The following colorectal cancer research updates extend from August 4th to September 17th, 2020, inclusive and are intended for informational purposes only.
- Phase II LEAP Clinical Trial to Treat mCRC
- Health Canada approves VITRAKVI (Larotrectinib), first tumour agnostic cancer treatment for advanced solid tumours harbouring an NTRK gene fusion
- A Phase II, Open-Label, Multicentre, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population
- 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
- Initiation of Phase 2 Study to Assess Activation of Anti-cancer Immune Response in Colon Cancer
- Bevacizumab Plus mFOLFOX6 as First-Line Treatment for RAS Mutant Unresectable Colorectal Liver-Limited Metastases
- Radiosensitisation and Enhanced Tumour Growth Delay of CRC Cells by Sustained Treatment with Trifluridine/Tipiracil (Lonsurf) and X-rays
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Hospital
- Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
- Older Colon Cancer Patients May Be OK for Lap Surgery
- Bevacizumab Boosts Liver Resection in RAS-Positive mCRC
- First Long-term Oncologic Results of the ALPPS Procedure
- Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer
- Rising CRC Rates in Younger People
- Blood-Based Assay Could Soon Surface in CRC
- Young Adult Colorectal Cancer Clinic Available at Sunnybrook Hospital
- In Honour of Chadwick Boseman
- Trends in the Epidemiology of Young-Onset CRC
- Shared Experiences of Diagnosis and Treatment of Young-Onset CRC
- Pre-diagnostic Circulating Concentrations of Vitamin D Binding Protein and Survival among Patients with CRC
- Ten Cancer Prevention Recommendations from the American Institute for Cancer Research (AICR)
- Yes, You Can Get COVID-19 Again
- COVID-19 Antibody Evidence; Diabetes Drug May Treat Disease
- Frequently Asked Questions for COVID-19
DRUGS / SYSTEMIC THERAPIES
- 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 tumour-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 tumours 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.
Another submission will be made by Bayer to CADTH in the fall of 2020.
- 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.
- 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.
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.
- Initiation of Phase 2 Study to Assess Activation of Anti-cancer Immune Response in Colon Cancer (Aug.18/20)
Qu Biologics Inc. has received approval to proceed with their clinical trial of QBECO SSI in patients with colorectal cancer (CRC). The study is designed to assess the effect of QBECO SSI treatment on immune function in the tumour and systemically in patients newly diagnosed with colon cancer. CRC suppresses the patient’s immune response, which is recognized to have a detrimental effect on prognosis.
Participants will receive QBECO SSI treatment from the time of colon cancer diagnosis to the time the tumour is surgically removed 3-5 weeks later. The perioperative period (including immediate preoperative preparation and postoperative recovery) presents a window of opportunity to activate immune function in this patient population to overcome cancer-induced immune suppression and improve prognosis. If positive, the results could have transformative potential in colon cancer therapy.
It has long been recognized that activating innate anti-cancer mechanisms in this manner could lead to tumour regression. Researchers are hopeful that Qu’s SSIs can provide this response safely and consistently.
- Bevacizumab Plus mFOLFOX6 as First-Line Treatment for RASMutant Unresectable Colorectal Liver-Limited Metastases (Aug.04/20) (See Article #11 For Additional Information)
This article assesses the effects of bevacizumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) as first-line treatment of RAS mutant unresectable colorectal liver metastases.
From October 2013 to December 2017, patients with RAS mutant unresectable liver-limited metastases from colorectal cancer (CRC) were randomly assigned to receive mFOLFOX6 plus bevacizumab (arm A) or mFOLFOX6 alone (arm B). The primary end point was the rate of patients converted to R0 resection (complete resection) for liver metastases.
A total of 121 patients were randomly assigned to arm A and 120 to arm B. The median follow-up time was 37.0 months for all patients. The R0 resection rates for liver metastases were 22.3% (27 of 121 patients) in arm A and 5.8% (7 of 120 patients) in arm B. Patients in arm A had significantly better objective response rates (54.5% v 36.7%), median progression-free survival (9.5 v 5.6 months) and median overall survival (25.7 v 20.5 months) compared with those in arm B.
- Radiosensitisation and Enhanced Tumour Growth Delay of CRC Cells by Sustained Treatment with Trifluridine/Tipiracil and X-rays (Nov.28/20)
FTD/TPI is a novel oral formulation of trifluridine (FTD) and tipiracil hydrochloride (TPI), a thymidine phosphorylase inhibitor. It has now been approved for the treatment of patients with advanced metastatic colorectal (mCRC) and gastric cancer in the U.S. The direct comparison of capecitabine and FTD/TPI, both combined with bevacizumab in 1st line mCRC patients not eligible for intensive treatment, favoured FTD/TPI in terms of progression-free survival (PFS) with a median of 9.23 months compared to 7.82 months.
This study explores efficacy, mode of action and treatment scheduling of FTD/TPI for combined chemoradiation in an in vitro cell culture and an in vivo xenograft model of colorectal carcinoma. Treatments with FTD/TPI or capecitabine alone showed overall only a modest effect on relative tumour growth. Radiotherapy and especially radiochemotherapy with capecitabine and FTD/TPI caused a marked growth delay. Combined treatments tended to further delay tumour growth relative to radiation therapy alone.
While no robust molecular biomarker is available yet that could help identify those CRC patients, who would benefit most from FTD/TPI-based chemoradiation treatment, this study can demonstrate a radiosensitising effect at the cellular level, caused by sustained FTD/TPI treatment, as well as comparable efficacy of this agent and capecitabine, when used in combination with radiation. Based on these preclinical experimental data, a clinical trial in order to test radiochemotherapy with FTD/TPI for advanced rectal carcinoma is currently underway.
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program — Sunnybrook Odette Cancer Centre (July 16/20)
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 tumours 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.
- Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases (July 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.”
- Older Colon Cancer Patients May Be OK for Lap Surgery (Aug.17/20)
In an unblinded randomized trial involving patients aged 75+ needing colorectal cancer (CRC) resection, long-term results with laparoscopic procedures came out even with open surgery. Among 190 patients evaluable for 5-year outcomes, no significant differences were seen in any measure of survival [i.e. overall, disease-free, recurrence-free, or cancer-specific], according to Shoichi Fujii, MD, PhD, of Yokohama City University in Japan.
For instance, overall survival (OS) at 5 years for all primary tumour locations was just over 80% in both groups. Point estimates for the long-term outcomes favoured open surgery for many of the survival outcomes. For example, 20.4% of the laparoscopic group experienced recurrence compared with 13.0% of patients getting open surgery. Similarly, rates of disease-free survival (DFS) differed by about 5% in favour of open surgery.
While surgery type was not a significant predictor of recurrence in the study, Fujii and colleagues did identify three others that were:
- Vascular invasion: hazard ratio (HR) 2.74
- Lymph node metastasis: HR 3.05
- Rectal cancer: HR 3.19
Fujii acknowledged the “strong tendency toward local recurrence” with laparoscopic procedures, calling it “an important problem.” All such cases involved rectal tumours, he said. A larger trial is needed to establish definitively whether laparoscopic surgery is genuinely as effective as open procedures for elderly patients.
Image Source: https://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/articles/health_and_medical_reference/cancer/laparoscopic_surgery.jpg
- Bevacizumab Boosts Liver Resection in RAS Mutant mCRC (Aug.24/20)
A randomized trial showed almost four times as many patients with liver-limited, unresectable metastatic RAS-Mutant colorectal cancer (CRC) converted to resectable status when bevacizumab was added to chemotherapy.
The proportion of patients who had resectable post-therapy lesions increased from 5.8% with chemotherapy alone to 22.8% with the addition of bevacizumab. Response rate, progression-free survival (PFS), and overall survival (OS) all improved significantly with the angiogenesis inhibitor.
Analysis of the study showed response rates of 54.5% with bevacizumab versus 36.6% with chemotherapy alone. Disease control rates (response plus stable disease) were 86% and 65% with bevacizumab and the chemotherapy-alone arms, respectively. The median PFS was 9.5 months with bevacizumab and 5.6 months. The median OS was 37.8 months for patients with R0 resection of liver metastases and 22.5 months for patients without liver resection [in the bevacizumab arm].
This study confirmed that, for patients with RAS-mutant, initially unresectable colorectal liver-limited metastases, the addition of bevacizumab to chemotherapy increased radical resections of liver metastases with minimal perioperative complications and prolonged long-term survival.
- First Long-term Oncologic Results of the ALPPS Procedure (Sept.03/20)
A recently published paper analyzes the long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy).
Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centres to secure a comprehensive cohort. Overall, cancer-specific survival (CSS), and recurrence-free survival (RFS) were analyzed along with independent risk factors. The cohort included 510 patients from 22 ALPPS centres over a 10-year period. Ninety-day mortality was 4.9% and median overall survival (OS), CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months. Multivariate analysis identified tumour-characteristics (primary T4, right colon), biological features (KRAS/NRAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumours) as independent predictors of CSS. Traditional factors such as size of metastases, unilobar (one lobe) vs. bilobar (2 lobes) involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs. 30 months).
Petrowsky, H et al., First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases. Annals of Surgery. 2020
A Little Bit About ALPPS:
- ALPPS is the most advanced surgical treatment for colorectal cancer liver mets
- This is a two staged surgical therapy for patients who have liver mets to both lobes of the liver who are not candidates for traditional liver resection because they have multiple lesions to both lobes of liver
Here is what is involved:
- When both lobes contain tumours, the surgeon will identify the lobe with the lower tumour burden
- The surgeon will resect the metastases from one lobe containing fewer mets
- They then ligate the portal vein supplying blood to the other lobe containing the greater number of mets
- They also partition the liver with a transecting incision of the parenchyma (spongy tissued) to interrupt blood flow to the other lobe: result is no blood supply to the lobe containing more mets and blood flow is diverted to the lobe containing fewer tumours which will end up growing and be preserved
- Partitioning the liver helps enhance growth of the future liver remnant by stimulating growth factors
- This makes the lobe grow faster and larger
- Second surgery is performed wherein the diseased lobe is removed containing the greater tumour burden (2 weeks later)
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:
- Rising CRC Rates in Younger People (Aug.22/20)
The American Cancer Society published a report in CA: A Cancer Journal for Clinicians, which indicated colorectal cancer (CRC) cases are on the rise in young adults. While the rate is dropping among people aged 65+, largely because older adults are undergoing recommended screenings, the cancer society stated that in 2020, 12% or 17,930 CRC cases will be diagnosed in people under the age of 50. The American Cancer Society also predicted an estimated 53,200 CRC deaths with approximately 7% or 3,640 deaths in adults younger than age 50.
Rates have been rising since the mid-1980s in adults 20-39 years of age and since the mid-1990s in adults 40-54 years, with younger age groups experiencing the highest increase. Millennials are twice as likely to develop colon cancer and four times as likely to develop rectal cancer when compared to young adults in the 1950s when the risk was at its lowest. While it is uncertain what is causing the rise in people younger than 50 who are developing colon cancer, it does demonstrate the importance of prevention and early screening.
The most important action individuals can take to prevent colon cancer is to be screened regularly. However, one in three people between the ages of 50 and 75 have not been screened. The U.S. Preventive Services Task Force and other health organizations in the United States recommend routine screening for CRC begin at age 50. People who are at high risk (have a family history or other health conditions that predispose them to develop colon cancer) should be screened at an earlier age. There has also been some evidence that African-Americans should start screening at 45 years of age.
Some conditions that predispose you to colon cancer include family history, eating a lot of red meat and processed meat, obesity, little to no physical activity and a lack of fibre and vitamin D in your diet. In addition, smoking can increase the risk for developing colon cancer as well as excessive use of alcohol.
- Blood-Based Assay Could Soon Surface in CRC (Aug.04/20)
Shai Friedland, MD, mentioned that results from the blood-based assay can inform whether a patient should undergo a colonoscopy. “This is the first time we have convincingly shown that we can also detect pre-cancers in the blood. We can use a relatively noninvasive blood test to intervene earlier, before a patient develops cancer,” said Friedland.
At the 2020 ASCO Virtual Scientific Program, Friedland presented the interim results of a study evaluating the test in 354 patients with no prior history of CRC and who were scheduled to undergo a colonoscopy. Prior to colonoscopy, patients’ blood was drawn and analyzed with the FirstSight assay. The test achieved 90% specificity and 100% sensitivity for detecting CRC, in addition to 75.5% sensitivity for detecting advanced adenomas. Overall, the test elicited a 79.7% sensitivity for detecting advanced adenomas and CRC.
What biomarkers does the test analyze?
Friedland: This test uses 3 different factors to determine a risk score for who has polyps and cancer. Circulating epithelial cells are cells that come mainly from the colon and are shed into the bloodstream. There are significantly more of them in patients who have a [higher cancer burden], but there are still very, very few of these cells. The key component of this is [to use] a very sensitive assay to detect circulating epithelial cells.
The second component is DNA mutations that are associated with colon cancer. We check the blood for mutations in genes that are known to be involved in colon cancer. Number 2 is methylation, which is another component of the genetic changes that happen with colon cancer. Methylation, specifically of the SEPT9 gene, is available as a standalone blood test for colon cancer. However, it performs very poorly.
The assay we use incorporates all 3 of these elements, which is an important part of the study.
How does this blood-based assay compare with colonoscopy?
Friedland: In this study, colonoscopy was used as the gold standard because it really is the best test that we have available. We need to know who has cancer, the stage of the cancer, who has polyps, how many polyps they have, and how big those polyps are. All of that information is picked up by the colonoscopy. If any cancer is detected, the patient gets a CT scan and staged.
All of the patients in this study underwent colonoscopy. However, right before their colonoscopy, they had their blood drawn. The blood was sent to the lab and analyzed without the knowledge of what the colonoscopy results were. Then we compared the results of the blood test and the results of the colonoscopy to determine how good the blood-based test is at detecting patients with polyps and patients with cancers.
Image Source: https://this.deakin.edu.au/innovation/blood-tests-and-diagnosing-illness-what-can-blood-tell-us-about-whats-happening-in-our-body
- 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
- 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.
- In Honour of Chadwick Boseman (Aug.30/20)
On Friday, August 28, 2020 actor Chadwick Boseman, most known for his lead role in Marvel’s Black Panther, passed away after a private four-year battle with colon cancer. Diagnosed in 2016 at stage III, Boseman’s cancer progressed to stage IV before his passing at age 43.
The incidence of colorectal cancer (CRC) is higher among African Americans than any other population group in the United States. Research also shows that African Americans are being diagnosed at a younger average age than other people, thus experts suggest that they begin their CRC screenings at age 45.
The National Center for Health Statistics at the Centers for Disease Control and Prevention (CDC), reported that 1 in 41 Black males will die from CRC, compared to 1 in 48 White males. The risk is similar for women: 1 in 44 Black females will die from CRC, compared to 1 in 53 White females.
Recent studies show that “compared with adults born circa 1950, those born circa 1990 have double the risk of colon cancer and quadruple the risk of rectal cancer.” Additionally, younger patients are often diagnosed at a later stage, when the disease is more challenging to treat, due to delays in seeking medical care and being misdiagnosed.
- Trends in the Epidemiology of Young-Onset CRC (Sept.09/20)
Recent data suggests that the risk of young-onset colorectal cancer (yCRC), in adults less than 50 years of age, is increasing. A systematic review of studies was conducted by experts to examine population-level trends in yCRC epidemiology.
They identified 40 studies from 12 countries across five continents. One study assessed yCRC prevalence trends reporting an annual percent change (APC) of + 2.6 and + 1.8 among 20–39 and 40–49 year olds, respectively. 39 studies assessed trends in yCRC incidence but with substantial variability in reporting. Meta-analysis of the most commonly reported trend estimate yielded an overall APC of + 1.33 that is largely driven by findings from North America and Australia. Also contributing to these trends is the increasing risk of rectal cancer as among 14 studies assessing cancer site, nine showed an increased risk of rectal cancer in adults less than 50 years with APC up to + 4.03.
Image Source: https://www.ccalliance.org/about/never-too-young
Khalid Saad El Din, et al., Trends in the epidemiology of young-onset colorectal cancer – a world wide systematic review.. BMC Cancer; 2020 20:288. https://doi.org/10.1186/s12885-020-06766-9
- Shared Experiences of Diagnosis and Treatment of Young-Onset CRC (Sept.04/20)
In a qualitative study, individuals who have been diagnosed with young-onset colorectal cancer (yCRC) that is below the age of 50 years, or care for an individual with yCRC were invited to complete an online survey. It was primarily comprised of an open-ended question asking participants to share their yCRC experiences in a text box, much like posting on a social media platform.
From May to June 2019, experiences from 109 patients with yCRC and 11 caregivers were gathered. The majority of patients with yCRC were female (86, 71.7%) and diagnosed between the ages of 30 and 39 (49, 40.9%) and 40 and 49 years (61, 50.8%).
Eight themes were identified:
- Symptoms experienced
- Being misdiagnosed
- Advocating for oneself
- Appreciation of the healthcare team
- Frustration with the healthcare team and healthcare system
- Lasting effects of yCRC and its treatment
- Connecting with others
- Reflections on experiences with yCRC.
The study highlights challenges experienced by yCRC patients across diagnosis, during treatment, and after treatment, notably misdiagnosis and need for access to information and support. The work also serves as a demonstration of how collaborations between patient and research communities can facilitate education and awareness of yCRC for patients and healthcare providers.
- Pre-diagnostic Circulating Concentrations of Vitamin D Binding Protein and Survival Among Patients with CRC (Sept.15/20)
Higher total 25-hydroxyvitamin D [25(OH)D] levels are associated with improved survival among patients with colorectal cancer (CRC), yet the relationships between vitamin D binding protein (VDBP), and bioavailable or free 25(OH)D, and CRC survival remain unknown. Thus, a recent study examined the associations between pre-diagnostic plasma levels of vitamin D–related markers and survival among 603 white participants diagnosed with CRC from two U.S. cohorts.
Higher VDBP levels were associated with improved overall and CRC–specific survival. Compared with patients in the lowest quartile, those in the highest quartile of VDBP had a multivariate hazard ratio (HR) of 0.58 for overall mortality and 0.58 for CRC–specific mortality. The results remained similar after further adjustment for total 25(OH)D levels. In contrast, neither bioavailable nor free 25(OH)D levels were associated with overall or CRC–specific mortality. Therefore, pre-diagnostic circulating concentrations of VDBP were positively associated with survival among patients with CRC.
- Nine Cancer Prevention Recommendations from the American Institute for Cancer Research (AICR) (Jun.29/20)
- Maintain a healthy weight: obesity is a risk factor for colorectal cancer and other cancers.
- Be physically active: Walk more and sit less. A sedentary lifestyle is a risk factor for colorectal cancer and other cancers. Just 30 minutes of physical activity 5 times a week can go a long way towards improving your health. Three 10-minute walks each day provide as much physical benefits as one 30-minute stroll. If you’ve never been physically active, consider starting your journey towards regular activity with a series of moderate, 15-minute exercise sessions. Do five sessions during week one. Then gradually add five, ten, or fifteen minutes over the next several weeks until each session gets past the 30-minute mark. If you want to start really simply, then go for brisk walks. By walking 30 minutes a-day, five days a week you easily meet AICR’s recommendation to be physically active 150 minutes a-week and reduce your cancer risk.
- Eat a diet rich in:
- Whole Grains
- Beans and lentils
- Limit consumption of fast foods and other processed foods that are high in fat, starches, or sugars. Limiting these products helps you control your caloric intake and makes it easier to maintain a healthy weight.
- Limit consumption of red and processed meat. Eat no more than moderate amounts (12-18 ounces per week) of red meat, such as beef, veal, pork and lamb. Eat little, if any, processed meat.
- Limit consumption of sugar-sweetened drinks. Drink mostly water and unsweetened drinks.
- Limit alcohol consumption. For cancer prevention, it is best not to drink alcohol but here is the recommendation from the World Cancer Research Fund regarding alcohol consumption:
For Women: 1 drink per day (max); For Men: 2 drinks per day (max)
What constitutes one drink? One drink is e quivalent to 12 ounces of beer, 5 ounces of wine or 1.5 ounces of spirits (hard liquor).
- Do not use supplements for cancer prevention. Instead, aim to meet your nutritional needs through diet alone.
- After a cancer diagnosis, follow these recommendations, if you can. Check with your health care provider about what is right for you!
- Yes, You Can Get COVID-19 Again (Aug.27/20)
Researchers have found that a man contracted the new coronavirus a second time months after his original illness. The case suggests reinfection can occur a few months after recovering from an initial bout of COVID-19. Although, much more research is needed to determine how common reinfections could be.
After testing positive again for SARS-CoV-2, his second infection remained asymptomatic throughout its entire course. By sequencing the virus behind each infection, the researchers determined that the infections were caused by different variants of the new coronavirus. “All viruses mutate, and these are a way to distinguish that this was a new infection and not prolonged shedding of the prior one,” explained Dr. Amesh Adalja, infectious disease physician and senior scholar for Johns Hopkins University’s Center for Health Security. This is the first documented case of a SARS-CoV-2 reinfection, but health experts suspect the patient isn’t the only one to contract the new coronavirus twice already.
Adalja isn’t surprised the patient didn’t have symptoms the second time around, as this is common with other coronavirus reinfections. Researchers suspect the first infection may prime a person’s immunity to fight a second infection. There may have been other parts of his immune system that were not checked at the time, memory B cells or T cells perhaps, that still remembered the first infection and were able to help clear up the second. In general, second and third infections tend to be less severe, and that may have to do with your immune response. Researchers want to determine whether reinfections are common events or rare occurrences to better understand how they could affect a vaccine and herd immunity.
- COVID-19 Antibody Evidence; Diabetes Drug May Treat Disease (Sept.04/20)
A new study published in the New England Journal of Medicine finds antibody levels held steady for about 4 months after developing COVID-19. “Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3%,” wrote the study authors.
The findings are in line with those in a preprint article published last month showing antibody levels were stable for at least 3 months in patients who had recovered from the virus in New York City. New research suggests not only that diabetes is a risk factor for severe COVID-19, but the disease may also induce diabetes. Danish drug company Novo Nordisk A/S is investigating the effectiveness of a new class of diabetes treatment called GLP-1 drugs, to fight COVID-19.
image Source: https://www.atlantaendocrine.com/blog/now-offering-covid-19-antibody-testing
- Frequently Asked Questions for COVID-19
Q: What is COVID-19 (or novel Coronavirus Disease – 19)?
A: Coronaviruses are a large family of viruses that can cause illnesses in humans and animals. Coronaviruses can cause illnesses that range in severity from the common cold, to more severe diseases such as Severe Acute Respiratory Syndrome (SARS) and most recently, COVID-19. COVID-19 or novel coronavirus originated from an outbreak in Wuhan, China in December 2019. The most common symptoms associated with COVID-19 can include fever, fatigue, and a dry cough. Though additional symptoms have now been linked with the disease, which may include aches and pains, nasal congestion, runny nose, sore throat, diarrhea, skin rash and vomiting. It is also possible to become infected with COVID-19 and not experience any symptoms or feeling ill. The spread of COVID-19 is mainly through the transmission of droplets from the nose or mouth when a person coughs, exhales or sneezes. These droplets land on surfaces around a nearby person. COVID-19 can be transmitted to that nearby person who may end up touching the surface contaminated with COVID-19 and then end up touching their nose, mouth, or eyes. A person can also contract COVID-19 through inhaling these droplets from someone with COVID-19. Although research is still ongoing, it is important to note that older populations (over the age of 65), those with a compromised immune system and those with pre-existing conditions including heart disease, high blood pressure, lung disease, diabetes or cancer may be at a higher risk of severe illness due to COVID-19.
Q: What can I do to avoid getting Coronavirus?
A: There are various ways in which we can reduce our risk of contracting COVID-19. Below are some measures suggested by the World Health Organization
- Keep at least 2 metres (or 6 feet) between yourself and other people. This will reduce the risk of inhaling droplets from those infected with COVID-19.
- Regularly clean your hands for at least 20 seconds with warm water and soap, or an alcohol-based hand rub. This will kill any viruses on your hands.
- Avoid touching your eyes, nose and mouth. If the virus is on your hands, it can enter the body through these areas.
- Follow good respiratory hygiene by covering your mouth and nose with a tissue or elbow when you cough and sneeze. This prevents the droplets from settling on surfaces or being released into the air around you.
- Stay home as much as possible, especially if you are feeling unwell. If you think you may have the Coronavirus, please see “What should I do if I think I have Coronavirus?” section.
- Please wear a face covering or mask in public when physical distancing is not possible.
Q: Are there any treatments available for Coronavirus?
A: People with cancer are at a higher risk of severe illness due to COVID-19 as cancer is considered a pre-existing health issue. Some cancer treatments including chemotherapy, radiation and surgery can weaken the immune system, making it harder for the body to fight infections and viruses, such as Coronavirus. It is important to diligently follow the World Health Organization’s recommendations above to reduce the risk of contracting COVID-19. If you have any concerns about your risk, it is best to contact your doctor or healthcare team.
There are currently no treatments available for COVID-19 but trials are underway to determine how to best treat and manage those afflicted with the virus. Vaccine candidates are being vigorously tested in a number of countries around the world, Canada included. The US government is funding 3 major phase 3 trials on potential COVID-19 vaccines and all 3 trials are being conducted by 3 different pharmaceutical companies looking at different vaccine candidates. The hope is to have a vaccine by the end of the year!
Q: Are there special precautions that people with cancer can take?
A: People with cancer (and other chronic ailments such as heart disease, diabetes, high blood pressure and lung disease) are at a higher risk of severe illness due to COVID-19 as cancer is considered a pre-existing health issue. Some cancer treatments including chemotherapy, radiation and surgery can weaken the immune system, making it harder for the body to fight infections and viruses, such as Coronavirus. It is important to diligently follow the World Health Organization’s recommendations above to reduce the risk of contracting COVID-19. If you have any concerns about your risk, it is best to contact your doctor or healthcare team.
Will anything change with regards to my cancer related medical visits? As each patient and treatment plan is unique, it is always best to contact your health care provider for updated information about your treatment plan. In some cases, it is safe to delay cancer treatment until after the pandemic risk has decreased. In other cases, it may be safe to attend a clinic that is separate from where COVID-19 patients are being treated. Oral treatment options could be prescribed by your care provider virtually, without the need to attend the clinic. Finally, some follow-up appointments or discussions could be held virtually (via skype or zoom for example) or over the phone to minimize your risk. As we know, conditions and protocols are changing daily due to the nature of the COVID-19 outbreak, and vary based on location, therefore, the best first step is to reach out to your care provider for guidance.
Should you wish to contact your local public health agency, please see below.
COVID-19 info for Albertans
Social media: Instagram @albertahealthservices, Facebook @albertahealthservices, Twitter @GoAHealth
Phone number: 811
British Columbia COVID-19
Social media: Facebook @ImmunizeBC, Twitter @CDCofBC
Phone number: 811
Social media: Facebook @manitobagovernment, Twitter @mbgov
Phone number: 1-888-315-9257
New Brunswick Coronavirus
Social media: Facebook @GovNB, Twitter @Gov_NB, Instagram @gnbca
Phone number: 811
Newfoundland and Labrador
Newfoundland and Labrador COVID-19 information
Social media: Facebook @GovNL, Twitter @GovNL, Instagram @govnlsocial
Phone number: 811 or 1-888-709-2929
Northwest Territories coronavirus disease (COVID-19)
Social media: Facebook @NTHSSA
Phone number: 811
Nova Scotia novel coronavirus (COVID-19)
Social media: Facebook @NovaScotiaHealthAuthority , Twitter @healthns, Instagram @novascotiahealthauthority
Phone number: 811
Nunavut COVID-19 (novel coronavirus)
Social media: Facebook @GovofNunavut , Twitter @GovofNunavut, Instagram @governmentofnunavut
Phone number: 1-888-975-8601
Ontario: The 2019 Novel Coronavirus (COVID-19)
Social media: Facebook @ONThealth, Twitter @ONThealth , Instagram @ongov
Phone number: 1-866-797-0000
Prince Edward Island
Prince Edward Island COVID-19
Social media: Facebook @GovPe, Twitter @InfoPEI,
Coronavirus disease (COVID-19) in Québec
Social media: Facebook @GouvQc, Twitter @sante_qc
Phone number: 1-877-644-4545
Social media: Facebook @SKGov, Twitter @SKGov
Phone number: 811
Yukon: Find information about coronavirus (COVID-19)
Social media: Facebook @yukonhss, Twitter @hssyukon
Phone number: 811