MedicalResearch.com Interview with: Dr. H. Jaap Bonjer, PhD, FRCSC Professor of Surgery Chair Department of Surgery VU University Medical Center Amsterdam Amsterdam Medical Research: What is...
MedicalResearch.com Interview with:
Maria L. Wei, M.D., Ph.D.
Associate Professor of Dermatology
Director, Melanoma Surveillance Clinic
Multidisciplinary Melanoma Program
University of California, San Francisco
Staff Physician
Veterans Affairs Medical Center, San Francisco
Medical Research: What is the background for this study?
Dr. Wei: Effective physician-patient communication is essential for optimal medical care. There are now many methods available to notify patients of their biopsy results: a clinic visit (the method traditionally preferred by patients), a telephone call, secure online patient portals to access medical charts, email and texts. In addition, there is variability from state to state in the guidelines regulating the release of biopsy results online. Until recently, some states did not allow the on-line release of biopsy results. There have been few systematic studies on patient preferences for communication of biopsy results. (more…)
MedicalResearch.com Interview with:
Prof Xi-Chun Hu, Department of Oncology
Shanghai Medical College
Fudan University, Shanghai 200032, China
MedicalResearch: What is the background for this study? What are the main findings?
Prof. Hu: Triple-negative breast cancer (TNBC) is associated with higher rates of recurrence, shorter disease free survival, and poorer overall survival. Molecular targeting agents tried against Triple-negative breast cancer have nearly all failed. TNBC, concordant with BRCA-associated and basal-like breast cancer, has abnormal DNA repair and genome-wide instability, supporting the use of DNA-damaging agents such as platinum. However, platinum monotherapy is not very potent, combination with other agents, such as gemcitabine has a synergistic effect.
The GP regimen could be an alternative or even preferential first-line doublet chemotherapy strategy for patients with mTNBC.
(more…)[caption id="attachment_13080" align="alignleft" width="199"] CDC Image: Cardiorespiratory Fitness[/caption] MedicalResearch.com Interview with: Susan G. Lakoski, M.D. Assistant Professor of Medicine, Hematology/Oncology DivisionDepartment of Medicine...
MedicalResearch.com Interview with:
Susan Swetter, MD
Professor of Dermatology and Director, Pigmented Lesion and Melanoma Program
Stanford University Medical Center and Cancer Institute.
Medical Research: What is the background for this study?
Dr. Swetter: This retrospective cohort study sought to explore the role of the topical immunomodular - imiquimod 5% cream - as both primary and adjuvant therapy (following optimal surgery) for patients with the lentigo maligna subtype of melanoma in situ. Assessment of alternative treatments to surgery for this melanoma in situ subtype are warranted given the increasing incidence of lentigo maligna in older, fair-complexioned individuals in the United States. Surgical management of lentigo maligna is complicated by its location on cosmetically sensitive areas such as the face, histologic differentiation between lentigo maligna and actinic melanocytic hyperplasia in chronically sun-damaged skin, and potential surgical complications in the elderly who may have medical co-morbid conditions.
Medical Research: What are the main findings?
Dr. Swetter: We conducted a retrospective review of 63 cases of lentigo maligna in 61 patients (mean age 71.1 years) who used topical 5% imiquimod cream instead of surgery (22 of 63 cases, 34.9%) or as an adjuvant therapy following attempted complete excision (63 cases, 65.1%), in which no clinical residual tumor was present but the histologic margins were transected or deemed narrowly excised. Our study showed overall clinical clearance of 86.2% in the 58 patients analyzed for local recurrence at a mean of 42.1 months of follow-up (standard deviation 27.4 months), with primarily treated cases demonstrating 72.7% clearance at a mean of 39.7 months (standard deviation 23.9 months), and adjuvant cases showing 94.4% clearance at a mean of 39.7 months (standard deviation 23.9 months). We found a statistically significant association between imiquimod-induced inflammation and clinical or histologic clearance in primary but not adjuvant cases, although this latter finding may be explained by a lack of residual atypical melanocytes or true LM in the adjuvant setting, in which wide local excision had already been performed.
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MedicalResearch.com Interview with:
Michael H. Antoni, Ph.D.
Professor of Psychology and Psychiatry and Behavioral Sciences
Director, Center for Psycho-oncology Research
Program co-Leader, Cancer Prevention Control and Survivorship
Sylvester Cancer Center Sylvester Professor, Director Miami CTSI Pilot and Translational Studies Component University of Miami
Medical Research: What is the background for this study? What are the main findings?
Dr. Antoni: We have been conducting stress management intervention trials with breast cancer patients for the past two decades. We have shown that the form of stress management we developed, a 10-week cognitive behavioral stress management (CBSM) intervention, combining relaxation techniques, cognitive behavioral therapy techniques and coping and interpersonal skills training (assertiveness and anger management) delivered in a supportive group, can improve how women adapt during breast cancer treatment and up to one year later. These improvements in psychological status (less depressive symptoms, less negative mood and more positive mood) are associated with reductions in circulating serum cortisol levels, improved immune function and decreased inflammatory signaling over the first year of treatment. Since depressive symptoms are prevalent during cancer treatment our prior work showing that cognitive behavioral stress management reduces depressive symptoms over the 1st yr of treatment is significant . Since persisting depressive symptoms into survivorship are also common these new findings that women receiving cognitive behavioral stress management during primary treatment show beneficial effects out to 15 yrs suggests a real impact on their quality of life well into survivorship.
Further, since data just released this week at the American Psychosomatic Society meeting in Savannah, GA shows that depressive symptoms during breast cancer treatment predict greater odds of mortality over the next 8-15 yrs it is plausible that these cognitive behavioral stress management effects on reduced long-term depressive symptoms may have implications for survival. Finally since depressive symptoms relate to greater signs of inflammation in breast cancer patients and because inflammation promotes cancer disease progression via effects on angiogenesis, invasion and metastasis, then managing depressive symptoms during and after active treatment for breast cancer could have effects on health outcomes via lower inflammation.
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MedicalResearch.com Interview with:
Russel E. Kaufman, MD President Emeritus
Professor, Molecular and Cellular Oncogenesis Program
Molecular and Cellular Oncogenesis Program
The Wistar Institute
Medical Research: What is the background for this study? What are the main findings?
Response: Targeted therapies in cancer were hailed as a “magic bullet” because of their ability to act upon the mutations responsible for cancer while leaving nearby healthy cells alone. Using an approach like this, it would make sense that therapies designed to target mutations of BRAFV600E/K could be effective for melanoma, since that gene is mutated in about half of all cases of the disease.
However, we’ve learned over time that these targeted therapies simply aren’t as effective as we had hoped they would be. In the case of these BRAF inhibitors, while patients do live slightly longer, they eventually relapse within months of treatment. We wanted to know why this was happening.
We decided to look at macrophages, which are the most abundant inflammatory cells in melanoma. The more macrophages present in a patient with melanoma, the worse his or her outcome will be. They’ve been linked to cancer progression, but before this study, no one had really looked at the role they may play in the resistance to treatment with BRAF inhibitors.
We found that BRAF inhibitors activate the mitogen-activated protein kinase (MAPK) pathway in macrophages. When this pathway is activated, it leads to the production of vascular endothelial growth factor (VEGF), a signaling protein closely associated with angiogenesis. The VEGF produced in the macrophages is able to activate the MAPK pathway in melanoma cells, thereby stimulating the growth of cancer cells.
Taking these findings one step further, we discovered that when we blocked the MAPK pathway or VEGF signaling, we appeared to reverse macrophage-mediated resistance. When we targeted macrophages, we were able to increase the antitumor activity of BRAF inhibitors in mouse and human models.
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MedicalResearch.com Interview with:
Joann G. Elmore M.D., M.P.H.
Professor of Medicine,
Adjunct Professor of Epidemiology,
University of Washington School of Medicine
Harborview Medical Center
Seattle, WA 98104-2499
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Elmore: It is estimated that 1.6 million women in the United States each year undergo a breast biopsy. By interpreting these biopsies under the microscope, pathologists provide diagnoses on a spectrum from benign, to atypia, to ductal carcinoma in situ (DCIS), to invasive cancer. Using these diagnostic classifications, clinical doctors work with their patients to decide if they are at increased risk of developing breast cancer in the future, which can lead to additional surveillance, or how to treat them when the diagnosis is invasive breast cancer. As misclassification of breast lesions by pathologists may contribute to overtreatment and undertreatment of breast disease, we decided to study the accuracy of breast pathology diagnoses in the U.S.
In the Breast Pathology (B-Path) Study, we used a set of 240 breast biopsy cases to evaluate the interpretive accuracy of 115 U.S. pathologists who were actively interpreting breast biopsies in their clinical practices. Their diagnoses were compared with reference diagnoses established by a consensus panel of experienced breast pathologists. When the panel members each independently diagnosed the slides pre-consensus, they agreed unanimously on 75 percent of their diagnoses; ninety percent of the panel members’ initial independent diagnoses agreed with the final consensus-derived reference diagnoses.
When comparing participating pathologists’ diagnoses to the reference diagnoses, we found overall agreement for 75 percent of interpretations. The concordance rate for invasive breast cancer was reassuringly high at 96 percent, and fairly high for benign findings without atypia at 87 percent. However, concordance was lower for atypia at 48 percent and for DCIS at 84 percent. This means that nearly one out of five pathologists disagreed on the diagnosis of DCIS. We found disagreement with the reference diagnosis to be statistically more frequent when pathologists had lower weekly case volumes or worked in smaller labs. Disagreement was also statistically significantly more likely when the patient had dense breast tissue on mammogram; however, the absolute difference was small. Our accuracy findings were not altered when we used different methods of defining the reference diagnosis.
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MedicalResearch.com Interview with:
Matthew B. Yurgelun, MD
Instructor in Medicine
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Yurgelun: Germline mutations in the TP53 gene are linked to Li-Fraumeni syndrome, which is an inherited syndrome associated with a 73-100% lifetime risk of cancer. Classically, cancers linked to Li-Fraumeni syndrome include early-onset breast cancer, leukemias, soft tissue sarcomas, brain cancer, and adrenocortical cancer, although recent data have shown an increased risk of colorectal cancer as well. Our study’s primary aim was to determine the frequency of germline TP53 mutations in patients with early-onset colorectal cancer.
We studied 457 patients from the multinational Colon Cancer Family Registry who were diagnosed with colorectal cancer at age 40 or younger, and found that 1.3% carried a germline alteration in the TP53 gene. None of these individuals had personal or family histories of cancer that fulfilled clinical criteria for Li-Fraumeni syndrome. (more…)MedicalResearch.com Interview with: James Scheiman, M.D. Professor of Gastroenterology University of Michigan Medical School Medical Research: What is the background for this study? What...
MedicalResearch.com Interview with:
Carla M. Pugh, M.D., Ph.D. FACS
Associate Professor, Vice Chair, Education and Patient Safety
Clinical Director, UW Health Clinical Simulation Program
Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI
Medical Research: What is the background for this study? What are the main findings?
Dr. Pugh: The clinical breast examination is routinely performed on millions of women each year. It is used for screening breast cancer and is also routinely performed on women presenting with symptomatic breast conditions.
In this study we assessed the performance of the clinical breast examination among a large sample of practicing physicians. There were two main goals to the study. The first goal was to identify current recommendations for performing the clinical breast examination and investigating how this relates to examination sensitivity or finding a mass. The second and more general goal was to develop a method for objective assessment of clinical skills.
Novel clinical breast examination simulators were used in this study; in addition to their ability to present different pathologies and multiple clinical scenarios, they were all integrated with advanced force sensors. These sensors include approximately 2000 discrete sensing elements, measuring force level and distribution thought the breast examination. These sensors provide information at a level of detail that is not possible with observation alone.
Four models were used in this study; two models presenting superficial soft masses and two models representing hard chest wall masses. The study was performed from 2013 to 2014 with 553 physicians performing the clinical breast examination on our models. The participants were recruited at three annual clinical meetings: 136 at the American Society of Breast Surgeons, 236 at the American Academy of Family Physicians, and 181 at the American College of Obstetricians and Gynecologists.
The study found a significant relationship between the force used during palpation and the accuracy of the assessment of the deep-tissue lesions. More specifically, the study found that some physicians don’t apply enough force during the examination putting them at high risk of missing deep-tissue lesions. Since force can’t be measured by human observation this underscores the added value of integrating sensors into clinical simulators. (more…)
MedicalResearch.com Interview with:
Jean-Bosco Tagne Ph.D.
Assistant Professor of Medicine
Boston University School of Medicine; Pulmonary Center
Boston, MA
Medical Research: What is the background for this study? What are the main findings?
Response: The lung transcription factor Nkx2-1 is an important gene regulating lung formation, and normal respiratory functions after birth. Alteration in the expression of this transcription factor can lead to lung interstitial disease, postnatal respiratory distress and lung cancer. MicroRNAs repress gene expression, also controlling lung cell differentiation. In this study, we characterized miRNAs regulated by Nkx2-1 in lung cells by genome-wide analysis and confirm the expression patterns of highly regulated miRNAs in normal lung and in lungs lacking functional Nkx2-1. By in vitro studies in lung cell lines we found that down-regulation of Nkx2-1 de-represses miR-200c. Increased miR-200c, in turn, reduces the expression of its predicted targets Nfib and Myb. These findings add new components to the gene regulatory network controlled by Nkx2-1 in lung epithelial cells that may have implications in the various roles of Nkx2-1 in development and disease particularly in this case lung cancer where the levels are seriously altered.
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MedicalResearch.com Interview with:
Michael J. Orlich, MD, PhD
Program Director, Preventive Medicine Residency
Loma Linda University
Co-Investigator, Adventist Health Studies
Medical Research: What is the background for this study? What are the main findings?
Dr. Orlich: Colorectal cancer is the second leading cause of death from cancer in the United States. Screening efforts such as colonoscopies have helped save many lives by detecting pre-cancerous polyps and removing them. However, it is even better to prevent cancers from forming in the first place. We call this primary prevention. Diet is a potentially important approach to reduce the risk of developing colorectal cancer. In this analysis, we compared those eating different categories of vegetarian dietary patterns to those eating a non-vegetarian diet. About half of our study population was classified as non-vegetarian, which we defined as eating meat at least weekly. The other half of our population we called vegetarian and further divided them into four different vegetarian groups: semi-vegetarians ate meat but less than once per week; pesco-vegetarians ate fish but avoided other meats; lacto-ovo-vegetarians avoided meat but ate eggs and/or dairy products; and vegans avoided all meats, eggs, and dairy. All vegetarians together had on average a 22% relative reduction in the risk of developing colorectal cancer, compared to non-vegetarians, after carefully adjusting for many other factors. Pesco-vegetarians in particular had a much lower risk compared to non-vegetarians. (more…)
MedicalResearch.com Interview with:
Prof. Sigurdur Y Kristinsson
Professor of Hematology
University of Iceland
MedicalResearch: What is the background for this study? What are the main findings?
Prof. Kristinsson: Multiple myeloma is always preceded by a precursor condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS is characterized by a detectable monoclonal protein in persons without evidence for end-organ damage or other related plasma cell or lymphoproliferative disorders. MGUS is very common and is detected in approximately 5 percent of persons 70 years or older. However, only a small proportion of MGUS progresses to a malignant disorder, in fact the annual risk of progression to multiple myeloma or other related disorders is on average 1 percent, with varying risks according to risk groups. Current guidelines suggest, depending on the individual patient’s clinical risk score, life-long monitoring of MGUS individuals to detect progression to multiple myeloma or related disorders. At this time, the impact of annual monitoring on the outcome of patients who eventually develop multiple myeloma is unclear.
Using high-quality population-based data from Sweden, we estimated the impact of prior knowledge of MGUS diagnosis and comorbidities on multiple myeloma survival, by performing a large population-based study using data on more than 14,000 multiple myeloma patients diagnosed in Sweden 1976-2005, with follow-up through 2007. The hypothesis that detection and follow-up of MGUS may influence survival in multiple myeloma is unlikely to ever be tested in a prospective clinical study due to the large sample size required with long follow-up time, and consequent extreme costs.
We found that multiple myeloma patients with prior knowledge of MGUS had significantly 15% better survival, despite having significantly more comorbidities. Interestingly, low-risk MGUS (with very low M-protein) had highest risk of death. The observation that low M-protein concentration at MGUS diagnosis was associated with poorer multiple myeloma survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in MGUS, regardless of risk stratification.
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MedicalResearch.com Interview with:
Pedram Gerami MD
Associate Professor of Dermatology and Pathology
Northwestern University
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Gerami: The outcomes for patients with cutaneous melanoma are highly variable and there are limitations to the conventional staging system for melanoma. For example while the status of the sentinel lymph node biopsy is considered the strongest prognosticator, approximately 2/3 of cutaneous melanoma patients that ultimately die from their melanoma will have a negative sentinel lymph node biopsy result. In this study we showed that using a technique known as mRNA expression profiling to determine which genes are highly active and which are not that a molecular prognostic assay with accuracy could be developed. This assay can accurately classify patients based on their gene signature as having a high or low risk for metastasis and death from their melanoma. In an independent validation cohort, patients with a class I or low risk signature had a 5 year disease free survival rate of 97% while those with a class II or high risk signature had a 5 year disease free survival rate of only 31%.
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Medicalresearch.com Interview with:
Dr. Clarice R. Weinberg Ph.D
Biostatistics and Computational Biology Branch
National Institute of Environmental Health Sciences
Research Triangle Park, NC 27709
MedicalResearch: What is the background for this study?
Dr. Weinberg: Hormone therapy (HT) was commonly prescribed in the U.S. late in the 20th century to help women through the challenges of menopause. Several decades ago, therapy with estrogen alone was shown to cause endometrial cancer, and the combined use of both estrogen and progesterone replaced treatment with estrogen alone. But research published around 2002 had far reaching effects on gynecologic practice. Both the randomized trial component of the US Women’s Health Initiative and the observational European Million Women’s Study reported that postmenopausal women who were older than 50 and were taking the combination HT had an increased risk of breast cancer. Physicians and patients responded quickly, and Hormone therapy use plummeted.
However, it remained unclear whether there were risks of Hormone therapy use in women under age 50. Some factors, for example obesity, have opposite effects on the risk of breast cancer in pre- and post-menopausal women, so one cannot assume risk findings from older women necessarily apply to younger women. We carried out a sibling-based study of 1,419 women with breast cancer diagnosed under the age of 50 (http://sisterstudy.niehs.nih.gov/English/2sis.htm). Each case had a sister (also studied) who had never been diagnosed with breast cancer, who could serve as her control. The study was funded by Susan G. Komen for the Cure, and the National Institutes of Health.
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MedicalResearch.com Interview with:
M. Minhaj Siddiqui, MD
Director of Urologic Robotic Surgery
Assistant Professor of Surgery - Urology
University of Maryland School of Medicine
Baltimore MD 21201
Medical Research: What is the background for this study?
Response: A history of testicular cancer has been suggested to have an association with an increased risk of developing prostate cancer (PCa) in epidemiologic studies. We hypothesized that there may be an increased risk of developing intermediate to high-risk prostate cancer as well.
Medical Research: What are the main findings?
Response: 147,044 men with melanoma and 32,435 men with testicular cancer were identified. Prostate cancer was diagnosed in 3,205 men in total. The cumulative incidence of all prostate cancer by age 80 was 2.8% in the control melanoma cohort and 12.6% in the case cohort of men with history of testicular cancer (p<0.0001 for KM survival curves, Figure 1). For intermediate/high-risk disease, the incidence was 1.1% versus 5.8% for each cohort respectively (p<0.0001 for KM survival curves, Figure 2). No association with prostate cancer was seen with non-seminomatous versus seminomatous germ cell tumors. Upon multivariate analysis, testis cancer was associated with an increased risk of all prostate cancer (HR 4.7, p<0.0001) and intermediate/high-risk PCa (HR 5.2, p<0.0001) when controlling for race and radiation history.
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MedicalResearch.com Interview with:
Dr. Michaela A. Dinan Ph.D
Department of Medicine
Duke University
Medical Research: What is the background for this study? What are the main findings?
Dr. Dinan: We wanted to examine how Oncotype DX® Breast Cancer Test (ODX) was being used in real-world practice at the population level. ODX has been examined in clinical trials and limited academic settings but we know that these patients are often younger, have fewer medical comorbidities, and do not necessarily accurately reflect the majority patients with cancer. In our study, we observed that Oncotype DX® Breast Cancer Test was being used predominately in accordance with guidelines which recommend the test for women with estrogen-receptor positive, disease. We also looked just at women under the age of 70 who met guideline criteria for testing, because this population would include those women who were more likely to be chemotherapy candidates, and we saw a rapid uptake of the test between 2005 and 2009, with use of the test increasing from 8% to 39%.
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MedicalResearch.com Interview with:
Halle C.F. Moore, M.D.
Cleveland Clinic Foundation
Taussig Cancer Institute
Cleveland, OH 44195
Medical Research: What is the background for this study? What are the main findings?
Dr. Moore: Ovarian failure is a common long-term side effect of chemotherapy. Previous studies investigating whether suppressing ovarian function during chemotherapy treatment will preserve ovarian function following chemotherapy have had mixed results. Our study found that suppressing the ovaries with the GnRH analog goserelin during chemotherapy treatment for early stage ER-negative breast cancer resulted in a reduced risk of ovarian failure two years after initiation of treatment.
Also, more women who received the goserelin with chemotherapy became pregnant than women who received chemotherapy without goserelin.
In addition, there was an apparent improvement in survival among the goserelin group, confirming the safety of this approach in this patient population.
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MedicalResearch.com Interview with:
Linda Chin, MD
Department Chair, Department of Genomic Medicine, 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. Chin: BRAF inhibitors have worked very well against melanoma in the clinic, but when the tumors relapse on treatment, it is not always clear what causes it. Without this information, it can be difficult for doctors to identify specific second-line therapies likely to overcome the drug resistance. In this study, we used both mouse and patient melanoma samples to identify patterns of selected protein levels that can categorize modes of drug resistance when other assays such as DNA sequencing are uninformative. We hope that this information can provide missing clues for clinicians. (more…)MedicalResearch.com Interview with Irene Shui ScD MPH Staff Scientist Fred Hutchinson Cancer Research Center Seattle, WA 98109 MedicalResearch: What is the background for this study?...
MedicalResearch.com Interview with:
Dr. Anil Sood MD
Professor of Gynecologic Oncology and Reproductive Medicine
The University of Texas MD Anderson Cancer Center
Medical Research: What is the background for this study? What are the main findings?
MedicalResearch: What is the background for this approach? What are the main findings?
Dr. Sood: The background involves several different issues: management approaches have varied quite a bit across the US; definition of “optimal” surgery and rates of complete surgical removal of tumor (R0) have also varied. It is quite apparent that patients who benefit the most from surgery upfront are those who have removal of tumor resection. To address these issues, we have implanted a much more personalized approach whereby patients with suspected advanced ovarian cancer undergo laparoscopic assessment using a validated scoring system (based on the pattern and extent of disease noted during laparoscopic assessment); patients with a score <8 undergo upfront debulking surgery and those with a score ≥8 receive neoadjuvant chemotherapy followed by surgery after 3-4 cycles. To date, this program has been fully implemented as part of the Moonshot Program at M.D. Anderson. This program has already resulted in several benefits – for example, prior to this algorithm being put into place among all patients with suspected advanced ovarian cancer, around 20% would have removal of tumor resection; after the implementation of the algorithm, of those going to upfront debulking surgery (after laparoscopic assessment), almost 85% of times removal of tumor resection can be achieved. Also, this method of treatment is allowing for new and innovative clinical trial designs. (more…)