The following colorectal cancer research updates extend from September 21st, 2019 to November 16th, 2019 inclusive and are intended for informational purposes only.
DRUGS / SYSTEMIC THERAPIES
- Immunotherapy Keytruda (Pembrolizumab) – Approved by Health Canada for the treatment of MSI-H and dMMR colorectal cancer
- Phase II LEAP Clinical Trial to Treat mCRC
- BEACON Results Light Way for Chemo-Free Therapy in Colorectal Cancer
- Health Canada approves VITRAKVI (Larotrectinib), first tumour agnostic cancer treatment for advanced solid tumours harbouring an NTRK gene fusion
- Discovery of How Cetuximab Works Will Help More Patients
- Panitumumab (Vectibix) Helps Colorectal Cancer Patients Get to Surgery
- Precision Cancer Medicines for Colorectal Cancer
- A Phase II, Open-Label, Multicentre, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population
- Know Your Treatment Options for Colorectal Cancer Liver & Abdominal Metastases
- 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
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Hospital
- Living donor liver transplantation for unresectable colorectal cancer liver metastases
- Improving Patient Selection for Re-Resection of Metastatic Disease in Colorectal Cancer
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
- Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer
- Candirect Research Study: Learn more about a study for patients who have completed their cancer treatments and are experiencing low mood
- Global Analysis Finds Early Onset Colorectal Cancer Rising in Many High-Income Countries
- Young CRC Patients Are Going Undiagnosed
- Young Adult Colorectal Cancer Clinic Available at Sunnybrook Hospital
NUTRITION/ HEALTHY LIFESTYLE
- Study Zeroes in On Gut Bacteria That May Cause Bowel Cancer
- New Guidelines Say Continue Red Meat Consumption Habits, but Recommendations Contradict Evidence
- Red or Processed Meat Could Increase Colorectal Cancer Risk
- How sugary drinks can fuel and accelerate cancer growth
- Colon cancer: could exercise halt tumour growth?
- Omega -3 Fish oil intake linked to small colorectal cancer risk reduction
- Exercise for adults diagnosed with rectal cancer: a feasibility study
- A Phase III study of the impact of a physical activity program on disease-free survival in patients with high risk stage II or stage III colon cancer: a randomized controlled trial (CHALLENGE)
- High dose vitamin D supplementation in Stage 4 colorectal cancer patients
- SUNSHINE trial: high-dose vitamin D may benefit patients with metastatic colorectal cancer
- Study Looking for Female Survivors to participate in an Exercise Program
DRUGS / SYSTEMIC THERAPIES
- Immunotherapy Keytruda – approved by Health Canada for the treatment of MSI-H and dMMR colorectal cancer (Apr 18/19)
The immunotherapy Keytruda (pembrolizumab) is a monoclonal antibody or targeted cancer therapy that is directed against the PD-1 (programmed cell death – 1) receptor on the cancer cell surface. The drug blocks the PD-1 receptor, preventing the binding and activation by its ligands PD-L1 and PD-L2. By blocking this interaction, T-cell (an immune cell) mediated immune responses are activated against tumour cells.
As of April 18, 2019, Keytruda has been issued a marketing authorization with conditions in Canada, pending the results of studies to verify its clinical benefit. The drug is indicated for adult patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC), whose tumours have progressed following treatment with a fluoropyrimidine, oxaliplatin and irinotecan regimen. For more information on Keytruda: www.keytruda.com, and for Health Canada’s Notice of Compliance with conditions – drug products website: https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/notice-compliance/conditions.html#k.
Keytruda blocking the PD-1 receptor to prevent interaction with the PD-L1 and PD-L2 ligands, thereby activating T-cell mediated immune responses against tumour cells.
- Phase II LEAP Clinical Trial For mCRC (Sept 20/19)
The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and lenvatinib (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 into 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. More information may be obtained by visiting the link below.
- BEACON Results Light Way for Chemo-Free Therapy in Colorectal Cancer (August 1/19)
New results from the BEACON clinical trial offer hope for a chemotherapy-free treatment option for certain patients with colorectal cancer (CRC). Combinations of targeted therapies yielded significantly improved response rates and overall survival rates compared with traditional chemotherapy regimens among patients with previously treated BRAF V600E–mutated metastatic CRC. This BRAF V600E mutation is found in 10% to 15% of metastatic CRC patients and is usually associated with a poor prognosis. The BEACON trial had three treatment arms.
One group (Group I) of patients received triplet therapy with three targeted agents —
- the BRAF inhibitor encorafenib (Braftovi, Array BioPharma),
- the MEK inhibitor binimetinib (Mektovi, Array BioPharma), and
- the EGFR inhibitor monoclonal antibody cetuximab (Erbitux, Eli Lilly).
Another group (Group II) received doublet targeted therapy with encorafenib and cetuximab.
A third (control) group received standard chemotherapy (FOLFIRI).
The new results, presented at the World Conference on Gastrointestinal Cancer (WCGC) 2019, were from an initially unplanned interim analysis. Presenter Scott Kopetz, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, showed that the triplet therapy was associated with a remarkable 48% improvement in overall survival vs standard chemotherapy. Furthermore, progression-free survival (PFS) was improved by 62%, at 4.3 months with the triplet regimen vs 1.5 months with standard therapy. This improvement was reflected in a highly significant increase in the objective response rate (ORR) with triplet therapy, at 26%. ORR increased to 34% among patients who had previously received just one therapy. It was only 2% with chemotherapy. Importantly, these improvements were achieved without increasing toxicity, Kopetz added.
The triplet therapy has already been added to the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of metastatic CRC. Hence, this is now available to U.S.-based patients for treatment of this difficult disease. The BEACON trial is active in Canada but is no longer recruiting. Please see the following link: https://clinicaltrials.gov/ct2/show/study/NCT02928224?show_locs=Y#locn
- Health Canada approves VITRAKVI (Larotrectinib), first tumour agnostic cancer treatment for advanced solid tumours harbouring an NTRK gene fusion (Sept 19/19)
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 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.
- Discovery of How Cetuximab Works Will Help More Patients (Sept. 24/19)
Colorectal cancer is a common lethal disease, and treatment decisions are increasingly influenced by which genes are mutated within each patient. Some patients with a certain gene mutation benefit from a drug called cetuximab, although the mechanism of how this drug worked was unknown. Salk scientists have combined computational biology with experimental investigations to discover, for the first time, the mechanism for why these patients respond to cetuximab, which will help doctors identify more effective, targeted treatment plans for people diagnosed with colorectal cancer. The findings were published in Science Signaling on September 24, 2019 and demonstrate the power of blending computational and experimental approaches as well as how foundational scientific research can translate to an immediate impact for patients. Approximately 40 percent of patients with colorectal cancer have a mutated KRAS gene in cells in their tumors. Most KRAS mutants cause the patient not to benefit from cetuximab. Patients with the KRAS G13D mutation are exceptions and have appeared to respond to cetuximab, but the mechanism of action has not been apparent, so this drug is not commonly used on these patients. Doctors are hesitant to prescribe a drug without a known mechanism due to possible interaction with other medications or unforeseen side effects. “Our goal was to elucidate a mechanism for why tumors that harbor KRAS G13D mutations are sensitive to cetuximab,” says Thomas McFall, first author on the paper and a postdoctoral fellow in the Stites lab. “Understanding this mechanism will aid doctors in receiving insurance support for prescribing cetuximab, which could benefit upwards of 10,000 colorectal cancer patients per year.”
To understand why KRAS G13D tumors responded to cetuximab, the researchers first used computational models to simulate complex reactions and tease out biochemical differences between healthy and mutant genes based on the biochemical understanding of each process and previous clinical trial data. This told them where to look in their laboratory tests to identify and quantify the molecular mechanism that explains why KRAS G13D patients respond differently. The researchers replicated their findings across three genetically distinct cell lines to demonstrate the reliability of the results. In a cell with no KRAS mutations, a known tumor suppressor called neurofibromin keeps healthy KRAS proteins well-behaved. But most KRAS mutations are overly active and cannot be controlled by neurofibromin. When mutated KRAS is present, neurofibromin attempts to control the mutant KRAS at the expense of controlling the healthy KRAS. So why is the KRAS G13D mutation any different? Why does it respond to Cetuximab? The scientists discovered that even though KRAS G13D is overly active, it is doing so without neurofibromin being aware. Thus, neurofibromin can still keep the healthy KRAS under control. Additionally, the researchers demonstrated that cetuximab will only work to suppress tumors as long as there is neurofibromin available to suppress the activity of healthy KRAS. “This work demonstrates the power of computational systems biology approaches to address problems in personalized medicine,” says Stites. “Doctors could sequence the gene to find out if the patient has this KRAS G13D variant, and if they do, then doctors could confidently prescribe cetuximab. That’s important, because it will give many cancer patients a new treatment option.”
Next, the authors plan to examine the mechanisms of more KRAS gene mutation variants that do not bind to neurofibromin, as patients with these variants may also benefit from taking cetuximab.
Thomas Mcfall, Jolene K. Diedrich, Meron Mengistu, Stacy L. Littlechild, Kendra V. Paskvan, Laura Sisk-Hackworth, James J. Moresco, Andrey S. Shaw, and Edward C. Stites. A systems mechanism for KRAS mutant allele–specific responses to targeted therapy. Science Signaling, 2019 DOI: 10.1126/scisignal.aaw8288
- Panitumumab (Vectibix) Helps Colorectal Cancer Patients Get to Surgery (Oct.23/19)
Patients with colorectal cancer had high response rates with a modified triplet regimen of fluorouracil (5FU)/folinic acid, oxaliplatin (Eloxatin), and irinotecan (FOLFOXIRI) plus panitumumab (Vectibix) compared with FOLFOXIRI alone. Recently published in the Journal of Clinical Oncology, the phase II VOLFI trial data1 also show that the high response rates meant more patients who received panitumumab were able to undergo surgery. The VOLFI trial enrolled 105 patients with RAS wild-type metastatic colorectal cancer who were randomly assigned in a 2 to 1 fashion to receive modified FOLFOXIRI plus panitumumab or FOLFOXIRI alone. In all, 63 patients received modified FOLFOXIRI plus panitumumab and 33 received FOLFOXIRI alone. The panitumumab regimen would be considered active if the panitumumab arm achieved an overall response rate (ORR) of 75% or higher. Ultimately, the panitumumab arm achieved an ORR higher than 75%. In fact, 87.3% of patients who received modified FOLFOXIRI plus panitumumab had a response compared with 60.6% of patients who received FOLFOXIRI alone and the difference was statistically significant.
Modest MD, D., et al. (2019). FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109) | Journal of Clinical Oncology. [online] Ascopubs.org. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.19.01340 [Accessed 23 Oct. 2019].
- Precision Cancer Medicines for Colorectal Cancer (Oct. 18/19)
Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack colon cancer cells with specific genetic abnormalities, leaving normal cells largely unharmed and can often be used instead of chemotherapy. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy that attacks a specific mutation or other cancer-related change in the DNA programming of the cancer cells can be selected for treatment.
All newly diagnosed individual with colorectal cancer should make sure genomic-biomarker testing is performed on their cancer tissue. Once established, these genomic markers can be followed in the blood using a “liquid biopsy” to evaluate response to treatment and the development of new mutations.
Not all colon cancer cells are alike. They may differ from one another based on what genes have mutations. Genomic testing is performed to test for certain genetic mutations or the proteins they produce because the results can help select treatment including newer precision cancer medicines designed to attack specific colon cancer cells with specific genetic mutations.
The image below illustrates some of the mutations identified by genomic testing and their location in the colon. Cancers that originate on the left side of the colon may have a better prognosis and require different targeted treatments than right sided cancers.
Mutations in Colon Cancer that can be Targeted with Precision Cancer Medicines
Epidermal growth factor receptor (EGFR): A mutation in EGFR occurs in ~ 10% of colon cancer. EGFR is involved in cellular growth and replication. Some colon cancers produce too much EGFR, and this leads to more rapid growth of the cancer. Some medicines specifically target EGFR and the spread of cancer can be reduced or delayed.
The RAS Genes: KRAS and NRAS are a family of proteins found in cells that when mutated promote cancer cell growth. An estimated 40–50% of colorectal cancers contain these genes. Some colon cancer treatments don’t work if the RAS gene is abnormal. If cancer has a KRAS or NRAS mutation, drugs that inhibit cancer cell growth and survival by targeting a protein known as the EGFR are ineffective. Cancers lacking these genetic mutations are referred to as “wild type”.
- Erbitux® (cetuximab) and Vectibix (panitumumab) are a type of precision cancer medicine called a monoclonal antibody that works by binding to EGFR which is involved in cellular growth and replication. By targeting EGFR the spread of cancer can be reduced or delayed. Either Vectibix or Erbitux can be combined with chemotherapy to improve outcomes in patients that test positive for EGFR and do not have a RAS mutation.
BRAF: BRAF is also a gene that signals cells to divide. About 10% of patients have a specific mutant BRAF gene called BRAFV600 although other BRAF mutations do exist. BRAFV600 colon cancers may benefit from treatment with specific precision cancer medicines that target BRAF. Targeting BRAF and EGFR in patients with metastatic colorectal cancer that have a BRAF V600E mutation has been shown to double survival time without cancer progression.
PIK3CA: While somewhat new, a growing number of clinicians are testing for mutant PIK3CA genes; particularly in patients who have early-stage colorectal cancer. There is some suggestion that aspirin use may help decrease the risk of recurrent colorectal cancer in patients with early stage disease and PIK3CA mutation.
Microsatellite Instability High (MSI-H): MSI-H is a DNA abnormality found in about 15% of colon cancers. It is most often found in tumors associated with genetic syndromes like Lynch syndrome but can also occur sporadically. MSI-H is what “happens” when the genes that regulate DNA function don’t work correctly. These DNA regulating genes, known as Mismatch Repair Genes (MMR), work like genetic “spell checkers.” When problems occur in these spell-checking MMR genes, it means that areas of DNA start to become unstable. A high frequency of instability is called MSI-H and these individuals often respond to checkpoint inhibitor immunotherapy and may be able to avoid chemotherapy all together.
- Checkpoint inhibitors are a novel precision cancer immunotherapy that help to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the colon cancer cells. A diagnostic test to measure the level of PD-L1 is available.
- PD-1: PD-1 is a protein that inhibits certain types of immune responses, allowing cancer cells to evade an attack by certain immune cells. Drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer and are referred to as checkpoint inhibitors for their ability to help the immune system recognize and attack cancer.
- Keytruda (pembrolizumab) and Opdivo (nivolumab) belong to a new class of medicines called “checkpoint inhibitors” and both have significant anti-cancer activity in advanced colorectal cancer patients with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) abnormalities.
HER 2: is a protein involved in normal cell growth and well known as a target for treatment in breast cancer. Approximately 4% of colon cancers also over-express (make too much of) the HER2 protein, and this over-expression contributes to cancer cell growth and survival. HER2 targeted therapies can dramatically improve outcomes for HER2 + colon cancers and all colorectal cancers should be tested for HER 2. There are several medications available that target HER2 and stronger ones in development.
TRK: TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but can occur in colon cancer. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). A Health Canada approved therapy is available to treat a gene fusion cancer: Larotrectinib (Vitrakvi).
MET: The MET signaling pathway is abnormal in a wide variety of cancers and stimulates cell growth, invasion, and metastasis and promotes resistance to apoptosis. Inhibition of the MET pathway could be beneficial in blocking the growth of a number of different cancers. MET inhibitors are a class of small molecules that inhibit the enzymatic activity of the c-Met tyrosine kinase. These inhibitors may have therapeutic application in the treatment of various types of cancers.
FGFR: Fibroblast Growth Factor Receptor (FGFR) are a family of receptor tyrosine kinases involved in cell proliferation and survival. Mutations, amplifications, and translocations in these receptors have been implicated in the development of numerous cancers including colon cancer.
Other targeted treatments have emerged to match a person’s genetic makeup or a tumor’s genetic profile. As a result, all patients should undergo molecular testing.
CEA (Carcinoembryonic Antigen): CEA is a protein that may be higher in colorectal cancer patients. High levels of CEA may indicate that cancer is present, or a treatment is not working. Low levels may indicate that the body is responding to a treatment.
- A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population (Nov. 16/19)
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.
- Know Your Treatment Options for Colorectal Cancer Liver & Abdominal Metastases (Oct.18/19)
Nearly 140,000 Americans are expected to be diagnosed with colorectal (CRC) cancer this year, and more than 50% will have their cancer spread to their liver. Many individuals with CRC involving the liver erroneously conclude that they have no treatment options other than systemic therapy. There are however several therapeutic options for the treatment of liver metastases that significantly prolong survival, and others being developed in clinical trials.
For patients with liver metastases that can be surgically removed, surgery offers a potentially curative treatment approach however:
- radiofrequency ablation (RFA),
- chemoembolization (TACE), and
- radioactive microspheres
are appropriate options in certain situations. The type of liver directed therapy used is determined by the size of the cancer, the number of metastases, the location of the cancer within the liver, and the ability of the patient to undergo the treatment. Patients need to understand that many advanced treatment options are only available at cancer centers specializing in the treatment of CRC and patients should consider getting an opinion at one of those centers.
Cancer Connect has dedicated a great deal of time summarizing the literature on the four therapeutic options for the removal of colorectal cancer metastases to the liver. Please visit the following to read a comprehensive review on Surgery, RFA, TACE and Microspheres Therapy as well as HIPEC for Abdominal Metastases: https://news.cancerconnect.com/colon-cancer/know-your-treatment-options-for-colorectal-cancer-liver-abdominal-metastases-PVUjqZL8jUaH3JQfFtvSkg/
- 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 (Nov.12/10)
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.
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.
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Odette Cancer Centre (Oct.15/19)
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.
- Living donor liver transplantation for unresectable colorectal cancer liver metastases (Oct.16/19)
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 a 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 are 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.”
- Improving Patient Selection for Re-Resection of Metastatic Disease in Colorectal Cancer
Researchers found that a higher number of recurrent liver metastatic sites, the presence of positive primary colorectal lymph nodes, and a shorter disease-free duration following first liver resection were risk factors for worse outcome in patients with metastatic colorectal cancer. The findings from this study were published in the Journal of Surgical Oncology.
Although liver resection offers the greatest likelihood of cure in patients with metastatic colorectal cancer confined to the liver, previous studies have shown that the risk of disease recurrence after surgery is high. While re-resection of recurrent disease remains an option for some patients, only limited data are available to guide treatment decisions in this setting.
Within the population of patients with recurrent disease following first liver resection, the median overall survival (OS) of the subgroup of patients with more than 1 site of recurrent disease or disease-free duration less than 5 months and node-positive disease was 19 months compared with 36 months for the rest (ie, low-risk group) of the study population. Furthermore, each risk factor was independently associated with decreased median OS in patients with disease recurrence following first liver surgery.
Following disease recurrence after first liver resection, 46% of patients were treated with chemotherapy only, 42% of patients underwent second resection involving liver (28%) and lung (46%), and 12% of patients received best supportive care only.
A second surgery for metastatic disease was associated with an improvement in OS compared with not undergoing re-resection of metastatic disease. However, a comparison of patients who did or did not undergo second resection for recurrent metastatic disease showed that those in the former subgroup were less likely to have node-positive primary colorectal cancer (65% versus 73%), had fewer sites of disease recurrence (1.1 versus 1.4), and a longer disease-free duration (19 versus 15 months) following first liver resection. Recurrence of disease occurred in 72 patients (64%) undergoing a second re-section for metastatic disease, with lung (56%) and liver (43%) as the most common sites of disease recurrence. Of the 72 patients with disease recurrence following second liver resection, 30 (42%) underwent a third curative-intent surgery, and disease recurred in 63%, with the lung being the most common site.
The study authors noted that re-resection of recurrent metastatic disease is “feasible, not only in the setting of liver‐limited disease, but also among patients with extrahepatic recurrence…”
They further commented that “the exact role of second, third, or even fourth surgical resection following recurrence is unknown, but it is possible that surgeons are choosing to resect patients in the low-risk group; therefore surgical resection may be a prognostic factor that is linked with, and dependent on, tumor biology.”
Serrano PE, Gu CS, Husien M, et al. Risk factors for survival following recurrence after first liver resection for colorectal cancer liver metastases [published online October 14, 2019]. J Surg Oncol. doi:10.1002/jso.25735
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
- Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer (Oct. 14/19)
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 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:
- CanDirect research study: Learn more about a study for patients who have completed their cancer treatments and are experiencing low mood (May 2019)
15% of cancer survivors are estimated to experience mood problems even one year post-treatment. The CanDirect research study aims to support cancer survivors with mood problems by providing study participants with a self-care toolkit designed to help users better manage their mood and anxiety as well as phone coaching for a maximum duration of 6 months. Participation is open to eligible adult survivors residing in Quebec and Ontario who have completed cancer treatment for a non-metastatic cancer and who are experiencing depressive symptoms. For additional information, please access the following link:
- Global analysis finds early onset colorectal cancer rising in many high-income countries (Sept.13/19)
A new American Cancer Society study finds that colorectal cancer (CRC) incidence is increasing exclusively in young adults in nine high-income countries spanning three continents. The study, appearing in the journal Gut, finds the rising rates are in contrast to stable or declining trends in older adults, suggesting that changes in early-life exposures are increasing CRC risk. studies of cancer registry data indicate that favorable overall trends in the United States and Canada are masking an increase in young-onset CRC. To learn more about contemporary patterns of early onset CRC on a global scale, investigators led by Rebecca Siegel, MPH, analyzed long-term population-based data on CRC occurrence in adults under 50 versus those 50 and older for 43 countries covering six continents using high-quality cancer incidence data from population-based cancer registries. Of the 36 countries with sufficient numbers of cases to analyze trends, CRC incidence among adults under 50 was stable over the past ten years in 14 countries, decreased in three (Italy, Austria, and Lithuania), and increased in 19. In nine of those 19, the rise in early-onset CRC was in contrast to trends in those 50 and older, which were either dropping (Australia, New Zealand, Canada, Germany, and United States) or stable (Denmark, Slovenia, Sweden, and United Kingdom). In all but one of these countries with long-term data, the uptick in early-onset CRC began in the mid-1990s.
Rebecca L Siegel, Lindsey A Torre, Isabelle Soerjomataram, Richard B Hayes, Freddie Bray, Thomas K Weber, Ahmedin Jemal. Global patterns and trends in colorectal cancer incidence in young adults. Gut, 2019; gutjnl-2019-319511 DOI: 10.1136/gutjnl-2019-319511
- Young Colorectal Cancer Patients Are Going Undiagnosed (Nov.2/19)
Patients under the age of 50 are more likely to initially experience non-specific symptoms of colorectal cancer (CRC) before referral to cancer specialists, according to the findings of a study published in the journal Colorectal Disease. CRC occurrences are on the rise in young patients, and by 2030 it is estimated that one in 10 colon cancers and one four rectal cancers will be diagnosed in this age group. Contributing factors that explain this trend might be decreasing physical activity and heightened levels of obesity.
In this national population‐based study, researchers assessed 10,463 patients with colorectal cancer whose data were provided by the Clinical Practice Research Datalink (CPRD), a primary-care based dataset which comprises approximately 8-10% of the population in England. The CPRD provided linked data for any patients with a CRC diagnosis in the cancer registry between 2006 and 2013. Of the total number of patients, 7% were younger than 50 years of age, 16% were aged 50-59, 31.4% were aged 60-69, and 45.7% were aged 70-79. Any patients over the age of 80 years old were excluded as they were more likely to be diagnosed as an emergency. All symptoms, diagnoses, and investigations were recorded by the general practitioner (GP) into an electronic database based on Read codes, which translated into numerical ‘medcodes’ which were supplied to the researchers. The researchers compared odds ratios (ORs) for presenting with a specific symptom for an age group, and appraised data adjusted for patient demographics, and emergency diagnosis. The researchers compared categorical data utilizing the chi-square test with generalized estimating equation modeling used for regression analysis. The study results revealed that young patients were more likely to present with abdominal pain and via an emergency showed the lowest percentage of early stage cancer. These patients experienced a longer interval between referral and diagnosis (12.5 days) juxtaposed to those aged 60–69, reflecting the higher proportion of referrals via nonurgent visits. “Compared with older patients also presenting with nonspecific symptoms, younger patients were more likely to be diagnosed as an emergency,” the study authors wrote. However, there was no difference in the risk of an emergency presentation if the presenting consultation included a red‐flag.”
Colorectal cancer patients under the age of 50 experience delays in primary care leading to emergency diagnoses: a population‐based study. C. S. Arhi P. Ziprin A. Bottle E. M. Burns P. Aylin A. Darzi First published: 06 August 2019 https://doi.org/10.1111/codi.14734
- Young Adult Colorectal Cancer Clinic Available at Sunnybrook (Nov.14/19)
A recent study led by 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.
- Study Zeroes in On Gut Bacteria That May Cause Bowel Cancer (Nov.4/19)
Scientists have identified a certain type of gut bacteria that may raise the risk of bowel cancer by up to 15%. The research method used in the new study indicates that these gut bacteria may likely play a causal role in the development of this form of cancer. The new study goes beyond merely finding associations and suggests that certain bacteria in our guts may cause colorectal cancer. Kaitlin Wade, Ph.D., from the University of Bristol, in the United Kingdom, is the lead author of the new research, which she presented at the National Cancer Research Institute Cancer Conference in Glasgow. The study revealed that “an unclassified type of bacteria from a bacterial group called Bacteroidales increased the risk of bowel cancer by between 2–15%,” reports Wade. “We were able to use Mendelian randomization to understand the causal role that these bacteria may have on the disease,” she says. Our findings support previous studies that have shown that Bacteroidales bacteria are more likely to be present, and in larger quantities, in individuals with bowel cancer, compared to those without the disease.” However, Wade explains, much more research is necessary before firmer conclusions can be drawn. For instance, researchers “need to classify the exact species or strain of bacteria in the Bacteroidales group, and […] do more work to understand how and why human genetic variation can alter the gut microbiome.” Furthermore, the scientist adds, even if additional studies reinforce the conclusion that these bacteria do cause bowel cancer, researchers would still need to investigate what effects interfering with these bacteria would have on other health outcomes.
- New Guidelines Say Continue Red Meat Consumption Habits, but Recommendations Contradict Evidence (Nov.5/19)
Most people can continue to eat red and processed meat as they do now. A major study led by researchers at McMaster and Dalhousie universities has found cutting back has little impact on health.
A panel of international scientists systematically reviewed the evidence and have recommended that most adults should continue to eat their current levels of red and processed meat. The researchers performed four systematic reviews focused on randomized controlled trials and observational studies looking at the impact of red meat and processed meat consumption on cardiometabolic and cancer outcomes. In one review of 12 trials with 54,000 people, the researchers did not find statistically significant or an important association between meat consumption and the risk of heart disease, diabetes or cancer. In three systematic reviews of cohort studies following millions of people, a very small reduction in risk among those who had three fewer servings of red or processed meat a week, but the association was uncertain. The authors also did a fifth systematic review looking at people’s attitudes and health-related values around eating red and processed meats. They found people eat meat because they see it as healthy, they like the taste and they are reluctant to change their diet. The five systematic reviews, a recommendation and an editorial on the topic were published in the Annals of Internal Medicine today. McMaster professor Gordon Guyatt, chair of the guideline committee, said the research group with a panel of 14 members from seven countries used a rigorous systematic review methodology, and GRADE methods which rate the certainty of evidence for each outcome, to move from evidence to dietary recommendations to develop their guidelines. “There is a worldwide interest in nutrition and the issue of red meat in particular. People need to be able to make decisions about their own diet based on the best information available,” he said.
Bradley Johnston, corresponding author on the reviews and guideline, said the research team realizes its work is contrary to many current nutritional guidelines. “This is not just another study on red and processed meat, but a series of high quality systematic reviews resulting in recommendations we think are far more transparent, robust and reliable,” said Johnston, who is a part-time associate professor at McMaster and an associate professor of community health and epidemiology at Dalhousie. He added: “We focused exclusively on health outcomes and did not consider animal welfare or environmental concerns when making our recommendations. “We are however sympathetic to animal welfare and environmental concerns with a number of the guideline panel members having eliminated or reduced their personal red and processed meat intake for these reasons.”
The accompanying editorial by authors at the Indiana University School of Medicine said: “This is sure to be controversial but is based on the most comprehensive review of the evidence to date. Because that review is inclusive, those who seek to dispute it will be hard pressed to find appropriate evidence with which to build an argument.” Other researchers involved in the work included those from the Netherlands, Poland and Spain, including the Iberoamerican Cochrane and Polish Cochrane centres and the guideline committee included lay people as well as the scientists. Dena Zeraatkar and Mi Ah Han, a visiting professor from South Korea, also had leadership roles on the McMaster team working on the reviews.
- Red or Processed Meat Could Increase Colorectal Cancer Risk (Nov.6/19)
A new study suggests some popular foods may be linked to a higher risk of developing colorectal cancer. It’s popular on breakfast plates but a new study may make you rethink eating sausage or bacon.
Research published in the International Journal of Epidemiology suggests those much loved processed breakfast meats are linked to higher rates of colorectal cancer for people who eat them often, with chances of getting the disease being nearly 20 percent higher for every processed meat the size of a slice of bacon eaten per day. Red meat appears linked to the risk as well. Researchers say, people who ate 76 grams of red or processed meat per day, which is roughly the same as a burger with a quarter pound of beef, had a 20 percent higher chance of developing colon cancer compared to those who ate about a third that much per day. The study tracked the diets of nearly half a million British adults between the ages of 40 and 69 during a roughly five-year period. More than 2,600 of the study’s participants developed colorectal cancer. The Centers for Disease Control and Prevention says the most effective way to reduce your risk of colorectal cancer is to get screened for the disease routinely beginning at age 50.
- How sugary drinks can fuel and accelerate cancer growth (Nov.10/19)
To date, cancer researchers have acknowledged that obesity increases the risk of cancer. A high intake of sugar through the repeated consumption of processed foods and sugary drinks is one important factor that is known to lead to obesity. Despite this fact, there has been limited research that examines the effects of sugar on tumour growth independent of obesity. Recently, a team of specialists from Baylor College of Medicine in Houston, TX and Weill Cornell Medicine in New York City has collaborated to examine the relationship between sugar intake and tumour growth in colorectal cancer (CRC). Specifically, the team studied the effects of consuming a daily modest amount of high-fructose corn syrup, a commonly used sweetener in the food and beverage industry, on CRC in mouse models.
The team conducted their research in mice with early-stage CRC in which a specific gene “APC” was deleted. This gene deletion simulated a mutation that characterizes fast-growing CRC in humans – more than 90% of CRC patients have this type of APC mutation. Deleting APC is like removing the brakes on cellular growth – without it, normal intestinal cells neither stop growing nor die, thereby forming early stage tumours also known as polyps. In the first stage of the study, the researchers allowed the mice to drink a beverage rich in high-fructose corn syrup at will. The sweetened water was 25% high-fructose corn syrup, which is composed of glucose and fructose in a 45:55 ratio. Within 1 month, the rodents put on a lot of excess body weight. To determine whether or not the high intake of corn syrup would boost cancer growth independently of obesity, the team administered the sugary drink in such a way that would allow the mice to ingest it without putting on weight, mimicking a human daily consumption of one can of soda. The mice were given the drink orally once a day for 2 months. Following the 2-month intervention, the investigators found that the rodents did not put on too much weight, but they had developed larger, more advanced tumours than the rodents who had only received water. The findings suggest that when the animals had early stage tumours in the intestines – an occurrence that can show up in many young adult humans without notice – consuming even modest amounts of high-fructose corn syrup in liquid form can boost tumour growth and progression even if the individual is not obese. In other words, the researchers’ findings in animal models suggest that chronic consumption of sugary drinks can shorten the time it takes for cancer to develop. Further research will be needed to translate the study’s discovery to humans, as it usually takes 20-30 years for CRC to grow from early stage benign tumours to more aggressive cancers. These findings observed in animal models might explain why increased consumption of sugary drinks and other high-sugar foods over the past 30 years is correlating with an increase in CRC among 25-50 year olds in the US.
In a later stage of the study, the researchers examined the mechanisms by which the sugar in corn syrup fuelled tumour growth. The researchers found that the sugar fructose underwent certain chemical changes in the body which allowed it to boost glucose’s tumour-promoting effects. Specifically, the researchers found that fructose enhanced glucose’s role of directing fatty acids synthesis to form cellular membranes and signalling molecules to grow or to influence inflammation, a key contributor to cancer development. While many studies have linked increased rates of CRC with diet, this study has shown a direct molecular mechanism for the correlation between sugar consumption and CRC.
- Colon cancer: could exercise halt tumour growth? (Sept.1/19)
New research published in the Journal of Physiology suggests that short bursts of intense, physical activity may decrease the growth of colorectal tumour cells and improve patient outcomes. The research team from the University of Queensland in Australia found that short bursts of high-intensity exercise may have the same protective effects as repeatedly exercising over a long period of time. In the study, the research team recruited individuals with colorectal cancer (CRC) and asked them to perform either one session of high-intensity interval training (HIIT) or 12 sessions of HIIT over a 4-week period. HIIT is a training method that aims to make the person who exercises do more physical work at a high intensity during a single session by alternating high-intensity exercise intervals with low-intensity exercise or rest intervals. Blood serum samples were collected at baseline, immediately after finishing the HIIT session, and 120 minutes after the workout. The serum collected immediately after HIIT, but not 120 minutes after HIIT, demonstrated significantly reduced colon cancer cell numbers. The researchers found “significant increases” in certain cytokines or signalling proteins that help to modulate the body’s immune and inflammatory responses. These cytokines were interleukin-6, interleukin-8, and the tumour necrosis factor alpha. The short-term effects of HIIT and the cytokine flux may be important mediators of reducing colon cancer cell progression. Repetitive exposure to these acute effects may contribute to the relationship between exercise and improved CRC survival. These findings suggest that a physically active lifestyle may be instrumental in tackling human colorectal tumours, but the researchers note that the method they used to study colon cancer cell growth in the lab differs vastly from how these cells grow in the body. Further research will be necessary to observe how these changes in tumour growth occur in humans and to understand the mechanisms by which biomarkers in the blood can impact cell growth.
- Omega-3 Fish oil intake linked to small colorectal cancer risk reduction (Aug.2/19)
Exposure to omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) via fish consumption is associated with a slightly reduced risk of colorectal cancer (CRC), pan-European research shows. The analysis makes a substantial contribution to the growing body of evidence linking fish consumption to potentially lower risk of crc. Its consumption should be encouraged as part of a healthy diet.
The World Cancer Research Fund (WCRF) concludes there is limited but suggestive evidence that fish decreases crc risk. Nevertheless, uncertainty remains whether fish consumption is beneficial for crc prevention and how consumption of different fish types (ie fatty/oily, white/lean) relates to crc risk.
- Exercise for adults diagnosed with rectal cancer: a feasibility study (Oct.30/19)
The purpose of the study is to examine the safety and feasibility of a supervised 12-week exercise intervention for adults diagnosed with rectal cancer. The exercise program will take place at the Behavioural and Metabolic Laboratory (200 Lees Ave., Ottawa) 3x a week and will be tailored to each individual.
Below are the inclusion criteria for the study:
- Men and women 18 to 85 years of age;
- Diagnosed with stage I-III rectal cancer and currently undergoing treatment or have completed treatments with the last 5 years;
- Able to read/understand English or French;
- Live <50km of the University of Ottawa;
- Approval of healthcare provider to participate in the intervention.
Individuals will be asked to complete a brief questionnaire and physical assessments (e.g., resting blood pressure) before and after the 12-week intervention.
- A Phase III study on the impact of a physical activity program on disease-free survival in patients with high risk stage II or stage III colon cancer: a randomized controlled trial (CHALLENGE) (Oct.31/19)
The purpose of this study is to compare the disease-free survival of patients involved in a physical activity program (designed to increase physical activity participation) who also receive general health education materials (about diet and physical activity) to patients who receive the general health education materials only. This study is being done because, as of yet, there is no conclusive evidence that physical activity will decrease the likelihood of colon cancer recurrence. This study will also obtain important information about the impact of physical activity on patients’ physical functioning, body composition, quality of life, fatigue, mood, cytokines and the insulin pathway, and their influence on prognosis, as well as cost-effectiveness.
Eligibility: Medically fit colon cancer patients (high risk stage II and stage III) who have completed adjuvant chemotherapy within the past 60-180 days. Current physical activity levels must not meet the recommended guidelines (>150 minutes of moderate-to-vigorous or >75 minutes of vigorous exercise/week). Following registration, and prior to randomization, patients must successfully complete at least two stages of a submaximal exercise test to ensure they are able to safely exercise at a moderate to vigorous intensity.
Participation: Limited to invited centres. For more information, visit the link below:
- High dose Vitamin D supplementation in Stage 4 Colorectal Cancer Patients (Nov.15/19)
A large body of evidence suggests that high blood levels of Vitamin D decreases the risk of developing cancer, especially colorectal cancer. Very little is known about what role optimum blood levels of Vitamin D can play in the treatment of cancer. The purpose of this clinical trial is to study the therapeutic effect and the safety of high-dose vitamin D supplementation in stage 4 (metastatic) colorectal cancer patients. Who is eligible to participate? Anyone who has a stage four colorectal cancer diagnosis, living in Ontario or British Columbia, may be eligible to participate. All participants need to have access to a Lifelabs facility for blood and urine collections. What is involved? This 40-month study involves regular lab tests and follow up phone calls. Participation is fully voluntary, and participants may withdraw at any time. Participants will be randomized into either a high-dose vitamin D treatment group or a control group. Participants in both groups may continue all other cancer treatments including chemotherapy. Treatment group: Participants in the treatment group receive daily oral high dose Vitamin D supplementation provided free of charge through the clinical study. They also receive daily calcium supplementation 1000mg daily as per guidelines, provided free through the clinical study. Participants will have monthly blood and urine tests for monitoring purposes. All laboratory tests are free of charge. Participants also need to be available for a 15-minute phone consultation with a study coordinator every 2 months. Control group: Participants in the control group will continue their usual amount of Vitamin D and/or calcium if they wish to do so. No supplements will be provided through the study. Participants will be asked to provide a small blood and urine sample at the beginning of the study, every 8 months and at the end of the study. These blood and urine tests will be free of charge. Contact person: If you have any further questions regarding this study or you are interested in participating in this study, please contact us: British Columbia: 604-734-7125, toll free 1- 888-734-7125 or vitDstudy@inspirehealth.ca Ontario: 613-792-1222, toll free 1-855-546-1244 or email@example.com
- SUNSHINE Trial: high-dose vitamin D may benefit patients with metastatic colorectal cancer (Nov.1/19)
Findings from a small clinical trial suggest that supplementing chemotherapy with high doses of vitamin D may be beneficial to patients with metastatic colorectal cancer (mCRC) by delaying the progression of the disease. Vitamin D is necessary for bone health and is made in the body through a chemical reaction that depends on sun exposure and intake of some fortified foods. In lab studies, vitamin D has shown anti-cancer properties such as triggered programmed cell death, inhibiting cancer cell growth, and reducing metastasis. While previous studies have linked higher blood levels of vitamin D with a lower risk of CRC and improved survival of patients, they were unable to prove that vitamin D was the direct cause.
In the SUNSHINE trial, 139 patients were recruited across the United States. All patients received standard chemotherapy (mFOLFOX6 plus bevacizumab). Patients were then randomly assigned to one of two treatment groups. Patients in the high-dose vitamin D group initially took 8,000 international units (IU) a day for 14 days, then 4,000 IU a day thereafter. Patients in the low or standard-dose vitamin D group took 400IU daily during all cycles. In the high-dose group, median progression-free survival (PFS) was 13. vs. 11 months in the standard dose group. Patients in the high-dose group were 36% less likely to have disease progression or death during the follow-up period of 22.9 months. No significant differences were found between the high-dose and standard-dose group in terms of tumour overall response rate or overall survival. Blood samples from participants were taken to measure the change in the levels of vitamin D before and after treatment. The test demonstrated that only 9% of the patients in the clinical trial had sufficient vitamin D at the beginning of treatment. Over the course of the study, patients in the high-dose group reached and maintained the vitamin D-sufficient range, while patients in the low-dose group had no substantial change in their vitamin D levels. The researchers found that the benefits of a high-dose vitamin D appeared to be less among obese patients and among those with tumours which contained a mutated KRAS gene, suggesting that certain subsets of CRC patients may need even higher doses of vitamin D for antitumour activity. High doses of vitamin D should not be taken except within the context of a clinical trial and under the supervision of specialists. The most common grade 3 and higher adverse events for chemotherapy plus high-dose vs. standard-dose vitamin D were neutropenia (35% vs. 31%) and hypertension (13% vs. 16%). The researchers conclude that the SUNSHINE trial findings are “extremely important” as they point to a cost-effective, safe, and easily accessible agent as a potential new treatment for mCRC.
- Study Looking for Female Survivors to participate in an Exercise Program (Nov.16)
Researchers from the University of Toronto are performing a study investigating how female cancer survivors feel during and after different types of exercise. If you are a woman diagnosed with cancer and:
- Are 18-75 years old
- Completed treatment within 5 years
- Not exercising regularly
You can help out! Study includes: three sessions over the course of 1.5 weeks consisting of a variety of exercises for 20 minutes (with breaks). You will be compensated $20 for participation in each session for a total of $60.
Please contact Allyson for more information: 416-946-5856 or firstname.lastname@example.org