24 Jun Breast Cancer Surgery Can Be Improved By Turning Patient Over For MRI
Posted at 15:29h
in Author Interviews, Breast Cancer, Brigham & Women's - Harvard, MRI, Surgical Research
MedicalResearch.com Interview with:
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Dr. Eva Gombos[/caption]
Eva C. Gombos, MD
Assistant Professor, Radiology
Harvard Medical School
Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study?
Response: Treatment of early stage breast cancer, breast-conserving therapy (BCT), which consists of lumpectomy followed by whole-breast irradiation, requires re-excision 20 %–40% of patients due to positive margins.
Breast MR is the imaging modality with the highest sensitivity to detect breast cancer. However, patients who undergo breast MR imaging have not experienced reduced re-excision or improved survival rates.
Our hypothesis is that supine (performed with patient lying on her back) MR imaging within the operating room can be used to plan the extent of resection, to detect residual tumor immediately after the first attempt at definitive surgery, and to provide feedback to the surgeon within the surgical suite. The aim of this study was to use intraoperative supine MR imaging to quantify breast tumor deformation and displacement secondary to the change in patient positioning from imaging (prone performed the patient lying on her stomach) to surgery (supine) and to evaluate the residual tumor immediately after BCT.
Lindsay Kohler[/caption]
Lindsay Kohler MPH
Mel and Enid Zuckerman College of Public Health
Tucson, Arizona
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Several studies have reported that following health promotion guidelines for diet, physical activity, and maintenance of a healthy body weight may reduce the risk of getting cancer or dying from cancer. We performed a systematic review to examine the associations between established cancer prevention guidelines for diet and physical activity and cancer outcomes. We found that adhering to cancer prevention guidelines set forth by the American Cancer Society or the World Cancer Research Fund/American Institute for Cancer Research consistently reduced the risk of overall cancer incidence and mortality (10-61%) in the studies included in this review. In addition, higher adherence to the guidelines consistently reduced the risk of breast, colorectal, and endometrial cancers. Adherence to a pattern of healthy behaviors may significantly reduce cancer incidence and mortality.
Prof. Peter Johnson[/caption]
Peter Johnson MA, MD, FRCP
Professor of Medical Oncology
Cancer Research UK Centre
Southampton General Hospital
Southampton
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Johnson: Based upon retrospective series looking at the ability of interim PET to predict the outcomes of treatment, we aimed to test the idea of modulating treatment in response to an early assessment of the response to ABVD: could we safely reduce the amount of treatment by omitting bleomycin in the group who had responded well? Although the risk of severe toxicity from bleomycin is generally low, for the small number of patients who experience it, it can be life-changing or even fatal. We also wanted to test whether it might be possible to reduce the use of consolidation radiotherapy by comparison to our previous trials, and this seems to have worked too: we used radiotherapy in less than 10% of patients in RATHL, as compared to around half in our previous trials. We have seen better survival figures than in our previous studies with less treatment overall, so it feels as though we are on the right track.
Dr. Ying Bao[/caption]
Dr. Ying Bao Sc.D., M.D
Assistant Professor of Medicine
Channing Division of Network Medicine
Department of Medicine
Brigham and Women's Hospital
Harvard Medical School,
Boston, MA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Nuts are rich in bioactive macronutrients, micronutrients, tocopherols and phytochemicals. Current epidemiological evidence has consistently linked increased nut consumption to reduced risk of several chronic conditions including cardiovascular diseases, type 2 diabetes, and inflammation. In contrast, evidence on nut consumption and cancer risk has been insufficient and equivocal.
Prostate cancer is the leading cancer among U.S. men, with approximately 220,800 new cases diagnosed in 2015. However, very few studies have investigated the association between nut intake and prostate cancer. Thus, in the current study, we followed 47,299 US men from 1986-2012, and examined
(1) whether consuming more nuts prevents getting prostate cancer, and
(2) whether consuming more nuts reduces death rates among non-metastatic prostate cancer patients.
During 26 years of follow-up, 6,810 men were diagnosed with prostate cancer, and 4,346 of these patients were without metastasis at diagnosis. We found no association between nut intake and being diagnosed with prostate cancer. However, among non-metastatic prostate cancer patients, those who consumed nuts 5 or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month.
Dr. Lan Huang[/caption]
Dr. Lan Huang PhD
Co-founder, Chairman and CEO
Dr. Orit Markowitz[/caption]
Orit Markowitz, MD
Director of Pigmented Lesions and Skin Cancer
The Mount Sinai Hospital and
Assistant Professor of Dermatology
Icahn School of Medicine at Mount Sinai
Director of Pigmented lesions clinic
Brooklyn VA,
Adjunct Professor, Dermatology
SUNY Downstate Medical Center, Brooklyn, NY
Chief of Dermatology
Queens General Hospital, Jamaica, NY
MedicalResearch.com Editors’ Note: As part of an ongoing series of occasional article on cancer prevention, Dr. Markowitz from The Mount Sinai Hospital discusses skin cancer and the use Optical Coherence Tomography in skin cancer diagnosis and treatment.
MedicalResearch.com: How common is the problem of non-melanoma skin cancer? Are they difficult to detect and treat?
Dr. Markowitz: Skin cancer is the most commonly diagnosed cancer in the United States. Non melanoma skin cancers, including basal cell carcinomas and squamous cell carcinomas, are the most common malignancies of the skin, constituting around 80 percent of all skin cancers. The annual cost of treating skin cancers in the U.S. is estimated at $8.1 billion, with $3.3 billion for melanoma.
Prof. Frances Balkwill[/caption]
Professor Frances Balkwill OBE, FMedSci
Lead, Centre for Cancer and Inflammation
Barts Cancer Institute
Queen Mary University of London
London
MedicalResearch.com: What is the background for this study?
Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors.
We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation.
Dr. Petkov[/caption]
Valentina Petkov, MD, MPH
Health Scientist/Program Officer
NIH/NCI/DCCPS/Surveillance Research Program
MedicalResearch.com: What is the background for this study?
Dr. Petkov: The number of breast cancer diagnoses is increasing in older patients because of increasing life expectancy and changing population demographics. Despite high incidence, little is known about breast cancer biology and outcomes in patients older than 70, which are often under-represented in clinical trials. The 21-gene Oncotype DX Breast Recurrence Score assay has been used in clinical practice to predict distant recurrence risk and chemotherapy benefit in lymph node negative, hormonal receptor positive (estrogen and/or progesterone receptor positive) invasive breast cancer since 2004. The goal of our study was to evaluate the role of the 21 gene assay in older patients at population level.
We used Surveillance Epidemiology and End Results (SEER) data. We included in the analysis 40,134 patients who were diagnosed with invasive breast cancer between 2004 and 2011, had negative nodes and their tumors were hormonal receptor positive and HER2 negative. Breast Cancer Specific Mortality (BCSM) was assessed at 5 years after diagnosis in patients with low risk (Recurrence Score <18), intermediate risk (Recurrence Score 18-30) and high risk (Recurrence Score >30).
Dr. Donald Burke[/caption]
Donald S. Burke, M.D.
Dean of the University of Pittsburgh Graduate School of Public Health
Director of the University of Pittsburgh Center for Vaccine Research
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Burke: At the University of Pittsburgh we developed a unique method for detecting antibodies in the blood of patients in a proof-of-principle study that opens the door to development of simple diagnostic tests for diseases for which no microbial cause is known, including auto-immune diseases, cancers and other conditions.
We used a technique pioneered by co-author Thomas Kodadek, Ph.D., of the Scripps Research Institute, that synthesizes random molecular shapes called “peptoids” hooked onto microscopic plastic beads. The technique can produce millions of molecular shapes. The peptoids are not organic, but if they match to the corresponding shape on an antibody, that antibody will connect to them, allowing the scientist to pull out that bead and examine that peptoid and its corresponding antibody.
My team chemically generated a huge library of random molecular shapes. Then, using blood from HIV-infected patients and from non-infected people, we screened a million of these random molecular shapes to find the ones that bound only to antibodies present in the blood of HIV-infected patients, but not the healthy controls. No HIV proteins or structures were used to construct or select the peptoids, but the approach, nonetheless, successfully led to selection of the best molecular shapes to use in screening for HIV antibodies.
We then resynthesized that HIV-antibody-targeting peptoid in mass and tested it by screening hundreds of samples from the Multicenter AIDS Cohort Study (MACS), a confidential research study of the natural history of treated and untreated HIV/AIDS in men who have sex with men (supported by the National Institutes of Health). Study co-author Charles Rinaldo, Ph.D., chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology and director of the Pittsburgh arm of the MACS, selected the samples, but blinded the testers to which samples were HIV-positive or -negative. The test distinguished between the samples of HIV-positive blood and HIV-negative blood with a high degree of accuracy.
Dr. Arjun Balar[/caption]
Dr. Arjun Balar MD
Assistant Professor, Department of Medicine
Co-Leader Genitourinary Cancers Program
NYU Langone Medical Center
Laura and Isaac Perlmutter Cancer Center
MedicalResearch.com: What is the background for this study?
Dr. Balar: Standard treatment for advanced urothelial cancer includes cisplatin chemotherapy. But more than half of patients are not expected to tolerate
it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative
to cisplatin. Atezolizumab is a PD-L1 blocking antibody that reactivates
the body¹s immune system to fight bladder cancer and has been recently
FDA approved in the management of advanced urothelial cancer in the
second-line setting after failure of platinum-based chemotherapy.
Dr. Robert Ferris[/caption]
Robert L. Ferris, M.D., Ph.D.
Robert L. Ferris, M.D., Ph.D.
UPMC Endowed Professor and Vice-Chair
Associate Director for Translational Research
Co-Leader, Cancer Immunology Program
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ferris: Investigators at the University of Pittsburgh Cancer Institute<http://upci.upmc.edu/> (UPCI) co-led CheckMate-141<https://clinicaltrials.gov/ct2/show/NCT02105636> a large, randomized international phase III clinical trial that enrolled 361 patients with recurrent or metastatic head and neck squamous cell carcinoma who had not responded to platinum-based chemotherapy, a rapidly progressing form of the disease with an especially poor prognosis. Patients were randomized to receive either nivolumab or a single type of standard chemotherapy until tumor progression was observed.
Nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer. The nivolumab group achieved better outcomes than the standard chemotherapy group by all accounts. After 12 months, 36 percent of the nivolumab group was alive, compared to just 17 percent of the standard chemotherapy group.
Nivolumab treatment also doubled the number of patients whose tumors shrunk, and the number whose disease had not progressed after six months of treatment. Importantly, these benefits were achieved with just one-third the rate of serious adverse events reported in the standard chemotherapy group. In addition, on average, patients receiving nivolumab reported that their quality of life remained stable or improved throughout the study, while those in the chemotherapy group reported a decline. The new trial was considered so successful that it was stopped early to allow patients in the comparison group to receive the new drug.
Dr. Laura Ferris[/caption]
MedicalResearch.com Interview with:
Laura Ferris, M.D., Ph.D.
Associate professor, Department of Dermatology
University of Pittsburgh School of Medicine and
Member of the Melanoma Program
University of Pittsburgh Cancer Institute
MedicalResearch.com: What is the background for this study?
Dr. Ferris: Rates of melanoma, the most dangerous form of skin cancer, are on the rise, and skin cancer screenings are one of the most important steps for early detection and treatment. Typically, patients receive skin checks by setting up an appointment with a dermatologist. UPMC instituted a new screening initiative, which was modeled after a promising German program, the goal being to improve the detection of melanomas by making it easier for patients to get screened during routine office visits with their primary care physicians (PCPs). PCPs completed training on how to recognize melanomas and were asked to offer annual screening during office visits to all patients aged 35 and older. In 2014, during the first year of the program, 15 percent of the 333,788 eligible UPMC patients were screened in this fashion.
Dr. Catherine Diefenbach[/caption]
Dr. Catherine S. M. Diefenbach MD
Assistant Professor of Medicine
NYU Cancer Center
New York, NY 10016
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Diefenbach: It is well known that age is important prognostic factor in non-Hodgkin’s lymphoma (NHL). Multiple studies have illustrated that elderly lymphoma patients have inferior survival outcomes as compared to their younger counterpart. While the tumor biology is often different in these two groups, and may play a role in this discordancy, elderly patients are often frail or have multiple medical comorbidities. These include geriatric syndromes, such as: cognitive impairment, falls, polypharmacy, and potentially inappropriate medication (PIM) use. All of these may contribute to poor outcomes for elderly patients. In addition, elderly patients are often under-treated for their aggressive lymphoma out of concern for toxicity or side effects, even though the data clearly demonstrates that elderly patients can still benefit from curative intent chemotherapy.
Dr. Maria Schwaederle[/caption]
Maria Schwaederle PharmD
Clinical Research Scientist
Center for Personalized Cancer Therapy
UCSD Moores Cancer Center
La Jolla, CA 92093
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Schwaederle: We performed this analysis with experts in the field, including but not limited to Drs Schilsky, Lee, Mendelsohn and Kurzrock, all known for their experience in the area of precision/personalized medicine.
Historically, phase I trials (which are often first in human or highly experimental in other ways) were believed to be examining only toxicity. Our meta-analysis of 13,203 patients shows that in the era of precision medicine, this historical belief needs to be discarded. Second, it is the use of precision medicine that makes this belief outdated.
Indeed, Phase I trials that utilized a biomarker-driven approach that is the essence of precision medicine had a median response rate of about 31%, which is higher than many FDA approved drugs, and this is in spite of the fact that phase I patients are a highly refractory group having failed multiple lines of conventional therapy.
Importantly, however, it was not the use of targeted agents alone that was important. It was the biomarker-based approach where patients are matched to drugs. Without matching, response rates were dismal—about 5%.
Dr. Dawn Hershman[/caption]
Dawn L. Hershman, MD MS
Professor of Medicine and Epidemiology
Leader, Breast Cancer Program
Herbert Irving Comprehensive Cancer Center
Columbia University
NY NY
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Hershman: Chemotherapy induced peripheral neuropathy is a common side effect of anti cancer therapy and there are currently no ways to prevent it. We used a large clinical trials database, SWOG, and linked it to Medicare claims for patients over the age of 65. We found that age and type of taxane were associated with the development of CIPN. We also found a significant increase when a taxane was given along with a platinum agent. We found a doubling of risk among patients with a prior history of diabetes. No other chronic condition was associated with an increased risk of CIPN. We found a suggestion of a decreased risk among patients with a prior history of auto-immune disease.
Dr. Katie Greenzang[/caption]
Katie Greenzang, MD
Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Greenzang: Advances made over the last several decades mean that more than 80 percent of children diagnosed with cancer will become long-term survivors. However, many of these survivors experience physical and cognitive late effects of the treatment that cured them. We surveyed 352 parents of children recently diagnosed with cancer to assess how well they understood their children’s risk of future limitations in physical abilities, intelligence, and quality of life. We found that an overwhelming majority of parents (92 percent) are very interested in learning about possible late effects, and most (86 percent) seek detailed information. Yet, parent and physician predictions of a child’s risk of experiencing late effects of treatment often don’t match. Among children identified by their oncologists as being at high risk for such challenges, only 38 percent of parents recognized this risk in physical abilities, 21 percent in intelligence, and 5 percent in quality of life.
Dr. Gregory Idos[/caption]
Gregory Idos MD
Division of Gastroenterology and Hepatology
Keck School of Medicine
University of Southern California
Los Angeles, CA 90033
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Idos: Identifying individuals at increased risk for hereditary cancer prompts enhanced cancer surveillance as early detection mitigates disease specific morbidity and mortality. This justifies germ line genetic testing for specific cancer risk alleles. In recent years, the field of cancer genetics has moved from a gene by gene sequencing approach to now having the ability to examine multiple genes concurrently. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. As a result, more pathogenic mutations and variants of uncertain significance (VUS) are discovered. MGP tests are increasingly being used by cancer genetic clinics, but questions remain about the clinical utility and complexities of these tests.
We are conducting a multi center prospective trial to measure the added yield of detecting pathogenic mutations using the MGP approach. In our interim analysis of the first 1000 participants, we found that multiplex gene panel testing increased the yield of detection of pathogenic mutations by 26%. In some cases, we found patient’s who had a mutation in the BRCA gene, but their family history did not indicate a history of breast or ovarian cancer.
Dr. Sarmad Sadeghi[/caption]
Sarmad Sadeghi MD, MS, PhD
Assistant Professor of Medicine
Norris Comprehensive Cancer Center
University of Southern California
MedicalResearch.com: What is the background for this study?
Dr. Sadeghi: Several years ago analyses of outcomes for radical prostatectomy highlighted the significant impact of surgical experience on the oncological outcome for the patients. In this case experience was measured by the number of radical prostatectomies performed by the surgeon, and oncological outcome was measured by treatment failure rates (rising PSA). Despite this data, the move for redirecting patients to “high volume centers” where more experienced surgeons perform the operation has been sluggish. There was insufficient data on what is involved in referring patients to high volume centers and whether or not such action is cost effective.
In a previous study we demonstrated that for every referral to a high volume center, there would be an average of $1,800 over a follow-up period of 20 years in societal cost savings. The main source of these savings is fewer treatment failures.
The next question was who is a good candidate for referral and whether these savings can offset the referral costs.
Dr. Philip McCarthy[/caption]
Philip McCarthy, BA, MD
Professor of Oncology
Director, Blood and Marrow Transplant Program
Roswell Park Cancer Institute
Associate Professor of Medicine
Jacobs School of Medicine and Biomedical Sciences
State University of New York at Buffalo
Buffalo, NY 14263
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. McCarthy: There have been three Phase III studies that examined the role of maintenance lenalidomide after autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma patients. IFM 2005-02 (France), CALGB 100104 (Alliance, USA), GIMEMA-RVMM-PI-209 (Italy). All three studies had progression free survival (PFS) as their primary endpoint and all demonstrated a superior PFS when compared to placebo or no therapy after ASCT. However only the CALGB 100104 study demonstrated a statistically superior overall survival (OS). Thus, a meta-analysis was necessary to assess the effect of post-ASCT lenalidomide maintenance on overall survival. This study utilized a pooled analysis of updated primary-source patient data from all three studies after the primary efficacy analyses had been conducted. The meta-analysis demonstrated that there is a statistically superior OS (P value=0.001, HR=0.74 (0.62-0.89)), Median OS for no maintenance or placebo was 86 months and the median OS for lenalidomide had not been reached. The median OS for lenalidomide treatment arm was extrapolated to be 116 months based on median of the control arm and HR (median, 86 months; HR = 0.74). Thus, there is a 26% reduction in the risk of death which is an estimated 2.5 year increase in median OS. There is an increased incidence of second primary malignancies with lenalidomide maintenance when compared to placebo but this risk is less than the risk of dying when not receiving lenalidomide.
Dr. Kenneth Iczkowski,[/caption]
Kenneth A. Iczkowski, M.D.
Department of Pathology
Medical College of Wisconsin
Milwaukee, WI 53226
MedicalResearch.com: What is the background for this study?
Dr. Iczkowski: The International Society of Urological Pathology (ISUP) in 2014 proposed use of a new 5-tier grade grouping system to supplement traditional Gleason grading to facilitate prognosis stratification and treatment1. The 5 categories subsume: Gleason 3+3=6, Gleason 3+4=7, Gleason 4+3=7, Gleason 8, and Gleason 9-10.
We desired to determine whether men with a highest Gleason score of 3+5=8 or 5+3=8 in their set of prostate biopsy specimens, would have differing outcomes from those with Gleason 4+4=8. Because Gleason 5 cancer has been demonstrated to have a higher biologic potential than Gleason 4, it was expected that Gleason score 8 pattern with any Gleason 5 pattern would have a worse outcome.
Dr. Wayne Furman[/caption]
Wayne L. Furman, MD
Department of Oncology
Jude Children's Research Hospital
Memphis, TN 38105-3678
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Furman: Despite improvement in 2-yr EFS from 46% to 66% with the inclusion of dinutuximab, a monoclonal antibody that recognizes a glycoprotein on neuroblasts called ‘GD2’ (disialoganglioside), more than one-third of children with high-risk neuroblastoma still are not cured. Therefore novel therapeutic approaches are needed for this subset of patients. The clinical evaluation of various anti-GD 2 monoclonal antibodies in children with neuroblastoma has been exclusively focused on treatment of patients after recovery from consolidation, in a state of ‘minimal residual disease’. This is because traditionally chemotherapy has been thought to be too immunosuppressive to combine with monoclonal antibodies. However recent studies suggest, even in the setting of “bulky” solid tumors, the combination of chemotherapy with monoclonal antibodies can enhance the effectiveness of the antibodies. First, chemotherapy can increase the efficacy of antibodies by depleting cells of the immune system that suppress immune function. Also chemotherapy-induced tumor cell death can trigger tumor antigen release, uptake by antigen processing cells and an enhanced antitumor immune response. There is also data that anti-GD2 monoclonal antibodies can suppress tumor cell growth independent of immune system involvement. Furthermore anti-GD2 monoclonal antibodies and chemotherapy have non-overlapping toxicities. All of these reasons were good reasons to evaluate the addition of a novel anti-GD2 monoclonal antibody, called hu14.18K322A, to chemotherapy, outside the setting of minimal residual disease, in children with newly diagnosed children with high-risk neuroblastoma.