We’re not delivering appropriate, evidence-based guideline-driven information about colorectal cancer to people early enough for them to take an appropriate action. We need to start our messaging earlier.” — Whitney Jones, MD, Colon Cancer Prevention Project
With that straight-forward message, Dr. Whitney Jones kicked off the seventh annual Early-Age Onset Colorectal Cancer Summit kicked off on Friday, May 14. The three-day conference, which is being held online because of ongoing Covid-19 precautions, is organized by the Colon Cancer Foundation, a New York-based 501(c)3 non-profit organization dedicated to reducing colorectal cancer incidence and death.
According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and in women in the U.S., and the second most common cause of cancer deaths when men and women are combined. It’s expected to cause about 52,980 deaths in the U.S. in 2021. The overarching etiology of the disease has not been established; there is no definitive cause of colorectal cancer.
Although the rate of people being diagnosed with colon cancer or rectal cancer each year has dropped overall since the mid-1980s, that’s mainly due to the increased prevalence of people getting screened and reducing lifestyle-related risk factors.
From 2013 to 2017, incidence rates dropped by about 1 percent each year. But that downward trend is mostly in older adults and masks rising incidence among younger adults since at least the mid-1990s. From 2012 through 2016, it increased every year by 2 percent in people younger than 50 and 1 percent in people 50 to 64.
The hypothesis, Jones says, is that under age-50 colon cancer is driving up the overall colorectal cancer incidence rate because healthcare providers and organizations are talking about it to patients too late, particularly in states with the highest colon cancer prevalence.
While it is believed the United States Preventive Task Force (USPSTF) is on the verge of announcing a new recommendation that will lower the age of screening to 45 to 49, Jones, the founder of the Colon Cancer Prevention Project, reinforced the need for primary care physicians, nurses, hospitals, pharmacies, GI surgeons, OB-GYNs and other healthcare providers and organizations to begin communicating to patients much earlier than age 50, which has been the status quo for decades.
In his introductory presentation, titled, “Improving the Earliest Possible Diagnosis and Treatment through Timely Recognition of the Symptoms and Signs of Young Adult Colorectal Cancer,” Jones said earlier messaging and lead time can help change people’s behaviors, especially for individuals with challenging socioeconomic variables or a known high-risk genetic history.
Identifying symptoms, understanding family history and preventative lifestyle modifications are often discussed too late with patients, he said. Even when an individual experiences initial symptoms, because process typically starts so late, there is often a long lag until definitive diagnosis and treatment can occur.
Early messaging needs to begin much earlier — perhaps extending all the way back to the early 20s or even teenage years, he said, especially because 60 percent of early age onset colon cancer cases are sporadic and not related to family history. That, he said, is the only way to go on offense against colon cancer and allow individuals to be proactive, rather than being on defense and forcing patients to be reactive.
“For us to really combat this and make progress in the next 10 years, we don’t need to study first and then act. We need to act on what we know right now. We need more awareness, more messaging. We need patients, hospitals and healthcare providers to get onboard and be aware, and we can simultaneously try to better understand the etiology, do dissemination and implementation research and better use logistics and technology. But we don’t need to wait on action until we have got the research puzzle figured out.”
In addition to Dr. Jones’s introduction, Friday’s kick-off session also included related topics from four other presenters:
– Introduction of the Echo Chamber Challenge and Clinical Alert: Erin Peterson, Director of Mission & Partnerships, Colon Cancer Coalition;
– How will EAO-CRC Incidence and Mortality Rank in 2040? Lola Rahib, PhD, Director of Scientific & Clinical Affairs, Cancer Commons’
– How to Involve Primary Care in Improving Earliest Stage Diagnosis: Len Lichtenfeld, MD, MACP, Former Deputy Chief Medical Officer, American Cancer Society; Board of Trustees, CancerCare;
– and a Colorectal Cancer Patient Story: Lisette Caesar, EdD, Founding Principal, Mosaic Preparatory Academy.
Friday’s events concluded with a virtual cocktail and networking event and a conversation with digital artist Andre’ Oshea, who was commissioned to create an inspirational tribute piece in memory of actor Chadwick Boseman that will be auctioned. Boseman died of colon cancer last year at the age of 43. Proceeds from the auction will benefit the Colon Cancer Foundation.
To watch Friday’s presentations, register for the Early Age Onset Colorectal Cancer Summit and access the recorded program.
On Day 2 on Saturday, May 15, opening remarks will be made by Susan Wysoki, Interim Executive Director, Paltown Development Foundation and Shannon Lee-Sin, a stage IIIc colon cancer survivor. Cindy R. Borassi, EAO-CRC Host and President, Colon Cancer Foundation, will present, “Framing the Conversation: Strategic Challenges in Current Medical Care that Contribute to Young Adult Colorectal Cancer (CRC) Incidence and Mortality,” followed by the keynote address by Stephen B. Gruber, MD, PhD, MPH, Vice President, City of Hope National Medical Center.
Early-Age Onset Colorectal Cancer Summit, Day 2 A Call to Action: Keynote address by Dr. Stephen B. Gruber highlights need for greater examination of CRC risk factors
Suggesting a call to action for a more comprehensive and collaborative effort against the rise of colorectal cancer in patients under 40, Stephen B. Gruber, MD, PhD, MPH, presented the Keynote Address of the seventh annual Early-Age Onset Colorectal Cancer Summit on Saturday, May 15.
Gruber’s lecture was the highlight of Day 2 of the three-day conference, which is being held online in a virtual format because of ongoing Covid-19 precautions. It is organized by the Colon Cancer Foundation, a New York-based 501(c)3 non-profit organization dedicated to reducing colorectal cancer incidence and death.
Gruber, the vice president of the City of Hope National Medical Center in Duarte, Calif., began his presentation with the story of a young patient, who at age 28, was diagnosed with colon cancer that led to metastatic disease and ultimately her death despite having had no known risk factors for colon cancer.
Despite all of the best efforts to understand how she developed colon cancer at such a young age, it wasn’t possible to trace her disease back to any specific genetic or environmental causes. Unfortunately, that’s the status quo for early age onset colorectal cancer as of 2021, Dr. Gruber said. Although overall incidence rates of colorectal cancer have declined over the past 30 to 40 years, the incidence rate has increased substantially since the mid-1990s in adolescents and young adults.
According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and in women in the U.S., and the second most common cause of cancer deaths when men and women are combined. It’s expected to cause about 52,980 deaths in the U.S. in 2021. The overarching etiology of the disease has not been established; there is no definitive cause of colorectal cancer.
From 2013 to 2017, incidence rates dropped by about 1 percent each year. But that downward trend is mostly in older adults and masks rising incidence among younger adults since at least the mid-1990s. From 2012 through 2016, it increased every year by 2 percent in people younger than 50 and 1 percent in people 50 to 64.
“The reasons remain unknown. We don’t know why cancer is increasing in this group,” Dr. Gruber said. “As we think about all of the possible explanations, including Western-style diet, obesity, physical inactivity, antibiotic use, especially in the early life period of time, it’s not clear why this increase incidence and epidemic of early onset colorectal cancer is being observed.”
Dr. Gruber presented regional findings from his experience and research at the City of Hope National Medical Center in Duarte, Calif., work from the USC Norris Comprehensive Cancer Center in Los Angeles, as well as numerous other national and international studies to help understand some of the reasons that might be contributing as to why the disease is increasing in younger people.
He presented papers that outlined risk factors classified into systems and institutions, including screening policies within healthcare systems that contribute to early diagnosis or fail to diagnose. He questioned how microbiome changes within family environments could impact the change in incidence of the disease, and highlighted papers that explored the possibilities of germline genetics.
He referenced two papers based on studies of colorectal cancer patients under the age of 40 and under the age of 35 that showed relatively low relationships to genetic predisposition based on incidence rates of germline mismatch repair mutations (Lynch Sydrome) bi-allelic MutYH mutations or Li-Fraumeni Syndrome.
“These data are actually quite consistent, whether or not from a single institution or whether or not it’s from a large national family registry over a longer period of time, what we’re actually recognizing is that much of what we actually see is not easily explained by mendelian cancer genetic syndromes,” Dr. Gruber said.
He also explored whether or not population genetics is a likely explanation for the rising incidence of early age onset colorectal cancer. Gruber pointed out that polygenic risk scores — which can identify numerous, individual loci across the human genome that contribute modest risk of colorectal cancer — can ultimate help measure genetic susceptibility. But he said doubts that any singular genetic factor has influenced the rise in adolescent and early adult incident rates.
Dr. Gruber put a lot of his emphasis on the need to address modifiable risk factors as possible correlations to the rise of early-age onset colorectal cancer risk. He highlighted a paper that presented factors that decreased risk (including aspirin, physical activity, statins, vegetable consumption) and those that increased risk (alcohol consumption, Body Mass Index, smoking, processed meat consumption).
He also specifically highlighted coffee consumption and the risk of colorectal cancer and highlighted a study conducted by Stephanie Schmit of the Cleveland Clinic that showed the more coffee people drank, the lower their risk of colorectal cancer. He also pointed out that decrease in coffee consumption and the slight rise of energy drinks over the past decade or so might have led to a microbiome change that might have led to increased risked, but he said it would be hard to postulate that any single risk would be hard to correlate that to the rise in early onset colorectal cancer incidence.
Dr. Gruber also acknowledged and expressed concern about the significant factor that systemic racism plays in the inability to address these disparities in incident and survival rates. He pointed out that the survival rates for those who have early onset colorectal cancer are lowest among individuals with lower socioeconomic status, while the highest survival rates are associated with the people with the highest socioeconomic status.
Ultimately, more questions than answers still remain in the fight against the rising tide of early-age onset colorectal cancer.
“I think it’s actually less likely to be polygenetic risk than it is poly risk, which will include things like medications, physical activity, diet and other trends and changes in risk factors that hopefully we will be able to explore with the same specificity that we are now understanding through genetic studies,” Dr. Gruber said. “It is going to take our collaboration and a lot of work to answer the question that we do not yet understand: Why is there an epidemic of early age onset of colorectal cancer? We have an obligation and an opportunity to understand why the risk of colorectal cancer is rising in early age onset individuals.”
Other highlights of Day 2 included Session II: “The Dimensions of the EAO-CRC Problem: Do We Have Accurate, Regular, Up to Date Measurement of Key Metrics Describing the Early Age Onset Colorectal Cancer Public Health Crisis.” That included an updated about the rising early-onset CRC trends and racial disparities, the impact of COVID-19 on CRC screening and an under-19 incidence and mortality report. Session III was a panel discussion that explored “Risk Assessment/Family History Ascertainment” and included discussions about CRC screening guidelines, increased access to genetic testing and patient access to appropriate care.
To watch Friday’s or Saturday’s presentations, register for the Early Age Onset Colorectal Cancer Summit and access the recorded programs.
The Early-Age Onset Colorectal Cancer Summit continues on Sunday, May 16 with Session IV: a moderated panel discussion titled, “How to Provide Timely, Effective, Quality of Life & Fertility Preserving Treatment: What Are Key Elements of Coordinated Care for Early Onset Colorectal Cancer?” at 10:30 a.m. ET. A panel of experts will offer input about patient perspective, nurse navigation, genetics, medical oncology and new therapeutics, surgery, financial burden/toxicity, radiation oncology, psychological needs, pediatrics and palliative care.
That will be followed at 1 p.m. ET by breakout sessions about “Understanding and Addressing Disparities in Early-Age Onset Colorectal Cancer” and “Integrating Music Therapy in Cancer” before the conference concludes with Session V at 2:25 p.m. ET, a program titled “How Did This Happen? Investigating the Causes of Early Onset Colorectal Cancers.”
Early-Age Onset Colorectal Cancer Summit, Day 1: Don’t Wait Until 50: We all need to talk about colon cancer symptoms and the need for screenings much earlier
We’re not delivering appropriate, evidence-based guideline-driven information about colorectal cancer to people early enough for them to take an appropriate action. We need to start our messaging earlier.” — Whitney Jones, MD, Colon Cancer Prevention Project
With that straight-forward message, Dr. Whitney Jones kicked off the seventh annual Early-Age Onset Colorectal Cancer Summit kicked off on Friday, May 14. The three-day conference, which is being held online because of ongoing Covid-19 precautions, is organized by the Colon Cancer Foundation, a New York-based 501(c)3 non-profit organization dedicated to reducing colorectal cancer incidence and death.
According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and in women in the U.S., and the second most common cause of cancer deaths when men and women are combined. It’s expected to cause about 52,980 deaths in the U.S. in 2021. The overarching etiology of the disease has not been established; there is no definitive cause of colorectal cancer.
Although the rate of people being diagnosed with colon cancer or rectal cancer each year has dropped overall since the mid-1980s, that’s mainly due to the increased prevalence of people getting screened and reducing lifestyle-related risk factors.
From 2013 to 2017, incidence rates dropped by about 1 percent each year. But that downward trend is mostly in older adults and masks rising incidence among younger adults since at least the mid-1990s. From 2012 through 2016, it increased every year by 2 percent in people younger than 50 and 1 percent in people 50 to 64.
The hypothesis, Jones says, is that under age-50 colon cancer is driving up the overall colorectal cancer incidence rate because healthcare providers and organizations are talking about it to patients too late, particularly in states with the highest colon cancer prevalence.
While it is believed the United States Preventive Task Force (USPSTF) is on the verge of announcing a new recommendation that will lower the age of screening to 45 to 49, Jones, the founder of the Colon Cancer Prevention Project, reinforced the need for primary care physicians, nurses, hospitals, pharmacies, GI surgeons, OB-GYNs and other healthcare providers and organizations to begin communicating to patients much earlier than age 50, which has been the status quo for decades.
In his introductory presentation, titled, “Improving the Earliest Possible Diagnosis and Treatment through Timely Recognition of the Symptoms and Signs of Young Adult Colorectal Cancer,” Jones said earlier messaging and lead time can help change people’s behaviors, especially for individuals with challenging socioeconomic variables or a known high-risk genetic history.
Identifying symptoms, understanding family history and preventative lifestyle modifications are often discussed too late with patients, he said. Even when an individual experiences initial symptoms, because process typically starts so late, there is often a long lag until definitive diagnosis and treatment can occur.
Early messaging needs to begin much earlier — perhaps extending all the way back to the early 20s or even teenage years, he said, especially because 60 percent of early age onset colon cancer cases are sporadic and not related to family history. That, he said, is the only way to go on offense against colon cancer and allow individuals to be proactive, rather than being on defense and forcing patients to be reactive.
“For us to really combat this and make progress in the next 10 years, we don’t need to study first and then act. We need to act on what we know right now. We need more awareness, more messaging. We need patients, hospitals and healthcare providers to get onboard and be aware, and we can simultaneously try to better understand the etiology, do dissemination and implementation research and better use logistics and technology. But we don’t need to wait on action until we have got the research puzzle figured out.”
In addition to Dr. Jones’s introduction, Friday’s kick-off session also included related topics from four other presenters:
– Introduction of the Echo Chamber Challenge and Clinical Alert: Erin Peterson, Director of Mission & Partnerships, Colon Cancer Coalition;
– How will EAO-CRC Incidence and Mortality Rank in 2040? Lola Rahib, PhD, Director of Scientific & Clinical Affairs, Cancer Commons’
– How to Involve Primary Care in Improving Earliest Stage Diagnosis: Len Lichtenfeld, MD, MACP, Former Deputy Chief Medical Officer, American Cancer Society; Board of Trustees, CancerCare;
– and a Colorectal Cancer Patient Story: Lisette Caesar, EdD, Founding Principal, Mosaic Preparatory Academy.
Friday’s events concluded with a virtual cocktail and networking event and a conversation with digital artist Andre’ Oshea, who was commissioned to create an inspirational tribute piece in memory of actor Chadwick Boseman that will be auctioned. Boseman died of colon cancer last year at the age of 43. Proceeds from the auction will benefit the Colon Cancer Foundation.
To watch Friday’s presentations, register for the Early Age Onset Colorectal Cancer Summit and access the recorded program.
On Day 2 on Saturday, May 15, opening remarks will be made by Susan Wysoki, Interim Executive Director, Paltown Development Foundation and Shannon Lee-Sin, a stage IIIc colon cancer survivor. Cindy R. Borassi, EAO-CRC Host and President, Colon Cancer Foundation, will present, “Framing the Conversation: Strategic Challenges in Current Medical Care that Contribute to Young Adult Colorectal Cancer (CRC) Incidence and Mortality,” followed by the keynote address by Stephen B. Gruber, MD, PhD, MPH, Vice President, City of Hope National Medical Center.
Comparing the Outcomes From Real-World Observational Studies and Targeted Clinical Trials
The titular study published on March 30, 2021 was a comparative effectiveness study, a study that compares two or more health interventions to evaluate which poses the greatest benefit and harm, and was inspired by and relied on the International Duration Evaluation of Adjuvant (IDEA) trial. The IDEA trial was a pooled analysis of six randomized clinical trials that studied patients with stage III colon cancer and compared the effects of three months of adjuvant chemotherapy to the standard duration of six months.
Adjuvant chemotherapy refers to the additional therapy given to cancer patients after their primary therapy; in this case, the primary therapy was surgery. Adjuvant chemotherapy is administered to maximize the benefits of the primary therapy and to decrease the risk of cancer recurrence.
In the IDEA trial, the adjuvant therapy was either adjuvant 5-flourouracil/leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). Both FOLFOX and CAPOX are chemotherapy regimens used for advanced colorectal cancer, and, as stated, both contain oxaliplatin, a known neurotoxic agent. Therefore, the implications of reducing the duration of adjuvant therapy are immense, as it could potentially decrease the neuropathic effects of the drug, as well as reduce treatment cost and increase treatment adherence.
The IDEA trial in particular was chosen as a benchmark due to the many controversies that surrounded the study’s findings. The IDEA trial found that “a shortened duration of adjuvant chemotherapy was noninferior among patients with T1 to T3 and N1 stage disease and among patients prescribed CAPOX.” In this case, noninferior means that the experimental treatment, i.e. the shortened adjuvant chemotherapy, is not substantially worse than the control treatment, i.e. the standard six month duration of adjuvant chemotherapy.
This was controversial, as a worldwide survey of 145 oncologists showed that 1 in 3 supported the six months duration of adjuvant chemotherapy. Additionally, there were concerns as to how these findings could be generalizable to a real-world population of cancer patients.
This current study aimed to remedy these controversies by conducting a target trial emulation, a method used by investigators to mimic a clinical trial using observational techniques. Though randomized clinical trials continue to provide the strongest evidence for comparing the effectiveness of two or more interventions, they can be slow, costly, and at times impossible to conduct due to ethical considerations. Therefore, target trial emulations, in which an ideal clinical trial is imitated using already-existing, real-world data, can prove useful.
This study utilized the data of patients who were diagnosed with stage III colon cancer between January 2004 and December 2015 in Alberta, Canada, and the eligibility criteria mimicked that of the IDEA trial. Overall, 485 patients were included in the trial emulation, with 230 being women and the median age being 59 years.
Both a target trial emulation and a naive observational analysis were conducted, a naive observational analysis being one that did not take into account any of the factors of the target trial emulation. More specifically, the naive observational analysis did not factor in allowable reasons for therapy cessation, values that change over time like treatment dosage, or immortal time bias.
In this study, the findings of the target trial emulation and the naive observational analysis differed. The findings of the target trial emulation mirrored that of the original IDEA trial; a shortened duration of adjuvant therapy, specifically CAPOX, was found to be noninferior to the standard six month duration. However, the naive observational analysis found that a shortened duration of CAPOX therapy was associated with a decreased overall survival for patients.
According to the authors, these disparate findings show “the importance of explicitly emulating a target trial when conducting comparative efficacy research using real-world data.”
Artificial Intelligence Could Be the Key to Improving the Accuracy of Colonoscopies
Earlier this month, the U.S. Food and Drug Administration (FDA) authorized Medtronic and Cosmo Pharmaceuticals to start marketing its novel artificial intelligence (AI) device, the GI Genius, that improves the quality of colonoscopies by detecting precancerous polyps that clinicians may otherwise overlook if they are flat or are located in areas of the colon that are difficult to see with an endoscope.
According to a systematic review and meta-analysis of 43 international publications, 13 of which were conducted in the United States, many cases of colorectal cancer can be attributed to polyps and adenomas that are not detected during routine screenings. The study found that 26% (95% CI: 23%-30%) of adenomas are missed during colonoscopies as well as 27% of serrated polyps (95% CI: 16%-40%). GI Genius is one of a few devices cleared by the FDA to aid in colonoscopies and is the first computer-aided detection (CADe) system that uses AI to recognize polyps. The tool was reviewed through the FDA’s De Novo premarket review pathway for low-to-moderate risk novel devices.
The GI Genius works by emitting a sound and displaying green markers that are superimposed over the endoscope video when it recognizes a potential lesion; it is compatible with many video endoscopy systems. GI Genius utilizes an algorithm to recognize polyps that was developed by reviewing over 13 million colonoscopy videos. Gastroenterologists labeled tissues as being either healthy or unhealthy to help “teach” the GI Genius how to distinguish the two. While the GI Genius can recognize unhealthy tissue, it does not characterize lesions and is not a substitute for lab sampling to diagnose the tissue in question.
The safety and effectiveness of the GI Genius were assessed through a large randomized controlled trial in Italy. Out of a subpopulation of 263 subjects who required screening or surveillance at least every three years, 136 patients had a colonoscopy with the assistance of the GI Genius, while 127 patients served as controls and underwent a standard colonoscopy. In the experimental group, adenomas or carcinomas were detected in 55.1% of patients, while they were only identified in 42% of patients in the control group. No adverse events related to the use of GI Genius were reported, although its use led to a small increase in the amount of healthy tissue that was biopsied.
Overall, GI Genius shows great promise as a way to enhance the quality and reliability of colonoscopies by aiding physicians who may otherwise miss polyps that are hard to see.
Phase III BEACON Trial Results Promising for Patients With Metastatic Colorectal Cancer
Updated phase III results from the BEACON study have found that encorafenib with cetuximab can lead to promising survival outcomes among patients with advanced colorectal cancer (CRC) who had received previous lines of treatment.
The third most common cancer and the third most common cause of cancer-related deaths in the U.S., CRC occurs when there is development of mutations in oncogenes, tumor suppressor genes, and genes that aid in DNA repair. Depending on the site of the mutation, CRC can be classified as familial, inherited, or sporadic. Chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP) are pathogenic mechanisms through which CRC can develop. These mutations, changes in the chromosomes, and translocations can affect various signaling pathways (Wnt, TP53, TGF-β, and MAPK/PI3K) and genes such as c-MYC, KRAS, BRAF, SMAD2, and SMAD4. Oftentimes, mutations in these genes can serve as important predictive markers in the context of patient outcomes.
In addition to CRC, mutations in BRAF have been found to be responsible for various other cancers such as melanoma, thyroid, small-cell lung, and hairy cell leukemia. BRAF encodes for the B-RAF serine/threonine kinase protein, which is a part of the RAS/RAF/MEK/ERK pathway. Most of the mutations that take place in the BRAF gene lead to a V600E substitution, which often leads to a poor prognosis in patients. The BRAFV600E mutation initiates activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which causes the tumor cells to rapidly divide. It has been estimated that approximately 10% of patients with metastatic CRC have a mutation in BRAF.
In the past, treating metastatic CRC with BRAFV600E mutations has led to low response rates, partly due to incomplete inhibition of the MAPK signaling. Recently, the combination of a BRAF (encorafenib) and EGFR (cetuximab) inhibitor has shown promising results compared to BRAF inhibitor monotherapy. The BEACON CRC study is a randomized, open-label, phase III trial that enrolled 665 patients and compared triple combination therapy; encorafenib (300 mg x1 a day) plus binimetinib (45 mg 2x a day) plus cetuximab (400 mg/m2 x1 a week) versus double combination therapy; encorafenib plus cetuximab versus cetuximab plus irinotecan or FOLFIRI. Of the total 665 patients, 224 received triple therapy, 220 received double therapy, and 221 received the control therapy.
The objective of the BEACON trial was to detect the overall survival in relation to the triple combination therapy/double combination therapy as compared to the control. It was determined that triple/double therapy led to a median overall survival of 9.3 months, while the control group showed an overall survival of 5.9 months. This indicates that both triple/double therapy improved the overall survival rate and can therefore be used as the new standard of care in patients with metastatic CRC with BRFV600E mutations.
Brett Walker, M.D., Awarded the 2021 Thomas K. Weber Colorectal Cancer Research Scholar Award
In February 2021, Brett Walker, M.D., became the 10th awardee of the Thomas K. Weber Colorectal Cancer Research Scholar Award, awarded by the Colon Cancer Foundation in partnership with the Society of Surgical Oncology.
The award was renamed in 2020 after Thomas K. Weber, M.D. (1954-2019), founder and former president of the Colon Cancer Foundation. Dr. Weber devoted his life to increasing colorectal cancer awareness, detection, and prevention, and his dedication to “a world without colon cancer” lies at the heart of the Colon Cancer Foundation. Thus, the award was renamed to keep his legacy alive while celebrating members of the community that display excellence in translational research pertaining to the molecular biology of colorectal cancer.
This year, Dr. Walker received the award for his abstract submission on circulating hybrid cells (CHCs) as a potential biomarker for treatment response in gastrointestinal cancers. CHCs are a type of hybrid cell created by the fusion of an immune cell and a tumor cell. Research pertaining to CHCs is novel as the primary focus of previous studies on cancer cell biomarkers has been on circulating tumor cells (CTCs), cells that bud off from a primary tumor and circulate in the bloodstream.
Though CHCs also disseminate outward from a primary tumor and circulate in the peripheral blood, the difference between the two lies in their names. Whereas CTCs only express cytokeratin, a tumor protein, CHCs express both cytokeratin and CD45, an immune cell marker. It is postulated that CHCs have both immune and tumor cell markers in order to successfully evade the immune system to form new tumors.
“CHCs have this opportunity to escape out of the primary tumor and migrate to different areas and potentially seed new metastatic tumors,” said Dr. Walker in an email correspondence with the Colon Cancer Foundation.
According to Dr. Walker, CHCs have the potential to be a better evaluative marker of treatment response and disease progression compared to CTCs because there are more of them circulating in the bloodstream.
Dr. Walker’s research itself indicates the effectiveness of CHCs as biomarkers. According to The ASCO’s Post description of his research, CHCs “successfully discriminated pathologic complete response from non–pathologic complete response in both rectal and esophageal cancers.”
Additionally, Dr. Walker mentioned that CHCs can provide information on the actual tumor itself.
“By collecting CHCs, we can actually gain information on the tumor, specifically what proteins they express and their genetic makeup including mutations, which could potentially help guide targetable treatments for patients,” said Dr. Walker.
Though more studies need to be conducted into CHCs, the implications of the research conducted by Dr. Walker’s laboratory are immense. If indeed CHC levels can be used as an effective biomarker, then patients with colorectal cancer can opt for non-invasive blood tests to track disease and treatment progression, as opposed to undergoing traditionally invasive imaging techniques and endoscopies. This in turn improves patients’ quality of life by avoiding intensive procedures that can cause stress and fear.
Dr. Walker expressed excitement over CHCs as a biomarker and hopes that his research will inspire others in the field to conduct their own studies.
“I think that there’s a huge opportunity here for us to really affect how we both detect and manage colon cancer. And so I really think this is an awesome opportunity to bring attention to hybrid cells and hopefully expand the number of researchers in this field.”
A Deep Dive into a Cancer Survivor’s Return to Work
Cancer has a massive impact globally, with an estimated 1.8 million cases per year in the U.S. The advances in screening, early diagnosis, and treatment modalities have greatly improved cancer-related morbidity and mortality. With approximately 16.9 million cancer survivors as of January 2019 in the U.S. alone, this number is only expected to grow. When diagnosed, many of these survivors were probably working, thus needing to adapt their lifestyle and work ability around their diagnosis and upcoming treatment. However, this aspect of cancer survival receives very little coverage in research and modern-day media.
The National Comprehensive Cancer Network’s (NCCN) 2021 Virtual Annual Conference highlighted many important aspects of cancer survivorship. Speaker, Anna J. Tevaarwerk, M.D., from the University of Wisconsin Carbone Cancer Centre, highlighted the importance of accommodating cancer survivors returning to work. Her talk, titled, ‘Helping Cancer Survivors Return to Work,’ discussed the impact of cancer and its treatment on a survivor’s work ethic, performance, and/or employment satisfaction and how employers can better assimilate survivors who choose to or need to work during or after their treatment.
The ‘Return to Work’ Issue
During her presentation, Dr. Tevaarwerk shared that around 46% of those diagnosed with cancer are in the 20-64 age group—the ‘working age group’ in the U.S. So, most are either in the workforce, in school, or not in the workforce. Additionally, the average retirement age in the U.S. is 64, but this is predicted to rise. This highlights how cancer survivors may have to undergo and recover from treatment while remaining within the working age group.
This also means, that the majority of patients or survivors will either want or need to continue working after their diagnosis. But evidence indicates that their successful return to work post-diagnosis is much more challenging than it should be. Some of these work limitations are physical and are likely to impair their ability to work:
While most survivors appear ‘normal’ on the outside, many of these psychological and psychosocial stressors associated with cancer treatment and self-confidence/body dysmorphia anxiety (e.g., hair loss associated with chemotherapy), can often make it very hard for survivors to return to work. Unfortunately, many are unable to stop working or reducing their work hours even during active treatment – especially with patients receiving palliative (treatment targeting the symptoms rather than the cancer itself) or non-curative (treatments that slow progression and tumour growth) treatments that are ongoing and need to remain in the workforce.
Consequences of Work Limitations
Explaining the impact of the above stressors on patients who need to work, Dr. Tevaarwerk said, “Cancer treatment creates demands on patient time that may impact employment and may require job accommodation such as increased personal calls or messages during work hours, perioding breaks for rest, reduced physical exertion, job restructuring and/or modification, provision or mobility assistance, improved building access and parking close to your work area, or modified office temperatures.”
As a survivor with, undergoing, or recovering from cancer and its treatment it can be quite challenging to ask for these adjustments from your employer and can leave survivors feeling productively inadequate. Additionally, the impact of reducing work hours may lead to financial toxicity that culminates in treatment delays/lack of treatment adherence, treatment discontinuation, health insurance threat (becoming uninsured/paying for increased out-of-pocket expenses), lack of stable income, and psychosocial distress.
For many survivors, work also means a lot more than income—survivors may continue or want to return to work because, as Dr. Tevaarwerk says it creates a “sense of normalcy, distraction, need for activity, and social contacts.” While there is no direct line between these concepts, it is important to highlight that work is important for a lot of reasons outside of income, and many survivors may find a sense of purpose that encourages them to continue to return to work.
Post-Diagnosis Work Outcomes
Cancer employment support varies widely in the U.S. depending on the system you are operating in, according to Dr. Tevaarwerk. “Work-related productivity due to loss of health may change significantly, with lower levels of productivity happening after diagnosis and at the end of treatment,” she said, with the main driver being absenteeism, which includes a loss of working days due to treatment. Additionally, patients receiving curative treatment have shown increased work ability, decreased work limitations, and a steady rise in hours worked when compared to their counterparts receiving palliative cancer therapy.
Dr. Tevaarwerk added that due to the stigma surrounding cancer, and the possibility of being laid off or misrepresented at work, patients find it extremely difficult to share their diagnosis and treatment plans with their employer. Thus, a majority of the time the type of treatment a cancer patient is receiving is unclear, meaning that employment facilities tend to be inadequately prepared to support a cancer patient either during (if they decide that they are in the position where they are able to comfortably continue working) or after their treatment. She added that the phrase ‘return to work’ is misleading as it “implies that a cancer survivor stops working and then re-starts only once at the exact same job,” when in reality a cancer survivor may never stop working, or may stop and start more than once, or may take up a very different level or job.
Overcoming Work Limitations and Barriers
To make returning to work successful, it is important for employers and their employees who are survivors to work together to create an accommodative environment that supports both their needs. A proactive discussion between both parties can help establish physical and emotion boundaries. Dr. Tevaarwerk highlighted several key things an employer can do to support the successful return of a cancer survivor to work:
Conclusion
Overall, the return to work of a survivor is complicated and influenced by numerous factors and the work ability and performance of a survivor or patient often depends on survivor characteristics, work conditions (flexibility/climate), and the interplay between complex employee-employer social systems. Being at work is considered both necessary and fulfilling, and is strongly associated with mental, emotional, physical, and therapeutic benefits for those suffering from chronic conditions like cancer. Therefore, understanding the ‘return-to-work’ dilemma that cancer survivors face and adjusting it to be more accommodative would open up a range of opportunities that could benefit both the employer and the survivor.
Fight CRC Urges Congress to Provide Funding for CRC Research
The American Cancer Society’s 2021 Cancer Facts and Figures includes staggering statistics about colorectal cancer (CRC) in the United States:
These shocking figures are why Fight CRC, a patient advocacy group with a mission to “cure colorectal cancer,” is working with members of Congress to provide funding for CRC research.
Fight CRC calls for the allocation of $20 million for a CRC research program within the Department of Defense (DoD). Congressional champions of the group are leading a letter to the House Appropriations Committee in support of this effort. According to the letter, CRC is the only cancer among the top five cancer killers without its own program within the DoD’s Congressionally Directed Medical Research Program (CDMRP).
Fight CRC wants to change that. They believe it is past time for CRC to be spotlighted, and they have “no plans of slowing down or stopping until they reach their goal: a cure.” At the Colon Cancer Foundation, we wholeheartedly stand by this mission and we will continue to work towards, in the words of founder Dr. Thomas K. Weber, “a world without colon cancer.”
Imagine a world in which CRC is not one of the most common types of cancers. Imagine a world in which CRC does not cause deaths anymore. Now, imagine that you don’t have to imagine any of this: you can make this world a reality by clicking on Fight CRC’s action alert and urging your members of Congress to sign the letter to create a distinct program for CRC research. Share it with your friends, family, and colleagues so that together, we can all create a world without CRC.
Awareness Activities During National Colorectal Cancer Awareness Month 2021
In 1999, the Prevent Cancer Foundation designated March as the National Colorectal Cancer Awareness Month. The foundation partnered with the American Digestive Health Foundation and the National Colorectal Cancer Roundtable to raise awareness and advocate for policy change for the third most common type of cancer in the United States. On November 19, 1999, an official declaration came through from the United States Senate and the House of Representatives.
With approximately 100,000 new cases of colorectal cancer (CRC) every year, March is an important month to cast a spotlight on the value of preventative measures such as screening. The American Cancer Society estimates there will be 149,500 new cases of CRC and 52,980 deaths in 2021. In December 1995, the United States Preventive Services Task Force (USPSTF) recommended that adults with an average risk of CRC should be screened between the ages of 50-75 years. Due to increasing evidence over the last few decades, in December 2020 the USPSTF released draft recommendations saying screening should start at the age of 45 years.
The COVID-19 pandemic led to a drastic reduction in the number of colonoscopies in 2020: about a 90% drop compared to previous years. Approximately 1.7 million Americans missed their annual screening test in 2020, and 18,800 CRC diagnoses were either delayed or missed altogether.
In recognition of the month of March, the Colon Cancer Foundation (CCF) had several activities planned, including the #GiveACrap Challenge. The Challenge encouraged individuals to sign up to receive a free Fecal Immunochemical Test (FIT), and the chance to receive a special limited-edition beer. People also had the option of making a donation to the foundation to receive the test kit and the beer. Other activities included the CCF Challenge which is a 45-mile walk-run and a concert celebrating the culmination of a week full of activities.
In his proclamation for National Colorectal Cancer Awareness Month, President Joseph Biden urged Americans to call attention to CRC risk factors and increase annual screening practices. He emphasized that March is the perfect opportunity to improve public understanding of CRC and to educate individuals about the age for proper screening. He reiterated that if caught early, CRC is highly treatable and curable. “Because of the Affordable Care Act, most health insurance plans must cover a set of preventive services with no out-of-pocket cost. This includes colorectal cancer screening in adults aged 50 and older,” President Biden said.
Fight Colorectal Cancer and the Colon Cancer Coalition urged business leaders and landmarks to go blue to spread CRC awareness. As of March 9, 2021, businesses, healthcare systems, and landmarks in 21 states had confirmed their status to “Go Blue” in honor of CRC Awareness Month. Moreover, the Colon Cancer Coalition hosted a ‘Get Your Rear in Gear’ event on March 21, 2021, in-person and virtually, as a 5K untimed run/walk-in Charlotte, North Carolina.
Every year in March, various events take place all throughout the U.S. with the hope of spreading awareness and advocating for CRC. It is essential to spread the word about CRC and emphasize the importance of regular screening to prevent, manage, and treat CRC.
American College of Gastroenterology Updates Its CRC Screening Guidelines
March 2021 brought 21 updated recommendations and guidelines from the American College of Gastroenterology (ACG) regarding colorectal cancer (CRC) screening.
While the American Cancer Society recommends CRC screening for those aged 45 and up, the ACG recommends regular CRC screening for those aged 50-75, which follows the current recommendations set by the U.S. Preventive Services Task Force and the Multi-Speciality Task Force. For those aged 76 and beyond, the ACG recommends that the decision to screen for CRC be dependent on the health status and lifestyle of each individual, as the risks of CRC screening can outweigh the benefits depending on the individual’s situation.
The recommendation to start screening at age 50 is only for those at average risk for CRC. For those who have a family history of CRC or advanced polyps and are therefore at a two-fold increased CRC risk, the ACG recommends screening starting at the age of 40 or 10 years before the youngest affected relative—whichever comes first.
The various CRC screening options include:
The ACG recommends that colonoscopy and FIT should be the primary CRC screening methods. While advising against the Septin 9 blood test due to its low CRC detection sensitivity, the ACG does recommend the other screening methods outlined above for individuals who do not want to undergo a colonoscopy or FIT. It is important to note that all non-colonoscopy screening methods require a follow-up colonoscopy in the case of a positive result.
In terms of chemopreventive methods, multiple long term studies have indicated that aspirin can reduce CRC incidence and mortality. However, these studies showed mixed results and did not break down the results by individual CRC screening history, so the ACG recommends against the usage of aspirin as a substitute for traditional CRC screening methods.
Recommendations for Improving the Quality of Colonoscopy Screening
Of all the screening methods, a direct visualization test like the colonoscopy is the most commonly performed procedure in the U.S. However, the colonoscopy does come with a main drawback: the results of the test are dependent upon the colonoscopist. The Adenoma Detection Rate (ADR), defined by “the fraction of persons aged 50+ who have one or more adenomas detected and removed,” is a good indicator of colonoscopy performance quality. Several studies have identified a link between colonoscopists with higher ADR rates and a reduction in CRC in their patients. Therefore, the ACG recommends remedial training for colonoscopists with an ADR of <25%.
The ACG further recommends that colonoscopists spend at least six minutes inspecting the mucosa before the scope is withdrawn from the anus, as a withdrawal time of six minutes or more increased the detection of neoplastic lesions and reduced the risk of post-colonoscopy CRC (PCCRC). An additional indicator of colonoscopy quality is the cecal intubation rate (CIR), which is defined as “the passage of the colonoscope tip into the cecal caput.” It is recommended that colonoscopists achieve a CIR of at least 95%, as studies have shown that a low CIR is associated with an increased risk of PCCRC.
Recommendations for Increasing Awareness About CRC Screening
As CRC remains the third leading cause of cancer in the U.S. among men and women, screening outreach is essential to increase participation in CRC screening. Studies have found that various screening outreach methods like brochures, invitations, reminders, patient navigation, patient reminders, clinical interventions, and clinical reminders were associated with increased CRC screening rates. Additionally, having primary care providers involved in screening outreach methods increased patient participation in CRC screenings. Therefore, the ACG recommends all the above to increase screening participation.
To improve adherence to follow-up colonoscopies after positive non-colonoscopy results, the ACG recommends mail and phone reminders, patient navigation, and provider interventions.
The Colon Cancer Foundation implemented various campaigns this March to increase CRC screening participation in honor of National Colon Cancer Awareness Month. One of the most notable was the #GiveaCrapChallenge, where CCF partnered with Squatty Potty and DuClaw Brewing Company to screen 100 people for colon cancer. Participants traded a stool sample via a FIT kit for a limited edition, six-pack brew sample from DuClaw. These types of innovative screening outreach methods can increase participation in CRC screening, allowing for earlier detection of CRC.
Early detection can significantly reduce the incidence and mortality of CRC. Though there are currently no randomized clinical trials that compare the various CRC screening intervals in terms of the number of life-years gained, the Cancer Intervention and Surveillance Modeling Network, through various studies, recommends the following: