Cancer Research
28 Nov Breast Cancer: Gene Mediating Tamoxifen Resistance Identified
MedicalResearch.com Interview with:
Ben Ho Park, M.D., Ph.D.
Associate Professor of Oncology, Breast Cancer Program
Associate Director, Hematology/Oncology Fellowship Training Program The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD 21287
Medical Research: What is the background for this study? What are the main findings?
Dr. Park: To discover genetic mediators of tamoxifen resistance in breast cancers, we used genetic screening of breast cancer cell line models and patient data to identify a new gene that can mediate drug resistance. We found that amplification and overexpression of this gene in estrogen receptor positive breast cancers results in resistance and is associated with worse outcomes in patients whose tumors demonstrate amplification/overexpression of this gene.
28 Nov Cancer Survival Varies Widely By Country and Cancer Type
MedicalResearch.com Interview with:
Dr Claudia Allemani PhD FHEA MFPH
Senior Lecturer in Cancer Epidemiology
Cancer Research UK Cancer Survival Group
Department of Non-Communicable Disease Epidemiology
London School of Hygiene and Tropical Medicine, London UK
Medical Research: What is the background for this study?
Dr. Allemani: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control.
The first CONCORD study was published in 2008.1 It brought together data from 101 cancer registries in 31 countries, and included 1.9 million patients diagnosed during 1990-94 with a cancer of the colon, rectum, breast or prostate and followed up to the end of 1999. It revealed very wide international differences in five-year survival, and it confirmed the well-known racial discrepancy in cancer survival in the USA.
CONCORD-2 is the most comprehensive international comparison of trends in population-based cancer patient survival to date. It extends the first study in three ways:
- it covers 10 common cancers: collectively, these account for almost two-thirds (63%) of all cancer patients diagnosed each year in both developed and developing countries
- it includes data on more than 25 million cancer patients, provided by 279 cancer registries in 67 countries, in 40 of which the data provide complete (100%) coverage of the national population
- it examines trends in cancer survival for patients diagnosed over the 15-year period 1995-2009
25 Nov Telephone Reminders May Increase Breast Cancer Screening
MedicalResearch.com Interview with Dr. Jonathan Myles Centre for Cancer Prevention, Queen Mary, University of London Wolfson Institute of Preventive Medicine, Charterhouse Square, London Medical Research: What is the background for this study? What are the main findings? Dr. Myles: Breast cancer screening uptake is low in areas of high social deprivation and large populations of some ethnic groups. The main finding of this study is that an intervention in the form of contacting women by telephone a few days before the date of their screen, reminding them of their appointment and answering any queries they may have, significantly increases uptake.24 Nov Skin Cancer Lesions Not Affected By Agent Orange Exposure
MedicalResearch.com Interview with: Naveed Nosrati MD Indiana University School of Medicine Staff Surgeon, Roudebush VAMC Medical Research: What is the background for this study? Dr. Nosrati: We originally began this study as a broader project investigating the effect of trauma induced by biopsies on the spontaneous clearance of a non-melanoma skin cancer. As part of that, we created a large database with many patient variables. Since we undertook this project at our local VA hospital, one of the variables available to us was Agent Orange exposure. Shortly after completing the study, Clemens et al published their study linking Agent Orange exposure to higher rates of invasive non-melanoma skin cancer. Their study was a pilot study of only 100 patients. As we had well over 1,000 patients, we decided to pursue a side project of how Agent Orange specifically affects our results. Our study was operating under the hypothesis that trauma induced by biopsies led to an inflammatory response that often led to the immunologic clearance of the remaining skin cancer. We actually coined the term “SCORCH” lesion, or spontaneous clearance of residual carcinoma histologically, for this phenomenon. With that mind, we would expect patients exposed to Agent Orange to theoretically have a more invasive form of malignancy and thus have lower rates of spontaneous clearance.23 Nov US Skin Cancer Costs Top $8 Billion Annually
Medical Research.com Interview with:
Gery P. Guy Jr., PhD, MPH, Health economist
CDC: Division of Cancer Prevention and Control’s Epidemiology and Applied Research Branch.
Medical Research: What is the background for this study?
Dr. Guy: Skin cancer is the most commonly diagnosed cancer in the United States and is a growing public health problem. Melanoma, the deadliest form of skin cancer, is responsible for more than 12,000 deaths each year and is diagnosed in over 70,000 people per year. The number of skin cancer cases continues to increase every year, however little is known about the economic burden of treatment. The purpose of our study was to examine trends in the number of people treated for skin cancer and the cost of treatment.
20 Nov More Women Choosing Mastectomy For Early Breast Cancer Management
MedicalResearch.com Interview with: Dr. Kristy Lynn Kummerow MD Division of Surgical Oncology and Endocrine Surgery Vanderbilt University Medical Center Tennessee Valley Healthcare System, Veterans Affairs Medical Center Geriatric Research, Education, and Clinical Center Nashville, Tenn Medical Research: What is the background for this study? What are the main findings? Dr. Kummerow: This study looked at how we are currently treating early stage breast cancer in the US – early stage breast cancer includes small cancers with limited or no lymph node involvement and no spread to other body site – it was prompted by something we observed an our own cancer center, which is that more and more women seem to be undergoing more extensive operations than are necessary to treat their cancer. It is helpful to understand the historical context of how we treat early breast cancer. Prior to the 1980s, the standard of care for any breast cancer was a very extensive procedure, which involved removal of the entire breast, as well as underlying and overlying tissues and multiple levels of lymph nodes drained by that area. Informative clinical trials were completed in the 1980s demonstrated that these extensive procedures were unnecessary, and that equivalent survival could be achieved with a much more minimal operation, by removing only the tumor, with a margin of normal breast tissue around it, and performing radiation therapy to the area; this technique is now known as breast conservation surgery, also known as lumpectomy with radiation. In the 1990s, breast conservation was established by the national institutes of health and was embraced as a standard of care for early stage breast cancer; performance of breast conservation surgery also became a quality metric – accredited breast centers in the US are expected to perform breast conservation surgery in the majority of women who they treat for breast cancer. However, what our research team observed at our institution didn’t fit – over time it appears more aggressive surgical approaches are being used for more women. This has been found in other institutions as well, and is supported by smaller national studies. We wanted to understand how surgical management of early breast cancer is changing over time at a national level using the largest data set of cancer patients in the United States.20 Nov DNA Test May Distinguish Primary From Metastatic Lung Cancer
MedicalResearch.com Interview with:
Marie-Christine Aubry, M.D.
Professor of Laboratory Medicine and Pathology
Consultant, Department of Laboratory Medicine and Pathology,
Mayo Clinic in Rochester, Minn.
Medical Research: What is the background for this study? What are the main findings?
Dr. Aubry: Up to 20% of patients will present with multifocal lung cancer or will develop a second lung cancer. The main clinical issue is distinguishing between independent primaries from true intrapulmonary metastases since this distinction will drive the therapy of the patient. Currently no ancillary studies allows for this distinction and the distinction is provider specific based on a combination of clinical, radiologic and pathologic assumptions. Based on our prior research using a method called mate pair sequencing , we observed that the probability of detecting identical chromosomal breakpoints in two unrelated tumors, from 2 different patients was basically zero. Similarly, when assessing different components within a single tumor, we always found identical chromosomal breakpoints between these components. We thus hypothesized that if two tumors within a patient were related, i.e. true metastasis, we should always find a number of identical chromosomal breakpoints between the tumors. And in contrast, if 2 tumors were truly independent primaries, we should not observe any chromosomal breakpoints in common.
We first studied a control group of patients that had
1- a primary lung cancer with a known distant metastasis (usually brain metastasis),
2- two lung cancers of different histologic subtype, adenocarcinoma and squamous cell carcinoma which are accepted as true independent primaries and
3- 1 tumor with different portions of the tumor being analyzed individually and compared as true relatedness.
There were thus a total of 11 pairs of tumors with predetermined status of independent primaries versus relatedness (ie metastasis or same tumor). The mate pair generated data showed a perfect concordance with this status. We then studied 11 pairs of lung tumors of similar histology (2 adenocarcinomas or 2 squamous cell carcinomas). The current gold standard for the distinction between independent primaries and intrapulmonary metastasis relies on a pathologist’s comparative morphologic assessment. In order to strengthen this gold standard, 2 pulmonary pathologists independently made this assessment. Interestingly, the pathologists agreed on the status of independent primaries and intrapulmonary metastasis in 9 (of 11) cases demonstrating the shortcomings of this gold standard. Furthermore, there were discordance between the pathologists’ prediction and the clinicians’ assessment in 3 of the 11 patients and the clinician could not come to a final assessment in 1 patient. The MP data was concordant with the pathology assessment in 8 of these 9 cases, and supported the pathologists’ prediction in 2 (of the 3) discordance with the clinical assumptions.
20 Nov Obesity, Sedentary Lifestyle May Increase Risk of Breast Cancer
MedicalResearch.com: Interview Invitation Dr. Wenji Guo University of Oxford Medical Research: What is the background for this study? Response: Previous studies report increased risk for breast cancer in postmenopausal women who have a higher Body Mass Index (BMI) – a measure of body fat based on height and weight. However, BMI is unable to distinguish between excess weight due to fat rather than muscle. More direct measures of fatness, such as body fat percentage, may be better indicators of disease risk. And although probable evidence for the relationship between physical activity and breast cancer now exists, questions still remain over the role of vigorous compared to lower intensity physical activity.19 Nov Cannabis Extracts Enhance Anti-Tumor Radiation Effects
MedicalResearch.com Interview with: Dr Wai Liu Senior Research Fellow St George's University of London London, SW17 Medical Research: What is the background for this study? What are the main findings? Dr. Liu: It has been known for some time that certain chemicals called cannabinoids that are isolated from the cannabis plant possess anticancer action through the ability to enhance/engage apoptosis and autophagy. These effects are both dependent and independent upon the cognate receptors. These are found at relatively high levels in brain cells. Brain tumors tend to express these at high levels and so we felt these would be good candidates. The main findings of the current study is the ability that combining the cannabinoids THC and CBD with irradiation can cause a reduction in tumor that is greater than the sum of the individual treatments. That is, when using doses of irradiation or cannabinoids individually, the effects were minimal; however, if they were used simultaneously, the effect was synergistic, and tumor growth was significantly impeded.13 Nov Colon Cancer: Improved Screening and Chemotherapy Contribute To Improved Survival
MedicalResearch.com Interview with: Xianglin L. Du, MB, MS, Ph.D. Professor of Epidemiology, Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, TX 77030, USA. Medical Research: What is the background for this study? Dr. Du: Widespread use of screening and advances in screening strategies played a key role in colorectal cancer survival improvement. With the increasing evidence on the benefit of fecal occult blood test and sigmoidoscopy during 1990s, the U.S. Preventive Service Task Force for the first time in 1996 recommended the annual use of fecal occult blood test, periodic use of sigmoidoscopy, or routine use of both modalities for all persons aged 50 or older. Because colonoscopy is able to detect lesions in the entire colon and has a high sensitivity for lesions of over 10mm in size, Medicare began to cover colonoscopy since 2001 for individuals with average-risk of colorectal cancer. Advances in chemotherapy, particularly some new therapeutic regimens approved by Food and Drug Administration (FDA) over the past decades also played a key role in survival improvement for patients with colorectal cancer. However, the overall impact of newly approved chemotherapy regimens on survival in population-based elderly patients remains unclear. It is also unknown what proportion of survival improvement was attributable to changes in tumor stage and size due to screening, and what proportion was attributable to more effective chemotherapy regimens. Hence, we studied a large nationwide and population-based cohort of elderly colorectal cancer patients to examine the changes in tumor stage and tumor size from 1992 to 2009, and to further quantify the effects of changes in stage/size and chemotherapy regimens on improved survival over the two decades.13 Nov Omega-3 Fish in Diet May Reduce Cancer Risk
MedicalResearch.com Interview with:
James J. DiNicolantonio, PharmD
Associate Editor BMJ Open Heart
Cardiovascular Research Scientist
Saint Luke's Mid America Heart Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. DiNicolantonio: Daily low-dose aspirin has been shown to decrease the risk for cancer in a meta-analysis of randomized controlled trials, which is likely attributable to its ability to modestly decrease the activity of cyclooxygenase-2 (cox-2), an enzyme which contributes importantly to the genesis and progression of adenocarcinomas. Adenocarcinomas are cancer of the glands, the most common type of breast cancer (invasive ductal carcinoma) is an adenocarcinoma, additionally many cancers of the lung, intestine, esophagus, colon are adenocarcinomas.
We show that an ample dietary intake of long-chain omega-3 fats—the type prominent in fatty fish—would oppose cox-2 activity. Additionally, we cite numerous evidence that a higher intake of long-chain omega-3 fats has been found to reduce the risk for numerous types of cancer - especially when looking at trials that excluded fried or preserved fish (or fish high in omega-6), excluded trials with a high background intake of omega-6, and included trials where the "high" intake group - actually ate 2 servings of fish or more per week. Additionally, basic science as well as randomized data showing that long-chain omega-3s can reduce the number and size of colon polyps supports this argument.
12 Nov Hospice Care For Advanced Cancer Decreased Aggressive Care and Costs in Last Year of Life
MedicalResearch.com Interview with:
Ziad Obermeyer, MD, MPhil
Emergency Medicine, Brigham & Women's Hospital
Assistant Professor, Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Obermeyer: More patients with cancer use hospice today than ever before, but there are indications that care intensity outside of hospice is increasing, and length of hospice stay decreasing. We examined how hospice affects health care utilization and costs and found that, in a sample of elderly Medicare patients with advanced cancer, hospice care was associated with significantly lower rates of both health care utilization and total costs during the last year of life.
Patients who did not enroll in hospice had considerably more aggressive care in their last year of life—most of it related to acute complications like infections and organ failure, and not directly related to cancer-directed treatment. Hospice and non-hospice patients had similar patterns of health care utilization until the week of hospice enrollment, when care began to diverge. Ultimately, non-hospice patients were five times more likely to die in hospitals and nursing homes. These differences in care contributed to a statistically-significant difference in total costs of $8,697 over the last year of life ($71,517 for non-hospice and $62,819 for hospice).
10 Nov Breast Cancer: Overcoming Tumor Resistance With Combinatinon Therapy
MedicalResearch.com Interview with:
Ruth Keri, PhD, Professor and Vice Chair Department of Pharmacology
Case Western Reserve University School of Medicine, and Associate Director for Basic Research in the Case Comprehensive Cancer Center Case Western Reserve University
Medical Research: What is the background for this study?
Dr. Keri: Over the last several decades, the discovery of targeted therapies for certain types of breast cancer, and their use in the clinic, have greatly improved the long-term outcome of patients. Yet some breast cancers don’t respond to these therapies, and ones that do often become resistant over time, resulting in patient relapse and metastatic disease. Why does resistance occur? There are many tricks a tumor employs to evade death. When a drug targets a certain protein or pathway the cancer cell relies on for survival, one potential route of resistance is the cancer cell’s ability to adapt and find another pathway to maintain growth. We reasoned that targeting two separate proteins or pathways important for cancer cell growth may be more effective at preventing or delaying this adaptation.
07 Nov CT Screening For Lung Cancer Can Be Cost-Effective If Right Patients Offered Screening
MedicalResearch.com Interview with:
William C. Black, MD
Professor of Radiology
Department of Radiology
Dartmouth-Hitchcock Medical Center
Lebanon, NH 03756
Medical Research: What is the background for this study? What are the main findings?
Dr. Black: Lung cancer is the leading cause of cancer related death in the U.S., killing more people than cancers of the colon, breast, and prostate combined. In 2011, the National Lung Screening Trial (NLST) demonstrated that screening for lung cancer with low-dose CT could reduce lung cancer mortality by 20% in adults at high risk for the disease. Since then, several medical organizations have recommended that eligible adults be offered screening. The U.S. Preventive Services Task Force (USPSTF) released a grade B recommendation for low-dose CT screening in December 2012, which means that private insurers must cover the cost of screening by January 1, 2015. The Centers for Medicare and Medicaid (CMS) is expected to issue a final decision on national coverage for CT screening in February 2015 and a preliminary decision for public comment on November 10, 2014.
07 Nov Does Dental Trauma Play A Role in Oral Cavity Cancer?
MedicalResearch.com Interview with: Brendan J. Perry, BSc, MBBS Princess Alexandra Hospital Brisbane, Queensland, Australia MedicalResearch: What is the background for this study? What are the main findings? Dr. Brendan J. Perry: Oral cavity cancer is usually attributed to the “Five S’s” - smoking, spirits (alcohol), spices, syphillis and sharp (or septic) teeth. Cigarettes and alcohol are the most important recognised factors. Spices, such as betel nut, and syphillis are known carcinogens but are not commonly seen in western practice. The role of chronic dental trauma on the mucosa of the mouth to cause cancer has only been examined in a limited number of studies previously and its importance has not been elucidated and has never really affected clinical practice. This retrospective review examined the position in the oral cavity where cancers occurred with respects to smoking status and other variables over a 10 year period in a major Australian hospital. The edge of the tongue, a site of potential dental trauma, was the most common site affected, accounting for 35% of oral cavity cancers in smokers. However, in lifelong non-smokers without other significant risk factors, 65% of cancers occurred on the edge of the tongue. A significant number also occurred on the buccal mucosa (inner lining of cheek) which is also exposed to dental trauma, but to a much lesser degree than the more mobile tongue. The floor of the mouth and the alveolar ridge (gums) were also common sites of cancer, but tended to occur in an older age group. This is possibly due to irritation caused by the movement of dentures in this age group against these areas of the mouth. In recent years, dentists have been recommending clients to get removable denture nyc to tackle down on discomfort. We also found that males had an equal chance of developing oral cavity versus oropharyngeal cancer (255 cases vs 265). However, females are almost twice as likely to develop an oral cavity cancer than an oropharyngeal cancer (135 cases vs 69), and this ratio jumps to 4 times the risk for lifelong non-smoking females (53 vs 12). Although a lot of attention has been given to HPV in causing oropharyngeal cancer, for non-smokers, especially females, it appears that oral cavity cancer is a more common disease, and also that chronic dental trauma may be a significant contributing factor.06 Nov Scientists Identify Factors That Promote Breast Cancer Metastases
MedicalResearch.com Interview with:
Antoine E. Karnoub, Ph.D.
Assistant Professor of Pathology
Beth Israel Deaconess Medical Center
Harvard Medical School Center for Life Science 0634
Boston, MA 02215
Medical Research: What are the main findings of the study?
Dr. Karnoub: The main findings of the study are:
(1) that the metastatic propensities of cancer cells can be remarkably modulated by otherwise ‘normal’ mesenchymal stem/stromal cells found in their vicinity;
(2) that generation of highly malignant tumor-initiating cells can be significantly triggered by microenvironmental cues;
(3) that repression of the gene FOXP2 by a miR-199a-led microRNA network enables the propagation of cancer stem cell and metastatic traits in otherwise weakly metastatic cancer cells; and
(4) that such a signaling axis appears to forecast poor patient outcome.
04 Nov Scalp Cooling Prevents Chemotherapy Induced Hair Loss
MedicalResearch.com Interview with:
N. T. Georgopoulos, PhD
Senior Lecturer in Biological Sciences
Department of Biological Sciences
School of Applied Sciences
University of Huddersfield
Medical Research: What is the background for this study? What are the main findings?
Dr. Georgopoulos: Chemotherapy-induced alopecia (CIA) is one of the most distressing side effect of chemotherapy and the anxiety caused by the prospect of Chemotherapy-induced alopecia can cause some cancer patients to even refuse treatment. Various classes of chemotherapeutic drugs such as taxanes (e.g. docetaxel), alkylating agents (e.g. cyclophosphamide) and anthracyclines/DNA intercalating agents (e.g. doxorubicin) target tumour cells due to their rapid division rate; however, these drugs also target the hair matrix keratinocytes, the most rapidly dividing cell subset in the hair follicle, thus resulting in follicle damage and ultimately hair loss.
The only currently available preventative treatment for Chemotherapy-induced alopecia is head (scalp) cooling; scalp cooling during chemotherapy drug administration can substantially reduce hair loss and has been used since the 1970s. However, until recently there was inadequate biological data to support the cyto-protective capacity of cooling; yet such experimental evidence would be important to convince clinicians and patients of the efficacy of cooling. Moreover, it is not clear why in some patients scalp cooling fully protects from Chemotherapy-induced alopecia whereas in other patients it is less efficient. Finally, although scalp cooling can substantially reduce the incidence of hair loss in response to individual drugs, for some combined treatment regimens scalp cooling has much lower (and often quite limited) reported efficacy. Collectively, the need to answer these questions, and to provide ‘real’ experimental data that will support the ability of cooling to ‘rescue’ cells from the cytotoxic effects of chemotherapy drugs, led us to carry out the study.
Using several cell culture models (including human hair follicular keratinocytes), we showed for the first time that cooling dramatically reduces or completely prevents the cytotoxic capacity of drugs such as docetaxel, doxorubicin and the active metabolite of cyclophosphamide (4-OH-CP), whilst combinatorial treatment showed relatively poor response to cooling. Our experimental, in vitro findings are in close agreement with clinical observations. Moreover, we have provided evidence that the minimum temperature achieved may be critical in determining the efficacy of cooling; as the lowest temperature achieved by scalp cooling can differ between patients (our unpublished observations), our findings may also explain why cooling protects from Chemotherapy-induced alopecia better in some patients but not others.
04 Nov Mindfulness Meditation Improved Telomere Length in Breast Cancer Patients
MedicalResearch.com Interview with:
Linda E. Carlson, Ph.D., R.Psych.
Enbridge Research Chair in Psychosocial Oncology
Alberta Innovates-Health Solutions Health Scholar
Professor, Department of Oncology, Faculty of Medicine
Adjunct Professor, Department of Psychology, Faculty of Arts
University of Calgary Clinical Psychologist, Director of Research
Department of Psychosocial Resources
Medical Research: What is the background for this study? What are the main findings?
Dr. Carlson: We have been investigating the effects of cancer support programs including the two in this study, Mindfulness-based cancer recovery, an 8-week group program in which patients learn mindfulness meditation and gentle yoga, and supportive-expressive therapy, a 12-week program where patients share difficult emotions in a supportive group environment. We know there is psychological benefit of these programs, but what about effects in the body?
Telomeres are the protective caps on the end of chromosomes (like the tips on shoelaces) that protect them from damage and degredation. They are longest when we are young and naturally get shorter as we age. Shorter telomere's are associated with higher risk for many diseases, including cancer, and people with higher stress levels tend to have shorter telomeres.
This is the first study to investigate whether short psychosocial interventions can affect telomere length in cancer pateints. We randomly assigned breast cancer survivors with cancer-related distress, feelings such as anxiety, fear, worry, and depression, to either mindfulness-based cancer recovery, supportive expressive therapy or a control group that just had a minimal intervention. We took blood samples before and after the groups (or at equal time points for those in the control condition) and measured the length of the telomeres.
Women in both of the active support groups maintained the length of their telomeres over time, but the telomere length of women in the control group became shorter. This is the first controlled study to show that short-term interventions can actually have some effect on cellular aging in the telomeres.
03 Nov Hematologic Cancers: Umbilical Cord Transplantation – One vs Two Units
MedicalResearch.com Interview with:
John E. Wagner, M.D.
Principal Investigator
Professor Director, Division of Blood and Marrow Transplantation Department of Pediatrics McKnight Presidential Endowed Chair Hageboeck Family / Children's Cancer Research Fund Endowed Chair University of Minnesota Minneapolis, MN 55455
Medical Research: What is the background for this study? What are the main findings?
Dr. Wagner: Earlier studies of umbilical cord blood transplantation (UCB) in children with hematological malignancies demonstrated a survival rate of approximately 50%. While single UCB transplant was very effective despite HLA mismatch, few adults had access to umbilical cord blood as a treatment option due to the cell dose requirement of 2. 5 x 10^6 nucleated cells per kilogram recipient body weight. For this reason, at the University of Minnesota we explored the co-transplantation of two partially HLA matched umbilical cord blood units in adults as a straightforward strategy to achieving the cell dose requirement. Early results were remarkable with survival rates higher than that observed in children. This in turn led to the design of the BMT CTN 0501 study, a randomized trial comparing single versus double umbilical cord blood transplantation in children aged 2-21 years with hematological malignancies. All patients received a uniform conditioning regimen of fludarabine, cyclophosphamide and total body irradiation and GVHD prophylaxis of cyclosporine A and mycophenylate mofetil. 224 patients were randomized.
There were four major findings:
- 1) survival results overall, regardless of treatment arm, have improved,
- 2) for children, an adequately dosed single umbilical cord blood unit is sufficient, giving a survival result of 72% at one year,
- 3) double umbilical cord blood transplant is associated with more GVHD and poorer platelet recovery but survival is comparable to an adequately dosed single unit, and
- 4) HLA mismatch is well tolerated with potentially better disease free survival in patients transplanted with HLA mismatched umbilical cord blood , a provocative finding that requires further investigation.
03 Nov Ovarian Cancer: ADNEX Tool Helps Distinguish Benign From Malignant Ovarian Cysts
MedicalResearch.com Interview with:
Ben Van Calster PhD
Department of Development and Regeneration
KU Leuven, Herestraat Leuven, Belgium
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Van Calster: Ovarian cancer is a very common type of cancer among women, with over 200,000 new cases per year worldwide. It is the most lethal of gynecological malignancies. Research has shown that the referral of patients with ovarian cancer to specialized gynecological oncologists in high volume centers improves survival. However, audits in Europe and the United States also show that only a minority of women with ovarian cancer are appropriately triaged to receive specialist care. In addition, different types of malignancies are not treated in the same way. Hence optimal personalized management of an ovarian tumor hinges on the detailed preoperative diagnosis of its nature. Unfortunately, current prediction models focused on the discrimination between benign and malignant tumors without further specification of the likely type of malignancy.
Various prediction models and rules have been developed to help predict whether an ovarian mass is benign or malignant. A recent systematic review meta-analysis has shown that the IOTA model LR2 and simple rules perform better than any other previous test. However none of these tests give anything other than a dichotomous outcome – i.e. cancer or non-cancer. In practice the position is more nuanced.
The ADNEX model estimates the likelihood that a tumor is benign, borderline malignant, stage I cancer, stage II-IV cancer, or secondary metastatic cancer. This model is the first that is able to differentiate between benign and these four subtypes of malignancy. To do so, ADNEX uses three clinical predictors (age, serum CA-125 level, and type of center), and six ultrasound characteristics of the tumor (maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites). The model is based on data from almost 6,000 women recruited at 24 centers in 10 countries.
03 Nov Exploring microRNAs as Blood Biomarkers of Pancreatic Cancer
MedicalResearch.com Interview with
Dr. Murray Korc MD, Professor
Department of Medicine, Division of Endocrinology, Biochemistry and Molecular Biology, and the Pancreatic Cancer Signature Center
IU Simon Cancer Center, Indiana University School of Medicine
Indianapolis, Indiana
Medical Research: What is the background for this study? What are the main findings?
Dr. Korc: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with an overall 5-year survival rate of 6%. Currently, there are no highly specific and sensitive biomarkers in the blood that can be used for definitively diagnosing the presence of this cancer. In addition, in spite of the usefulness of CA19-9 in differentiating between patients with pancreatic cancer and chronic pancreatitis, this test may yield a significant number of false positive and false negative results, and it may be influenced by the presence of jaundice. These difficulties are compounded by the fact that patients with pancreatitis are at-risk for developing Pancreatic ductal adenocarcinoma.
We decided to carry out a study of microRNAs using plasma from treatment-naïve PDAC patients, chronic pancreatitis patients, and controls without pancreatic disease. We focused on microRNAs because they are known to be present in the blood and to be very stable. We chose to conduct these assays in plasma because we reasoned that there would be fewer confounding factors by comparison with either whole blood or serum. We determined that five microRNAs were elevated in plasma from PDAC patients by comparison with either chronic pancreatitis or controls. Importantly, among these five microRNAs, high levels of miR-10b, miR-155, and miR-106b in the plasma were highly accurate in diagnosing Pancreatic ductal adenocarcinoma with ~95% sensitivity and ~100% specificity.
02 Nov Colon Cancer Screening: Stool Biomarker May Be Equivalent To Colonoscopy
MedicalResearch.com Interview with:
Enrique Quintero MD, PhD
President, Asociación Española de Gastroenterología (AEG)
Chief of Gastroenterology, Hospital Universitario de Canarias
Professor of Medicine, Universidad de La Laguna
La Laguna. Tenerife Spain
Medical Research: What is the background for this study? What are the main findings?
Dr. Quintero: First degree relatives (FDRs) of patients with colorectal cancer (CRC) are at increased risk of developing the disease compared with the general population. For that reason, clinical practice guidelines recommend colonoscopy every five years starting at the age of 40 years or ten years less than the youngest case in the family. However, this approach has some drawbacks:
- first, several studies have shown that the benefit of colonoscopy is limited by a low uptake (less than 40%);
- second, it represents an important colonoscopy burden, as about 70-80% of explorations are normal or without relevant lesions, which implies a high resource consumption; and
- third, this recommendation is not based on evidence, as no randomized controlled trials have compared the efficacy of screening colonoscopy with that of other strategies.On the other hand, pilot studies have shown that one-time fecal immunochemical tests (FIT) have acceptable capacity to detect advanced neoplasia (defined as cancer or advanced adenoma) in family members of patients with CRC. For these reasons we conducted a prospective randomized trial to compare the efficacy of repeated fecal immunochemical tests versus one-time colonoscopy for detecting advanced colorectal neoplasia in asymptomatic FDRs of patients with colorectal cancer.
30 Oct Prostate Cancer: Androgen Deprivation Therapy May Be Harmful For Some Men
MedicalResearch.com Interview with:
David R. Ziehr B.S., MD Candidate
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Response: Androgen deprivation therapy (ADT), commonly achieved with gonadotropin-releasing hormone agonists or antagonists, is a mainstay of prostate cancer therapy. While randomized controlled trials demonstrate that ADT improves survival among men with unfavorable risk prostate cancer, retrospective studies have suggested that some men with comorbid illnesses such as heart disease may not derive a benefit from—or may even be harmed by—ADT. However, the nature of this harm has not been characterized. We studied over 5000 men with prostate cancer who were treated with brachytherapy (implanted radioactive seeds) with or without ADT. We analyzed the men based on pre-treatment cardiac comorbidity and examined the association between ADT and death from cardiac causes. We found that among men with congestive heart failure or a past myocardial infarction (MI), Androgen deprivation therapy was associated with a three-times greater risk of death from heart disease. However, Androgen deprivation therapy was not associated with greater risk of cardiac mortality in men without heart disease or with a risk factor for heart disease, such as diabetes, hypertension or hyperlipidemia.
30 Oct Screening Chemotherapies for Effectiveness On Cultures Of Breast Cancer Biopsy Cells
MedicalResearch Interview with:
Melissa Skala, Ph.D.
Assistant Professor of Biomedical Engineering
Assistant Professor of Cancer Biology
Vanderbilt University Nashville, TN 37235
Medical Research: What is the background for this study? What are the main findings?
Dr. Skala: We developed a new metabolic imaging technique that is highly sensitive to tumor cell response to anti-cancer drug treatment. We coupled this imaging technique with new, three-dimensional cultures that can be grown from breast tumor biopsies. Together, our data indicate that this approach could be used to perform rapid, low-cost, and accurate drug screens for individualized treatment of cancer patients.
27 Oct Imaging May Predict Which Breast Cancers Will Respond To Chemotherapy
MedicalResearch.com Interview with: Shidong Jiang Associate professor of Engineering Thayer School of Engineering at Dartmouth Medical Research: What is the background for this study? What are the main findings? Dr. Jiang: Breast cancer is the most common non-skin cancer in women worldwide, and the second leading cause of women’s cancer mortality in the United States. A common treatment strategy after diagnosis is to shrink breast cancer tumors larger than 3 centimeters with a 6 to 8 month course of Neoadjuvant Chemotherapy prior to surgery. Clinical studies have shown that patients who respond to Neoadjuvant Chemotherapy have longer disease-free survival rates, but only 20 to 30 percent of patients who receive Neoadjuvant Chemotherapy fit this profile. Our work represents the first clinical evidence that tumor total hemoglobin estimated from DOST images differentiates women with locally advanced breast cancer who have a complete pathological response with Neoadjuvant Chemotherapy from those who do not with predictive significance based on image data acquired before the initiation of therapy. The implication of this prognostic information is that certain tumors are pre-disposed to responding to Neoadjuvant Chemotherapy, and that this predisposition should be known prior to choosing the therapy. The study also demonstrates the potential of dramatically accelerating the validation of optimal Neoadjuvant Chemotherapy regimes through future randomized clinical trials by reducing the number of patients required and the length of time they need to be followed by using a validated imaging surrogate as an outcome measure.25 Oct Chemotherapy For Colon Cancer May Come With Financial Strain
MedicalResearch.com Interview with:
Dr. Christine Marie Veenstra MD
Department of Internal Medicine, Division of Hematology/Oncology Division of Colorectal Surgery
Center for Healthcare Outcomes and Policy Division of General Medicine Cancer Surveillance and Outcomes Research Team
University of Michigan, Ann Arbor
Medical Research: What is the background for this study?
Dr. Veenstra: Nearly 50,000 patients are diagnosed with stage III colorectal cancer each year. Chemotherapy is known to increase survival by up to 20% and is the standard recommendation for these patients after surgery. However, use of chemotherapy may be associated with financial strain.
In order to better understand the financial burden and worry associated with colorectal cancer treatment, we surveyed 956 patients being treated for stage III colorectal cancer. We asked patients to answer questions about financial burden such as whether they had used savings, borrowed money, skipped credit card payments, or cut back on spending for food, clothing or recreational activities because of their cancer treatment. We also asked patients how much they worry about financial problems because of their cancer or its treatment.
24 Oct Familial Pancreatic Cancer Linked To Increased Melanoma and Endometrial Cancer Risk
MedicalResearch.com Interview with: Jeremy L. Humphris MBBS The Kinghorn Cancer Center, Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia and Andrew V. Biankin Regius Professor of Surgery Director, Wolfson Wohl Cancer Research Centre, University of Glasgow Garscube Estate, Switchback Road, Bearsden, Glasgow Scotland United Kingdom Medical Research: What are the main findings of the study? Response: Familial pancreatic cancer (FPC) is a family with at least 2 first degree (parent-child or siblings) with pancreatic cancer. We found these patients represent nearly 9% of our cohort. In addition we found those with familial pancreatic cancer were more likely to have other first degree relatives with a history of extra-pancreatic cancer, in particular melanoma and endometrial cancer. Patients with familial pancreatic cancer had more high grade precursor lesions in the pancreas adjacent to the tumour but the outcome was similar. Smoking was more prevalent in sporadic pancreatic cancer and active smoking was associated with significantly younger age at diagnosis in both groups. Long-standing diabetes mellitus (> 2 years duration) was associated with poorer survival in both groups.22 Oct Metastatic Colon Cancer: Survival Improved With FOLFOXIRI and Bevacizumab
MedicalResearch.com Interview with:
Alfredo Falcone MD
Chiara Cremolini Fotios Loupakis
University of Pisa and Azienda-Ospedaliero Universitaria Pisana
Italy
Medical Research: What are the main findings of the study?
Dr. Falcone: In the TRIBE study the main findings are that the use of an initial more intensive therapy with a triplet of cytotoxics (FOLFOXIRI) plus bevacizumab vs a doublet (FOLFIRI) + bevacizumab improves the outcome of metastatic colorectal cancer patients with unresectable metastases. In particular FOLFOXIRI + bevacizumab vs FOLFIRI+bevacizumab improved RECIST response-rate (65% vs 53%, p=0.006), progression-free survival which was the primary endpoint (median 12,1 vs 9,7 months, HR=0,75, p=0.003) and overall survival (median 31,0 vs 25,8 months, HR=0.79, p=0.054). These results, also compared to those reported in previous phase III studies in molecularly unselected patients, represent an important advance in the treatment of this disease.
21 Oct CHEST 2014: Breath Test May Become Accurate Enough For Lung Cancer Detection
MedicalResearch.com Interview with:
Peter J. Mazzone, MD, FCCP MPH
Director of the Lung Cancer Program for the Respiratory Institute
Cleveland Clinic
Medical Research: What are the main findings of this study?
Dr. Mazzone: There were 2 parts to this study. In the first part we looked at how the breath collection instrument and sensor were performing and made adjustments to both in order to optimize its performance.
In the second part we used the improved device and sensor to see if we could accurately separate a sensor signal of our patients with lung cancer from those without lung cancer. We found good separation of lung cancer from non-cancer breath signals, and very good separation of signals of one type of lung cancer from another.
We have concluded that a colorimetric sensor array based breath test is capable of separating those with lung cancer from those without.