The following colorectal cancer research updates extend from June 30th, 2019 to September 20th , 2019 inclusive and are intended for informational purposes only.
DRUGS / SYSTEMIC THERAPIES
- Immunotherapy Keytruda – approved by Health Canada for the treatment of MSI-H and dMMR colorectal cancer
- Phase II LEAP Clinical Trial To Treat mCRC
- Daily aspirin reduces bowel cancer risk in people with Lynch syndrome
- BEACON Results Light Way for Chemo-Free Therapy in Colorectal Cancer
- Health Canada approves VITRAKVI (Larotrectinib), first tumour agnostic cancer treatment for advanced solid tumours harbouring an NTRK gene fusion
- Tumour mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer
- NGS Testing Available at Sick Kids through Dr. Cynthia Hawkins
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Hospital
- Living donor liver transplantation for unresectable colorectal cancer liver metastases
- Adjuvant HIPEC in Advanced CRC
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
- New Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer
- Psychosocial factors increase complication risk with cancer surgery
- Candirect research study: Learn more about a study for patients who have completed their cancer treatments and are experiencing low mood
- Global analysis finds early onset colorectal cancer rising in many high-income countries
- Sidedness of colorectal cancer impacts risk of second primary gastrointestinal malignancy
- More young Canadians are getting colorectal cancer, study finds
- Young CRC Patients Are Going Undiagnosed
- Some dying cancer patients still receive active therapies
- Young adult colorectal cancer clinic available at Sunnybrook Hospital
NUTRITION/ HEALTHY LIFESTYLE
- Physically active people have lower colon cancer risk
- How sugary drinks can fuel and accelerate cancer growth
- Colon cancer: could exercise halt tumour growth?
- Omega -3 Fish oil intake linked to small colorectal cancer risk reduction
- Exercise for adults diagnosed with rectal cancer: a feasibility study
- A Phase III study of the impact of a physical activity program on disease-free survival in patients with high risk stage II or stage III colon cancer: a randomized controlled trial (CHALLENGE)
- High dose vitamin D supplementation in Stage 4 colorectal cancer patients
- SUNSHINE trial: high-dose vitamin D may benefit patients with metastatic colorectal cancer
- Study Looking for Female Survivors to participate in an Exercise Program
DRUGS / SYSTEMIC THERAPIES
- Immunotherapy Keytruda – approved by Health Canada for the treatment of MSI-H and dMMR colorectal cancer (Apr 18/19)
The immunotherapy Keytruda (pembrolizumab) is a monoclonal antibody or targeted cancer therapy that is directed against the PD-1 (programmed cell death – 1) receptor on the cancer cell surface. The drug blocks the PD-1 receptor, preventing the binding and activation by its ligands PD-L1 and PD-L2. By blocking this interaction, T-cell (an immune cell) mediated immune responses are activated against tumour cells.
As of April 18, 2019, Keytruda has been issued a marketing authorization with conditions in Canada, pending the results of studies to verify its clinical benefit. The drug is indicated for adult patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC), whose tumours have progressed following treatment with a fluoropyrimidine, oxaliplatin and irinotecan regimen. For more information on Keytruda: www.keytruda.com, and for Health Canada’s Notice of Compliance with conditions – drug products website: https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/notice-compliance/conditions.html#k.
Keytruda blocking the PD-1 receptor to prevent interaction with the PD-L1 and PD-L2 ligands, thereby activating T-cell mediated immune responses against tumour cells.
- Phase II LEAP Clinical Trial For mCRC (Sept 20/19)
The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in patients with triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), or biliary tract cancers (BTC). Participants will be enrolled into initial tumor-specific cohorts which will be expanded if adequate efficacy is determined. The trial is available at the Odette Cancer Centre and at the Princess Margaret Cancer Centre in Toronto as well as the following Centres throughout Canada: Abbotsford, BC; Winnipeg, MB; CHU de Quebec. More information may be obtained by visiting the link below.
- Daily aspirin reduces bowel cancer risk in people with Lynch syndrome (Aug 5/19)
Taking a daily aspirin for more than two years could reduce the risk of bowel cancer in people with Lynch syndrome, according to new draft guidance from National Institute for health and Care Excellence (NICE). People with the inherited condition have an increased risk of developing a number of different cancers. It’s estimated that 4 in 5 will develop bowel (colorectal) cancer during their lifetime. Results from clinical trials showed that “taking daily aspirin for more than two years reduces the risk of colorectal cancer in people with Lynch syndrome. NICE’s draft guidance comes after reviewing evidence from a clinical trial, in which 427 people with Lynch syndrome were assigned to take aspirin, and a separate group of 434 patients were given a dummy drug (placebo). Nearly 5 years later, 18 of those who took aspirin had developed bowel cancer, as opposed to 30 of those given the placebo. Reduction in bowel cancer risk was seen after 2 years of taking aspirin. Referring to the risks associated with long-term use of aspirin, for those with Lynch syndrome, the benefits are likely to outweigh any potential harms. Trials are ongoing to find out what the most effective dose of aspirin is for people with Lynch syndrome. With research still ongoing, patients should consult their doctor before taking aspirin as a preventative medicine, he added.
NICE (2019) Effectiveness of aspirin in the prevention of colorectal cancer in people with Lynch syndrome. https://www.nice.org.uk/guidance/gid-ng10060/documents/evidence-review
- BEACON Results Light Way for Chemo-Free Therapy in Colorectal Cancer (August 1/19)
New results from the BEACON clinical trial offer hope for a chemotherapy-free treatment option for certain patients with colorectal cancer (CRC). Combinations of targeted therapies yielded significantly improved response rates and overall survival rates compared with traditional chemotherapy regimens among patients with previously treated BRAF V600E–mutated metastatic CRC. This BRAF V600E mutation is found in 10% to 15% of metastatic CRC patients and is usually associated with a poor prognosis. The BEACON trial had three treatment arms.
One group (Group I) of patients received triplet therapy with three targeted agents —
- the BRAF inhibitor encorafenib (Braftovi, Array BioPharma),
- the MEK inhibitor binimetinib (Mektovi, Array BioPharma), and
- the EGFR inhibitor monoclonal antibody cetuximab (Erbitux, Eli Lilly).
Another group (Group II) received doublet targeted therapy with encorafenib and cetuximab.
A third (control) group received standard chemotherapy (FOLFIRI).
The new results, presented at the World Conference on Gastrointestinal Cancer (WCGC) 2019, were from an initially unplanned interim analysis. Presenter Scott Kopetz, MD, PhD, from the University of Texas MD Anderson Cancer Center, Houston, showed that the triplet therapy was associated with a remarkable 48% improvement in overall survival vs standard chemotherapy. Furthermore, progression-free survival (PFS) was improved by 62%, at 4.3 months with the triplet regimen vs 1.5 months with standard therapy. This improvement was reflected in a highly significant increase in the objective response rate (ORR) with triplet therapy, at 26%. ORR increased to 34% among patients who had previously received just one therapy. It was only 2% with chemotherapy. Importantly, these improvements were achieved without increasing toxicity, Kopetz added.
The triplet therapy has already been added to the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of metastatic CRC. Hence, this is now available to U.S.-based patients for treatment of this difficult disease. The BEACON trial is active in Canada but is no longer recruiting. Please see the following link: https://clinicaltrials.gov/ct2/show/study/NCT02928224?show_locs=Y#locn
- Health Canada approves VITRAKVI (Larotrectinib), first tumour agnostic cancer treatment for advanced solid tumours harbouring an NTRK gene fusion (Sept 19/19)
Bayer announced that there is now a treatment in Canada for tyrosine receptor kinase fusion protein-driven childhood and adult cancers. Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusions can result in the production of TRK fusion proteins that can lead to uncontrolled cell growth and cancer. Health Canada issued a Notice of Compliance with Conditions (NOC/c) for VITRAKVI® (larotrectinib). VITRAKVI® is approved for the treatment of adult and pediatric patients with solid tumours that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory treatment options. Treatment with VITRAKVI® should be initiated following confirmation of an NTRK gene fusion in a tumour specimen using a validated test.
This is the first time Health Canada has approved a tumour agnostic treatment, such that patients with advanced solid tumours harbouring an NTRK gene fusion may be eligible for treatment with VITRAKVI®, across multiple tumour types and ages. VITRAKVI® is a first-in class oral and highly selective TRK inhibitor that may shrink the tumour, or may slow or stop it from growing. In the clinical trials that were the basis for this approval, TRK fusion cancer patients treated with larotrectinib experienced clinical benefit across numerous tumour types, including lung, thyroid, melanoma, GIST (gastrointestinal stromal tumour), colon, soft tissue sarcoma, salivary gland, and infantile fibrosarcoma. The overall response rate (ORR) was 75% (95% CI, 64%, 85%) with 22% of patients experiencing a complete response (CR) to treatment. The ORR observed was 90% in pediatrics and 69% in adults, and responses were rapid and durable.
What is TRK Fusion Cancer?
TRK fusion cancer is rare and occurs when an NTRK gene fuses with another unrelated gene, producing a TRK fusion protein that becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless where it originates in the body. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumours with varying frequency, including lung, thyroid, gastrointestinal cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma). TRK fusion proteins are rare in common cancers (such as colorectal cancer) and common in rare cancers.
NB: The pan Canadian Oncology Drug Review Expert Committee (pERC) has recently issued a funding recommendation in respect of Larotrectinib. It conditionally recommends the reimbursement of Larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with locally advanced solid tumors that have an NTRK gene fusion This recommendation pertains only to adult and pediatric patients with salivary gland tumours, adult or pediatric patients with soft tissue sarcoma (STS) and pediatric patients with cellular congenital mesoblastic nephroma or infantile fibrosarcoma, without a known acquired resistance mutation, that are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory treatment options, only if the following conditions are met:
- Cost-effectiveness being improved to an acceptable level
- Feasibility of adoption (budget impact and access to testing) is addressed
Stay tuned as the expert committee is currently reviewing feedback submissions from various stakeholders.
NB: Bayer has launched a testing program called FastTRK. As per an information sheet that may be obtained from CCRAN, FastTRK is a clinical testing program for the diagnosis of NTRK gene fusions. Sponsored by Bayer, this is a complimentary service for clinicians to determine whether their patients’ cancer has an NTRK gene fusion. Solid tumour samples from eligible patients (in the form of a solid tumour block or prepared slides) will be tested by immunohistochemistry (IHC) and/or next generation sequencing (NGS). Currently, Bayer has partnered with LifeLabs and the Kingston Health Sciences Centre (KHSC) to provide NTRK gene fusion testing services for Canadians. The FastTRK program will be supported at least until the end of 2021.
- Tumour mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer (May 9/19)
A recent study aimed to evaluate how the tumour mutational burden can be used to predict how a patient with microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC) will respond to immunotherapy. Among patients with MSI-H mCRC, immunotherapeutic PD-1 checkpoint inhibitors have demonstrated a high disease control rate and good progression-free survival. Reported response to immunotherapy agents pembrolizumab and nivolumab, however, are variable and often less than 50%, suggesting that further predictive biomarkers are needed. Pembrolizumab is an anti-PD-1 receptor antibody which lifts suppression of the immune system so that immune cells are activated and respond to invading tumour cells. Nivolumab is another PD-1 receptor inhibitor, which aids in the activation of the immune system’s anti-tumour response. The study found that the tumour mutational burden (the measurement of mutations carried by tumour cells) was most strongly associated with objective response and progression-free survival associated with these two immunotherapies. Tumour mutational burden appears to be an important biomarker which could be used to stratify MSI-H mCRC patients according to their likelihood of response to immunotherapy checkpoint inhibitors.
- NGS Testing Available at Sick Kids through Dr. Cynthia Hawkins (Sept 20/19)
Dr. Cynthia Hawkins’ lab at the Hospital for Sick Kids has developed an RNA sequencing based Next Generating Sequencing (NGS) test designed to look for fusion genes (including NTRK). The assay will also find point mutations. The requisition form can be obtained from CCRAN for clinicians to use on behalf of their patients. As for any NGS test the sensitivity is best if they know what specific genes they are looking for. NTRK gene fusion status may be determined through NGS testing to help identify Larotrectinib candidacy. The fee for NGS testing at Sick Kids is $950.
- Hepatic Artery Infusion Pump (HAIP) Chemotherapy Program – Sunnybrook Odette Cancer Centre (May 14/19)
The HAIP program is a first-in-Canada for individuals where colon or rectal cancer (colorectal cancer) has spread to the liver and cannot be removed with surgery. The program involves a coordinated, multidisciplinary team approach to care, with close collaboration across surgical oncology, medical oncology (chemotherapy), interventional radiology, nuclear medicine, and oncology nursing. The Hepatic Artery Infusion Pump (HAIP) is a small, disc-shaped device that is surgically implanted just below the skin of the patient and is connected via a catheter to the hepatic (main) artery of the liver. About 95 percent of the chemotherapy that is directed through this pump stays in the liver, sparing the rest of the body from side effects. Patients receive HAIP-directed chemotherapy in addition to regular intravenous (IV) chemotherapy (systemic chemotherapy), to reduce the number and size of tumours. Drs. Paul Karanicolas and Yooj Ko are the program leads and happy to see patients eligible for the therapy.
Presently at Sunnybrook Odette Cancer Centre, HAIP is being used in patients with colorectal cancer that has spread to the liver that cannot be removed surgically and has not spread to anywhere else in the body. Patients who have few (1-5) and very small tumors in the lungs may be considered if the lung disease is deemed treatable prior to HAIP. If you believe you may benefit from this therapy and/or would like to learn more about the clinical trial, your medical oncologist or surgeon may fax a referral to 416-480-6179. For more information on the HAIP clinical trial, please click on the link provided below.
- Living donor liver transplantation for unresectable colorectal cancer liver metastases (May 14/19)
Approximately half of all colorectal cancer (CRC) patients develop metastases, commonly to the liver and lung. Surgical removal of liver metastases (LM) is the only treatment option, though only 20-40% of patients are candidates for surgical therapy. Surgical therapy adds a significant survival benefit, with a 5-year survival after liver resection for LM of 40-50%, compared to 10-20% 5-year survival for chemotherapy alone. Liver transplantation (LT) would remove all evident disease in cases where the colorectal metastases are isolated to the liver but considered unresectable.
Image Source: https://www.slideshare.net/AhmedAdel65/preoperative
While CRC LM are considered a contraindication for LT at most cancer centers, a single center in Oslo, Norway demonstrated a 5-year survival of 56%. A clinical trial sponsored by the University Health network in Toronto will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases limited to the liver and are non-progressing on standard chemotherapy. Patients will be screened for liver transplant suitability and must also have a healthy living donor come forward for evaluation. Patients who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a control group who discontinue the study before transplantation due to reasons other than cancer progression. Despite the trial’s negative outcome, investigation of HIPEC, and other strategies to prevent peritoneal metastasis, should continue, they concluded in Lancet Gastroenterology & Hepatology. “The 21% peritoneal recurrence noted in the overall study population indicates the magnitude of the clinical problem in locally advanced colon cancer, and therapeutic strategies have to be further explored,” they said. “Outcomes of other trials investigating adjuvant HIPEC are eagerly awaited.”
- Adjuvant HIPEC in Advanced CRC (July 31/19)
Adding intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) to standard adjuvant therapy failed to reduce peritoneal metastasis in patients with locally advanced colon cancer, a multicenter Dutch study showed.
Patients randomized to HIPEC had a 19% incidence of peritoneal metastasis after 18 months versus 23% for patients who received adjuvant chemotherapy without additional HIPEC. However, almost half of the peritoneal recurrences in the experimental group occurred early, before adjuvant HIPEC had been administered, reported Pieter Tanis, MD, of the University of Amsterdam, and colleagues. he trial, known as COLOPEC, was the third in as many years to show no benefit of adjuvant oxaliplatin-based HIPEC for high-risk colorectal cancer, authors of an accompanying commentary pointed out. Collectively, the studies have added to “emerging literature questioning HIPEC’s benefit beyond cytoreductive surgery alone,” said Benny Johnson, MD, of the MD Anderson Cancer Center in Houston and Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center in Nashville. COLOPEC had limitations that could have obscured any benefit of HIPEC, Johnson and Eng continued. Perhaps most notably, imaging methods used in the trial lacked sensitivity to identify peritoneal metastases, reflected in the nine patients who had metastases before they had a chance to receive HIPEC. The intent-to-treat analysis included those nine patients in the total number of events for the HIPEC group.
Additionally, HIPEC was administered laparoscopically or by an open approach at physician discretion. Most patients had a 5- to 8-week delay in initiation of HIPEC, which pushed the start of conventional adjuvant therapy to a median of 10 weeks compared with six for the control group P<0.0001. Data on completion of chemotherapy and dose intensity were not available. Still another limitation, molecular characterization of tumors, was not reported. Patients with metachronous peritoneal metastases “have significantly worse overall survival than those with liver or lung involvement,” Johnson and Eng said. “Therefore, the need for novel approaches in patients with the highest risk for developing peritoneal metastasis remains unmet, and we congratulate the authors for designing this trial.”
More than 20% of patients with stage IV or perforated colon cancer develop peritoneal metastases, which have few treatment options and poor prognosis. Multiple clinical trials and comparative cohort studies showed that extended adjuvant fluoropyrimidine-based intraperitoneal chemotherapy (including HIPEC) significantly reduced the incidence of peritoneal recurrence, and the cohort studies also showed improvement in overall survival (OS), Tanis and colleagues noted. All of the studies showed a low incidence of major complications related to HIPEC.
Most recently, the randomized PRODIGE-7 trial showed no improvement in progression-free survival (PFS) or OS with postoperative administration of HIPEC. The discussion that followed the presentation at the 2018 American Society of Clinical Oncology meeting in Chicago revealed considerable disagreement about the value of adjunctive HIPEC.
Tanis and colleagues sought to determine whether intraoperative HIPEC with oxaliplatin, followed by standard adjuvant chemotherapy, reduced the risk of peritoneal recurrence versus adjuvant therapy alone in patients with locally advanced colon cancer. Eligible patients had clinical or pathologic T4No-2M0 tumors or perforated colon cancer. Investigators at nine centers in the Netherlands randomized 204 patients to receive intraoperative HIPEC plus adjuvant chemotherapy or adjuvant chemotherapy alone. The primary endpoint was peritoneal metastasis-free survival at 18 months in the intention-to-treat population. The results showed diagnosis of peritoneal metastases in 19 patients assigned to HIPEC and 23 in the control group. The absolute numbers translated into an 18-month peritoneal metastasis-free survival of 80.9% in the HIPEC group and 76.2% in the control group.
Lancet Gastroenterology & Hepatology Source Reference: Klaver CEL, et al “Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): A multicenter, open-label, randomized trial” Lancet Gastroenterol Hepatol 2019; DOI: 10.1016/S2468-1253(19)30239-0.
Lancet Gastroenterology & Hepatology Source Reference: Johnson B and Eng C “More questions regarding HIPEC in colorectal carcinomatosis” Lancet Gastroenterol Hepatol 2019; DOI: 10.1016/S2468-1253(19)30254-7.
RADIATION THERAPIES/INTERVENTIONAL RADIOLOGY
- Study Offered at the Odette Cancer Centre to Treat Recurrent Rectal Cancer (May 14/19)
Magnetic resonance-guided focused ultrasound (MRg-FU) is a noninvasive, outpatient modality being investigated for the thermal treatment of cancer. In MRg-FU, a specially designed transducer is used to focus a beam of low intensity ultrasound energy into a small volume at a specific target site in the body. MR is used to identify and delineate the tumour, focus the ultrasound beam on the target and provide real-time thermal mapping to ensure accurate heating of the designated target with minimal effect to the adjacent healthy tissue. The focused ultrasound beam produces therapeutic hyperthermia (40-42°C) in the target field causing protein denaturation and cell damage. Currently, there is no prospective clinical data reported on the use of MRg-FU in the setting of recurrent rectal cancer. Recurrent rectal cancer is a vexing clinical problem. Current retreatment protocols have limited efficacy. The addition of hyperthermia to radiation and chemotherapy may enhance the therapeutic response. With recent advances in technology, the investigators hypothesize that MRg-FU is technically feasible and can be safely used in combination with concurrent reirradiation and chemotherapy for the treatment of recurrent rectal cancer without increased side-effects. The study is being offered at the Odette Cancer Centre. Here is the link to the study protocol:
- Psychosocial factors increase complication risk with cancer surgery (May 22/19)
According to study results published in Annals of Surgical Oncology, psychosocial risk factors considerably increased risk for complications among patients with medical comorbidities who underwent cancer surgery. Patients who had a biomedical risk factor who also had two or more psychosocial risk factors were three times as likely as those with zero or one psychosocial risk factor to experience a complication. The research team from the Johns Hopkins University School of Medicine was surprised at the drastic risk increase, which is on par with other major biomedical risks that are typically seen when patients have diabetes, heart failure or chronic obstructive pulmonary disease (COPD). In the study, the researchers developed a questionnaire to assess psychosocial risk factors among 142 patients preparing to undergo surgery for gastrointestinal cancer. The questionnaire assessed the patient’s resourcefulness and resilience, as well as depression, smoking history, alcohol use and addiction history. Questions included how well patients recover from a difficult event, and how likely they were to cope with and care for a minor infection at home after surgery.
Nearly half (43.5%) of patients had high-risk biomedical comorbidities, and 73.4% of patients had at least one psychosocial risk. Patients with at least one psychosocial risk factor appeared significantly more likely than those with no psychosocial risks to experience a surgical complication (54.4% vs. 26.2%). Multiple psychosocial risk factors were associated with a 3.37-fold increased risk for complications compared with no or one psychosocial risk factor. The researchers suggest that psychosocial risk factors are a predictive measure for one’s ability to cope with stress after surgery – in other words, what psychosocial resources a patient has after surgery. Having limited psychosocial reserve leads to small problems worsening and ultimately, turning into a surgical complication. Most psychosocial risks, however, are modifiable. Assessing psychosocial risks before surgery and then including them in the risk counselling that all surgeons give patients before surgery in important. If a patient has a poor psychosocial support network, there may be ways to provide more support during recovery or leading up to surgery and reduce the increased risk for a complication.
- CanDirect research study: Learn more about a study for patients who have completed their cancer treatments and are experiencing low mood (May 2019)
15% of cancer survivors are estimated to experience mood problems even one year post-treatment. The CanDirect research study aims to support cancer survivors with mood problems by providing study participants with a self-care toolkit designed to help users better manage their mood and anxiety as well as phone coaching for a maximum duration of 6 months. Participation is open to eligible adult survivors residing in Quebec and Ontario who have completed cancer treatment for a non-metastatic cancer and who are experiencing depressive symptoms. For additional information, please access the following link:
- Global analysis finds early onset colorectal cancer rising in many high-income countries (Sept.13/19)
A new American Cancer Society study finds that colorectal cancer (CRC) incidence is increasing exclusively in young adults in nine high-income countries spanning three continents. The study, appearing in the journal Gut, finds the rising rates are in contrast to stable or declining trends in older adults, suggesting that changes in early-life exposures are increasing CRC risk. studies of cancer registry data indicate that favorable overall trends in the United States and Canada are masking an increase in young-onset CRC. To learn more about contemporary patterns of early onset CRC on a global scale, investigators led by Rebecca Siegel, MPH, analyzed long-term population-based data on CRC occurrence in adults under 50 versus those 50 and older for 43 countries covering six continents using high-quality cancer incidence data from population-based cancer registries. Of the 36 countries with sufficient numbers of cases to analyze trends, CRC incidence among adults under 50 was stable over the past ten years in 14 countries, decreased in three (Italy, Austria, and Lithuania), and increased in 19. In nine of those 19, the rise in early-onset CRC was in contrast to trends in those 50 and older, which were either dropping (Australia, New Zealand, Canada, Germany, and United States) or stable (Denmark, Slovenia, Sweden, and United Kingdom). In all but one of these countries with long-term data, the uptick in early-onset CRC began in the mid-1990s.
Rebecca L Siegel, Lindsey A Torre, Isabelle Soerjomataram, Richard B Hayes, Freddie Bray, Thomas K Weber, Ahmedin Jemal. Global patterns and trends in colorectal cancer incidence in young adults. Gut, 2019; gutjnl-2019-319511 DOI: 10.1136/gutjnl-2019-319511
- Sidedness of colorectal cancer impacts risk of second primary gastrointestinal malignancy (May 6/19)
A history of colorectal cancer (CRC) is known to increase one’s risk of a second primary gastrointestinal (GI) cancers. Depending on where the primary cancer is located – right colon, left colon, or rectum – molecular profiles, responses to treatment, and disease outcomes may differ. A study published in Annals of Surgical Oncology aimed to determine if CRC location is associated with variance in risk for developing a secondary primary GI malignancy. Using data from 281,413 adults with CRC in the SEER database, the incidence of secondary GI cancers was compared based on location of the initial CRC (right colon, left colon, or rectum). Within the median follow-up of 4.9 years, 4.3% of patients developed a second primary GI cancer. Those with CRC at any location had higher than expected incidences of small intestine, bile duct, and other CRCs, and lower incidences of liver and gallbladder cancer. The incidence of cancer of the small intestine was higher after primary CRC in the right colon. The incidence of esophageal cancer was higher after primary CRC in left colon. Pancreatic cancer was higher than expected among individuals whose primary CRC arose in the right colon. In conclusion, the researchers found that the location of the primary CRC results in differences in the incidence and location of the second primary GI cancer. These findings reinforce how CRC location not only impacts treatment response and outcomes, but should also be considered during subsequent surveillance of the disease.
- More young Canadians are getting colorectal cancer, study finds (Aug.4/19)
A new study has found that colorectal cancer rates continue to rise in younger Canadians. The researchers suspect that a heavier population may be to blame. The study in JAMA Network Open looked at data from all Canadians diagnosed with colorectal cancer between 1969 and 2016. The researchers found that the risk of colorectal cancer in the youngest cohort of men (those aged 20 to 29 in 2015) was more than double that age group’s risk in 1936. For women, the incidence rates were also higher in younger cohorts, although the difference was not considered significant.
Rates of the disease in Canadians under 50 have been steadily increasing since the mid-1990s, while rates have been mostly falling for those over 50 since the 1980s, according to the paper, international studies have found a similar pattern. A study published in the Lancet earlier this year looked at rates among 143 million people in Australia, Canada, Denmark, Norway, New Zealand, Ireland, and the U.K. found the presence of the disease has declined overall in the past 10 years but has increased dramatically among those under the age of 50. The authors of the new study, led by Dr. Darren Brenner of the University of Calgary, say an increase in colonoscopies for purposes other than cancer screening “cannot explain most of the new cases.”
- Young Colorectal Cancer Patients Are Going Undiagnosed (Aug.9/19)
Patients under the age of 50 are more likely to initially experience non-specific symptoms of colorectal cancer (CRC) before referral to cancer specialists, according to the findings of a study published in the journal Colorectal Disease. CRC occurrences are on the rise in young patients, and by 2030 it is estimated that one in 10 colon cancers and one four rectal cancers will be diagnosed in this age group. Contributing factors that explain this trend might be decreasing physical activity and heightened levels of obesity.
In this national population‐based study, researchers assessed 10,463 patients with colorectal cancer whose data were provided by the Clinical Practice Research Datalink (CPRD), a primary-care based dataset which comprises approximately 8-10% of the population in England. The CPRD provided linked data for any patients with a CRC diagnosis in the cancer registry between 2006 and 2013. Of the total number of patients, 7% were younger than 50 years of age, 16% were aged 50-59, 31.4% were aged 60-69, and 45.7% were aged 70-79. Any patients over the age of 80 years old were excluded as they were more likely to be diagnosed as an emergency. All symptoms, diagnoses, and investigations were recorded by the general practitioner (GP) into an electronic database based on Read codes, which translated into numerical ‘medcodes’ which were supplied to the researchers. The researchers compared odds ratios (ORs) for presenting with a specific symptom for an age group, and appraised data adjusted for patient demographics, and emergency diagnosis. The researchers compared categorical data utilizing the chi-square test with generalized estimating equation modeling used for regression analysis. The study results revealed that young patients were more likely to present with abdominal pain and via an emergency showed the lowest percentage of early stage cancer. These patients experienced a longer interval between referral and diagnosis (12.5 days) juxtaposed to those aged 60–69, reflecting the higher proportion of referrals via nonurgent visits. “Compared with older patients also presenting with nonspecific symptoms, younger patients were more likely to be diagnosed as an emergency,” the study authors wrote. However, there was no difference in the risk of an emergency presentation if the presenting consultation included a red‐flag.”
Colorectal cancer patients under the age of 50 experience delays in primary care leading to emergency diagnoses: a population‐based study. C. S. Arhi P. Ziprin A. Bottle E. M. Burns P. Aylin A. Darzi First published: 06 August 2019 https://doi.org/10.1111/codi.14734
- Some dying cancer patients still receive active therapies (Apr 17/19)
According to a new study, some patients who had been recently diagnosed with metastatic cancer and who died within 1 month of their diagnosis received aggressive but ineffective treatment during that brief period. The researchers found that the probability of receiving chemotherapy was lower for older patients regardless of cancer type. In the study, researchers identified 100,848 adult patients in the National Cancer Data Base with de novo metastatic lung, colorectal, breast, or pancreatic cancer (i.e. their cancers were metastatic from the start) and who died within 1 month of diagnosis. Of patients who received at least one type of treatment despite their de novo metastatic cancer diagnosis, 37.2% had CRC, 12.5% had pancreatic cancer, 29% had lung cancer, and 34.9% had breast cancer. 72.6% of patients did not receive any type of cancer-directed therapy. Older patients with lung cancer were less likely to receive radiotherapy. The odds of receiving chemotherapy and radiotherapy were also lower for lung and pancreatic cancer patients who had higher comorbidity scores. Among patients who were uninsured, the odds of receiving chemotherapy were lower for those with lung cancer or breast cancer. Furthermore, the type of treatment options offered varied considerably by facility type. The researchers note that determining the most appropriate care for these patients is very difficult, as they are a unique population who die soon after being newly diagnosed with metastatic cancer. The decision to administer aggressive treatment needs a thorough analysis of the patient’s prognosis in order to guide care decisions and should involve physicians, patients, and their families. Among patients with imminently fatal de novo metastatic cancer, better prognostication can help to avoid unnecessary aggressive and expensive therapies.
- Young adult colorectal cancer clinic available at Sunnybrook (Sept. 14/19)
A recent study led by University of Toronto doctors has observed a rise in colorectal cancer rates in patients under the age of 50. The study mirrors findings from the U.S., Australia and Europe. The growing colorectal cancer rates in young people come after decades of declining rates in people over 50, which have occurred most likely due to increased use of colorectal cancer screening (through population-based screening programs) which can identify and remove precancerous polyps. Patients diagnosed under the age of 50 have a unique set of needs, challenges and worries. They are unlike those diagnosed over the age of 50. Dr. Shady Ashamalla (colorectal cancer surgical oncologist), and his team at the Sunnybrook Health Sciences Centre understand the needs of this patient population.
Dr. Ashamalla belongs to a multidisciplinary team of experts in the Young Adult Colorectal Cancer Clinic who will work with young colorectal cancer patients, regardless of disease stage, to create an individualized treatment plan to support each patient through their cancer journey. Their needs and concerns will be addressed as they relate to:
- Fertility concerns and issues
- Young children at home
- Dating/intimacy issues
- Challenges at work
- Concerns about hereditary cancer
- Relationships with family and friends
- Psychological stress due to any or all of the above
The team of experts consists of:
- Oncologists (medical, surgical, radiation)
- Social workers
- Nurse navigator
Should a patient wish to be referred to Sunnybrook, they may have their primary care physician or their specialist refer them to Sunnybrook via the e-referral form which can be accessed through the link appearing below. Once the referral is received, the Young Adult Colorectal Cancer Clinic will be notified if the patient is under the age of 50. An appointment will then be issued wherein the patient will meet with various members of the team to address their specific set of concerns.
- Physically active people have lower colon cancer risk (Aug.9/19)
People who exercise regularly may be less likely to develop precursors to colorectal cancers, a research review suggests. Compared to people who get the smallest amount of physical activity, individuals who get the most exercise are 23% less likely to get so-called precancerous neoplasia, or abnormal tissue that can sometimes progress into full-blown colorectal cancer. And regular exercisers are also 27% less likely than sedentary people to get the most aggressive types of precancerous neoplasia with the most potential to progress to full-blown cancer.
“This gives us a strong support to promote exercise for prevention of colorectal neoplasia,” said Martin Wong, senior author of the study and a researcher at the Chinese University of Hong Kong. Of course, there are other ways for those who are not willing or unable to increase physical activity levels (to lower their risk), including quitting smoking, limiting intake of processed meat, and maintaining a healthy body weight,” Wong said by email. Globally, colorectal cancer accounts for 10% of all new cancer cases and 9% of all cancer deaths, Wong and colleagues note in the British Journal of Sports Medicine.
While previous research has linked regular exercise to a lower risk of colorectal cancer, researchers don’t have a clear picture of the relationship between physical activity and the precancerous growths that can turn into tumors, the study team notes. In the current study, more exercise was tied to a lower risk of precancerous colorectal growths in both men and women and for a variety of exercise routines. One drawback of the study is that it relied on data from smaller studies that weren’t controlled experiments – so they couldn’t prove more exercise causes fewer cancer cases. Some of the smaller studies in the analysis also relied on participants to report their own levels of activity instead of using objective measures like accelerometers to assess exactly how much exercise people got. It’s possible that regular exercise might help reduce the risk of colorectal tumors by accelerating digestion, which might reduce the amount of time the intestinal lining is exposed to acid or cancer-causing agents people ingest, the study team writes. Regular physical activity might also help prevent colorectal tumors by improving the body’s ability to use the hormone insulin to turn sugars in the diet into energy, reducing blood sugar levels, the study authors note. Even if the study doesn’t show why exercise prevents cancer, it does add to a large and growing body of evidence suggesting that people who get more physical activity may be less likely to get certain types of tumors, said Vandana Sheth, a spokesperson for the Academy of Nutrition and Dietetics who wasn’t involved in the study. “Physical activity is inversely associated with any type of colorectal neoplasia in both men and women,” Sheth said by email. “Increasing physical activity and decreasing sedentary behavior can have a significant positive impact on our overall health especially in terms of colorectal neoplasia.”
- How sugary drinks can fuel and accelerate cancer growth (May 22/19)
To date, cancer researchers have acknowledged that obesity increases the risk of cancer. A high intake of sugar through the repeated consumption of processed foods and sugary drinks is one important factor that is known to lead to obesity. Despite this fact, there has been limited research that examines the effects of sugar on tumour growth independent of obesity. Recently, a team of specialists from Baylor College of Medicine in Houston, TX and Weill Cornell Medicine in New York City has collaborated to examine the relationship between sugar intake and tumour growth in colorectal cancer (CRC). Specifically, the team studied the effects of consuming a daily modest amount of high-fructose corn syrup, a commonly used sweetener in the food and beverage industry, on CRC in mouse models.
The team conducted their research in mice with early-stage CRC in which a specific gene “APC” was deleted. This gene deletion simulated a mutation that characterizes fast-growing CRC in humans – more than 90% of CRC patients have this type of APC mutation. Deleting APC is like removing the brakes on cellular growth – without it, normal intestinal cells neither stop growing nor die, thereby forming early stage tumours also known as polyps. In the first stage of the study, the researchers allowed the mice to drink a beverage rich in high-fructose corn syrup at will. The sweetened water was 25% high-fructose corn syrup, which is composed of glucose and fructose in a 45:55 ratio. Within 1 month, the rodents put on a lot of excess body weight. To determine whether or not the high intake of corn syrup would boost cancer growth independently of obesity, the team administered the sugary drink in such a way that would allow the mice to ingest it without putting on weight, mimicking a human daily consumption of one can of soda. The mice were given the drink orally once a day for 2 months. Following the 2-month intervention, the investigators found that the rodents did not put on too much weight but they had developed larger, more advanced tumours than the rodents who had only received water. The findings suggest that when the animals had early stage tumours in the intestines – an occurrence that can show up in many young adult humans without notice – consuming even modest amounts of high-fructose corn syrup in liquid form can boost tumour growth and progression even if the individual is not obese. In other words, the researchers’ findings in animal models suggest that chronic consumption of sugary drinks can shorten the time it takes for cancer to develop. Further research will be needed to translate the study’s discovery to humans, as it usually takes 20-30 years for CRC to grow from early stage benign tumours to more aggressive cancers. These findings observed in animal models might explain why increased consumption of sugary drinks and other high-sugar foods over the past 30 years is correlating with an increase in CRC among 25-50 year olds in the US.
In a later stage of the study, the researchers examined the mechanisms by which the sugar in corn syrup fuelled tumour growth. The researchers found that the sugar fructose underwent certain chemical changes in the body which allowed it to boost glucose’s tumour-promoting effects. Specifically, the researchers found that fructose enhanced glucose’s role of directing fatty acids synthesis to form cellular membranes and signalling molecules to grow or to influence inflammation, a key contributor to cancer development. While many studies have linked increased rates of CRC with diet, this study has shown a direct molecular mechanism for the correlation between sugar consumption and CRC.
- Colon cancer: could exercise halt tumour growth? (Sept.1/19)
New research published in the Journal of Physiology suggests that short bursts of intense, physical activity may decrease the growth of colorectal tumour cells and improve patient outcomes. The research team from the University of Queensland in Australia found that short bursts of high-intensity exercise may have the same protective effects as repeatedly exercising over a long period of time. In the study, the research team recruited individuals with colorectal cancer (CRC) and asked them to perform either one session of high-intensity interval training (HIIT) or 12 sessions of HIIT over a 4-week period. HIIT is a training method that aims to make the person who exercises do more physical work at a high intensity during a single session by alternating high-intensity exercise intervals with low-intensity exercise or rest intervals. Blood serum samples were collected at baseline, immediately after finishing the HIIT session, and 120 minutes after the workout. The serum collected immediately after HIIT, but not 120 minutes after HIIT, demonstrated significantly reduced colon cancer cell numbers. The researchers found “significant increases” in certain cytokines or signalling proteins that help to modulate the body’s immune and inflammatory responses. These cytokines were interleukin-6, interleukin-8, and the tumour necrosis factor alpha. The short-term effects of HIIT and the cytokine flux may be important mediators of reducing colon cancer cell progression. Repetitive exposure to these acute effects may contribute to the relationship between exercise and improved CRC survival. These findings suggest that a physically active lifestyle may be instrumental in tackling human colorectal tumours, but the researchers note that the method they used to study colon cancer cell growth in the lab differs vastly from how these cells grow in the body. Further research will be necessary to observe how these changes in tumour growth occur in humans and to understand the mechanisms by which biomarkers in the blood can impact cell growth.
- Omega-3 Fish oil intake linked to small colorectal cancer risk reduction (Aug.2/19)
Exposure to omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) via fish consumption is associated with a slightly reduced risk of colorectal cancer (CRC), pan-European research shows. The analysis makes a substantial contribution to the growing body of evidence linking fish consumption to potentially lower risk of crc. Its consumption should be encouraged as part of a healthy diet.
The World Cancer Research Fund (WCRF) concludes there is limited but suggestive evidence that fish decreases crc risk. Nevertheless, uncertainty remains whether fish consumption is beneficial for crc prevention and how consumption of different fish types (ie fatty/oily, white/lean) relates to crc risk.
- Exercise for adults diagnosed with rectal cancer: a feasibility study (May 2019)
The purpose of the study is to examine the safety and feasibility of a supervised 12-week exercise intervention for adults diagnosed with rectal cancer. The exercise program will take place at the Behavioural and Metabolic Laboratory (200 Lees Ave., Ottawa) 3x a week and will be tailored to each individual.
Below are the inclusion criteria for the study:
- Men and women 18 to 85 years of age;
- Diagnosed with stage I-III rectal cancer and currently undergoing treatment or have completed treatments with the last 5 years;
- Able to read/understand English or French;
- Live <50km of the University of Ottawa;
- Approval of healthcare provider to participate in the intervention.
Individuals will be asked to complete a brief questionnaire and physical assessments (e.g., resting blood pressure) before and after the 12-week intervention.
- A Phase III study on the impact of a physical activity program on disease-free survival in patients with high risk stage II or stage III colon cancer: a randomized controlled trial (CHALLENGE) (May 14/19)
The purpose of this study is to compare the disease-free survival of patients involved in a physical activity program (designed to increase physical activity participation) who also receive general health education materials (about diet and physical activity) to patients who receive the general health education materials only. This study is being done because, as of yet, there is no conclusive evidence that physical activity will decrease the likelihood of colon cancer recurrence. This study will also obtain important information about the impact of physical activity on patients’ physical functioning, body composition, quality of life, fatigue, mood, cytokines and the insulin pathway, and their influence on prognosis, as well as cost-effectiveness.
Eligibility: Medically fit colon cancer patients (high risk stage II and stage III) who have completed adjuvant chemotherapy within the past 60-180 days. Current physical activity levels must not meet the recommended guidelines (>150 minutes of moderate-to-vigorous or >75 minutes of vigorous exercise/week). Following registration, and prior to randomization, patients must successfully complete at least two stages of a submaximal exercise test to ensure they are able to safely exercise at a moderate to vigorous intensity.
Participation: Limited to invited centres. For more information, visit the link below:
- High dose Vitamin D supplementation in Stage 4 Colorectal Cancer Patients (May 14/19)
A large body of evidence suggests that high blood levels of Vitamin D decreases the risk of developing cancer, especially colorectal cancer. Very little is known about what role optimum blood levels of Vitamin D can play in the treatment of cancer. The purpose of this clinical trial is to study the therapeutic effect and the safety of high-dose vitamin D supplementation in stage 4 (metastatic) colorectal cancer patients. Who is eligible to participate? Anyone who has a stage four colorectal cancer diagnosis, living in Ontario or British Columbia, may be eligible to participate. All participants need to have access to a Lifelabs facility for blood and urine collections. What is involved? This 40-month study involves regular lab tests and follow up phone calls. Participation is fully voluntary, and participants may withdraw at any time. Participants will be randomized into either a high-dose vitamin D treatment group or a control group. Participants in both groups may continue all other cancer treatments including chemotherapy. Treatment group: Participants in the treatment group receive daily oral high dose Vitamin D supplementation provided free of charge through the clinical study. They also receive daily calcium supplementation 1000mg daily as per guidelines, provided free through the clinical study. Participants will have monthly blood and urine tests for monitoring purposes. All laboratory tests are free of charge. Participants also need to be available for a 15-minute phone consultation with a study coordinator every 2 months. Control group: Participants in the control group will continue their usual amount of Vitamin D and/or calcium if they wish to do so. No supplements will be provided through the study. Participants will be asked to provide a small blood and urine sample at the beginning of the study, every 8 months and at the end of the study. These blood and urine tests will be free of charge. Contact person: If you have any further questions regarding this study or you are interested in participating in this study, please contact us: British Columbia: 604-734-7125, toll free 1- 888-734-7125 or vitDstudy@inspirehealth.ca Ontario: 613-792-1222, toll free 1-855-546-1244 or email@example.com
- SUNSHINE trial: high-dose vitamin D may benefit patients with metastatic colorectal cancer (Apr 23/19)
Findings from a small clinical trial suggest that supplementing chemotherapy with high doses of vitamin D may be beneficial to patients with metastatic colorectal cancer (mCRC) by delaying the progression of the disease. Vitamin D is necessary for bone health, and is made in the body through a chemical reaction that depends on sun exposure and intake of some fortified foods. In lab studies, vitamin D has shown anti-cancer properties such as triggered programmed cell death, inhibiting cancer cell growth, and reducing metastasis. While previous studies have linked higher blood levels of vitamin D with a lower risk of CRC and improved survival of patients, they were unable to prove that vitamin D was the direct cause.
In the SUNSHINE trial, 139 patients were recruited across the United States. All patients received standard chemotherapy (mFOLFOX6 plus bevacizumab). Patients were then randomly assigned to one of two treatment groups. Patients in the high-dose vitamin D group initially took 8,000 international units (IU) a day for 14 days, then 4,000 IU a day thereafter. Patients in the low or standard-dose vitamin D group took 400IU daily during all cycles. In the high-dose group, median progression-free survival (PFS) was 13. vs. 11 months in the standard dose group. Patients in the high-dose group were 36% less likely to have disease progression or death during the follow-up period of 22.9 months. No significant differences were found between the high-dose and standard-dose group in terms of tumour overall response rate or overall survival. Blood samples from participants were taken to measure the change in the levels of vitamin D before and after treatment. The test demonstrated that only 9% of the patients in the clinical trial had sufficient vitamin D at the beginning of treatment. Over the course of the study, patients in the high-dose group reached and maintained the vitamin D-sufficient range, while patients in the low-dose group had no substantial change in their vitamin D levels. The researchers found that the benefits of a high-dose vitamin D appeared to be less among obese patients and among those with tumours which contained a mutated KRAS gene, suggesting that certain subsets of CRC patients may need even higher doses of vitamin D for antitumour activity. High doses of vitamin D should not be taken except within the context of a clinical trial and under the supervision of specialists. The most common grade 3 and higher adverse events for chemotherapy plus high-dose vs. standard-dose vitamin D were neutropenia (35% vs. 31%) and hypertension (13% vs. 16%). The researchers conclude that the SUNSHINE trial findings are “extremely important” as they point to a cost-effective, safe, and easily accessible agent as a potential new treatment for mCRC.
- Study Looking for Female Survivors to participate in an Exercise Program
Researchers from the University of Toronto are performing a study investigating how female cancer survivors feel during and after different types of exercise. If you are a woman diagnosed with cancer and:
- Are 18-75 years old
- Completed treatment within 5 years
- Not exercising regularly
You can help out! Study includes: three sessions over the course of 1.5 weeks consisting of a variety of exercises for 20 minutes (with breaks). You will be compensated $20 for participation in each session for a total of $60.
Please contact Allyson for more information: 416-946-5856 or firstname.lastname@example.org