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Molecular Markers Predict Need For Adjuvant Treatment of Colon Cancer


 

The findings, which are considered preliminary, are being validated among an additional 500 patients, according to Dr. Sargent. "We think this is a very promising marker to be able to give patients with stage II disease an accurate prediction of what’s their likelihood of recurrence," he commented.

"We were able to define two-thirds of the population that have such a low risk for recurrence that I think it would be quite questionable whether there would be any potential reason to treat such patients," Dr. Sargent said, "whereas in the one-third of patients with high risk, they really look like stage III patients, and you might consider them as appropriate for treatment."

Tumor CDK1 Activity

Tumor activity of cyclin-dependent kinase 1 (CDK1), a key regulator of cell cycle progression, is a very strong and independent predictor of recurrence in patients with stage II colon cancer, investigators also reported.

"We believe that cell cycle profiling, the speed of the cell cycle, could be really important to predict tumor recurrence," said Dr. Masaki Shibayama of the Sysmex Corp. in Kobe, Japan, in an interview. Rapid proliferation "is one of the central hallmarks of cancer," he noted.

The investigators used the Cell Cycle Profiling (C2P) system (manufactured by Sysmex) to assess CDK1 enzymatic activity in fresh-frozen tumor samples from 254 patients from Germany and the Netherlands who underwent resection for stage II colon cancer and did not receive adjuvant therapy. With a median follow-up of 86 months, 11% developed distant metastases.

Some 40% of patients had a specific activity level of CDK1 that exceeded the cutoff of 11 and were classified as high risk, whereas 60% had a level of 11 or less and were classified as low risk. Relative to their low-risk peers, the high-risk patients were markedly more likely to develop distant metastases (HR, 6.2; P = .005) and to die from their cancer (HR, 7.6; P = .001).

These very high hazard ratios set this assay apart from other prognostic assays in stage II colon cancer, according to lead investigator Dr. Matthias Maak, a surgeon at the Technical University of Munich.

The hazard ratio for distant metastases was essentially the same after adjustment for age, sex, grade, and pathological T stage. It was still high (although no longer significant) after adjustment for tumor stroma content, possibly as a result of missing data for this parameter in about a third of cases.

"We believe this is a very nice result," Dr. Shibayama commented, and the assay may also extend to other solid tumors. "For example, we have a similar study for breast cancer, and it is also successful."

"This looks very promising," Dr. Maak concurred. "But this is, let’s say, the first test [of this assay] in colorectal carcinoma. Now we need more validation to find out if this works with another cohort, for example, or for another hospital. But we are rather positive that it will be as promising as it was in this trial."

Dr. Lenehan is an employee of Everist Genomics Inc. Dr. Sargent reported that his institution received research funding from DiagnoCure Inc. Dr. Shibayama is an employee of Sysmex Corp.; Dr. Maak did not report any conflicts of interest.

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