Olsi Gjyshi

Socioeconomic and Racial Determinants of Brachytherapy Utilization for Cervical Cancer: Concerns for Widening Disparities

PURPOSE: Cervical cancer (CC) disproportionately affects minorities who have higher incidence and mortality rates. Standard of care for locally advanced CC involves a multimodality approach including brachytherapy (BT), which independently improves oncologic outcomes. Here, we examine the impact of insurance status and race on BT utilization with the SEER database. MATERIALS AND METHODS: In total, 7,266 patients with stage I-IV CC diagnosed from 2007 to 2015 were included. BT utilization, overall survival (OS), and disease-specific survival (DSS) were compared. RESULTS: Overall, 3,832 (52.7%) received combined external beam radiation therapy (EBRT) + BT, whereas 3,434 (47.3%) received EBRT alone. On multivariate logistic regression analysis, increasing age (OR, 0.98; 95% CI, 0.98 to 0.99; P < .001); Medicaid (OR, 0.80; 95% CI, 0.72 to 0.88; P < .001), uninsured (OR, 0.67; 95% CI, 0.56 to 0.80; P < .001), and unknown versus private insurance (OR, 0.61; 95% CI, 0.43 to 0.86; P < .001); Black (OR, 0.68; 95% CI, 0.60 to 0.77; P < .001) and unknown versus White race (OR, 0.30; 95% CI, 0.13 to 0.77; P = .047); and American Joint Committee on Cancer stage II (OR, 1.07; 95% CI, 0.93 to 1.24; P = .36), stage III (OR, 0.82; 95% CI, 0.71 to 0.94; P = .006), stage IV (OR, 0.30; 95% CI, 0.23 to 0.40; P < .001), and unknown stage versus stage I (OR, 0.36; 95% CI, 0.28 to 0.45; P < .001) were associated with decreased BT utilization. When comparing racial survival differences, the 5-year OS was 44.2% versus 50.9% ( P < .0001) and the 5-year DSS was 55.6% versus 60.5% ( P < .0001) for Black and White patients, respectively. Importantly, the racial survival disparities resolved when examining patients who received combined EBRT + BT, with the 5-year OS of 57.3% versus58.5% ( P = .24) and the 5-year DSS of 66.3% versus 66.6% ( P = .53) for Black and White patients, respectively. CONCLUSION: This work demonstrates notable inequities in BT utilization for CC that particularly affects patients of lower insurance status and Black race, which translates into inferior oncologic outcomes. Importantly, the use of BT was able to overcome racial survival differences, thus highlighting its essential value.

Human Papilloma Virus Circulating Cell-Free DNA Kinetics in Patients with Cervical Cancer Undergoing Definitive Chemoradiation

Abstract Purpose: Human papillomavirus (HPV) is a significant cause of cervical cancer. We hypothesized that detecting viral cell-free HPV DNA (cfDNA) before, during, and after chemoradiation (chemoRT) could provide insights into disease extent, clinical staging, and treatment response. Experimental Design: A total of 66 patients with locally advanced cervical cancer were enrolled between 2017 and 2023, with 49 receiving standard-of-care treatment and 17 participating in a clinical trial combining a therapeutic HPV vaccine (PDS0101; IMMUNOCERV). Plasma was collected at baseline, weeks 1, 3, and 5 of chemoRT, and 3 to 4 months after chemoRT. HPV cfDNA was quantified using droplet digital PCR targeting the HPV E6/E7 oncogenes of 13 high-risk types. MRI was performed at baseline and before brachytherapy. Results: The median follow-up was 23 months, with recurrence-free survival (RFS) of 78.4% at 2 years. Baseline nodal disease extent correlated with HPV cfDNA levels. HPV cfDNA levels peaked in week 1 of radiation and decreased through treatment. Patients receiving the PDS0101 vaccine had a higher rate of undetectable HPV type 16 cfDNA compared with those who received standard-of-care therapy. HPV cfDNA clearance correlated with better 2-year RFS (92.9% vs. 30%, log-rank; P = 0.0067). The strongest predictor of RFS was HPV cfDNA clearance in follow-up achieving a concordance index score of 0.83, which improved when combined with MRI response (concordance index, 0.88). Conclusions: HPV cfDNA levels change dynamically during chemoRT. HPV cfDNA levels at follow-up predict RFS, and delivery of therapeutic HPV vaccine with chemoRT was linked to rapid HPV cfDNA decline. Monitoring HPV cfDNA during and after chemoRT may guide tailoring of personalized treatment.