A new genetic test for patients with colorectal cancer (CRC) is under investigation at AdventHealth Cancer Institute in Orlando, Florida. From a simple blood draw, the test, called Signatera, can detect whether a patient has cancer and might allow them to avoid chemotherapy after tumor resection. The sequencing technology searches for circulating tumor DNA (ctDNA), which are very small amounts of tumor DNA in the bloodstream. 

“What we knew is that a lot of patients [with CRC] were cured with surgery alone. We just didn’t have a way to know which ones had microscopic cancer left in the blood, who needed chemotherapy and who did not,” Mohamedtaki Tejani, MD, FACS, a medical oncologist and director of the Gastrointestinal Oncology Program at the AdventHealth Cancer Institute said in an interview.

Before the test existed, any patient with stage II or III colon cancer was prescribed 6 months of chemotherapy. “I tell patients, it’s a game of chess and we want to know what the cancer’s next move is,” Tejani noted. “Rather than wait until we see it on the scan, we want to stem it right when it is starting, and this test allows for that.” 

There are multiple ctDNA testing approaches, and this one is called tumor-informed. It’s “what is used in a lot of ongoing trials, Tejani explained. “The tumor-informed approach is when providers take the patient’s tumor, sequence it, and know exactly what its genome is. Then they look for it in the blood. It’s a longer turnaround, but when providers get the results, they are confident that they are measuring the DNA…the patient’s tumor has.”

CRC is the fourth most common cancer in the United States and the second leading cause of cancer-related deaths.

 At AdventHealth, Tejani is leading a National Cancer Institute clinical trial and a large national study aimed at harnessing this technology to improve patient care. The trials are as follows. 

The BESPOKE study (NCT04264702) of ctDNA-guided therapy in CRC is being conducted under the leadership of principal investigator Ahmed Zakari, MD, chairman of AdventHealth Orlando’s Division of Hematology and director of Gastrointestinal Oncology. This is a multicenter, prospective, observational study of 2000 patients who have undergone surgery for stage I to IV colorectal cancer. Patients will receive tumor-informed ctDNA test results and may be recommended for postoperative systemic therapy or observation by their treating clinician. They will be followed for up to 2 years with serial ctDNA analysis performed during standard-of-care visits. The control arm includes matched stage I to IV CRC cases with a minimum of 2 years of clinical follow-up data. The primary end points include the effect of ctDNA testing on adjuvant treatment decisions and recurrence rates and the asymptomatic and without correlate imaging.

NCT04068103 is a phase 2/3 NCI collaborative trial investigating how well ctDNA testing works at predicting treatment for patients with stage IIA colon cancer after surgery. Tejani serves as principal investigator of this study, which aims to enroll over 1400 participants. After completion of study treatment, patients will be followed at 12 months and every 6 months thereafter for 2 years. Primary outcome measures include recurrence-free survival and clearance of ctDNA to undetectable levels in patients who had baseline ctDNA.

CIRCULATE-US (NCT05174169) is another NCI collaborative trial evaluating the use of adjuvant chemotherapy in patients with colon cancer based on evaluation of residual disease. The phase 2/3 trial will consider the type of chemotherapy to recommend to patients based on the presence or absence of ctDNA after surgery. Tejani will also serve as principal investigator of this study, and primary outcome measures will include time from randomization to both first ctDNA positive status and disease-free survival.

Another ongoing trial at AdventHealth is a phase 3 study evaluating chemotherapy with or without atezolizumab (Tecentriq) in patients with stage III mismatch repair–deficient colon cancer (NCT02912559).

This and the BESPOKE study are currently enrolling participants through a referral process with the AdventHealth Gastrointestinal Oncology Program.

CRC treatments are associated with many risks, including infertility, which may be mitigated by incorporating ctDNA testing into medical decisions, Tejani said, and he hopes that the test can also be used to prescreen for very early-stage colon cancer and to more effectively treat other cancers, like gynecologic and pancreatic tumors.

Estimated number of new cases for the four major cancers by sex and age group, 2022. American Cancer Society. Accessed March 30, 2023. bit.ly/3M1jseu

Estimated number of deaths for the four major cancers by sex and age group, 2022. American Cancer Society. Accessed March 30, 2023. bit.ly/3Uertip

BESPOKE study of ctDNA guided therapy in colorectal cancer. ClinicalTrials.gov. Updated March 21, 2023. Accessed March 31, 2023. https://clinicaltrials.gov/ ct2/show/NCT04264702 

Circulating tumor DNA testing in predicting treatment for patients with stage IIA colon cancer after surgery. ClinicalTrials.gov. Updated March 2, 2023. Accessed March 31, 2023. https://clinicaltrials.gov/ct2/show/NCT04068103

Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-US). ClinicalTrials.gov. Updated March 24, 2023. Accessed March 31, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05174169

A021502 randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III colon cancer and deficient DNA mismatch repair. AdventHealth Research Institute. Accessed March 31, 2023. bit.ly/42XH0qs

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A new genetic test that may allow patients with colorectal cancer to avoid chemotherapy after tumor resection is under investigation at AdventHealth Cancer Institute in Orlando, Florida. 

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