Sergey Postovsky

Positron emission tomography/computed tomography with 18fluoro‐deoxyglucose in the detection of local recurrence and distant metastases of pediatric sarcoma

Combined positron emission tomography with 18fluoro‐deoxyglucose and computed tomography (FDG‐PET/CT) has been used in the diagnosis and staging of various malignancies, but their use in the management of pediatric sarcomas is less well defined. The potential role of FDG‐PET/CT in the diagnosis of local recurrence and distant metastases of pediatric sarcomas was investigated.

The incremental value of 18F-FDG PET/CT in paediatric malignancies

Purpose18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging has been used in the assessment of paediatric malignancies. PET/CT increases the diagnostic accuracy in adult cancer patients. The present study assesses the incremental value of FDG PET/CT in paediatric malignancies.MethodsA total of 118 18FDG PET/CT studies of 46 paediatric patients were reviewed retrospectively. PET and PET/CT results were classified as malignant, equivocal or benign, compared on a site- and study-based analysis, and also compared with the clinical outcome.ResultsThree hundred and twenty-four sites of increased FDG uptake were detected. Discordant PET and PET/CT interpretations were found in 97 sites (30%) in 27 studies (22%). PET yielded a statistically significant higher proportion of equivocal and a lower proportion of benign lesion and study results (p < 0.001) than PET/CT. With PET there were 153 benign (47%), 84 (26%) equivocal and 87 (27%) malignant sites, while PET/CT detected 226 benign (70%), 10 (3%) equivocal and 88 (27%) malignant lesions. PET/CT mainly improved the characterisation of uptake in brown fat (39%), bowel (17%), muscle (8%) and thymus (7%). The study-based analysis showed that 17 equivocal and seven positive PET studies (20%) were interpreted as benign on PET/CT, while three equivocal studies were interpreted as malignant. The study-based sensitivity and specificity of PET/CT were 92% and 78% respectively.ConclusionPET/CT significantly improved the characterisation of abnormal 18FDG foci in children with cancer, mainly by excluding the presence of active malignancy in sites of increased tracer activity.

Assessing the use of FDG-PET in the detection of regional and metastatic nodes in alveolar rhabdomyosarcoma of extremities.

Alveolar rhabdomyosarcoma (ARS) accounts for 20% to 30% of childhood rhabdomyosarcoma and is known to have a worse prognosis than embryonal rhabdomyosarcoma. Metastatic disease is more frequent in patients with alveolar tumors and these children with metastatic disease fare poorly, with a 5-year survival between 20% and 30%. Therefore, ARS represents a significant diagnostic and therapeutic challenge that requires techniques to provide better assessment of the disease than provided by traditional means. F18 fluorodeoxyglucose-positron emission tomography (FDG-PET) depicts the increased metabolism in abnormal tissues, enabling accurate evaluation of suspicious regional and metastatic disease. The new combined PET/CT systems can further improve PET interpretation and affect patient management. The value of FDG in patients with soft tissue sarcomas has been demonstrated in several series, but none specifically in ARS. This report assesses the use of FDG-PET/CT in the detection of regional and metastatic nodes in 3 children diagnosed with ARS of the extremities. All the 3 patients we present had focally increased tracer uptake in nodal stations on a pretherapy PET performed at diagnosis. Tissue confirmation available in 2 patients was negative in 1 patient and positive for metastatic nodal spread in the other. Metastatic axillary disease was possibly also present in the third patient according to his later course of disease.

Pharmacokinetic Analysis of Gentamicin Thrice and Single Daily Dosage in Pediatric Cancer Patients

Fifty-two children suffering from different types of malignancies were included and evaluated for the pharmacokinetics of gentamicin thrice or single daily dosage protocols. All the study population received a total dose of 5 mg/kg daily. Thirty children received gentamicin thrice daily, and 22 were treated using the single daily protocol; all had fever and neutropenia when included. The individual pharmacokinetic parameters were calculated using a one-compartment model for two blood gentamicin samples. The mean (SD) t 1/2 (h), clearance (mL/min/BSA), Vss (L/kg), Cmax (micrograms/mL), and Cmin (micrograms/mL) were 3.05 (1.0) and 3.9 (0.6) h, 136 (61.3) and 99.9 (65.3) mL/min/BSA, 0.4035 (0.167) and 0.457 (0.17) L/kg, 5.2 (2.0) and 11.5 (4.2) micrograms/mL, 0.8 (0.6) and 0.18 (0.1) microgram/mL for thrice and single daily dosage schedules, respectively. The single gentamicin daily dose protocol had a significantly longer t 1/2, shorter clearance normalized to BSA, higher Cmax, and lower Cmin in comparison with the thrice daily schedule. We recommend the use of gentamicin at 5 mg/kg daily delivered as a single daily dose for pediatric cancer patients with fever and neutropenia, in spite of the measured pharmacokinetic differences, which in our opinion have no clinical significance.

Pharmacokinetic Analysis of Vancomycin in Steady State in Pediatric Cancer Patients

Thirty children suffering from different types of malignancies, neutropenic fever, and suspected staphylococcal bacteremia were evaluated for the pharmacokinetics of vancomycin in steady-state conditions and compared with eight children suffering from proven methicillin-resistant staphylococcal infection. All the studied population received intravenous vancomycin at 40 mg/kg daily divided into four daily doses. The individual pharmacokinetic parameters were calculated using a one-compartment model for two blood vancomycin samples. The mean (+/- SD) half-time (t1/2, hours), clearance (L/h/kg), Vss (L/kg), Cmax (microgram/mL), and Cmin (microgram/mL) were 10.5 (7.9) and 14.9 (9.1) hours; 0.11 (0.14) and 0.06 (0.06) L/h/kg; 0.62 (0.33) and 1.3 (0.6) L/kg; 28.3 (11.8) and 22.3 (9.8) micrograms/mL; and 5.7 (6.0) and 7.4 (4.8) micrograms/mL for the malignancy and control groups, respectively. The malignancy group had a significantly shorter t1/2 (P = .005), higher clearance (P = .005), and lower Cmin (P = .03) in comparison with the control group. It is suggested that the prescription of vancomycin at 40 mg/kg daily, divided into four daily doses, is safe and will provide a peak blood level of vancomycin sufficient to cover the broad spectrum of staphylococcal bacteria. The vancomycin dose should be individualized, based on an individual pharmacokinetic profile.

Does regular follow-up influence the survival of patients with sarcoma after recurrence? The Miri Shitrit pediatric oncology department experience.

Despite comprehensive management of pediatric sarcomas, only 60% to 70% of children become long-term survivors. This study was undertaken to evaluate whether regular follow-up improves overall survival of children with recurrent sarcomas. The medical charts of 107 children diagnosed with soft tissue and bone sarcomas were reviewed, of whom 29 relapsed. They were divided into 2 groups according to the way of relapse diagnosis: due to complaints/physical examination (14) or on routine imaging studies (15). All were followed by regular physical examination and imaging studies (chest computed tomography, magnetic resonance imaging, and bone scan/positron emission tomography-computed tomography scan with fluorodeoxyglucose) at regular intervals. Analysis of the results showed that (1) regular imaging studies do not facilitate earlier recognition of relapse in children with sarcomas; (2) regular follow-up with imaging studies does not influence overall survival of children with sarcomas; (3) other diagnostic and treatment approaches are needed to improve the survival of children with recurrent sarcomas.

Metastatic Rhabdoid Meningioma with BRAF V600E Mutation and Good Response to Personalized Therapy: Case Report and Review of the Literature.

Rhabdoid meningioma is an aggressive phenotype of meningioma, associated with a poor prognosis. We present a very rare case of high-grade meningioma with rhabdoid features that eventually expressed in a coma state. Comprehensive genomic profiling using a Next Generation Sequencing (NGS) assay revealed three genomic alterations: activating BRAF mutation (V600E), loss of CDKN2A/2B, and APC I1307K. After treatment with BRAF inhibitor (dabrafenib), the childs clinical condition improved progressively. After seven months, an MEK inhibitor was added (trametinib).

Clinical and radiographic response in three children with recurrent malignant cerebral tumors with high-dose tamoxifen.

The purpose of this study was to deliver tamoxifen as antiangiogenic therapy to children with recurrent progressive malignant brain tumors. Tamoxifen was administered orally in very high dosage to one child as monotherapy and to two children in combination with oral etoposide and dexamethasone. One boy was diagnosed with high-grade astrocytoma in the brain stem, one girl with anaplastic ependymoma of the fourth ventricule, and one girl with high-grade astrocytoma in the midbrain. Conventional treatment with multiple surgeries, first- and second-line chemotherapy, and external beam therapy had failed. Tumor reduction was seen in radiographic images together with clinical improvement in 2 children, and clinical and radiographic halting of tumor progression was demonstrated in the patient with anaplastic ependymoma. None of the patients developed complications from the treatment. Follow up of the patients ranged from 15 to 30 months with a mean of 17 months. These encouraging preliminary results suggest a potential for this type of therapy. More studies are needed to start clinical trials and prove that angiostatic activity may contribute to the therapeutic effect of antiestrogens in estrogen receptor-negative tumors.

DETECTION OF ISOLATED DISTANT METASTASIS IN SOFT TISSUE SARCOMA BY FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY: Case Report

Fluorodeoxyglucose (FDG), labeled with F-18, is a glucoseanalog that accumulates in cells in proportion to the rate of glucose metabolism, and increased carbohydrate metabolism has been recognized as a feature of malignant cells versus normal cells. In addition, it permits the detection of metastases not discovered by bone scan. Although detection of the primary site of disease is usually accomplished well with conventional techniques, the performance of FDG positron emission tomography(PET)may be useful to determine metastases that are not clinically evident. The authors describe a case of early detection of distant metastasesby FDG-PET in a young patient diagnosed with rhabdomyosarcoma of the hand.

Pharmacokinetic analysis of amikacin twice and single daily dosage in immunocompromised pediatric patients.

SummaryTen children received amikacin twice daily and 13 were treated using the single daily protocol. All had fever and neutropenia on admission, and received a total daily dose of 20 mg/kg when included in the study. Individual pharmacokinetic parameters were calculated using a one-compartment model for two blood amikacin samples. The mean (±SD) of elimination half-life (h), amikacin clearance (l/h/kg), volume of distribution (l/kg), peak concentration (μg/ml) and trough concentration (μg/ml) were: 2.51 (0.74) and 2.85 (0.32) h; 0.26 (0.16) and 0.115 (0.02) l/h/kg; 0.74 (0.44) and 0.47 (0.11) l/kg; 19.1 (12.3) and 42.6 (12.6) μg/ml; 0.85 (0.74) and 0.18 (0.24) μg/ml with twice and single daily dosage schedules, respectively. A single daily dose of amikacin had a significantly longer elimination half-life, lower clearance, higher peak concentration and lower trough concentration in comparison to the twice-daily schedule. The use of amikacin 20 mg/kg daily delivered in a single daily dose is recommended for immunocompromised pediatric patients with fever and neutropenia, in spite of the measured pharmacokinetic differences.