The following colorectal cancer research updates extend from September 18th to October 15th, 2020, inclusive and are intended for informational purposes only.
CONTENT
1. Phase II LEAP Clinical Trial to Treat mCRC
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. Lonsurf® (TAS 102) Treatment for CRC
6. Onvansertib Precision Medicine Being Developed for KRAS mutant Colon Cancers
7. Checkpoint Inhibitor Immunotherapy Delays CRC Progression
8. Tumour Mutational Burden Identifies Cancer Responsive to Immunotherapy
9. Can Aspirin Prevent The Development of Colon Cancer Recurrence?
10. Bavencio Shows Activity as ‘Rechallenge’ Therapy Strategy in Metastatic CRC
11. Growing Data on Vitrakvi Demonstrates Enduring Activity Across Variety of NTRK-Positive Tumor Types
12. Molecular Profiling for mCRC
13. TRACON Pharmaceuticals Highlights Updated Envafolimab Clinical Results in MSI-H/MMR-D CRC
14. Higher ctDNA Fraction Decreases Survival in Regorafenib-Treated mCRC Patients
15. Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Hospital
16. Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
17. A Life-Saving Transplant Trial
18. Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer
19. Trials Confirm Preoperative Chemo-Radiation Improves Outcomes for Rectal Cancer
20. Screening Colonoscopy Reduces Deaths from CRC
21. Young Adult Colorectal Cancer Clinic Available at Sunnybrook Hospital
22. The Importance of Getting a Second Opinion
23. Neuropathy (Numbness and Tingling) Prevention and Treatment
24. Prevalence of Colorectal Neoplasia in Adults Younger than 50
25. Incidence of Young-Onset CRC in Canada Continues to Increase
26. How Medical Marijuana Helps To Ease Cancer Treatment Side Effects
27. Flu Shot 101 – What You Need to Know for the Influenza Season
28. CRC in Young People
29. Study Shows Disparities in Access to Molecular Diagnostics for CRC
30. Healthy Lifestyle Improves CRC Outcomes
31. Top 12 Foods to Improve Your Health
32. Researchers Find changing Gut Microbiota, Taming Inflammation May Help Battle CRC
33. Tips For Dealing with Fatigue
34. Exercise and CRC
35. Drinking Coffee Tied to Better Outcomes in Colon Cancer Patients
36. Will Curcumin be a Valid Therapy for CRC?
37. These Foods & Medications May Lower Bowel Cancer Risk
38. Frequently Asked Questions for COVID-19
DRUGS / SYSTEMIC THERAPIES
- Phase II LEAP Clinical Trial For mCRC (Mar.1/20)
The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and Levantine (E7080/MK-7902) in patients with triple-negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), or biliary tract cancers (BTC). Participants will be enrolled in initial tumor-specific cohorts, which will be expanded if adequate efficacy is determined. The trial is available at the Odette Cancer Centre and at the Princess Margaret Cancer Centre in Toronto as well as the following Centres throughout Canada: Abbotsford, BC; Winnipeg, MB; CHU de Quebec. For information, visit the link below.
- Health Canada Approves VITRAKVI (Larotrectinib), First Tumour Agnostic Cancer Treatment For Advanced Solid Tumours Harbouring an NTRK Gene Fusion (Mar.5/20)
Bayer announced that there is now a treatment in Canada for tyrosine receptor kinase fusion protein-driven childhood and adult cancers. Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusions can result in the production of TRK fusion proteins that can lead to uncontrolled cell growth and cancer. Health Canada issued a Notice of Compliance with Conditions (NOC/c) for VITRAKVI® (Larotrectinib). VITRAKVI® is approved for the treatment of adult and pediatric patients with solid tumours that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options. Treatment with VITRAKVI® should be initiated following confirmation of an NTRK gene fusion in a tumour specimen using a validated test.
This is the first time Health Canada has approved a tumour agnostic treatment, such that patients with advanced solid tumours harbouring an NTRK gene fusion may be eligible for treatment with VITRAKVI®, across multiple tumour types and ages. VITRAKVI® is a first-in class oral and highly selective TRK inhibitor that may shrink the tumour or may slow or stop it from growing. In the clinical trials that were the basis for this approval, TRK fusion cancer patients treated with Larotrectinib experienced clinical benefit across numerous tumour types, including lung, thyroid, melanoma, GIST (gastrointestinal stromal tumour), colon, soft tissue sarcoma, salivary gland, and infantile fibrosarcoma. The overall response rate (ORR) was 75% (95% CI, 64%, 85%) with 22% of patients experiencing a complete response (CR) to treatment. The ORR observed was 90% in pediatrics and 69% in adults, and responses were rapid and durable.
What is TRK Fusion Cancer?
TRK fusion cancer is rare and occurs when an NTRK gene fuses with another unrelated gene, producing a TRK fusion protein that becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless where it originates in the body. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumours with varying frequency, including lung, thyroid, gastrointestinal cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma). TRK fusion proteins are rare in common cancers (such as colorectal cancer) and common in rare cancers.
NB: The pan Canadian Oncology Drug Review Expert Committee (pERC) has recently issued a funding recommendation in respect of Larotrectinib. It conditionally recommends the reimbursement of Larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with locally advanced solid tumors that have an NTRK gene fusion This recommendation pertains only to adult and pediatric patients with salivary gland tumours, adult or pediatric patients with soft tissue sarcoma (STS) and pediatric patients with cellular congenital mesoblastic nephroma or infantile fibrosarcoma, without a known acquired resistance mutation, that are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options, only if the following conditions are met:
- Cost-effectiveness being improved to an acceptable level
- Feasibility of adoption (budget impact and access to testing) is addressed
Stay tuned as the expert committee is currently reviewing feedback submissions from various stakeholders.
Please note: the expert review committee has as of October 31st, 2019 issued a negative funding recommendation in respect of Larotrectinib. Bayer is making a resubmission in late 2020 and cancer patient groups, such as CCRAN, will support that resubmission with a patient group submission of its own.
Bayer’s Commitment
- Bayer has launched a testing program called FastTRK. As per an information sheet that may be obtained from CCRAN, FastTRK is a clinical testing program for the diagnosis of NTRK gene fusions. Sponsored by Bayer, this is a complimentary service for clinicians to determine whether their patient’s cancer has an NTRK gene fusion. Solid tumour samples from eligible patients (in the form of a solid tumour block or prepared slides) will be tested by immunohistochemistry (IHC) and/or next-generation sequencing (NGS). Currently, Bayer has partnered with LifeLabs and the Kingston Health Sciences Centre (KHSC) to provide NTRK gene fusion testing services for Canadians. The FastTRK program will be supported at least until the end of 2021.
- Bayer will continue to offer the therapy to patients who are identified to have TRK fusion cancers and who are responding to the therapy.
- Bayer will provide a TRAKTION Patient Support Program to assist patients while on the therapy.
https://www.bayer.ca/en/media/news/?dt=TmpBPQ==&st=1
- A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment for the MSI High Colorectal Cancer Metastatic Population (Oc.1/20)
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.1/20)
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.
About 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.
https://sunnybrook.ca/trials/item/?i=293&page=49335 and https://clinicaltrials.gov/ct2/show/NCT03750786
https://isofolmedical.com/arfolitixorin/
- Lonsurf® (TAS 102) Treatment for CRC (Jul.03/19)
The FDA has approved the oral agent, Lonsurf® (trifluridine and tipiracil), specifically, for the treatment of advanced colorectal cancer (CRC) that has stopped responding to standard therapies including chemotherapy and biologic therapy. In preclinical studies, Lonsurf showed anti-tumour activity against cancer cell lines that were resistant to flourouracil (5FU) a standard therapy for CRC. The RECOURSE study was a global phase III trial conducted in 13 countries. Patients had metastatic CRC (mCRC) refractory to all standard therapies including with wild-type KRAS tumors. Patients were treated with TAS-102 (534 patients) and placebo (266 patients) and directly compared.
The researchers found that TAS-102 prolonged overall survival (OS) experiencing a median OS of 7.1 months for TAS-102 and 5.3 months for placebo. TAS-102 also improved progression-free survival (PFS) and was well tolerated with the most common side-effect being neutropenia (low white blood cell count).
In patients with chemo-refractory mCRC, Lonsurf combined with Avastin (bevacizumab) improved survival according to results presented at the ESMO 21st World Congress on Gastrointestinal Cancer. The study enrolled 93 patients with chemo-refractory mcrc to receive treatment with Lonsurf with or without Avastin. The combination improved survival duration from 6.7 months with Lonsurf to 9.4 months with the addition of Avastin. The most common side effects with Lonsurf were low levels of blood cells and fatigue/weakness.
Image Source: https://en.50bestpharma.com/producto/llonsurf-trifluridine-tipiracil/
- Onvansertib Precision Medicine Being Developed for KRAS mutant Colon Cancers (Sep.21/20)
The FDA granted Fast Track Designation to Onvansertib, an orally administered, highly selective PLK1 inhibitor that is being developed in patients with KRAS-mutated metastatic colorectal cancer (mCRC). KRAS mutations are the most common oncogenic alteration in all of human cancers and there are currently no effective treatments available for patients with KRAS-mutant cancers.
Onvansertib is being developed by Cardiff Oncology who recently announced an Expanded Access Program (EAP) to access onvansertib in combination with standard-of-care FOLFIRI and bevacizumab for second-line treatment of patients with KRAS-mutated mCRC who are not be able to participate in the ongoing clinical trial. The trial will enroll up to 44 patients with a KRAS mutation and histologically confirmed metastatic and unresectable disease. In addition, patients must have failed treatment or be intolerant of FOLFOX (fluoropyrimidine and oxaliplatin) with or without bevacizumab. Initial data confirming the effectiveness of onvansertib and durability of response in KRAS-mutated mCRC was released at the European Society of Medical Oncology (ESMO) Virtual Congress in September 2020. Overall 10 of 11 (91%) of patients treated with onvansertib in combination with FOLFIRI, achieved disease control with only 1 patient progressing in while on treatment.
Additionally:
- 5 (45%) patients achieved a partial response with 1 patient going on to curative surgery.
- 8 of 11 (73%) patients demonstrated durable response ranging from 6 months to over 12 months, and 4 patients remain on treatment.
- All the responses were associated with different KRAS mutation variants, including the 3 most common that comprise nearly 80% of mutations in CRC.
- Treatment was safe and well tolerated with no major or unexpected toxicities attributed to Onvansertib
An EAP provides a potential pathway for patients with a serious or life-threatening condition to gain access to an investigational drug for treatment outside of a clinical trial, particularly when no comparable or satisfactory alternative therapy options are available. The Cardiff Oncology EAP is intended for use in combination with FOLFIRI and bevacizumab for the second-line treatment of patients with KRAS-mutated mCRC that has progressed on prior FOLFOX (with or without bevacizumab) therapy.
- Checkpoint Inhibitor Immunotherapy Delays CRC Progression (Jun.30/20)
Checkpoint inhibitors are a type of precision cancer immunotherapy that helps to restore the body’s immune system to fight the cancer. In doing so they release checkpoints that the 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 colon cancer cells. Keytruda (pembrolizumab) and Opdivo (nivolumab) are “checkpoint inhibitors” with significant anti-cancer activity in advanced colorectal cancer (CRC) patients with mismatch repair deficient (MMR-D) and microsatellite instability high (MSI-high) abnormalities. The Phase 3 Keynote-177 trial evaluated first-line treatment with Keytruda for patients with MSI-high or MMR-D in 307 patients with unresectable or metastatic CRC (mCRC). Keytruda treated patients survived on average 16 months without cancer progression compared to 8.2 months for those treated with standard chemotherapy. At 24-months follow up, progression-free survival (PFS) was 55.3% with Keytruda compared to 18.6% with chemotherapy. All patients with colon cancer should undergo genomic biomarker testing to determine whether they have MSI-high or either markers that can help determine optimal treatment.
Image Source: https://www.pharmaceutical-journal.com/news-and-analysis/features/immune-checkpoint-inhibitors-bring-new-hope-to-cancer-patients/20067127.article?firstPass=false
- Tumour Mutational Burden (TMB) Identifies Cancer Responsiveness to Immunotherapy (Oct.02/20)
The Food and Drug Administration (FDA) granted accelerated approval to Keytruda® (pembrolizumab) for the treatment of adult and pediatric patients with unresectable or metastatic tumour mutational burden-high (TMB-H) cancers that have progressed following prior treatment and who have no satisfactory alternative treatment options.
High levels of microsatellite instability (MSI-high) occur in about 10% to 15% of colorectal cancers (CRCs). Research has demonstrated that about 50% of MSI-high patients with advanced colon cancer respond to treatment with immune checkpoint inhibitor medications like Keytruda, which improves survival compared to chemotherapy.
Research suggests that the tumor mutational burden (TMB) may help further predict which patients with MSI-high disease can be optimally treated with immune checkpoint inhibitors. Tumor cells with high TMB may have more novel antigens (targets) which are associated with an increase in cancer-fighting T cells to direct an anti-cancer response. The presence of MSI-high is associated with higher TMB, however TMB does not guarantee the presence of MSI-high.
Doctors have evaluated TMB in colon cancer patients and found a very strong association between TMB and response to treatment. Researchers estimated the optimal predictive cut point for TMB to be between 37 mutations/megabyte and 41 mutations/megabyte. Patients who fall outside of the cut-point range may be less likely to benefit from checkpoint inhibitor immunotherapy therapy. The best approach to these patients is still being determined. This data supports the integration of a TMB score as a potential decision tool in the sequencing of checkpoint inhibition and chemotherapy.
https://news.cancerconnect.com/treatment-care/tumor-mutational-burden-identifies-cancer-responsive-to-immunotherapy-4EWpGXCSSUeY8edi-nQ-1w
- Can Aspirin Prevent The Development of Colon Cancer Recurrence? (Oct.10/20)
Women who take a low-dose aspirin every other day have a reduced risk of colon cancer according to this study. These results came from the 18-year of follow-up of the Women’s Health Study, which was a 10-year randomized trial that evaluated the effects of aspirin and vitamin E on cardiovascular disease and cancer risk. The study included 35,876 women aged 45 or older with no history of cardiovascular disease or cancer. The women were randomly assigned to take 100 mg of aspirin or placebo every other day for 10 years. Overall, there were 5,071 confirmed cancer cases (including 2,070 breast, 451 colorectal, and 431 lung). Women in the aspirin group had a 20% reduced risk of colon cancer, but the benefit didn’t appear until after a decade.
Research also suggests that daily doses of 75 mg or more of aspirin taken for five or more years reduces the long-term incidence and mortality of colorectal cancer (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 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 (right sided) colon cancer. 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. Thus, researchers concluded that 75 mg daily (or more) of aspirin taken for five years or more reduced the long-term risk of developing and dying from CRC.
Image Source: https://www.inquirer.com/philly/health/aspirin-daily-preventative-use-arrive-ascend-aspree-20181029.html
- Bavencio Shows Activity as ‘Rechallenge’ Therapy Strategy in mCRC (Sep.20/20)
The combination of an anti-EGFR monoclonal antibody and an immune checkpoint inhibitor may be a beneficial “rechallenge” treatment strategy in previously treated RAS wild-type metastatic colorectal cancer patients who have become resistant to anti-EGFR treatment, researchers reported at the European Society for Medical Oncology’s Virtual Congress on Saturday.
The single-arm CAVE study “provides the first clinical evidence” in a Phase II trial that avelumab (Pfizer/EMD Serono’s Bavencio) plus cetuximab (Eli Lilly’s Erbitux) is “effective, well-tolerated, and feasible” as a treatment for RAS wild-type metastatic colorectal cancer patients who have become resistant to first-line anti-EGFR monocolonal antibodies, are given a temporary reprieve from anti-EGFR treatment, and are challenged again with these drugs, said Erika Martinelli from the University of Campania in Naples, Italy, in a conference presentation.
The CAVE study met its prespecified endpoint of median overall survival, suggesting that a subset of chemo-refractory RAS wildtype colorectal cancer patients may benefit from receiving a checkpoint inhibitor alongside an anti-EGFR monoclonal antibody as a rechallenge strategy. However, Martinelli cautioned that the precise contribution of the two drugs in spurring immune responses cannot be definitively concluded in a single-arm trial, and that these Phase II findings need to be confirmed in a randomized Phase III trial.
Furthermore, she suggested that in a Phase III trial patients should be stratified based on circulating tumor DNA (ctDNA) analysis to identify best responders in this advanced and previously treated population.
The CAVE study enrolled 77 RAS wild-type, metastatic colorectal cancer patients who had previously received first-line treatment with chemotherapy and anti-EGFR drugs and then went on to receive subsequent lines of therapy that did not include an anti-EGFR therapy. In the study, most patients had received two lines of prior therapy and around a quarter of patients had previously received three or more treatments. After this, patients were given avelumab and cetuximab and followed until they progressed or had to stop treatment due to toxicities.
The benefit of immune checkpoint inhibitors is now well established as a treatment for patients with microsatellite-unstable metastatic colorectal cancer. However, the precise role of immunotherapy in microsatellite-stable colorectal cancer is still being explored. Some preclinical and single-arm early clinical studies have suggested that a checkpoint inhibitor and anti-EGFR monoclonal antibody may work together to activate NK cell-driven immune responses against cancer cells.
The CAVE study investigators set out to explore this combination specifically as a rechallenge treatment strategy in refractory, RAS wild-type metastatic colorectal cancer patients, for whom the standard of care in the first-line setting is anti-EGFR monoclonal antibodies, such as cetuximab and panitumumab (Amgen’s Vectibix). The downside of this treatment is that patients eventually become resistant through the emergence of RAS mutant clones. “Circulating tumor DNA analysis has shown that at disease progression, a treatment break from antigen receptor drug is able to restore sensitivity” by suppressing RAS-mutant cancer cells, Martinelli explained.
In their study, Martinelli and colleagues prespecified their aim to demonstrate 11-month median overall survival, resulting in a three-month improvement over a median overall survival of 8 months, which is what is typically seen in this third-line setting with standard treatments. At data cut-off on July 13, seven patients had progressed on the avelumab-cetuximab regimen, 37 had died, 32 patients were still being followed for survival, seven patients were still on the treatment regimen, and one patient had been lost in follow up.
The study met its primary endpoint and demonstrated a median overall survival of 13.1 months and a median progression-free survival of 3.6 months. The objective response rate was 7 percent, and 57 percent had stable disease. The regimen appeared to be well-tolerated in this study, with 14 percent and 4 percent of patients experiencing grade 3 skin rash and diarrhea, respectively.
“This chemotherapy-free regimen compares favorably with concurrent standard third-line therapies with respect to safety and efficacy,” Martinelli said.
In the study, researchers collected plasma samples at baseline and conducted central ctDNA analysis in 56 patients for RAS, BRAF, and EGFR mutations. They found that after receiving a break from anti-EGFR antibody treatment, 41 had no mutations in RAS or BRAF but 15 patients still had mutations in these genes. The overall response rate to the avelumab-cetuximab combination was 9 percent in the wildtype population and there were no responders in the mutated population. The median progression-free survival was 4.3 months versus 3.2 months, and the median overall survival was 16.1 months and 11.5 months in the wildtype and mutated ctDNA groups, respectively.
“The evaluation of plasma ctDNA as assessed at baseline by liquid biopsy allowed [us] to further define the activity and the safety” of the combination, Martinelli said, noting that the findings need to be confirmed in a Phase III randomized trial. “Moreover, plasma DNA analysis before treatment should contribute to better selecting patients who may benefit from this treatment.”
In reviewing the data, Chiara Cremolini, a colorectal cancer specialist from the University of Pisa recognized that stratifying patients based on ctDNA analysis certainly seems to have improved the identification of the population benefiting from the avelumab-cetuximab treatment, judging by the response rate increasing from an initial 7 percent to 9 percent and similar improvements in median progression-free and overall survival.
The CAVE study, in her view, showed “a certain degree” of activity with this anti-EGFR treatment rechallenge strategy, though “not impressive” activity. However, she agreed that liquid biopsy may have a role in identifying best responders among previously treated, advanced colorectal cancer patients. She noted there are several other ongoing studies exploring an anti-EGFR rechallenge strategy in RAS wildtype metastatic colorectal cancer patients, and a few of them are even using ctDNA analysis to select patients.
- Growing Data on Vitrakvi Demonstrates Enduring Activity Across Variety of NTRK-Positive Tumor Types (Sep.24/20)
Adult and pediatric patients with refractory solid tumors characterized by NTRK gene fusions and treated with Bayer’s larotrectinib (Vitrakvi), on average, lived for more than three years without their tumors progressing.
Larotrectinib has accelerated approval in the US, Europe, and other regions as a treatment for refractory solid tumor patients with NTRK gene fusions who are out of treatment options. NTRK fusions are rare, occurring in 0.5%-1% of solid tumors. The US FDA approved the drug for a tissue-agnostic indication in November 2018 based on data on 55 patients who had a variety of tumor types, including melanoma, soft tissue sarcoma, infantile fibrosarcoma, cholangiocarcinoma, as well as salivary gland, thyroid, lung, melanoma, colon, gastrointestinal stromal, appendix, breast, and pancreatic cancers.
The expanded analysis involved 120 additional patients, bringing the total number of larotrectinib-treated patients across three studies to 175, including 116 adult and 59 pediatric patients. At the time of data cutoff on July 15, 2019, the overall response rate among 175 adult and pediatric patients with NTRK fusion-positive cancers was 78%, with 19% experiencing a complete response and 59% having partial responses.
Although the median duration of response is not yet mature, 81% of patients were responding at one year. At a median follow-up of 13.8 months, the median progression-free survival was 36.8 months. Median overall survival was not reached at 15.3 months follow up, though 90% of patients were alive at one year, and 83% were alive at two years.
- Molecular Profiling for mCRC (Sep.25/20)
According to researchers, a “better understanding of the heterogeneity of mCRC, including primary tumor location, microsatellite instability (MSI-High) status, and other clinically actionable tumor mutations, is reshaping the therapeutic landscape.”
The link below includes the interview with CancerNetwork®, in which Benjamin A. Weinberg, MD, assistant professor of medicine, Ruesch Center for the Cure of Gastrointestinal Cancers, and Samantha A. Armstrong, MD, a third year medical hematology/oncology fellow at Georgetown Lombardi Comprehensive Cancer Center, discuss the article and what the future may hold for colorectal cancer research.
- TRACON Pharmaceuticals Highlights Updated Envafolimab Clinical Results in MSI-H/MMR-D CRC (Sept.21/20)
Single agent envafolimab (PD-L1 inhibitor) was shown to have a 32% confirmed objective response rate (ORR) by review of 41 patients with MSI-H/MMR-D colorectal cancer (CRC) who failed a fluoropyrimidine, oxaliplatin and irinotecan, and had at least two tumor assessments. Duration of response (DOR) was greater than or equal to 12 months in 75% of patients and overall survival (OS) was greater than or equal to 12 months in 65% of patients. The ORR in the overall population was 43%, DOR was greater than or equal to 12 months in 92% of patients and OS was greater than or equal to 12 months in 75% of patients. The confirmed ORR in MSI-H/MMR-D CRC patients treated with envafolimab who failed a fluoropyrimidine, oxaliplatin and irinotecan was 32%. Envafolimab demonstrated good tolerability and safety, as there continued to be no infusion-related reactions.
- Higher ctDNA Fraction Decreases Survival in Regorafenib‐Treated mCRC Patients (Sep.19/20)
The objective of this study was to investigate a possible prognostic/predictive value of circulating tumor DNA (ctDNA) under regorafenib treatment. This phase II pilot study enrolled 30 metastatic colorectal cancer (CRC) patients (67% men, 33% women) treated with regorafenib. ctDNA was assessed in plasma before treatment start and at defined time points during administration. The results showed that the disease control rate was 30%. Median tumor fraction was 18.5%. Mutations in CRC driver genes or genes involved in angiogenesis (development of new blood vessels) were identified in 25 patients (83.3%). KRAS mutations were detected in 13 out of 14 KRAS positive tumors, in three patients without KRAS mutation in the respective tumor acquired mutations as a consequence of prior anti‐EGFR treatment were detected. A tumor fraction of 5% and higher at baseline was significantly associated with a decreased overall survival. ctDNA is detectable in a high proportion of mCRC patients. Higher ctDNA levels are associated with survival among regorafenib treatment. Despite the small sample size of this prospective study, the data demonstrates that the assessment and monitoring of ctDNA levels by integrating various genetic alterations is a promising approach and may have significant potential to improve monitoring in late stage CRC.
https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.33303
What is circulating tumor DNA (ctDNA) and how is it used to diagnose and manage cancer?
Circulating tumor DNA (ctDNA) is found in the bloodstream and refers to DNA that comes from cancerous cells and tumors. Most DNA is inside a cell’s nucleus. As a tumor grows, cells die and are replaced by new ones. The dead cells get broken down and their contents, including DNA, are released into the bloodstream. ctDNA are small pieces of DNA, usually comprising fewer than 200 building blocks (nucleotides) in length.
The quantity of ctDNA varies among individuals and depends on the type of tumor, its location, and for cancerous tumors, the cancer stage.
Detection of ctDNA can be helpful in the following cases:
- Detecting and diagnosing a tumor. Because tumor DNA has acquired multiple genetic mutations, leading to tumor development, ctDNA is not an exact match to the individual’s DNA. Finding DNA with genetic differences aids in tumor detection. Diagnosing the type of tumor using ctDNA can reduce the need for getting a sample of the tumor tissue (tumor biopsy), which can be challenging when a tumor is difficult to access, such as a tumor in the brain or lung.
- Guiding tumor-specific treatment. Analyzing the genome of tumor cells using ctDNA can help doctors determine which treatment will be most effective. Currently, however, approval from the U.S. Food and Drug Administration for ctDNA testing to personalize cancer treatment is limited.
- Monitoring treatment. A decrease in the quantity of ctDNA suggests the tumor is shrinking and treatment is successful.
- Monitoring periods with no symptoms (remission of cancer). A lack of ctDNA in the bloodstream indicates that the cancer has not returned.
Scientists have discovered that dying tumor cells release small pieces of their DNA into the bloodstream. These pieces are called cell-free circulating tumor DNA (ctDNA).
Source: https://medlineplus.gov/genetics/understanding/testing/circulatingtumordna/
Source: https://www.mycancergenome.org/content/page/circulating-dna/
SURGICAL THERAPIES
- 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.
http://sunnybrook.ca/content/?page=colorectal-colon-bowel-haip-chemotherapy
- 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.”
https://clinicaltrials.gov/ct2/show/NCT02864485
- A Life-Saving Transplant Trial (Oct.1/20)
Research conducted in Oslo, Norway has shown that patients with inoperable liver metastases from colorectal cancer (CRC) who receive a liver transplant have a 5-year survival rate of 60%. In Canada, transplantation hasn’t been an option for these patients due to a chronic shortfall of deceased liver donors. About 30% of Canadians waiting for a liver transplant actually die before they can get one.
Dr. Sapisochin, transplant surgeon with the Sprott Department of Surgery at the University Health Network in Toronto, launched a clinical trial in August 2016 to see if living donor liver transplants could become an effective treatment for these patients. While still investigational, the early results of the trial are promising. Dr. Sapisochin has completed two transplants so far and both patients are doing well. The first patient, who is 16 months post-op, had a recurrence in their lungs, but it is treatable and the patient is enjoying a good quality of life. The second patient, Sandra Elhilali, CCRAN Member, had her transplant a month later. About a year after her diagnosis, chemotherapy and surgery had successfully eradicated the cancer in Elhilali’s colon, but her liver was still full of tumours. “It looked like a spotted Dalmatian,” she recalls. “I knew I would have to look at alternative solutions”.
To qualify for a transplant, trial candidates must be monitored for at least 6 months to ensure their cancer remains stable and has not spread to any other organs. They also need to find someone they know who is willing to be a liver donor, is in good health and has a matching blood type. The liver is a large organ in which our major blood vessels are attached to, carrying a phenomenal amount of blood. To prevent blood loss, the surgeons clamp the various arteries and veins as they cut out the diseased liver, ensuring they leave enough length on the blood vessel for grafting of the donated lobe. The bile duct is then attached and the clamps are removed to restore blood flow.
Following her surgery, Elhilali remained in the hospital for two weeks to make sure none of the sutures were leaking, there were no infections and that she was responding well to the immunosuppressant drugs that would prevent her body from rejecting the new liver. She will continue to be monitored for five years as part of the clinical trial, so far she has remained cancer free. Dr. Sapisochin hopes to include 20 patients in the trial by 2023.
https://tgwhf.ca/about-us/publications/sprott-magazine-2020/
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
- Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer (Mar.12/20)
Magnetic resonance-guided focused ultrasound (MRg-FU) is a noninvasive, outpatient modality being investigated for the thermal treatment of cancer. In MRg-FU, a specially designed transducer is used to focus a beam of low-intensity ultrasound energy into a small volume at a specific target site in the body. MR is used to identify and delineate the tumour, focus the ultrasound beam on the target, and provide a real-time thermal mapping to ensure accurate heating of the designated target with minimal effect to the adjacent healthy tissue. The focused ultrasound beam produces therapeutic hyperthermia (40-42°C) in the target field, causing protein denaturation and cell damage. Currently, there is no prospective clinical data reported on the use of MRg-FU in the setting of recurrent rectal cancer. Recurrent rectal cancer is a vexing clinical problem. Current retreatment protocols have limited efficacy. The addition of hyperthermia to radiation and chemotherapy may enhance the therapeutic response. With recent advances in technology, the investigators hypothesize that MRg-FU is technically feasible and can be safely used in combination with concurrent reirradiation and chemotherapy for the treatment of recurrent rectal cancer without increased side-effects. The study is being offered at the Odette Cancer Centre. Here is the link to the study protocol:
- Trials Confirm Preoperative Chemo-Radiation Improves Outcomes for Rectal Cancer (Jun.01/20)
Results from a large clinical trial continue to provide evidence that treatment with pre-operative radiation significantly decreases local cancer recurrences in patients with rectal cancer that has not spread to distant sites and should be considered the standard of care for this disease. A decrease in cancer recurrences often correlates to improved long-term survival. The goal of pre-operative radiation is to shrink cancer and kill undetectable cancer cells that may exist directly outside the site of cancer origin. By shrinking the site of cancer and killing nearby cancer cells, more complete surgical removal of the cancer may be obtained, resulting in fewer recurrences and improved chances for a cure. According to the results of the phase 3 RAPIDO clinical trial released at the 2020 American Society of Clinical Oncology Annual Meeting, pre-operative short-course radiation therapy (RT) followed by chemotherapy should be the new standard of care for treating locally advanced rectal cancer. One group of patients received short-course RT followed by 6 cycles of CAPOX or 9 cycles of FOLFOX4 chemotherapy followed by surgical removal of the cancer and this was compared to “standard” therapy consisting of capecitabine-based chemo-radiotherapy and surgery.
Patients participating in this trial have now been followed in excess of 4.5 years. The 3-year probability of disease-related treatment failure is 23.7% in the short course RT group compared to 30.4% in the standard treatment group. The improved outcomes were attributed to a lower rate of distant cancer spread and this resulted in a 3-year overall survival rate of 89% for those treated with the pre-surgery short-course RT followed by chemotherapy before surgery.
SCREENING
- Screening Colonoscopy Reduces Deaths from CRC (Aug.08/20)
A colonoscopy is the preferred method for detecting early colon cancer and is recommended every 5-10 years beginning at age 40-50 years for average-risk individuals, according to this study. During a colonoscopy, a flexible tube attached to a camera is inserted through the rectum, allowing physicians to examine the internal lining of the colon and rectum for cancer or precancerous polyps. If polyps are identified, they can be removed during the colonoscopy. Such identification and removal of polyps during screening colonoscopy substantially reduces the risk of death from colorectal cancer (CRC).
A study published in the New England Journal of Medicine evaluated information from 2,602 people who had precancerous polyps removed during colonoscopy. During more than 15 years of follow-up, people who had had colorectal polyps removed during colonoscopy were roughly half as likely to die of CRC as people in the general population.
OTHER
- Young Adult Colorectal Cancer Clinic Available at Sunnybrook (Mar.12/20)
A recent study led by the University of Toronto doctors has observed a rise in colorectal cancer rates in patients under the age of 50. The study mirrors findings from the U.S., Australia and Europe. The growing colorectal cancer rates in young people come after decades of declining rates in people over 50, which have occurred most likely due to increased use of colorectal cancer screening (through population-based screening programs) which can identify and remove precancerous polyps. Patients diagnosed under the age of 50 have a unique set of needs, challenges and worries. They are unlike those diagnosed over the age of 50. Dr. Shady Ashamalla (colorectal cancer surgical oncologist), and his team at the Sunnybrook Health Sciences Centre understand the needs of this patient population.
Dr. Ashamalla belongs to a multidisciplinary team of experts in the Young Adult Colorectal Cancer Clinic who will work with young colorectal cancer patients, regardless of disease stage, to create an individualized treatment plan to support each patient through their cancer journey. Their needs and concerns will be addressed as they relate to:
- Fertility concerns and issues
- Young children at home
- Dating/intimacy issues
- Challenges at work
- Concerns about hereditary cancer
- Relationships with family and friends
- Psychological stress due to any or all of the above
The team of experts consists of:
- Oncologists (medical, surgical, radiation)
- Social workers
- Psychologists
- Geneticists
- Nurse navigator
Should a patient wish to be referred to Sunnybrook, they may have their primary care physician, or their specialist refer them to Sunnybrook via the e-referral form, which can be accessed through the link appearing below. Once the referral is received, the Young Adult Colorectal Cancer Clinic will be notified if the patient is under the age of 50. An appointment will then be issued wherein the patient will meet with various members of the team to address their specific set of concerns.
http://sunnybrook.ca/content/?page=young-adult-colorectal-cancer-clinic
- The Importance of Getting a Second Opinion (Sep.02/20)
A second opinion is a review of the cancer diagnosis and the treatment recommendations of the physician who is treating the cancer by another, independent physician. Usually, patients obtain a second opinion after being referred to a second physician or to a special team of experts in a cancer center, called a multidisciplinary team through a tumour board review. Second opinions are more likely to be comprehensive, or inclusive of every possible perspective, when performed in a cancer center with a multidisciplinary team.
The treatment of cancer has evolved tremendously. As a result, many cancers are now more treatable than they once were, especially if the appropriate initial treatment is selected. In order to receive appropriate treatment, patients must understand the type of cancer they have and the treatment options that are available. However, there are also many more options for treatment and these options are more complicated than in the past. For these reasons and others, it is advantageous to seek more than one opinion about how your cancer can be treated.
If you decide to obtain an independent second opinion, it is important to communicate with the primary physician not only to obtain needed information for review, but also to keep the treating physician informed. Most of the time, you simply need to make sure you are getting the best advice.
Image Source: https://www.yalemedicine.org/stories/second-opinions/
- Neuropathy (Numbness and Tingling) Prevention and Treatment (Oct.10/20)
Neuropathy means “disease of the nerves.” The peripheral nerves are those that branch out from the spinal cord into the arms and legs. “The peripheral nervous system is like the body’s electrical wiring,” says Tina Tockarshewsky, executive director of the Neuropathy Association, “When the peripheral nerves are damaged, the electrical system goes haywire. Sometimes there are sparks, and sometimes the lights go out.” Colorectal cancer patients may suffer from peripheral neuropathy when undergoing treatments for their colorectal cancer. Treatments such as oxaliplatin may cause tingling and numbness.
Pain and numbness, particularly in the hands and feet, are hallmark symptoms of PN (peripheral neuropathy). The condition can also cause a wide variety of other symptoms, depending on which nerves are damaged. These other symptoms include:
- Blurred vision
- Constipation
- Difficulty with fine motor tasks (such as buttoning, picking up small objects, and turning pages)
- Dizziness, loss of balance, stumbling, or tripping when walking
- Hearing loss or ringing in the ears (tinnitus)
- Loss of sensitivity to heat and cold
- Painful, electric shock–like sensations in the spine
- Tingling or burning sensations in the extremities (“pins and needles”)
The symptoms may begin during or after cancer treatment. They tend to worsen over time, and they may persist for a year or more after treatment is completed. For many patients, damaged nerves do eventually heal and symptoms clear up. For some patients, however, the nerve damage—and the symptoms—may be permanent.
Understanding what causes PN symptoms can reduce feelings of fear and panic and help patients feel more in control. In addition, some simple lifestyle changes can help patients deal with its effects on daily life.
- Use a night-light to reduce the risk of stumbling in the dark.
- Install grab bars in the shower or sit on a stool while showering.
- Sleep with the head elevated 30 degrees to reduce dizziness on rising.
- Use specially designed utensils to make it easier to eat with numb fingers.
Image Source: https://www.verywellhealth.com/nerve-tingling-is-it-a-stroke-3145943
- Prevalence of Colorectal Cancers in Adults Younger than 50 (Sep.14/20)
The American Cancer Society (ACS) recommends screening for colorectal cancer (CRC) in average-risk individuals starting at age 45 years. However, there is little population-based data regarding the prevalence of precursor colorectal polyps in average-risk individuals younger than 50. To fill this data gap, investigators identified nearly 41,000 colonoscopy recipients; colonoscopy indication was screening in those aged ≥50 years and “screening equivalent” in the 14% who were younger than 50. “Screening equivalent” referred to low-risk diagnostic indications (abdominal pain, constipation) or screening.
The results were as follows:
- The prevalence of advanced neoplasia (AN) was similar between those aged 45–49 (3.7%) and 50–54 (3.6%).
- The prevalence of clinically significant serrated polyp (CSSP) was also similar between the two groups (5.9% and 6.1%, respectively).
- Adjusted odds ratios for AN (3.6–3.7) and CSSP (2.2–2.4) were similar between the two age groups.
- AN prevalence was 1% in those aged <40 years, 3% in those 40–44 years, and 6.7% after age 60.
- Sensitivity analyses that varied diagnostic indications and family history of CRC supported the main findings.
https://www.jwatch.org/na52408/2020/09/14/prevalence-colorectal-neoplasia-adults-younger-50
- Incidence of Young-Onset CRC in Canada Continues to Increase (Sep.28/20)
Despite decreases in the overall incidence of colorectal cancer (CRC) in Canada, a concerning increase has been observed among adults under the age of 50 in recent years. The aim of this study was to update age-specific incidence trends of CRC from 1971 to 2017 in Canada. Data was obtained from the National Cancer Incidence Reporting System and the Canadian Cancer Registry. Results highlighted the importance of future studies examining potential risk factors responsible for these trends among young adults. While obesity, poor diet, and sedentary behaviour have been hypothesized as culprits, there are a lack of studies that have examined risk factors for young-onset CRC. Additionally, in the last 10 years in Canada the largest increases have occurred among the 20−29 age group for colon cancer and the 30−39 age group for rectal cancer, respectively. These results suggest that early life exposures and exposures novel to recent cohorts could play a role in these increases.
The incidence of CRC among young adults, particularly those under 40, continues to increase among men and women in Canada. Studies examining potential risk factors for young-onset CRC are required. Moreover, incidence trends by geographical location and socioeconomic status should be explored since this could have relevance for healthcare interventions.
https://www.sciencedirect.com/science/article/pii/S1877782120301624
- How Medical Marijuana Helps To Ease Cancer Treatment Side Effects (Jul.24/20)
Various medical uses and health benefits have been attributed to medical marijuana. In fact, a medicine derived from cannabis known for its generic name Nabiximols is a mainstay medication for treating the spasticity and neuropathic pain caused by diseases like multiple sclerosis and cancer. Much of the scientifically proven benefits of marijuana for a cancer patient is in the management of the symptoms and side effects of cancer therapies. Marijuana’s benefits for cancer are still being investigated and no specific study has conclusively found that marijuana can cure cancer. Both the American Cancer Society and the American Psychological Association have also observed that marijuana research, despite the leaps and bounds gained throughout the years, has many stumbling blocks. Thus, both organizations have called upon the federal government to cultivate an enabling environment for scientists to conduct scientific studies on marijuana.
Image Source: https://www.forbes.com/sites/sarabrittanysomerset/2019/07/11/of-mice-and-men-is-cbd-toxic-to-the-liver/
- Flu Shot 101 – What You Need to Know for the Influenza Season (Sep.09/20)
The flu, also known as influenza, is a respiratory virus that is able to mutate and evolve over time. Therefore, the vaccine needs to change and evolve as well to keep people protected every year. Because parts of the world experience flu season at opposite times, there are actually two vaccines developed every year – one for the northern hemisphere and one for the southern hemisphere. Each vaccine is developed nine months prior to flu season in a collaborative effort between the World Health Organization (WHO), the FDA, and the CDC.
Everyone is at risk for the flu, and therefore with a few exceptions, it is recommended that everyone get vaccinated. Some research has suggested that cancer survivors are less likely than other people to receive routine preventive care or management of chronic conditions such as diabetes or heart disease. Flu vaccines are an important part of preventive care, particularly for people with a history of cancer or certain other health conditions. As a cancer survivor, you’re at increased risk of complications from the flu. These complications can lead to hospitalization or even death. To prevent the flu, cancer patients, cancer survivors and people who live with someone with a history of cancer are advised to get both a seasonal flu shot and an H1N1 flu shot (not the nasal spray vaccines).
Image Source: https://www.limestone.on.ca/news/what_s_new/public_health_urges_families_to_get_flu_shot
- CRC in Young People (Oct.09/20)
The decline in the incidence and mortality of colorectal cancer (CRC) has declined among all races and ethnicities in the United States, but at different rates. The incidence rates of CRC differs across racial subgroups, with the highest incidence among non-Hispanic Black individuals, followed by American Indian/Alaskan Native, and non-Hispanic White individuals, with the lowest rates among Asian Americans/Pacific Islanders.
The incidence of CRC was 50% higher among Black individuals than Asian Americans/Pacific Islander individuals, and 20% higher than White individuals between 2012 and 2016. This disparity persists among young people, among whom the proportion of CRC diagnoses is highest among non-Hispanic Black individuals at 16% compared with 9% among non-Hispanic White patients. The rate of death due to CRC also differs by race/ethnicity. Regardless of stage of disease, the longest overall survival is found among Asian American/Pacific Islander groups, followed by Hispanic groups, non-Hispanic American Indian/Alaskan Native groups, and non-Hispanic White groups, with the shortest survival found among non-Hispanic Black groups.
Approximately 44% of racial disparities are attributable to risk factors, whereas the remaining are likely due to socioeconomic status and access to screening and treatment. This trend is also present among young people with CRC. The established risk factors for CRC — regardless of a person’s age — include obesity, smoking, diet (eg, alcohol, red or processed meats, micronutrients), exercise, a sedentary lifestyle, and certain chronic conditions.
Patients can lower their risk of CRC by changing their lifestyle and habits, but also being aware of potential symptoms of CRC. Patients should begin CRC screening by age 45, but should also report any potential symptoms to their health care provider at any age.
- Study Shows Disparities in Access to Molecular Diagnostics for CRC (Oct.05/20)
Study results presented at American Association for Cancer Research Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, showed testing occurred less frequently among:
- older patients,
- those in historically underrepresented groups, and
- among uninsured or Medicaid-insured patients.
Researchers used multivariable logistic regression to evaluate the association between MSI and MMR-D testing and patient demographic, socioeconomic and care setting characteristics, as well as with receipt of immunotherapy.
Results showed 26.5% of patients underwent MSI and MMR-D testing. Older age was significantly associated with a lower likelihood to undergo testing (age 70-79 years vs. 60-69 years). Testing also appeared less common among men and Blacks compared with whites. Moreover, testing was less common among patients who were uninsured, Medicaid-insured and Medicare-insured compared with privately insured, as well as among those diagnosed at a community or comprehensive community cancer program compared with those diagnosed at an academic or NCI comprehensive cancer program.
Given this study, researchers are finding that many of the same socioeconomic factors associated with disparities in patients’ access to treatment and high-quality care are also associated with disparities in access to molecular testing. More research is needed to convert what they are learning from national data into effective strategies for reducing those disparities. For their projects, that means finding ways to improve cancer patients’ access to critical molecular diagnostics.
NUTRITION/HEALTHY LIFESTYLE
- Healthy Lifestyle Improves CRC Outcomes (Oct.13/20)
Lifestyle risk factors for colorectal cancer (CRC) include:
- obesity,
- physical inactivity,
- smoking,
- heavy alcohol consumption,
- a diet high in red or processed meats,
- and a diet inadequate in fruits and vegetables.
High Fruit and Veggie Intake Reduces Development of Colorectal Adenomas in Women
According to an article recently published in Cancer Research, high consumption of fruit and vegetables significantly reduces the incidence of colorectal polyps among women.
Results from the study showed:
- Women who ate five or more servings of fruit per day had a 40% reduced incidence of colorectal polyps.
- Women who ate five or more servings of vegetables per day had a 38% reduced incidence of colorectal polyps.
- Women who ate four or more servings of legumes per week had a 33% reduced incidence of colorectal polyps.
Alcohol and Tobacco Use Linked with Younger Age at Colorectal Cancer Diagnosis
A study published in the Archives of Internal Medicine reports that current users of alcohol and tobacco are diagnosed with CRC at a younger age than non-users of alcohol and tobacco.
Results confirmed:
- Current users of both alcohol and tobacco had an average age at CRC diagnosis of 63 years, eight years younger than the average age among individuals who never smoked or drank.
- Use of alcohol and tobacco influenced the location of the CRC. Users were more likely than non-users to have distal cancers (cancers in the rectum or the lower part of the colon).
- Gender also influenced age at CRC diagnosis and location. Men were diagnosed at a younger age than women, and were more likely to have distal cancers.
Heart Disease and Diabetes Increase Risk of Colorectal Cancer
According to results presented at the 2006 Digestive Disease Week meeting, individuals who are diabetic or those with coronary artery disease have an increased risk of developing CRC. This study included 100 women with diabetes and 500 women who did not have diabetes.
- 37% of women with diabetes had an adenoma, versus 24% for those who were not diabetic.
- 14% of women with diabetes had advanced adenomas, compared with 6% of women without diabetes.
- At 42%, obese women with diabetes had the highest incidence of adenomas, and non-obese, non-diabetic women had the lowest rate of adenomas (23%).
Image Source: https://www.vectorstock.com/royalty-free-vector/no-smoking-no-drinking-vector-2496726
- Top 12 Foods to Improve Your Health (Aug.30/20)
California Health & Longevity Institute suggests how to stock your pantry to avoid bad food choice.
- Canned beans. Keep a variety of canned beans on hand (kidney, black, pinto) for a quick and easy source of vegetarian protein. Rinse and drain them, then eat with brown rice and salsa, use to make your own hummus or bean spreads, or add to pasta, salads, and soups.
- Frozen vegetables. Look for “steam fresh” varieties for quick and easy veggie sides. Add to take-out, pasta, salads, and low-sodium canned soups to incorporate a variety of veggies year-round.
- Frozen fruit. Frozen fruit is better than imported when fruits are not in season. Use frozen berries, mangoes, and peaches in smoothies, oatmeal, and desserts.
- Foil-packed wild salmon. Use salmon in place of tuna to avoid mercury and for a full dose of healthy omega-3 fats. No need for refrigeration or a can opener—just open the package and use in sandwiches, salads, and pastas.
- Organic non-fat Greek yogurt. Keep calories under 130 to control sugar content. Add to smoothies, mix with fruit and nuts, or top with crunchy cereal. It’s a great source of protein and probiotics.
- Nuts. Eight walnut halves or 12 almonds equal one serving of nuts. Add to salads or pair with fresh fruit for a filling dose of protein, fibre, and healthy fat.
- Double-fibre English muffins. Fibre helps keep us full, regulate blood sugar, and manage body weight. Use these muffins for sandwiches, pizza, or breakfast to help reach your daily fibre quota (25 to 30 grams). One whole English muffin is equal to only one carbohydrate serving.
- Frozen shelled edamame (soybeans). For a quick and easy source of vegetarian protein, use edamame in soups, salads, and snacks.
- Oatmeal. Real, whole, unprocessed oats are a great option for breakfast; add fruit, nuts, and cinnamon for extra flavour and nutritional value. (Avoid instant packets due to sugar and sodium content.)
- Shredded wheat with bran. Add this to your morning routine. Shredded wheat is as unprocessed as it gets; it contains no additives and only two ingredients (wheat and bran).
- Tomatoes. Get tomatoes any way that you can. Use fresh, sundried, or boxed tomatoes in soups, sauces, and pasta. Boxed Pomi tomatoes do not have the harmful BPA (Bisphenol A) found in canned tomatoes. Add fresh tomatoes to everything, and try cocktail tomatoes by the handful for a sweet snack.
- Apples. Buy organic apples and leave the peel on. The peel provides much of the fibre found in apples; just be sure to wash well before eating. Add diced apples to your oatmeal, slice thinly for salads, or enjoy whole as a quick snack.
- Researchers Find Changing Gut Microbiota, Taming Inflammation May Help Battle CRC (Sep.21/20)
Findings from a study led by University of Florida researchers suggests that colon cancer may be treated or even prevented by altering microorganisms in the intestine and by combating inflammation with a clinical treatment previously used to treat inflammatory bowel diseases. Inside a human gut resides trillions of microorganisms, which are collectively termed microbiota. Research has linked microbiota activity to a variety of diseases. Particularly in the gut, an abnormal microbiota can contribute to inflammation and colorectal cancer (CRC) development. Previous research has shown that people with inflammatory bowel disease have a higher risk of developing CRC.
Ye Yang, Ph.D., assistant scientist in the UF College of Medicine’s division of gastroenterology, hepatology and nutrition, and his team studied how combating inflammation using an anti-inflammatory treatment could affect colon cancer development in mice. Mice with colon cancer and inflammation were treated with an anti-inflammatory therapy known as anti-tumor necrosis factor (TNF therapy), which is a drug typically used to treat inflammatory bowel disease.
The study found that after anti-TNF therapy, the microbiota was less capable of driving cancer development. Therefore, reducing inflammation changes the microbiota from a pro-cancer to an anti-cancer state. This study suggests further research needs to be done to understand interaction between certain therapies, the microbiota and cancer development. “We need to pay more attention to the microbiota changes in response to inflammation-targeting drugs and figure out the best way to manipulate the microbiota for cancer prevention in patients,” Yang said.
Image Source: https://badgut.org/information-centre/a-z-digestive-topics/gut-microbiota-balanced/
- Tips for Dealing with Fatigue (Aug.15/20)
Fatigue is a common side effect that is experienced by individuals with cancer and may persist for months after completing treatment. Fatigue may be caused by the disease itself and may also be a side effect of therapy. Left unchecked, it can lead to severe consequences such as malnutrition and dehydration, which contribute to additional fatigue, thus creating a dangerous cycle. The best advice for people with cancer treatment fatigue is to eat a balanced diet that includes protein foods such as meat, eggs, cheese, peas, and beans and to drink 8 to 10 glasses of fluids per day. Preventing malnutrition and dehydration can help keep baseline energy levels up and provide the body with the fuel it needs to maintain basic activities.
Here are some tips to make meeting your nutritional needs easier during this difficult time:
- Ask for help. Friends and family members are usually happy to prepare meals or go to the grocery store.
- Set a timer for 60-minute intervals. Eat a few bites and drink some fluids every time the timer goes off.
- Eat a few bites every time a commercial comes on TV.
- Keep a cooler or mini refrigerator in the room where you rest or next to your chair or bed. Keep it stocked with yogurt, pudding, cheese, milk, juice, or nutritional supplement drinks.
- Keep nonperishable food items such as nuts, dried fruit, juice boxes, crackers, and peanut butter next to your chair or bed and nibble often.
- Eat high-calorie, high-protein foods to maximize your nutritional intake.
Exercise reduces fatigue and improves strength, physical functioning, and emotional wellbeing in men and women undergoing chemotherapy, according to the results of a study published in the British Medical Journal. A randomized, controlled trial in Denmark involved 269 cancer patients (73 men, 196 women) ranging in age from 20-65 years. Patients were randomized to receive conventional care only or conventional care plus a supervised exercise program that included high-intensity cardiovascular and resistance training, relaxation and body awareness training, and massage for a total of nine hours per week for 6 weeks. The results indicated that patients in the exercise group experienced a significant reduction in fatigue. In addition, they had improved vitality, aerobic capacity, muscular strength, emotional wellbeing, and physical and functional activity. However, there was not a significant effect on quality of life.
https://news.cancerconnect.com/treatment-care/tips-for-dealing-with-fatigue-943YhFvlC0SfymaL83Fy-g
- Exercise and CRC (Sep.24/20)
Observational findings indicate that physical activity is associated with higher overall, as well as disease-specific survival in individuals with colorectal cancer (CRC). Specifically, following CRC, higher post-diagnosis physical activity has shown to be protective against cancer-specific mortality and all-cause mortality. This meta-analysis evaluated the safety, feasibility and effect of exercise among individuals with colorectal cancer.
For the 19 trials included, there was no difference in adverse event risk between exercise and usual care (UC). Median withdrawal rate was 12% and adherence was 86%. Significant effects of exercise compared to UC were observed for quality of life (QoL), fatigue, aerobic fitness, upper-body strength, depression, sleep and reduced body fat. Subgroup analyses suggested larger benefits for Quality of Life (QoL) and fatigue for supervised interventions; for QoL, aerobic fitness and reduced body fat for ≥12-week interventions; and for aerobic fitness when interventions were during chemotherapy.
Therefore, findings support that exercise is safe and feasible in CRC. Further, participation in mixed-mode exercise, including unsupervised exercise, leads to improvements in various health-related outcomes.
https://ijbnpa.biomedcentral.com/articles/10.1186/s12966-020-01021-7
Image Source: https://visionexercisephysiology.com.au/top-tips-for-starting-an-exercise-regime-lauren-turner-aep/
- Drinking Coffee Tied to Better Outcomes in Colon Cancer Patients (Sep.23/20)
A new study suggests that drinking coffee may extend survival time in people with colorectal cancer (CRC). Both regular and decaf coffee stimulates colonic motor activity. For some people, a cup of coffee can have a laxative effect. Chen Yuan, SCD and Kimmie Ng, MD, MPH noted that it’s not clear whether how you take your coffee (milk, sugar, both, or neither) has an effect on colon health—especially for patients with metastatic CRC.
The study included 1,171 patients diagnosed with advanced or metastatic colon or rectal cancer who could not be treated with surgery. The patients completed diet and lifestyle questionnaires, including information about their coffee consumption, at the start of the study. Compared with people who drank none, those who drank a cup a day had an 11 percent increased rate of overall survival (OS), and a 5% increased rate of living progression-free. The more coffee they drank, the better. Those who drank four or more cups a day had a 36% increased rate of OS and a 22% increased rate of surviving without their disease getting worse. Whether the coffee was decaf or regular made little difference.
The co-lead author, Christopher Mackintosh, a fourth-year medical student at the Mayo Clinic Alix School of Medicine, emphasized that drinking coffee is not a cure or treatment for cancer. “If a patient already drinks coffee,” he said, “they should feel fine about it. They won’t harm themselves. But I would not suggest that people begin drinking coffee to try to treat or prevent cancer.”
https://www.verywellhealth.com/coffee-longer-survival-colorectal-cancer-patients-5081385
Image Source: https://www.kickinghorsecoffee.com/en/coffee/ground
- Will Curcumin be a Valid Therapy for CRC? (Oct.02/20)
“Previous findings from our group have shown that curcumin could enhance the therapeutic action of some important chemotherapy drugs that are currently given to colorectal cancer patients, so we decided to take a look at all the studies that have been done recently on curcumin as a treatment for this disease” says Vicenç Ruiz de Porras of the Germans Trias Pujol Research Institute and the Badalona Applied Research Group in Oncology of the Catalan Institute of Oncology.
Curcumin, the active ingredient in turmeric, has been used for centuries in Ayurveda medicine and many claims are made for it being good for people with inflammation and several diseases including colon cancer. However, to be used as a therapy, proper clinical trials must be carried out to find out if it is safe and also if it will negatively affect other therapies already in use. It is also difficult for the body to take up curcumin, simply from eating turmeric or curcumin extract, so finding the best way to administer it is important.
On its own, curcumin has been shown to have anti-cancer effects on cells and living animals. It interacts with many different processes in cells that affect proliferation, cell death, the ability of cells to travel and form metastases or for larger tumours to grow blood vessels. “Most chemotherapies work on these same pathways, so it is vital to understand the interaction between them and curcumin,” explains Martinez-Balibrea, lead author. “In fact there is some evidence that curcumin will slow resistance to certain therapies.”
The news is promising for curcumin in CRC treatment, but it is not ready for use within standard treatment programs yet. Many of these studies are very preliminary or are in early stages. Large trials are needed in order to demonstrate that curcumin improves current treatments, especially by using new promising bioavailable formulations.
Image Source: https://www.healthline.com/nutrition/turmeric-vs-curcumin#turmeric-vs-curcumin
- These Foods and Medications May Lower Bowel Cancer Risk (Oct.07/20)
A review of 80 studies conducted by a team of scientists located in France, the Netherlands and Canada found that some foods and medications may help prevent colorectal cancer (CRC). The review found that medications like aspirin, low-dose aspirin and NSAIDS (the class of medications that aspirin belongs to) were associated with decreased risk. Nutritional factors that were associated with decreased risk included magnesium, folate, dairy products, fiber, soy, fruits, and vegetables. The review dealt with a population with average risk. Those with a history of adenoma (polyp) removal, diabetes, inflammatory bowel disease, or genetic factors that increase the risk for colorectal cancer were excluded. It was noted however, that the level of evidence appears to be “low to very low”.
Image Source: https://www.diabetes.co.uk/blog/2019/01/13-easy-ways-to-add-fibre-to-your-diet/
COVID-19 UPDATES
- 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.
https://www.who.int/news-room/q-a-detail/q-acoronaviruses)
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.
https://www.who.int/news-room/q-adetail/q-a-coronaviruses
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!
Source: https://www.who.int/news-room/q-a-detail/q-acoronaviruses
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.
https://www.cancer.gov/contact/emergencypreparedness/coronavirus
Should you wish to contact your local public health agency, please see below.
Alberta
COVID-19 info for Albertans
Social media: Instagram @albertahealthservices, Facebook @albertahealthservices, Twitter @GoAHealth
Phone number: 811
British Columbia
British Columbia COVID-19
Social media: Facebook @ImmunizeBC, Twitter @CDCofBC
Phone number: 811
Manitoba
Manitoba COVID-19
Social media: Facebook @manitobagovernment, Twitter @mbgov
Phone number: 1-888-315-9257
New Brunswick
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
Northwest Territories coronavirus disease (COVID-19)
Social media: Facebook @NTHSSA
Phone number: 811
Nova Scotia
Nova Scotia novel coronavirus (COVID-19)
Social media: Facebook @NovaScotiaHealthAuthority , Twitter @healthns, Instagram @novascotiahealthauthority
Phone number: 811
Nunavut
Nunavut COVID-19 (novel coronavirus)
Social media: Facebook @GovofNunavut , Twitter @GovofNunavut, Instagram @governmentofnunavut
Phone number: 1-888-975-8601
Ontario
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,
Quebec
Coronavirus disease (COVID-19) in Québec
Social media: Facebook @GouvQc, Twitter @sante_qc
Phone number: 1-877-644-4545
Saskatchewan
Saskatchewan COVID-19
Social media: Facebook @SKGov, Twitter @SKGov
Phone number: 811
Yukon
Yukon: Find information about coronavirus (COVID-19)
Social media: Facebook @yukonhss, Twitter @hssyukon
Phone number: 811
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