The Colon Cancer Foundation (CCF) spoke with Dr. Rami James Aoun, 11th winner of the Dr. Thomas K. Weber Colorectal Cancer Research Scholar Award, for his work looking at biomarkers of radiation response in rectal cancer patients. He is a surgical resident at The Ohio State Wexner Medical Center. Instituted in 2011 by CCF and the Society of Surgical Oncology to recognize translational research focused on the molecular biology of colorectal cancer, the award was renamed in 2020 to honor CCF’s founder, the late Dr. Thomas K. Weber.
Born in West Palm Beach, Florida, Dr. Aoun was raised in Beirut, Lebanon, where he was a student at the American University of Beirut. After completing his undergraduate years and medical school, Dr. Aoun joined Columbia University in New York where he received a Master of Public Health degree in Healthcare Management and Policy. As part of his ongoing residency at The Ohio State Wexner Medical Center, he is completing a research fellowship with Dr. Matthew Kalady, a colorectal surgeon at The James Cancer Center.
Dr. Rami James Aoun
Q: What motivated you to work in the oncology research space, and colorectal cancer in particular?
Dr. Aoun: I am motivated to work in oncology research because I have seen some of my own family members suffer from cancer. However, what specifically interests me in colon cancer research are the patients that I encounter here at The James Cancer Center and my mentors. Their guidance when I was a junior resident was extremely important to set the direction for me as a future colorectal surgeon. That’s how I met Dr. Kalady, and now I am a part of his lab conducting research on colorectal cancer, with the goal of improving patient care outcomes.
Q: Can you summarize the significance of your findings for which you have received this award? Can you also share the prior work or observations that laid the foundation for this project?
Dr. Aoun: We observed a difference in how patients with rectal cancer reacted to neoadjuvant radiation therapy. Some of the patients who were exposed to neoadjuvant therapy had a complete response—the cancer disappeared. However, there were patients who had almost no response to the therapy. The response can be determined and graded by examining the tumor under a microscope. Patients who had a better response end up living longer without cancer.
We sought to identify the reason certain cancers responded to neoadjuvant radiation and certain cancers did not. To do that, we tried to understand these cancers at the genetic level by studying how a rectal cancer expressed particular genes, as measured by mRNA. By comparing the gene expression in both, patients who responded to radiation therapy and those who did not, we were able to obtain a gene signature that helps us identify patterns of gene expression that are different between responders and non-responders.
While this is just a starting point, it can help us develop a more predictive model to use clinically. Once we validate this model, we could be able to distinguish between a responder and non-responder to radiation based on the gene expression that we obtained from their biopsies even before any treatment is administered. This would allow us to provide individualized patient-specific therapy and avoid any unnecessary treatments and procedures.
We also think that certain genes in this signature can be further studied to see if they might be able to be blocked or changed to improve the response to treatment.
Q: What was the size of your current cohort and what is the ‘n’ that you are looking for to be able to validate your study results?
Dr. Aoun: Our ‘n’, or sample size, was 33 patients for this study. In genetic studies like this, it is difficult to design a statistical power needed to validate, but we hope to test this in about 100 different patients.
Q: Did you see any commonality in the gene signatures between rectal cancer and colon cancer?
Dr. Aoun: The gene signature we investigated was related to radiation resistance in rectal cancer, whereas colon cancer is not usually treated with radiation therapy. So, we did not study this for colon cancer. However, some of the pathways we identified are known to be relevant to colon cancer. In terms of the common pathways, what we know is the WNT pathway specifically is involved in the development and progression of colon cancer and rectal cancer. In the gene signature that we identified, six of the genes are involved in the WNT pathway. So, the question is whether the WNT pathway is also involved in radiation resistance in rectal cancer.
Q: Rectal cancer has been steadily increasing in the younger population. Do we know why that may be happening?
Dr. Aoun: An increasing number of younger patients are being afflicted with colorectal cancer and we don’t fully know why. There are lots of different theories about diet, lifestyle, and the microbiome (i.e. the bacterial content in the colon and rectum). This is a hot area of research and many groups are trying to figure out this question.
PD-1 Inhibition Effective in Treating Mismatch Repair-Deficient, Locally Advanced Rectal Cancer
Locally advanced rectal cancer may involve multistep neoadjuvant therapy to shrink the tumor before the main treatment, which is often surgery. Although this approach results in a complete pathological response in up to 25% of patients, it involves the risk of complications and toxic effects, including bowel, urinary, and sexual dysfunction; infertility; and altered quality of life in a significant number of patients. A new study, published in the New England Journal of Medicine, has found that patients with mismatch repair-deficient, locally advanced rectal cancer can be effectively treated with neoadjuvant programmed death-1 (PD-1) blockade.
Approximately 5-10% of rectal adenocarcinomas are attributed to mismatch-repair deficiency, and this subset of tumors respond poorly to standard chemotherapy treatments. Immune checkpoint blockade could be an effective treatment option for this subset of patients. PD-1 elicits an immune checkpoint response of T-cells, allowing tumor cells to bypass the immune system defense, as well as resist the effects of chemotherapy. To test this hypothesis, researchers at Memorial Sloan Kettering Cancer Center and Yale University School of Medicine conducted a phase 2 investigation to analyze the overall response and frequency of sustained clinical complete response to neoadjuvant treatment with a PD-1 inhibitor, dostarlimab.
PD-1 Blockade Eliminated Rectal Tumors
Of the sixteen patients enrolled in the study, twelve were enrolled for more than six months and completed nine cycles of dostarlimab. The resulting clinical complete response was measured by a combination of rectal MRI, visual endoscopic inspection, and digital rectal examination in twelve patients who had at least six months of follow-up. Endoscopic biopsies were performed at baseline and during visual inspection of tumor response at six weeks, three months, and 6 months, and then every four months thereafter. Serial FDG-PET scans to evaluate tumor eradication presented similar results to that seen with pathological examination and genomic analysis of the evolution of tumor eradication.
The elimination of tumors after six months of therapy with PD-1 blockade allowed Dr. Cercek and her team to be able to omit both chemoradiotherapy and surgery and to move forward with observation alone. Single-agent dostarlimab was significantly influential in treating mismatch repair-deficient, locally advanced rectal cancer. It provided a clinical complete response in all 12 patients who completed treatment to date.
Surgery and radiation can permanently impact fertility, sexual health, and bowel and bladder function. With the rise in incidence of rectal cancer among young patients of child-bearing age, anti-PD-1 antibodies can be a good alternative to chemoradiotherapy and surgery and may specifically benefit this cohort of patients. Dostarlimab promotes a refined approach toward treatment that can significantly improve the quality of life of patients, especially younger patients who may not yet have started a family. These findings also encourage the potential for using PD-1 inhibitors in the treatment of other mismatch repair-deficient tumors, such as localized pancreatic, gastric, and prostate cancers.
Sahar Alam is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.
Computer-Assisted Colonoscopy Better at Detecting Precancerous Polyps
Colonoscopy is the most effective test for colorectal cancer (CRC) screening and prevention. This procedure minimizes the incidence and mortality of colorectal cancer through early detection. During a colonoscopy, a physician inserts, and threads a flexible tube with a tiny camera called a colonoscope into the rectum and through the entire colon, or large intestine. This helps identify abnormal growths and excise any polyps which can then be sent for diagnosis.
However, research has shown that despite being the gold-standard for CRC screening, 23-30% of adenomas are overlooked and missed during a traditional colonoscopy, the success of which can vary depending on operator skills.
“Colorectal cancer is the second leading cause of cancer-related deaths in the United States and it is one of the few cancers that can be prevented if caught early,” said Aasma Shaukat, MD, MPH at NYU Grossman School of Medicine and the Robert M. and Mary H. Glickman Professor of Medicine and Gastroenterology and Director of Outcomes Research for the Division of Gastroenterology and Hepatology. “Our mission remains to improve and enhance the quality and efficacy of the colonoscopy across the board to provide the best care for patients.”
In order to improve the efficiency and efficacy of colonoscopies, Dr. Shaukat and her team have developed an artificial intelligence (AI) platform to assist endoscopists. The findings of their prospective, randomized, multicenter collaborative study to test the AI platform were recently published in the journal Gastroenterology. Between January and September 2021, twenty-two skilled, board-certified gastroenterologists performed colonoscopies on 1,440 patients. The patients were randomized to receive a traditional colonoscopy or a colonoscopy with computer-aided detection software —the software detects colorectal polyps during high-definition white-light colonoscopy procedures. This device can identify potential polyps and identify areas of concern, refining the results of the procedure in real-time.
The researchers found that using AI during a screening colonoscopy increased the adenoma per colonoscopy rate by 22%: from 0.82 to 1.05. This evidence indicates that AI can be an effective and efficient tool for gastroenterologists and endoscopists to reduce the number of overlooked polyps left behind in the colon, many of which can be precancerous.
Dr. Shaukat states, “Our findings add to the growing amount of literature that shows using computer-aided technology during an endoscopy procedure can improve the quality of exams performed and improve outcomes for our patients. Several software technologies are currently available for clinicians and incorporating the use of these resources will only enhance the care we provide our patients and improve the quality of exams we as physicians are able to perform.”
Sahar Alam is a Colorectal Cancer Prevention intern with the Colon Cancer Foundation.
Younger Patients at Greater Risk of Distant Stage Early-Onset Colorectal Adenocarcinoma
With an observed increase of distant-stage colorectal cancer (CRC) among young patients in recent years, researchers have been searching for the reasons behind rising numbers and ways to counteract them. Carcinoids, a subtype of slow-growing cancer, have been found to contribute to the steadily rising incidence rate of early-onset colorectal cancer, which is diagnosed before the age of 50. This has created a need to assess the shifts toward distant-stage adenocarcinoma and its impact on public health.
Why Are We Seeing This Increase?
A study recently published in Cancer Epidemiology, Biomarkers & Prevention sought to understand how the proportions of distant-stage disease changed over time. Several studies have identified a significant increase (49%) in the average annual percent change for distant stage colorectal cancer in the 20-34 years age group. However, many of these studies do not report histological subtypes of CRC.
With carcinoids increasing in younger patients, it is important to look at adenocarcinoma (most common cancer of the colon and rectum) staging independently from carcinoids (neuroendocrine tumors). Therefore, these researchers focused specifically on adenocarcinomas. Yearly adenocarcinoma incidence rates from the 2000-2016 Surveillance Epidemiology And End Results (SEER) data were stratified by stage, age, subsite, and race for 103,975 patients. Changes in the three-year annual incidence rate were calculated with the percent contribution of each cancer stage. Lastly, the subgroup with the highest proportion of distant-stage disease was determined.
The greatest percent increases were seen in distant-stage cancer when comparing data from 2000-2002 with 2014-2016. Here are a few significant findings of the study:
From these findings, we can conclude that the greatest burden of disease was on younger patients, highest in the non-Hispanic Black and Hispanic subgroups (despite relatively low absolute case counts). The researchers also uncovered that there is a decrease in early-stage disease in these early-onset groups. As we now know, younger patients are presented with higher risks, but the absolute incidence rates in the youngest subgroups remain relatively low.
These findings are important because they set a new precedent for patients under 50 who may not be aware that preventive screening for those at average risk of CRC starts at 45 years. Studies moving forward should also note that not all adenocarcinomas are categorized as early-onset CRC. Although this study is limited in its observational nature, it raises important questions in analyzing staging results, promoting screening opportunities, and keeping the general public aware of their risks. This study also presents potential solutions, including optimizing earlier screening and the risk-stratification of younger patients by family history and symptoms.
Juhi Patel is Colon Cancer Prevention Intern.
Golf Clubs, Colonoscopies, and Colorectal Cancer Awareness with Suzanne Miller
Mom, wife, realtor, runner, cellist, and colon cancer survivor for five and a half years. Suzanne Miller was taken aback when she was diagnosed with Stage I colon cancer at the age of 40. Colorectal cancer screenings start at 45 years for average-risk adults. She was in good health, trained for marathons, and ate well. Luckily, she was able to undergo surgery on November 18, 2016, to remove the cancer.
Suzanne realized she aspired to turn this event in her life into something good rather than dwelling on the fact that she had cancer. Since her surgery, on the 18th of each month, she spreads awareness by posting on Instagram and Facebook to remind individuals to “keep their rear in the clear.” Everyone who is over 45, under 45 with symptoms, or has a family history of colon or rectal cancer should get screened for colorectal cancer. Those with a family history of colorectal cancer should start screenings at 40 years or 10 years prior to the earliest diagnosis age in their family.
Survivor and Colon Cancer Awareness Advocate
Suzanne came across the Colon Cancer Foundation (CCF) while she was researching for a marathon to run in New York while raising money for a charity. She reached out to the Foundation and planned to run in the 2020 marathon, but it was canceled due to the COVID-19 pandemic. That didn’t dampen Suzanne’s spirit. She completed the marathon in her hometown and raised the money with support from her friends and family members who participated in the run. She looks forward to running again in the 2023 Colon Cancer Challenge.
Suzanne emphasizes that people need to be more comfortable discussing colon cancer, as they do other topics. Ever since she began raising awareness on social media, Suzanne has received messages from individuals when they received a colonoscopy, got a polyp removed, or discovered they have a family history of colon cancer. Through her experience as a young, healthy woman diagnosed with colon cancer, she brings attention to the fact that cancer does not discriminate. She always tells individuals to remind their friends and family to get a colonoscopy. “Even having one person find out that they do not have cancer is a win,” she says. Suzanne loves that we live in a world where we can speak our mind, while being kind and courteous, and have people that listen and don’t discount the matter at hand.
Kenadi Kaewmanaprasert is an intern with the Colon Cancer Foundation.
The Unintended Burden of a Cancer Diagnosis: Financial Toxicity
The past few years have seen a concerted effort from stakeholders to raise colorectal cancer awareness; however, those undergoing treatment can face significant financial impact. Financial hardship is one of several factors that has a recognized consequence on treatment outcomes. Many organizations like the National Cancer Institute and American Society for Clinical Oncology are ardent advocates for interventions to diminish the effects of “financial toxicity” that results from medical bills, indirect costs, and non-medical costs faced by patients and their families.
Several retrospective studies have previously found that 25-50% of long-term cancer survivors experience financial hardship. A study recently published in the Journal of the National Cancer Institute is the first prospective cohort study led by the SWOG Cancer Research Network to evaluate financial hardship in metastatic colorectal cancer (mCRC) patients over 12 months. The researchers evaluated the financial impact on newly diagnosed patients who may have an advanced illness. Self-reporting questionnaires were administered over 12 months and considered new debt accumulations in analyses. Of the 380 patients initially enrolled in the study, several became ineligible due to lack of baseline data or death, leaving 302 patients to be evaluated at the end of the one-year follow-up.
Age, race, income, or marital status did not have a significant impact on major financial hardship. Additionally, unemployed individuals were less likely to face significant financial hardship, which the authors believe may be confounded by age and older individuals having more assets and savings. What the researchers observed was a trend of increased risk of major financial hardship in younger, non-white, lower-income patients (but no statistically significant association). They also found that financial toxicity increases over time, where two-thirds of the study subjects faced hardship during the 12-month study period.
The bottom line is that patients with limited resources are more likely to be negatively impacted by the financial burden of a cancer diagnosis. Interventions to help ease the effects are only successful when there is a sense of trust between patients and clinicians and a working dialogue about cost and financial concerns surrounding treatment plans. Critical solutions include:
The first step to change is an acknowledgment of the issue and screening patients to identify those most vulnerable to financial hardship.
Image credit: Thomas Breher from Pixabay
Juhi Patel is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.
Improving Colorectal Cancer Screening Rates in Mississippi
In past years, the rate of colorectal cancer (CRC) has become a serious public health problem in Mississippi. A study conducted in 2020 showed that Mississippi had one of the highest mortality rates from CRC as well as one of the CRC lowest screening rates between 2015 and 2019. The state also leads the nation in cardiovascular disease mortality rates as well as diabetes mortality. These are both known comorbidities for many types of cancers, including CRC.
One theory as to why the screening rates are so low in Mississippi is that about 55% of the state’s population resides in rural locations, which may make it hard for some individuals to access regular medical care. The rural population in Mississippi has a high rate of uninsured individuals making it hard for this population to afford regular screenings. In 2016, 14% of the population under 65 were uninsured.
Another theory as to why CRC rates are so prevalent in Mississippi is that the diet of many of the residents is high in red meat and low in fiber. This is in part due to a culture that relies on red meat and processed foods. This diet is also more prevalent in areas that have a low socioeconomic background, as it can be difficult to obtain healthy food if one lives in a food desert.
Colorectal cancer-related mortality in those over 50 (2014-2018).
Data source: https://statecancerprofiles.cancer.gov/map/map.noimage.php.
Fortunately, the Mississippi government recognized the issue and has developed a plan to help increase the screening rate of residents in Mississippi and decrease mortality rates —70X2020 was initiated in 2014. Since the start of the program, there has been an increase in individuals who got screened, specifically in minority communities. So far, screening rates have improved from 55% in 2014 to 69.9% in 2020. For white individuals there was a compliance rate of just under 70% and for black individuals there was a compliance rate of just above 70% in 2020.
From this case study, we are able to theorize that screening and diet play a crucial role in the development of CRC. We are also able to see that there is a strong correlation between screening rates and CRC mortality rates.
Researchers Focus on Equity to Improve Colorectal Cancer Screening Rates
A recent article published in the New England Journal of Medicine stressed the need to make health equity our national priority. The researchers identified significant differences in the screening rates between black and white Americans. Additionally, they found that improvements in screening rates, more timely treatments, as well as earlier detection of cancer significantly improved cancer outcomes.
The researchers evaluated the association between rates of colorectal cancer screening as well as age-standardized incidence rates between 2000 to 2019 among non-Hispanic black (hereafter black) and non-Hispanic white (hereafter white) persons 50 to 75 years of age who were members of the Kaiser Permanente Northern California (KPNC) health plan. The researchers then conducted follow-ups with participants until the age of 79 years to investigate screening patterns as well as incidence rates.
Between the years 2006 and 2008, KPNC began a population-based colorectal cancer screening program that utilized proactive mail-in fecal tests and colonoscopies upon request. The study found that screening rates for black individuals increased from 42% in 2000 to 80% in 2019 and those for white individuals increased from 40% in 2000 to 83% in 2019. The study also investigated colorectal cancer-specific mortality in both groups. Among black populations, there were 54 deaths per 100,000 in 2007, which dropped to 21 cases per 100,000 in 2019. Among white populations, colorectal cancer-specific mortality decreased from 33 per 100,00 in 2007 to 20 per 100,000 in 2019.
After evaluating the yearly trends, the researchers were able to hypothesize that one of the major reasons for this drop in incidence as well as mortality from colorectal cancer in both black and white individuals was the sustained delivery strategies across the care continuum, including advancements in prevention methods, earlier detection of treatable cancers, and more timely treatments. Overall, the results of this study showed that it is possible to increase screening and decrease the incidence and mortality of colorectal cancer when the correct methods are implemented.
Abigail Parker is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.
The Urban-Rural Divide in Colorectal Cancer Screening
Image source: anarosadebastiani (Pixaby)
Colorectal cancer and breast cancer screening programs, when implemented properly, have led to significant reduction in death. However, screening uptake varies greatly across the U.S. Rural communities, specifically in Appalachia, the Mississippi delta, frontier lands, and prairie lands face issues with access that are accentuated by poor health behaviors.
A 2021 cross-sectional study by Shete et al, which was recently published in JAMA found that urban women were significantly more likely to be adherent to colorectal cancer screening as compared to women residing in rural areas (82% vs 78%, respectively; P=.01). When they conducted a multi-variable mixed effects analysis, they found that rural women had 19% lower odds of being adherent to colorectal cancer screening guidelines.
Along with a difference in screening adherence, there was a significant difference in beliefs and understanding of cancer, health, and screening. When comparing the thoughts of women dwelling in rural vs. urban areas regarding cancer and cancer screening:
Despite the differences in beliefs and perception of cancer screening overall, rural and urban women were similarly adherent (81% vs 81%) to breast cancer screening. Here the authors hypothesize that the difference in colorectal cancer screening is likely due to the difference in screening diffusion in the rural areas.
Newer colorectal screening technologies like fecal immunochemical tests (FIT) may work better in a rural setting because rural women are 69% more likely to skip going to a doctor due to cost. Taking away the face to face component can reduce cost for insurance companies and by effect patients, which could increase screening uptake.
FIT tests can also be useful for working women. Among women over the age of 65, the adherence rate to colorectal cancer screening recommendations was significantly higher than among women ages 50-64 years. This difference in uptake due to age is likely because older/retired women do not have to take time off of work for screening tests such as a colonoscopy or a sigmoidoscopy.
Furthermore, patients with insurance were 2 to 3 times more likely to get screened, so changes in insurance care coverage—particularly, the removal of a copayment for a preventive service—through the Affordable Care Act would increase screening uptake. In order to increase rural colorectal cancer screening uptake, programs that identify and act on access issues are needed as are policies that can improve access at the local level.
Dr. Cynthia Sears Explains the Connection Between Our Diet, The Gut Microbiome and Colorectal Cancer
The Colon Cancer Foundation recently had the opportunity to speak with Dr. Cynthia Sears, Professor of Medicine and Oncology, Johns Hopkins University School of Medicine; Professor of Molecular Microbiology and Immunology at the Bloomberg School of Public Health. She is also the leader of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins. Her current research focus is on the microbiome and how specific bacteria can contribute to colon cancer.
Dr. Sears, received her medical degree at Thomas Jefferson Medical College and completed her training in internal medicine at the Cornell Medical School, and trained in infectious diseases at The Memorial Sloan Kettering Cancer Institute and the University of Virginia. Over the past 20 years, Dr. Sears has conducted research on colonic microbiota and colon cancer, making her an expert in this field.
Q. What enticed you to start studying bacteria and the microbiome in relation to colon cancer.
Dr. Sears: I am an infectious disease doctor who got into internal medicine because of previous work I conducted. I conduct research on how the microbiome is impacted by organisms and bacteria. I am also looking at improving immunotherapy response among colon cancer patients, since, unfortunately, only 20% to 30% of colon cancer patients respond to immunotherapy—a majority of patients do not respond. I am currently working to help improve treatments for cancer patients.
Dr. Cynthia Sears
Q. Can you help us improve our understanding of the interaction between a person’s dietary habits and the gut microbiome and how it relates to colorectal cancer?
Dr. Sears: There’s been substantial research showing that diet is a major driver of the composition and function of the microbiome. Individuals who shifted from a meat based diet to a vegetarian diet can see a shift in their microbiome in the first 24 to 48 hours. This shows that we have the ability to impact our microbiome based on the foods we eat. It also shows that we all have the capacity to have a “good” microbiome. It is also important to note that each person is different in their response to a particular diet. For example, some individuals can eat ice cream and pizza and have no change in their physiology, while others may have a terrible response.
Q. Talking about the “ideal” diet, is there really an “ideal” diet? What impact does an individual’s genetics or environmental factors have on the gut microbiome?
Dr. Sears: We are not very good at targeting the individual level. As a society we can’t afford the type of testing it would require to figure out exactly what each individual should and should not be eating. We really must rely on public health and what’s best for most people. In relation to genetics, it’s published that less than 10% of the effect in our microbiome is related to our genetic makeup. There’s a lot of redundancy in the microbiome. We can have three perfectly healthy individuals and when we sequence their microbiomes, they would all look totally different. In one person a certain bug may be taking up a niche and promoting the production of short-chain fatty acids and in another individual, a totally different bug could be doing the exact same thing.
Q. There has been a lot of research comparing the Mediterranean diet with the Western Diet, with the Mediterranean diet being rich in grains, fiber, fruit, vegetables, and fish meanwhile the Western diet is high in fat and red meat. Do you have any advice for individuals on what diet they should follow?
Dr. Sears: People should try and follow a Mediterranean diet or the DASH [Dietary Approach to Stop Hypertension] diet. I’m a big fan of the idea that food is medicine.
Q. What would you like the public to know about the gut microbiome?
Dr. Sears: We are at least as many microbes as we are human cells but the microbes are just much smaller so the human cells are more evident. Microbes are critical to our overall health. Individual’s should strive to foster a good microbiome whether it’s on your skin, your mouth, or in your colon. There is also literature about the impact that exercise and physical activity can have on your gut microbiome as well as brain health and vascular health. The more an individual is focused on healthy living, the better they will be overall.
Q. What do you think is the future of this field?
Dr. Sears: The future direction in this field is immunotherapy, where we can use the microbiome as a biomarker. When you do a stool test or a plasma test the doctors will be able to tell you if you are more or less likely to respond to this therapy based on a microbial signal. This can relate to colorectal cancer because early-age onset colorectal cancer [EAO-CRC] is becoming frighteningly common but it is still rare enough that we are not doing colonoscopies on everyone under the age of 50. We can hopefully do something to see if a person is at a higher risk and then we can focus our care and try to prevent EAO-CRC.
Here are some additional resources on diet and lifestyle and how they can influence your colon health and overall wellness:
In Conversation With Dr. Rami James Aoun: Biomarkers for Radiation Response in Rectal Cancer
The Colon Cancer Foundation (CCF) spoke with Dr. Rami James Aoun, 11th winner of the Dr. Thomas K. Weber Colorectal Cancer Research Scholar Award, for his work looking at biomarkers of radiation response in rectal cancer patients. He is a surgical resident at The Ohio State Wexner Medical Center. Instituted in 2011 by CCF and the Society of Surgical Oncology to recognize translational research focused on the molecular biology of colorectal cancer, the award was renamed in 2020 to honor CCF’s founder, the late Dr. Thomas K. Weber.
Born in West Palm Beach, Florida, Dr. Aoun was raised in Beirut, Lebanon, where he was a student at the American University of Beirut. After completing his undergraduate years and medical school, Dr. Aoun joined Columbia University in New York where he received a Master of Public Health degree in Healthcare Management and Policy. As part of his ongoing residency at The Ohio State Wexner Medical Center, he is completing a research fellowship with Dr. Matthew Kalady, a colorectal surgeon at The James Cancer Center.
Dr. Rami James Aoun
Q: What motivated you to work in the oncology research space, and colorectal cancer in particular?
Dr. Aoun: I am motivated to work in oncology research because I have seen some of my own family members suffer from cancer. However, what specifically interests me in colon cancer research are the patients that I encounter here at The James Cancer Center and my mentors. Their guidance when I was a junior resident was extremely important to set the direction for me as a future colorectal surgeon. That’s how I met Dr. Kalady, and now I am a part of his lab conducting research on colorectal cancer, with the goal of improving patient care outcomes.
Q: Can you summarize the significance of your findings for which you have received this award? Can you also share the prior work or observations that laid the foundation for this project?
Dr. Aoun: We observed a difference in how patients with rectal cancer reacted to neoadjuvant radiation therapy. Some of the patients who were exposed to neoadjuvant therapy had a complete response—the cancer disappeared. However, there were patients who had almost no response to the therapy. The response can be determined and graded by examining the tumor under a microscope. Patients who had a better response end up living longer without cancer.
We sought to identify the reason certain cancers responded to neoadjuvant radiation and certain cancers did not. To do that, we tried to understand these cancers at the genetic level by studying how a rectal cancer expressed particular genes, as measured by mRNA. By comparing the gene expression in both, patients who responded to radiation therapy and those who did not, we were able to obtain a gene signature that helps us identify patterns of gene expression that are different between responders and non-responders.
While this is just a starting point, it can help us develop a more predictive model to use clinically. Once we validate this model, we could be able to distinguish between a responder and non-responder to radiation based on the gene expression that we obtained from their biopsies even before any treatment is administered. This would allow us to provide individualized patient-specific therapy and avoid any unnecessary treatments and procedures.
We also think that certain genes in this signature can be further studied to see if they might be able to be blocked or changed to improve the response to treatment.
Q: What was the size of your current cohort and what is the ‘n’ that you are looking for to be able to validate your study results?
Dr. Aoun: Our ‘n’, or sample size, was 33 patients for this study. In genetic studies like this, it is difficult to design a statistical power needed to validate, but we hope to test this in about 100 different patients.
Q: Did you see any commonality in the gene signatures between rectal cancer and colon cancer?
Dr. Aoun: The gene signature we investigated was related to radiation resistance in rectal cancer, whereas colon cancer is not usually treated with radiation therapy. So, we did not study this for colon cancer. However, some of the pathways we identified are known to be relevant to colon cancer. In terms of the common pathways, what we know is the WNT pathway specifically is involved in the development and progression of colon cancer and rectal cancer. In the gene signature that we identified, six of the genes are involved in the WNT pathway. So, the question is whether the WNT pathway is also involved in radiation resistance in rectal cancer.
Q: Rectal cancer has been steadily increasing in the younger population. Do we know why that may be happening?
Dr. Aoun: An increasing number of younger patients are being afflicted with colorectal cancer and we don’t fully know why. There are lots of different theories about diet, lifestyle, and the microbiome (i.e. the bacterial content in the colon and rectum). This is a hot area of research and many groups are trying to figure out this question.