A PATIENT-FOCUSED ORGANIZATION
COLORECTAL CANCER TREATMENT & CLINICAL RESEARCH UPDATES
Month Ending January 14th, 2021
The following colorectal cancer treatment and research updates extend from November 12th , 2020 to January 14th, 2021, inclusive and are intended for informational purposes only.
This content is not intended to be a substitute for professional medical advice. Always consult your treating physician or guidance of a qualified health professional with any questions you may have regarding your health or a medical condition. Never disregard the advice of a medical professional or delay in seeking it because of something you have read on this website.
1. Phase II LEAP Clinical Trial to Treat mCRC 2.
2. Health Canada approves VITRAKVI (Larotrectinib), first tumour agnostic cancer treatment for advanced solid tumours harbouring an NTRK gene fusion.
3. A Phase II, Open-Label, Multicentre, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population
4. 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
5. Triple Chemotherapy Combination Improves mCRC Outcomes
6. FDA Approves Pembrolizumab As First-Line Treatment For CRC
7. Three Drugs Top Two for BRAF+ mCRC
8. Can KRAS Positive Colorectal and Lung Cancer Finally be Targeted?
9. Can Aspirin Prevent The Development of Colon Cancer and Cancer Recurrence?
10. Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC)
11. Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Hospital
12. Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
13. Tissue-Sparing Surgery Safe in Early Rectal Cancer
14. Polypectomy Associated With Decreased Long-Term Risk for CRC
15. Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer
16. Understanding The CEA Test in Colon Cancer
17. Differences in Right vs. Left Colon in Black vs. White Individuals
18. Young Adult Colorectal Cancer Clinic Available at Sunnybrook Hospital
19. What Does PD-L2 Tell Us About Advanced CRC?
20. Recurrence Risk Low After One Year of Watch-and-Wait for Rectal Cancer
21. Cancer Cells Can Hibernate to Survive Chemotherapy
22. Poor Diet Quality Linked To Increased Risk For Early-Onset CRC Precursors
23. Eating Yogurt May Reduce Your CRC Risk
24. Tips for Eating Well During Chemotherapy & Cancer Treatment
25. Nutrition for Cancer Patients
26. Carbs and Cancer
27. CCRAN Proudly Issues “My Foods For Life” Booklet, in Partnership with the American Institute for Cancer Research
28. CCRAN’s Position on Colorectal Cancer Patients Accessing the COVID-19 Vaccine
29. Understanding COVID-19 Infection Transmission Immunity and Testing
30. The Coronavirus is Mutating: What We Know About the New Variants
31. Frequently Asked Questions for COVID-19
DRUGS / SYSTEMIC THERAPIES
- Phase II LEAP Clinical Trial For mCRC (Mar.01/20)
The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and Levantine (E7080/MK-7902) in patients with triple-negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), or biliary tract cancers (BTC). Participants will be enrolled in initial tumor-specific cohorts, which will be expanded if adequate efficacy is determined. The trial is available at the Odette Cancer Centre and at the Princess Margaret Cancer Centre in Toronto as well as the following Centres throughout Canada: Abbotsford, BC; Winnipeg, MB; CHU de Quebec. For information, visit the link below.
- Health Canada Approves VITRAKVI (Larotrectinib), First Tumour Agnostic Cancer Treatment For Advanced Solid Tumours Harbouring an NTRK Gene Fusion (Mar.05/20)
Bayer announced that there is now a treatment in Canada for tyrosine receptor kinase fusion protein-driven childhood and adult cancers. Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusions can result in the production of TRK fusion proteins that can lead to uncontrolled cell growth and cancer. Health Canada issued a Notice of Compliance with Conditions (NOC/c) for VITRAKVI® (Larotrectinib). VITRAKVI® is approved for the treatment of adult and pediatric patients with solid tumours that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options. Treatment with VITRAKVI® should be initiated following confirmation of an NTRK gene fusion in a tumour specimen using a validated test.
This is the first time Health Canada has approved a tumour agnostic treatment, such that patients with advanced solid tumours harbouring an NTRK gene fusion may be eligible for treatment with VITRAKVI®, across multiple tumour types and ages. VITRAKVI® is a first-in class oral and highly selective TRK inhibitor that may shrink the tumour or may slow or stop it from growing. In the clinical trials that were the basis for this approval, TRK fusion cancer patients treated with Larotrectinib experienced clinical benefit across numerous tumour types, including lung, thyroid, melanoma, GIST (gastrointestinal stromal tumour), colon, soft tissue sarcoma, salivary gland, and infantile fibrosarcoma. The overall response rate (ORR) was 75% (95% CI, 64%, 85%) with 22% of patients experiencing a complete response (CR) to treatment. The ORR observed was 90% in pediatrics and 69% in adults, and responses were rapid and durable.
What is TRK Fusion Cancer?
TRK fusion cancer is rare and occurs when an NTRK gene fuses with another unrelated gene, producing a TRK fusion protein that becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless where it originates in the body. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumours with varying frequency, including lung, thyroid, gastrointestinal cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma). TRK fusion proteins are rare in common cancers (such as colorectal cancer) and common in rare cancers.
NB: The pan Canadian Oncology Drug Review Expert Committee (pERC) has recently issued a funding recommendation in respect of Larotrectinib. It conditionally recommends the reimbursement of Larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with locally advanced solid tumors that have an NTRK gene fusion This recommendation pertains only to adult and pediatric patients with salivary gland tumours, adult or pediatric patients with soft tissue sarcoma (STS) and pediatric patients with cellular congenital mesoblastic nephroma or infantile fibrosarcoma, without a known acquired resistance mutation, that are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options, only if the following conditions are met:
- Cost-effectiveness being improved to an acceptable level
- Feasibility of adoption (budget impact and access to testing) is addressed
Stay tuned as the expert committee is currently reviewing feedback submissions from various stakeholders.
Please note: the expert review committee has as of October 31st, 2019 issued a final negative funding recommendation in respect of Larotrectinib. Efforts are currently underway to assemble a massive campaign to address this final recommendation by working to secure a sustainable, long-term funding solution for TRK fusion cancer patients.
- Bayer 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 Life Labs 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.
PLEASE NOTE: A RESUBMISSION HAS BEEN MADE IN EARLY DECEMBER FOR VITRAKVI TO THE EXPERT COMMITTEES IN CANADA WHO OVERSEE FUNDING RECOMMENDATIONS. WE ANXIOUSLY EXPECT A DECISION IN EARLY-MID 2021.
- A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population (Oct.01/20)
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 (Oct.01/20)
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.
- Triple Chemotherapy Combination Improves mCRC Outcomes (Dec.24/20)
Researchers from SWOG Cancer Research Network have shown that a triple drug combination (of irinotecan, cetuximab, and vemurafenib) is a more powerful tumor fighter and keeps people with metastatic colon cancer disease free for a significantly longer period of time compared with patients treated with irinotecan and cetuximab.
In the SWOG study Scott Kopetz, MD, Ph.D., of MD Anderson Cancer Center, and his team pursued combination therapies to see what might work best. In this trial, they tested 106 patients whose mCRC includes the V600E mutation. All the patients had been previously treated with chemotherapy, and their cancer didn’t respond. The team randomly assigned study participants to one of two treatment groups—those who received irinotecan and cetuximab and those who received that combination with a third drug, vemurafenib.
They found that patients who received the triple combination had better tumor response rates to the drugs (17% compared to 4%) and stayed cancer-free longer. On a molecular level, Kopetz said, here’s how the triplet works: Irinotecan, a traditional chemotherapy drug, kills cancer cells. Cetuximab, a monoclonal antibody, is a targeted drug that blocks cancer growth by blocking the action of a protein called epidermal growth factor receptor, or EGFR. Lastly, vemurafenib, a BRAF inhibitor and another targeted therapy, attacks the BRAF protein directly, further slowing tumor growth.
“That 1-2-3 action, that triple threat, shuts off a powerful growth pathway in these cancers,” Kopetz said. “In this trial, unlike in BEACON, we added chemo and found that it makes for a more effective way to treat this aggressive form of CRC.”
- FDA Approves Pembrolizumab As First-Line Treatment For CRC (Dec.18/20)
Patients newly diagnosed with advanced or metastatic microsatellite instability-high (MSI-High) or mismatch repair deficient (MMR-D) CRC previously would have been prescribed pembrolizumab only after exhausting standard chemotherapy treatments. The FDA approved pembrolizumab, also known under the brand name Keytruda, as first-line treatment for metastatic MSI-High and MMR-D CRC based on early results from a phase III clinical trial.
“When compared to traditional treatment, pembrolizumab was superior with fewer side effects for MSI-High/MMR-D colorectal patients. There are other solid tumor cancers in adults and children that have these same MSI-High/MMR-D defects, so our research may also have ramifications for other cancer types”, said Luis A. Diaz, MD, Head of the Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, Leader of the SU2C Colorectal Cancer Dream Team.
The study involved 307 MSI-High/MMR-D CRC patients in 23 countries who were treated either with pembrolizumab or standard chemotherapy. Pembrolizumab targets and blocks a protein called PD-1 that can prevent immune cells called T cells from eliminating cancer cells effectively. Dr. Diaz and his team found that MSI-High/MMR-D CRC patients treated with pembrolizumab didn’t see their cancer spread for a median 16.5 months, compared to patients treated with standard chemotherapy who saw their tumors grow after a median 8.2 months. Patients receiving standard chemotherapy also had more severe side effects than patients receiving pembrolizumab.
- Three Drugs Top Two for BRAF+ mCRC (Dec.30/20)
The current S1406 study included 106 patients with previously treated, BRAFV600E–mutant metastatic colorectal cancer (mCRC). About 40% of the patients had prior exposure to irinotecan and half had prior adjuvant chemotherapy. The patients received irinotecan and cetuximab with or without concomitant vemurafenib, and the primary endpoint was PFS.
Adding a second targeted agent to chemotherapy significantly increased progression-free survival (PFS) in BRAF-mutant mCRC, a multicenter randomized trial showed. Median PFS increased from 2.0 months with irinotecan and cetuximab to 4.2 months with the same two drugs plus the BRAF inhibitor vemurafenib. Overall survival (OS) improved numerically from 5.9 months with two drugs to 9.6 months with the addition of vemurafenib. Objective response rate (ORR) and disease control rate (DCR) were 3-4x higher with the three-drug combination, Scott Kopetz, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and co-authors reported in the Journal of Clinical Oncology.
Analysis of ct (circulating tumor) DNA showed that BRAFV600E variant allele frequency decreased in 87% of patients randomized to vemurafenib versus none of the patients who received the irinotecan-cetuximab doublet. Grade 3/4 adverse events occurred more often with the triplet regimen, including neutropenia (30% vs. 7%), anemia (13% vs. 0%), and nausea (19% vs. 2%). The authors reported that 11 (22%) patients in the vemurafenib arm discontinued treatment as compared with four (8%) in the control group.
“The VIC regimen is notable for the addition of irinotecan in the treatment, in contrast to other strategies only using targeted therapies,” the authors noted. “Preclinical data have demonstrated the ability of irinotecan to increase the depth of response and induce apoptosis (process of programmed cell death). This is consistent with low response rates seen in prior studies of vemurafenib and cetuximab and suggests strategies to combine optimal BRAF and EGFR targeting with irinotecan.”
- Can KRAS Positive Colorectal and Lung Cancer Finally be Targeted? (Oct.27/20)
According the results from the phase I – II Krystal clinical trials, the investigational KRAS G12C inhibitor drug, Adagrasib yielded clinical responses in patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), and other solid tumors harboring KRAS G12C mutations.
Adagrasib is an investigational, orally available small molecule that is designed to potently and selectively inhibit a form of KRAS which harbors a substitution mutation (G12C). Adagrasib works by irreversibly and selectively binding to KRAS G12C in its inactive state, blocking its signaling to other cells and preventing cancer cell growth and proliferation; this leads to cancer cell death.
Out of 18 CRC patients 3 (17%) had a confirmed objective response and 2 of them continue to receive treatment. Disease control was seen in 17 of the patients (94%) and 12 of these patients continue to be treated. Side effects included nausea (54%), diarrhea (51%), vomiting (35%), fatigue (32%) and increased levels of an enzyme that indicates minor liver irritation (20%). The only serious adverse side effect to occur in more than one patient was low sodium in the blood.
If the early findings with MRTX849 hold true doctors may finally have a treatment for this difficult to treat genetically driven cancer.
- Can Aspirin Prevent The Development of Colon Cancer and Cancer Recurrence? (May 22/20)
Research suggests that aspirin can reduce the risk of developing colorectal cancer (CRC). To evaluate the relationship between aspirin and other non-steroidal anti-inflammatory drugs (NSAID) use and the risk of CRC, researchers analyzed data from a study of over 82,000 nurses. The nurses provided information about their medication use every two years starting in 1980. Over a period of 20 years, 962 of the nurses developed CRC. The lowest risk of CRC was observed among women who had taken more than 14 standard (325 mg) aspirin tablets per week for more than 10 years. These women had roughly half the risk of developing CRC as women who did not regularly use aspirin. Fewer women were regular users of other NSAIDS, but high doses of other NSAIDS appeared to produce a similar reduction in CRC risk. Among women who regularly used acetaminophen (a pain reliever that is not an NSAID), there was no reduction in risk of CRC.
20-year follow-up data from over 14,000 individuals indicate that daily doses of 75 mg or more of aspirin taken for 5 or more years reduces the long-term incidence and mortality of CRC. The study evaluated patient data from four randomized trials in order to determine the preventive effect of aspirin on CRC over 20 years. Patients enrolled in these trials were randomized to either receive aspirin or not to receive aspirin. Average duration of scheduled treatment was 6 years.
- Patients who received aspirin were less likely to develop colon cancer during 20 years of follow-up “with a latent period of 7-8 years between aspirin intake and its preventive effect.”
- Patients taking aspirin for five years or more appeared to benefit the most with a 70% reduction in risk of developing proximal colon cancer, which is in the upper bowel.
- Doses of aspirin above 75 mg daily did not demonstrate an improvement in risk reduction of developing CRC; however, doses of 30 mg daily appeared to be less effective.
The researchers concluded that 75 mg daily (or more) of aspirin taken for 5 years or more reduced the long-term risk of developing and dying from CRC.
Research also suggests that CRC patients treated with surgery and chemotherapy, experience less recurrences and fatalities with regular aspirin use. According to the results of a study reported in the Journal of the National Cancer Institute, patients with stage III colon cancer who take aspirin or other agents that inhibit cyclooxygenase-2 near the time of adjuvant chemotherapy appear to have a lower risk of cancer recurrence.
Researchers also evaluated 830 patients with stage III colon cancer from another study evaluating two different chemotherapeutic regimens. It was determined that 8.7% of these patients were regular aspirin users. Analysis revealed that 72 of the 830 patients consistently used aspirin during and after treatment and a comparison of this group with non-aspirin users determined that consistent aspirin use was associated with a significant reduction (48%) in the risk of CRC disease recurrence and death.
Many individuals can certainly benefit from daily aspirin for other reasons; however, some individuals, particularly those with various gastrointestinal conditions, may have their condition worsened with aspirin. Patients should always make their doctor aware of any non-prescribed medicines or supplements they are taking.
- Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) (Jun.18/20)
What is PIPAC?
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment technique that gives chemotherapy in the form of a pressurized aerosol, or spray. It may be an option if you have stomach cancer; platinum-resistant, recurrent ovarian cancer; or colorectal cancer (CRC) that has spread to the peritoneum, and surgery isn’t an option for you. PIPAC is a simple procedure that takes less than an hour. It’s known as a minimally invasive surgery because the doctor only has to make small cuts. They’ll use them to put a tube called a trochar inside the abdomen. It will help them guide a camera, or laparoscope, and other surgical tools for the procedure. During PIPAC, the doctor injects the medication into the abdomen through a nebulizer (a machine that turns liquid medicine into a fine mist). This helps it go more deeply into your body. Once the drug is inside your body, you’ll wait for 30 minutes as it goes to work. With PIPAC, you may have fewer side effects than you do with regular chemotherapy. You could have some discomfort, slight pain in the abdomen, or mild nausea.
What do studies show?
(PIPAC) in Patients with Peritoneal Metastasized Colorectal, Appendiceal and Small Bowel Cancer
Patients with intestinal cancer (i.e. colorectal, appendiceal, and small bowel) with peritoneal metastases (PM) may have a poor prognosis. Researchers assessed whether PIPAC together with systemic chemotherapy is an effective treatment option for these entities in palliative intent. 13 patients with intestinal cancer [median age 61 years] underwent 26 PIPAC procedures with a median number of 2 interventions per patient. A chemoaerosol consisting of cisplatin/doxorubicin was administered during standard laparoscopy. 6 patients who received 2 or more PIPAC procedures had decreased and stable ascites volumes, while only 1 patient displayed increased ascites. The median overall survival was 303 days after the first PIPAC procedure. PIPAC offers a novel treatment option for patients with PM, as data shows that PIPAC is safe and well tolerated. Ascites production can be controlled by PIPAC in patients with intestinal cancer. Further studies are required to document the significance of PIPAC within palliative therapy concepts.
PIPAC for the Treatment of Colorectal PM
This ongoing clinical trial, provided by Imperial College London, aims to assess the efficacy of PIPAC for advanced CRCs with PM. A CapnoPen device will be used to aerosolise Oxaliplatin 92mg/m2 chemotherapy 6-8 weekly intervals for intraperitoneal distribution via laparoscopy. The estimated study completion date is September 30, 2021.
The estimated enrollment of 30 participants (18 years or older) must meet the following inclusion criteria:
- Patients with colorectal peritoneal metastases (CPM) with expected life expectancy of > 6 months
- ECOG Scale of Performance Status (PS) scores 0 or 1
- 15 mile catchment area to facilitate overseeing systemic chemotherapy administration
- Concomitant systemic chemotherapy regimens with FOLFIRI, FOLFOX, Mitomycin C & Fluorouracil, Capecitabine (excluding Lonsurf) or without systemic chemotherapy if no systemic options available to patient
- Neutrophil count on or just before chemotherapy due date of >1.5
Primary Outcome Measures:
- Progression free survival assessed by laparoscopy and cross sectional imaging
Secondary Outcome Measures:
- Quality of life assessments
- Serious CTCAE adverse events / operative complications related to PIPAC
- PIPAC related safety regulation breaches / adverse events in theatre
PIPAC for the Treatment of Peritoneal Carcinomatosis in Patients with Ovarian, Uterine, Appendiceal, Colorectal, or Gastric Cancer
This active trial, lead by City of Hope Comprehensive Cancer Center, studies the side effects of PIPAC in treating patients with ovarian, uterine, appendiceal, stomach (gastric), or CRC that has spread to the lining of the abdominal cavity (peritoneal carcinomatosis). Giving chemotherapy through PIPAC may reduce the amount of chemotherapy needed to achieve acceptable drug concentration, and therefore potentially reduces side effects and toxicities.
Patients are assigned to 1 of 2 arms. ARM I: Patients with ovarian, uterine, or gastric cancer, undergo PIPAC with cisplatin intraperitoneally (IP), followed by doxorubicin IP. Treatment repeats every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients with colorectal/appendiceal cancer undergo PIPAC with oxaliplatin IP. For cycles 2 and 3, patients receive leucovorin intravenously (IV) over 10 minutes and fluorouracil IV over 15 minutes 1-24 hours before undergoing PIPAC. Treatment repeats every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for up to 3 years.
- To evaluate the safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in 2 groups of patients with peritoneal carcinomatosis (PC), either due to primary ovarian, uterine, or gastric carcinoma (Arm 1) or to primary colorectal/appendiceal carcinoma (Arm 2).
- Efficacy will be assessed by:
- Response Evaluation Criteria in Solid Tumors (RECIST)
- Peritoneal regression grading score (PRGS)
- Peritoneal carcinomatosis index (PCI) at the time of laparoscopy
- Post-operative surgical complications evaluated at 4, 10, and 16 weeks (4 weeks after each PIPAC)
- Progression-free survival.
- PIPAC technical failure rate.
- Patient-reported health state/quality of life and symptoms before treatment and at 6, 12, and 18-weeks/off study.
- Functional status, as measured by the number of daily steps before and after treatments.
- 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 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 (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.”
- Tissue-Sparing Surgery Safe in Early Rectal Cancer (Dec.14/20)
A treatment regimen of short-course radiotherapy and organ-preserving transanal endoscopic microsurgery for early rectal cancer (TREC) was associated with fewer acute and late patient-reported side-effects than total mesorectal excision, a small randomized British feasibility study found. The study showed high levels of compliance, low toxicity and morbidity, significant downstaging and high rates of organ preservation, and better overall quality of life (QoL), reported Simon P. Bach, FRCS, of the University of Birmingham, and colleagues.
Between 2012 and 2014, a total of 55 patients were randomly assigned at 15 sites in the U.K., with 27 assigned to organ preservation and 28 to radical surgery. No patients died within 30 days of initial treatment, but one in the organ-preservation group died within 6 months of conversion to total mesorectal excision, which led to anastomotic leakage. 8 patients (30%) required conversion to total mesorectal excision, and 4 of 27 (15%) had serious adverse events compared with 11 of 28 (39%) in the surgical arm. Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in 3 cases). In contrast, radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (2 patients), kidney injury (2 patients), cardiac arrest (1 patient), and pneumonia (2 patients).
Additionally, 8 of 27 patients (30%) assigned to organ preservation achieved a complete response to radiation therapy. Organ preservation also led to sustained benefits for up to 3 years in the patient-reported factors of social function, body image, and decreased embarrassment about bowel function, and the risk of unsalvageable local recurrence was low in TREC.
Geerard L. Beets, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, noted that times have changed since radical excision was the only treatment approach for patients presenting with large rectal cancers. “Current colorectal cancer screening programs are detecting many rectal tumors when they are small, and it is now time to move beyond the time-honored concept of radical cancer surgery,” he said.
“The results are promising, with the treatment being effective and the pre-surgery short course of radiation allowing for greater organ preservation,” said David A. Greenwald, MD, who is director of Clinical Gastroenterology and Endoscopy at Mount Sinai Hospital in New York City. “This is great news for those with rectal cancer, as the data show comparable outcomes using less extensive surgery and an associated better post-treatment QoL.”
- Polypectomy Associated With Decreased Long-Term Risk for CRC (Dec.28/20)
The incidence of colorectal cancer (CRC) was found to be reduced by 67% with polypectomy and by 70% with adenomatous or advanced histology polypectomy in patients undergoing 24 years of follow-up in the Minnesota Colon Cancer Control Study (MCCCS), according to research published in Gastroenterology.
Participants underwent fecal occult blood test screening consisting of 6 guaiac-impregnated paper slides. Diagnostic colonoscopy was offered to participants who had at least 1 positive slide. Polyps were removed during the procedure and sent for analysis. A total of 46,445 participants (average age, 62.2 years; 51.9% women) were randomly assigned to 1 of 3 arms: annual CRC screening (annual), biennial CRC screening (biennial), or usual care (control). Among the 31,082 participants in the screening arms, 11,518 (37%) underwent at least 1 colonoscopic examination during the follow-up period. Of this group, 3542 (31%) had at least 1 polyp detected, and 3109 (27%) underwent removal of at least 1 polyp. Of the 3109 participants in the screening arms who underwent polypectomy, 1408 (45%) had more than 1 polyp removed. A total of 5806 polyps were removed in the screening arms, and the average polyp size was 7.5 mm. Approximately half of the polyps were adenomatous (48%), and the most common location for polyps was distal (63%). CRC was diagnosed in 926 (3.0%) and 560 (3.7%) patients in the screening and control arms, respectively, in the 24 years of follow-up and 862,669 person-years of follow-up.
“These findings strengthen our knowledge about long-term benefits of polypectomy and provide information for patient–physician shared decision making when weighing risks and benefits of colonoscopy and polypectomy,” the researchers concluded. “Our study supports the current practice of searching for and removing polyps at colonoscopy.”
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 lessinvasive, 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:
- 16. Understanding The CEA Test in Colon Cancer (Oct.22/20)
What is the Carcinoembryonic antigen (CEA)?
CEA is an antigen (small protein) that is found on the surface of many types of cancer cells and high levels of CEA can be detected in the blood of some patients with cancer (such as colorectal cancer) and the developing fetus. The CEA is measured in the blood and the normal range is <2.5 ng/ml in an adult non-smoker and <5.0 ng/ml in a smoker. The most common cancers that elevate CEA are in the colon and rectum, but it can be elevated with gastric, ovarian and other cancers. The most frequent cancer, which causes an increased CEA, is cancer of the colon and rectum. Benign conditions that can elevate CEA include smoking, infections, inflammatory bowel disease, pancreatitis, cirrhosis of the liver, and some benign tumors in the same organs in which an elevated CEA level indicates cancer.
What do the studies show?
The CEA blood test could improve treatment for more than 1 in 6 stage 2 colon cancer patients and many patients who could benefit from the test likely aren’t receiving it.
Using data from the National Cancer Database for 40,844 patients, Mayo Clinic physicians and scientists teamed up to look at benefits of measuring the CEA. Researchers found that knowing these blood test results prior to treatment could have changed the classification for 17% of stage 2 colon cancer patients from average risk to high risk. High-risk stage 2 colon cancer patients are more likely to benefit from chemotherapy treatment following surgery. The researchers also discovered that, for stage 2 patients who had surgery but not chemotherapy, the five-year survival rate was 66% for those with elevated protein levels and 76% for those without elevated levels. And for patients with elevated protein levels, those who had chemotherapy and surgery fared better than those who only had surgery.
More intensive screening improves overall survival among patients diagnosed with stage II colon cancer
According to an article published in the Journal of Clinical Oncology, more intensive screening up to the fifth year following treatment for patients diagnosed with stage II colon cancer yields improved survival compared with simpler screening strategy.This trial included 259 patients: 132 patients underwent a simple surveillance strategy including a clinical evaluation and CEA levels, 127 patients underwent an intensive surveillance strategy including abdominal computed tomography (CT) or ultrasound, chest X-rays, and colonoscopy in addition to a clinical evaluation and CEA levels.
Patients with stage II colon cancer had improved outcomes with an intensive surveillance strategy:
- After a median follow-up of 4 years, there was no difference in survival among patients with stage III colon cancer.
- There were no differences in time before cancer recurred and type of recurrence between the two groups screening groups.
- Patients with stage II colon cancer had improved survival when undergoing intensive screening compared to simple screening (81.6 months versus 70.9 months, respectively).
- Patients with cancers in the rectum had improved survival with intensive screening compared to simple screening.
- 51% of patients who underwent intensive screening were able to have their cancer recurrence completely removed, compared with only 29% of patients who underwent simple screening.
- Although intensive screening was more expensive than simple screening, surgery for recurrences was more expensive for those who underwent simple screening.
The researchers concluded that a more intensive screening strategy improves overall survival among patients diagnosed with stage II colon cancer more than a simpler strategy. A consensus on the exact routine of screening for patients with this disease has not yet been confirmed. These results may provide important information on establishing follow-up screening guidelines for stage II colon cancer.
CEA and Albumin Levels Associated with Survival in Colorectal Cancer
According to an article recently published in the Journal of Clinical Gastroenterology, levels of the CEA and albumin (ALB) are associated with survival among patients with early CRC.Levels of the protein CEA in the blood may be indicative of the presence or spread of colon cancer. ALB, also a protein that can be measured in the blood, may also indicate some levels of cancerous activity. Researchers are still evaluating CEA and ALB levels and their potential associations with outcomes among cancer patients. Researchers recently evaluated data to determine the relationship of CEA and ALB levels prior to treatment among patients with early colon cancer. This study included 170 patients who were divided into four groups: 1) low CEA levels and high ALB levels; 2) low CEA and low ALB; 3) high CEA and high ALB; 4) high CEA and low ALB. At five years, survival rates were 66% for group 1, 63% for group 2, 46% for group 3, and 34% for group 4. The researchers concluded that levels of CEA and ALB prior to treatment are significantly associated with long-term survival among patients with early CRC.
- Differences in Right vs. Left Colon in Black vs. White Individuals (Jan.08/21)
According to results from a biopsy study, the right colon appears to age faster in Black people than in White people, perhaps explaining the higher prevalence of right-side colon cancer among Black Americans.
Investigators analyzed colon biopsy specimens from 128 individuals who underwent routine colorectal screening. The researchers compared DNA methylation levels in right and left colon biopsy samples from the same patient. They then assigned epigenetic ages to the tissue samples using the Hovarth clock, which estimates tissue age on the basis of DNA methylation. DNA methylation is influenced by age and environmental exposures. Abnormal DNA methylation is a hallmark of colorectal cancer (CRC), the researchers explain. The epigenetic age of the right colon of the 88 Black patients was 1.51 years ahead of their left colon; the right colon of the 44 White patients was epigenetically 1.93 years younger than their left colon. The right colon was epigenetically older than the left colon in 60.2% of Black patients; it was younger in more than 70% of White patients. A unique pattern of DNA hypermethylation was found in the right colon of Black patients. “Our results provide biological plausibility for the observed relative prevalence of right colon cancer and younger age of onset in African Americans as compared to European Americans,” comment the investigators. “Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC burden,” they suggest.
If these findings are “corroborated in African Americans in future studies, these results could potentially explain racial differences in the site predilection of colorectal cancers,” said Amit Joshi, MBBS, PhD, and Andrew Chan, MD, gastrointestinal molecular epidemiologists at Harvard University, Boston, Massachusetts, in an accompanying editorial. However, “it is not clear if the higher epigenetic aging measured using the Horvath clock…directly translates to a higher risk of colorectal cancer,” they note.
Some differences between the Black patients and the White patients in the study could explain the methylation differences, they point out. A higher proportion of Black patients smoked (37.5% vs. 15%), and Black patients were younger (median age, 55.5 years, vs. 61.7 years). In addition, the study included more Black women than White women (67% vs. 58%), and body mass indexes were higher for Black patients than White patients (31.36 kg/m2 vs. 28.29 kg/m2). “One or more of these factors, or others that were not measured, may be linked to differential methylation in the right compared with left colon,” the editorialists write. Even so, among the Black patients, almost 70% of differentially methylated positions in the right colon were hypermethylated, compared to less than half in the left colon. These included positions previously associated with colorectal cancer, aging, and ancestry, “suggesting a role for genetic variation in contributing to DNA methylation differences in AA right colon,” the investigators say.
- 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.
- What Does PD-L2 Tell Us About Advanced CRC? (Dec.30/20)
The role of programmed cell death 1 ligand (PD-L1) in suppressing immune response is well known in many cancers. But what about PD-L2? Now, investigators from China Medical University Hospital in Taichung, Taiwan, have published results that show how the presence of PD-L2 in the tumor may be an independent predictor of survival outcomes for patients with advanced stage colon carcinoma.
The study involved 1264 patients diagnosed at different stages of CRC: 175 at stage I, 456 at stage II, 406 at stage III, and 227 at stage IV. These patients underwent surgery between 2006 and 2014; postoperative chemotherapy was recommended for high-risk stage II patients and lymph node metastasis stage III patients. Immunohistochemical staining was performed, and PD-L2 levels were graded based on a sliding scale. Patients who had elevated tumor PD-L2 levels had better overall survival (OS) compared with those patients with low PD-L2 levels; this was especially true in advanced stage colon carcinoma patients, the authors reported. Conversely, low tumor PD-L2 expression was associated with an increased 5-year OS risk among advanced stage colon carcinoma patients.
The authors note that the link between PD-L2 expression and survival outcomes has been noted in other cancers, including pancreatic and esophageal cancer, although some studies have connected PD-L2 expression with poor survival. The authors note topic is controversial because of inconsistencies and that more data are needed. The current study also found evidence that PD-L2 expression was inversely associated with the lymphocytic reaction in advanced stage colon carcinoma, which the authors say suggests “that PD-L2 may be up-regulated by a compensatory mechanism to inhibit T cell-mediated anticancer immunity.”
- Recurrence Risk Low After One Year of Watch-and-Wait for Rectal Cancer (Dec.21/20)
According to a study published online in The Lancet Oncology, risks for local regrowth and distant metastases during the subsequent two years are low after sustaining a clinical complete response for 1 year with a watch-and-wait strategy following a complete response to rectal cancer treatment.
Laura M. Fernandez, M.D., from the Champalimaud Foundation in Lisbon, Portugal, and colleagues conducted conditional survival modelling using the International Watch & Wait Database (47 clinics across 15 countries). The analysis included 793 adults with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy and who were subsequently managed by a watch-and-wait strategy between Nov. 25, 1991, and Dec. 31, 2015.Researchers found that during a median follow-up of 55.2 months, the probability of remaining free from local regrowth for an additional 2 years was 88.1%, 97.3%, and 98.6% if a patient sustained a clinical complete response for 1, 3, and 5 years, respectively. Among patients who had a clinical complete response without distant metastases for 1 year, the probability of remaining free from distant metastases for a further 2 years was 93.8%. This probability increased to 97.8% and 96.6% for patients with a clinical complete response without distant metastases for 3 and 5 years, respectively.
“These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach,” the authors write.
- Cancer Cells Can Hibernate to Survive Chemotherapy (Jan.08/21)
All cancer cells can enter a sluggish, slow-dividing state if they come under threat. Then, after the threat has passed, they can wake up and begin replicating at full tilt. By entering and leaving a dormant state in such coordinated fashion, the cancer cells can defeat a round of chemotherapy—and gain enough time to acquire resistance to additional rounds of chemotherapy. The cancer cells can act like an organism that is going through hibernation. However, a more accurate term is diapause, a reversible state of suspended embryonic development triggered by unfavourable environmental conditions.
The ability of cancer cells, as a group, to hijack diapause, a highly conserved developmental mechanism, was discovered by scientists affiliated with the Princess Margaret Cancer Center and the University of Toronto. “We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer (CRC) models to identify and characterize drug-tolerant persister (DTP) states in response to chemotherapy,” the article’s authors wrote.
Human CRC cells in a petri dish were treated with chemotherapy. This induced a slow-dividing state across all the cancer cells in which they stopped expanding, requiring little nutrition to survive. As long as the chemotherapy remained in the dish, the cancer cells remained in this low-energy state, which the scientists described as a “diapause-like DTP state.” It appears that the cancer cells can co-opt diapause, an embryonic survival program used by more than 100 species of mammals to keep their embryos safe inside their bodies in times of extreme environmental conditions, such as high or low temperatures or lack of food. In this state, there is minimal cell division, greatly reduced metabolism, and embryo development is put on hold.
O’Brien, who is a surgeon specializing in gastrointestinal cancer, explained that cancer cells under attack by the harsh chemotherapy environment are able to adopt the embryonic survival strategy. “The cancer cells are able to hijack this evolutionarily conserved survival strategy, even as it seems to be lost to humans,” she said, adding that all of the cancer cells enter this state in a coordinated manner, in order to survive. Similar to embryos, cancer cells in the slow-dividing state require activation of the cellular process called autophagy, meaning “self-devouring.” This is a process in which the cell “devours” or destroys its own proteins or other cellular components to survive in the absence of other nutrients. O’Brien tested a small molecule that inhibits autophagy and found that the cancer cells did not survive. The chemotherapy killed the cancer cells without this protective mechanism.
“This gives us a unique therapeutic opportunity,” explained O’Brien. “We need to target cancer cells while they are in this slow-cycling, vulnerable state before they acquire the genetic mutations that drive drug-resistance.
- Poor Diet Quality Linked To Increased Risk For Early-Onset CRC Precursors (Dec.03/20)
According to study results published in Journal of the National Cancer Institute, a poor-quality diet appeared associated with an increased risk for early-onset, high-risk distal and rectal adenomas. Investigators assessed the effect of two dietary patterns (Western and prudent) and three recommendation-based indexes [Dietary Approaches to Stop Hypertension (DASH), Alternative Mediterranean Diet (AMED) and Alternative Healthy Eating Index 2010 (AHEI-2010)] on the risk for early-onset colorectal cancer (CRC), using early-onset adenomas and those of high malignant potential as surrogate endpoints.
The analysis included 29,474 women who underwent at least one lower endoscopy before age 50 years between 1991 and 2011. High-risk adenomas included those with any of the following characteristics: size of at least 1 cm, tubulovillous/villous histology (carries a high risk of turning cancerous), high-grade dysplasia or the presence of at least three adenomas. The investigators categorized all other adenomas as low risk. Results showed women who had a higher Western dietary pattern score, indicating high consumption of red and processed meats, were less likely to exercise or use multivitamins and more likely to have a greater number of pack-years of smoking. Conversely, women more adherent to the prudent dietary pattern and DASH, AMED and AHEI-2010 were more likely to demonstrate healthier behaviours. Of the 1,157 early-onset adenomas identified among all women, 375 were considered high-risk.
Researchers observed inverse associations between risk for early-onset adenoma and the prudent diet, DASH, AMED and AHEI-2010, whereas as a positive association was found with the Western diet. The associations mostly were confined to high-risk adenomas, with overall responses (ORs) of 1.67 for the Western diet, 0.69 for the prudent diet, 0.65 for DASH, 0.55 for AMED and 0.71 for AHEI-2010. High-risk adenomas appeared most likely to occur in the distal colon and rectum, but not among those with higher AMED scores. “The slightly different associations based on dietary index classification system might inspire future work exploring the specific mechanisms involved,” Yin Cao, MPH, ScD, researcher in the division of public health sciences of the department of surgery at Washington University School of Medicine in St. Louis, and colleagues wrote. More detailed studies of differences in dietary index adherence and CRC risk by anatomic site in youth are also warranted.
- Eating Yogurt May Reduce Your CRC Risk (Dec.21/20)
Yogurt consumption was associated with a reduced risk of colon cancer, even after adjusting for potential confounders like increased calcium intake. “The results showed that baseline yogurt consumption of one serving per week versus zero servings per week was associated with a reduced risk of colon cancer 26 to 32 years later,” said Anne Agler, PhD, senior vice president of nutrition research at the National Dairy Council.
Probiotics enhance immune functions by preventing inflammation and producing immune-supporting elements such as short-chain fatty acids. Additionally, certain probiotic strains produce lactic acid as a by-product. Lactic acid can lower the pH in the gut and can inactivate cancer-causing substances found in the body and in the feces. Eating fermented foods (i.e. yogurt, kimchi, and kefir) that contain certain probiotics play an important physiological role in the pathogenesis of colorectal cancer (CRC).
To evaluate risk reduction, researchers used data from two large, prospective cohort studies. During 32 years of follow-up in 83,054 women and 26 years of follow-up in 43,269 men, 2,666 new CRC diagnoses were found within these subjects (1,965 colon and 579 rectal cancers). Yogurt consumption was assessed via a food frequency questionnaire. Unfortunately, no statistically significant trend was observed between yogurt consumption and reduced CRC mortality.
It is important to note that participants with more frequent yogurt consumption also:
- Were more physically active
- Were more likely to have had a colonoscopy
- Were more likely to use multivitamins
- Had lower alcohol intake
- Ate less frequent red and processed meat
- Had a higher intake of vitamin D when compared with those who did not consume a lot of yogurts
In the case of this data, yogurt eaters participated in other cancer risk-reducing lifestyle choices, which introduces the question of whether it was the actual yogurt or the overall healthy lifestyle that resulted in risk reduction. “Overall, this paper contributes to the broader body of evidence, providing support to the World Cancer Research Fund (WCRF)/American Institute of Cancer Research (AICR) findings and reaffirms the association of dairy’s role in reducing colon cancer incidence,” Agler says.
- Tips for Eating Well During Chemotherapy & Cancer Treatment (Dec.19/20)
If you’re receiving treatment for cancer with chemotherapy, proper nutrition is as important now as ever. Side effects of chemotherapy, as well as effects of cancer itself, can affect your appetite, your tastes, and make eating uncomfortable or unpleasant. A balanced diet, however, can help you tolerate treatment and can support your recovery, so it’s important to find ways to fuel your body even when you don’t feel like eating. Certain food choices and eating habits can help you enjoy needed nutrition while helping manage side effects of treatment.
The following tips can help you eat well during chemotherapy:
- Chemotherapy can affect your taste buds, making certain foods you once enjoyed unpalatable. Some patients complain of a metallic taste, often with water or meat. Try substitutes for foods that don’t taste right (such as chicken or another source of protein in place of meat). If plain water is no longer appealing, try adding a lemon slice to your glass or try flavoured mineral water. Likewise, add different seasonings to food to enhance flavour.
- Some patients experience constipation during treatment. This can be eased by staying hydrated and making sure your diet contains enough fibre. Add fibre (such as fruits, vegetables, and whole grains) gradually to let your digestive system adjust.
- Diarrhea can also be a problem for patients during chemotherapy. Avoid foods that aggravate this condition. These include fried foods, caffeine, beverages high in sugar, and high-fibre foods like raw fruits and vegetables, whole grains, nuts, seeds, and dried fruit. Diarrhea can put you at risk of dehydration, so make sure to drink plenty of fluids.
- If you lose your appetite during chemotherapy, a dietician can help you find foods that are appealing and easy to digest. Examples include oatmeal, soups, and yogurt. You may also find that you prefer frequent small meals; make the most of what you eat with calorie- and nutrient-dense foods. Taking a short walk before meals may also improve your appetite. As well, try changing your routine at mealtime (such as eating with friends or trying a differently location) and try new foods—both may make eating more pleasant.
- If mouth sores or dry mouth make it difficult to eat, avoid foods that may further irritate your mouth (spicy foods, citrus, tomato, and alcohol, for example) and eat foods that are cool or at room temperature. Staying hydrated can keep your mouth from getting too dry. You may also want to avoid solid foods; if so juices, soups, and smoothies can keep you nourished.
- Nausea is a common complaint among patients undergoing chemotherapy. Peppermint or ginger tea can help control nausea and so can crystallized ginger (eaten or chewed). You may also feel better if you eat several small meals throughout the day and avoid large meals. Stay away from things that can make nausea worse like foods that are warm, hot, greasy, fried, or sugary.
- If you’re having trouble getting enough nutrients through diet alone, your doctor or nurse may be able to suggest nutrition supplements. Don’t, however, begin to take supplements (including vitamins and minerals) without talking to your healthcare team. Some supplements may interfere with chemotherapy, and some may be harmful at high levels.
- Talk to your doctor about alcohol consumption. Your liver may already be working overtime during chemotherapy to help metabolize potential toxins, so alcohol can be an extra burden. As well, there are other concerns about consuming alcohol during treatment, so it’s likely that you’ll need to limit intake or avoid it entirely.
- Nutrition for Cancer Patients (Feb.03/20)
Nutrition is for everyone, not just those fighting illness. Research has consistently indicated that a diet rich in fruits, vegetables, and whole grains may reduce the risk of cancer as well as heart disease. Furthermore, a sound diet is your best defense against obesity and diabetes.
Nutrition is perhaps the easiest place to begin in order to build health – whether you are living with cancer, surviving after cancer treatment, caring for a loved one with cancer, or simply interested in preventing cancer. Of course, the combination of a healthy diet with regular physical activity is likely to provide more health benefits than either behaviour alone.
If you’ve been diagnosed with cancer, nutrition will likely become an important component of your treatment plan. You will find that there are certain foods that will help build your immune system, give you energy in the face of fatigue, keep nausea at bay, help you gain weight or lose weight, and more. If you are a survivor or a caregiver, you will find that sound nutrition is critical to maintaining your health and vitality. It will give you energy and boost your immune system – in short, it will keep you going.
The link below contains several articles, which present the most current, well-researched information about the relationship between diet and health. The recipes will help you enjoy food that is not only good, but also good for you.
- Carbs and Cancer (May.23/20)
Cancer cells require a lot of glucose for energy—more than normal cells. This is because cancer cells metabolize, or break down, sugars using a different and less efficient process than that of normal, healthy cells. Cells typically use oxygen to burn glucose for energy. Because cancer cells grow in excess and become densely packed, however, they often survive in a low-oxygen environment and have adapted to breaking down sugars in the absence of oxygen—a process called anaerobic metabolism. Unfortunately, anaerobic metabolism is much less efficient than breaking down sugars aerobically (with oxygen). As a result, cancer cells may need as much as 40x more glucose than normal cells that function with sufficient levels of oxygen to generate the same amount of energy.
To supply the excessive sugars that the cancer demands, the liver breaks down proteins and fats to make more glucose. If inadequate carbohydrates are consumed, the body resorts to using protein from muscles and stored fats to meet energy demands. Thus the high-energy demands of the cancer may explain why cancer patients often experience weight loss and fatigue.
One purpose of nutritional therapy for cancer is to limit the amount of excess glucose available to the growing cancer while providing enough energy for the brain and other vital functions. A practice that can help accomplish this is maintaining even blood sugar levels and avoiding spikes in glucose, which provide extra sugars that can be used by the cancer. There are several tools for managing blood sugar. Using the glycemic index and following a low-carbohydrate diet are both well-known options, but a whole-foods diet may be easier and more effective.
The glycemic index (GI) is a measure of how fast the carbohydrates in food increase blood sugar levels. It is a scale from 1 to 100; 100 corresponds with pure glucose. Foods with a higher glycemic index are those that cause blood glucose levels to rise more quickly. Foods with a GI of 70 or more are considered high-GI foods. Foods with a GI of 55 or less are considered low-GI foods. The carbohydrates in a low-GI food do not cause a large spike in blood sugar.
While the glycemic index does help explain how different foods affect blood sugar, it does have the following limitations:
- Limited foods tested – only a small number and variety foods have been tested for their glycemic index.
- Food combinations – GI is based on how foods affect blood sugar when consumed alone, but most people do not eat one food at a time. Combining foods changes how those foods affect blood sugar (i.e. meals that include fiber or fat will have a less dramatic effect on glucose).
- Food preparation – the same food prepared in different ways can have very different affects on blood sugar (i.e. more-processed foods increase glucose more dramatically).
- Individual variability – the response to a food varies from person to person and from day to day.
Another way to control glucose levels is to follow a low-carb diet. These diets have been around since the 1800s and go in and out of favour. A woman on a low-carb diet usually gets 40% of her calories from carbohydrates and the remaining 60% from equal proportions of protein and fat. Like the GI, low-carb diets are difficult to follow even when you are healthy because food choices are so limited. When you are not feeling well, following such a diet may be impossible. Also, low-carb diets often do not contain foods rich in the antioxidants, vitamins, and minerals the body needs to fight cancer.
The whole-foods diet is rich in whole grains, legumes, fruits, vegetables, and fibre and also happens to have a low GI. There are no charts to interpret, and, unlike the low-carb diet, a bounty of food choices is available. To follow a whole-foods diet, avoid foods that are overly processed and/or refined, foods that are high in added sugar, and those that are made with refined flour. By following this cardinal rule of the whole-foods diet, you will get most of your calories from slow-burning, unrefined carbohydrates.
Here are a few more tips for controlling blood sugar with a whole-foods diet:
- Always eat a balanced meal with mixed foods. A meal rich in complex carbohydrates and fibre will slow the release of food from the stomach, thereby slowing the release of glucose from the meal.
- Avoid eating or drinking anything that tastes sweet on an empty stomach. This includes sweet-tasting fruit and vegetable juices, fruit, soda, sweetened refined cereals, honey, or any liquid sweetened with any form of sugar.
- Eat sweet whole foods such as fruit only with meals.
- Drink diluted or low-sugar fruit and vegetable juices only with fat-containing meals.
- CCRAN Proudly Issues “My Foods for Life” Booklet, in Partnership with the American Institute for Cancer Research (Jan.14/21)
In partnership with the American Institute for Cancer Research, CCRAN has proudly issued its “My Foods For Life” Booklet: a primary and secondary cancer prevention program aimed at not only helping to prevent a cancer diagnosis but also helping to prevent a recurrence for patients who have been successfully treated for cancer. The program also goes above and beyond in so far as it furnishes patients who are actively undergoing treatments for their disease with goals of nutrition during their cancer therapies and common nutrition-related side effects of treatments, as well as strategies to help manage those treatment-induced toxicities.
The program and the booklet contain tasty, easy to prepare recipes to follow a nutritious and healthy diet to help prevent a cancer diagnosis, or recurrence. Check it out:
You can access the booklet or the entire program on the CCRAN website: https://ccran.org/programs-advocacy/
Hardcopy versions are also available upon request. Please contact Frank Pitman at email@example.com . We are happy to furnish you or organization with copies.
- CCRAN’s Position on Colorectal Cancer Patients Accessing the COVID-19 Vaccine (Jan.14/21)
Colorectal Cancer patients undergoing treatment may, theoretically, experience a diminished immune response to the COVID-19 vaccine due to their cancer therapy. However, significant experience with other vaccines suggests that COVID-19 vaccines will still be critical in reducing the risk of COVID-19 in patients with cancer.
If you have been identified as eligible for the vaccine based on the provincial prioritization and you are on active cancer treatment or are concerned that you may be immunocompromised, please discuss this with your oncologist before receiving the vaccine.
Your Provincial Government’s prioritization framework outlines the eligibility criteria and timelines for COVID-19 vaccination and may be accessed through the following link by entering your province/territory: Overview: Coronavirus disease (COVID-19) vaccines – Canada.ca .
- Understanding COVID-19 Infection Transmission Immunity and Testing (Dec.20/20)
How is SARS-CoV-2 transmitted?
Respiratory viruses are transmitted three main ways:
- Contact transmission occurs when someone comes into direct contact with an infected person or touches a surface that has been contaminated.
- Droplet transmission of both large and small respiratory droplets that contain the virus can occur when an individual is near an infected person.
- Airborne transmission of smaller droplets and particles that are suspended in the air over longer distances and time than droplet transmission.
The most recent research suggests that contact transmission from a surface is unlikely to be a major route and respiratory transmission is the main route. Most respiratory virus transmission occurs from large infected droplets produced by coughing, sneezing, and breathing in close proximity to another person. This understanding has led to social distancing being the cornerstone of public health advice, but there is disagreement as to what constitutes a safe distance. For social distancing to be effective, infective respiratory particles would need to fall to the ground or be in low enough concentrations at 2 meters from the source to not cause transmission. Airborne transmission of SARS-CoV-2 was initially thought to be unlikely but growing evidence has highlighted that infective microdroplets are small enough to remain suspended in the air and expose individuals at distances beyond 2 meters from an infected person and this may be a likely route of spread. Whether droplet or airborne transmission is the main route, the risk of infection is known to be much lower outside where ventilation is better. Additionally, individuals with SARS-CoV-2 infection are likely to be most infectious in the first week of illness. This finding is supported by the observation in contact-tracing studies that the highest risk of transmission occurs very early in the disease course (a few days before and within the first 5 days after symptom onset).
What About Immunity?
It is unknown whether people are immune to reinfection because not enough studies have been done yet. However, research does suggest that people who recover from even mild cases of COVID-19 do produce antibodies that are believed to protect against infection for at least 5 to 7 months and that people who recovered from mild COVID-19 had memory B cells and memory T cells with hallmarks of functionality.
IgM-IgG Antibodies Against COVID-19
The immune system makes IgG and IgM antibodies that can be detected in the blood and provide useful information about an individuals past exposure to the virus but not much is known about immunity. This test cannot determine if you have an active infection, determine if you are infectious to other people, or confirm immunity to re-infection with certainty. In fact the sensitivity of antibody testing is poor until at least 3-4 weeks after the initial infection. A positive result means that one has been exposed to and has developed an immune response to the SARS-CoV-2 virus.
How Do Doctors Test for COVID-19 Infection?
Until August 2020 the main way people were tested for COVID-19 was to place a sterile swab at the back of a patient’s nasal passage, where it connects to the throat via the nasopharynx, for several seconds to absorb secretions. To determine whether a nasopharyngeal sample is positive for the coronavirus, biotechnicians use a technique known as reverse transcriptase polymerase chain reaction, or RT-PCR. To perform this test a technician extracts viral genetic material called RNA (if it is present) from the sample and uses it to produce a complimentary strand of DNA that the RT-PCR technique amplifies, or makes thousands of copies of, to get a measurable result. The primary difference from one kit to another is which coronavirus genes each test targets.
The FDA granted authorization to a COVID-19 Home Test December 19th, 2020. This is the first over the counter (OTC) at-home diagnostic antigen test for COVID-19. The test will cost $30 and is designed to detect active COVID-19 in individuals aged 2 years and older with or without symptoms. The test kit includes a nasal swab, a dropper, processing fluid, and a Bluetooth® connected analyzer for use with an app on a smartphone (app contains step-by-step video instructions to aid the user in performing the test). Real-time test results are then transmitted to the user’s smartphone in less than 15 minutes and can be shared with health care professionals, employers and schools. In a simulated home-setting clinical study which included 198 individuals aged 2 to 82 years, the COVID-19 Home Test achieved 96% accuracy, with an overall sensitivity of 95% and a specificity of 97% when compared to an RT-PCR laboratory test. Although highly accurate the test is a little less sensitive and less specific than PCR tests run in a lab.
- The Coronavirus is Mutating: What We Know About the New Variants (Jan.06/20)
All viruses mutate often. Typically, the mutations aren’t functional and have no significant impact on the behaviour of the virus. As viruses mutate, their chance of survival increases. That is, the more diverse a species is, the more chances it has to survive, said Dr. Benjamin Neuman, a virologist at Texas A&M University Texarkana.
“Mostly the changes are bad for each individual virus, but together, a population of weaker but more diverse viruses has a better chance of survival than the same sized population of identical viruses,” Neuman said. Sometimes, those mutations can improve the performance of the virus, as we may be seeing with the new variants detected in the United Kingdom and South Africa.
A New Strain in South Africa
Called the B.1.351 lineage, the new strain identified in South Africa is thought to be more transmissible. The strain has also been associated with a higher viral load, further suggesting it’s more transmissible than previous strains. Some medical experts have sounded the alarm that the variant could potentially be resistant to vaccines or medications. There is no evidence that suggests that the new variant in South Africa won’t respond to the vaccines, experts say. Researchers will need to follow the variant to determine if it may reduce vaccine performance.
One of the mutations involves the spike protein, the piece of the virus that binds to receptors in our cells. The vaccine immunizes people against the spike protein, which is why some infectious disease experts have expressed concern. But the vaccine induces a broad immune response that will likely be able to recognize and respond to most variants. However, antibody treatment may not work as well if the virus has mutated, according to former FDA Commissioner Dr. Scott Gottlieb. Antibody treatment consists of using antibodies taken from people who had COVID-19 to treat new patients.
The U.K. Variant
The new strain identified in the United Kingdom, that’s now also swarming around the United States, is thought to be up to 70% more infectious than the original variant dominating outbreaks in the U.K. Known as the B.1.1.7 lineage, the strain has caused a spike in infections among people under 20. According to the WHO, like the variant detected in South Africa, the strain in the United Kingdom has mutations in the spike protein. A more transmissible variant will inevitably make the pandemic harder to control. Though the strain isn’t thought to cause a more severe disease, it could lead to more cases overall, along with more illness, hospitalizations, and deaths. At this point, scientists believe the vaccines will be effective against the strain originally detected in the U.K.
The bottom Line
More research is needed to determine if and how the mutations impact the virus’s behaviour. Experts continue to stress the importance of wearing a mask, practicing physical distancing, and washing our hands. These measures will likely protect against all variants.
- 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