Martin Charron

Image analysis in patients with cancer studied with a Combined PET and CT scanner

Purpose To compare combined whole-body PET and CT images of different cancers with PET images alone. Materials and Methods Thirty-two patients with known or possible cancers were examined using a combined positron emission tomographic (PET) and computed tomographic (CT) scanner. All data were acquired using this same combined scanner. After an injection of F-18 fluorodeoxyglucose (FDG), noncontrast helical CT imaging of the neck, chest, abdomen, or pelvis was performed. The spiral CT was followed by a PET scan covering the same axial extent as the CT. Results Coregistered PET–CT images identified and localized 55 lesions. In 10 patients (31%), areas with variable amounts of normal physiologic FDG uptake were distinguished from potential uptake of FDG in a nearby neoplastic lesion. Improved localization was achieved in 9 patients (for a total of 13 lesions, or 24%). Conclusion Combined PET–CT images appear more effective than PET images alone to localize precisely neoplastic lesions and to distinguish normal variants from juxtaposed neoplastic lesions.

Pediatric FDG PET/CT: Physiologic Uptake, Normal Variants, and Benign Conditions

Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) is increasingly being used in the evaluation of pediatric oncology patients. However, the normal distribution of (18)F FDG uptake in children is unique and may differ from that in adults. A number of physiologic variants are commonly encountered, including normal physiologic uptake in the head and neck, heart, breast, thymus, liver, spleen, gastrointestinal tract, genital system, urinary collecting system, bone marrow, muscles, and brown adipose tissue. Benign lesions with increased (18)F FDG uptake are also frequently seen and can be misinterpreted as malignancies. In addition, the use of combined PET/computed tomographic (CT) scanners is associated with pitfalls and artifacts such as attenuation correction and misregistration. Proper interpretation of pediatric (18)F FDG PET/CT studies requires knowledge of the normal distribution of (18)F FDG uptake in children, as well as of the aforementioned physiologic variants, benign lesions, and PET/CT-related artifacts. Knowing these potential causes of misinterpretation can increase accuracy in PET image interpretation, decrease the number of unnecessary follow-up studies or procedures, and improve patient treatment.

Hematologic Toxicity of High-Dose Iodine-131–Metaiodobenzylguanidine Therapy for Advanced Neuroblastoma

PURPOSE Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) has been shown to be active against refractory neuroblastoma. The primary toxicity of (131)I-MIBG is myelosuppression, which might necessitate autologous hematopoietic stem-cell transplantation (AHSCT). The goal of this study was to determine risk factors for myelosuppression and the need for AHSCT after (131)I-MIBG treatment. PATIENTS AND METHODS Fifty-three patients with refractory or relapsed neuroblastoma were treated with 18 mCi/kg (131)I-MIBG on a phase I/II protocol. The median whole-body radiation dose was 2.92 Gy. RESULTS Almost all patients required at least one platelet (96%) or red cell (91%) transfusion and most patients (79%) developed neutropenia (< 0.5 x 10(3)/microL). Patients reached platelet nadir earlier than neutrophil nadir (P <.0001). Earlier platelet nadir correlated with bone marrow tumor, more extensive bone involvement, higher whole-body radiation dose, and longer time from diagnosis to (131)I-MIBG therapy (P <or=.04). In patients who did not require AHSCT, bone marrow disease predicted longer periods of neutropenia and platelet transfusion dependence (P <or=.03). Nineteen patients (36%) received AHSCT for prolonged myelosuppression. Of patients who received AHSCT, 100% recovered neutrophils, 73% recovered red cells, and 60% recovered platelets. Failure to recover red cells or platelets correlated with higher whole-body radiation dose (P <or=.04). CONCLUSION These results demonstrate the substantial hematotoxicity associated with high-dose (131)I-MIBG therapy, with severe thrombocytopenia an early and nearly universal finding. Bone marrow tumor at time of treatment was the most useful predictor of hematotoxicity, whereas whole-body radiation dose was the most useful predictor of failure to recover platelets after AHSCT.

Targeted radiotherapy with submyeloablative doses of 131I-MIBG is effective for disease palliation in highly refractory neuroblastoma.

Purpose Treatment of refractory neuroblastoma remains a significant clinical problem. Targeted radiotherapy with 131I-MIBG has demonstrated antitumor activity in heavily pretreated neuroblastoma patients with recurrent disease. Response rates may be correlated with total radionuclide dose per kilogram body weight delivered, but higher dose levels are associated with protracted grade 4 hematologic toxicity. The optimal method for using single-agent 131I-MIBG for patients with relapsed high-risk neuroblastoma has not been defined. This study was designed to retrospectively determine the clinical response to 131I-MIBG therapy at submyeloablative doses in patients with refractory neuroblastoma and to describe the toxicities. Patients and Methods A retrospective chart review of 20 patients with neuroblastoma treated with 131I-MIBG at the Childrens Hospital of Philadelphia from 1988 to 2000 was performed. Demographic data, 131I-MIBG dose delivered, toxicities, and clinical responses were reviewed. Results A median dose of 9.5 mCi/kg of 131I-MIBG was delivered in 32 courses to 20 patients. Three patients were treated in first complete response, and the remaining 17 patients for residual and/or progressive disease. The objective response rate to the first therapy was 31%, and the remaining patients achieved disease stabilization. In addition, 9 of 11 patients with pain at study entry had significant improvement. Disease response was not correlated with 131I-MIBG dose delivered. No unanticipated toxicities were observed. Conclusions Submyeloablative-dose 131I-MIBG is an effective and relatively nontoxic method for neuroblastoma disease palliation. Most patients show subjective improvement in pain and/or performance status. Increased availability and experience with 131I-MIBG therapy would benefit a large number of children with end-stage neuroblastoma and no realistic hope for cure.

Evaluation of Semi-Quantitative Scoring System for Metaiodobenzylguanidine (mIBG) Scans in Patients With Relapsed Neuroblastoma

The purpose of this study was to determine the accuracy of two semi‐quantitative scoring systems to assess response to 131I‐metaiodobenzylguanidine (mIBG) therapy in recurrent neuroblastoma.

Rapid Pulmonary Delivery of Inhaled Tobramycin for Pseudomonas Infection in Cystic Fibrosis : A Pilot Project

Patients with cystic fibrosis spend as much 30 min a day inhaling tobramycin. Could a new rapid system deposit the equivalent amount of tobramycin faster?

Higher Tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis

Poor adherence to recommended therapy in cystic fibrosis (CF) is often because of the time demands of therapy. Tobramycin (TOBI®, 300 mg at 60 mg/ml) inhaled from the PARI LC PLUS® nebulizer requires about 20 min. This study determined if equivalent levels of pulmonary deposition could be achieved in shorter time using 1.5 ml of 100 mg/ml tobramycin solution delivered by an investigational eFlow® nebulizer. Sixteen males with stable CF, 8 children and 8 adults, and an FEV1 > 45% predicted inhaled both preparations on two occasions with 99mTc‐DTPA added to the tobramycin. Blood samples were taken for quantification of tobramycin in the serum. The PARI LC PLUS® delivered 45.4 (39.3–51.6), mean and 95% CI, mg to the lungs in 17.0 ± 2.5 min (mean ± SD) with serum levels of 1,089 ± 388 µg/L. The investigational eFlow® delivered 46.3(40.3–51.7) mg in 4.0 ± 1.0 min with blood levels of 909 ± 458 µg/L. Only the time of delivery was significantly different with P < 0.0001 (paired t‐test). Tolerability of the treatment was comparable for both inhalation regimes, but the shorter treatment was preferred by all patients. These results demonstrate the possibility of delivering equivalent levels of tobramycin much faster into the lungs of CF patients when using eFlow®, a very efficient electronic nebulizer. Pediatr Pulmonol. 2011; 46:401–408.

A Comparison of Amount and Speed of Deposition Between the PARI LC STAR® Jet Nebulizer and an Investigational eFlow® Nebulizer

BACKGROUND The potency and physical properties of many of the drugs used in the treatment of cystic fibrosis necessitates the use of nebulization, a relatively time-consuming pulmonary delivery method. Newer, faster, and more efficient delivery systems are being proposed. The purposes of this study was to compare the length of time it took to deliver the equivalent of normal saline nebulized for 10 min in a PARI LC STAR(®) nebulizer to that of an investigational PARI eFlow(®). METHODS Six normal adults inhaled a 4-mL (36-mg) charge volume of saline from the LC STAR(®) or a 2.5-mL (22.5-mg) charge volume from the investigational eFlow(®). The saline was mixed with (99m)Tc-DTPA to allow two-dimensional imaging. The inhalation was preceded by a xenon equilibration scan to allow more accurate separation of deposition into central and peripheral lung regions. RESULTS The investigational eFlow(®) delivered 8.6 ± 1.0 mg, approximately 90% of the lung dose compared to the LC STAR(®), 9.6 ± 1.0 mg, but did in less than half the time (p < 0.02 for both). There were no differences in central versus peripheral distribution for either device. CONCLUSIONS In conclusion the investigational eFlow(®) was both faster and more efficient than the LC STAR(®).

Dual–Time-Point FDG PET/CT for the Evaluation of Pediatric Tumors

OBJECTIVE The utility of dual-time-point (18)F-FDG PET/CT in differentiating benign from malignant processes in pediatric patients was assessed. SUBJECTS AND METHODS Twenty-one patients (13 girls and eight boys; age range, 1-17 years) with suspected malignancy underwent dual-time-point FDG PET/CT. Scan 1 was performed at approximately 60 minutes after i.v. injection of 5.18 MBq/kg of FDG, and scan 2 was performed at 121 ± 43 minutes after the first scan. Regions of interest were overlaid onto each non-attenuated-corrected image, and semiquantitative analysis was performed using the standardized uptake value (SUV) obtained from early and delayed images. A retention index was calculated according to the following equation: [(delayed SUV - early SUV) / early SUV] × 100. Results were compared prospectively in relation to pathologic examination or other conventional radiologic imaging or clinical follow-up. A retention index of 10% or higher was chosen as a cutoff for differentiating malignant from benign entities. RESULTS For patients with malignant disease, the average SUV increased from 7.3 ± 1.2 to 10.9 ± 2.7 between the two time points, whereas the SUV changed from 4.5 ± 0.8 to 4.2 ± 1.0 for patients with benign lesions. The average retention index was 37.1% ± 10.8% for patients with malignant lesions versus -9.9% ± 7.1% for benign lesions (p < 0.01). With a cutoff value of 10% or higher for the retention index, the sensitivity and specificity of dual-time-point FDG PET/CT were 77% and 80%, respectively. CONCLUSION These data show that dual-time-point FDG PET/CT is useful in distinguishing malignant from benign processes in pediatric patients.

FDG‐PET and magnetoencephalography in presurgical workup of children with localization‐related nonlesional epilepsy

2‐[18F]Fluoro‐2‐deoxy‐d‐glucose positron emission tomography (FDG‐PET) and magnetoencephalography (MEG) may assist in identifying the epileptogenic zone in children with nonlesional localization‐related epilepsy. The aim of this study was to evaluate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG‐PET, MEG, FDG‐PET + MEG, and FDG‐PET/MEG in children with nonlesional localization‐related epilepsy.