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Tumor Mutational Burden: Predictive Biomarker in Some Patients With Colorectal Cancer

By: Cordi Craig
Posted: Monday, September 24, 2018

Tumor mutational burden is linked to responses in lung cancer, melanoma, and bladder cancer. Now a recent study, conducted by Samuel J. Klempner, MD, of The Angeles Clinic and Research Institute, Los Angeles, suggests that a subgroup of patients with colorectal cancer may also benefit from immune checkpoint inhibitor–based therapeutic approaches. The report, published in the Journal of Gastrointestinal Oncology, identified patients with microsatellite-stable colorectal cancer and used comprehensive genomic profiling to quantify tumor mutational burden as a predictive biomarker.

“Tumor mutational burden derived from [comprehensive genomic profiling] may represent a more robust surrogate [compared with microsatellite instability status] for predicting response to PD-1 blockade and can be derived from [comprehensive genomic profiling] data,” the study authors explained.

The investigators sequenced formalin-fixed, paraffin embedded tissue sections from about 6,000 cases of colorectal cancer with a comprehensive genomic profiling assay. They computationally determined microsatellite instability and tumor mutational burden statuses.

Microsatellite-stable tumors were observed in 5,702 cases (95%) compared with 302 cases (5%) identified with microsatellite instable–high tumors. Of those identified as having microsatellite-stable tumors, 5,538 (97%) were identified as having a low tumor mutational burden, whereas 164 (2.9%) individuals were confirmed to have a high tumor mutational burden status. These results represent an increase in patients with colorectal cancer who may respond to checkpoint inhibitor therapy by 54% (466 vs. 302, respectively).

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