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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Factors That Expose Cardiologists To More Radiation During Procedures Outlined

MedicalResearch.com Interview with:

Alessandro Sciahbasi, MD, PhD  Sandro Pertini Hospital Rome, Italy

Dr. Sciahbasi

Alessandro Sciahbasi, MD, PhD
Sandro Pertini Hospital
Rome, Italy

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

Response: Radiation exposure is an important issue for interventional cardiologists due to the deterministic and stochastic risks for operators, staff and patients. Consequently, it is important to know which are the determinants of operator radiation exposure during percutaneous coronary procedures in order to reduce radiation exposure. Despite different studies have already evaluated the radiation dose during percutaneous coronary procedures, most data were obtained using an indirect measure of the operator dose expressed in term of fluoroscopy time or dose area product (DAP) and only in a minority of studies dedicated operator dosimeters were used. The aim of our study was to evaluate operator radiation exposure during percutaneous coronary procedures with dedicated electronic dosimeters in a high volume center for transradial procedures.

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Radiation Therapy Improves Pain and Quality of Life in Bone

MedicalResearch.com Interview with:
Rachel McDonald, MD(C)

Department of Radiation Oncology
Odette Cancer Centre
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada

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

Response: Radiation treatment has been demonstrated in numerous studies to provide effective and timely pain relief to those suffering from painful bone metastases. However, as a palliative treatment, the goal should be not only to reduce pain but also to maintain and even improve quality of life. To date, studies have not effectively demonstrated this; most of these have included either small sample sizes or utilize questionnaires that aren’t tailored to the palliative cancer population with bone metastases.

We aimed to determine how soon after radiation treatment one can expect an improvement in quality of life. Our results showed that patients who had a pain response to radiation also had significantly greater improvements in pain, pain characteristics, functional interference, and psychosocial aspects of well-being at day 10 post-treatment. Further improvements in most domains of quality of life were found for responders at day 42.

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Therapies That Target Accessory Cells in a Tumor May Enhance Standard Care

MedicalResearch.com Interview with:

Sudarshan Anand, PhD Department of Cell, Developmental and Cancer Biology Department of Radiation Medicine Oregon Health and Science University Portland, Oregon

Dr. Sudarshan Anand

Sudarshan Anand, PhD
Department of Cell, Developmental and Cancer Biology
Department of Radiation Medicine
Oregon Health and Science University
Portland, Oregon

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

Response: Almost half of all cancer patients receive radiation therapy during the course of their disease.

While the impact of radiation on the cancer cells has been well studied in experimental models, its effects on the accessory cells that are present in the tumor are not well known. One of the major interests of our lab is studying these accessory cells of the tumor aka “the tumor microenvironment”. These group of cells consists of blood vessel cells, fibroblasts and immune cells that are normal cells that have been recruited by the tumor and generally support tumor growth.

The goal of this study was to understand the impact of radiation (and broadly DNA damaging agents) on the blood vessel cells in the tumor. We focused on a specific type of molecule called microRNAs (miRs) in these cells. miRs are small RNA molecules that bind to dozens of messenger RNAs and the production of proteins.

We discovered a group of microRNAs that was induced in blood vessel cells by radiation, a chemotherapy agent cisplatin and peroxide an agent that mimics oxidative stress that is often present in cancers. We found that the top candidate on this list was a microRNA that mimicked radiation by inducing DNA damage and eventually killing the blood vessel cells. Administering this microRNA, either within a tumor or using a specific nanoparticle that delivers cargo to the tumor blood vessels, decreased tumor growth in mouse models of breast cancer, brain cancer and colorectal cancer. We found that the efficacy of this agent was a result of its ability to suppress a protein TREX1, that is often mutated in human lupus.

In other words, this microRNA was able to create some of the immune and inflammatory features of lupus within a tumor and induce proteins that triggered cell death on tumor cells. Overall, our work illustrates how the tumor accessory cells respond to radiation and highlights the cross-talk between different accessory cells and the tumor cells.

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Localized Prostate Cancer: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy

MedicalResearch.com Interview with:

Professor Jenny Donovan  PhD   OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for  Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Bristol, UK

Prof. Jenny Donovan

Professor Jenny Donovan  PhD
OBE FMedSci NIHR-SI AcSS FFPHM
Director, NIHR CLAHRC West
(National Institute for Health Research Collaboration for
Leadership in Applied Health Research and Care West)
at University Hospitals Bristol NHS Trust
Bristol, UK

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

Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years.

The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al).

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