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SRI Magazine 2016

SRI Magazine 2016

Colorectal cancer advances

Including DIY kit in the mail raises screening rates and taking a break from chemotherapy OK

Regular colorectal cancer screening can save lives. That’s the take-home message from Dr. Jill Tinmouth, a scientist in the Odette Cancer Research Program at Sunnybrook Research Institute (SRI) and a physician at Sunnybrook who specializes in screening for gastrointestinal cancers.

Small lumps of precancerous cells called polyps often form in the colon or rectum as we age. Over time, some of these polyps can become cancerous and spread to other organs in the body, making them harder to treat. Colorectal cancer is the third most common cancer and the fourth-leading cause of death worldwide. It doesn’t have to end that way, however.

“The good thing about colorectal cancer is that it can be caught early with screening. There are large, grade-A randomized controlled trials that show screening with fecal tests can reduce colorectal cancer-related death,” says Tinmouth, who is also the lead scientist of the ColonCancerCheck program at Cancer Care Ontario (CCO).

ColonCancerCheckwas launched in 2008. It is Canada’s first province-wide colorectal cancer screening program. It enables family physicians to give patients aged over 50 years who are at average risk of colorectal cancer (meaning no family history) a guaiac (pronounced gwai-ak) fecal occult blood test (gFOBT). The test comprises a stool-collection kit that is used to look for small amounts of blood. Individuals who have an abnormal test should undergo a colonoscopy to determine the source of the bleeding, which can result from a cancer, polyp or other cause, such as ulcers, haemorrhoids or colitis, an inflammatory bowel disease.

The program conducted a pilot project to test the feasibility of mailed invitations for cancer screening. Invitations from 102 family physicians were sent to their patients who were due for screening asking them to visit and obtain a gFOBT stool sample kit, or get a referral for a colonoscopy based on family history. Invitations were mailed to 11,000 people aged between 50 and 74 years; a gFOBT kit was not included. Only 22% of invitees responded and completed the gFOBT kit. Researchers concluded that better strategies were needed to get people to participate in colorectal cancer screening.

In 2011, Tinmouth led a randomized controlled trial to build on ColonCancerCheck’spilot study. She looked at whether making it easier to do the screening would help with participation. To test this theory, the trial studied the impact of including a gFOBT kit along with a second mailed invitation compared to a second invitation alone among people who did not respond in the pilot project.

The participants were randomly allocated to one of two arms: the intervention group received a second mailed screening invitation along with the gFOBT kit from their family doctor; and the control group received a second mailed invitation alone from their family doctor.

Tinmouth and colleagues found that the completion rate of a gFOBT test within six months of the mailing date was twice as high in the intervention group at 20% compared to the control group at 10%. The findings suggest that mailing gFOBT kits to participants increases colon cancer screening in harder-to-screen persons; only 10 additional kits need to be sent to screen one more person. Results were published in the International Journal of Cancer.

“This research is at the cusp of policy,” says Tinmouth. “It has the potential to have an impact in the very near future, because it’s actually studying how we’re delivering health care to Ontarians in the here and now.”

But how are patients treated when prevention measures are too late and the cancer has spread?

Improving survival rates and quality of life for patients with inoperable colorectal cancer is a priority for Tinmouth and Dr. Scott Berry, a researcher at SRI and medical oncologist at Sunnybrook.

We can now reassure patients that if they want to take a break, it will help their quality of life and not have an impact on their overall survival.

Since the late 1990s, many new chemotherapy and biologic agents have emerged to treat metastatic colorectal cancer. These new treatments have improved the median life expectancy for people whose colorectal cancer has spread from 12 months to about 29 months. With patients living longer, however, concerns have emerged about the side effects associated with extended exposure to chemotherapy and the impact on patients’ quality of life.

Researchers have conducted trials looking at a “stop-and-go” approach to treatment to see whether patients can take “chemotherapy holidays” to improve their quality of life without negatively affecting survival. These trials have compared the outcome of patients receiving therapies continuously to those receiving breaks from treatment for three to four months, and then receiving treatment again.

Berry and his colleagues in CCO’s gastrointestinal disease site group and program in evidence-based care did a meta-analysis of the randomized clinical trials in this arena. They identified 11 trials that looked at variations in the continuity of drugs given during chemotherapy. The meta-analysis included more than 3,800 patients. The researchers found there was no significant reduction in overall survival when patients took breaks from treatment. Intermittent chemotherapy, moreover, maintained or improved quality of life compared to continuous treatment. The results were published in the Annals of Oncology and used to craft an evidence-based guideline to provide direction for practitioners caring for patients with metastatic colorectal cancer.

“Based on the results of this meta-analysis, we can now reassure patients that if they want to take a break, it will help their quality of life and not have an impact on their overall survival,” says Berry, noting patients often ask for time away from the hospital to enjoy a holiday down south or up north at the cottage. “Giving breaks from chemotherapy is a reasonable option that maintains the benefits of the therapy but reduces the toxicities.”

Careful clinical assessment is important, however, as treatment breaks are not for everyone. For some patients with more aggressive disease it may not be suitable to take a complete break, notes Berry. Patients who are off treatment also require careful monitoring so physicians know when to reintroduce therapy.

Berry says the results are practice-affirming. Physicians who may have hesitated to give breaks are now able to have an informed discussion with their patients about treatment options based on the data.

“The goal of our work was to help inform practice in an area of clinical controversy using the power of meta-analysis to collect data from multiple trials and thousands of patients to answer a clinical question: Do treatment breaks have an impact on overall survival?” says Berry. “The answer is no.”

Berry’s research was supported by Cancer Care Ontario (CCO). Tinmouth’s research was supported by CCO and the Ontario Institute for Cancer Research.