Immunotherapy aids your immune system to fight off cancer. There are five types of immunotherapy: treatment vaccines, immune checkpoint inhibitors, T-cell transfer therapy, monoclonal antibodies, and immune system modulators. While there have been no treatment vaccines approved for colorectal cancer (CRC) yet, BioNTech’s mRNA-based treatment vaccine has recently reached phase 2 clinical trials for CRC. The vaccine, individualized to each patient, is being developed as a treatment for CRC as well as to prevent relapse in those who have undergone CRC surgery. 

How Does Immunotherapy Work?

The immune system is built to detect and destroy abnormal/mutated cells. Tumor-infiltrating lymphocytes are often found around tumors and they are an indication that the immune system is working to eliminate the tumor. Cancer cells typically undergo genetic changes that allow them to escape the immune system—they often have proteins on their surface that inactivate immune cells, and they can even change cells surrounding them to interfere with the immune system. Therefore, a therapy that can train the immune system to identify and destroy cancer cells capable of defying the immune system is important.

Cancer Treatment Vaccines

Cancer treatment vaccines are designed for people who already have cancer, and trains their body’s immune system to find well-hidden cancer cells. These vaccines can be made in three different ways. 

  1. From the patient’s own cancer cells to cause an immune response against features that are unique to their cancer.
  2. From tumor-associated antigens that are found on cancer cells. These are made for cancer subtypes.
  3. From dendritic cells, which are a type of immune cell that respond to an antigen on tumor cells. This type of a vaccine is already being used for treating prostate cancer.

Matias Riihimäki et al. in their 2016 epidemiologic study published in Scientific Reports found that up to 18% of all CRC patients have recurrence and up to 25% have metastasis. A treatment vaccine would be able to help prevent recurrence and help patients with metastasis suppress small tumors that are often difficult to remove surgically.

BioNTech Chief Medical Officer and Co-founder Özlem Türeci, M.D., noted in a press release, “This trial is an important milestone in our efforts to bringing individualized immunotherapies to patients. Many cancers progress in such a way that the patient initially appears tumor-free after surgery, but after some time tumor foci that were initially invisible grow and form metastases. In this clinical trial in patients with colorectal cancer, we aim to identify high-risk patients with a blood test and investigate whether an individualized mRNA vaccine can prevent such relapses.”

Gargi Patel is a Colon Cancer Prevention Intern at the Colon Cancer Foundation.

The COVID-19 pandemic has affected nearly every aspect of life from schools to offices and, most importantly, healthcare. While certain things may have gone back to normal, the healthcare space continues to struggle. During a discussion at the National Colorectal Cancer Roundtable (NCCRT) Annual Meeting, panelists shared how their respective organizations  adapted to the pandemic to ensure continued delivery of colorectal cancer (CRC) screening.

Rachel Issaka from the Fred Hutchinson Cancer Research Center kicked off the discussion with the history of the COVID-19 pandemic in the U.S., starting with when the SARS-CoV-2 virus reached the U.S and the government declared a national emergency on March 13th, 2020, due to the rapid spread of the virus. A day later, on March 14th, the office of the U.S. Surgeon General advised hospitals to reschedule all elective procedures. Subsequently, the Gastroenterology Society released a statement that recommended all endoscopies and clinical practices be rescheduled along with other non-urgent procedures and the Centers for Disease Control & Prevention (CDC) recommended that healthcare systems prioritize urgent visits and delay elective care. The American Cancer Society (ACS) advised patients to postpone elective care, including cancer screenings, if they are at average risk for cancer and did not have any signs or symptoms. 

Following these recommendations, many adults delayed or avoided medical care. A study conducted in June 2020 by the CDC found that:

  • 41% of U.S. adults had delayed or avoided treatment
  • 12% had avoided urgent and emergency care 
  • 32% avoided routine care

Another study conducted in April 2020 found that cancer diagnoses decreased by 46% as compared to the year before, and CRC diagnoses dropped by 49%. The primary cause for this drop in diagnoses was delayed screenings for individuals who had symptoms but did not want to use the healthcare system during the pandemic. CRC screenings were down 25% between March of 2020 and March of 2021. It is estimated that these delays in screening and diagnoses will be responsible for an additional 4,500 deaths from CRC by the year 2030. 

Fortunately, organizations such as the Lincoln Community Health System in Newport, Oregon, recognized this growing gap in screening and diagnosis of CRC and came up with solutions. Jaraka Carver, LPN, from Lincoln Community Health Center, who was planning on running a CRC awareness campaign in March 2020, witnessed the project being derailed by the pandemic. Instead, after seeing the growing gap in CRC diagnosis she and her team implemented a bi-annual FIT mailing program to reach out to individuals and remind them that they were overdue for a CRC screening, and then sent them an at-home FIT test. Of the kits that were sent out:

  • 33.5% came back for testing, of which 15 came back as abnormal 
  • 30 individuals were referred for colonoscopies, 20 of whom completed the colonoscopy and 1 was diagnosed with cancer 

Virginia Mason Franciscan Health in the Pacific Northwest was also looking to increase CRC screenings among their constituents. Their divisional vice president, Michael Anderson, had partnered with ACS on a program to increase CRC screenings to 70%. However, once the pandemic hit, they had to change directions. With the goal of scheduling annual wellness visits during the pandemic, they specifically focused on vulnerable populations and clearly communicated Medicare’s new rule that a patient could complete a visit in person, online, or by phone. 

The organization also began reaching out to patients who were overdue for an annual visit and implemented a digital tool that helped prioritize patients by their likelihood of completing a CRC screening test. The program had a 40% success rate: they scheduled 5,300 annual wellness visits, completed 1,325 cancer screenings, and saved nearly 8.16 years of life. On a population level, this program allowed 41 more men and women to spend an extra year of life with their friends and family because they were screened for CRC. 

The panel concluded with a question and answer session where participants were able to ask the presenters questions regarding the effects of SARS-CoV-2 on CRC screenings. This meeting stressed the importance of annual screenings as well as the importance of adapting to different situations and needs, with a focus on ensuring that patients are able to achieve the best health outcome possible. 

 

*Additional Information on the NCCRT annual meeting can be found at 2021 80% in Every Community Conference & NCCRT Annual Meeting – National Colorectal Cancer Roundtable  

Presenters slides can be downloaded using this link https://nccrt.org/download/101349/ 

 

Abigail Parker is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

Will Holman is a writer-producer and is the founder of the post-production company Super Star Power Productions. Having lost his dad Willie Holman, and his friend, actor Chadwick Boseman, to colorectal cancer (CRC), Will was inspired to create a non-fungible token (NFT) series in their honor that will be auctioned online starting January 10th, and proceeds from the auction will be donated to charitable causes, including the Colon Cancer Foundation  (CCF). “I wanted to honor Chadwick’s legacy and also give back to the community,” Will told the CCF in an interview.

At 46 years, Will is very aware of his personal risk for CRC. His father, Willie Holman, a football player—defensive lineman for the Chicago Bears—was diagnosed with and died from colon cancer in 2002 at age 57. His family, however, was unaware of his diagnosis. Consequently, Will has started screening himself early. He first got tested at 41 years—the recommendation is to start screening at age 40 or 10 years before your first-degree relative was diagnosed with CRC. The USPSTF recommends that all average-risk adults should initiate screening at 45 years. He is also very conscious of his dietary habits and the important connection between eating healthy and preventive wellness.

Willie Holman was from South Carolina. “A country boy who used to work out a lot but did not know much about health and wellness and what it was to take care of himself,” Will said describing his father’s lifestyle. Being aware of the lineage he carries, Will does not want himself or his children going down that same path. “My father’s experience has a big influence on my healthy lifestyle.”

The risk of colon cancer “is not talked about and dealt with, especially in the black community,” he said.  Will is also aware of the lack of access to healthy food for those living in low-income neighborhoods. Many of these neighborhoods are identified as “food deserts”: the residents in these areas lack access to supermarkets or food vendors that sell affordable yet nutritious food such as fresh fruits and vegetables. If the residents do not have easy access to transportation, they may not be able to reach supermarkets that sell fresh food and may have to depend on their corner grocery store that sells processed foods that may not be healthy. Research has shown that survival is worse among colorectal cancer patients living in food deserts.

By paying homage to both his father and to Boseman through his digital art pieces, Will hopes to give back to the community via his charitable contribution to CCF.

The NFT collection is available on Opensea and the individual links are below:

OpenSea_1

OpenSea_2

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OpenSea_4

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OpenSea_9

Slow-transit constipation (STC) is reported to occur in 15-30% of people in the U.S. The most widely accepted definition of STC is two or fewer bowel movements per week or straining at stool more than 25% of the time. Research continues to point to STC as a risk factor for colorectal cancer (CRC).

A study published in 2020 that looked at 2,165 patients (median age 54 years), found that the cumulative probability of CRC was 0.2% 5 years after STC diagnosis and 0.4% 10 years after STC diagnosis. This was not significantly different (p=0.575) than among those without STC diagnosis. However, this may be due to the small number of patients (5) who were diagnosed with CRC.

Although the authors of the 2020 study did not find a significant difference among those with and without STC diagnosis, it is well established that STC increases CRC risk. Gurérin et al. in their 2014 study of over 100,000 patients identified a statistically significant risk of CRC among those with STC:

  • 56% higher for CRC
  • 260% higher for benign neoplasm
  • 256% higher for benign neoplasm in colon
  • 262% higher for anal and rectal polyps

Current management options for STC range from dietary counseling, pharmacological therapy, and surgery. 

While the etiology of STC remains unclear, there is increasing evidence that it is caused by an imbalance in the gut microbiome. Zhang et al. in their 2021 review published in Gastroenterology Report found that gut microbiota may play a major role in modulating colonic motility, secretion, and absorption. However, there is still much research needed to understand how the gut microbiome modulates movement of fecal matter through the small intestine and colon.

Conversations about the role of the gut microbiome in CRC development were a part of the Early-Age Onset Colorectal Cancer Summit held by the Colon Cancer Foundation in May 2022.

 

Gargi Patel is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

 

A recently conducted systematic electronic search investigated keywords relating to colorectal cancer (CRC) and nutrition to define the association between diet and CRC. We summarize their findings here. 

What Can Change in My Dietary Habits?

According to the World Cancer Research Fund and American Institute of Cancer Research, 50% of CRC cases can be prevented by dietary and lifestyle modifications. While previous research studies concluded that high-fat and high-calorie diets had a carcinogenic effect, new research is showing that there is a specific role for nutrients such as fiber, vitamins, and minerals on intestinal metabolism. Consuming whole grains, dietary fiber, and dairy products decreases the risk of CRC, while consuming red and processed meats and fats increases the risk of CRC. Dietary interventions have increasingly been used over the past decade to reduce the occurrence and progression of CRC.

While there are some dietary habits that can reduce the risk of CRC, others can increase that risk. High-risk diets include those with red and processed meats, and diets made up of high fats and high carbohydrates. 

  • Processed meats are categorized as Group 1, meaning they are carcinogenic 
  • Red meats are categorized as Group 2A, meaning they are most likely to be carcinogenic 

Growth hormones in red and processed meats may be responsible for their carcinogenic effects. It is recommended that individuals limit the intake of red meats to 12-18 oz each day, and processed meats should be completely avoided. Many components of our diet may help prevent CRC: dietary fiber intake, for example, is inversely related to CRC development. Vitamins and minerals also play an important role in CRC prevention. 

  • Vitamins E and C have been shown to have a direct tumor suppressing effect on CRC 
  • Vitamin D has been shown to reduce the risk of developing CRC 
  • Calcium and selenium have also been shown to have an inverse effect on CRC

However, more research is needed to fully understand the role that fiber, vitamins, calcium, and selenium play in CRC development. 

There has also been significant interest in the role of gut microbiota (the bacteria in our gut) on CRC development. Research findings so far indicate that the microbiome and microbial metabolite health is pivotal to the prevention of several diseases such as CRC. The Mediterranean diet has positive effects on protecting individuals against CRC. Thus, nutritional therapies that are based on epigenetically active nutrients are likely to represent a good research direction.

In summary, dietary factors have a strong influence on CRC development. Consuming whole grains, dietary fiber, and dairy products can reduce the risk of CRC. Evidence also points to a role for vitamins in preventing CRC development. Ultimately, it is important to remember that future dietary recommendations will need to consider each person individually—looking at their cultural identities, risk factors, and the interaction between nutrients and the microbiota.

 

Abigail Parker is a Colorectal Cancer Prevention Intern with the Colon Cancer Foundation.

The month of November is designated as National Hospice and Palliative Care Month. While the terms are often used interchangeably, it is important for patients and their caregivers to understand the difference and realize the value of these services in the care journey.

Palliative care is offered to those suffering from serious illnesses such as cancer, stroke, or heart failure, with a focus on providing relief from the symptoms and stress because of the illness. Palliative support can be integrated into the care plan of both life-threatening as well as curable conditions and can be offered during active treatment. It is supportive care that can be offered to young and old patients, early-stage and advanced-stage patients. 

Hospice is specialized palliative care for people who are at the end of their life who may have less than 6 months of life expectancy. Hospice is focused on patient care and comfort while maintaining a decent quality of life close to the end. It is designed for when a serious health condition is not curable or when a patient chooses to not undergo certain treatments. The hospice care team does not attempt to slow disease progression. Rather, the sole focus is to manage symptoms so that the person’s last days are spent with dignity. Hospice care can be provided at home, in a hospital, or at an extended-care facility. 

 

Patient Perceptions of Hospice and Palliative Care 

A 2014 study published in British Medical Journal, which looked at 594 text responses of patients documenting their experience with palliative care, found that the emotional experience of care was the most significant and the most important to patients. A majority of patients said the emotional care they received for themselves and their families allowed them to cope with the newfound challenges with their illness. Another study that evaluated patient perceptions of palliative care quality in hospice inpatient care, daycare, and nursing homes found that “honesty”, “atmosphere”, and “respect and empathy” were the most important aspects of hospice care that they appreciated.

Insurance Coverage for Hospice and Palliative Care

Whether insurance covers hospice and palliative care, or how much is covered, depends on the insurance plan. Most insurance plans cover palliative care, but coverage may vary. It’s best to speak with your insurance plan for details. 

Most private insurance plans cover hospice care. Medicare and Medicaid provide complete coverage for hospice services. Medicare-certified hospice care is usually provided at home. Details on Medicare-covered hospice care can be found here and Medicaid coverage information is available here

 

Gargi Patel is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

At the American College of Surgeons, Clinical Congress 2021, in October, 2021, Kristine Kenning, MD, chief general surgery resident at Virginia Commonwealth University, presented results from a survey among 765 age-eligible (50 and older) adults for colorectal cancer (CRC) screening. Her team found that about 30% of those who participated on the survey had completed stool-based tests when compared to before the pandemic.

The study also looked at how barriers to screening changed before and after the pandemic. They found about a 5% increase in the percentage of unemployed respondents, from 2.6% to 7.4%. Of the 41% of respondents who were concerned about co-pays, 57.6% said they delayed undergoing screening as a consequence.

It was also found that: 

  • 59% of respondents delayed their colonoscopy out of concern for COVID-19 exposure
  • 48.1% were open to at-home fecal occult blood tests (FOBT) as an alternative 
    • 93% of them would get a follow up colonoscopy if the FOBT was positive 

FOBT analyses blood in feces that is not visible to the naked eye. A positive result for this test would indicate lesions present in the digestive tract.

Impact of the Pandemic

Perception towards at-home tests and colonoscopies have changed as a result of the pandemic. More people now than before are uncomfortable undergoing a colonoscopy because of the associated costs and potential for exposure to COVID-19. At-home tests such as FOBTs may be potential alternatives to a colonoscopy. 

Dr. Kenning explained the significance of her research findings in the Clinical Congress 2021 press release. “The key message from our findings is that barriers to screening have increased during the pandemic, and we have to find a way to work with the community to increase those rates. Our study found that people are compliant with, and willing to do, home-based fecal occult blood testing. This test provides a very important way for us to increase screening for colorectal cancer.”

Dr. Kenning noted that a larger survey is in the planning with principal investigator Carrie Miller, PhD, MPH, to further explore the changes in attitudes towards CRC screening.

 

Gargi Patel is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

Early-age onset colorectal cancer (EAO-CRC) rates have been steadily increasing in the U.S.. EAO-CRC, defined as colorectal cancer (CRC) found in patients under 50, has more than doubled since the 1990s. The recently concluded Early-Age Onset Colorectal Cancer Summit hosted by the Colon Cancer Foundation gave global experts a platform to discuss the underlying factors behind this concerning pattern. Diet, lifestyle, early-life exposures, and the microbiome made up a majority of the conversation during one of the summit’s sessions, as these are all factors that play a role in EAO-CRC. Diet in particular is a factor that must be explored further. According to a prospective cohort study published in the Journal of the National Cancer Institute (JNCI) in May 2021, hyperinsulinemia, chronic inflammation, and gut dysbiosis caused by a poor diet can lead to CRC. 

The JNCI study investigated the potential link between poor diet and rising incidence of EAO-CRC. The study’s researchers analyzed the documented behaviors of participants in the Nurses’ Health Study II (NHSII). NHSII is the second generation of the Nurses’ Health Study, established in 1976 to investigate risk factors for chronic diseases in women. NHSII contains a cohort of young women with well-documented endoscopic histories and assessments of diet and lifestyle factors, which “provides a unique opportunity” to address the knowledge gaps in the potential link between diet and EAO-CRC. 

The study looked at the history of 29,474 women aged 25-42 from 1991 to 2011. Every two years, participants were given questionnaires on demographics, life factors, and medical diagnoses. This allowed the study’s researchers to distinguish between participants with colorectal adenomas and those without, an important distinction as colorectal adenomas are postulated to be precursors to EAO-CRC. The adenomas were then categorized by their malignant potential based on size and histology.

To procure information about diet, the researchers looked at the food frequency questionnaires (FFQs) participants filled out every four years. The FFQs revealed two dominant dietary patterns: 1) the Western diet, characterized by refined grains, processed meats, and high-sugar foods, and 2) the prudent diet, characterized by vegetables, fruits, whole grains, and seafoods. Three indices were used to determine overall food quality: Dietary Approaches to Stop Hypertension (DASH), Alternative Mediterranean Diet (AMED), and Alternative Health Eating Index-2010 (AHEI-2010). For all three indices, higher scores indicated higher diet quality. 

Results from statistical analyses showed that participants in the highest quintile of Western dietary patterns had an increased risk of early-onset adenoma compared to those in the lowest quintile. Additionally, adherence to the Western diet was positively associated with early onset high-risk adenomas in particular. Conversely, there was an inverse association between adherence to DASH, AMED, and AHEI-2010 and risk of early-onset adenoma. 

These findings indicate that poor diet quality contributes to the increase in EAO-CRC found in the U.S.. However, it is important to note that participants following the Western diet were also more likely to engage in unhealthy behaviors, e.g. smoking and being sedentary, compared to participants following the prudent diet, DASH, AMED, and AHEI-2010. These confounding variables display the necessity for further research into the link between diet and EAO-CRC. 

 

Aspirin is a non-steroidal anti-inflammatory drug (NSAIDs) that is commonly used as a pain reliever, antipyretic (fever reducer), and preventative medication for cardiovascular illnesses. It is cost-effective, generic, and available over the counter. Aspirin has also been recommended as being beneficial in preventing the development of colorectal cancer (CRC). 

Aspirin has the ability to inhibit proliferation and allow apoptosis (cell-programmed death) of CRC cell lines. Approximately 10-20 billion aspirin tablets are consumed annually in the United States, making it one of the most commonly used medications in the world. The U.S. Preventive Services Task Force (USPSTF) has recommended that the use of aspirin can be of benefit in reducing the risk of CRC. Andrew Chan, M.D. wrote in Nature Reviews Cancer that the USPSTF recommendation is a ‘crucial step’ for cancer prevention.

The CAPP2 trial tested the effect of high-dose aspirin in carriers of the Lynch Syndrome. Also known as hereditary nonpolyposis CRC, Lynch syndrome is a hereditary condition that increases the risk of CRC and endometrial cancers. The trial concluded that 63% of patients who were given high-dose aspirin (600 mg/day) for a mean period of about 2 years saw a reduction in CRC development compared to the placebo group, over a period of about 5 years.  Comparably, the Cancer Prevention Program trial (CAPP3 trial) is a randomized trial that began recruitment in 2014 also targeted individuals with Lynch Syndrome but used varying doses of aspirin (100 mg, 300 mg, or 600 mg/day) for a duration of 2 years. Their follow-up period was 5-10 years later. Similarly, two large prospective cohort studies led by Dr. Chan at Harvard University established that the use of aspirin for 6 years or longer led to a 19% decreased risk of CRC. 

The data currently available on the benefits of aspirin were reviewed by Cuzick et al. who reiterated that the use of aspirin (75-325 mg/day) for greater than 5 years when started between the ages of 55-65 years, has shown benefit.

Although aspirin is chemopreventive for CRC, it is not without its adverse effects. Aspirin is an antiplatelet medication, which makes bleeding one of its most serious risk factors and therefore increases the risk for a hemorrhagic stroke by 32-36% and gastrointestinal bleeds by 30-70%. However, once the chemopreventive effects of aspirin are taken into consideration, the benefits outweigh the risk which is confirmed by an overall 4% reduction in CRC mortality. 

While there is an abundance of evidence as to the benefits of aspirin in the prevention of CRC, questions remain around the adequate dosage and duration of administration. 

 

Slow-transit constipation (STC) is reported to occur in 15-30% of people in the U.S. The most widely accepted definition of STC is two or fewer bowel movements per week or straining at stool more than 25% of the time. Research continues to point to STC as a risk factor for colorectal cancer (CRC).

A study published in 2020 that looked at 2,165 patients (median age 54 years), found that the cumulative probability of CRC was 0.2% 5 years after STC diagnosis and 0.4% 10 years after STC diagnosis. This was not significantly different (p=0.575) than among those without STC diagnosis. However, this may be due to the small number of patients (5) who were diagnosed with CRC.

Although the authors of the 2020 study did not find a significant difference among those with and without STC diagnosis, it is well established that STC increases CRC risk. Gurérin et al. in their 2014 study of over 100,000 patients identified a statistically significant risk of CRC among those with STC:

  • 56% higher for CRC
  • 260% higher for benign neoplasm
  • 256% higher for benign neoplasm in colon
  • 262% higher for anal and rectal polyps

Current management options for STC range from dietary counseling, pharmacological therapy, and surgery. 

While the etiology of STC remains unclear, there is increasing evidence that it is caused by an imbalance in the gut microbiome. Zhang et al. in their 2021 review published in Gastroenterology Report found that gut microbiota may play a major role in modulating colonic motility, secretion, and absorption. However, there is still much research needed to understand how the gut microbiome modulates movement of fecal matter through the small intestine and colon.

Conversations about the role of the gut microbiome in CRC development were a part of the Early-Age Onset Colorectal Cancer Summit held by the Colon Cancer Foundation in May 2022.

 

Gargi Patel is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.