Prognostic value of biomarkers in colorectal cancer hinge on tumor location

Last Updated: 2017-02-23

By Megan Brooks

NEW YORK (Reuters Health) – The utility of tumor-infiltrating lymphocytes for predicting colorectal cancer survival depends on the location of the tumor, new research suggests.

“The prognostic value of tumor-infiltrating lymphocytes appears to be most evident in patients with right-sided tumors. This may be of particular interest for treatment stratification of patients with microsatellite stable tumors,” lead researcher Dr. Jonna Berntsson of Lund University in Sweden, told Reuters Health.

“However, one study is not sufficient to change recommendations for therapeutic decisions, and further studies are warranted to confirm our results. Nonetheless, it is likely that the response from immunotherapy may also depend on tumor subsite and that future immunotherapy research should take this into consideration,” said Dr. Berntsson by email.

The study was released February 21 ahead of presentation at the inaugural American Society of Clinical Oncology (ASCO)/Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Symposium in Orlando, Florida.

Several studies have demonstrated improved prognosis in CRC patients with dense tumor-infiltrating lymphocytes (TILs) and natural killer cells, but the current study is the first to examine the prognostic impact of these cells in relation to tumor location, the researchers say.

Dr. Berntsson and colleagues analyzed tumor tissue samples from 557 patients with newly diagnosed CRC. In each specimen, they assessed the density of different types of TILs (cytotoxic T cells, regulatory T cells, and natural killer or natural killer T cells).

Overall, dense infiltration of all of these immune cells correlated significantly with improved five-year overall survival regardless of tumor location. This association was independent of patient age, cancer stage and other relevant factors.

However, the prognostic impact of specific types of TILs differed by tumor location.

Dense infiltration of CD3+ and CD8+ regulatory T cells were independent favorable prognostic factors for tumors in the right colon (hazard ratio, 0.53; 95% confidence interval, 0.29-0.95; and HR, 0.35, 95% CI, 0.19-0.65, respectively), but not in the left colon or rectum, they report in a conference abstract.

After including microsatellite instability status in the adjusted model, only CD8+ cells remained an independent favorable prognostic factor in right-sided tumors.

Dense infiltration of FoxP3+ cells was an independent favorable prognostic factor for tumors in the rectum (HR, 0.54; 95% CI, 0.30-0.99), but not in the right or left colon. Infiltration of CD56+ cells did not have any independent prognostic value after stratifying for primary tumor location.

“The results from this study demonstrate that the prognostic impact of certain T cell subsets in CRC differs by primary tumor site, being most evident in right-sided tumors. These findings indicate that tumor location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy,” the researchers conclude.

Dr. Berntsson told Reuters Health, “We have initiated (January 1, 2017) a prospective study including all incident cases of colorectal cancer in our region in Sweden, wherein comprehensive immuno-profiling will be performed and tumor subsite will be taken into account.”

Commenting on the study in a conference statement, ASCO expert Dr. Lynn Schuchter from the University of Pennsylvania in Philadelphia said, “We’ve seen prior research showing that the location of a colorectal cancer tumor can help predict a patient’s survival, and this study adds another layer of information that can help further personalize treatment.”

The study had no commercial funding and the authors have disclosed no relevant financial relationships.

SOURCE: http://bit.ly/2lp03r8

2017 ASCO-SITC Clinical Immuno-Oncology Symposium.