Novel Immunotherapy Combination Shows Promise in Some with Resistant Metastatic Colon Cancer

MedicalResearch.com Interview with:

Dr James Kuo, MBBS Medical oncologist and Deputy Medical Director Scientia Clinical Research Sydney, Australia 

Dr. Kuo

Dr James Kuo, MBBS
Medical oncologist and Deputy Medical Director
Scientia Clinical Research
Sydney, Australia

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

Response: Immune checkpoint inhibitors (ICI) that have seen success in the treatment of patients with various tumour types have not been as effective in patients with metastatic pancreatic cancer and therefore immune-therapeutic agents of novel mechanism of action, in particular in combination with existing ICI, need to be investigated.

This study set out to test the safety and efficacy of pixatimod, a novel immunomodulatory agent, in combination with nivolumab, firstly in the dose escalation cohorts in patients with any solid tumour for the maximal tolerable dose, and then using this dose to further treat an expansion cohort of patients with pancreatic cancer. Altogether 16 patients had received the combination and in 10 patients in whom treatment response was evaluable, 4 patients experienced a clinical benefit and continued treatment in the trial, with 1 patient having a significant partial response now treated for 48 weeks. Interestingly, all these 4 patients had metastatic colorectal cancer. Side effect profile has been consistent with other immunotherapeutic agent combination and in the patients who had clinical benefit, no treatment related side effects were observed.  Continue reading

Higher BMI Linked to Increased Risk of Younger Colon Cancer

MedicalResearch.com Interview with:

Stuart Po-Hong Liu, MD, MPH

Dr. Po-Hong Liu

Stuart Po-Hong Liu, MD, MPH
Clinical and Translational Epidemiology Unit Massachusetts General Hospital and
Harvard Medical School
Boston

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

Response: Although there were global decreases in overall colorectal cancer (CRC) incidence, CRC rates have increased dramatically in those aged 20 to 49 years in the United States, parts of Europe, and Asia. The etiology and early detection of young-onset becomes an emerging research and clinical priority. Another important fact that is that this emerging public health concern has resulted in updated guidelines from the American Cancer Society advising average-risk screening begin at age 45, rather than 50.

However, up to this point, the etiology of young onset CRC remains largely unknown. Elucidating the role of traditional CRC risk factors in the etiopathogenesis of young-onset CRC is one of the first research agenda. Continue reading

Text Messages Improved Colonoscopy Adherence

MedicalResearch.com Interview with:

Nadim Mahmud, MD, MS, MPH Hospital of the University of Pennsylvania

Dr. Mahmud

Nadim Mahmud, MD, MS, MPH
Hospital of the University of Pennsylvania

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

Response: Colonoscopy is an effective screening technique for colorectal cancer (CRC) prevention, but many patients either do not show up or have poor bowel preparation for the procedure. There are many contributors to this issue, including challenges with colonoscopy bowel preparations and communication barriers between healthcare systems and their patients. To address this, we performed a pilot of 21 patients using automated text messages sent over the course of one week prior to scheduled colonoscopy. These messages included instructional, educational, and reminder messages regarding aspects of the colonoscopy preparation process.

We found significantly improved colonoscopy adherence among patients who received the text message program as compared to routine care controls (90% versus 62%). Furthermore, patient satisfaction and likelihood to recommend the text messaging program was high. Similar texting programs are simple to create and manage, and should be considered to improve outpatient colonoscopy adherence. 

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Education Using VR Can Encourage Patients To Get Colon Cancer Screening

MedicalResearch.com Interview with:

Nathaniel Ernstoff, MD University of Miami

Dr. Ernstoff

Nathaniel Ernstoff, MD
University of Miami

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

Response: Despite the best efforts of all healthcare providers, colon cancer screening is underutilized with screening rates ranging anywhere from 58-76% based on the state (American Cancer Society 2017). At best we are still failing to screen 25% of the population.  Patients have serious concerns about colorectal cancer (CRC) screening with the most common barriers to screening being fear of colonoscopy and of the bowel preparation, amongst others. These barriers coupled with the lack of understanding of the risks, benefits, and the efficacy of screening contribute to our inadequate screening.

This study aims to prove that through education, and most importantly comprehension, patients will choose one of the 6 recommended colorectal cancer screening tests that best fits their preferences. In this study we had 24 patients who previously refused colonoscopy on 3 separate occasions, and had no other CRC screening, undergo a virtual reality (VR) demonstration, created by TheBodyVR, to see if education would improve the uptake of screening. Prior to the virtual reality demonstration, the patients completed a 5-item questionnaire which evaluated their baseline knowledge of CRC risk, polyps and screening as well as determining barriers to prior screening. The patient then viewed the VR demonstration which starts with an overview of colorectal cancer, followed by a tour through a virtual colon explaining and showing the viewer polyps and cancer.

Finally, the demonstration reviews and compares the strengths and weaknesses of all USPSTF-recommended CRC screening tests.  After the study, the patients complete the same questionnaire, and in this study there was a statistically significant improvement in knowledge in all questions.  Ultimately, 23 of 24 patients who previously refused colorectal cancer screening on 3 separate occasions chose to undergo screening after the VR demonstration, and about 50% have performed the screening 60 days out from the study’s completion.

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Who Might Benefit From Early Screening for Colorectal Cancer?

MedicalResearch.com Interview with:

Mohammad Bilal, MD University of Texas Medical Branc

Dr. Bilal

Mohammad Bilal, MD
University of Texas Medical Branch

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

Response: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer among adults in the United States and the second leading cause of cancer related deaths. Recent studies have shown an increasing incidence of CRC in younger patients. This has led to increasing interests in identifying patient populations who might be at increased risk of developing CRC.

The U.S. Multi-Society Task Force of Colorectal Cancer (MSTF) recommends that CRC screening should begin at age 50 in average-risk persons. However, recently the American Cancer Society (ACS) have published recommendations to begin CRC screening at age 45 years in average risk patient population.

These recommendations were primarily based of modeling studies since there is little outcomes data in younger age groups in regards to prevention and detection of CRC. Despite these new recommendations from the ACS, there is limited direct evidence to support CRC screening at a younger age. In our study, we have evaluated the predictors of increased prevalence of adenomas in the 40 to 49-year-old individuals undergoing colonoscopy.  Continue reading

Obesity Linked to Alarming Risk in Gastric and Colon Cancers in Young Adults

MedicalResearch.com Interview with:

Hisham Hussan, M.D. Assistant Professor of Clinical Medicine Director, Obesity and Bariatric Endoscopy Section Division of Gastroenterology, Hepatology, and Nutrition Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus, OH 43210

Dr. Hussan

Hisham Hussan, M.D.
Assistant Professor of Clinical Medicine
Director, Obesity and Bariatric Endoscopy Section
Division of Gastroenterology, Hepatology, and Nutrition
Department of Internal Medicine
The Ohio State University Wexner Medical Center
Columbus, OH 43210

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

Response: Obesity, a major healthcare burden, is an established risk factor for many gastrointestinal cancers. With obesity being on the rise, we inspected whether obesity related gastrointestinal cancers are increasing in different age groups, and relation to obesity.

MedicalResearch.com: What are the main findings? 

Response: We identify an alarming increase in incidence of gastric and colorectal cancers in young adults (less than 50 years of age) between 2002-2013.

This was paralleled by an uptrend in obese patients undergoing surgeries for these cancers during the same period. 

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

Response: Our results suggest, for the first time, a contributing role of obesity in the etiology as well as the increasing incidence of gastric and colorectal cancers in young adults. 

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

Response: More studies are needed to investigate the interplay of epigenetics factors such as young-onset obesity and western diet in relation to risk of adults developing colorectal and gastric cancers at an earlier age. Also public policies are needed to counter obesity and the rising incidence of gastric and colorectal cancer in this young high risk group.

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

Response: My main career focus is translational and clinical research at the interface of energy balance, the microbiome and gastrointestinal cancer.

We have no financial disclosers or conflict of interest.

Citation:

 ACG18 abstract:

Rising, Age‐Specific, Trends of Obesity‐Related Gastrointestinal Cancers Correspond With Increasing Cancer Resections in Obese Patients: A 2002‐2013 National Analysis Using the SEER and NIS Databases

Oct 9, 2018 @ 11:58 am

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Serial Liquid Biopsies May Predict Response to Colon Cancer Treatment

MedicalResearch.com Interview with:

Andrea Sottoriva, PhD, MSc Reader in Cancer Evolutionary Dynamics | Evolutionary Genomics & Modelling Lab Centre for Evolution and Cancer | The Institute of Cancer Research London

Dr. Sottoriva

Dr. Andrea Sottoriva, PhD
Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom


MedicalResearch.com: What is the background for this study?
Would you briefly explain what is meant by a liquid biopsy?


Response:
Cetuximab is a targeted treatment available for metastatic colorectal cancer patients. Unfortunately, although many patients benefit from Cetuximab, after an initial response to the treatment many patients relapse and become resistant to the drug.

We know that this resistance is due to the tumour evolving and adapting to therapy. Liquid biopsies allow to look for residual cancer DNA in the blood of a patient and hence monitor the emergence of resistance over time. We used blood samples take every 4 weeks (quite frequently for this type of study) to monitor the evolution of the cancers under treatment and see if there were some measurements that would predict if and when patients will relapse.

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Vitamin D and Colorectal Cancer Risk – What is the Correlation?

MedicalResearch.com Interview with:

Stephanie J. Weinstein, M.S., Ph.D.  Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH 

Dr. Weinstein

Stephanie J. Weinstein, M.S., Ph.D. 
Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics
National Cancer Institute, NIH  

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

Response: Vitamin D, known for its role in maintaining bone health, is hypothesized to lower colorectal cancer risk via several pathways related to cell growth and regulation. Previous prospective studies have reported inconsistent results for whether higher concentrations of circulating 25-hydroxyvitamin D, the accepted measure of vitamin D status, are linked to lower risk of colorectal cancer. The few randomized clinical trials of vitamin D supplementation and colorectal cancer completed thus far have not shown an effect; but study size, relatively short supplementation duration, and only moderate compliance may have contributed to their null findings.

To address inconsistencies in prior studies on vitamin D, and to investigate associations in population subgroups, we harmonized and analyzed participant-level data from over 5,700 colorectal cancer cases who had blood collected before colorectal cancer diagnosis, and 7,100 matched cancer-free controls. Study participants were drawn from 17 prospective cohorts from the United States, Europe, and Asia and were followed for an average of 5.5 years (range: 1 – 25 years). We used a single, widely accepted assay and laboratory for new vitamin D measurements and calibrated existing vitamin D measurements. In the past, substantial differences between assays made it difficult to integrate vitamin D data from different studies. Our novel calibration approach enabled us to explore risk systematically over the broad range of vitamin D levels seen internationally.  Continue reading

Marked Increase in Colorectal Cancer in Teenagers and Younger Adults

MedicalResearch.com Interview with:

Anas Raed,MD Section of General Internal Medicine Augusta University

Dr. Raed

Anas Raed, MD
Section of General Internal Medicine
Augusta University

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

Response: Colorectal cancer (CRC) incidence and mortality rates have been decreasing in the US since mid 1980s, however, recent evidence shows that incidence and mortality rates of CRC in patients younger than 50 years have been increasing significantly.

In spite of the increasing trend of colorectal cancer, routine screening of this population has not been addressed due to lack of evidence and cost-effectiveness. Administering screening colonoscopy for all individuals younger than 50 years might not be feasible and, therefore routine screening colonoscopy for specific age groups might reduce the disparity of the incidence in this disease.

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Could Some Iron Supplements Raise Your Risk of Colon Cancer?

MedicalResearch.com Interview with:

Nathalie Scheers PhD Asst. Professor Chalmers University of Technology Dept of Biology and Biological Engineering Food and Nutrition Science Göteborg, Sweden 

Dr. Scheers

Nathalie Scheers PhD
Asst. Professor
Chalmers University of Technology
Dept of Biology and Biological Engineering
Food and Nutrition Science
Göteborg, Sweden 

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

Response: Many different forms of iron supplements are used to treat iron deficiency symptoms or as phosphate binders in patients with renal disease. two of these iron supplements, the chelates ferric citrate and ferric EDTA have been observed to drive colon cancer in mice. In the newly published study in Oncotarget, we are reporting our work on how these iron compounds differ compared to the simple salt ferrous sulphate, which is another common iron supplement.

The main finding of this study was that ferric citrate and ferric EDTA promoted the cancer biomarker amphiregulin which in turn activated the MAP kinase ERK in gut epithelial cancer cells. There were no such effects in ferrous sulphate-treated cells.  Continue reading

Reassessment of Tumor Sequencing For Patients with Potentially Inheritable Colon 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  4322

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

Response: The background is that we had recently shown that some colorectal cancer patients who underwent traditional screening for Lynch syndrome were eventually found to have double somatic (two acquired) mutations in the MMR genes and they did not have Lynch syndrome at all. This was discovered after their tumor had already had MSI and/or IHC screening test, followed by MLH1 methylation and/or BRAF testing, followed by germline DNA testing on a blood sample from the patient for MMR gene mutations, then finally by sequencing their tumor. This gave us the idea to reverse the sequence and start with tumor sequencing since it might streamline testing, save time, and prevent several other tests.

In addition, we knew that all stage IV colorectal cancer are already supposed to have tumor sequencing of the KRAS, NRAS, and BRAF genes and MSI testing for treatment purposes. Our hypothesis was that an upfront tumor sequencing test could replace all these separate tests with similar sensitivity and specificity.

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Animal Study Finds Tiny Dose of Sildenafil (Viagra) May Reduce Colon Cancer Risk

MedicalResearch.com Interview with:

Darren D. Browning, PhD | Professor Department of Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University Georgia Cancer Center, Augusta, Georgia 30912-2100

Dr. Darren Browning

Darren D. Browning, PhD | Professor
Department of Biochemistry and Molecular Biology,
Medical College of Georgia at Augusta University
Georgia Cancer Center,
Augusta, Georgia 30912-2100

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

Response: Cancer of the colon and rectum is one of the most commonly diagnosed and has a high mortality because it is often identified at an advanced stage. In the United States the average overall risk of having to deal with this disease at some point is around one in twenty-five, but the risk is much higher for people who have previously had polyps removed or if a close relative was diagnosed with colon cancer. The risk is even higher for patients with inflammatory bowel disease or heritable disorders such as familial adenomatous polyposis and lynch syndrome. While chemoprevention is clearly warranted, there are currently no drugs available that can reduce the risk for those predisposed to colorectal cancer.

Previous work from our laboratory has shown that drugs like sildenafil that inhibit phosphodiesterase 5 (PDE5), have a profound effect on the epithelial lining of the intestine. Our recent work has shown that these drugs can prevent intestinal cancers in two different mouse models of human disease. While this class of drugs is best known for treating erectile dysfunction, due to a low side-effect profile they are also prescribed for long-term daily use to treat pulmonary arterial hypertension (PAH) and benign prostate hyperplasia

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BEACON Triplet Therapy for BRAF Mutant Metastatic Colorectal Cancer Shows Promise

MedicalResearch.com Interview with:

Scott Kopetz, M.D., Ph.D., FACP Associate Professor Department of Gastrointestinal Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX

Dr. Kopetz

Scott Kopetz, M.D., Ph.D., FACP
Associate Professor Department of Gastrointestinal Medical Oncology
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX

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

Response: The BRAF mutation carries a very poor prognosis for patients with advanced colo-rectal cancer (CRC), and is particularly unresponsive after first-line therapy, so additional treatment options for these patients are needed. While treatment with a BRAF inhibitor alone has not been effective in treating this disease, combination therapies have shown promise and lead to the initiation of the BEACON study. The safety lead-in phase of the BEACON CRC trial was designed to assess the safety and tolerability of encorafenib, binimetinib  and cetuximab triplet combination prior to the Phase 3 randomized portion of the study. Thirty patients were treated in the safety lead-in and received the triplet combination (encorafenib 300 mg daily, binimetinib 45 mg twice daily, and cetuximab per label). Out of the 30 patients, 29 had a BRAFV600E mutation. Microsatellite instability-high (MSI-H) (resulting from defective DNA mismatch repair) was detected in only 1 patient. The triplet demonstrated good tolerability, supporting initiation of the randomized portion of the study. In addition, promising initial clinical activity was observed.

In patients with the BRAFV600E mutation, the estimated median progression-free survival (mPFS) at the time of analysis was 8 months. The confirmed overall response rate (ORR) in patients with the BRAFV600E mutation was 48%, and 3 patients achieved complete responses (CR). Further, the ORR was 62% in the 16 patients (10/16) who received only one prior line of therapy.

Additionally, the triplet combination was generally well-tolerated. Two patients discontinued treatment due to AEs with only one of these considered related to treatment. The most common grade 3 or 4 AEs seen in at least 10% of patients were fatigue (4/30), urinary tract infection (3/30), increased aspartate aminotransferase (AST; 3/30) and increased blood creatine kinase (CK; 3/30).

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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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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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