A phase I study of zoledronic acid and low-dose cyclophosphamide in recurrent/refractory neuroblastoma: a new approaches to neuroblastoma therapy (NANT) study.

BACKGROUND: Zoledronic acid, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone is a common metastatic site of advanced neuroblastoma. We previously reported efficacy of zoledronic acid in a murine model of neuroblastoma bone invasion prompting this Phase I trial of zoledronic acid with cyclophosphamide in children with neuroblastoma and bone metastases. The primary objective was to determine recommended dosing of zoledronic acid for future trials. PROCEDURE: Escalating doses of intravenous zoledronic acid were given every 28 days with oral metronomic cyclophosphamide (25 mg/m(2)/day). Toxicity, response, zoledronic acid pharmacokinetics, bone turnover markers, serum IL-6, and sIL-6R were evaluated. RESULTS: Twenty-one patients, median age 7.5 (range 0.8-25.6) years were treated with 2 mg/m(2) (n = 4), 3 mg/m(2) (n = 3), or 4 mg/m(2) (n = 14) zoledronic acid. Fourteen patients were evaluable for dose escalation. A median of one (range 1-18) courses was given. Two dose limiting toxicities (grade 3 hypophosphatemia) occurred at 4 mg/m(2) zoledronic acid. Other grades 3-4 toxicities included hypocalcemia (n = 2), elevated transaminases (n = 1), neutropenia (n = 2), anemia (n = 1), lymphopenia (n = 1), and hypokalemia (n = 1). Osteosclerosis contributed to fractures in one patient after 18 courses. Responses in evaluable patients included 1 partial response, 9 stable disease (median 4.5 courses, range 3-18), and 10 progressions. Zoledronic acid pharmacokinetics were similar to adults. Markers of osteoclast activity and serum IL-6 levels decreased with therapy. CONCLUSIONS: Zoledronic acid with metronomic cyclophosphamide is well tolerated with clinical and biologic responses in recurrent/refractory neuroblastoma. The recommended dose of zoledronic acid is 4 mg/m(2) every 28 days.

18F-FDG PET/CT of transitional cell carcinoma.

OBJECTIVE: The objective of this article is to provide a practical illustrated review of PET/CT in the imaging evaluation of transitional cell carcinoma. CONCLUSION: Local evaluation of the primary tumor in patients with transitional cell carcinoma on PET is often limited by the obscuring effect of excreted FDG, but assessment of metabolic activity may still be possible through close correlation with CT images. PET/CT may also be helpful in the detection of disease outside the bladder at nodal or more distant sites and in the assessment of recurrent disease.

Calciphylaxis and bone scintigraphy: case report with histological confirmation and review of the literature.

We present a patient with a history of end-stage renal disease, who developed skin lesions in the bilateral calves a month after the initiation of hemodialysis. The lesions were biopsied, and the histological findings were consistent with a diagnosis of calciphylaxis. The patient had a baseline pretreatment bone scan that showed extensive systemic disease. The patient died 20 days after the imaging study. A review of the literature on bone scans and calciphylaxis is presented.

Validation of FDG uptake in the arterial wall as an imaging biomarker of atherosclerotic plaques with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT).

BACKGROUND AND PURPOSE: From the literature, the prevalence of fluorodeoxyglucose (FDG) uptake in large artery atherosclerotic plaques shows great heterogeneity. We retrospectively reviewed 100 consecutive patients who underwent FDG-positron emission tomography-computed tomography (PET/CT) imaging of their whole body, to evaluate FDG uptake in the arterial wall. MATERIALS AND METHODS: We retrospectively evaluated 100 whole-body PET-CT scans. The PET images coregistered with CT were reviewed for abnormal 18F-FDG uptake. The mean standard uptake value (SUV) was measured in regions of interest (ROIs). The prevalence of PET+ plaques was determined based on the qualitative PET review, used as the gold standard in a receiver-operating characteristic (ROC) curve analysis to determine an optimal threshold for the quantitative PET analysis. RESULTS: The qualitative, visual assessment demonstrated FDG uptake in the arterial walls of 26 patients. A total of 85 slices exhibited FDG uptake within the arterial wall of 37 artery locations. 11, 17, and 2 patients exhibited FDG uptake within the wall of carotid arteries, of the aorta, and of the iliac arteries, respectively. Only 4 of the 26 patients had positive FDG uptake in more than one artery location. In terms of quantitative analysis, a threshold of 2.8 SUV was associated with a negative predictive value of 99.4% and a positive predictive value of 100% to predict qualitative PET+ plaques. A threshold of 1.8 SUV was associated with a negative predictive value of 100% and a positive predictive value of 99.4%. Area under the ROC curve was .839. CONCLUSION: The prevalence of PET uptake in arterial walls in a consecutive population of asymptomatic patients is low and usually confined to one type of artery, and its clinical relevance in terms of vulnerability to ischemic events remains to be determined.

Imaging Keratitis-Icthyosis-Deafness (KID) syndrome with FDG-PET (F18-fluorodeoxiglucose-Positron Emission Tomography).

Keratitis-Icthyosis-Deafness (KID) syndrome is a rare dysplasia characterized by vascularizing keratitis, congenital sensorineural hearing-loss, and progressive erythrokeratoderma. To our knowledge, this is the first KID syndrome imaged with FDG-PET in the literature. This paper is intended to help familiarize with the FDG abnormalities related to this rare entity.

Frequency and etiology of solitary hot spots in the pelvis at whole-body positron emission tomography/computed tomography imaging.

PURPOSE: To determine the frequency and etiology of a single hypermetabolic focus within the pelvis with no other areas of increased 18-fluorodeoxyglucose (FDG) uptake in the reminder of the whole body in an oncological population. METHOD AND MATERIALS: We retrospectively examined the first 700 whole-body PET/CT scans performed at our institution for baseline staging or follow-up of cancer and identified all patients with a solitary focus of increased FDG uptake in the pelvis. All available medical records and imaging findings in these patients were reviewed in order to determine the etiology of increased FDG uptake. RESULTS: Eight (1.1%) of the 700 patients had a solitary hot spot in the pelvis at positron emission tomography (PET)/computed tomography (CT) imaging, consisting of seven of 380 women and one of 320 men. In the seven women, increased FDG uptake was due to physiological endometrial uptake (n=2), leiomyoma (n=1), corpus luteum cyst (n=1), physiological ovarian uptake (n=1), urinary leak (n=1), and nonspecific colitis (n=1). In the man, uptake was due to recurrent rectosigmoid adenocarcinoma. None of the 700 patients was found to have metastatic disease in the pelvis. CONCLUSION: Isolated pelvic hot spots at PET/CT imaging in an oncological population are not common and usually benign; physiological endometrial or ovarian uptake is the single commonest cause.