Next-generation sequencing identifies thousands of cancer patients who cannot receive immunotherapy

Brigham researchers’ next-generation sequencing findings suggest that updating current cancer treatment guidelines could allow approximately 6,000 more patients in the United States to benefit from immunotherapy treatment each year. suggests

Immunotherapy is a highly effective treatment for patients whose cancer has mismatch repair defects, and new research identifies more cancer patients who could benefit from this form of treatment. Masu. Researchers at Brigham and Women’s Hospital, a founding member of the Massachusetts General Brigham Health System, found that about 6 percent of endometrial cancer patients and about 1 percent of colorectal cancer patients have mismatch repair defects. , discovered that the current standard of care test, immunohistochemistry, missed the mark. This state. In these missed cases, symptoms were instead detected by next-generation sequencing, which researchers estimate could identify an additional 6,000 patients in the United States who were not offered immunotherapy. I am.The results will be published in a magazine cancer cell.

For colorectal cancer and endometrial cancer, the two cancer types most commonly found to have mismatch repair defects, immunotherapy is not standard treatment unless the patient has the disease. However, patients with this disease, even those with terminal cancer, can survive for years and even be cured with immunotherapy. Including next-generation sequencing as a free test offering could benefit patients at all stages of cancer, from pre-treatment to advanced stages. ”

Elias Bou Farhat, MD, first author, postdoctoral fellow in the Department of Respiratory and Clinical Care Medicine, Brigham and Women’s Hospital

Each year in the United States, more than 150,000 people are diagnosed with colorectal cancer and more than 65,000 people are diagnosed with endometrial cancer. In these two types of cancer, patients often have a high rate of mismatch repair deficiency, a genetic condition in which errors in DNA occur due to the lack of specific repair proteins. This condition impairs her DNA’s ability to self-repair and can lead to various types of cancer. Previous studies have shown that cancer patients with this condition usually respond well to immunotherapy treatments that harness a person’s own immune system to fight cancer.

In this study, researchers from Brigham and Women’s Hospital and Dana-Farber Cancer Institute examined patients with colorectal or endometrial cancer who received immunohistochemistry and next-generation sequencing tests. We studied a cohort of 1,655 patients who received both. Researchers found that about 6 percent of endometrial cancer patients and about 1 percent of colorectal cancer patients were missed by immunohistochemistry but were detected by next-generation sequencing. I observed that. These patients responded better to immunotherapy than other treatments, with survival rates and outcomes similar to those found to be immunocompromised by both tests.

Immunohistochemistry detects only mutations that affect the antigen. Next-generation sequencing is a more sensitive test because it looks for more mutational signatures. The current study suggests that next-generation sequencing may be a more sensitive diagnostic tool in these cases, but further research is needed to confirm and generalize the results of this study.

Data from this study also showed that among patients of the same type and stage, those who did not receive immunotherapy had worse outcomes than those who did.

“We don’t want to miss these patients, or we could be depriving them of potentially long-term effective treatments,” said lead author Amin, a member of the Yale Cancer Center. said Nassar, MD. He was a medical resident at Brigham and Women’s Hospital. “We also want to avoid giving patients treatments that may be more toxic or less effective. We want to treat patients with the appropriate therapy.”

Next, the researchers want to see if these findings apply to other sequencing panels and other types of cancer. They also plan to investigate the potential role of other genetic defects involved in mismatch repair-deficient conditions.