion in both knees of one patient, focal physeal thickening in one, osteonecrosis in eight patients (present at enrollment in one), and bony spicules crossing the physis in two patients (bilateral in one). MRI follow-up period averaged 5.3 months (range, 0-25.5 months; median, 3.5 months). Radiographs delineated normally fused physes in two patients but no cases of premature physeal fusion, osteonecrosis or bony spicules. CONCLUSIONS: As MRI provided greater information than radiographs, and thus would be a more sensitive test to assess skeletalgenesis in pediatric patients. Pediatr Blood Cancer 2013;9999:XX-XX. (c) 2013 Wiley Periodicals, Inc.
Pediatric Blood & Cancer 03/2013; · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: A prognostic indicator of outcome for Legg-Calvé-Perthes disease (LCP) is needed to guide treatment decisions during the initial stage of the disease (stage 1), before deformity occurs. Radiographic prognosticators are applicable only after fragmentation (stage II). OBJECTIVE: We investigated pre- and postcontrast MRI in depicting stage I femoral head involvement. MATERIALS AND METHODS: Thirty children with stage I LCP underwent non-contrast coronal T1 fast spin-echo (FSE) and corresponding postcontrast fat-suppressed T1-weighted fast spin-echo (FSE) sequences to quantify the extent of femoral head involvement. Three pediatric radiologists and one pediatric orthopedic surgeon independently measured central head involvement. RESULTS: Interobserver reliability of percent head involvement using non-contrasted MR images had intraclass correlation coefficient (ICC) of 0.72. Postcontrast MRI improved interobserver reliability (ICC 0.82). Qualitatively, the area of involvement was more clearly visible on contrast-enhanced MRI. A comparison of results obtained by each observer using the two MRI techniques showed no correlation. ICC ranged from -0.08 to 0.03 for each observer. Generally, greater head involvement was depicted by contrast compared with non-contrast MRI (Pearson r = -0.37, P = 0.04). CONCLUSION: Pre- and postcontrast MRI assess two different components of stage I LCP. However, contrast-enhanced MRI more clearly depicts the area of involvement.
[show abstract][hide abstract] ABSTRACT: Background. Obesity rates for pediatric acute lymphocytic leukemia (ALL) survivors vary from 11% to 57%. Researching dietary behaviors may identify dietary risks leading to obesity and opportunities for intervention. Objective. To evaluate the relationship between caloric and macronutrient intake on the incidence of obesity in pediatric ALL. Design/setting/participants. Retrospectively reviewed data of 142 participants was examined. Participants were grouped into categories based on body mass index (BMI) for adults and Centers for Disease Control and Prevention growth charts for children. Twenty-four-hour food recall records were reviewed to assess dietary intake. Confounding factors and caloric/macronutrient intake were compared across obesity classes. Main outcome measurements. Macronutrient levels were compared between groups. Descriptive data examined. BMI at enrollment on BONEII, age at diagnosis, ethnicity, gender, corticosteroid use, cranial radiation therapy, and standard/high risk. ALL group. Results. Thirty-nine percent of participants were overweight/obese. ALL survivors who consumed a higher percentage of their calories from protein were more likely to be underweight/normal weight while participants who consumed more calories and total carbohydrates were more likely to be overweight/obese. There was no relationship with the other factors examined. Conclusion. Dietary interventions should be designed to ensure patients consume adequate amounts of protein while limiting portion sizes and carbohydrate-based snacks.
[show abstract][hide abstract] ABSTRACT: PURPOSETo measure longitudinal changes in body mass and composition in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS
Body mass index (BMI) was analyzed in 179 survivors by category (underweight, healthy-weight, overweight, and obese) and by z score. Fat and lean body mass measured by dual-energy x-ray absorptiometry was analyzed as z scores.ResultsOver a median 6.6 years of follow-up, BMI z scores diminished significantly (0.32 pre-HSCT v -0.60 at 10 years post-HSCT; P < .001). Mean z scores for fat mass stayed within population norms, but those for lean mass remained below normal levels and diminished significantly over time (P = .018). Pre-HSCT BMI category and/or z score were strongly predictive of post-HSCT BMI (P < .001) and of fat and lean mass z scores (both P < .001). Survivors with extensive chronic graft-versus-host disease were more likely than others to have low BMI (P = .004) and low lean mass (P < .001) post-HSCT. Older age at HSCT (P = .015) and T-cell-depleted graft (P = .018) were predictive of lower post-HSCT BMI. Female patients had higher body fat (P = .002) and lower lean mass (P = .013) z scores than male patients, and black patients had higher fat mass z scores than white patients (P = .026). CONCLUSIONBMI declines significantly after allogeneic HSCT for childhood hematologic malignancies, reflecting primarily a substantial decrease in lean mass but not fat mass. Monitoring and preservation of BMI and lean mass are vital, especially in those with the identified risk factors.
Journal of Clinical Oncology 10/2012; · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: Our objective was to evaluate the association between low bone mineral density (BMD) and incidental renal stones among long-term survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: Adult participants who were 10+ years from their childhood ALL diagnosis and members of the St. Jude Lifetime Cohort study were recruited between December 2007 and March 2011. During their risk-based medical evaluations, they underwent quantitative computed tomography (QCT) to evaluate BMD. Incidental renal stones were identified by radiologists' review of axial QCT source images. Demographic and dietary information were abstracted from health surveys and the Block Food Frequency questionnaire, respectively. The multivariable logistic regression model was used for analysis. RESULTS: At a median of 26.1 years from diagnosis, BMD Z scores were ≤-2 in 34 of 662 (5.2 %) and renal stones detected in 73 of 662 (11 %) participants. Adjusted for age, renal radiation, dietary vitamin D, gender, and body mass index, when compared to those with BMD Z scores ≥0, the risk of renal stones was increased among those with BMD Z scores ≤-2 (odds ratio [OR], 2.92; 95 % confidence interval [CI] 1.14-7.48). Risk of renal stones significantly increased for older age (45-54 vs.18-24 years; OR, 3.70; 95 % CI 1.11-12.35) whereas the risk was higher but nonsignificant for >141.5 IU (sample median) daily intake of vitamin D (OR, 1.64; 95 % CI 0.98-2.75). CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Older ALL survivors with BMD Z scores ≤-2 are at risk for renal stones and should be counseled so that appropriate follow-up care can be provided for those among whom renal stones are detected.
Journal of Cancer Survivorship 09/2012; · 3.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE Children with Hodgkin's lymphoma (HL) routinely undergo surveillance computed tomography (CT) imaging for up to 5 years after therapy, resulting in cost and radiation exposure, without clear benefit. The objective of this study was to determine the contribution of surveillance CT, as compared with clinical findings, to detection of disease recurrence. PATIENTS AND METHODS Two hundred sixteen patients, age ≤ 21 years old, were treated on the multicenter Pediatric Oncology Group 9425 trial. Data for patients who experienced relapse were retrospectively reviewed to determine whether imaging or clinical events prompted suspicion of disease recurrence. Correlation was made to disease stage, time to recurrence, relapse site, and overall survival (OS). Results With a median follow-up time of 7.4 years, 25 (11.6%) of 216 patients had experienced a relapse, of whom 23 experienced local relapse. Median time to relapse was 7.6 months (range, 0.2 to 48.9 months). Nineteen relapses (76%) were detected based on symptoms, laboratory or physical examination findings, and two relapses (8%) were detected by imaging within the first year after therapy. Only four patients (16%) had their recurrence detected exclusively by surveillance imaging after the first year. Six deaths occurred, all in patients who experienced relapse within the first year after therapy. No patient with a recurrence after 1 year off treatment has died, regardless of how the recurrence was detected. CONCLUSION The majority of pediatric HL relapses occurred within the first year after therapy or were detected based on change in clinical status. Detecting late relapse, whether by imaging or clinical change, did not affect OS. These findings indicate that CT is overused for routine surveillance of patients with HL.
Journal of Clinical Oncology 06/2012; 30(21):2635-40. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Osteonecrosis is a potential complication of glucocorticoid chemotherapy in children surviving leukemia. Early diagnosis may allow effective interventions to minimize or ameliorate joint deterioration and obviate surgical intervention. We investigated the significance of MRI signal changes that precede the currently recognized "double-line" changes, which are considered pathognomic of osteonecrosis.
We retrospectively reviewed MRI scans acquired during prospective screening and follow-up of pediatric patients with leukemia for osteonecrosis.
Of 481 patients, we identified 21 cases (4.3%; 12 boys; median age at leukemia diagnosis, 12.8 years) with subtle poorly defined geographically delineated MRI signal abnormalities in knees or hips, or both, that progressed over a median of 4 months (range, 1.6-18.5 months) to florid MRI signs of osteonecrosis. Articular surface collapse developed in three hips (two patients) and three knees (three patients). Three patients subsequently underwent surgical intervention (one bilateral total hip arthroplasty and one bilateral and one unilateral hip core decompression). The median duration of follow-up was 27 months (range, 1.9-90.7 months).
The MRI signal abnormalities described here appear to herald extensive osteonecrosis and precede the typical MRI findings of osteonecrosis previously reported in the literature.
American Journal of Roentgenology 05/2012; 198(5):W432-9. · 2.90 Impact Factor