How Do Stem Cells Respond To Diagnostic Radiation Studies?

MedicalResearch.com Interview with:
http://www.insilico.com/
Andreyan Osipov PhD
Insilico Medicine and
Dmitry Klokov PhD
Canadian Nuclear Laboratories, Chalk River, Ontario, Canada 

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

Response: Cells and tissues can be damaged when exposed to ionizing radiation. In case of radiotherapy, it is a desirable effect in tumor cells. In case of occupational, medical and accidental exposures, typically to low-dose radiation, this may pose health risk to normal cells and tissues.

In both cases, short-term assays that quantify damage to DNA and help evaluate long-term outcome are key to treatment/risk management. One such short-term assay is based on quantification of a modified histone protein called gH2AX in exposed cells up to 24 hrs after exposure. This protein marks sites in DNA that have both strands of the DNA helix broken or damaged. This assay is also widely used for various applications, including determination of individual radiosensitivity, tumor response to radiotherapy and biological dosimetry. With the advent of regenerative medicine that is based on stem cell transplantation, the medical and research communities realized that there is a need to understand how stem cells respond to low-dose diagnostic radiation exposures, such as CT scans. Stem cell therapies may have to be combined with diagnostic imaging in recipient patients. The gH2AX assay comes in very handy here, or at least it seemed this way.

We exposed mesenchymal stem cells isolated from human patients to low or intermediate doses of X-rays (80 and 1000 mGy) and followed formation of gH2AX in their nuclei. First we found that residual gH2AX signal in cells exposed to a low dose was higher than in control non-irradiated cells. If the conventional assumptions about this assay that it is a surrogate for long-term detrimental effects was followed it would mean that the low-dose exposed cells were at a high risk of losing their functional properties. So we continued growing these cells for several weeks and assayed gH2AX levels, ability to proliferate and the level of cellular aging. Surprisingly, we found that low-dose irradiated cells did not differ from non-irradiated cells in any of the measured functional end-points. This was in contrast to 1000 mGy irradiated cells that did much worse at those long-term end points.

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Thinking Abilities May Decline After Treatment For Head and Neck Cancers

MedicalResearch.com Interview with:

Lori J Bernstein, PhD, CPsych Neuropsychologist, Dept. of Supportive Care Core Member, Cancer Rehabilitation & Survivorship Program ELLICSR Centre for Health Wellness and Cancer Survivorship Princess Margaret Cancer Centre, UHN Clinical Research Unit Member, Princess Margaret Research Institute Assistant Professor, Dept. of Psychiatry, Faculty of Medicine University of Toronto Adjunct Faculty, Graduate Program in Psychology, York University

Dr. Bernstein

Lori J Bernstein, PhD, CPsych
Neuropsychologist, Dept. of Supportive Care
Core Member, Cancer Rehabilitation & Survivorship Program
ELLICSR Centre for Health Wellness and Cancer Survivorship
Princess Margaret Cancer Centre, UHN
Clinical Research Unit Member,
Princess Margaret Research Institute
Assistant Professor, Dept. of Psychiatry, Faculty of Medicine
University of Toronto
 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Despite the increasing role of (chemo-)radiation treatment for head and neck cancer (HNC), and involvement of central nervous system structures in the radiation field, we don’t know a lot about whether there are short or long term consequences in thinking abilities in survivors. So our question was this: Do people treated for head and neck cancer with radiation or chemoradiation have short or long term neurocognitive deficits after treatment?

We assessed head and neck cancer patients and healthy non-cancer controls four times, first at baseline (after diagnosis but before treatment), and then again 6, 12, and 24 months later. We found that compared to the controls, patients decline over time in several different neurocognitive domains, including concentration, verbal memory, and executive function. We found that as many as 38% of patients suffered from impaired global neurocognitive functioning by two years after treatment compared to none of the controls.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: The findings indicate that some (but not all) head and neck cancer survivors are at risk of suffering from declines in thinking abilities such as attention and memory. These changes can be subtle and increase gradually. We didn’t follow people beyond 2 years after treatment, so we don’t know whether these deficits would improve, worsen, or stabilize after that.

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

Response: Longer longitudinal follow-up is needed to determine if symptoms change after 2 years. More investigation of the relationships between treatment variables such as radiation dosing and long term neurocognitive function is important. Further research is also needed to find ways to avoid, reduce and compensate for declines.

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

Response: We are extremely grateful to the people who participated in this study. We plan to reassess participants for several more years, so we hope to know more about even longer term cognitive function in people treated for head and neck cancer. In addition, I want to acknowledge that we could not have done this work without the support of the Princess Margaret Cancer Foundation and The Canadian Institutes of Health Research.

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

Citation:

Alona Zer, Gregory R. Pond, Albiruni R. Abdul Razak, Kattleya Tirona, Hui K. Gan, Eric X. Chen, Brian O’Sullivan, John Waldron, David P. Goldstein, Ilan Weinreb, Andrew J. Hope, John J. Kim, Kelvin K. W. Chan, Andrew K. Chan, Lillian L. Siu, Lori J. Bernstein. Association of Neurocognitive Deficits With Radiotherapy or Chemoradiotherapy for Patients With Head and Neck Cancer. JAMA Otolaryngol Head Neck Surg. Published online November 22, 2017. doi:10.1001/jamaoto.2017.2235

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

 

 

 

 

 

 

Interventional Cardiologists Can Face Risks To Brain From Unprotected Radiation Exposure

MedicalResearch.com Interview with:

Dr. Maria Grazia Andreassi

Dr. Andreassi

Dr. Maria Grazia Andreassi, PhD
Director, Genetics Research Unit
CNR Institute of Clinical Physiology, Pisa- Italy

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

Response: In recent years, there has been a growing concern about the health risks for contemporary interventional cardiologists who have a high and unprecedented levels of occupational ionizing radiation (IR) exposure. Because dysregulation of microRNAs (miRNAs) have been shown in many human diseases, we investigated the differential expression of miRNAs in the plasma of interventional cardiologists professionally exposed to IR and unexposed controls.

In this study, our microarray analysis with 2,006 miRNAs and subsequent validation identified brain-specific miR-134 as one of the miRNAs that is highly dysregulated in the response to ionizing radiation exposure, supporting the notion that the brain damage is one of the main potential long-term risks of unprotected head irradiation in interventional cardiologists, with possible long-lasting cognitive consequences. Indeed, miR-134 was first identified as a brain-specific miRNA, which is involved in synapse development and directly implicated in learning and memory.

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Prostate Cancer: Immune Content May Predict Response To Post-Op Radiation

MedicalResearch.com Interview with:

Dr. Shuang George Zhao, MD House Officer, Radiation Oncology University Hospital Ann Arbor, MI 48109-5010

Dr. Zhao

Dr. Shuang George Zhao, MD
House Officer, Radiation Oncology
University Hospital
Ann Arbor, MI 48109

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

Response: Targeting cancer through the immune system has been a longstanding goal of cancer research, and with recent advances in immunotherapy, it is now a reality. However, the role of immunotherapy in prostate cancer is still being defined. Sipuleucel-T was the first FDA approved immunotherapy in prostate cancer, and is a personalized cellular therapy that has been shown to prolong survival in patients with metastatic prostate cancer. On the other hand, two recent phase III randomized trials looking at ipilimumab, a CTLA-4 checkpoint inhibitor in metastatic prostate cancer have both been negative for their primary endpoint of OS. Interestingly, there was a PSA response, suggesting that there may be some therapeutic effect in a subset of patients. Therefore, understanding the immune infiltrate is likely critical to selecting patients and therapeutic strategies utilizing the immune system. Unfortunately, it is difficult and laborious to histologically assess immune infiltrate directly. Therefore, we used existing high throughput transcriptomic data with new computational methods in order to more fully characterize the immune landscape of localized prostate cancer.

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Early Breast Cancer: Radiation Before Surgery Reduce Risk of Second Tumors

MedicalResearch.com Interview with:

Heiko Enderling, Ph.D. Associate Member & Director for Education and Outreach Dept. of Integrated Mathematical Oncology Dept. of Radiation Oncology H. Lee Moffitt Cancer Center & Research Institute Tampa, FL 33612

Dr.Enderling

Heiko Enderling, Ph.D.
Associate Member & Director for Education and Outreach
Dept. of Integrated Mathematical Oncology
Dept. of Radiation Oncology
H. Lee Moffitt Cancer Center & Research Institute
Tampa, FL 33612

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

Response: Although radiation therapy after breast-conserving surgery for early-stage breast cancer has significantly improved patient prognosis, many patients will face a second cancer diagnosis within 20 years of primary treatment. Experimental and clinical studies have shown that local radiation therapy can activate an immune response that can propagate systemically to attack distant untreated metastases. However, current radiotherapy practice has not specifically focused on enhancing immune responses.

We asked the question if pre-operative irradiation, when applied to the bulk of disease, could have potentially higher immune stimulatory effects. To study this, we analyzed historic outcomes of breast cancer patients treated with either adjuvant (radiation after surgery) or neoadjuvant (radiation before surgery) radiotherapies.

Our analysis showed that the risk of developing a second tumor after neoadjuvant compared with adjuvant RT was significantly lower, especially for estrogen receptor-positive women who underwent breast conserving surgery or mastectomy. Historic data revealed an increase in disease-free survival of 12% over 20 years after treatment of the original tumor.

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Promising Study of Shorter Course of Radiation Therapy After Mastectomy

MedicalResearch.com Interview with:

Bruce G. Haffty, MD Professor and Chair, Department of Radiation Oncology Rutgers Cancer Institute of New Jersey Rutgers Robert Wood Johnson Medical School and Rutgers New Jersey Medical School

Dr. Haffty

Bruce G. Haffty, MD
Professor and Chair, Department of Radiation Oncology
Rutgers Cancer Institute of New Jersey
Rutgers Robert Wood Johnson Medical School and
Rutgers New Jersey Medical School

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

Response: Shorter courses of radiation for patients treated by lumpectomy are now commonly employed. For patients receiving radiation to the chest wall and lymph nodes after mastectomy, the standard 5 to 6 week course is used and shorter courses have not been adopted.

We initiated this trial of a shorter course of radiation to the chest wall and lymph nodes after mastectomy to test its feasibility, safety and outcome.
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Radiation Exposure and Vascular Access in Acute Coronary Syndromes: The RADMatrix Trial

MedicalResearch.com Interview with: Dr. Marco Valgimigli,

Dr. Marco Valgimigli

MedicalResearch.com Interview with:
Dr. Marco Valgimigli, MD, PhD

Interventional Cardiology
Sandro Pertini Hospital, ASL RM2, Rome, Italy

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

Response: Every year millions of people with coronary artery disease are treated worldwide with percutaneous coronary intervention (PCI). Radial access as compared to femoral access reduces bleeding and mortality in patients with acute coronary syndrome (ACS) undergoing invasive management. However, prior studies have raised concerns over the increased risk of radiation exposure for both patients and operators with radial instead of femoral access and it remains still unclear whether radial access increases the risk of operator or patient radiation exposure in contemporary practice when performed by expert operators.

The MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial is the largest randomized trial comparing radial versus femoral access in ACS patients undergoing invasive management. In this radiation sub-study (RAD-MATRIX), we collected fluoroscopy time and dose area product (DAP) and equipped radial operators consenting to participate with dedicated dosimeters, each wearing a thorax (primary endpoint), wrist and head (secondary endpoints) lithium fluoride thermo luminescent dosimeter, during study conduct to establish non-inferiority of radial versus femoral access.

Among eighteen operators, performing 777 procedures in 767 patients, the non-inferiority primary endpoint was not achieved. Operator equivalent dose at the thorax was significantly higher with radial than femoral access. After normalization of operator radiation dose by fluoroscopy time or DAP, the difference remained significant. Radiation dose at wrist or head did not differ between radial and femoral access. Thorax operator dose did not differ in the right radial compared to the left radial access. In the overall MATRIX population, fluoroscopy time and DAP were higher with radial as compared to femoral access.

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Shorter Term Precision Radiation Found Effective For Prostate Cancer

MedicalResearch.com Interview with:

Charles N Catton, MD, FRCPC Cancer Clinical Research Unit (CCRU) Princess Margaret Cancer Centre UHN

Dr. Catton

Charles N Catton, MD, FRCPC
Cancer Clinical Research Unit (CCRU)
Princess Margaret Cancer Centre
UHN 

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

Response: Prostate cancer is a very common malignancy which is frequently treated with external beam radiotherapy. A typical standard treatment course can extend over 7.5-8.5 weeks.

The introduction of high-precision radiotherapy treatment techniques provided the opportunity to compress treatment courses by delivering fewer, but more intensive daily treatments. The concerns with giving fewer and larger daily treatments (hypofractionation) is that toxicity may increase and that cancer control may become worse.

This international randomized trial enrolled 1206 men with intermediate risk prostate cancer and compared a standard 8 week course of external beam radiation treatment with a novel hypofractionated treatment course that was given over 4 weeks. Cancer control as measured by PSA control and clinical evidence of failure, bowel and bladder toxicity and quality of life were compared.

At a median follow-up of 6 years the hypofractionated regimen was found to be non-inferior to the standard regimen for cancer control. There was no difference early or late bladder toxicity between the two treatments. There was slightly worse early bowel toxicity during and immediately after treatment with the hypofractionated regimen, but there was actually slightly less long-term bowel toxicity with this same regimen.

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Using a Spacer During Prostate Radiation May Help Preserve Sexual Function

MedicalResearch.com Interview with:

Daniel A. Hamstra, MD PhD The Texas Center for Proton Therapy Irving, TX

Dr. Hamstra

Daniel A. Hamstra, MD PhD
Radiation Oncologist
Beaumont Hospital
Dearborn Michigan

MedicalResearch.com: What is the background for the The SpaceOAR phase 3 trial study and the hydrogel spacer?

Response: External beam radiation therapy is commonly used to treat men with prostate cancer. As part of this treatment, side effects can occur involving bowel, urinary, and sexual symptoms.

This study was performed to test if an absorbable hydrogel placed between the prostate and rectum (using a simple outpatient procedure) could move the rectum away from the prostate and thus result in sparing of the rectum and decreased bowel toxicity. The study randomized 222 men and the three-year data were just published (The International Journal of Radiation Oncology Biology and Physics). With three years of follow-up, we saw that the spacer did improve the radiation plans and decreased both rectal toxicity and urinary toxicity.

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Reduction in Radiation Has Reduced Second Tumors in Pediatric Cancer Patients

MedicalResearch.com Interview with:

Lucie Turcotte, MD, MPH University of Minnesota Masonic Children's Hospital Division of Pediatric Hematology-Oncology Assistant Professor Minneapolis, MN 55455

Dr. Lucie Turcotte

Lucie Turcotte, MD, MPH
University of Minnesota Masonic Children’s Hospital
Division of Pediatric Hematology-Oncology
Assistant Professor
Minneapolis, MN 55455

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

Response: We have observed dramatic improvements in the number of survivors of childhood cancer over the last 60 years. As more children are surviving, we have identified many important late health consequences of cancer therapy. One of the most devastating of these late health consequences is the diagnosis of a second cancer. As we have identified late effects, such as second cancers, we have modified therapy in an effort to prevent long-term sequelae of therapy, while still maintaining superior survival rates.

For this study, we utilized data from the Childhood Cancer Survivor Study (CCSS), which is a cohort of more than 23,000 survivors of childhood cancer from multiple centers in North America, who were initially diagnosed between 1970 and 1999. Our analysis focused on elucidating whether survivors diagnosed more recently were experiencing fewer second cancers, and determining whether a reduction in second cancers could be associated with treatment modifications.

The most important finding from this study is that the reductions in therapeutic radiation exposure that occurred between 1970-1999 resulted in a significant reduction in the second cancers experienced by survivors of childhood cancer.

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