Prior Cancer Excludes Many Patients From Lung Cancer Trials

Dr. David Gerber MD Associate Professor of Internal Medicine Division of Hematology and Oncology Harold C. Simmons Cancer Center at UT Southwestern Medical CenterMedicalResearch.com Interview with:
Dr. David Gerber MD
Associate Professor of Internal Medicine
Division of Hematology and Oncology
Harold C. Simmons Cancer Center at UT Southwestern Medical Center

Medical Research: What are the main findings of the study?

Dr. Gerber: Fewer than 3% of adult cancer patients in the United States are enrolled in clinical trials.  Increasingly numerous and stringent eligibility criteria are a major factor limiting participation in clinical trials.  We examined the longstanding and widespread practice of excluding patients with prior cancer from oncology clinical trials.  This policy presumably reflects concerns that a prior cancer would interfere with the conduct, outcomes, or interpretation of a clinical trial, although there is no clear evidence supporting that assumption.

We examined more than 50 National Cancer Institute (NCI)-sponsored lung cancer clinical trials.  We found that 80% excluded patients with prior cancers.  This exclusion criterion was applied broadly, including to more than two-thirds of trials with non-survival endpoints.  We then examined national Surveillance Epidemiology and End Results (SEER)-Medicare linked data to estimate the proportion of patients who would be excluded from these trials due to prior cancer.  We found that up to 18% of potential patients are excluded for this reason alone.  In large phase 3 clinical trials, that corresponds to more than 200 patients.

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Engineering A Probiotic To Reduce Obesity

Sean Davies PhD Department of Pharmacology Vanderbilt UniversityMedicalResearch.com Interview with:
Sean Davies PhD
Department of Pharmacology
Vanderbilt University

Medical Research: What are the main findings of the study?

Dr. Davies: N-acyl phosphatidylethanolamine (NAPE) is a fat-like molecule normally produced by small intestine of mammals in response to eating high fat foods that helps signal a feeling of fullness to the brain.  This sensation of fullness is what normally helps us decide to stop eating, but in obese people it appears that not enough NAPE is produced so that not enough of that signal gets sent to the brain.  So we wanted to find a way to increase the amount of NAPE made in the intestinal tract, with the hope that this would help protect against obesity. Our approach was to engineer a probiotic bacteria that normally colonizes the gut of humans and other mammals so that it would make NAPE.  Our hope was that when this gut bacteria made the NAPE, it would be absorbed by the intestine and help supplement the NAPE already being made by the intestine so that a more complete sensation of fullness would be send to the brain.

What we found was that our engineered bacteria made a significant amount of NAPE and that when fed to mice, the bacteria would colonize the gut like normal and that the intestinal cells could absorb this NAPE.  Most importantly, we found that mice that received this bacteria ate less of the high fat diet than mice that were not treated or that received bacteria that did not make NAPE. Because the mice ate less of the high fat diet, and also because they burned the fat they had more effectively, the mice receiving the bacteria producing NAPE had only 50% of  the body fat of the control mice.  While the control mice showed the early signs of developing diabetes, the mice that received the NAPE producing bacteria showed almost no signs of developing diabetes. So the presence of these NAPE producing bacteria protected the mice from the harmful effects of the high fat diet.

Another key findings was that because the bacteria live in the GI tract and keep producing the NAPE for many weeks, we didn’t have to keep administering the bacteria to the mice to keep up the protective effect.  Even a month after we stopped giving the bacteria producing NAPE, the mice were still protected from the effects of the high fat diet.  Eventually after about six weeks, the bacteria died out and the mice started eating the same amount of food as the control mice, but even for at least another six weeks after this, they still weighed less than the control mice.

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Links Between Breast Cancer and Obesity Studied

Sai-Ching Jim Yeung, MD, PhD, FACP Professor of Medicine The University of Texas MD Anderson Cancer Center Department of Emergency Medicine Department of Endocrine Neoplasia & Hormonal Disorders Houston, Texas  77230-1402MedicalResearch.com Interview with
Sai-Ching Jim Yeung, MD, PhD, FACP
Professor of Medicine
The University of Texas MD Anderson Cancer Center
Department of Emergency Medicine
Department of Endocrine Neoplasia & Hormonal Disorders
Houston, Texas  77230-1402

MedicalResearch: What are the main findings of the study?

Dr. Yeung: We believe that this study has bridged a significant gap in knowledge between epidemiological data (the association of obesity and poor breast cancer prognosis) and biological mechanisms mediating the impact of obesity on cancer. This study provides an important mechanistic insight into the causal relationship between obesity and breast cancer growth.

  1. Direct evidence for the links between obesity-associated changes in the biological processes and hallmarks of cancer in human estrogen receptor-positive (ER+) breast cancer. 

It is well known that obesity is associated epidemiologicaly with decreased survival in ER+ breast cancer patients. Although a body of experimental literature exists to suggest important roles for estrogen, insulin/IGF-1 and adipokine signaling and inflammation in the mechanisms mediating the impact of obesity on cancer, direct evidence for these mechanisms and their importance relative to one another is lacking in cancers from obese humans.

Functional transcriptomic analysis of a prospective observation cohort with treatment-naïve ER+ breast cancer samples identified the insulin/PI3K signaling and secretion of cytokines among the top biological processes involved. Many of the obesity-associated changes in biological processes can be linked to cancer hallmarks.  Upstream regulator analysis identified estrogen (?-estradiol), insulin (INS1), insulin-like growth factor-1 (IGF1), and adipokines [vascular endothelial growth factor A (VEGFA), tissue necrosis factor (TNF), interleukin-6 (IL6), oncostatin-M (OSM), chemokine ligand 5 (CCL5), leptin (LEP), leukemia inhibitory factor (LIF), C-reactive protein (CRP), adiponectin (ADIPOQ), and interleukin-10 (IL10)] in mediating the impact of obesity on human ER+ breast cancer.

  1. Experimental evidence that obesity causes accelerated oncogene-driven ER+ breast cancer carcinogenesis.

While it is not possible to conduct a human experiment to prospectively examine the causal relationship between obesity and breast cancer, we created a transgenic mouse model with genetically induced obesity and oncogene-driven breast cancer.  With this model we found strong in vivo evidence using both longitudinal experiments and cross-sectional experiments that obesity accelerated oncogene-driven breast carcinogenesis.
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Aspirin and Lifestyle Changes May Modulate Colon Cancer Risk

Kaspar Truninger, MD, FMH Gastroenterology and Internal Medicine Langenthal, SwitzerlandMedicalResearch.com Interview with:
Kaspar Truninger, MD, FMH
Gastroenterology and Internal Medicine
Langenthal, Switzerland

MedicalResearch: What are the main findings of the study?

Dr. Truninger: In our study, we investigated the effect of lifestyle exposure on DNA methylation. We measured genome-wide promoter CpG methylation in 1092 normal colon biopsies from 546 healthy females. We observed that fewer CpGs acquired age-dependent methylation in users of aspirin and hormonal replacement therapy compared with nonusers, whereas more CpGs were affected in smokers and individuals with a body mass index > 25 compared with nonsmokers and less obese females. Half of the CpGs showing age-dependent methylation gain were hypermethylated in tissue of colorectal cancer. These loci gained methylation with a higher rate and were particularly susceptible to lifestyle exposure compared to age-only methylated CpGs. In addition, these CpGs were enriched for polycomb regions.  Finally, all effects were different according to the anatomic location along the colon.

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Prostate Cancer: Tomato Products May Reduce Risk

Edward Giovannucci, MD, ScD Department of Nutrition Harvard School of Public Health Boston, MAMedicalResearch.com Interview with:
Edward Giovannucci, MD, ScD
Department of Nutrition
Harvard School of Public Health
Boston, MA


MedicalResearch: What are the main findings of the study?

Dr. Giovannucci: In 50,000 men followed over 24 years, we found that those regularly consuming tomato products, which are high in lycopene, had a 30% lower risk of developing lethal prostate cancer. Among men being screened regularly with PSA, the risk reduction from high tomato consumption was 50%. We also examined the prostate cancer tissue and found that higher dietary lycopene intake was associated with less new blood vessel formation, which may help explain why the cancers were less likely to progress.
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Breast Cancer: High Fat Diet Raises Risk of Hormone Sensitive Cancer

dr_sabina-sieriMedicalResearch.com Interview with:
Sabina Sieri, PhD
Epidemiology and Prevention Unit
Department of Preventive & Predictive Medicine
Fondazione IRCCS Istituto Nazionale dei Tumori
20133 Milan – Italy

MedicalResearch.com: What are the main findings of this study?

Dr. Sieri: In our study we found that there was an increased risk of developing breast cancer from high saturated fat intake. High total and saturated fat intake were associated with greater risk of ER PR positive breast cancer. High saturated fat intake was also associated with a greater risk of HER2 negative disease. So, a high-fat diet increases breast cancer risk and, most conspicuously, a high saturated fat intake increases the risk of developing hormone-sensitive diseases, suggesting saturated fat involvement in the etiology of hormone-sensitive breast cancer.

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Breast Cancer Survivors: Increased Marker of Aging Accompanies Standard Chemotherapy

Hanna Sanoff MD, MPH Lineberger Comprehensive Cancer Center Department of Medicine University of North Carolina, Chapel Hill, NCMedicalResearch.com Interview with:
Hanna Sanoff MD, MPH
Lineberger Comprehensive Cancer Center
Department of Medicine
University of North Carolina, Chapel Hill, NC


MedicalResearch.com: What are the main findings of the study?

Dr. Sanoff: We measured p16, a protein that increases with cellular aging, in blood cells of women receiving chemotherapy for breast cancer. We found that a standard course of chemotherapy led to an increase in p16 expression equivalent to what we have previous seen in people over the course of 10-15 years of chronological aging. This increase persisted in cancer survivors an average of three and half years after treatment.
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Mucin Profiling of Pancreatic Cysts to Improve Pancreatic Cancer Detection

Dr. Karolina Sjöberg Jabbar, MD, Medicine Policlinic II, Bla Straket 5, Sahlgrenska University Hospital Gothenburg, SwedenMedicalResearch.com Interview with
Dr. Karolina Sjöberg Jabbar, MD,

Medicine Policlinic II, Bla Straket 5, Sahlgrenska University Hospital
Gothenburg, Sweden

 

MedicalResearch.com: What are the main findings of the study?

Answer: The main finding of this study is that the presence of mucin proteins in pancreatic cyst fluid, as evaluated by mass spectrometry, can predict with high accuracy (97%) which pancreatic cysts contain premalignant and malignant tumours. This is important, given that pancreatic cystic lesions are an increasingly common incidental finding on imaging. While most of them pose no threat to the patient, a minor proportion has malignant potential, and may be considered precursors to pancreatic cancer.

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Castration-Resistant Prostate Cancer: Serum Biomarkers of Bone Metabolism

Primo N. Lara, Jr, MD, Professor of Medicine, University of California Davis School of Medicine Associate Director for Translational Research UC Davis Comprehensive Cancer Center Sacramento, CA 95817MedicalResearch.com Interview with:
Primo N. Lara, Jr, MD,
Professor of Medicine, University of California Davis School of Medicine
Associate Director for Translational Research
UC Davis Comprehensive Cancer Center
Sacramento, CA 95817

MedicalResearch.com: What are the main findings of the study:

Dr. Lara:  “We found that blood markers of bone turnover can be used to predict outcomes in men with advanced prostate cancer with spread to bone. We also found that a small proportion of men could be predicted to benefit from an investigational drug based on these same markers.”
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Colon Cancer Patients Have Less Diverse Gut Bacteria

MedicalResearch.com Interview with:
Jiyoung Ahn, PhD Assistant Professor of Epidemiology Department of Population Health NYU School of Medicine New York, NY 10016Jiyoung Ahn, PhD
Assistant Professor of Epidemiology
Department of Population Health
NYU School of Medicine
New York, NY 10016


MedicalResearch.com: What are the main findings of the study?

Dr. Ahn: Before we did our research, it was suspected that gut bacteria were related to colorectal cancer. We, for the first time, found colorectal cancer patients have a different gut bacteria composition than healthy subjects.

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Breast Cancer Risk: Increased by Pre- First Pregnancy Alcohol Intake

MedicalResearch.com Interview with:

Ying Liu, MD, PhD
Instructor, Division of Public Health Sciences
Department of Surgery
Washington University School of Medicine
660 South Euclid Ave Campus Box 8100
St. Louis, MO 63110

MedicalResearch.com: What are the main findings of the study?

Answer: Alcohol intake between menarche (first menstrual period) and first pregnancy was consistently associated with increased risks of breast cancer and proliferative benign breast disease. For every 10 gram/day alcohol intake (approximately a drink a day) during this specific time period, the risk for breast cancer increased by 11% and the risk for proliferative benign breast disease increased by 16%.
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Lung Cancer: Micropapillary Morphology To Guide Resection vs Lobectomy Choice

Prasad Adusumilli MD, FACS Associate Member, Thoracic Surgery Memorial Sloan-Kettering Cancer Center New YorkMedicalResearch.com Interview with: Prasad Adusumilli MD, FACS
Associate Member, Thoracic Surgery
Memorial Sloan-Kettering Cancer Center
New York


MedicalResearch.com: What are the main findings of the study?

Answer: The current standard of care of for early-stage lung adenocarcinoma, the common form of lung cancer is curative-intent surgery either by limited resection, LR (removal of tumor with clear margins) or lobectomy, LO (removal of one-third to one-half of the lung harboring the tumor). Although lung-sparing LR is preferable, there is a reported incidence of 30-40% of recurrences within the same lung. The causative factor/s for these local recurrences is not known.

In our study, we analyzed recurrence patterns and pathological features in patients who underwent 476 LO and 258 LR performed at the Memorial Sloan-Kettering Cancer Center, New York. We investigated the morphological patterns in pathology specimens utilizing the recently proposed International Association for the Study of Lung Cancer / European Respiratory Society / American Thoracic Society (IASLC/ERS/ATS) classification. We noticed that presence of micropapillary morphology was associated with three times higher recurrences in patients undergoing LR compared to LO, these recurrences were lower when there is an adequate margin (2 cm) resected beyond the tumor. In patients undergoing LO, the recurrences were 75% less.
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HIV-Lymphoma Survival – Not Improving in Anti-Retroviral Therapy Era

MedicalResearch.com Interview with: Satish Gopal, MD, MPH
Program in Global Oncology, Lineberger Comprehensive Cancer Center
UNC Project-Malawi, Tidziwe Center, Private Bag A-104, Lilongwe, Malawi

MedicalResearch.com: What is the primary message our physician readers should take away from the piece?”

Answer: Lymphoma is one of the leading causes of HIV-associated death in the modern ART era. In our analyses of a large multicenter US cohort, survival for HIV-associated lymphoma patients receiving routine care has not clearly improved since the modern ART era began, and remains significantly worse than SEER outcomes for the same lymphoma subtypes in the general population. This was somewhat surprising in an era of normalizing life expectancy for HIV-infected patients on ART, and quite different from the outstanding results achieved for this population in recent clinical trials conducted by AMC and NCI.
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Regional Variation in Spending and Survival for Older Adults With Advanced Cancer

Gabriel Brooks MD Fellow, Medical Oncology Dana-Farber Cancer InstituteMedicalResearch.com Interview with Gabriel Brooks MD
Fellow, Medical Oncology
Dana-Farber Cancer Institute

MedicalResearch.com: What are the main findings of the study?

Dr. Brooks: First, we found that there is substantial regional variation in Medicare spending for patients with advanced cancer.  For patients with a new diagnosis of advanced stage cancer, spending in the six months following diagnosis varied by 32% between regions in the highest and lowest quintiles of spending.  And for patients who died from cancer, spending in the last six months of life varied by 41% between the highest and lowest spending regions.

Second, we tested the association between area-level spending and survival from the time of advanced cancer diagnosis.  We found that there was no consistent association between increasing spending and survival for any of the five cancer sites included in our study (non-small cell lung cancer, colorectal cancer, pancreas cancer, breast cancer and prostate cancer).
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Selection Criteria for Lung-Cancer Screening

Dr. Martin C. Tammemägi  Professor (Epidemiology) Brock University Department of Community Health Sciences Walker Complex – Academic South, Room 306 St. Catharines, Ontario, Canada L2S 3A1Medical Research.com
Author Interview: Dr. Martin C. Tammemägi

Professor (Epidemiology) Brock University
Department of Community Health Sciences
St. Catharines, Ontario, Canada L2S 3A1

Medical Research.com What are the main findings of the study? 

Dr. Tammemägi: Our study accomplished three things:

1. We presented an updated Lung Cancer Risk Prediction Model, which compared to our previously JNCI-published model, incorporates more predictors but is simpler to use because we changed the way we modeled nonlinear effects.

2. We demonstrated that using the Lung Cancer Risk Prediction Model to select individuals for lung cancer screening was much more effective than using the National Lung Screening Trial (NLST) enrolment criteria.  41.3% fewer lung cancers were missed.  Sensitivity and positive predictive value of identifying individuals who develop lung cancer were significantly improved.  Shortly after our NEJM paper was published, Ma et al published in CANCER their findings that 8.6 million Americans are NLST-criteria positive and if they were CT screened under ideal conditions 12,000 lung cancer deaths would be averted.  Our NEJM article findings indicate that an additional 2,764 lives would be saved if the selection criteria had enrolled 8.6 million individuals for screening based on highest risk by our Lung Cancer Risk Prediction Model.

3. Importantly, using NLST data we demonstrated that the beneficial effect of CT screening did not vary by model predicted lung cancer risk.
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