MedicalResearch.com Interview with: [caption id="attachment_32943" align="alignleft" width="180"] Dr. Boessen[/caption] Lars Boesen MD PhD Department of Urology Herlev Gentofte University Hospital Herlev MedicalResearch.com: What is the background...
MedicalResearch.com Interview with: [caption id="attachment_32662" align="alignleft" width="150"] Dr. Yu Chen[/caption] Yu Chen PhD MPH Associate Professor, Department of Population Health Associate Professor, Department of...
Dr. Kun Zhang[/caption]
Kun Zhang, PhD
Professor
UCSD Department of Bioengineering
La Jolla, CA 92093-0412
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood.
MedicalResearch.com Interview with: [caption id="attachment_32727" align="alignleft" width="150"] Dr. Donghao Lu[/caption] Donghao Lu PhD student Department of Medical Epidemiology and Biostatistics Karolinska Institute MedicalResearch.com: What is...
Dr. Gery Guy[/caption]
Gery P. Guy Jr., PhD, MPH
Senior Health Economist
Division of Unintentional Injury
CDC
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The incidence of skin cancer is increasing in the United States, and individuals who indoor tan are at an increased risk of skin cancer. Treating skin cancer costs $8.1 billion annually.
The number of high school students who indoor tan dropped by half from 2009 to 2015. In 2015, 1.2 million high school students indoor tanned, down from 2.5 million in 2009. This is a much bigger decrease than we have seen in the past and is an encouraging finding. We also found that 82% of indoor tanners reported sunburn in the past year compared with 54% of those who did not engage in indoor tanning.
Dr. Caram[/caption]
Megan Elizabeth Veresh Caram MD
Clinical Lecturer
Internal Medicine, Hematology & Oncology
University of Michigan
MedicalResearch.com: What is the background for this study?
Response: Abiraterone and enzalutamide are oral medications that were approved by the Food & Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer. Most men with advanced prostate cancer are over age 65 and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D and Dartmouth Atlas data.
Dr. Hamstra[/caption]
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.
Dr. Behera[/caption]
Reeti Behera, Ph.D.
Postdoctoral fellow in the Weeraratna lab
The Wistar Institute
Philadelphia PA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance.
Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young.
Dr. Kyrgiou[/caption]
Dr Maria Kyrgiou MSc, PhD, MRCOG
Clinical Senior Lecturer & Consultant in Gynaecologic Oncology
IRDB - Department of Surgery and Cancer, Imperial College London
West London Gynaecological Cancer Centre, Queen Charlotte's & Chelsea-Hammersmith Hospital, Imperial Healthcare NHS Trust
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Obesity has become a major public health challenge and it's prevalence worldwide has more than doubled amongst women n the last four decades. Excess body weight has been associated with an increased risk of developing and dying from numerous cancers. Although the reported associations may be potentially causal, some of the associations may be flawed due to inherent study biases such as residual confounding and selective reporting of positive results.
We included 204 meta-analyses investigating associations between adiposity and the development or death from 36 primary cancers and their sub-types. Adiposity was associated with a higher risk of developing esophageal adenocarcinoma, gastric cardia, colon and rectal cancer in men, biliary tract system, pancreatic, postmenopausal breast among HRT non-users, endometrial, ovarian, and kidney cancer and multiple myeloma.
Dr. Lucie Turcotte[/caption]
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.
Dr. Murphy[/caption]
Maureen E. Murphy, Ph.D.
Professor and Program Leader, Molecular and Cellular Oncogenesis Program
Associate Vice President for Faculty Affairs
Associate Director for Education and Career Development
The Wistar Institute
Philadelphia, PA 19104
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Murphy group discovered a coding-region variant of the p53 tumor suppressor gene, called Pro47Ser, that exists in individuals of African descent. In previous studies this group reported that this amino acid change reduces the ability of p53 to function as a tumor suppressor.
In this study, African American women from two different large cohorts were assessed for the incidence of the Pro47Ser variant in pre-menopausal breast cancer. A modest but statistically significant association was found between Pro47Ser and pre-menopausal breast cancer.
Dr. Philip Haycock[/caption]
Philip C. Haycock, PhD
MRC Integrative Epidemiology Unit
University of Bristol
Bristol, England
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The direction and causal nature of the association of telomere length with risk of cancer and other diseases is uncertain. In a Mendelian randomization study of 83 non-communicable diseases, including 420,081 cases and 1,093,105 controls, we found that longer telomeres were associated with increased risk for several cancers but reduced risk for some other diseases, including cardiovascular diseases.
Associate Professor
Department of Physiology
Michigan State University
East Lansing, MI
MedicalResearch.com: What is the background for this study?
Response: Of the various types of breast cancer, triple negative breast cancer (lacking estrogen receptor, progesterone receptor and HER2) has the worst outcome and is largely limited to chemotherapy for treatment. Other types can be treated with personalized medicine, resulting in better outcome. For instance, a HER2+ve breast cancer can be treated with Herceptin, which targets HER2 itself. The fact that triple negative breast cancer lacks these sort of targeted treatments presents a clear need in breast cancer therapy.
The goal of this study was to bring together our computational work using large databases from breast cancer with research into therapeutic options. Essentially we wanted to ask if we could use patterns in what genes were being expressed to predict optimal therapy for triple negative breast cancer. 
Dr. N. Scott Litofsky,[/caption]
N. Scott Litofsky, M.D.
Chief of the Division of Neurological Surgery
University of Missouri School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Radiosurgery is being used more often for treatment of brain metastases to avoid potential side effects of whole-brain radiation, such as cognition and mobility impairment. After surgical resection of a brain metastases, some radiation treatment is generally needed to control brain disease. Few studies have directly compared efficacy of tumor control between surgery followed by whole-brain radiation and surgery followed by radiosurgery.
Our objective was to compare outcomes in two groups of patients – one whose brain metastasis was treated with surgery followed by whole-brain radiation and one whose surgery was followed by radiosurgery to the post-operative tumor bed.
We found that tumor control was similar for both groups, with survival actually better in the radiosurgery group. The complications of treatment were similar.
Dr. Neeraj Agarwal[/caption]
Neeraj Agarwal, MD
Associate Professor, Division of Oncology, Department of Medicine
University of Utah School of Medicine
MedicalResearch.com: What is the background for this study?
Response: Biomarkers predicting response to cancer therapy help guide physicians personalize medicine. Significant advances have been made in the development of therapeutic biomarkers in various malignancies, but not in prostate cancer. Dr. Nima Sharifi’s group at the Cleveland Clinic recently discovered that a germline inherited polymorphic variant (1245A→C) in the HSD3B1 gene correlates with shorter duration of response to androgen deprivation therapy (ADT) in hormone sensitive prostate cancer (HSPC). HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen.
The authors found that the variant allele of HSD3B1 led to decreased progression-free survival in a dose-dependent manner in post-prostatectomy biochemical recurrence and metastatic HSPC (mHSPC). These results needed external validation before application in the clinic. In our study, we sought to provide the first independent validation of these results in patients with mHSPC.
Dr. John Gore[/caption]
Dr. John L. Gore, MD
Associate Professor
Adjunct Associate Professor-Surgery
Department of Urology
University of Washington
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The rationale for our study derives from the uncertainty that both patients and clinicians confront when trying to make decisions about adjuvant therapy for prostate cancers found to have aggressive pathologic features at the time of radical prostatectomy. There is level 1 evidence in support of adjuvant radiation therapy in this setting, but several factors restrain providers from recommending adjuvant radiation. We found that interjecting a genomic test that predicts the risk of clinical metastases 5 years after surgery impacts the treatment recommended and helps men and clinicians feel more confident in the decision they are making or recommending.
Dr. Carlos Barcenas[/caption]
Carlos H. Barcenas M.D., M.Sc.
Assistant Professor
Department of Breast Medical Oncology
MD Anderson Cancer Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Over the last decade we have realized that we were over-treating many early stage breast cancer patients. In addition to the chemotherapy’s obvious side effects, there are also long term complications for breast cancer survivors. Since 2005, we are using a 21-gene-expression assay that predicts the risk of distant recurrence among early stage breast cancer patients. In 2015, initial results from the international clinical trial, TAILORx, found that women with hormone receptor positive, HER2 and lymph node negative early stage disease that had a low recurrence score (RS) of 0-10 from this assay could have chemotherapy omitted altogether. While these findings changed care for women with a low RS, questions remain regarding the management of women with an intermediate RS, defined by this trial as a RS of 11-25. For our retrospective, single-institution study we identified 1,424 stage I and II breast cancer patients with hormone receptor positive, HER2 and lymph node negative treated between 2005 and 2011 who underwent the 21-gene expression assay. The RS distribution was: 297 (21 percent) scored 0–10; 894 (63 percent) scored 11-25; and 233 (16 percent) scored >25.
Of those groups, 1.7, 15 and 73.4 percent received chemotherapy, respectively. With a median follow up of 58 months, those with a RS of 11-25 had an invasive disease-free survival (IDFS) rate at five years of 92.6 percent, regardless if patients received chemotherapy or not. Among those patients who did not receive chemotherapy, the estimated rates of IDFS and overall survival was 93 percent and 98 percent, respectively, which was comparable to those who did receive chemotherapy.
Margaret Rosenzweig[/caption]
Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN
Acute and Tertiary Care Department
University of Pittsburgh School of Nursing
MedicalResearch.com: What is the background for this study?
Response: A significant survival disparity still exists between African American and non-Hispanic white women diagnosed with breast cancer. There is evidence that symptom incidence, associated distress, and overall cancer-related distress may be unexplored, important contributing factors. The current study was a secondary, exploratory aim from the Attitudes, Communication, Treatment, and Support (ACTS) Intervention to Reduce Breast Cancer Treatment Disparity study, which is a randomized controlled trial of a psychoeducational intervention to encourage acceptance and adherence to chemotherapy compared with usual care for African American women with breast cancer. The purpose of the current study was to:
1) describe and compare the number of chemotherapy-related symptoms and associated distress among AA women with breast cancer over the course of chemotherapy at 3 time points (at baseline before initiating chemotherapy, midpoint, and at the completion of chemotherapy); and
2) to describe the relationship between the number of chemotherapy-related symptoms and overall cancer distress compared with the ability to receive at least 85% of the prescribed chemotherapy within the prescribed timeframe.
Dr. Rachel Wuerstlein[/caption]
Dr. med. Rachel Würstlein
Senior Specialist
Clinic and Polyclinic for Obstetrics and Gynecology
Klinikum der Ludwig-Maximilians-Universität München • Campus Innenstadt
Munich
MedicalResearch.com: What is the background for this study?
Response: Gene expression profiles provide important information on the risk of recurrence, and subtyping in HR+ HER2- early breast cancer, in addition to conventional clinicopathological factors. The PRIMe study was performed by the West German Study Group (WSG) and prospectively investigated the impact of the gene expression tests MammaPrint, a 70-Gene Breast Cancer Recurrence Assay, and the corresponding 80-Gene Molecular Subtyping Assay, BluePrint, on adjuvant chemotherapy decisions for early-stage breast cancer patients.
To do this, a risk assessment (chemotherapy followed by endocrine therapy, versus endocrine therapy alone) for distant metastasis was performed in 452 patients from 27 study centers using conventional clinicopathological factors such as tumour size and grade first, then compared to the results of the gene expression tests MammaPrint and BluePrint. Doctors and patients then reviewed the results and made a decision on the optimal treatment plan, namely in deciding whether or not patients would benefit from, and should therefore be treated with adjuvant chemotherapy.
Dr. Julie Nangia[/caption]
Julie Rani Nangia, M.D.
Assistant Professor
Breast Center - Clinic
Baylor College of Medicine
Houston, TX, US
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study was fueled by the feedback from women undergoing chemotherapy treatment for breast cancer. One of the most distressing side effects of their treatment is hair loss. It robs them of their anonymity and, for many, their femininity. Scalp cooling therapy has been available for a few years in the UK, but has faced obstacles in FDA clearance in the states. The makers of the scalp cooling device used in this study, Paxman Coolers Ltd., have a personal connection to breast cancer, as the company founder’s wife passed away from the disease.
This was the first randomized scalp cooling study, and it shows that the Paxman Hair Loss Prevention System is an effective therapy for reducing chemotherapy-induced alopecia. The results show a 50% increase in hair preservation of grade 0 or 1, meaning use of a scarf or wig is not necessary, in patients who received the scalp cooling therapy as opposed to those who did not.
Dr. Edwin Posadas[/caption]
Edwin Posadas, MD, FACP, KM
Director, Translational Oncology Program
Medical Director, Urologic Oncology Program
Samuel Oschin Comprehensive Cancer Institute
Clinical Chief, Division of Hematology/Oncology
Associate Professor, Department of Medicine
Cedars-Sinai
MedicalResearch.com: What is the background for this study? What are the main findings of your work so far?
Response: The technology we are using is called a NanoVelcro assay. This is a nanotechnology that can be used to isolate rare cells and cell-like particles in the blood stream. We have focused the use of the NanoVelcro on isolating circulating tumor cells (or CTCs). This technology is about 10 times more sensitive than that currently used in clinics. More importantly, because of some modification in our approach, we can now not only capture CTCs, but also examine them under the microscope and even analyze them using advanced molecular techniques. In this way, we take a classic and modern approach to our work.
We firmly believe that there is much to be learned by studying the shapes of these CTCs. We in the cancer field have long known that shape and cellular function are intimately related. In fact, a young pathologist in our group readily recognized that patients with the most aggressive cancers had CTCs with small nuclei, which we verified in a larger study. We are now exploring the importance of these shape variations in CTCs by coupling this classic microscopy-driven approach with RNA characterizations, giving us insight into the molecular nature of the CTC. My collaborator, UCLA Professor Hsian-Rong Tseng, PhD, is a brilliant engineer who has found ways of altering the system to allow us to capture and release live cells for analysis. By using this system, we believe that one day we may be able to avoid performing invasive tissue biopsies to study a cancer.