2752 - Homologous Recombination Deficiency: Is It Relevant in Locally Advanced Cervical Cancer?
Presenter(s)
J. S. Gonzalez Diaz1, R. Wang1, D. Negrón-Figueroa1, M. B. El Alam1, X. Wu2, T. Harris1, D. K. Lo1, A. Fontillas1, T. Cisneros Napravnik1, D. Walters1, S. F. Ehsan1, N. J. Ajami2, M. Wong2, L. Boatright1, A. Judge1, C. Charles1, E. J. Lynn1, A. H. Klopp3, and L. Colbert3; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): The homologous recombination deficiency (HRD) score has been utilized as a predictor of response to therapies that induce or enhance double-strand DNA damage, particularly in BRCA1-mutated cancers, serving as a valuable tool to assess patient candidacy for these therapies. The standard of care for locally advanced cervical cancer is platinum-based chemoradiotherapy (CRT); however, despite a high overall response rate, a subset of tumors remains resistant to this regimen. This analysis quantifies HRD frequency and evaluates its association with clinical variables, CRT response, and survival in locally advanced cervical cancer
Materials/Methods: Cervical tumor swabs were collected from 120 patients diagnosed with locally advanced cervical cancer. Swabs were collected prior to treatment and were subjected to whole exome sequencing (WES). The HRD Score was calculated by running the WES data through the ScarHRD pipeline. Subsequently, we reviewed medical records to check for clinical variables including age at diagnosis, self-reported race, tumor histology, FIGO staging, overall survival (OS) and recurrence-free survival (RFS). To assess associations between HRD score, clinical variables, treatment response, and survival, we performed statistical analyses using independent t-test, ANOVA, linear regression, logistic regression, and Kaplan-Meier survival analysis models.
Results: The median HRD score among patients was 21 with an interquartile range of 16 (13-29). Approximately 7.5% and 19% of patients had an HRD score greater or equal to 42 and 33, respectively. Additionally, top mutated genes in the homologous recombination (HR) DNA damage repair pathway included BRCA 1 (n = 5), BRCA 2 (n = 4), and ATRX (n = 4). We did not observe any statistically significant associations between HRD score and age at diagnosis (p = 0.46), BMI (p = 0.88), smoking status (p = 0.08), tumor dimensions on MRI at diagnosis (p = 0.20), FIGO staging (p = 0.84), maximum SUV at diagnosis (p = 0.33), tumor histology (p = 0.69) and HPV status (p = 0.19). Moreover, logistic regression showed no significant association between HRD score and response to CRT (p = 0.86). The Kaplan-Meier analysis indicated no association with OS (p = 0.84, 0.62) or recurrence-free survival RFS (p = 0.86, 0.96) for HRD thresholds of =42 and =33, respectively. We found a statistically significant difference in HRD scores between Hispanic and White women (p = 0.04), with Hispanic women exhibiting higher HRD scores (mean = 25 vs. 19).
Conclusion: This is the first study to associate HRD score with clinical variables in the cervical cancer setting. Our data suggests that our cohort's overall distribution of HRD scores is considered low compared to the current literature, with a low prevalence of mutations in genes involved in the HR DNA damage repair pathway. Aside from the observed difference by race, no statistically significant associations were found between HRD scores and clinical variables.