Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation.

Background: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI.

Total-Body PET Imaging in Infectious Diseases.

Total-body PET enables high-sensitivity imaging with dramatically improved signal-to-noise ratio. These enhanced performance characteristics allow for decreased PET scanning times acquiring data "total-body wide" and can be leveraged to decrease the amount of radiotracer required, thereby permitting more frequent imaging or longer imaging periods during radiotracer decay. Novel approaches to PET imaging of infectious diseases are emerging, including those that directly visualize pathogens in vivo and characterize concomitant immune responses and inflammation.

Total-Body Quantitative Parametric Imaging of Early Kinetics of F-FDG.

Parametric imaging has been shown to provide better quantitation physiologically than SUV imaging in PET. With the increased sensitivity from a recently developed total-body PET scanner, whole-body scans with higher temporal resolution become possible for dynamic analysis and parametric imaging. In this paper, we focus on deriving the parameter using compartmental modeling and on developing a method to acquire whole-body F-FDG PET parametric images using only the first 90 s of the postinjection scan data with the total-body PET system.

First Human Imaging Studies with the EXPLORER Total-Body PET Scanner.

Within the EXPLORER Consortium, the construction of the world's first total-body PET/CT scanner has recently been completed. The 194-cm axial field of view of the EXPLORER PET/CT scanner is sufficient to cover, for the first time, the entire human adult body in a single acquisition in more than 99% of the population and allows total-body pharmacokinetic studies with frame durations as short as 1 s. The large increase in sensitivity arising from total-body coverage as well as increased solid angle for detection at any point within the body allows whole-body F-FDG PET studies to be acquired with unprecedented count density, improving the signal-to-noise ratio of the resulting images.

Evaluation of CyberKnife® Fiducial Tracking Limitations to Assist Targeting Accuracy: A Phantom Study with Fiducial Displacement.

Introduction  The underlying assumptions of the CyberKnife® (Accuray, Sunnyvale, CA, US) fiducial tracking system are: i) fiducial positions are accurately detected; ii) inter-fiducial geometry remains consistent (rigid); iii) inter-fiducial geometric array changes are detected and either accommodated with corrections or treatment is interrupted. However: i) soft-tissue targets are deformable & fiducial migration is possible; ii) the accuracy of the tracking system has not previously been examined with fiducial displacement; iii) treatment interruptions may occur due to inter-fiducial geometric changes, but there is little information available to assist subsequent troubleshooting. The purpose of this study was to emulate a clinical target defined with a two, three, or four-fiducial array where one fiducial is displaced to mimic a target deformation or fiducial migration scenario.

Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity.

Background: Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and gastro-intestinal (GI) toxicity remains a key concern.

Methods: Patients with inoperable non-metastatic pancreatic cancer who received CyberKnife® SABR (18-36 Gy) in three fractions as primary, adjuvant, consolidation or re-treatment options were studied.

Designing for impact: identifying stakeholder-driven interventions to support recovery after major cancer surgery.

Purpose: Complex bladder and colorectal cancer surgeries are associated with significant patient morbidity, yet few resources exist to prepare patients for the high levels of distress and complications they may experience. After ethnographic research to identify design challenges, we held a user-centered design (UCD) workshop to begin to develop patient- and caregiver-centered interventions to support preparation for and recovery after complex cancer surgery.

Methods: Concepts that emerged from brainstorming sessions were visually represented on storyboards and rated.

CyberKnife Radiosurgery of Skull-base Tumors: A UK Center Experience.

The study aim was to evaluate patient individualized Cyberknife® treatment for heterogeneous skull-base tumors. Patients treated between 2009 and 2013 at The Harley Street Clinic were studied. In total, 66 patients received 15-30 Gy in 1-5 fractions to a median planning target volume (PTV) of 6.

An effective deep-inspiration breath-hold radiotherapy technique for left-breast cancer: impact of post-mastectomy treatment, nodal coverage, and dose schedule on organs at risk.

Background: We developed, applied, and prospectively evaluated a novel deep-inspiration breath-hold (DIBH) screening and delivery technique to optimize cardiac sparing in left-breast radiotherapy (RT) at our clinic. The impact of set-up and dose variables upon organs at risk (OAR) dose in DIBH RT was investigated.

Methods And Materials: All patients with left-breast cancer referred between 2011 and 2014 - of all disease stages, set-up variations, and dose prescriptions - were included.

Phase II Trial of Cetuximab and Conformal Radiotherapy Only in Locally Advanced Pancreatic Cancer with Concurrent Tissue Sampling Feasibility Study.

Background: Preclinical data have indicated the anti-epidermal growth factor receptor (EGFR) agent cetuximab (Erbitux) as a radiosensitizer in pancreatic cancer, but this has not been specifically addressed in a clinical study. We report the results of an original study initiated in 2007, where cetuximab was tested with radiotherapy (RT) alone in locally advanced pancreatic cancer in a phase II trial (PACER).

Methods: Patients (n = 21) received cetuximab loading dose (400 mg/m(2)) and weekly dose (250 mg/m(2)) during RT (50.

How Kaiser Permanente uses video ethnography of patients for quality improvement, such as in shaping better care transitions.

Keeping patients and caregivers at the center of quality improvement is critical. Kaiser Permanente's Care Management Institute adapted video ethnography to achieve this aim, using video to capture interviews with-and observations of-patients and caregivers, identify patient-centered improvement opportunities, and communicate them effectively to clinical and administrative leaders and front-line staff. This method is particularly effective for helping understand the needs of frail elders, patients nearing the end of life, those with multiple chronic conditions, and other vulnerable people who are not well represented in focus groups and patient advisory councils.

Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors.

Purpose: Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.

Experimental Design: Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors.

Results: Doses were escalated in single-patient cohorts from 0.

Molecular Imaging and Pharmacokinetic Analysis of Carbon-11 Labeled Antisense Oligonucleotide LY2181308 in Cancer Patients.

Antisense oligonucleotides (ASOs) have potential as anti-cancer agents by specifically modulating genes involved in tumorigenesis. However, little is known about ASO biodistribution and tissue pharmacokinetics (PKs) in humans, including whether sufficient delivery to target tumor tissue may be achieved. In this preliminary study in human subjects, we used combined positron emission and computed tomography (PET-CT) imaging and subsequent modeling analysis of acquired dynamic data, to examine the in vivo biodistribution and PK properties of LY2181308 - a second generation ASO which targets the apoptosis inhibitor protein survivin.

Computed tomography overestimation of esophageal tumor length: Implications for radiotherapy planning.

Aim: To assess the relationship between preoperative computed tomography (CT) and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data.

Methods: A retrospective study was carried out in 56 patients who underwent curative esophagogastrectomy. Tumor lengths were measured on the immediate preoperative CT and on the post-operative resection specimens.

VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment.

Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments for cancer. In this study, we evaluated the role of VEGF-PET as a biomarker of dynamic angiogenic changes in tumors following treatment with the kinase inhibitor sunitinib. The effects of sunitinib treatment and withdrawal on the tumor was investigated using the new VEGF-PET tracer (89)Zr-ranibizumab as well as (18)F-FDG PET, and (15)O-water PET in mouse xenograft models of human cancer.

Optimization of the injected activity in dynamic 3D PET: a generalized approach using patient-specific NECs as demonstrated by a series of 15O-H2O scans.

Unlabelled: The magnitude of the injected activity (A(0)) has a direct impact on the statistical quality of PET images. This study aimed to develop a generalized method for maximizing the statistical quality of dynamic PET images by optimizing A(0).

Methods: Patient-specific noise-equivalent counts (PS-NECs) were used as a metric of the statistical quality of each time frame of a dynamic PET image.

Assessment of bladder motion for clinical radiotherapy practice using cine-magnetic resonance imaging.

Purpose: Organ motion is recognized as the principal source of inaccuracy in bladder radiotherapy (RT), but there is currently little information on intrafraction bladder motion.

Methods And Materials: We used cine-magnetic resonance imaging (cine-MRI) to study bladder motion relevant to intrafraction RT delivery. On two occasions, a 28 minute cine-MRI sequence was acquired from 10 bladder cancer patients and 5 control participants immediately after bladder emptying, after abstinence from drinking for the preceding hour.

A new model for prediction of drug distribution in tumor and normal tissues: pharmacokinetics of temozolomide in glioma patients.

Difficulties in direct measurement of drug concentrations in human tissues have hampered the understanding of drug accumulation in tumors and normal tissues. We propose a new system analysis modeling approach to characterize drug distribution in tissues based on human positron emission tomography (PET) data. The PET system analysis method was applied to temozolomide, an important alkylating agent used in the treatment of brain tumors, as part of standard temozolomide treatment regimens in patients.

Carbogen and nicotinamide increase blood flow and 5-fluorouracil delivery but not 5-fluorouracil retention in colorectal cancer metastases in patients.

Purpose: To examine whether carbogen and nicotinamide increases 5-fluorouracil (5-FU) delivery to colorectal cancer metastases.

Experimental Design: Six patients were scanned using positron emission tomography. Two scans were done to coincide with the start of separate chemotherapy cycles.

Imaging vascular physiology to monitor cancer treatment.

The primary physiological function of the vasculature is to support perfusion, the nutritive flow of blood through the tissues. Vascular physiology can be studied non-invasively in human subjects using imaging methods such as positron emission tomography (PET), magnetic resonance imaging (MRI), X-ray computed tomography (CT), and Doppler ultrasound (DU). We describe the physiological rationale for imaging vascular physiology with these methods.

Hypoxia-inducible factor 1alpha expression as an intrinsic marker of hypoxia: correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix.

Purpose: Hypoxia-inducible factor (HIF)-1alpha expression was studied retrospectively in locally advanced carcinoma of the cervix in relation to other methods for measuring/assessing tumor hypoxia and outcome after radiotherapy.

Experimental Design: HIF-1alpha expression was examined in formalin-fixed tumor biopsies using a semiquantitative scoring system and correlated with measurements of hypoxia obtained using oxygen electrodes, pimonidazole staining, and carbonic anhydrase 9.

Results: High HIF-1alpha expression showed a weak correlation with low pO2 (r = -0.

Use of positron emission tomography in anticancer drug development.

Positron emission tomography (PET) is increasingly being used in anticancer drug development. The technique is applicable to studies of drug delivery, and where specific probes are available, to provide pharmacodynamic readouts noninvasively in patients. Mathematical modeling of the imaging data enhances the quality of information that is obtained from such studies.

Assessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate.

Purpose: Clinical evaluation of novel agents that target tumor blood vessels requires pharmacodynamic end points that measure vascular damage. Positron emission tomography (PET) was used to measure the effects of the vascular targeting agent combretastatin A4 phosphate (CA4P) on tumor and normal tissue perfusion and blood volume.

Patients And Methods: Patients with advanced solid tumors were enrolled onto part of a phase I, accelerated-titration, dose-escalation study.

Phase I clinical trial of weekly combretastatin A4 phosphate: clinical and pharmacokinetic results.

Purpose: A phase I trial was performed with combretastatin A4 phosphate (CA4P), a novel tubulin-binding agent that has been shown to rapidly reduce blood flow in animal tumors.

Patients And Methods: The drug was delivered by a 10-minute weekly infusion for 3 weeks followed by a week gap, with intrapatient dose escalation. Dose escalation was accomplished by doubling until grade 2 toxicity was seen.