No abstract

A 71-year-old man with coronary artery disease, coronary artery bypass grafting in 2000, baseline ejection fraction of 0.24, and implantation of a single chamber implanted cardioverter defibrillator (ICD) in 2009 for ventricular tachycardia (VT) presented with continuous episodes of nonsustained and sustained VT refractory to sotalol and mexiletine. Despite angioplasty and stent for coronary artery disease, VT continued for 2 years. Medical history included atrial fibrillation and oxygen-dependent chronic obstructive pulmonary disease. Baseline electrocardiogram (ECG) showed atrial fibrillation with a ventricular rate of 82 beats per minute with inferior Q waves and QRS duration of 90 ms. Twelve-lead ECG during VT showed a regular, wide-complex tachycardia at 160 beats per minute (CL 380-400 ms), with a right bundle branch block pattern, superior axis, precordial transition at V3-V4. His ICD log showed numerous VT episodes, with a single morphology seen on intracardiac ventricular electrogram, cycle length 380-411ms. Episodes were nonsustained, pace-terminated, and shock-terminated. As catheter ablation was relatively medically contraindicated, he consented to a Food and Drug Administration and Institutional Review Board-approved compassionate-use protocol of stereotactic arrhythmia radioablation (STAR), noninvasive ablation of VT substrate by stereotactic ablative radiotherapy (SABR) techniques for tumors. STAR therapy was delivered in October, 2012. STAR Planning and DeliveryBaseline echocardiogram showed a dilated left ventricle (LV), ejection fraction of 0.24, with basal inferior aneurysm, and apical and infero-posterior akinesis. Positron emission tomography-computed tomography showed extensive hypometabolic scar in the LV extending between the LV base and the apex, involving the inferior, inferoseptal, and inferolateral walls. A target for STAR was delineated using proprietary visualization and contouring software (CardioPlan™, CyberHeart™, Portola Valley, CA), outlining the target volume corresponding to what would have been the likely catheter ablation volume for this VT substrate based on imaging-defined inferior LV scar and 12-lead ECG QRS morphology during VT, implying a likely inferior LV VT circuit location ( Figure 1A). The target volume was transferred to the radiation treatment planning software (MultiPlan 4.6.0, Accuray, Sunnyvale, CA) of the treatment system (CyberKnife®, Accuray, Sunnyvale, CA), with normal organs delineated, including lungs, esophagus, and stomach.A temporary pacing wire (Oscor, Inc., Miami Lakes, FL) was fluoroscopically placed in the RV apex as an imaging fiducial marker that could be dynamically tracked to compensate for respiratory motion (Synchrony® Respiratory Tracking 9.6.0, Accuray, Sunnyvale, CA). The magnitude of the remaining cardiac motion was determined by fluoroscopy of the fiducial marker during transient breath holds, and the final target volume included an expansion to encompass this residual motion. The finalized target was then used for treatment planning.A...

Purpose: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen–targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging. Experimental Design: Men with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three 18F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety. Results: A total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2–98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%–87.0% (lower bound of 95% CI: 77.8–80.4). A total of 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers). Conclusions: Performance of 18F-DCFPyL-PET/CT achieved the study’s primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer. See related commentary by True and Chen, p. 3512

Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)] ( 68 Ga-PSMA-11) is a PET tracer that can detect prostate cancer relapses and metastases by binding to the extracellular domain of PSMA. 68 Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-AlaVal-Gly-His-Sta-Leu-NH2 ( 68 Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors. We present pilot data on the biodistribution of these PET tracers in a small cohort of patients with biochemically recurrent prostate cancer. Methods: Seven men (mean age ± SD, 74.3 ± 5.9 y) with biochemically recurrent prostate cancer underwent both 68 Ga-PSMA-11 PET/ CT and 68 Ga-RM2 PET/MRI scans. SUV max and SUV mean were recorded for normal tissues and areas of uptake outside the expected physiologic biodistribution. Results: All patients had a rising level of prostate-specific antigen (mean ± SD, 13.5 ± 11.5) and noncontributory results on conventional imaging. 68 Ga-PSMA-11 had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, whereas 68 Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake outside the expected physiologic biodistribution did not significantly differ between 68 Ga-PSMA-11 and 68 Ga-RM2; however, 68 Ga-PSMA-11 localized in a lymph node and seminal vesicle in a patient with no abnormal 68 Ga-RM2 uptake. Abdominal periaortic lymph nodes were more easily visualized by 68 Ga-RM2 in two patients because of lack of interference by radioactivity in the small intestine. Conclusion: 68 Ga-PSMA-11 and 68 Ga-RM2 had distinct biodistributions in this small cohort of patients with biochemically recurrent prostate cancer. Additional work is needed to understand the expression of PSMA and gastrinreleasing peptide receptors in different types of prostate cancer.

Purpose:To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fl uorine 18 ( 18 F) FPPRGD2 (2-fl uoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets a v b 3 integrin, in the fi rst volunteers imaged with this tracer. Materials and Methods:The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi 6 3. Results:The administration of With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% 6 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 6 0.096).

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.