Dr Bryant on the Background For Investigating Germline DNA Repair Mutations in PDAC

John Michael Bryant, MD, resident, Radiation Oncology, Moffit Cancer Center, discusses research investigating the effects of germline DNA repair mutations on radiosensitivity in patients with pancreatic ductal adenocarcinoma (PDAC).

The correlation between homologous recombination deficiency in patients with PDAC and their responsiveness to platinum-based chemotherapy underscores the importance of delving deeper into how germline DNA repair mutations impact the effectiveness of various treatments. With recent data affirming that chemotherapy alone is an acceptable standard of care to improve R0 resection in patients with PDAC, attention has shifted toward understanding the role of radiotherapy in this population. However, there is still limited comprehension regarding the connection between germline DNA repair mutations in general and radiosensitivity. Therefore, investigators launched retrospective research evaluating the association between germline mutations and the Radiosensitivity Index Gene Signature.

The investigators’ focus was on patients with PDAC who underwent genomic adjusted radiation dosing testing at Moffit Cancer Center, Bryant begins. This specific testing allows for the assessment of the inherent radiosensitivity of a tumor, providing a radiosensitivity index score, Bryant says. Analyzing a substantial cohort of surgical specimens dating back to 1999, investigators also examined how many of these patients had undergone genomic testing for germline DNA repair mutations, he adds. Bryant says that after meticulous examination, he and the other investigators established a well-matched cohort, comprising 13 patients with germline DNA repair mutations and 12 without.

The primary objective of this research was to determine whether patients with germline DNA repair mutations exhibited significant differences in their radiosensitivity scores compared with those without mutations, he expands. The findings indicate that patients with germline DNA repair mutations demonstrated increased sensitivity to radiation based on the genomic adjusted radiation dosing testing, Bryant emphasizes.

Overall, these results reveal heightened radiosensitivity in patients with germline DNA repair mutations, indicating that these cancers may exhibit greater vulnerability to DNA damage induced by radiation; however, notable limitations were imposed by the small sample size, Bryant concludes.