Patients with cancer who experience unexpected and long-lasting treatment outcomes are considered exceptional responders, but researchers and clinicians had no insight as to why the patients did so well with treatment. Results of a new study now show that genomic characterizations of cancer can uncover genetic alterations that may contribute to the phenomenon, researchers reported in Cancer Cell.
In a retrospective study, researchers reviewed detailed medical histories and tumor samples from 111 patients identified through the National Cancer Institute’s Exceptional Responders Initiative. The patients had received standard treatment for various types of cancer and were considered exceptional responders because they had a partial or complete response that would be expected in less than 10% of similar patients and the duration of their response was at least three times longer than the median response time.
For 26 of the 111 (23.4%) patients, the researchers found molecular features that could potentially explain the exceptional responses, such as co-occurrence of multiple rare genetic changes in the tumor genome or the infiltration of the tumor with certain types of immune cells. For example, two patients had BRCA1 or BRCA2 variations with cancers that are rarely associated with those variants. They theorized that the variants may have impaired the tumor’s ability to fix damaged DNA and increased the effectiveness of DNA-based treatments.
“Our findings demonstrate the importance of testing patient tumors for alterations that may point to available treatments,” the researchers said. “There is a need for a shift toward molecular diagnosis of cancer that provides information that cannot be gleaned from looking at tumors through a microscope.”