Malignancies More Common In Men With BRCA Germline Mutations

MedicalResearch.com Interview with:
Roy Mano, MD and
David Margel, MD, PhD
Department of Urology, Rabin Medical Center
Petach Tikva, Israel

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

Response: According to previous reports, male BRCA mutation carriers have a higher risk of developing malignancies of the prostate, pancreas, breast, colon and melanoma. While malignancy screening protocols for female BRCA carriers are well established and widely implemented, little is known about the optimal screening protocol for male BRCA carriers, and current screening protocols focus on malignancies of the breast and prostate rather than offer a comprehensive screening protocol for all BRCA associated malignancies.

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CLL: Long-term efficacy of ONO/GS-4059 is maintained without emergence of new toxicities

MedicalResearch.com Interview with:

Martin J.S. Dyer, D.Phil MA FRCP FRCPath Ernest and Helen Scott Haematological Research Institute University of Leicester, UK

Prof. Dyer

Martin J.S. Dyer, D.Phil MA FRCP FRCPath
Ernest and Helen Scott Haematological Research Institute
University of Leicester, UK

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

Response: This study follows on from a world-first clinical trial of a new drug to treat particular blood cancers. Results of that international clinical trial were published in the journal Blood in November 2015 and looked at the efficacy of a new inhibitor, ONO/GS-4059, in the treatment of CLL and Non-Hodgkin Lymphoma patients, refractory or resistant to current chemotherapies.

ONO/GS-4059 targets BTK, a protein essential for the survival and proliferation of the tumour cells.

The study opened in January 2012 and 90 patients were enrolled in different centres in the UK and in France, with 28 coming from Leicester. Patients with CLL showed the best response and most of them were still on the study after 3 years, and remarkably without notable toxicities.

In the new paper, we are reporting the long-term follow-up results. This work, published in the journal Blood, was funded by the Ernest and Helen Scott Haematological Research Institute, ONO Pharmaceuticals, Gilead Pharmaceuticals and the Cancer Research UK Leicester Experimental Cancer Medicine Centre. Local charity Hope Against Cancer fund the Clinical Trials Facility based at the Leicester Royal Infirmary.

This current paper describes the long term follow up and shows that in patients with CLL the remissions are durable and associated with no new toxicities. Furthermore, in collaboration with Sistemas Genomicos, a company in Valencia, we have shown that mutations associated with aggressive disease respond well to treatment with ONO/GS-4059.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy

MedicalResearch.com Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School

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

Response:
Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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New Breast Cancer Genes May Identify Women Who Can Benefit From Enhanced Screening

MedicalResearch.com Interview with:

Fergus J. Couch, Ph.D. Zbigniew and Anna M. Scheller Professor of Medical Research Chair, Division of Experimental Pathology Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, MN 55905

Dr. Couch

Fergus J. Couch, Ph.D.
Zbigniew and Anna M. Scheller Professor  of Medical Research
Chair, Division of Experimental Pathology
Department of Laboratory Medicine  and Pathology
Mayo Clinic
Rochester, MN

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

Response: The main finding is that RAD51D, BARD1, and MSH6 can now be included in the list of moderate risk breast cancer genes. In contrast, other genes such as MRE11A and RAD50 do not increase risk of breast cancer. In addition, we provide initial estimates of the level of breast cancer risk associated with mutations in the genes that cause breast cancer. The “new” breast cancer genes may now be useful for identifying women who can benefit from enhanced screening. These new data will need to be considered by the National Comprehensive Cancer Network (NCCN) which provides guidelines for clinical management of individuals with mutations in cancer predisposition genes. These results will also be useful for identifying members of families who are at increased risk of breast cancer.

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Sleep Difficulties Linked to Survival Among Women With Breast Cancer

MedicalResearch.com Interview with:

Claudia Trudel-Fitzgerald Ph.D. FRQS Postdoctoral research fellow & Clinical psychologist (OPQ) Department of Social and Behavioral Sciences Harvard T.H. Chan School of Public Health Boston, MA 02115

Dr. Trudel-Fitzgerald

Claudia Trudel-Fitzgerald Ph.D. 
FRQS Postdoctoral research fellow & Clinical psychologist (OPQ)
Department of Social and Behavioral Sciences
Harvard T.H. Chan School of Public Health
Boston, MA 02115

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

Response: There is very limited research on the association between sleep characteristics and survival among individuals with cancer. However, this is an important question, especially among breast cancer patients because sleep disturbances are frequently reported by these women. Preliminary studies have suggested that sleep duration is related to mortality. The novel findings of our research indicate that not only sleep duration, but also changes in sleep duration before versus after diagnosis, as well as regular difficulties to fall or stay asleep, may also be associated with mortality among women with breast cancer over a period of up to 30 years.

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Suicide Risk Increased in Cancer Patients

MedicalResearch.com Interview with:

Raffaella Calati, Psy.D., Ph.D. University of Montpellier INSERM U 1061: Neuropsychiatry: Epidemiological and Clinical Research Department of Emergency Psychiatry and Post Acute Care Lapeyronie Hospital, Centre Hospitalier Universitaire Montpellier, France

Dr. Calati

Raffaella Calati, Psy.D., Ph.D.
University of Montpellier
INSERM U 1061: Neuropsychiatry: Epidemiological and Clinical Research
Department of Emergency Psychiatry and Post Acute Care
Lapeyronie Hospital, Centre Hospitalier Universitaire
Montpellier, France

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

Response: A number of previous original studies investigated suicidal thoughts and behaviours in cancer patients, finding them to be higher than those in the general population. However, to our knowledge, we performed the first meta-analysis on this link, pooling all the published data to calculate the size of this increased risk.

Our main finding is an increased suicide risk in patients with cancer compared to individuals without it.

It should be underlined that the analyses presented are the first stage in our work, since at the moment we are analyzing a higher number of studies and we are planning to control for confounders, not considered in our first analyses. This means that the exact strength of this association will be more precisely known.

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Newly Recognized Connection Between Immune System and Sperm Opens Window to Some Male Infertility and Cancer Vaccine Failures

MedicalResearch.com Interview with:
Kenneth S. K. Tung, M.D.
Professor of Pathology and Microbiology
Director of UVA Research Histology Core
Beirne B. Carter Center for Immunology Research
University of Virginia

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

Response: The immune system needs to see tissue antigens to avoid responding to them in order to prevent autoimmune disease development. The current dogma, stated in all Immunology and Reproductive Biology textbooks, considers the sperm antigens in the testis to be exempted from this process. They are considered totally hidden behind a tissue barrier, and are invisible to the immune system.

Because sperm antigens are treated as foreign molecules, they should stimulate strong immune response when employed in cancer vaccines against antigens common to sperm and cancers. It is also believed that sperm molecules are protected by local factors that inhibit inflammation, whereas systemic mechanisms such as regulatory T cells would not exist.

The paradigm has restrained ongoing research on systemic tolerance to sperm, and the need to understanding systemic regulation in infertility research

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Based on Genetic Profile, Longer Adjuvant Treatment Recommended for Some GIST Tumors

MedicalResearch.com Interview with:
Heikki Joensuu, MD

Department of Oncology
Helsinki University Hospital
University of Helsinki
Helsinki, Finland 

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

Response: The randomized Scandinavian Sarcoma Group (SSG) XVIII trial compared three years of adjuvant imatinib to one year of adjuvant imatinib as adjuvant treatments of patients who had undergone macroscopically complete surgery for a GIST with a high risk for tumor recurrence. In this trial, patients treated with 3 years of imatinib had improved overall survival as compared to those who were allocated to one year of adjuvant imatinib. In 2 other randomized trials that compared either 1 year of adjuvant imatinib to one year or placebo, or 2 years of adjuvant imatinib to observation, no improvement in overall survival was found, although in all three trials adjuvant imatinib improved recurrence-free survival (RFS). The reasons for the discrepant findings with respect of overall survival in the 3 trials have been unclear.

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Racial Disparities in Genetic Testing of Women With Breast Cancer

MedicalResearch.com Interview with:

Cary P. Gross, MD Section of General Internal Medicine Yale University School of Medicine New Haven, CT

Dr. Cary Gross

Cary P. Gross, MD
Section of General Internal Medicine
Yale University School of Medicine
New Haven, CT

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

Response: Prior work has demonstrated racial and socioeconomic disparities in breast cancer diagnosis, treatment, and outcomes.  As the oncology field has progressed over the past decade, the use of genetic testing to guide treatment decisions is one of the most exciting new developments.

Our team was concerned that these new gene tests, which can offer important benefits, may have the potential to exacerbate disparities further.  That is, if there is unequal access to gene testing among patients for whom it is recommended, then our progress against cancer will not be equitably shared among people of all races and ethnicities.

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Gene “Decorations” Can Serve as Blood Biomarkers To Detect Cancer

MedicalResearch.com Interview with:

Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412

Dr. Kun Zhang

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.

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11 Cancer Types Have Strong Connection to Obesity

MedicalResearch.com Interview with:

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

Dr. Kyrgiou

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 decadesExcess 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.

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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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