In Colon Cancer, Genomic Classifiers Aid in Prognosis

Caroline Helwick

Uncategorized

Genomic classifiers – in particular, ColoPrint and MSI-Print, and best when combined – can identify high-risk subsets among surgically resected stage II and stage III colon cancer patients, MD Anderson Cancer Center researchers reported at the 2013 GI Cancers Symposium.

“The combination of ColoPrint and MSI-Print improves the prognostic accuracy in stage II and stage III patients and may help identify patients at higher risk who are more likely to benefit from additional treatment,” said Scott Kopetz, MD, PhD, lead author.

“Although the benefit of chemotherapy in stage II and III colon cancer patients is significant, many patients might not need adjuvant chemotherapy because they have a good prognosis even without additional treatment,” he added.

ColoPrint is a gene expression classifier that distinguishes patients with low or high risk of disease recurrence. It was developed using whole genome expression data and has been validated in public data sets, independent European patient cohorts, and technical studies. The 64-gene MSI-signature, MSI-Print, is a genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency and is linked to deficient mismatch repair (dMMR). A dMMR system is present in 10% to 20% of patients with sporadic colon cancer and is associated with a favorable prognosis in early-stage disease.

The population included 96 stage II patients and 94 stage III patients followed a median of 64 months. In this cohort, ColoPrint was prognostic for recurrence. The test classified 56% of stage II and stage III patients as being at low risk for recurrence. The 3-year recurrence-free survival (RFS) was 90.6% for low-risk and 78.4% for high-risk patients, with a hazard ratio of 2.33 (P=.012). In univariate and multivariate analyses,
ColoPrint and stage (stage III vs stage II) were the only significant factors to predict outcome.

The MSI-Print classified 24.6% of patients as MSI-high (which is prognostically favorable), and most of these (81%) were low risk by ColoPrint.
“Patients who were ColoPrint low risk and MSI-
high by signature had the best outcome, with a 3-year RFS of 95%, while patients with ColoPrint high risk had a worse outcome independently of the MSI status,” Kopetz reported.

One-fourth of patients were characterized as “MSI-Print-high,” which was previously defined to incorporate both MSI-high tumors and additional tumors that share similar gene expression features. In this population, MSI-Print did not provide independent prognostic ability but did provide additional information when combined with ColoPrint.

Low-risk ColoPrint patients had a good outcome independent of stage or chemotherapy treatment. RFS at 3 years was 90.1% for treated patients and 91.4% for untreated patients. ColoPrint high-risk patients treated with adjuvant chemotherapy had a 3-year RFS of 84%, compared with 70.1% for untreated patients (P=.037).

Kopetz added that ColoPrint is independent of traditional American Society of Clinical Oncology (ASCO) high-risk features, with 50% of cases discordant based on the presence or absence of high-risk features and ColoPrint results. For example, among patients classified as high risk by ASCO clinical features, only 34% were high risk by ColoPrint and 41% were low risk. Among those at low risk by ASCO clinical features, 16% were low risk by ColoPrint and 9% were high risk.

The genomic classifiers, therefore, add information above and beyond that obtained through conventional means, he said.

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