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Dr. Bastian[/caption]
MedicalResearch.com Interview with:
Boris C. Bastian, MD, PhD
Professor of Dermatology and Pathology
Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research
University of California, San Francisco
Medical Research: What is the background for this study? What are the main findings?
Dr. Bastian: The cost of DNA sequencing has dropped substantially since the initial sequencing of the human genome in 2001. As a result, the most common cancer subtypes have now been sequenced, revealing the pathogenic mutations that drive them. A typical cancer is driven by 5-10 mutations, but we still do not understand the order in which these mutations occur for most cancers.
Determining the order in which mutations occur is challenging for cancers that are detected at a late stage. Melanomas, however, lend themselves to this type of analysis because they are pigmented and found on the surface of the skin, allowing them to be identified early. Sometimes, melanomas are even found adjacent to their remnant precursor neoplasms, such as benign nevi (also known as common moles). We performed detailed genetic analyses of 37 cases of melanomas that were adjacent to their intact precursor neoplasms. We microdissected and sequenced the surrounding uninvolved normal tissue, the precursor neoplasm, and the descendent neoplasm. By comparing the genetic abnormalities in each of the microdissected areas, we were able to decipher the order of genetic alterations for each case.
Our work reveals the stereotypic pattern of mutations as they occur in melanoma. Mutations in the MAPK pathway, usually affecting BRAF or NRAS, occur earliest, followed by TERT promoter mutations, then CDKN2Aalterations, and finally TP53 and PTEN alterations. Benign nevi typically harbor a single pathogenic alteration, whereas fully evolved melanomas harbor three or more pathogenic alterations. We also identified an intermediate stage of neoplasia with some but not all of the pathogenic mutations required for fully evolved melanoma. There has been a longstanding debate whether morphologically intermediate lesions, such as dysplastic nevi, truly constitute biological intermediates or whether they simply represent a gray zone of histopathological assessment. Our data indicates that these neoplasms are genuine biological entities. Finally, we observe evidence of UV-radiation-induced DNA damage at all stages of pathogenesis, implicating UV radiation in both the initiation and progression of melanoma.
Prof. Stephen W. Duffy[/caption]
MedicalResearch.com Interview with:
Prof Stephen Duffy BSc MSc CStat
Professor Of Cancer Screening
Wolfson Institute Of Preventive Medicine
Queen Mary University of London
Medical Research: What is the background for this study? What are the main findings?
Prof. Duffy: There is debate on the value of diagnosing and treating ductal carcinoma in situ (DCIS) of the breast, depending mainly on different theories about the risk of progression to invasive breast cancer if DCIS were untreated. No-one asserts that no DCIS is progressive and no-one asserts that all DCIS is progressive. There is, however, a range of opinions on the proportion of progressive disease.
We found that those mammography screening units in the UK with higher detection rates of DCIS had lower subsequent rates of invasive cancers in the three years after screening.
Dr. Boiselle[/caption]
MedicalResearch.com Interview with:
Phillip Boiselle, M.D.
Staff, Cardiothoracic Imaging
Beth Israel Deaconess Medical Center
Associate Dean for Academic and Clinical Affairs
Professor of Radiology, Harvard Medical School
Boston, Mass
Medical Research: What is the background for this study? What are the main findings?
Dr. Boiselle: Previous studies have shown that women have a greater mortality benefit from lung cancer screening then men, and that this test (CT screening) is more cost-effective for women than men. Our purpose was to determine whether the relative risk of lung cancer for women and men differed depending on the specific type of lung nodule that was discovered at screening. Such differences could potentially help to influence a more personalized approach to patient management in lung cancer screening.
Dr. Haque[/caption]
MedicalResearch.com Interview with:
Reina Haque, PhD, MPH
Research scientist
Department of Research & Evaluation
Kaiser Permanente Southern California
Pasadena Calif
Medical Research: What is the background for this study? What are the main findings?
Dr. Haque: Tamoxifen is a commonly prescribed generic drug taken by women with breast cancer to reduce their chances of developing a recurrence. Tamoxifen is recommended for five years, but has notable side effects, including hot flashes, night sweats and depression. Since hormone replacement therapy is not recommended to alleviate these symptoms in breast-cancer survivors, antidepressants have been increasingly prescribed for relief. Almost half of the 2.4 million breast-cancer survivors in the U.S. take antidepressants.
However, previous studies have suggested that antidepressants reduce tamoxifen's effectiveness in lowering subsequent breast-cancer risk. This study was conducted to determine whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer.
Dr. Hamanishi[/caption]
MedicalResearch.com Interview with:
Junzo Hamanishi M.D., Ph.D.
Department of Gynecology and Obstetrics,
Kyoto University Graduate School of Medicine
Assistant Professor
Kyoto Japan
Medical Research: What is the background for this study?
Dr. Hamanishi: More than 70% of patients with advanced ovarian cancer who achieve remission ultimately relapse and there are few effective treatments for these patients. Because the development of new treatment strategies for these patients is urgently required, we have focused on and studied the potential of cancer cells to escape from host immunity with PD-1/PD-L1 immunosuppressive signal in the tumor microenvironment to find new treatment strategies to overcome this phenomenon, 
Dr. Wang[/caption]
MedicalResearch.com Interview with:
Shiyi Wang, MD, PhD
Assistant Professor of Epidemiology (Chronic Diseases)
Yale School of Public Health
Medical Research: What is the background for this study?
Dr. Wang: As magnetic resonance imaging (MRI) of the breast has become part of medical care, there is increasing concern that this highly sensitive test might identify health problems that otherwise would not have had an impact on the patient – so called “overdiagnosis”. However, even if MRI use leads to overdiagnosis, the main “theoretical” benefit of early detection by MRI is to prevent future advanced diseases, the prognosis of which is deleterious. A systematic literature review found that, compared to mammography and/or ultrasound, MRI had a 4.1% incremental contralateral breast cancer (breast cancer in the opposite breast) detection rate. At this point, the impact of MRI on long-term contralateral breast cancer outcomes remains unclear.
Medical Research: What are the main findings?
Dr. Wang: Analyzing the Surveillance, Epidemiology, and End Results-Medicare dataset, we compared two groups of women who had breast cancer (one group receiving an MRI, and the other not) in terms of stage-specific contralateral breast cancer occurrences. We found that after five years, the MRI group had a higher detection rate of cancer in the opposite breast than the non-MRI group (7.2 % vs. 4.0%). Specifically, MRI use approximately doubles the detection rate of early stage contralateral breast cancer, but does not decrease the incidence of advanced stage contralateral breast cancer occurrences after a 5-year follow-up. Our results indicate that nearly half of additional breast cancers detected by the preoperative MRI were overdiagnosed, which means that many of these occult cancers not detected by MRI would not have become clinically evident over the subsequent 5 years. There was no evidence that MRI use was benefiting women because the rate of advanced cancer was similar in the MRI and the non-MRI groups.
Dr. Movsas[/caption]
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 
Prof. Nicolas James[/caption]
MedicalResearch.com Interview with:
Prof Nicholas James
STAMPEDE Trial Chief Investigator
Director of the Cancer Research Centre
Warwick Medical School
University of Warwick Coventry and
Professor of Clinical Oncology
Cancer Centre, Queen Elizabeth Hospital
Birmingham
Medical Research: What is the background for this study? What are the main findings?
Dr. James: The STAMPEDE trial is a multi-arm, multi-stage trials platform testing a range of different therapies in addition to standard of care (SOC) for men commencing long term androgen deprivation therapy (ADT) for newly diagnosed locally advanced or metastatic prostate cancer. These data from the control arm form part of a pair of publications detailing outcomes in the control arm of STAMPEDE and help to make sense of the forthcoming paper on the randomised comparisons currently in press at the Lancet.
Dr. Yao[/caption]
MedicalResearch.com Interview with:
Katharine Yao, MD
Director, Breast Surgical Program
NorthShore University HealthSystem
Illinois
Medical Research: What is the background for this study? What are the main findings?
Dr. Yao: A survey of breast surgeons was conducted to determine their knowledge level with contralateral breast cancer and how contralateral prophylactic mastectomy (CPM) affects survival. Of five knowledge questions, only 60% scored with high knowledge (4 or 5 questions correct) scores. Surgeons mostly scored low on contralateral cancer risks. Most surgeons correctly stated that 
Dr. Han[/caption]
MedicalResearch.com Interview with:
Xuesong Han, PhD
Director, Surveillance and Health Services Research
American Cancer Society, Inc.
Atlanta, GA 3030
Medical Research: What is the background for this study? What are the main findings?
Dr. Han: People with private insurance are more likely to be screened and more likely to be diagnosed at an early stage of cancer. An early provision of the Affordable Care Act implemented in September 2010 allows young adults to remain on their parents’ health insurance plan until age 26 years, following which there has been an increase in private insurance coverage among young adults aged 19-25 years. For young adults, the uterine cervix is the only cancer site for which screening is recommended with a starting age of 21 years, and diagnosis of cervical cancer at early stages allows use of fertility-sparing treatment.
Using data before and after the dependent coverage expansion provision of ACA, we found that compared with 26-34 year-olds who were not affected by the policy change, women 21-25 years of age experienced a net increase of 9 percentage points in early stage disease and 11.9 percentage points in receipt of fertility-sparing treatment.
Dr. Newton[/caption]
MedicalResearch.com Interview with:
Paul K Newton PhD
Professor of Aerospace & Mechanical Engineering, Mathematics, and Norris Comprehensive Cancer Center
USC Viterbi
University of Southern California
University Park Campus
Los Angeles, CA 90089-4012
Medical Research: What is the background for this study? What are the main findings?
Dr. Newton: We obtained a longitudinal data set of 446 breast cancer patients from Memorial Sloan Kettering Cancer Center, tracked from 1975 to 2009.
All of the patients had primary breast cancer at the time they entered, with no metastatic tumors. All subsequently developed metastatic breast cancer.
From this time-resolved data set, we first developed what we called tree-ring diagrams showing the full spatiotemporal patterns of progression. We then used this information
to develop a Markov chain dynamical model of metastatic breast cancer. This is a model based on the concept that where the disease currently is located strongly influences where it will spread next.
The systemic nature of metastatic breast cancer is clearly shown in these kinds of network based models.
The main findings are that survival depends very strongly on where the first metastatic tumor develops. For example, if the first metastatic tumor appears in the bone, as happens in roughly 35% of the patients, survival is much better than if it appears in the brain (less than 5% of the patients). Furthermore, for those patients with a first met to the bone, survival is far better for those who develop their next met in the lung area, as compared with those that develop it in the liver.
Metastatic sites are categorized as `spreader’ sites, or `sponge’ sites. Bone and chest wall are generally the primary spreader sites of metastatic breast cancer, dynamically involved in spreading the disease throughout the metastatic process. On the other hand, liver seems to be a key sponge site, where circulating tumor cells most likely accumulate. If one were to focus on an active therapeutic program targeting metastatic sites, most likely the spreader sites would give the most bang-for-buck in terms of survival.
Dr. Orian-Rousseau[/caption]
MedicalResearch.com Interview with:
Prof. Dr. Véronique Orian-Rousseau
Group Leader
Karlsruher Institut für Technologie (KIT)
Institut für Toxikologie und Genetik (ITG)
Campus Nord
Karlsruhe Germany
Medical Research: What is the background for this study? What are the main findings?
Response: Our group is working on the role of cell adhesion molecules in development and in tumor progression and metastasis. One protein in focus is CD44, a molecule that controls proliferation, differentiation and survival of cells. We have shown that one member of this family, namely CD44v6 acts as a co-receptor for receptor tyrosine kinases (RTKs) such as MET and VEGFR-2. CD44v6 has a dual function. It controls both the activation and signaling from the RTKs. We have identified a sequence in CD44v6 that is crucial for its function as a co-receptor. From this sequence we made a peptide that inhibits MET and VEGFR2 activation and signaling.
The CD44v6 peptide was used in several independent mouse models of pancreatic cancer including the transgenic PDAC mouse model. It could inhibit the growth of the primary tumor, metastasis and in addition could eliminate already established metastases.
In addition, we could show that MET and CD44v6 expression correlates with poor prognosis and metastasis in a cohort of pancreatic cancer patients.
Dr. Oktay[/caption]
MedicalResearch.com Interview with:
Kutluk Oktay, MD, PhD.
Professor of Obstetrics & Gynecology, Medicine, and Cell Biology & Anatomy
Director, Division of Reproductive Medicine & Institute for Fertility Preservation
Innovation Institute for Fertility and In Vitro Fertilization
New York Medical College, Valhalla, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Oktay: Cancer treatments cause infertility and early menopause in a growing number of young women around the world and US. One of the strategies to preserve fertility, which was developed by our team, is to cryopreserve ovarian tissue before chemotherapy and later transplant it back to the patient when they are cured of the cancer and ready to have children. However, success of ovarian transplantation has been limited due to limitation in blood flow to grafts. In this study we described a new approach which seems to improve graft function. The utility of an extracellular tissue matrix and robotic surgery seems to enhance graft function. With this approach both patients conceived with frozen embryos to spare and one has already delivered.
Dr. Jason Gold[/caption]
MedicalResearch.com Interview with:
Jason S. Gold MD FACS
Chief of Surgical Oncology, VA Boston Healthcare System
Assistant Professor of Surgery, Harvard Medical School
Brigham and Women’s Hospital
Medical Research: What is the background for this study?
Dr. Gold: Pancreas cancer is a lethal disease. While advances in the best available care for pancreas cancer are desperately needed, improvements can be made in addressing disparities in care. This study aimed to evaluate associations of social and demographic variables with the utilization of surgical resection as well as with survival after surgical resection for early-stage pancreas cancer.
Medical Research: What are the main findings?
Dr. Gold: The main findings are the following:
1: We found that less than half of patients with early-stage pancreas cancer undergo resection in the United States. Interestingly, the rate of resection has not changed with time during the eight-year study period.
2. We also found significant disparities associated with the utilization of surgical resection for early-stage pancreas cancer in the United States. African American patients, Hispanic patients, single patients, and uninsured patients were significantly less likely to have their tumors removed. There were regional variations in the utilization of surgical resection as well. Patients in the Southeast were significantly less likely to have a pancreas resection for cancer compared to patients in the Northeast.
3. Among the patients who underwent surgical resection for early-stage pancreas cancer, we did not see significant independent associations with survival for most of the social and demographic variables analyzed. Surprisingly, however, patients from the Southeast had worse long-term survival after pancreas cancer resection compared to those in other regions of the United States even after adjusting for other variables.
Dr. Weir[/caption]
MedicalResearch.com Interview with:
Hannah K. Weir, PhD, MSc
Senior Epidemiologist
CDC
Medical Research: What is the background for this study? What are the main findings?
Dr. Weir: Colorectal cancer (CRC) is one of the leading causes of cancer related deaths in the United States.
We know that the risk of dying from colorectal cancer is not the same across all communities – people living in poorer communities have a higher risk of dying from 
Dr. McDonald[/caption]
MedicalResearch.com Interview with:
Professor John McDonald PhD
Director of its Integrated Cancer Research Center
School of Biology at the Georgia Institute of Technology
Medical Research: What is the background for this study? What are the main findings?
Response: Ovarian cancer is a deadly disease because it cannot be diagnosed at early stages when it can be most effectively effectively treated.
It has long been recognized that there is a great need for an accurate diagnostic test for early stage ovarian cancer.
Until now, efforts to develop a highly accurate way to detect early stage ovarian cancer have been unsuccessful.
We have used a novel approach that integrates advanced methods in analytical chemistry with advanced machine learning algorithms to identify 16 metabolites that collectively can detect ovarian cancer with extremely high accuracy (100% in the samples tested in our study)
Dr. Klempner[/caption]
MedicalResearch.com Interview with:
Samuel Klempner, M.D. Assistant Professor
Division of Hematology/Oncology
UC Irvine Health
Orange, CA 92868
Medical Research: What is the background for this study? What are the main findings?
Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options. This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types. Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an 
Dr. Qin[/caption]
MedicalResearch.com Interview with:
Bo (Bonnie) Qin, PhD
Postdoctoral associate at Rutgers Cancer Institute of New Jersey
Medical Research: What is the background for this study? What are the main findings?
Response: Ovarian cancer is among the top five causes of cancer death among women in the US. Compared to white women, African-American women tend to have a worse 5-year survival rate of ovarian cancer. It highlights a critical need for identifying preventive factors in African Americans, particularly through dietary modification, which is relatively low cost and low risk compared to medical treatments.
We found that adherence to an overall healthy dietary pattern i.e. Alternate Healthy Eating Index (AHEI)-2010 may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal women. Adherence to the current Dietary Guidelines for Americans i.e. Healthy Eating Index-2010, were also strongly associated with reduced risk of ovarian cancer among postmenopausal African-American women.
Dr. Shah[/caption]
MedicalResearch.com Interview with:
Dr. Jatin J. Shah, MD
Associate Professor, Department of Lymphoma/Myeloma
Assistant Professor, Lymphoma/Myeloma
Division of Cancer Medicine
The University of Texas, MD Anderson Cancer Center
Houston, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells.
The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma.
Dr. Lei Xu[/caption]
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.
MedicalResearch.com Interview with:
Dr. Priscilla Kaliopi Brastianos MD
Instructor, Medicine, Harvard Medical School
Assistant Physician in Medicine
Hematology/Oncology, Massachusetts General Hospital
Medical Research: What is the background for this study? What are the main findings?
Response: Craniopharyngiomas are rare brain tumors that can cause serious problems because of their location near critical structures in the brain, such as optic and other cranial nerves, the pituitary gland and the hypothalamus. Not only does the growing tumor compromise neurological and hormonal functions by impinging on these structures, but treatment by surgical removal or radiation therapy can produce the same symptoms by damaging adjacent tissues. In addition, since the tumor adheres to these nearby critical structures, complete removal is difficult, which can lead rapid recurrence. Medical therapies have not been effective for craniopharyngiomas, namely because we did not understand the molecular underpinnings of these tumors. Last year, we performed genomic characterization of craniopharyngiomas, with the goal to identify potential therapeutic targets. We were surprised to find that nearly all papillary craniopharyngiomas have BRAF mutations, which are the same mutations that have been found in