Black Men and Women Continue To Have Lower Colon Cancer Survival Rates

MedicalResearch.com Interview with:

“Large Colon Cancer Arising in Adenoma” by Ed Uthman is licensed under CC BY 2.0

“Large Colon Cancer Arising in Adenoma” by Ed Uthman

Dr. Arica White PhD MPH
Division of Cancer Prevention and Control
CDC

MedicalResearch.com: What is the likelihood of reaching the 80% CRC screening rate goal by next year?

Response: As of 2016, 67% of adults age 50-75 years reported being up-to-date with colorectal cancer screening. The 80% by 2018 initiative represented an aspirational goal that public health, non-profit, and community-based organizations will continue to strive for regardless of the outcome in 2018.

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Insurance Coverage, Tumor Types Linked to Black-White Survival Disparity Among Younger Colorectal Cancer Patients

MedicalResearch.com Interview with:

Helmneh M. Sineshaw, MD, MPH American Cancer Society Atlanta, GA 30303

Dr. Sineshaw

Helmneh M. Sineshaw, MD, MPH
American Cancer Society
Atlanta, GA 30303

MedicalResearch.com: What is the background for this study?

Response: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the United Sates. Although overall CRC incidence and mortality rates are decreasing in the United States, rates are increasing in the younger population. Notwithstanding these patterns, CRC incidence and mortality rates continue to be higher in blacks than in whites. Although black-white survival disparity among patients with colorectal cancer is well documented in the literature and multiple factors have been proposed as potential contributors, the contributions of differences in demographic characteristics, insurance type, comorbidity, tumor presentation, and treatment receipt to the racial disparity in survival among nonelderly CRC patients are unknown.

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Patients With Dementia Less Likely To Receive Chemotherapy for Colon Cancer

MedicalResearch.com Interview with:

Yingjia Chen, M.Sc, MPH, Ph.D. Postdoctoral Fellow University of California, San Francisco

Dr. Chen

Yingjia Chen, M.Sc, MPH, Ph.D.
Postdoctoral Fellow
University of California, San Francisco 

MedicalResearch.com: What is the background for this study?

Response: Both colon cancer and dementia are prevalent among the elderly and have a high risk of co-occurrence. Previous studies found that patients with dementia were treated less aggressively. In this study, we hypothesized that presence of pre-existing dementia was associated with worse survival for stage III colon cancer patients, and that post-operative chemotherapy was on the causal pathway.

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Colorectal Cancer Deaths Rising Among Younger White Adults

MedicalResearch.com Interview with:

Rebecca Siegel, MPH Strategic Director, Surveillance Information Services American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303

Rebecca Siegel

Rebecca Siegel, MPH
Strategic Director, Surveillance Information Services
American Cancer Society, Inc.
250 Williams St.
Atlanta, GA 30303

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Colorectal cancer (CRC) incidence rates have been increasing in people under 55 since at least the mid-1990s, despite rapid declines in older age groups. We analyzed mortality data covering over 99% of the US population and found that death rates for CRC in adults under 55 have been increasing over the past decade of data (2004-2014) by 1% per year, in contrast to rapid declines in previous years. This indicates that the increase in incidence is not solely increased detection due to more colonoscopy use, but a true increase in disease occurrence that is of sufficient magnitude to outweigh improvements in survival because of better treatment for colorectal cancer.

The second major finding was that the rise in death rates was confined to whites, among whom death rates rose by 1.4% per year, for an overall increase of 14%. In blacks, the colorectal cancer death rate declined slowly during the entire study period (1970-2014). This racial disparity is consistent with incidence, but in contrast to trends for major risk factors for CRC, like obesity, which has increased across all racial and ethnic groups. This means that the obesity epidemic is probably not wholly responsible for the increase in disease.

Third major finding was that CRC death rates are increasing in people in their early 50s, for whom screening has been recommended for decades. This was particularly surprising since CRC screening has a two-fold impact on death rates by both preventing cancer and detecting it early when treatment is more effective. Rising death rates in this age group likely reflects lower screening rates in ages 50-54 than 55+ — 46% vs 67% in 2015, probably because of delayed initiation of screening.

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Bacteria Actively Drive Development of Colorectal Cancer

MedicalResearch.com Interview with:
Dr.Yi Xu PhD

Center for Infectious and Inflammatory Diseases
Institute of Biosciences and Technology
Department of Microbiology and Microbial Genetics,
University of Texas Health Science Center
Texas A&M Health Science Center
College Station, Texas

MedicalResearch.com: What is the background for this study?

Response: Colorectal cancer is fairly treatable when caught early with regular screenings, but it is still the second-leading cause of cancer-related deaths in American men and the third-leading cause in women. Researchers at Texas A&M have found that a subspecies of the bacterium Streptococcus gallolyticus appears to actively promote the development of colorectal cancer, which could lead to potential treatment strategies. Their findings are published in the journal PLOS Pathogens.

Scientists have known for some time that people infected with S. gallolyticus are more likely to have colorectal cancer. “This association was well established in the clinical literature,” said Yi Xu, PhD, associate professor at the Texas A&M Institute of Biosciences and Technology and principal investigator of the study. However, it was unclear if that relationship was cause or effect—that the bacteria promote cancer development—or if S. gallolyticus simply grows easily in the environment that the tumor cells provide.  Continue reading

Fecal Testing Better At Detecting Colon Cancer Than Advanced Atypical Changes

MedicalResearch.com Interview with:

Anastasia Katsoula, MD MSc Aristotle University of Thessaloniki Greece 

Dr. Katsoula

Anastasia Katsoula, MD MSc
Aristotle University of Thessaloniki
Greece 

MedicalResearch.com: What is the background for this study?

Response: Early detection of colorectal cancer (CRC) has proven to be effective in reduction of cancer-related mortality. Fecal immunochemical testing (FIT) has been recently advocated for population-based screening for CRC in average-risk individuals due to its high accuracy and potential for adherence, based on results from previous systematic reviews and meta-analyses in average-risk populations. However, the potential role of FIT for screening of subjects at increased risk for CRC has not yet been elucidated, hence colonoscopy is currently the only recommended screening option for subjects at increased risk of CRC. We performed a systematic review and meta-analysis to explore the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in patientswith personal or familial history of CRC, using colonoscopy as the reference standard.

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Healthy Diet and Exercise Reduce Colon Cancer Recurrence

MedicalResearch.com Interview with:
Dr. Erin Van Blarigan, ScD
Assistant Professor, Department of Epidemiology and Biostatistics
UC San Francisco

MedicalResearch.com: What is the background for this study?

Response: There are over 1.3 million colorectal cancer survivors in the United States. Cancer survivors often seek guidance on what they can do to lower their risk of cancer recurrence and death. In response to patient interest and the need for improved survivorship care, the American Cancer Society (ACS) published guidelines on nutrition and physical activity for cancer survivors.

The guidelines are to:
1) achieve and maintain a healthy body weight;
2) engage in regular physical activity; and
3) achieve a dietary pattern that is high in vegetables, fruits, and whole grains.

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Risk of Interval Colorectal Cancer Higher in Blacks Than Whites

MedicalResearch.com Interview with:

Stacey Fedewa PhD Strategic Director, Risk Factors & Screening Surveillance American Cancer Society, Inc. Atlanta, GA 30303

Dr. Fedewa

Stacey Fedewa PhD
Strategic Director, Risk Factors & Screening Surveillance
American Cancer Society, Inc.
Atlanta, GA 30303

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Screening for colorectal cancer is effective in reducing incidence and mortality by detecting precancerous lesions or cancer at more curable stages. But colorectal cancers can still develop in screened populations, some are missed at the time of screening; others can develop between recommended screenings. Patterns of risk for interval colorectal cancer, defined as cancers that develop after a negative result on colonoscopy, by race/ethnicity are not well known.

The risk for blacks was of interest to us because colorectal incidence and mortality rates in blacks are the highest among any race or ethnicity in the United States. We were also interested to see if quality of colonoscopy, measured by physician’s polyp detection rate, could account for differences.

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Preclinical Study Finds Cancer Stem Cell Inhibitor Sensitizes Colon Cancer Cells To Immunotherapy

MedicalResearch.com Interview with:
Dr. Yuan Gao

Assistant Investigator at Boston Biomedical

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Colorectal cancer (CRC) is the third most commonly diagnosed malignant disease and third most frequent cause of cancer-related death in the United States. Standard treatment for unresectable metastatic CRC currently includes first and second line 5-fluorouracil (5-FU)-based chemotherapy regimens. However, CRC patients often develop chemoresistance. Recently, immunotherapy has emerged as a revolutionary new treatment for CRC. However, with the exception of a small percentage of CRC patients that display microsatellite instability (MSI), the vast majority of colorectal cancer patients have been found to be resistant to immune checkpoint therapies.

Cancer stem cells (CSCs), a highly malignant tumor cell subpopulation capable of self-renewal, are considered to be fundamentally responsible for malignant growth and tumor recurrence. Emerging evidence indicates that CSCs and cancer stemness pathways, such as STAT3, beta-Catenin, CD44 and Nanog, are involved in the immune evasion of cancers. BBI-608 (napabucasin) is an orally-administered first-in-class cancer stemness inhibitor that works by targeting STAT3. In this study, we investigated the effect of cancer stemness inhibition on sensitizing colorectal cancer to immune checkpoint inhibitors in preclinical models.

In the syngeneic microsatellite stable (MSS) tumor model, CT26, an anti-PD-1 antibody delivered as a monotherapy, produced low level and temporary antitumor activity with rapid development of complete resistance to anti-PD-1 treatment. The anti-PD-1 antibody-treated CT26 tumors exhibited increased p-STAT3 activation and overexpression of a variety of stemness factors, as well as enrichment of sphere-forming stemness-high cancer cells. Napabucasin was able to reduce basal as well as anti-PD1-induced STAT3 activation and other CSC features within CT26 tumors. The combination of a stemness inhibitor – napabucasin – with the anti-PD-1 antibody led to tumor complete response (CR) in all treated CT26 tumors, with 40 percent of the mice remaining tumor-free for 30 days following treatment termination. This combination also had a synergistic effect on the influx of tumor infiltrating CD8+ T cells, which likely contributed to the rapid tumor regression. Finally, mice CR-induced by napabucasin and the anti-PD-1 antibody were able to reject CT26 tumors upon re-challenge, but not the unrelated breast cancer 4T1 tumors.

MedicalResearch.com: What should readers take away from your report?

Response: Our data suggest cancer stemness pathways contribute to immunotherapy resistance in MSS CRC, a subtype representing the vast majority of colorectal cancer cases. Furthermore, inhibition of cancer stemness by BBI-608 sensitizes colorectal cancer to immune checkpoint inhibition, producing striking regression in a large proportion of the tumors treated.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study provides compelling preclinical evidence to support the investigation of the combination of napabucasin with immune checkpoint inhibitors in CRC. While this study specifically investigated the combination with anti-PD-1, the combination with other immunotherapies could be studied as well.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: AACR 2017 Abstract

Inhibition of cancer stemness sensitizes colorectal cancer to immune checkpoint inhibitors
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Colorectal Cancer Risk Model Using Environmental and Genetic Factors

MedicalResearch.com Interview with:

Victor Moreno, PhD. Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain Department of Clinical Sciences, Faculty of Medicine University of Barcelona Barcelona, Spain

Dr. Moreno

Victor Moreno, PhD.
Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain
Department of Clinical Sciences, Faculty of Medicine
University of Barcelona
Barcelona, Spain

Gemma Ibáñez-Sanz, MD Gastroenterologist. *Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat, Barcelona, SPAIN *Gastroenterology Department, Bellvitge University Hospital-IDIBELL,  L’Hospitalet de Llobregat, Spain

Dr. Ibáñez-Sanz

Gemma Ibáñez-Sanz, MD
Gastroenterologist.
*Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat, Barcelona, SPAIN
*Gastroenterology Department, Bellvitge University Hospital-IDIBELL,
L’Hospitalet de Llobregat, Spain 

MedicalResearch.com: What is the background for this study?

Response: Colorectal cancer (CRC) screening by faecal occult blood testing has been demonstrated to reduce CRC incidence and mortality, as well as being a cost-effective strategy compared to no screening. Currently, the target population is defined basically by age (≥50 years old), which has been called a ‘one-size-fits-all’ strategy. This strategy implies performing unnecessary screening tests in low-risk people leading to avoidable risks for patients and extra costs for the healthcare system. On the other hand, high-risk patients may receive non-invasive testing, which is a suboptimal screening technique in their case. Several risk prediction models, either for  colorectal cancer or advanced neoplasia, have been previously developed, all with limited discriminating ability.

We have developed a risk stratification model that combines environmental factors with family history and genetic susceptibility. Furthermore, we have assessed the relative contribution of these factors and the utility of the model for risk stratification and public health intervention.

MedicalResearch.com: What are the main findings?

Response: Data from common genetic susceptibility loci could be useful to stratify colorectal cancer screening in average-risk population. Individuals in the top quintile of risk alleles have an 82% increased risk compared to those in the lower quintile. We have estimated the impact of determining an individual environmental and genetic risk score in a Spanish CRC screening population. In our model, although the genetic factors are significant contributors, the modifiable risk factors contribute more strongly. Risk assessment may increase screening participation and adoption of healthier lifestyles.

MedicalResearch.com: What should readers take away from your report?

Response: On average, each environmental risk factor increases CRC risk by 35%, while each risk allele only increases it by 7%. This implies that the change of one modifiable risk factor towards healthier lifestyle might offset the effect of 4 risk alleles. Given the fact that environmental factors explain part of the CRC risk, we believe it to be important to give thought to incorporating clinical data to encourage individuals to achieve a healthier lifestyle. As the European Code Against Cancer recommends, and our findings confirm, one should have a healthy diet, a healthy body weight, be physically active and should not smoke or a high consumption of alcohol.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Future prospective studies should aim to analyse if stratifying by genetic and lifestyle risk scores is useful and cost-effective to improve screening. Subjects with higher predicted risk should probably start screening earlier and decrease the intervals between tests, while low risk individuals could start later or space more the between test intervals.

MedicalResearch.com: Is there anything else you would like to add? 

Response: Population acceptability of genetic tests is not well known. We are currently recruiting subjects from colorectal cancer screening and gastroenterology clinics in a study called COLSCREEN to assess risk perception and attitudes regarding genetic testing to prevent cancer.

No disclosures

Citation:

Sci Rep. 2017 Feb 24;7:43263. doi: 10.1038/srep43263.

Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study.

Ibáñez-Sanz G1, Díez-Villanueva A1, Alonso MH1,2, Rodríguez-Moranta F2,3, Pérez-Gómez B2,4,5, Bustamante M2,6, Martin V2,7, Llorca J2,8, Amiano P2,9, Ardanaz E2,10, Tardón A2,11, Jiménez-Moleón JJ2,12, Peiró R2,13, Alguacil J2,14, Navarro C2,15, Guinó E1,2, Binefa G1,2, Navarro PF2,4,5, Espinosa A2,6, Dávila-Batista V7, Molina AJ2,7, Palazuelos C8, Castaño-Vinyals G2,6,16,17, Aragonés N2,4,5, Kogevinas M2,6,16,17,18, Pollán M2,4,5, Moreno V1,2,19.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Colon Cancer Incidence Rises Dramatically For Young People in Their 20s and 30s

MedicalResearch.com Interview with:
Rebecca L. Siegel, MPH

Surveillance and Health Services Research
American Cancer Society
Atlanta, GA 

MedicalResearch.com: What are the main findings?

Response: It was known that colorectal cancer incidence rates are declining rapidly in people 50 years and older, but curiously increasing in people younger than 50 years. For a more comprehensive understanding of incidence patterns, we examined CRC incidence trends by 5-year age group and year of birth using age-period cohort analysis. This modeling technique helps enhance the understanding of disease trends by disentangling factors that influence all ages (period effects) from those that vary by generation (birth cohort effects).

In incidence data for almost 500,000  colorectal cancer patients during 1974-2013, we found both period and cohort effects. However, the period effects were dwarfed by the cohort effects. The age-specific risk of colorectal cancer declined during the first half of the 20thcentury, but has increased for subsequent generations since around 1950, such that those born in 1990 have twice the risk of colon cancer and 4 times the risk of rectal cancer compared to people born in 1950. Said another way, someone in their 20s today is 4 times more likely to be diagnosed with rectal cancer than someone who was in their 20s in 1970. The risk for contemporary generations has escalated back to that of people born circa 1890.

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Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer

MedicalResearch.com Interview with:
Matthew B Yurgelun, M.D

Instructor in Medicine, Harvard Medical School
Dana-Farber Cancer Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It has long been known that hereditary factors play a key role in colorectal cancer risk. It is currently well-established that approximately 3% of all colorectal cancers arise in the setting of Lynch syndrome, a relatively common inherited syndrome that markedly increases one’s lifetime risk of colorectal cancer, as well as cancers of the uterus, ovaries, stomach, small intestine, urinary tract, pancreas, and other malignancies. Current standard-of-care in the field is to test all colorectal cancer specimens for mismatch repair deficiency, which is a very reliable means of screening for Lynch syndrome. The prevalence of other hereditary syndromes among patients with colorectal cancer has not been known, though other such factors have been presumed to be quite rare.

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Stool DNA Tests (Cologuard ) Increases Colon Cancer Screening and Detection Among Previously Noncompliant Patients

MedicalResearch.com Interview with:

Dr. Mark Prince MD USMD Health System Arlington, TX 76017

Dr. Mark Prince

Dr. Mark Prince MD
USMD Health System
Arlington, TX 76017

MedicalResearch.com: What is the background for this study?

Response: This 12-month retrospective study conducted to determine the screening compliance rates for a noninvasive multitarget stool DNA (mt-sDNA) screening test (Cologuard) for colon cancer among a cohort of nearly 400 average-risk Medicare patients who had previously not complied with recommended screening. These were patients who had never had a colonoscopy, had been more than ten years since last colonoscopy, or had been more than one year since last stool testing for occult blood.

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Younger Colon Cancer Patients Receive More Chemotherapy But No Greater Survival Benefit

MedicalResearch.com Interview with:
Kangmin Zhu, PhD, MD

John P. Murtha Cancer Center, Walter Reed National Military Medical Center
Professor at the Uniformed Services University of the Health Sciences in the
Department of Preventive Medicine and Biostatistics
Bethesda, Maryland

MedicalResearch.com: What is the background for this study?

Response: An article published on JAMA Surgery in 2015 showed more utilization of chemotherapy among young colon cancer patients.  To demonstrate the study findings, we analyzed the data from the Department of Defense healthcare system, in which all members have the same level of access to medical care and therefore the potential effects of insurance status and types on research results can be reduced.

MedicalResearch.com: What are the main findings?

Response: The main findings were that young and middle-aged colon cancer patients were 2 to 8 times more likely to receive postoperative chemotherapy and 2.5 times more likely to receive multiagent regimens, compared with their counterparts aged 65 to 75 years.  However, no matched survival benefits were observed for the young and middle-aged among patients who received surgery and postoperative chemotherapy.

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ACA Medicare Changes Increased Diagnosis of Early-Stage Colorectal Cancer Among Seniors.

MedicalResearch.com Interview with:

Nengliang “Aaron” Yao PhD Assistant professor Department of Public Health Sciences University of Virginia

Dr. Nengliang Yao

Nengliang “Aaron” Yao PhD
Assistant professor
Department of Public Health Sciences
University of Virginia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The ACA made several changes in Medicare that could increase the use of cancer screening and thus lead to more early cancer diagnoses. This includes waiving patient cost-sharing for screening, waiving patient cost-sharing for one wellness visit per year, and paying bonuses to physicians for doing more work in a primary care setting.

We studied how effective those changes were in facilitating more early diagnoses of breast and colorectal cancers. We found that the changes had no effect on early breast cancer diagnoses (likely because costs and other access barriers for mammograms were already low), but increased the number of early colorectal cancer diagnoses by 8 percent.

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Physical Activity Linked to Improved Survival from Metastatic Colon Cancer

MedicalResearch.com Interview with:

Brendan John Guercio, M.D. Clinical Fellow in Medicine (EXT) Brigham and Women's Hospital

Dr. Brendan Guercio

Brendan John Guercio, M.D.
Clinical Fellow in Medicine (EXT)
Brigham and Women’s Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Sedentary lifestyle is a known risk factor for the development of colon cancer and has been associated with increased disease recurrence and mortality in patients with early stage colorectal cancer. This is the first study to our knowledge to show an association between increased physical activity (i.e. non-sedentary lifestyle) and improved survival and progression-free survival in patients with metastatic colorectal cancer.

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ACA: Screening Disparities Fall For Mammograms But Not Colonoscopies

MedicalResearch.com Interview with:

Dr. Gregory Cooper, MD Program Director, Gastroenterology, UH Cleveland Medical Center Co-Program Leader for Cancer Prevention and Control, UH Cleveland Medical Center Professor, Medicine, CWRU School of Medicine Co-Program Leader for Cancer Prevention and Control UH Seidman Cancer Center

Dr. Gregory Cooper

Dr. Gregory Cooper, MD
Program Director, Gastroenterology
UH Cleveland Medical Center
Co-Program Leader for Cancer Prevention and Control, UH Cleveland Medical Center
Professor, Medicine, CWRU School of Medicine
Co-Program Leader for Cancer Prevention and Control
UH Seidman Cancer Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Affordable Care Act, among other features, removed out of pocket expenses for approved preventive services, and this may have served as a barrier to cancer screening in socioeconomically disadvantaged individuals. If so, then the gap in screening between socioeconomic groups should narrow following the ACA.

The main findings of the study were that although in the pre-ACA era, there were disparities in screening, they narrowed only for mammography and not colonoscopy.

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Cancer Susceptibility Genes Common In Early-Onset Colorectal Cancer

MedicalResearch.com Interview with:

Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH 43221

Heather Hampel

Heather Hampel, MS, LGC
Associate Director, Division of Human Genetics
Associate Director, Biospecimen Research
Professor, Internal Medicine
Licensed Genetic Counselor
The Ohio State University Comprehensive Cancer Center
Columbus, OH 43221

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study was part of the Ohio Colorectal Cancer Prevention Initiative, a statewide study being conducted at 50 hospitals that includes universal tumor screening for Lynch syndrome. For the subset of 450 colorectal cancer patients diagnosed under age 50, we performed multi-gene cancer panel testing regardless of the results of their tumor screening for Lynch syndrome since early age of diagnosis is a red flag that a cancer might be hereditary.

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Screening for Colorectal Cancer Issues Evolve For Patients and Physicians

MedicalResearch.com Interview with:

David Lieberman MD Professor of Medicine Chief, Division of Gastroenterology and Hepatology Oregon Health and Science University L461 Portland, OR 97239

Dr. David Lieberman

David Lieberman MD
Professor of Medicine
Chief, Division of Gastroenterology and Hepatology
Oregon Health and Science University
Portland, OR 97239

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: New guidelines for colorectal cancer (CRC) screening from the USPSTF were published in June 2016. They recommended any of 8 different screening programs.

The purpose of this review was to highlight elements not included in the USPSTF report:
1. Elements of informed decision making associated with each program
2. Quality metrics for each program
3. Recommendations for higher than average risk individuals

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How Does Gout Affect Risk of Colon Cancer?

MedicalResearch.com Interview with:

Michael Pillinger, MD Professor of Medicine and Biochemistry and Molecular Pharmacology NYU School of Medicine

Dr. Michael Pillinger

Michael Pillinger, MD
Professor of Medicine and Biochemistry and Molecular Pharmacology
NYU School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We are interested in the co-morbidities of gout and the fact that gout is accompanied by multiple cardiovascular, renal and other events. The implications of gout for cancer are less clear, but the basic biology suggests that either:

1) the acute and chronic inflammation of gout could contribute to a pro-cancer environment;
2) the anti-oxidant effects of urate could have anti-cancer properties;
3) the ability of uric acid to serve as a “danger signal” released from dying cells (potentially including cancer cells” could promote anti-cancer immunity.

The clinical literature is murky at best.

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Prognostic Survival Associated With Left vs Right-Sided Colon Cancer

MedicalResearch.com Interview with:
Fausto Petrelli, MD
Oncology Unit, Oncology Department
Treviglio ,Italy

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This meta-analysis evaluated if side (excluding rectum site) represents an independent prognostic factor for survival in patients with stages 1-4 colon cancer. This variable is in fact associated with an adverse outcome with a reduced risk of death by 20% if patients are affected by a left colon cancer compared to those with right colon cancers. Implications are enormous: for prognosis first but also for follow-up, stratification into clinical trials and treatment (for both medical and surgical therapies). The power of the study is relevant: it enclosed 66 studies with more than 1 million of patients retrospectively or prospectively analyzed for survival according to common variables known to be prognostic in colorectal cancer (age, sex, stage, race, adjuvant CT..etc) in multivariate analysis.

Side is significantly associated with survival independent of other covariates analyzed. The question of the side is old and partially known, but no study systematically explored the published literature to confirm this suggestion. Recent large randomized trials in metastatic disease showed different results according to the site of disease with right colon cancers usually less responsive to anti-EGFR treatment due to a different molecular behavior and conversely left colon cancers which attained the greater benefit from cetuximab and panitumumab due to less BRAF mutations in their tissue. Also, a less extensive and radical lymphadenectomy in right-sided cancers, without a complete mesocolon excision during surgery, could hamper their cure rate, as our colorectal surgeon’s team lead by Prof. Giovanni Sgroi and Luca Turati MD, suggested in the discussion. It is also well known the leads term bias with a later diagnosis of right cancers due to clinical and anatomic reasons.

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Study Supports Routine Colon Cancer Screening Through Age 75, With Individualized Decisions Afterwards

MedicalResearch.com Interview with:

Xabier Garcia-De-Albeniz MD PhD Research Associate Department of Epidemiology Mongan Institute for Health Policy, Massachusetts General Hospital. Board Member, GEMCAD. Member, Group for Cancer Prevention, SEOM

Dr. Xabier Garcia-De-Albeniz

Xabier Garcia-De-Albeniz MD PhD
Research Associate
Department of Epidemiology
Harvard T.H. Chan School of Public Health
Mongan Institute for Health Policy
Massachusetts General Hospital

MedicalResearch.com: What is the background for this study?

Response: Randomized controlled trials are considered the gold standard to inform health care delivery. Unfortunately, no randomized controlled trials of screening colonoscopy have been completed. Ongoing trials exclude persons aged 75 or older, and will not have mature results before 2025. However, healthy persons older than 75 may live long enough to benefit from colorectal cancer (CRC) screening. The Medicare program reimburses screening colonoscopy without an upper age limit since the year 2001. We used the extensive experience of Medicare beneficiaries to evaluate the effectiveness and safety of screening colonoscopy.

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Early Palliative Care Improved Patients’ Symptoms and Coping Skills

MedicalResearch.com Interview with:

Joseph A. Greer, Ph.D. Program Director, Center for Psychiatric Oncology & Behavioral Sciences Associate Director, Cancer Outcomes Research Program, Massachusetts General Hospital Cancer Center Yawkey Center, Boston, MA 02114

Dr. Joseph Greer

Joseph A. Greer, Ph.D.
Program Director, Center for Psychiatric Oncology & Behavioral Sciences
Associate Director, Cancer Outcomes Research Program,
Massachusetts General Hospital Cancer Center
Yawkey Center, Boston, MA 02114

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many patients with advanced cancer have a high symptom burden, increased depression symptoms, misperceptions about their prognosis, and difficulties in making decisions about care at the end of life.

To address these challenges and improve care for this vulnerable population, our research team initially conducted a small, single-group pilot study of early palliative care integrated with standard oncology care for patients with advanced lung cancer.

This study showed that the model of integrated care was feasible and acceptable to patients and their families. Specifically, the majority of patients in the study were able to meet with a palliative care clinician at least monthly from the time of diagnosis of metastatic lung cancer, in order to receive help with managing symptoms as well as support for coping with the disease and making decisions about treatment. We then conducted a follow-up randomized controlled trial of early, integrated palliative care in a sample of approximately 150 patients with metastatic non-small cell lung cancer. This study was published in the New England Journal of Medicine in 2010 and showed that those patients who received early palliative care reported significantly improved quality of life, mood, prognostic awareness, and end-of-life care compared to those who received standard oncology care alone.

To confirm the findings of our prior research and to determine whether the benefits of early integrated palliative care would apply to a larger sample of patients with diverse malignancies, we recently completed another randomized trial of this same model of care in a sample of 350 patients with incurable lung and gastrointestinal cancers. In this trial, we observed that patients who received the early palliative care intervention reported higher quality of life and improved mood by 24 weeks but not at the primary end-point of 12 weeks. Our team was surprised to find that the trajectory of quality of life and depression symptoms over time was different for individuals with incurable lung versus gastrointestinal cancers in this study. As expected, the palliative care intervention positively buffered the decline in quality of life by 12 weeks for patients with incurable lung cancer, as we had seen in our prior trial. However, the group of patients with gastrointestinal cancers reported an improvement in their quality of life by the 12-week time point regardless of whether they received the palliative care intervention.

We are still exploring possible reasons for this difference, such as whether changes in cancer therapy may have reduced symptoms and improved quality of life in the group of patients with gastrointestinal cancer.

In addition, we were pleased to learn that the early integrated palliative care intervention led to improvements in how patients cope with their illness. For example, compared to patients in the usual oncology care group, those who received early, integrated palliative care were more likely to learn ways to accept their diagnosis and to take positive actions to make their lives better. So, in addition to treating patients’ symptoms, the palliative care clinicians in this study were bolstering people’s adaptive coping skills.

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Molecular Subtyping of Rectal Cancers Can Guide Prognosis, Treatment and Future Screening

MedicalResearch.com Interview with:

Y. Nancy You, MD, MHSc Associate Professor Section of Colorectal Surgery Department of Surgical Oncology Medical Director Familial High-risk Gastrointestinal Cancer Clinic University of Texas MD Anderson Cancer Center

Dr. Y. Nancy You

Y. Nancy You, MD, MHSc
Associate Professor
Section of Colorectal Surgery
Department of Surgical Oncology
Medical Director
Familial High-risk Gastrointestinal Cancer Clinic
University of Texas MD Anderson Cancer Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Despite the progress in the treatment of many cancers, colorectal cancer (CRC) remains the third most common and lethal cancer in the US. Over 130,000 people are expected to be diagnosed and over 50,000 patients will die from CRC this year. In the recent years, the most exciting development has been our understanding of the molecular complexity of CRC.

Currently, four major molecular subtypes of colorectal cancer are recognized. Our study focuses on the Consensus Molecular Subtype 1, which accounts for up to 15% of CRCs, and is characterized by a deficiency in DNA mismatch repair (dMMR), a high level of mutations (i.e. hypermutated), by instability in parts of the genome called microsatellites, and by strong immune activation. Prior to our study, patients with rectal cancer that belong to this molecular subtype have represented an unknown, in terms of their prognosis, and how the tumors respond to current treatments. More importantly, this molecular subtype harbor a genetic condition that can be transmitted within the family called “Lynch Syndrome”. So we designed our study to fill these gaps in our understanding that exist in this subtype of CRCs and to highlight key clinical care issues related to the caring for patients with a genetic syndrome.

The main findings are that rectal cancers belonging to this molecular subtype have favorable prognosis, respond well to standard chemoradiation, and are linked to Lynch Syndrome and should be treated at centers with expertise in hereditary cancer syndromes. Continue reading

Circulating Tumor DNA Predicts Colon Cancer Relapse

MedicalResearch.com Interview with:

Jeanne Tie MBChB, FRACP, MD Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research Department of Medical Oncology, Western Health, St Albans, Victoria, Australia. Department of Medical Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne Parkville, Victoria, Australia

Dr. Jeanne Tie

Jeanne Tie MBChB, FRACP, MD
Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research
Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.
Department of Medical Oncology,
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne
Parkville, Victoria, Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study investigated the ability of circulating tumor DNA (ctDNA) in detecting residual microscopic cancer after surgery with curative intent in patients with stage II colon cancer. Although the majority of patients with stage II colon cancer are cured by surgery alone, our ability to accurately predict the risk of cancer relapse based on current clinical and pathological criteria is imprecise. Population-based study indicated that adjuvant chemotherapy is given to up to 40% of stage II colon cancer patients, meaning that we are over-treating a significant number of patients with cytotoxic therapy. A better indicator of residual disease and recurrence would be very useful clinically.

The current study collected tumor and blood samples from 230 patients with stage II colorectal cancer. A personalised assay was then designed to detect patient-specific tumor DNA in the plasma samples collected four to ten weeks after surgery. The presence of ctDNA (positive test) in the post-operative blood sample predicted recurrence in 100% of patients, while the relapse rate is only 10% in those with negative ctDNA test. We have also shown that the ctDNA test is a better predictor of recurrence than the standard clinic-pathological criteria.

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Vanderbilt Free Colonoscopies For Uninsured Detected Some Early Cancers and Was Cost Neutral

MedicalResearch.com Interview with:
Erica R. H. Sutton, MD
Assistant Professor
Department of Surgery, General
Vanderbilt

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Colorectal cancer is one of the most preventable diseases that we face; however, despite the great strides that we have made in the realm of early detection, many people still do not undergo screenings. We sought to increase the availability of screenings to those in our community who are at high risk for colorectal cancer and uninsured by providing free colonoscopies to them and to examine the cost-effectiveness of this intervention. Over a 12-month period, 682 uninsured people underwent screening colonoscopies, and 9 cancers were detected. Compared to the Surveillance, Epidemiology, and End Results (SEER) registry, our patient population included more early-stage cancers, and our program was found to be cost-neutral.

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Many Elderly Patients Not Receiving Adequate Colon Cancer Screening or Follow Up

MedicalResearch.com Interview with:

Carrie N. Klabunde, PhD Office of Disease Prevention Office of the Director NIH Rockville MD

Dr. Carrie Klabunde

Carrie N. Klabunde, PhD
Office of Disease Prevention
Office of the Director
NIH
Rockville MD

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many studies of colorectal cancer screening focus on adults 50-75 years of age; few specifically look at screening in the elderly. We wanted to examine colorectal cancer screening use, including follow-up diagnostic testing for those with abnormal fecal blood screening tests, in adults 65 years of age and older. We also wanted to assess whether screening use in this population is influenced more by elderly individual’s chronological age, or their health status (called comorbidity in our study). The study was conducted in three large, integrated healthcare systems: Kaiser Permanente in Northern California and Southern California, and Group Health in Washington state and Idaho. We examined data on nearly 850,000 patients aged 65-89.

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Study Reevaluates Colon Cancer Screening Methods

MedicalResearch.com Interview with:
Jennifer S. Lin, MD, MCR, FACP
Director, Kaiser Permanente Research Affiliates Evidence-based Practice Center
Investigator, The Center for Health Research, Kaiser Permanente Northwest
Portland, OR 97227

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Lin: Our systematic review was commissioned by the USPSTF, in tandem with a separate modeling exercise, to help update their 2008 colorectal cancer screening recommendations. Since the previous recommendation, there has been a wealth of new evidence, including more evidence on the long-term effectiveness of flexible sigmoidoscopy for reducing colorectal cancer mortality, the screening accuracy and decreasing radiation exposure from CT colonography, and the screening accuracy for a number FDA-approved stool tests using fecal immunochemical testing (FIT).

While we have large, well-designed RCTs demonstrating that screening for colorectal cancer using flexible sigmoidoscopy and older generation stool testing reduces colorectal cancer mortality, these screening tests are no longer widely used in the United States. Well-designed diagnostic accuracy studies of screening colonoscopy, CT colonography, and various stool based tests using FIT demonstrate adequate sensitivity and specificity to detect adenomas and/or colorectal cancer, making each of them viable screening options. However, each screening option has potential harms associated with their use, particularly those allowing for direct visualization of the colon. Colonoscopy harms include perforations and major bleeding events. CT colonography requires exposure to radiation; and CT colonography not uncommonly results in detection of extra-colonic findings which necessitate additional diagnostic follow-up which may result in a benefit or harm.
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Simple Blood Test May Help Assess Risk of Colorectal Cancer

MedicalResearch.com Interview with:
Gilles Jobin, MD, FRCP, MSc
Chief of Gastroenterology
Maisonneuve-Rosemont Hospital
Associate Professor of Medicine
University of Montreal
Montréal, Qc

MedicalResearch.com: What is the background for this study?

Dr. Jobin: It is known that the immune system has a role to play in keeping the body free of cancer and tumor cells. There is a lot of scientific literature that shows that when someone has cancer, certain cells from the immune system do not function very well. These cells are called natural killer or NK cells and they are the first ones to respond when there is a virus, a bacteria or a tumor cell in the body.

If the activity of these cells is very low, then there is a higher risk of someone developing a cancer, and if someone has cancer, there are greater chances that their NK cell activity is low.

In the last few decades, a few tests have been developed to measure NK Cell activity but they have been used in research only because they were complicated and difficult to use.

The current study measured NK Cell activity (NKA) with a new commercially available simple blood test to investigate its clinical application in the detection of colorectal cancer in patients presenting for prescribed colonoscopy. The aim of this study is to evaluate the sensitivity, specificity, positive and negative predictive values of this in vitro diagnostic device in patients with colorectal cancer (CRC) and adenomatous polyps (AP).
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French Grape Seed Extract May Help Eliminate Cancer Stem Cells

MedicalResearch.com Interview with:
Ajay Goel, Ph.D.
Professor, and Director of Center for Epigenetics and Cancer Preventio
Baylor Scott & White Research Institute
Baylor University Medical Center, Dallas, TX

MedicalResearch.com: What is the background for this study?

Dr. Goel: One of the areas in which I am interested is examining the activity of natural compounds as it relates to cancer prevention, progression, and treatment. Polyphenols have known antioxidant and anti-cancer activity, but it is important that we better understand the mechanisms of action. I have found in my research on curcumin and boswellia that these plants contain compounds that work on an epigenetic level and can influence microRNA in ways that chemotherapeutic agents cannot. MicroRNA is important because it is like a master control panel that turns on and off a multitude of genetic “switches.” Influencing the activity of microRNA influences a wide array of genetic expression. If you tell the general of the army what to do, it has a much greater impact than directions given to a private, because the general influences so many more soldiers.

Because grape seed extract contains oligomeric proanthocyanidins (OPC) that are also quite active in influential cancer mitigating genetic pathways, I wanted to determine its effects more exactly. I chose specifically tannin-free, low molecular weight OPCs because there is some evidence that the larger sized OPCs are not absorbable.

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Black Patients Five Times More Likely To Present With Advanced Colon Cancer

MedicalResearch.com Interview with:

Robert Wong, M.D., M.S. Attending Physician, Gastroenterology & Hepatology Director, GI Education & Research Highland Hospital I A member of Alameda Health System Oakland, CA

Dr. Robert Wong

Robert Wong, M.D., M.S.
Attending Physician, Gastroenterology & Hepatology
Director, GI Education & Research
Highland Hospital I A member of Alameda Health System
Oakland, CA

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Wong:  Colorectal cancer is a leading cause of morbidity and mortality in the United States. Early diagnosis through implementation of effective screening and surveillance programs leads to earlier staged tumor at time of diagnosis, which increases the treatment opportunities and improves overall survival. However, disparities in access to effective screening and surveillance can impair timely diagnosis and lead to advanced disease, limited treatment options and poor outcomes. The current study evaluated race/ethnicity-specific disparities in colorectal cancer epidemiology at a large urban safety net hospital and observed African American patients had significantly more advanced cancer stage at the time of diagnosis. Our study observed that African Americans were over 5 times more likely to have advanced stage 3-4 colon cancer at time of diagnosis compared with non-Hispanic white patients with colon cancer. While these findings are likely multifactorial, it sheds important light on race/ethnicity-specific disparities in colorectal cancer epidemiology and helps target future education and research to improve outcomes.

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Aerobic Exercise Linked To Decreased Digestive Cancer Risk

MedicalResearch.com Interview with:

NaNa Keum Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health

Nana Keum

NaNa Keum, ScD|
Harvard T. H. Chan
School of Public Health Department of Nutrition
Departments of Nutrition and Epidemiology,
Harvard T.H. Chan School of Public Health
Boston, MA 02115

MedicalResearch.com: What is the background for this study?

Response: While general health benefits of physical activity are well-known, evidence on its specific benefits on cancer endpoints is limited and physical activity guidelines for cancer prevention lack details in terms of the optimal dose, type and intensity of physical activity.

MedicalResearch.com: What are the main findings?

Response: We found that the optimal exercise regime to prevent overall digestive system cancers may be to accumulate 30 MET-hours/week of physical activity primarily through aerobic exercise and regardless of its intensity.

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Germline Mutation Predicts Response To Cetuximab in Colon Cancer

MedicalResearch.com Interview with:

Dr. Geoffrey Liu, MD MSC Princess Margaret Hospital/Ontario Cancer Institute University of Toronto Toronto, Ontario Canada

Dr. Geoffrey Liu

Dr. Geoffrey Liu, MD MSC
Princess Margaret Hospital/Ontario Cancer Institute
University of Toronto
Toronto, Ontario
Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials.

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Mitoxantrone for Severe MS Linked To Increased Risk of Colon Cancer and Leukemia

MedicalResearch.com Interview with:

PD Dr. Mathias Buttmann Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic University of Wuerzburg Wuerzburg, German

Dr. Mathias Buttmann

PD Dr. Mathias Buttmann
Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic
University of Wuerzburg
Wuerzburg, Germany 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated  multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer.

Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer.

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Oophorectomy Linked To Increased Risk of Colon Cancer

MedicalResearch.com Interview with:

Josefin Segelman MD, PhD Senior consultant colorectal surgeon Department of Molecular Medicine and Surgery Karolinska Institutet Ersta Hospital Stockholm Sweden

Dr. Josefin Segelman

Josefin Segelman MD, PhD
Senior consultant colorectal surgeon
Department of Molecular Medicine and Surgery
Karolinska Institutet
Ersta Hospital
Stockholm Sweden

MedicalResearch.com: What is the background for this study?

Dr. Segelman: Hormonal factors influence the development of colorectal cancer. Observational studies and clinical trials have reported a protective effect of hormone replacement therapy and oral contraceptives. Oophorectomy alters endogenous levels of sex hormones, but the effect on colorectal cancer risk is unclear. Removal of the ovaries alters levels of sex hormones in both pre- and postmenopausal women. In premenopausal women, bilateral oophorectomy is followed by surgical menopause as the endogenous estrogen levels drop. Both before and after natural menopause, bilateral oophorectomy promptly decreases endogenous androgen levels by half as the ovaries and adrenals are equally important for androgen production.

MedicalResearch.com:  What are the main findings?

Dr. SegelmanThe present nationwide cohort study explored the association between removal of the ovaries for benign indications and subsequent risk of colorectal cancer. Among 195 973 women who underwent the procedure from 1965 – 2011, there was a 30% increased risk of colorectal cancer compared with the general population. After adjustment for various factors, women who underwent bilateral oophorectomy had a higher risk of rectal cancer than those who had unilateral oophorectomy (HR 2.28, 95% CI 1.33-3.91).

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New Technology Can Detect Circulating Colon Cancer Cells In Less Than an Hour

MedicalResearch.com Interview with:
Dr. Elodie Sollier PhD
Chief Scientific Officer at Vortex Biosciences

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vortex Biosciences has developed a fast and simple way to isolate and collect intact circulating tumor cells (CTCs) directly from whole blood in less than an hour using a process based on microfluidics. To better understand the utility of the technology for the clinical setting, PCR-based Sanger sequencing was used to profile the mutations of CTCs isolated from blood from metastatic Colorectal cancer patients. The mutations were compared to primary tumor biopsies, secondary tumor biopsies and ctDNA. There are 3 primary take-aways:

  1. The Vortex technology captures CTCs with enough purity to perform sensitive and accurate PCR-based Sanger sequencing.
  2. Mutations present in primary and secondary tumors can be identified in both CTCs and ctDNA making liquid biopsies a valuable alternative to tissue biopsies.
  3. While there is general consistency of mutations identified, some mutations are only identified in CTCs while others only in ctDNA demonstrating how these are indeed complimentary.

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Advanced colorectal cancer still has a poor prognosis and more active drugs are urgently needed

MedicalResearch.com Interview with:
Silvia Marsoni, M.D.
Director Clinical Research Office
FPO – Istituto di Candiolo IRCCS
Institute for Cancer Research @ Candiolo
10060 Candiolo (TO) – Italy

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Marsoni: In the Lancet Oncology of April 20 2016, clinical investigators of 4 major Italian academic institutions presented the results of the HERACLES trial, the first phase 2 trial in patients with refractory colorectal cancer and HER2 amplification. HERACLES is based on robust preclinical data, previously generated by the same authors in patient-derived xenografts (PDX) of metastatic colorectal cancers harboring amplification of the HER2 oncogene. The HER2 positive PDXs responded to the anti HER2 combination of trastuzumab and lapatinib, but not to either drug alone.

After validation of the commercial assays to test for HER2 positivity in colorectal cancer specimens, the authors tested the experimentally selected combination of trastuzumab plus lapatinib in HER2-amplified metastatic colorectal cancer patients. They screened 914 patients who were refractory to chemotherapy and had KRAS codon 12/13 wild-type colorectal carcinoma, identifying 46 patients as having HER2-positive disease, enrolling 27 eligible patients into the study. Eight (30%) patients achieved objective responses — the highest proportion ever reported in treatment-refractory patients. One (4%) patient achieved a complete response; 20 (74%) achieved eithera complete response, partial response, or stable disease; median response duration was 9·5 months, median progression-free survival was 5·2 months (95% CI 4–8); and median overall survival was 11·5 months (95% CI 8–17). In this heavily pretreated population – all patients had received and failed standard chemotherapies and anti EGFR antibodies, and mostly also anti-agiogenic therapy – , these outcome data are extraordinary, and they show the relevance of HER2 as a target in the treatment of colorectal cancer. These results represent a breakthrough, even though they apply to a limited subgroup of patients of a very common and lethal malignancy.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Marsoni: This is the first trial to assess the combination of trastuzumab and lapatinib in patients with HER2-positive colorectal carcinoma. Our findings show that the dual HER2-targeted therapy of trastuzumab and lapatinib is active, in the absence of any chemotherapy backbone, in heavily pretreated patients with metastatic disease. Additionally, our results indicate that the extent of HER2 gene copy number elevation and HER2 expression might be associated with response to treatment.

Dr. Marsoni: What recommendations do you have for future research as a result of this study?

Dr. Marsoni: The results of this study could change the day-to-day clinical care management of patients with advanced HER2-positive colorectal cancer. Our findings could lead to the use of trastuzumab and lapatinib in earlier lines of treatment, with a possibility of chemotherapy-free regimens, for patients with HER2-positive tumors. A phase 3 trial is warranted to provide more definitive data.

MedicalResearch.com: Is there anything else the authors would like to state?

Silvia Marsoni, the trial clinical coordinator at the Candiolo Cancer Institute in Turin, states that “Our results show that HER2 amplification is a clinically relevant genetic alteration in metastatic colorectal cancer. This alteration can be screened for with established diagnostic tools, can be acted on at the therapeutic level, and occurs in 3–5% of patients with KRAS codon 12/13 wild-type metastatic colorectal cancer, similar to that of other genetic alterations for which licensed drugs are effective (eg, in lung cancer).”

Livio Trusolino, who conducted the preclinical studies at the Candiolo Cancer Institute, states that “Our results have been achieved through a precision oncology programme that started with preclinical findings in pertinent in-vivo models, was strengthened by a rigorous methodological effort for molecular diagnosis, and finally resulted in the identification of a new therapeutic option for patients with HER2-positive colorectal cancer tumours”.

Finally, Salvatore Siena from the Niguarda Cancer Center in Milan, the principal investigator of the clinical programme, states “We are proud to provide positive results of a targeted therapy for metastatic colorectal cancer, several years after the first publication in 2004 of the efficacy of EGFR-targeted monoclonal antibody. HER2-targeted therapy is a new tool in the therapeutic armamentarium for HER2-positive metastatic colorectal cancer”.

HERACLES is an independent research trial funded by the major Italian cancer charity AIRC (Associazione Italiana per la Ricerca sul Cancro – Programma Speciale AIRC 5per1000) and by the Fondazione Oncologia Niguarda. We also acknowledge contributions from F Hoffman-La Roche.

Citation:

Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial

Sartore-Bianchi, Andrea et al. Published Online: 20 April 2016

The Lancet Oncology , Volume 0 , Issue 0 ,
DOI: http://dx.doi.org/10.1016/S1470-2045(16)00150-9

 

Immunotherapy Drug Nivolumab May Help Some Aggressive HPV-Induced Anal Cancers

MedicalResearch.com Interview with:

Dr. Van K. Morris, MD Assistant Professor, GI Medical Oncology The University of Texas MD Anderson Cancer Center

Dr. Van Morris

Dr. Van K. Morris, MD
Assistant Professor, GI Medical Oncology
The University of Texas MD Anderson Cancer Center

MedicalResearch.com: What is the background for this study?

Dr. Morris: Anal cancer is a very rare cancer and accounts for approximately 2% of all gastrointestinal malignancies. Currently, there is no accepted standard of care for patients with metastatic disease, which raises challenges for oncologist who may not have extensive experience caring for patients with metastatic anal cancer given that there are not accepted agents to treat with. This clinical trial was the first clinical trial ever conducted for patients with stage IV disease who had received prior chemotherapy in the past.

Given the well-known association with human papilloma virus (HPV) and the development of anal cancer, we were interested in the use of immunotherapy drugs as a new possible way to awaken the immune system to attack this tumor, especially as there may be viral components in the tumor cells which the immune system could potentially recognize. Nivolumab is an immunotherapy drug which has shown activity in other solid tumors like melanoma, kidney cancer, non-small cell lung cancer, and bladder cancer.

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Screening For Colorectal Cancer Not Linked To Psychological Harm

Benedicte Kirkøen, PhD candidate Bowel Cancer Screening in Norway – a pilot study Cancer Registry of Norway (Kreftregisteret)

Benedicte Kirkøen

MedicalResearch.com Interview with:
Benedicte Kirkøen, PhD candidate
Bowel Cancer Screening in Norway – a pilot study
Cancer Registry of Norway (Kreftregisteret)

MedicalResearch.com: What is the background for this study?

Response: Randomised controlled trials have demonstrated that screening for colorectal cancer (CRC) can reduce CRC related mortality, but the total benefit and harm of national cancer screening programmes are under debate. Saving relatively few lives requires a large number of people to be screened. Most people who attend screening will never develop cancer, but may be exposed to potential psychological stress by participation. Cancer is one of the largest threats to peoples’ health, and participating in screening for cancer might therefore cause anxiety.

In Norway, colorectal cancer incidence has nearly tripled since the 1950s, and currently a large randomised pilot study of a national screening programme (Bowel Cancer Screening in Norway) is investigating the effect of screening on reduction in CRC incidence and mortality. As part of an evaluation of the benefits and harms of the pilot, we investigated the psychological effect of screening participation in a large group of participants. Of particular interest to us were participants who received a positive screening result and were referred to colonoscopy.

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Chemotherapy Plus Radiation Demonstrated Control of Liver Metastases in Colon Cancer

MedicalResearch.com Interview with:

Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia

Dr. Guy van Hazel

Dr Guy van Hazel
Clinical Professor of Medicine,
School of Medicine and Pharmacology,
University of Western Australia 

Medical Research: What is the background for this study? What are the main findings?

Dr. van Hazel: The SIRFLOX study is based on original work by Dr Bruce Gray and myself almost two decades ago, when we studied the combination of Selective Internal Radiation Therapy (SIRT) with Y-90 resin microspheres – which was absolutely new at the time – with hepatic artery chemotherapy. This study showed an increase in liver control with the addition of SIRT [Gray B et al. Ann Oncol 2001; 12: 1711–1720.].

We then proceeded to initiate a trial comparing systemic SIRT plus 5-FU/LV according to the Mayo Clinic regimen compared to the Mayo Clinic regimen alone, but unfortunately this had to be abandoned because new chemotherapy became available which made it unethical to offer the control arm. However, in those patients who were treated up to that point with SIRT plus 5-FU/LV [van Hazel G et al. J Surg Oncol 2004; 88: 78–85.] we did see a very high response rates compared to the control arm, with an impressive survival of 29 months. We subsequently did a phase l/ll study of modified FOLFOX6 with or without SIRT and again found very high response rates [Sharma R et al. J Clin Oncol 2007; 25: 1099–1106.].  This led us to launch the SIRFLOX study in 2007.

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Colon Cancer Rising In Transitional Economies

MedicalResearch.com Interview with:

Dr. Melina Arnold Section of Cancer Surveillance International Agency for Research on CancerLyon, France

Dr. Melina Arnold

Dr. Melina Arnold
Section of Cancer Surveillance
International Agency for Research on Cancer
Lyon, France

MedicalResearch.com: What is the background for this study? What are the main findings? 

Dr. Arnold: In this study, we looked at patterns and time trends in the incidence in and mortality from colorectal cancer on the global scale. In the analyses, we used data from the Globocan database, Cancer Incidence in Five Continents, both hosted by the International Agency for Research on Cancer (IARC), and the World Health Organisation mortality database. We documented a ten-fold variation in colorectal cancer incidence and mortality rates worldwide. We also found distinct gradients across human development levels, meaning that changes in patterns and trends of this cancer could be linked to economic development and that the adoption of a Western lifestyle may have a role. While incidence and mortality rates are on the increase in many countries in socioeconomic transition, stabilizing or decreasing trends are seen in highly-developed countries where rates remain among the highest in the world. These observations point to widening disparities and an increasing burden in transitioning countries.
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Younger Colon Cancer Diagnosed at Later Stage

More on Colon Cancer on MedicalResearch.com

Samantha Hendren, MD, MPH Associate Professor of Surgery Colorectal Surgery University of Michigan

Dr. Samantha Hendren

MedicalResearch.com Interview with:
Samantha Hendren, MD, MPH
Associate Professor of Surgery
Colorectal Surgery
University of Michigan 

Medical Research: What is the background for this study? What are the main findings?

Response: We studied colorectal cancer nationally, and found that about 1 in 7 colorectal cancer patients in the U.S. (that is, 14.7%) is diagnosed before the age of 50.  We also found that these younger colorectal cancer patients were diagnosed when their cancers were more advanced (higher “stage”, meaning more of them had spread to lymph nodes and/or to other organs).  Part of the reason for this is that these young patients are often diagnosed only after their cancers start to cause symptoms such as anemia, bowel bleeding or a blockage in the colon.

The age of 50 is when screening for colorectal cancer is started in the U.S.  This study means that a pretty large proportion of colorectal cancers are  happening in people who are too young to receive screening tests.  To put this in context, breast cancer screening often begins at age 40, and less than 5% of invasive breast cancers occur in women under that age. Our study found that about 15% of colorectal cancers are diagnosed before the screening age of 50.

Fortunately, the young patients with colorectal cancer do a little better than you might predict, knowing that they are diagnosed at a worse cancer “stage”.  For the young patients under 50, about 68% survived 5 years, while about 67% of the patients 50 and older survived 5 years.  It looks like patients’ young age helps them in their cancer treatment and survival; our study found that treatment may be a bit more aggressive in the younger patients.

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Stool Test May Get More People To Be Screened For Colon Cancer

Douglas A. Corley, MD, PhD Gastroenterologist and Research Scientist III Division of Research Kaiser Permanente Oakland, CA

Dr. Douglas Corley

MedicalResearch.com Interview with:
Douglas A. Corley, MD, PhD

Gastroenterologist and Research Scientist III
Division of Research
Kaiser Permanente
Oakland, CA 

Medical Research: What is the background for this study? What are the main findings?

Dr. Corley: Colorectal cancer is a leading cause of cancer death in the United States, so understanding how cancer screening tests for this cancer are used and if they are effective is extremely important.

There are two commonly used tests for colorectal cancer screening in the United States: colonoscopy and fecal immunochemical tests (also known as “FIT”). Colonoscopy requires a bowel preparation to clean you out and is invasive but, if normal, it is done infrequently (every ten years).

FIT is simple to do at home but, to be most effective, needs to be done every year. This has the advantage of potentially picking up cancers that grow between tests. There are few studies that have looked at how well FIT picks up cancers when used year after year. If a test picks up most cancers, it is said to be very “sensitive” for picking up cancer. Most studies only looked at 1 or 2 years of use for how well FITdetected cancers. It is possible that the first year of use may “clear out” most of the easily detectable cancers and that FIT might not work as well in subsequent years.

This very large study over several years at Kaisier Permanente, where we use both colonoscopy and FIT for colorectal cancer screening, looked at whether FIT worked as well at detecting cancer in years 3 and 4 as it did the first time someone used it.

We found that the sensitivity was highest in the first year, likely from clearing out cancers that were there for a while and easily detected, but that in subsequent years the sensitivity, though 5-10% lower, remained high. Also, most people who started with FIT continued doing it, suggesting that it is both feasible and effective for colorectal cancer screening.

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Male Pattern Baldness Linked To Increased Risk of Colon Polyps

Dr. Nana Keum, PhD Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MA

Dr. NaNa Keum

More on Colon Cancer on MedicalResearch.com
MedicalResearch.com Interview with:
Dr. Nana Keum, PhD
Department of Nutrition
Harvard T.H. Chan School of Public Health
Boston, MA

Medical Research: What is the background for this study? What are the main findings?

Dr. Keum: Male pattern baldness, the most common type of hair loss in men, is positively associated with androgens as well as IGF-1 and insulin, all of which are implicated in pathogenesis of colorectal neoplasia.  Therefore, it is biologically plausible that male pattern baldness, as a marker of underlying aberration in the regulation of the aforementioned hormones, may be associated with colorectal neoplasia.  In our study that examined the relationship between five male hair pattern at age 45 years (no-baldness, frontal-only-baldness, frontal-plus-mild-vertex-baldness, frontal-plus-moderate-vertex-baldness, and frontal-plus-severe-vertex-baldness) and the risk of colorectal adenoma and cancer, we found that frontal-only-baldness and frontal-plus-mild-vertex-baldness were associated with approximately 30% increased risk of colon cancer relative to no-baldness.  Frontal-only-baldness was also positively associated with colorectal adenoma.

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Paid Sick Leave May Help Cancer Patient Retain Jobs

4/23/13 Studio head shot portrait of Christine Veenstra for Hem/Oncol.

Dr. Veenstra

MedicalResearch.com Interview with:
Christine Veenstra MD

Clinical Lecturer, Internal Medicine
Medical Oncology
University of Michigan
Ann Arbor, MI  48109-5343

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Veenstra: Patients with cancer face many costs and incur financial burden as they go through diagnosis and treatment. For working patients, cancer diagnosis and treatment may come with the additional burden of time away from work, lost income, and even long-term job loss. Although 40% of US workers do not have access to paid sick leave, we hypothesized that availability of paid sick leave could reduce the need to take unpaid time away from work during cancer treatment and might therefore be associated with job retention and reduced personal financial burden.

In a survey of over 1300 patients with Stage III colorectal cancer, we found that only 55% of those who were employed at the time of their cancer diagnosis retained their jobs. Working patients with paid sick leave were nearly twice as likely to retain their jobs compared with working patients who did not have paid sick leave. This held true even when controlling for income, education and health insurance. Furthermore, working patients without paid sick reported significantly higher personal financial burden than those who had paid sick leave available.

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Split Bowel Prep For Colonoscopy Results In More Polyps Detected

Dr Franco Radaelli Division of Digestive Endoscopy and Gastroenterology Valduce Hospital Como, Italy

Dr. Franco Radaelli

MedicalResearch.com Interview with:
Dr Franco Radaelli
Division of Digestive Endoscopy and Gastroenterology
Valduce Hospital
Como, Italy 

Medical Research: What is the background for this study?

Dr. Radaelli: Split regimens of bowel preparation are strongly recommended by European and American Guidelines as they have been associated with a higher level of colon cleansing. However, there is still uncertainty on whether the higher level of cleansing associated with a split regimen also results in a higher proportion of subjects with at least one adenoma (adenoma detection rate, ADR), that represents by far a more relevant quality indicator than the level of cleansing itself.

On this background, we designed a randomized investigator-blinded controlled trial to evaluate whether a “split regimen” of low-volume 2-L PEG-ascorbate solution was superior to the traditional “full dose, the day before regimen” in terms of ADR. Differently from other studies on bowel preparation, we considered adenoma detection rate  instead of the level of colon cleansing, the primary study end-point, and we designed the sample size accordingly. A precise estimation of the sample size was facilitated by including an homogeneous population of asymptomatic subjects undergoing first colonoscopy after positive-FIT within CRC organized screening program. Besides, ADR represents a very solid end-point due to the very low inter-pathology variability in the differential diagnosis between neoplastic and non-neoplastic lesions, while the assessment of the level of cleansing is hampered by unavoidable degree of subjectivity and higher degree of inter-operator variability.

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Quality Improvement in Colon Cancer Care Linked to Lower Costs

MedicalResearch.com Interview with: Johannes Govaert MD Department of Surgery Leiden University Medical Center Leiden, The Netherlands Medical Research: What is the background for this study? Dr. Govaert: The Value Based Health Care agenda of prof. Porter (Harvard Business School) suggests that focus in healthcare should shift from reducing costs to improving quality: where quality of healthcare improves, cost reduction will follow. One of the cornerstones of potential cost reduction, as mentioned by Porter, could be availability of key clinical data on processes and outcomes of care. Despite the important societal and economical role the healthcare system fulfils, it still lags behind when it comes to standardised reporting processes. With the introduction of the Dutch Surgical Colorectal Audit (DSCA) in 2009, robust quality information became available enabling monitoring, evaluation and improvement of surgical colorectal cancer care in the Netherlands. Since the introduction of the DSCA postoperative morbidity and mortality declined. Primary aim of this study was to investigate whether improving quality of surgical colorectal cancer care, by using a national quality improvement initiative, leads to a reduction of hospital costs. Detailed clinical data was obtained from the 2010-2012 population-based Dutch Surgical Colorectal Audit. Costs at patient-level were measured uniformly in all 29 participating hospitals and based on Time-Driven Activity-Based Costing. Medical Research: What are the main findings? Dr. Govaert: Over three consecutive years (2010-2012) severe complications and mortality after colorectal cancer surgery respectively declined with 20% and 29%. Simultaneously, costs during primary admission decreased with 9% without increase in costs within the first 90 days after discharge. Moreover, an inverse relationship (at hospital level) between severe complication rate and hospital costs was identified among the 29 participating hospitals. Hospitals with increasing severe complication rates (between 2010 and 2012) were associated with increasing costs whereas hospitals with declining severe complication rates were associated with cost reduction. Medical Research: What should clinicians and patients take away from your report? Dr. Govaert: This report presents evidence for simultaneously quality improvement and cost reduction. By participation in a nationwide quality improvement initiative with continuous quality measurement and benchmarked feedback, opportunities for targeted improvements are revealed and therefore bringing the medical field forward in improving value of healthcare delivery. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Govaert: This is the first study outside the United States to describe such inverse relationship based on original financial and clinical data. Our conclusions provide additional evidence for cost reduction by quality improvement programs as seen in the American College of Surgeons National Surgical Quality Improvement Program. Therefore, we believe that our findings should be impetus for healthcare providers to focus on improving quality, which will catalyze costs savings as well. Citation: Nationwide Outcome-Measurement in Colorectal Cancer Surgery: Improving Quality and Reducing Costs Govaert, Johannes A. et al. Journal of the American College of Surgeons DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2015.09.020

Dr. Grovaert

MedicalResearch.com Interview with:
Johannes Govaert MD
Department of Surgery
Leiden University Medical Center
Leiden, The Netherlands

Medical Research: What is the background for this study?

Dr. Govaert: The Value Based Health Care agenda ofPprof. Porter (Harvard Business School) suggests that focus in healthcare should shift from reducing costs to improving quality: where quality of healthcare improves, cost reduction will follow. One of the cornerstones of potential cost reduction, as mentioned by Porter, could be availability of key clinical data on processes and outcomes of care. Despite the important societal and economical role the healthcare system fulfils, it still lags behind when it comes to standardised reporting processes. With the introduction of the Dutch Surgical Colorectal Audit (DSCA) in 2009, robust quality information became available enabling monitoring, evaluation and improvement of surgical colorectal cancer care in the Netherlands. Since the introduction of the DSCA postoperative morbidity and mortality declined.

Primary aim of this study was to investigate whether improving quality of surgical colorectal cancer care, by using a national quality improvement initiative, leads to a reduction of hospital costs. Detailed clinical data was obtained from the 2010-2012 population-based Dutch Surgical Colorectal Audit. Costs at patient-level were measured uniformly in all 29 participating hospitals and based on Time-Driven Activity-Based Costing.

Medical Research: What are the main findings?

Dr. Govaert: Over three consecutive years (2010-2012) severe complications and mortality after colorectal cancer surgery respectively declined with 20% and 29%. Simultaneously, costs during primary admission decreased with 9% without increase in costs within the first 90 days after discharge. Moreover, an inverse relationship (at hospital level) between severe complication rate and hospital costs was identified among the 29 participating hospitals. Hospitals with increasing severe complication rates (between 2010 and 2012) were associated with increasing costs whereas hospitals with declining severe complication rates were associated with cost reduction.

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Preventable Colon Cancer Deaths Take Large Fiscal Toll In Poor Communities

Hannah K. Weir, PhD, MSc Senior Epidemiologist CDC

Dr. Weir

MedicalResearch.com Interview with:
Hannah K. Weir, PhD, MSc
Senior Epidemiologist
CDC

Medical Research: What is the background for this study? What are the main findings?

Dr. Weir: Colorectal cancer (CRC) is one of the leading causes of cancer related deaths in the United States.

We know that the risk of dying from colorectal cancer  is not the same across all communities – people living in poorer communities have a higher risk of dying from colorectal cancer than people living in wealthier, better educated communities.

In this study, we estimated the number of potentially avoidable CRC deaths between 2008 and 2012 in poorer communities.  Then we estimated the value of lost productivity that resulted from these deaths. Lost productivity includes the value of future lost salaries, wages, and the value to household activities such as cooking, cleaning, and child care.

We focused on the age group 50 to 74 years because this is the age group where routine CRC screening is recommended. We estimated that more than 14,000 CRC deaths in poorer communities could have been avoided and that these CRC deaths resulted in a nearly $6.5 billion dollars loss in productivity.

This is tragic – for the person who died, their family and for their community. This loss in productivity contributes to the economic burden of these already disadvantaged communities.

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Plasma cfDNA Can Monitor Response To Metastatic Colon Cancer Treatment

Van K. Morris, M.D. Assistant Professor, GI Medical Oncology University of Texas – M.D. Anderson Cancer Center Houston, TX 77030

Dr. Morris

MedicalResearch.com Interview with:
Van K. Morris,  M.D.
Assistant Professor, GI Medical Oncology
University of Texas – M.D. Anderson Cancer Center
Houston, TX 77030 

Medical Research: What is the background for this study? What are the main findings?

Dr. Van K Morris: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer.  Patients were enrolled in a phase I clinical trial with the BRAF inhibitor vemurafenib, the anti-EGFR antibody cetuximab, and irinotecan.  Blood  samples were collected every two weeks with each dose, and plasma was analyzed for changes in the fraction of mutant BRAF V600E allele relative to wild-type BRAF allele with time.  Trends in circulating free DNA (cfDNA) changes were compared with radiographic changes by RECIST 1.1 criteria to examine this technique as a marker for response to therapy.

For patients who had a response radiographically, drastic reductions in the BRAF V600E allele fraction were observed even after two weeks of starting therapy, well before the first restaging scan.  Patients who did not have responses radiographically had less  dramatic changes relative to baseline in the BRAF V600E allele fraction.  This technique analyzing cfDNA from plasma was validated using two different approaches – digital droplet PCR and next-generation sequencing by Guardant Health.  Sequencing of cfDNA was also compared in pretreatment and post-progression samples, and novel mutations in MEK1 and GNAS were observed uniquely in post-progression samples.

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How Often Should Patients With Familial Colorectal Cancer Risk Be Screened?

Hans F.A. Vasen, MD Department of Gastroenterology Leiden University Medical Center and  Netherlands Foundation for the Detection of Hereditary Tumours Leiden, the Netherlands

Dr. Vasen

MedicalResearch.com Interview with:
Hans F.A. Vasen, MD

Department of Gastroenterology
Leiden University Medical Center and
Netherlands Foundation for the Detection of Hereditary Tumours
Leiden, the Netherlands

Medical Research: What is the background for this study?

Dr. Vasen: People with familial colorectal cancer (CRC) have a 3-6 fold increased risk of
colorectal cancer. It has been estimated that about 2% of the population have familial CRC (about 2.7 million people in the US). Previous studies showed that colonoscopic surveillance reduces the CRC-mortality by >80%. In people with hereditary CRC, i.e., Lynch syndrome (10 fold increased risk of CRC), an intensive screening program with colonoscopy 1x/1-2 years, is recommended. In familialcolorectal cancer, the optimal screening program  is unknown.

Medical Research: What are the main findings?

Dr. Vasen: In this randomized trial with 528 individuals at risk for familial CRC, we compared screening intervals of 3 and 6 years. We found that patients had significant more high-risk adenomas (precursor lesions of CRC) at 6-years-follow-up compared to at 3-years-follow-up. However, because of the relatively low rate of high-risk adenomas at 6 years (7%) and the absence of colorectal cancer in the 6-years group, we consider a 6-year-interval safe.

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