Photodynamic Therapy Being Developed To Target Prostate Cancer

MedicalResearch.com Interview with:
Dr. Susanne Lütje
Ärztlicher Dienst
Universitätsklinikum Essen (AöR)
Klinik für Nuklearmedizin
Essen Germany

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prostate cancer (PCa) is the most common cancer in men and accounts for a significant amount of morbidity and mortality. At present, the curative treatment option of choice for localized stages of PCa is radical prostatectomy, which may include extended lymph node dissection. Unfortunately, surgical procedures can be accompanied by complications such as urinary incontinence. Most importantly, small tumor deposits may not be seen by the surgeon during surgery and could ultimately lead to disease recurrence. To overcome these issues, new and innovative treatments are needed. The prostate-specific membrane antigen (PSMA) is a surface protein that is overexpressed in prostate cancer and can be used as a target to guide new therapies.

Photodynamic therapy (PDT) is an ablative procedure in which tumor cells can be destroyed effectively by irradiation of light of a specific wavelength, which activates previously administered photosensitizers. The photosensitizers can respond by emitting fluorescence or emitting oxygen radicals which can cause cellular damage. Coupling the photosensitizer to an agent that targets PSMA on the tumor surface offers the possibility to selectively and effectively destroy prostate tumor remnants and micrometastases, while surrounding healthy tissues remain unaffected.

In our study, the PSMA targeting antibody D2B was coupled to the photosensitizer IRDye700DX and radiolabeled with 111In. In a mouse model, this multi-modality agent was used to preoperatively visualize tumor lesions with SPECT/CT to allow rough localization of the tumors. During surgery, the fluorescent signal originating from the photosensitizer facilitates visualization of tumors and residual tumor tissue, so the surgeon can be guided towards accurate resection of the entire tumors and metastases. In addition, the PSMA-targeted PDT can be applied to destroy small tumor deposits in cases where close proximity of the tumors.

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MRI At Six Months Can Predict Which High Risk Babies Will Develop Autism

MedicalResearch.com Interview with:

Joseph Piven, MD The Thomas E. Castelloe Distinguished Professor of Psychiatry UNC School of Medicine Director of the Carolina Institute for Developmental Disabilities Co-senior author of the study

Dr. Piven

Joseph Piven, MD
The Thomas E. Castelloe Distinguished Professor of Psychiatry
UNC School of Medicine
Director of the Carolina Institute for Developmental Disabilities
Co-senior author of the study

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Babies with older siblings with autism are at an increased risk (20%) of getting autism over the general population (1%).  Infants who later are diagnosed with autism don’t have any of the stigmata of autism in the first year of life. The symptoms of autism unfold in the first and particularly in the second year of life and beyond.

We have evidence to support the idea that behavioral symptoms of autism arise from changes in the brain that occur very early in life. So we have employed MRI and computer analyses to study those early brain changes and abnormalities in infancy to see if early brain changes at 6 months of age can predict whether babies at high-risk of developing autism will indeed develop the condition at age two.

For this particular study, we used data from MRIs of six-month olds to show the pattern of synchronization or connection across brain regions throughout the brain and then predict which babies at high familial risk of developing autism would be most likely to be diagnosed with the condition at age two.

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Diagnostic Accuracy of FFR-CT Varies Across Spectrum of Coronary Artery Disease

MedicalResearch.com Interview with:
Dr Christopher Michael Cook MBBS Bsc(Hons) MRCP

MRC Clinical Research Fellow
NHLI, Cardiovascular Medicine, Imperial College London 

MedicalResearch.com: What is the background for this study?

Response: FFR-CT is a novel non-invasive technique for estimating the functional significance of a coronary stenosis from CT coronary angiography images. A number of meta-analyses already exist for determining the diagnostic accuracy of FFR-CT (compared to invasive FFR as the reference standard). However, although knowing the overall diagnostic accuracy of FFR-CT is reassuring, in clinical practice a clinician knows not only whether the FFR-CT is positive or negative, but also its actual value. The purpose of this study was to provide clinicians a means of interpreting the diagnostic accuracy of any individual FFR-CT result that may be received in clinical practice.

MedicalResearch.com: What are the main findings?

Response: The main finding of this study is that the diagnostic accuracy of FFR-CT varies markedly across the spectrum of disease. For vessels with FFR-CT above 0.90, 98% met the invasive FFR guideline criterion for deferral. At the other end of the spectrum, for vessels with FFR-CT below 0.60, 86% met the invasive FFR guideline criterion for stenting. However, in between, FFR-CT gives less certainty as to whether the invasive FFR will meet the stenting criterion or not.

MedicalResearch.com: What should readers take away from your report?

Response: Readers can combine the findings of our study with patient specific factors in order to judge when the cost and risk of an invasive angiogram may safely be avoided. Because we now have a more complete picture of what different levels of FFR-CT mean in terms of invasive FFR, it is apparent that a single cut-off value for FFR-CT in deciding on invasive coronary angiography need not always apply. For example, in the asymptomatic patient, further investigations may not be desirable even if an FFR-CT still left a substantial possibility of a positive invasive FFR. Conversely, in the symptomatic patient, the patient and clinician would likely pursue invasive angiography unless the possibility of a positive FFR is very remote.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study adopted novel methodology to ascertain the probability that both FFR-CT and invasive FFR agreed on the functional classification of a stenosis, for any given individual FFR-CT value. This type of analysis could be used to determine if further iterative versions of the FFR-CT software translate into improved diagnostic performance, particularly in more intermediate disease severities. 

MedicalResearch.com: Is there anything else you would like to add?

Response:

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Cook CM, Petraco R, Shun-Shin MJ, Ahmad Y, Nijjer S, Al-Lamee R, Kikuta Y, Shiono Y, Mayet J, Francis DP, Sen S, Davies JE. Diagnostic Accuracy of Computed Tomography–Derived Fractional Flow Reserve A Systematic Review . JAMA Cardiol. Published online May 24, 2017. doi:10.1001/jamacardio.2017.1314

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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MRI Guided Prostate Biopsies Can Improve Care and Reduce Costs

MedicalResearch.com Interview with:

Vikas Gulani, MD, PhD Director, MRI, UH Cleveland Medical Center Associate Professor, Radiology, CWRU School of Medicine

Dr. Gulani

Vikas Gulani, MD, PhD
Director, MRI, UH Cleveland Medical Center
Associate Professor, Radiology, CWRU School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We wanted to learn if performing MR before prostate biopsy, followed by MR guided strategies for biopsy, are cost effective for the diagnosis of prostate cancer in men who have not previously undergone a biopsy and who have a suspicion of prostate cancer.

The most significant findings are as follows:

We found that all three MR guided strategies for lesion targeting (cognitive targeting, MR-ultrasound fusion targeting, and in-gantry targeting) are cost effective, as the increase in net health benefits as measured by addition of quality adjusted life years (QALY), outweigh the additional costs according to commonly accepted willingness to pay thresholds in the United States.

Cognitive targeting was the most cost effective. In-gantry biopsy added the most health benefit, and this additional benefit was cost-effective as well.

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No Magic Age To Stop Performing Screening Mammograms

MedicalResearch.com Interview with:
Cindy S. Lee, MD

Department of Radiology and Biomedical Imaging
University of California, San Francisco, San Francisco
Now with Department of Radiology
NYU Langone Medical Center, Garden City, New York

MedicalResearch.com: What led you and colleagues to conduct this study?

Response: I am a breast imager. I see patients who come in for their screening mammograms and I get asked, a lot, if patients aged 75 years and older should continue screening, because of their age. There is not enough evidence out there to determine how breast cancer screening benefits women older than 75. In fact, all previously randomized trials of screening mammography excluded people older than 75 years.

Unfortunately, age is the biggest risk factor for breast cancer, so as patients get older, they have higher risks of developing breast cancer. It is therefore important to know how well screening mammography works in these patients.

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Cardiac Magnetic Resonance Can Exclude Clinically Relevant Coronary Artery Disease

MedicalResearch.com Interview with:

Pr. Juerg Schwitter MD Médecin Chef Cardiologie Directeur du Centre de la RM Cardiaque du CHUV Centre Hospitalier Universitaire Vaudois - CHUV Suisse

Pr. Schwitter

Pr. Juerg Schwitter MD
Médecin Chef Cardiologie
Directeur du Centre de la RM Cardiaque du CHUV
Centre Hospitalier Universitaire Vaudois – CHUV
Suisse 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Coronary artery disease (CAD) is still one of the leading causes of death in the industrialized world and as such, it is also an important cost driver in the health care systems of most countries. For the European Union, the estimated costs for CAD management were 60 billion Euros in 2009, of which approximately 20 billion Euros were attributed to direct health care costs (1). In 2015, the total costs of CAD management in the United States were estimated to be 47 billion dollars (2).

Substantial progress has been achieved regarding the treatment of CAD including drug treatment but also revascularizations procedures. There exists a large body of evidence demonstrating myocardial ischemia as one of the most important factors determining the patient’s prognosis and reduction of ischemia has been shown to improve outcome.

On the other hand, techniques to detect CAD, i.e. relevant myocardial ischemia, were insufficient in the past. Evaluation of myocardial perfusion by first-pass perfusion cardiac magnetic resonance (CMR) is now closing this gap (3) and CMR is recommended by most international guidelines for the work-up of known or suspected CAD (4,5).

Still, a major issue was not clarified until now, i.e. “how much ischemia is required to trigger revascularization procedures”. Thus, this large study was undertaken to assess at which level of ischemia burden, patients can be safely deferred from revascularization and can be managed by risk factor treatment only. Of note, this crucial question was addressed in both, patients with suspected CAD but also in patients with known (and sometimes already advanced) CAD, thereby answering this question in the setting of daily clinical practice.

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Doctors Continue To Order Mammograms Outside of Current Age Guidelines

MedicalResearch.com Interview with:
Archana Radhakrishnan MD MHS
Division of General Internal Medicine
Johns Hopkins University
Baltimore, Maryland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We were interested in understanding the current practice trends in breast cancer screening recommendations by doctors in light of the guideline changes.  We performed a national survey of primary care providers and gynecologists asking about their breast cancer screening practices.

We found that a large number of doctors recommend breast cancer screening to younger and older women—upwards of 80% of doctors recommend it for younger women (ages 40-44) and almost 70% for women 75 and older.  But this varies by the type of doctor that a woman see.  Gynecologists were, in general, more likely to recommend routine mammograms.

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Ischemic Stroke: Collateral Blood Vessels Detected by Arterial Spin Labeling MRI Correlates With Good Neurological Outcome

MedicalResearch.com Interview with:
Jalal B. Andre M.D., D.A.B.R.®

Drector of neurological MRI and
MRI safety officer at Harborview Medical Center
University of Washington 

MedicalResearch.com: What is the background for this study?

Response: Acute ischemic stroke (AIS) patients with good collaterals have better clinical outcomes. AIS is characterized by an ischemic penumbra, a region of salvageable brain tissue, that surrounds a core of irreversible ischemic infarct. The penumbra is tenuously perfused by collateral blood vessels which, if extensive enough, can maintain penumbral perfusion, improving the odds that a larger volume of brain tissue will survive. Standard, first-line methods for evaluating collaterals in the acute setting include CT angiography, MR angiography, and (less commonly) digital subtraction angiography. Arterial spin labeling (ASL) is an emerging MRI technique that assesses cerebral perfusion. Its advantages include relatively short scan time (4-6 minutes), lack of ionizing radiation, and independence from an exogenous contrast agent (contraindicated in patients with impaired renal function or documented sensitivity). Collaterals can be identified within ASL images as foci of curvilinear hyperintensity bordering regions of hypoperfusion. We sought to explore a novel relationship between the presence of ASL collaterals (ASLc) and neurological outcome in acute ischemic stroke patients.

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Instantaneous Wave-Free Ratio To Evaluate Coronary Artery Disease

MedicalResearch.com Interview with:

Matthias Götberg, MD, PhD Director Cardiac Cath Lab Department of Coronary Heart Disease Skane University Hospital- Lund Lund, Sweden

Dr. Matthias Götberg

Matthias Götberg, MD, PhD
Director Cardiac Cath Lab
Department of Coronary Heart Disease
Skane University Hospital- Lund
Lund, Sweden

MedicalResearch.com: What is the background for this study?

Response: Cardiologists encounter patients with narrowing of the coronary arteries on a daily basis. They typically use visual estimation of the severity of narrowing when performing coronary angiography, but it is difficult to accurately assess, based on a visual estimation alone, whether a stent is needed to widen the artery and allow the blood to more freely.

FFR (Fractional Flow Reserve) is more precise tool and results in better outcomes than using angiography alone to assess narrowing of the coronary arteries. With FFR, the doctor threads a thin wire through the coronary artery and measures the loss of blood pressure across the narrowed area. To acquire an accurate measurement, the patient must be given adenosine, which is a drug that dilates the blood vessels during the procedure. This drug causes discomfort; patients describe having difficulty breathing or feeling as if someone is sitting on their chest. The drug also adds to the cost of the procedure and can have other rare but serious side effects.

iFR (Instantaneous Wave-Free Ratio) is also based on coronary blood pressure measurements using a thin wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in the coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed.
iFR has been validated in smaller trials and have been found to be equally good as FFR to detect ischemia, but larger randomized outcome trials are lacking.

iFR-Swedeheart is a Scandinavian Registry-based Randomized Clinical Trial (RRCT) in which 2000 patients were randomized between iFR and FFR as strategies for performing assessment of narrowed coronary vessels. The primary composite endpoint at 12 months was all-cause death, non-fatal myocardial infarction, and unplanned revascularization.
RRCT is a new trial design originating from Scandinavia using existing web-based national quality registries for online data entry, randomization and tracking of events. This allows for a very high inclusion rate and low costs to run clinical trials while ensuring robust data quality.

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iFR Can Assess Need For Coronary Revascularization Without Adenosine

MedicalResearch.com Interview with:

Dr. Justin Davies PhD Senior Reserch Fellow and Hononary Consultant Cardiologist National Heart and Lung Institute, Imperial College Londo

Dr. Davies

Dr. Justin Davies PhD
Senior Reserch Fellow and Hononary Consultant Cardiologist
National Heart and Lung Institute,
Imperial College London

MedicalResearch.com: What is the background for this study?

Response: We know from the FAME study that compared to angiography alone, FFR guided revascularization improves long-term clinical outcomes for our patients. Despite this, adoption of FFR into everyday clinical practice remains stubbornly low. One major factor for this is the need for adenosine (or other potent vasodilator medications) in order to perform an FFR measurement. Adenosine is expensive, unpleasant for the patient, time consuming and even potentially harmful.

iFR is a newer coronary physiology index that does not require adenosine for its measurement. In the prospective, multi center, blinded DEFINE FLAIR study, 2492 patients were randomly assigned to either FFR guided revascularisation or iFR guided revascularization and followed up for a period of 1 year.
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