Liquid Biopsy Can Guide Radiation Therapy in Early Stage Breast Cancer

MedicalResearch.com Interview with:

Chelain Goodman, MD PhD PGY-3, Radiation Oncology Northwestern University Chicago, IL 60611

Dr. Goodman

Chelain Goodman, MD PhD
PGY-3, Radiation Oncology
Northwestern University
Chicago, IL 60611

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

Response: Circulating tumor cells are cancer cells that are shed from the primary tumor into the peripheral blood stream and are hypothesized to be one of the first steps in the initiation of metastatic progression. Prospective studies have demonstrated that approximately 15-25% of patients with early-stage breast cancer can be found to have at least one circulating tumor cell in a small sample of their blood. Currently, all patients with early-stage invasive breast cancer who undergo breast conserving surgery receive adjuvant radiation therapy. In these analyses, we wanted to determine whether presence of circulating tumor cells may be predictive of benefit of radiation therapy following surgery.

Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

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.
Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

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).

Continue reading

Knowledge of Risks From Imaging Radiation Has Room For Improvement

MedicalResearch.com Interview with:

David Leswick MD FRCPC Radiologist Saskatoon Health Region and the University of Saskatchewan

Dr. David Leswick

David Leswick MD FRCPC
Radiologist Saskatoon Health Region and the
University of Saskatchewan

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

Response: The background for this study is that the use of computed tomography (CT) is increasing, and there is a significant radiation dose imparted to the population through imaging. There have been multiple prior studies showing limited knowledge of both dose levels and its associated risk from medical imaging procedures, and we wanted to evaluate local knowledge in our Health Region. We surveyed a total of 308 health care providers, including 217 referring physicians, 32 radiologists and 59 technologists. Overall, most respondents were aware of the risk of malignancy from CT, with only 23% of physicians, 3% of radiologists, and 25% of technologists believing there was no increased risk of malignancy from a single CT scan. Underestimating radiation dose levels from a procedure is more concerning than overestimating as it may lead to minimization of the perceived risk. Although relatively few respondents (20%) selected the most appropriate dose estimate for an abdominal CT scan in chest x-ray equivalents, the majority (54%) correctly or overestimated dose, with better knowledge amongst radiologists and imaging technologists than referring physicians. In general, respondents were appropriately more concerned regarding radiation dose when imaging pregnant and pediatric patients as risks from radiation are higher in those groups of patients.

Continue reading

Synergy Between Radiation and Chemotherapy Enhances Melanoma Treatment

MedicalResearch.com Interview with:

James S. Welsh, MS, MD, FACRO President, American College of Radiation Oncology Professor and Medical Director Director of Clinical & Translational Research Department of Radiation Oncology Stritch School of Medicine Loyola University- Chicago Cardinal Bernardin Cancer Center Maguire Center, Rm 2932 Maywood, IL 60153 Chief of Radiation Oncology Hines VA Medical Center

Dr. James Welsh

James S. Welsh, MS, MD, FACRO
President, American College of Radiation Oncology
Professor and Medical Director
Director of Clinical & Translational Research
Department of Radiation Oncology
Stritch School of Medicine Loyola University- Chicago
Cardinal Bernardin Cancer Center
Maywood, IL 60153
Chief of Radiation Oncology
Hines VA Medical Center

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

Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.

Continue reading

Intra-operative Radiation For Breast Cancer Better For Patients and Environment

MedicalResearch.com Interview with:
Jayant S Vaidya MBBS MS DNB FRCS PhD  Professor of Surgery and Oncology,  Scientific Director, Clinical Trials Group, Division of Surgery and Interventional Science, University College London Whittington Health - Clinical Lead for Breast Cancer Royal Free Hospital University College London Hospital
Jayant S Vaidya MBBS MS DNB FRCS PhD 
Professor of Surgery and Oncology,
Scientific Director, Clinical Trials Group,
Division of Surgery and Interventional Science,
University College London
Whittington Health – Clinical Lead for Breast Cancer
Royal Free Hospital
University College London Hospital

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

Prof. Vaidya: TARGIT-A randomised clinical trial (ISRCTN34086741) compared giving TARGIT IORT during lumpectomy vs. traditional EBRT given over several weeks after lumpectomy for breast cancer; local-recurrence-free-survival was similar in the two arms of the trial, particularly when TARGIT was given simultaneously with lumpectomy. Also, there were significantly fewer deaths from other causes with TARGIT IORT.

This study calculated journeys made by patients with breast cancer to receive their radiotherapy, using the geographic and treatment data from a large randomised trial.

The study then assessed the same outcomes (travel distances, travel time and CO2emissions) in two semi-rural breast cancers—the results of this assessment confirm and reinforce the original results: the benefit of the use of TARGIT for patients from two semi=rural breast centres was even larger (753 miles (1212 km), 30 h, 215 kg CO2 per patient).

Continue reading

Chemotherapy Plus Radiation Demonstrated Control of Liver Metastases in Colon Cancer

MedicalResearch.com Interview with:

Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia

Dr. Guy van Hazel

Dr Guy van Hazel
Clinical Professor of Medicine,
School of Medicine and Pharmacology,
University of Western Australia 

Medical Research: What is the background for this study? What are the main findings?

Dr. van Hazel: The SIRFLOX study is based on original work by Dr Bruce Gray and myself almost two decades ago, when we studied the combination of Selective Internal Radiation Therapy (SIRT) with Y-90 resin microspheres – which was absolutely new at the time – with hepatic artery chemotherapy. This study showed an increase in liver control with the addition of SIRT [Gray B et al. Ann Oncol 2001; 12: 1711–1720.].

We then proceeded to initiate a trial comparing systemic SIRT plus 5-FU/LV according to the Mayo Clinic regimen compared to the Mayo Clinic regimen alone, but unfortunately this had to be abandoned because new chemotherapy became available which made it unethical to offer the control arm. However, in those patients who were treated up to that point with SIRT plus 5-FU/LV [van Hazel G et al. J Surg Oncol 2004; 88: 78–85.] we did see a very high response rates compared to the control arm, with an impressive survival of 29 months. We subsequently did a phase l/ll study of modified FOLFOX6 with or without SIRT and again found very high response rates [Sharma R et al. J Clin Oncol 2007; 25: 1099–1106.].  This led us to launch the SIRFLOX study in 2007.

Continue reading

Skipping Radiation Cancer Treatments Linked To Worse Outcomes

MedicalResearch.com Interview with:

Dr. Madhur Garg MD Professor, Clinical director, Department of Radiation Oncology Montefiore Einstein Center for Cancer Care Albert Einstein College of Medicine. Bronx, NY 10467

Dr. Madhur Garg

Dr. Madhur Garg MD
Professor, Clinical director, Department of Radiation Oncology
Montefiore Einstein Center for Cancer Care
Albert Einstein College of Medicine.
Bronx, NY 10467

Medical Research: What is the background for this study? What are the main findings?

Dr. Garg: In most curative settings, external beam radiotherapy (RT) for the treatment of solid tumors is delivered five days each week over multiple weeks in an outpatient setting. Unintended treatment prolongation, generally attributed to treatment toxicity or inter-current illness, has been associated with inferior tumor control in a number of disease sites. Montefiore Einstein Center for Cancer Care recently identified radiotherapy (RT) noncompliance as a prevalent issue among patients receiving RT with curative intent. Approximately 20% of patients were deemed to be noncompliant, and statistically significant predictors of noncompliance risk included diagnosis, treatment course length, and socioeconomic status (SES). In this report, we examined if radiotherapy noncompliance is associated with clinical outcomes in our patient population.

In this analysis, we have found that treatment noncompliance is associated with inferior clinical outcomes for patients receiving radiotherapy with curative intent. The associations we detected were both statistically significant and clinically meaningful and consistent across disease sites. This is a novel finding that may have significant implications for how cancer care delivery can be improved, particularly in disadvantaged patient populations. Our finding that  radiotherapy noncompliance is strongly associated with inferior outcomes, even after adjusting for confounders such as comorbidity index and SES, suggests to us that noncompliance may serve as a behavioral biomarker for other risk factors that contribute to poor outcomes. These may include noncompliance with other important clinician visits and procedures, lack of social support, and mood disorders.

Continue reading

Radiation Converts Some Resistant Head and Neck Cancer Cells Into Aggressive Stem Cells

MedicalResearch.com Interview with:

Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714

Dr. Erina Vlashi

Erina Vlashi, PhD
Assistant Professor
Department of Radiation Oncology
David Geffen School of Medicine at UCLA
Los Angeles, CA 90095-1714

Medical Research: What is the background for this study? What are the main findings?

Dr. Vlashi: It has been known for quite some time that head and neck squamous cell carcinomas (HNSCC) that test positive for human papilloma virus (HPV) respond to radiation therapy more favorably than HPV-negative HNSCCs. Our team reviewed a cohort of 162 patients with a head and neck squamous carcinoma diagnosis over a two-year period, and confirmed that the outcomes were correlated with the patient’s HPV status. The work that followed was prompted by a discovery we had made earlier in breast cancer suggesting that breast cancer cells that manage to survive radiation therapy have the capacity to convert into more de-differentiated, therapy-resistant cells with characteristics of cancer stem cells, and that the degree of this conversion depended on the type of breast cancer: the more aggressive types of breast cancer being more prone to the therapy-induced phenotype conversion. So, we hypothesized that this therapy-induced conversion phenomenon may especially be at play in  head and neck squamous cell carcinomas given the clinical observation that HPV-positive HNSCCs respond to radiation therapy much more favorably than HPV-negative HNSCCs, despite optimum treatment modalities. And indeed, that is what we found: tumor cells derived from a panel of  head and neck squamous cell carcinomas cell lines that do not respond well to radiation therapy have an enhanced ability to convert the cells that survive radiation into more aggressive cells, cancer stem-like cells that will resist the next round of radiation therapy.  Continue reading

Is Low Dose Radiation Exposure Really Harmful?

MedicalResearch.com Interview with:
Jeffry A. Siegel, PhD
President & CEO, Nuclear Physics Enterprises, Marlton, NJ
Charles W. Pennington, MS, MBA
NAC International, Norcross, GA, Retired; Executive Nuclear Energy Consultant
Bill Sacks, PhD, MD
Emeritus Medical Officer, FDA Center for Devices and Radiological Health
Silver Spring, MD
James S. Welsh, MS, MD, FACRO
Department of Radiation Oncology
Stritch School of Medicine Loyola University Chicago, Maywood, IL

Medical Research: What is the background for this study? What are the main findings?

Response: The background is the falsity of the widespread claim that all ionizing (high energy) radiation is harmful regardless of how low the dose.  This claim is expressed in the official policies of almost all radiation regulatory agencies around the world, as well as in many scientific journal papers.  It has been responsible for a common fear of radiation (radiophobia) among the public and members of the medical profession, including even most radiologists and nuclear medicine physicians.

The radiophobia resulting from this false allegation has been instrumental in the forced evacuations of hundreds of thousands of people near nuclear energy plants at Chernobyl and Fukushima that have produced thousands of deaths from the evacuations themselves of sick and/or elderly people, from consequent suicides, alcoholism, heart attacks, and strokes, as well as other health destroying reactions to the loss of homes, possessions, jobs, and communities.

This erroneous belief has acted to prevent many people from getting needed CT scans and x-ray studies, and to prevent many parents from permitting their children to get such imaging studies, with consequences such as surgical explorations that might have been otherwise unnecessary and carry risks of injury and mortality, or such as the foregoing of treatment that would otherwise be health restoring.

This unfounded proclamation and its resultant radiophobia have acted as obstacles to the development of clean and sustainable nuclear energy, and have underlain widespread irresponsible propaganda by all sorts of would-be anti-nuclear gurus.  There are other harmful effects of this unwarranted contention, including severe limitations on funding for further research into the beneficial effects of low-dose radiation.

The main findings in this article are that the very scientists whose experimental work gave rise to this false claim in the 1940s – Hermann Muller and Curt Stern and their colleagues – in fact demonstrated the exact opposite, namely that below certain threshold radiation doses there were no harmful effects at all and possible beneficial effects.  Even more importantly, there were no scientists at the time who realized that Muller and Stern’s conclusions flew in the face of their actual experimental results.  Or at least there were none who were inclined to point out the falsity of Muller and Stern’s unwarranted conclusions, perhaps intimidated by Muller’s status as a Nobel Prize winner (1946, for his earlier work on radiation-caused mutations in fruit flies).

Continue reading

Radiation Overutilized in Elderly Stage1 ER+ Breast Cancer Patients

MedicalResearch.com Interview with:

Quyen Chu, MD, MBA, FACS Charles Knight Professor in Surgery Professor of Surgery Chief, Surgical Oncology Director, Surface Malignancies Program Feist-Weiller Cancer Center Louisiana State University Health Sciences Center, Shreveport

Dr. Quyen Chu

Quyen Chu, MD, MBA, FACS
Charles Knight Professor in Surgery
Professor of Surgery
Chief, Surgical Oncology
Director, Surface Malignancies Program
Feist-Weiller Cancer Center
Louisiana State University
Health Sciences Center, Shreveport

Medical Research: What is the background for this study? What are the main findings?
Dr. Chu: In 2004, national treatment recommendations changed for a select group of elderly breast cancer patients with the Cancer and Leukemia Group B (CALGB) 9343 trial. Research found that postoperative radiation therapy was not needed to prolong survival in a select group of women 70 or older, mainly those with a small, estrogen receptor (ER) positive tumor, and receiving anti-hormone therapy.  Even with this information, nearly two thirds of the women who fit these criteria were still receiving radiation therapy after undergoing a lumpectomy although it has been proven to be safe to omit.

We found that as a nation, we are mostly not following the national guideline on breast cancer treatment and that the possible side effects of RT can be avoided.

Medical Research: What should clinicians and patients take away from your report?

Dr. Chu: Clinicians and patients should take away from this report that in U.S. women 70 or older with stage I, ER+ breast cancer and receiving anti-hormone therapy, radiation therapy is overly utilized as it is not needed to prolong survival.  

Continue reading

Lung Cancer: Intensity Modulated Radiation Therapy Linked to Improved Quality of Life

Benjamin Movsas, MD Chairman of Radiation Oncology Henry Ford Hospital Detroit, Michigan

Dr. Movsas

MedicalResearch.com Interview with:
Benjamin Movsas, MD

Chairman of Radiation Oncology
Henry Ford Hospital
Detroit, Michigan 

Medical Research: What is the background for this study? What are the main findings?

Dr. Movsas: The background is that a recent randomized lung cancer trial (RTOG 0617) showed a lower (rather than a higher) survival among the patients who received a higher dose of radiation (RT).  This unexpected finding was puzzling as there were few differences in toxicity between the radiation dose arms noted by health care providers.

The main finding of the quality of life (QOL) analysis was that there was indeed a large difference in QOL as reported by the patients themselves (with lower QOL on the high RT dose arm at 3 months).  Moreover, while this study was not randomized for RT technique, about half of the patients received intensity modulated RT (IMRT), a more sophisticated approach than the alternative (3D conformal RT), which can better protect normal tissues.  Despite the fact that patients with larger tumors received IMRT, their self reported QOL one year later was significantly better (ie, much less decline in QOL) relative to patients who received 3D conformal RT.  Finally, higher QOL at baseline significantly predicated for better survival.

Continue reading

Anti-VEGF Treatment Plus Radiation For Schwannoma Control

Dr-Lei-Xu.jpg

Dr. Lei Xu

MedicalResearch.com Interview with:
Lei Xu, MD, PhD
Steele Laboratory of Tumor Biology
Radiation Oncology Department
Massachusetts General Hospital

Medical Research: What is the background for this study?

Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing.

Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves.

Continue reading