The following colorectal cancer research updates extend from February 17 to March 13, 2020, inclusive and are intended for informational purposes only.
CONTENT
DRUGS / SYSTEMIC THERAPIES
1.Onvansertib Triplet Shows Promise in KRAS-Mutant Metastatic Colorectal Cancer
2. Phase II LEAP Clinical Trial to Treat mCRC
3. Health Canada approves VITRAKVI (Larotrectinib), first tumour agnostic cancer treatment for advanced solid tumours harbouring an NTRK gene fusion
4. A Phase II, Open-Label, Multicentre, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population
5. Phase III Study at the Odette Cancer Centre Comparing Arfolitixorin vs. Leucovorin: Both in Combination with 5FU, Oxaliplatin, and Bevacizumab in Patients with Advanced Colorectal Cancer
6. Taiho Oncology Presents Data on LONSURF® (trifluridine and tipiracil) and Futibatinib (TAS-120) at ASCO 2020 Gastrointestinal Cancers Symposium (ASCO GI)
SURGICAL THERAPIES
7. Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Hospital
8. Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
9. Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer
PSYCHOSOCIAL
10. Positive Relationship Confirmed Between Spiritual Well-Being, Mental Health, and Quality of Life in Cancer Patients Receiving Chemotherapy
OTHER
11. Young Adult Colorectal Cancer Clinic Available at Sunnybrook Hospital
12. A strain of E Coli Linked to About 5% of Colorectal Cancer Cases
13. Colon Cancer in Patients Under 25 Years Old: A Different Disease?
SCREENING
14. Increased Incidence of Colorectal Cancer Underestimated For Some Patients, Study Finds
NUTRITION/HEALTHY LIFESTYLE
15. Flax Seeds Are a Rich Source of Lignans, Which May Reduce Cancer Risk
16. Healthy Gut Promoting Compounds in Pulses May Help Protect Against Cancer
17. Phytochemicals in Blueberries May Offer Anti-Cancer Benefits
DRUGS / SYSTEMIC THERAPIES
- Onvansertib Triplet Shows Promise in KRAS-Mutant Metastatic Colorectal Cancer (Feb. 3/20)
A 100% clinical benefit (at eight weeks by radiographic response) was achieved in a recent study involving patients with metastatic colorectal cancer (mCRC). The treatment involved a combination of the investigational polo-like kinase 1 inhibitor (PLK1), onvansertib, plus FOLFIRI (Irinotecan, Fluorouracil [5-FU], and folinic acid [Leucovorin]), and bevacizumab (Avastin). Results have been presented by Mayo Clinic Oncologist, Daniel H. Ahn at the 2020 Gastrointestinal Cancers Symposium.
Image Source: http://www.eurekaselect.com/134311/article
What is a PLK1 Inhibitor?
Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13) is an enzyme made up of 603 amino acids that in humans is encoded by the PLK1 gene. PLK1 is studied as a target for cancer drugs. K-RAS mutations cause many colon and lung cancers. These cancers are dependent on PLK1.
Furthermore, at 16 weeks, 100% of patients had a confirmed tumor decrease and additional tumor regression (determined by radiographic scan). Here are the results:
- 1 of the patients had a partial response (PR) to the combination
- 4 patients had stable disease (SD)
- 25% of patients had tumor decrease, with one patient moving on to curative surgery
- Within the first cycle of treatment, 5 out of 6 patients with KRAS mutations developed undetectable KRAS mutant levels.
Most of the Adverse Effects (AEs) were grade 1 or 2. The most common of these were fatigue (88%), nausea (50%), and stomach pain (38%). Overall, the investigators concluded that the combination was tolerable in patients with KRAS-mutant mCRC. The primary endpoint of the study is to determine the objective response rate (ORR). The secondary endpoints will include;
- the number of participants with a complete response,
- the number of participants with a PR, SD, progression-free survival
- the number of participants with a reduction in KRAS allelic burden on liquid biopsies
In an interview with Targeted Oncology, Dr. Ahn recently discussed the phase Ib/II study of onvansertib plus FOLFIRI and bevacizumab for the treatment of patients with mCRC with a KRAS mutation. During the interview, he also predicts how the findings of this study may impact the treatment landscape for CRC.
The Q&A with Dr. Ahn follows:
TARGETED ONCOLOGY: Can you provide background on this study? What was the overall goal?
Ahn: KRAS mutations are prevalent in patients with mCRC. As we know from previously published data, patients with KRAS exon 2 mutation amount to greater than 40%, and the others are exon 3 and 4. KRAS mutations are associated with poor prognosis as well as anti-EGFR resistance. These mutations cannot receive agents such as cetuximab (Erbitux) or panitumumab (Vectibix). The poor prognostic indications highlight the need for new targeted agents against patients with KRAS alterations. Trovagene has been able to generate a lot of data showing that FOLFIRI backbone with onvansertib can create a synergistic effect.
TARGETED ONCOLOGY: What was the rationale for this study?
Ahn: Onvansertib is a first-in-class third-generation, oral, highly-selective adenosine triphosphate inhibitor of the serine/threonine enzyme, and based on preclinical studies, it has been shown that the combination of this agent with irinotecan has synergistic effects against cells with KRAS mutations. This preclinical data provided the rationale for the study, specifically with the chemotherapy regimen, FOLFIRI, plus bevacizumab, which is the standard first- or second-line therapy in patients with KRAS-mutated mCRC in combination with this investigational agent.
TARGETED ONCOLOGY: What promising signals were observed in this study?
Ahn: The preliminary results from the study are impressive because this is a phase Ib dose-escalation trial looking at the standard chemotherapy regimen FOLFIRI plus bevacizumab in combination with onvansertib. What we noticed is that when we looked at some of the correlative work, including capturing circulating tumor DNA (ctDNA), which demonstrated a decrease in the percentage of KRAS-mutated circulating tumor DNA. These were the patients that were treated with the investigational agents in combination with chemotherapy and bevacizumab. Not only did we see evidence of radiographic response, but we also saw evidence of a decrease in their KRAS-mutated ctDNA.
TARGETED ONCOLOGY: How can these findings impact the treatment landscape for mCRC?
Ahn: While I understand the limitations of early preclinical data, what these data suggest is that onvansertib may indeed affect KRAS-mutant mCRC in patients, a disease [in which] we know there are no targeted agents that can [reach] all KRAS gene alterations. Some early clinical data trials are looking at specific KRAS clones targeting specific KRAS mutations, specifically KRASG12C. There are no approved agents that are pan-RAS inhibitors. If this treatment does prove to be effective in the phase II study, it could eventually go on to a phase III study and eventually become a new standard of care patients with KRAS-mutated CRC. This therapy may be not only effective in CRC but also in other diseases where KRAS alterations are prevalent.
- Phase II LEAP Clinical Trial For mCRC (Mar.1/20)
The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and Levantine (E7080/MK-7902) in patients with triple-negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), or biliary tract cancers (BTC). Participants will be enrolled in initial tumor-specific cohorts, which will be expanded if adequate efficacy is determined. The trial is available at the Odette Cancer Centre and at the Princess Margaret Cancer Centre in Toronto as well as the following Centres throughout Canada: Abbotsford, BC; Winnipeg, MB; CHU de Quebec. For information, visit the link below.
- Health Canada Approves VITRAKVI (Larotrectinib), First Tumour Agnostic Cancer Treatment For Advanced Solid Tumours Harbouring an NTRK Gene Fusion (Mar.5/20)
Bayer announced that there is now a treatment in Canada for tyrosine receptor kinase fusion protein-driven childhood and adult cancers. Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusions can result in the production of TRK fusion proteins that can lead to uncontrolled cell growth and cancer. Health Canada issued a Notice of Compliance with Conditions (NOC/c) for VITRAKVI® (Larotrectinib). VITRAKVI® is approved for the treatment of adult and pediatric patients with solid tumours that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options. Treatment with VITRAKVI® should be initiated following confirmation of an NTRK gene fusion in a tumour specimen using a validated test.
This is the first time Health Canada has approved a tumour agnostic treatment, such that patients with advanced solid tumours harbouring an NTRK gene fusion may be eligible for treatment with VITRAKVI®, across multiple tumour types and ages. VITRAKVI® is a first-in class oral and highly selective TRK inhibitor that may shrink the tumour or may slow or stop it from growing. In the clinical trials that were the basis for this approval, TRK fusion cancer patients treated with Larotrectinib experienced clinical benefit across numerous tumour types, including lung, thyroid, melanoma, GIST (gastrointestinal stromal tumour), colon, soft tissue sarcoma, salivary gland, and infantile fibrosarcoma. The overall response rate (ORR) was 75% (95% CI, 64%, 85%) with 22% of patients experiencing a complete response (CR) to treatment. The ORR observed was 90% in pediatrics and 69% in adults, and responses were rapid and durable.
What is TRK Fusion Cancer?
TRK fusion cancer is rare and occurs when an NTRK gene fuses with another unrelated gene, producing a TRK fusion protein that becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless where it originates in the body. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumours with varying frequency, including lung, thyroid, gastrointestinal cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma). TRK fusion proteins are rare in common cancers (such as colorectal cancer) and common in rare cancers.
NB: The pan Canadian Oncology Drug Review Expert Committee (pERC) has recently issued a funding recommendation in respect of Larotrectinib. It conditionally recommends the reimbursement of Larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with locally advanced solid tumors that have an NTRK gene fusion This recommendation pertains only to adult and pediatric patients with salivary gland tumours, adult or pediatric patients with soft tissue sarcoma (STS) and pediatric patients with cellular congenital mesoblastic nephroma or infantile fibrosarcoma, without a known acquired resistance mutation, that are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options, only if the following conditions are met:
Cost-effectiveness being improved to an acceptable level
Feasibility of adoption (budget impact and access to testing) is addressed
Stay tuned as the expert committee is currently reviewing feedback submissions from various stakeholders.
Please note: the expert review committee has as of October 31st, 2019 issued a final negative funding recommendation in respect of Larotrectinib. Efforts are currently underway to assemble a massive campaign to address this final recommendation by working to secure a sustainable, long-term funding solution for TRK fusion cancer patients.
Bayer’s Commitment
Bayer has launched a testing program called FastTRK. As per an information sheet that may be obtained from CCRAN, FastTRK is a clinical testing program for the diagnosis of NTRK gene fusions. Sponsored by Bayer, this is a complimentary service for clinicians to determine whether their patients’ cancer has an NTRK gene fusion. Solid tumour samples from eligible patients (in the form of a solid tumour block or prepared slides) will be tested by immunohistochemistry (IHC) and/or next-generation sequencing (NGS). Currently, Bayer has partnered with LifeLabs and the Kingston Health Sciences Centre (KHSC) to provide NTRK gene fusion testing services for Canadians. The FastTRK program will be supported at least until the end of 2021.
Bayer will continue to offer the therapy to patients who are identified to have TRK fusion cancers and who are responding to the therapy.
Bayer will provide a TRAKTION Patient Support Program to assist patients while on the therapy.
https://www.bayer.ca/en/media/news/?dt=TmpBPQ==&st=1
- A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population (Mar.12/20)
The purpose of this study is to look at the effectiveness of the vaccine DPX-Survivac in combination with the drugs cyclophosphamide and the immunotherapy Pembrolizumab in patients with solid cancers who are identified to be MSI-High. All patients will receive combination therapy of DPX-Survivac, cyclophosphamide, and pembrolizumab. Patients participating will know which treatment they are receiving. The trial is currently hosted at the Odette Cancer Centre, and a new site is opening at Mt. Sinai Hospital.
- Phase III Study at the Odette Cancer Centre Comparing Arfolitixorin vs. Leucovorin in Combination with 5FU, Oxaliplatin and Bevacizumab in Patients with Advanced Colorectal Cancer (Mar.12/20)
The purpose of this study is to look at the effectiveness of the drug Arfolitixorin in combination with 5-fluorouracil (5FU), oxaliplatin, and bevacizumab in patients with colorectal cancer. Patients with advanced/metastatic colorectal cancer who meet certain criteria may be able to participate. There will be two groups of patients participating in this study;
one group will receive Arfolitixorin in combination with 5FU), oxaliplatin, and bevacizumab,
while the other group will receive the drug Leucovorin in combination with 5FU, oxaliplatin, and bevacizumab (standard of care).
The doctor and study staff will not know which group a patient is in. Patients will be randomized to receive one treatment or the other.
https://sunnybrook.ca/trials/item/?i=293&page=49335 and https://clinicaltrials.gov/ct2/show/NCT03750786
About Arfolitixorin:
(https://isofolmedical.com/arfolitixorin/ )
Arfolitixorin is Isofol’s proprietary drug candidate being developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. The drug candidate is currently being studied in a global Phase 3 clinical trial. As the key active metabolite of the widely used folate-based drugs, arfolitixorin can potentially benefit all patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.
Treating cancer patients with arfolitixorin – The goals:
- When treating colorectal cancer, for example, arfolitixorin is administered in combination with 5-FU to increase cell mortality in circulating cancer cells and in cancerous tumours.
• Arfolitixorin is administered in conjunction with rescue therapy after high-dose treatment with the cytotoxic agent, methotrexate, in order to suppress the cytotoxic effect in surrounding healthy tissue. The treatment is used for certain types of cancer, such as osteosarcoma, a type of bone cancer. This involves administering arfolitixorin separately, 24 hours after the chemotherapy.
- Taiho Oncology Presents Data on LONSURF® (trifluridine and tipiracil) and Futibatinib (TAS-120) at ASCO 2020 Gastrointestinal Cancers Symposium (ASCO GI) (Mar. 12/20)
On Jan. 25, 2020 Taiho Oncology announced the global Phase III TAGS and RECOURSE trials evaluating LONSURF® (trifluridine and tipiracil) in patients with metastatic colorectal cancer (mCRC), as well as metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). Updates were also presented on two (2) trials in progress with futibatinib:
1) Phase III FOENIX-CCA3 study of futibatinib as first-line treatment for patients with advanced cholangiocarcinoma (CCA) harboring FGFR 2 gene rearrangements
2) and a Phase II basket study of futibatinib in patients with advanced solid tumors harboring FGFR genomic aberrations.
Findings were highlighted at the ASCO 2020 Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco on January 23-25, 2020.
LONSURF Pooled Safety Analysis
The pooled safety analysis of the TAGS and RECOURSE trials determined that hematologic adverse events with LONSURF in subgroups of patients with mild to moderate renal impairment and mild hepatic impairment were manageable and similar to those in the overall patient population. Karin Blakolmer, MD, MBA, Senior Vice President and Head of Medical Affairs, Taiho Oncology, Inc. reiterated the importance of safety, and how any hematologic side effects of these trials were in line with the overall patient population and manageable in the same way. Blakomer further stated that this was positive news for people living with metastatic colorectal cancer and metastatic gastric cancer who are receiving treatment with LONSURF
https://finance.yahoo.com/news/taiho-oncology-presents-data-lonsurf-143000838.html
SURGICAL THERAPIES
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program — Sunnybrook Odette Cancer Centre (Feb.24.20)
The HAIP program is a first-in-Canada for individuals where colon or rectal cancer (colorectal cancer) has spread to the liver and cannot be removed with surgery. The program involves a coordinated, multidisciplinary team approach to care, with close collaboration across surgical oncology, medical oncology (chemotherapy), interventional radiology, nuclear medicine, and oncology nursing. The Hepatic Artery Infusion Pump (HAIP) is a small, disc-shaped device that is surgically implanted just below the skin of the patient and is connected via a catheter to the hepatic (main) artery of the liver. About 95 percent of the chemotherapy that is directed through this pump stays in the liver, sparing the rest of the body from side effects. Patients receive HAIP-directed chemotherapy in addition to regular intravenous (IV) chemotherapy (systemic chemotherapy), to reduce the number and size of tumours. Drs. Paul Karanicolas and Yooj Ko are the program leads and happy to see patients eligible for the therapy.
Presently at Sunnybrook Odette Cancer Centre, HAIP is being used in patients with colorectal cancer that has spread to the liver that cannot be removed surgically and has not spread to anywhere else in the body. Patients who have few (1-5) and very small tumors in the lungs may be considered if the lung disease is deemed treatable prior to HAIP. If you believe you may benefit from this therapy and/or would like to learn more about the clinical trial, your medical oncologist or surgeon may fax a referral to 416-480-6179. For more information on the HAIP clinical trial, please click on the link provided below.
http://sunnybrook.ca/content/?page=colorectal-colon-bowel-haip-chemotherapy
- Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases (Mar.12/20)
Approximately half of all colorectal cancer (CRC) patients develop metastases, commonly to the liver and lung. Surgical removal of liver metastases (LM) is the only treatment option, though only 20-40% of patients are candidates for surgical therapy. Surgical therapy adds a significant survival benefit, with 5-year survival after liver resection for LM of 40-50%, compared to 10-20% 5-year survival for chemotherapy alone. Liver transplantation (LT) would remove all evident disease in cases where the colorectal metastases are isolated to the liver but considered unresectable.
Image Source: https://www.slideshare.net/AhmedAdel65/preoperative
While CRC LM is considered a contraindication for LT at most cancer centers, a single center in Oslo, Norway demonstrated a 5-year survival of 56%. A clinical trial sponsored by the University Health Network in Toronto will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases limited to the liver and are non-progressing on standard chemotherapy. Patients will be screened for liver transplant suitability and must also have a healthy living donor come forward for evaluation. Patients who undergo LDLT will be followed for survival, disease-free survival, and quality of life for 5 years and compared to a control group who discontinue the study before transplantation due to reasons other than cancer progression. Despite the trial’s negative outcome, investigation of HIPEC, and other strategies to prevent peritoneal metastasis, should continue, they concluded in Lancet Gastroenterology & Hepatology. “The 21% peritoneal recurrence noted in the overall study population indicates the magnitude of the clinical problem in locally advanced colon cancer, and therapeutic strategies have to be further explored,” they said. “Outcomes of other trials investigating adjuvant HIPEC are eagerly awaited.”
https://clinicaltrials.gov/ct2/show/NCT02864485
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
- Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer (Mar.12/20)
Magnetic resonance-guided focused ultrasound (MRg-FU) is a noninvasive, outpatient modality being investigated for the thermal treatment of cancer. In MRg-FU, a specially designed transducer is used to focus a beam of low-intensity ultrasound energy into a small volume at a specific target site in the body. MR is used to identify and delineate the tumour, focus the ultrasound beam on the target, and provide a real-time thermal mapping to ensure accurate heating of the designated target with minimal effect to the adjacent healthy tissue. The focused ultrasound beam produces therapeutic hyperthermia (40-42°C) in the target field, causing protein denaturation and cell damage. Currently, there is no prospective clinical data reported on the use of MRg-FU in the setting of recurrent rectal cancer. Recurrent rectal cancer is a vexing clinical problem. Current retreatment protocols have limited efficacy. The addition of hyperthermia to radiation and chemotherapy may enhance the therapeutic response. With recent advances in technology, the investigators hypothesize that MRg-FU is technically feasible and can be safely used in combination with concurrent reirradiation and chemotherapy for the treatment of recurrent rectal cancer without increased side-effects. The study is being offered at the Odette Cancer Centre. Here is the link to the study protocol:
PSYCHOSOCIAL
- Positive Relationship Confirmed Between Spiritual Well-Being, Mental Health, and Quality of Life in Cancer Patients Receiving Chemotherapy (Mar.12/20)
Cancer is the second cause of death after cardiovascular diseases in the world. A reduction in quality of life (QoL) is experienced by cancer patients, creating negative physical and mental symptoms. A recent study of a cohort of 208 adults who have cancer and receiving chemotherapy was studied in Shiraz hospitals. During this research, participants completed two standard research questionnaires, which focussed on Spiritual Well-being, Mental Health, Quality of Life (QoL), and Excitement.
The results of the study revealed that:
There was a positive and significant correlation between mental health and QoL in cancer patients receiving chemotherapy
There was a positive and significant correlation between spiritual well-being and mental health in cancer patients undergoing chemotherapy
There was a negative and significant correlation between spiritual well-being and negative emotions and between mental health and negative emotions, respectively
In conclusion, the results of this study showed that there was a positive and significant relationship between spiritual well-being, mental health, and QoL in cancer patients.
Managing feelings is a part of improving mental health.
The National Institute of Health (NIH) offers the following guidance for patients on its website:
Ways to Cope with Your Emotions
Express Your Feelings
People have found that when they express strong feelings like anger or sadness, they’re more able to let go of them. Some sort out their feelings by talking to friends or family, other cancer survivors, a support group, or a counselor. But even if you prefer not to discuss your cancer with others, you can still sort out your feelings by thinking about them or writing them down.
Look for the Positive
Sometimes this means looking for the good even in a bad time or trying to be hopeful instead of thinking the worst. Try to use your energy to focus on wellness and what you can do now to stay as healthy as possible.
Don’t Blame Yourself for Your Cancer
Some people believe that they got cancer because of something they did or did not do. But scientists don’t know why one person gets cancer, and one person doesn’t. All bodies are different. Remember, cancer can happen to anyone.
Don’t Try to Be Upbeat If You’re Not
Many people say they want to have the freedom to give in to their feelings sometimes. As one woman said, “When it gets really bad, I just tell my family I’m having a bad cancer day and go upstairs and crawl into bed.”
You Choose When to Talk about Your Cancer
It can be hard for people to know how to talk to you about your cancer. Often loved ones mean well, but they don’t know what to say or how to act. You can make them feel more at ease by asking them what they think or how they feel.
Find Ways to Help Yourself Relax
Whatever activity helps you unwind, you should take some time to do it. Meditation, guided imagery, and relaxation exercises are just a few ways that we know help others; these may help you relax when you feel worried.
Be as Active as You Can
Getting out of the house and doing something can help you focus on other things besides cancer and the worries it brings. Exercise or gentle yoga and stretching can help too.
Look for Things You Enjoy
You may like hobbies such as woodworking, photography, reading, or crafts. Or find creative outlets such as art, movies, music, or dance.
Look at What You Can Control
Some people say that putting their lives in order helps. Being involved in your health care, keeping your appointments, and making changes in your lifestyle are among the things you can control. Even setting a daily schedule can give you a sense of control. And while no one can control every thought, some say that they try not to dwell on the fearful ones, but instead, do what they can to enjoy the positive parts of life.
https://www.ncbi.nlm.nih.gov/pubmed/31198740
https://www.cancer.gov/about-cancer/coping/feelings
OTHER
- Young Adult Colorectal Cancer Clinic Available at Sunnybrook (Mar.12/20)
A recent study led by the University of Toronto doctors has observed a rise in colorectal cancer rates in patients under the age of 50. The study mirrors findings from the U.S., Australia and Europe. The growing colorectal cancer rates in young people come after decades of declining rates in people over 50, which have occurred most likely due to increased use of colorectal cancer screening (through population-based screening programs) which can identify and remove precancerous polyps. Patients diagnosed under the age of 50 have a unique set of needs, challenges and worries. They are unlike those diagnosed over the age of 50. Dr. Shady Ashamalla (colorectal cancer surgical oncologist), and his team at the Sunnybrook Health Sciences Centre understand the needs of this patient population.
Dr. Ashamalla belongs to a multidisciplinary team of experts in the Young Adult Colorectal Cancer Clinic who will work with young colorectal cancer patients, regardless of disease stage, to create an individualized treatment plan to support each patient through their cancer journey. Their needs and concerns will be addressed as they relate to:
- Fertility concerns and issues
- Young children at home
- Dating/intimacy issues
- Challenges at work
- Concerns about hereditary cancer
- Relationships with family and friends
- Psychological stress due to any or all of the above
The team of experts consists of:
- Oncologists (medical, surgical, radiation)
- Social workers
- Psychologists
- Geneticists
- Nurse navigator
Should a patient wish to be referred to Sunnybrook, they may have their primary care physician, or their specialist refer them to Sunnybrook via the e-referral form, which can be accessed through the link appearing below. Once the referral is received, the Young Adult Colorectal Cancer Clinic will be notified if the patient is under the age of 50. An appointment will then be issued wherein the patient will meet with various members of the team to address their specific set of concerns.
http://sunnybrook.ca/content/?page=young-adult-colorectal-cancer-clinic
- A strain of E ColiLinked to About 5% of Colorectal Cancer (Feb. 27/20)
Certain probiotics may not be such a good idea when trying to prevent colorectal cancer. Researchers in a study by the Hubrecht Institute (KNAW) and the Princess Máxima Center for Pediatric Oncology (Utrecht, Netherlands), found that one strain of the common bacterium Escherichia coli may be involved in the development of colorectal cancer (CRC). In the future, this could result in new ways to diagnose CRC. But for now, it has led to a further question as to whether certain probiotics that contain toxin-secreting strains of E Coli may be harmful.
The study focused on a particular strain of E Coli that produces a toxin called colibactin, which is found more frequently in stool samples from people with CRC than in stool samples from healthy individuals. Colibactin is well known to cause DNA damage in cells in vitro, so researchers set out to determine if the same damage might be occurring in the cells’ linings in the gut. The study was executed by making mini replicas of intestinal tissue known as human intestinal organoids. They then exposed this cultured tissue to the toxin-secreted strain of E Coli. What they found was that these bacteria caused a specific unique DNA mutation pattern of human cells — while other strains of E Coli did not.
Researchers then analyzed tissue from over 5500 tumor samples from CRC patients both in the UK and Netherlands. The same unique pattern of mutations showed up in about 5% of the tumors. The conclusion was that the study points to a distinct mutational signature in CRC and implies that the reason was past exposure to bacteria. The researchers also note this is the first time such a distinctive pattern of DNA damage in CRC has to emerge specifically from a bacterium in the gut. Caution should be exercised in the use of probiotic products, specifically those that contain genotoxic strains of E Coli.
It is worth noting that some of these strains are utilized in specific clinical trials. Though these probiotics help with bodily discomfort in the short term, they could lead to cancer many years after the treatment. CRC Is a complex disease and is likely to have many contributing factors. The complexities of CRC should be considered in light of these new findings.
https://www.medscape.com/viewarticle/926121
- Colon Cancer in Patients Under 25 Years Old: A Different Disease? (Mar.1/20)
A recent study compared the stage-for-stage overall survival (OS) and recurrence-free survival (RFS) between adult and pediatric/adolescent colon cancer patients. Past patients treated between 1991 and 2017 under 25 years of age (pediatric/adolescent) were studied at the University of Texas MD Anderson Cancer Center. These patients were compared with a prospectively maintained database of adult patients. Researchers compared the group using models and tests employed in standard research practices.
Of the 94 pediatric patients and 765 adult patients, the following results were observed:
A 3-year OS rate of 90% for adult patients and 40.92% for pediatric patients
A 3-year RFS rate of 78% for adult patients and 32% for pediatric patients
The 5-year OS rates (by stage) for adult vs. pediatric patients were as follows:
Stage 1: 96% for adult patients and 100% for pediatric patients
Stage 2: 90% for adult patients and 64% for pediatric patients
Stage 3: 85% for adult patients and 58% for pediatric patients
Stage 4: 55% for adult patients and 16% for pediatric patients
The 5-year RFS rates (by stage) for adult vs. pediatric patients were as follows:
Stage 1: 95% for adult patients and 100% for pediatric patients
Stage 2: 85% for adult patients and 55% for pediatric patients
Stage 3: 73% for adult patients and 31% for pediatric patients
Stage 4: 27% for adult patients and 5% for pediatric patients
Pediatric/adolescent patients had a higher risk of recurrence or death and incidence of peritoneal metastases than adult patients. In conclusion, stage-for-stage, pediatric/adolescent patients had shorter 3- and 5-year OS and RFS rates than adult patients. Peritoneal disease and carcinomatosis were significantly higher in pediatric, adolescent, and young adult patients less than 25 years. Pre-disposing conditions such as polyposis or congenital colon disease did not contribute to this difference.
What is carcinomatosis?
A condition in which cancer is spread widely throughout the body, or, in some cases, to a relatively large region of the body. Also called carcinosis.
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/carcinomatosis
https://www.journalacs.org/article/S1072-7515(20)30167-8/fulltext
SCREENING
- Increased Incidence of Colorectal Cancer Underestimated For Some Patients, Study Finds (Feb. 3/20)
A new research study finds that the rising rate of colorectal cancer in patients aged 49 and 50 is underestimated and unaccounted for in the current investigational model, known as SEER.
What is SEER?
SEER (Surveillance, Epidemiology, and End Results) is a program created by the National Cancer Institute (NCI) in an effort to reduce the cancer burden in the U.S. by providing information on cancer incidences and survival rates.
Colorectal Cancer screening guidelines are created from this program. A significant increase in the incidence of early-onset colorectal cancer in patients between 45 and 50 years old is consistent with previously undetected colorectal cancers diagnosed before age 50. Still, they are not accounted for in SEER.
Image Source: https://pbs.twimg.com/media/C4jQnz2W8AAT1f3.jpg
Therefore, using SEER data alone to determine earlier screening could underestimate the number of diagnoses that could be prevented, according to research from JAMA Network Open.
Researchers believed SEER was underestimating the amount of colorectal cancer in patients younger than 50 compared to those who are older. This underestimate occurred because colorectal cancer screenings typically do not occur until the age of 50. As early-onset colorectal cancer rises, the debate continues as to whether patients require screening at 45 or 50 years old. In 2018, the screening age was lowered to 45 by The American Cancer Society. Other organizations, however, have kept the recommended age to 50.
Researchers note that early-onset patients are often asymptomatic and that the SEER registries don’t necessarily reflect the full picture of colorectal case burdens in younger patients. They feel that it is expected to see a degree of colorectal cancer incidence increase from 49 to 50 years of age, because of the new screening uptake and diagnosis of pre-existing (colorectal cancer diagnosis) that may have been clinically undetected before the screening.
Looking at the SEER 18 registries ( 28% of the U.S. population), they analyzed colorectal cancer incidence rates from January 1, 2000, to December 31, 2015. This one done at one-year age increments from 30-60 years old. This registry represents a total of 170,434 cases of colorectal cancer examined in 165,160 patients, of which 55.9% were men.
Image source: https://ruesch.georgetown.edu/wp-content/uploads/sites/136/2019/05/yacrc_1.png
Here are some of the critical points of the findings:
Between the ages of 49 and 50, researchers found a 46.1% increase of colorectal cancer incidences in for all U.S. regions, (men and women among both white and black populations)
This rate increase was significantly higher than any one-year age increase.
The findings were likely due to screening detection as opposed to advancing age
Increases occurred across geographical regions, in men and women, in white and black populations, and both colon and rectal cancer
92.9% of the cases were invasive and required surgery, they felt due to delayed screening and missed cancers
Researchers conclude that the findings suggest a high case burden of undetected preclinical (early-onset colorectal cancer) in younger patients, not reflected in observed SEER incidence rates. The underlying early-onset colorectal cancer burden (combined detected and undetected cases), therefore, for individuals aged 45 to 49 years, is shown to be underestimated and may approach that of individuals in their early 50s. Further studies are warranted. These would investigate and more deeply profile the proportion of colorectal cancer cases diagnosed at age 50 through a screening or diagnostic test, as well as model studies incorporating the increased incidence rates in patients between 49 and 50 years old.
NUTRITION/HEALTHY LIFESTYLE
- Flax Seeds Are a Rich Source of Lignans, Which May Reduce Cancer Risk (Mar.12/20)
Lignans are plant compounds that have antioxidant and estrogen properties, both of which can help lower the risk of cancer and improve health, with flax seeds containing up to 800 times more lignans than other plant foods. Observational studies show that those who eat flax seeds have a lower risk of breast cancer, particularly postmenopausal women. According to a Canadian study involving more than 6,000 women, those who eat flax seeds are 18% less likely to develop breast cancer. Men can also benefit from eating flax seeds. In a small study including 15 men, those given 30 grams of flax seeds a day while following a low-fat diet showed reduced levels of a prostate cancer marker, suggesting a lower risk of prostate cancer. Flax seeds also appeared to have the potential to prevent colon and skin cancers in laboratory and animal studies. Yet, more research is required to confirm this finding. The evidence so far points to flaxseed as potentially valuable in the fight against many cancers.
Nevertheless, the evidence thus far points to flax seeds being a potentially valuable food in the fight against various cancers.
Image source: https://shop.honeyville.com/flax-seeds.html
After a systematic review of the global scientific literature, including that of the National Institute of Cancer (NIH), AICR/WCRF analyzed many foods and their nutrients towards understanding their effect on the risk of developing cancer. There is probable and convincing judgment showing that foods with dietary fiber decrease the risk of colorectal cancer. Flaxseeds also have a high amount of healthy Omega 3 Acids. They may improve cholesterol and lower blood pressure. Also, they are nutrient-dense, easily sourced, and highly versatile.
Here are some easy ways to use flax seeds in your diet:
- Add to your water – for drinking or as an egg substitute
- Mixing them into your yogurt, smoothies, or veggie or meat patty recipes
- Adding them to your baking recipes
- Using Flaxseed Oil in dressings — or general food preparation
- Using them as a topping on its own or combined with other ingredients (tree nuts or fruit for example) on a variety of foods such as breakfast cereals, fish or vegetables
AICR/WCRF. Diet, Nutrition, Physical Activity, and Cancer: A Global Perspective, 2018.
aicr.org/cancer-prevention/food-facts/flaxseed/
healthline.com/nutrition/benefits-of-flaxseeds#section3
- Healthy Gut Promoting Compounds in Pulses May Help Protect Against Cancer (Mar.12/20)
Dietary fiber, resistant starch, and phenolic compounds in pulses all may support the growth of health-promoting gut bacteria (the microbiome). More research will help us understand how individual differences, and different forms of these compounds, contribute to protection against cancer.
What are Pulses?
Pulses are the dry, edible seed of the legume family. A legume is a plant with a seed pod.
Image source: www.manitobapulse.ca/wp-content/uploads/2018/03/LGume.png
Interpreting the data
As in the previously mentioned article about Flaxseeds, the AICR/WCRF studied literature from around the world. The goal was to analyze how plant foods and their nutrients might affect the risk of developing cancer. There is probable evidence that foods with high fiber decrease the chances of colorectal cancer, as well as weight gain, overweight, and obesity.
Here are some ideas on how to incorporate more pulses in your diet:
- Make homemade hummus or dip
- Try pea protein powder
- Adding black beans, white beans, chickpeas and other pulses to your baking and dessert recipes (chocolatecoveredkatie.com, as well as other recipe sites, have many ideas you can use)
- Substitute them where you would eat meat (wraps, patties, and with rice or pasta dishes)
- Dehydrate them as a snack
- Use them in salads or soups
https://www.aicr.org/cancer-prevention/food-facts/dry-beans-and-peas-legumes/
Phytochemicals in Blueberries May Offer Anti-Cancer Benefits (Mar.12/20)
Blueberries, which contain many phytochemicals and nutrients, show potential anti-cancer effects in laboratory studies. These studies found that eating blueberries increases antioxidant activity in the blood and shows the potential to prevent DNA damage. More research is needed to understand the role of the blueberry in these areas adequately. There is much more to cover in the future on the part of phytochemicals as new data emerges.
What Are Phytochemicals?
Phytochemicals are chemical compounds produced by plants, generally to help them thrive or thwart competitors, predators, or pathogens. Some phytochemicals serve as poisons and others as traditional medicine.
Red, blue, and purple colors of berries derive mainly from polyphenol phytochemicals known as anthocyanins.
https://en.wikipedia.org/wiki/Phytochemical
Image Source: https://www.pexels.com/photo/food-forest-blueberries-raspberries-87818/
Interpreting the data
After a systematic review of the global scientific literature, AICR/WCRF analyzed how fruits and their nutrients affect the risk of developing cancer. Limited evidence suggests that foods containing vitamin C may DECREASE the risk of colon cancer, lung cancer (in people who smoke), and squamous cell esophageal cancer.
https://www.aicr.org/cancer-prevention/food-facts/blueberries/
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