Lauren M. Andring

The Value of Patient-Reported Outcomes to Predict Symptom Burden and Health-Related Quality of Life After Chemoradiation for Cervical Cancer: A Prospective Study

Patients with cervical cancer undergoing chemoradiation have high symptom burden. We performed an analysis of prospectively collected data on patient-reported outcomes to determine characteristics predictive of poor treatment experience. Between 2021 and 2023, we prospectively collected data on patient-reported outcomes from patients with cervical cancer undergoing definitive chemoradiation. The European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Question-Core 30 and the EORTC-Quality of Life Question-Cervical Cancer module were completed at baseline (BL) and at the end of treatment (EOT). Poor treatment experience was defined as EOT poor health-related quality of life (HRQOL), low physical function, or significant overall symptom burden. Predictive factors analyzed included demographic, clinical, and disease-specific factors and BL financial toxicity, depression, social function, and emotional function. Receiver operating characteristic analysis provided appropriate predictive cutoff values. Univariable and multivariable (MVA) linear regression analyses were performed. Forty-nine patients completed BL and EOT questionnaires. Median age was 43 years (range, 18-85 years). Most patients (59%) had stage III disease. BL financial toxicity ≥66.7, depression ≥66.7, social function ≤50, and emotional function ≤58 on the EORTC linear transformed scale of 0 to 100 were significant predictors for poor treatment experience (p ≤ .04) based on receiver operating characteristic analysis. On MVA, poor BL social function was associated with reduced EOT HRQOL (β, -9.3; 95% CI, -16.1 to -2.6; p < .008), decreased physical function (β, -24.4; 95% CI, -36.3 to -12.6; p < .001), and high symptom burden (β, 26.9; 95% CI, 17.5-36.3; p < .001). Earlier disease stage predicted decreased symptom burden (β, -6.7; 95% CI, -13.1 to -0.3; p = .039). BL financial toxicity was a significant predictor in univariable analysis (p = .001-.044) and showed a significant interaction term on MVA (p = .024-.041) for all 3 domains of poor treatment experience. Demographic and treatment-related factors were not predictive. Patients with cervical cancer with poor BL social function or high financial toxicity were at risk for increased symptom burden and poor HRQOL. Screening for these factors provides an opportunity for early intervention to improve treatment experience.

Exploratory analysis of the cervix tumoral HPV antigen-specific T-cell repertoire during chemoradiation and after brachytherapy

Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020-1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-β/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2-50.2 fold-increase from baseline), frequency (1.2-1.7), rearrangements (1.2-40.2), and clonality (1.2-15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy.