1039 - Integration of Imaging and Blood-Based Biomarkers for Prognostication in Locally Advanced Cervical Cancer
Presenter(s)
S. Rajan1,2, A. Seo2, M. Jacobsen3, J. Sun2, P. Wei2, K. Court2, L. L. Lin4, A. Jhingran2, C. R. Weil4, M. M. Joyner4, T. Cisneros Napravnik2, A. Venkatesan3, S. Markovina5, S. Grover6, L. Colbert2, M. Gillison7, and A. H. Klopp4; 1Department of Radiation Oncology, University of Iowa Health Care, Iowa City, IA, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, 6Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 7Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):
In locally advanced cervical cancer (LACC), mid-treatment tumor response on MRI and viral cell-free HPV DNA (cfDNA) levels measured three months post-treatment have shown prognostic potential for recurrence. MRI has superior tumor delineation, but use is limited due to accessibility, with reliance on CT prevailing particularly in lower resource settings. By combining response-based imaging and blood-based biomarkers, we aim to improve early or mid-treatment outcome prediction for personalized treatment strategies across resource settings.Materials/Methods:
Fifty-seven patients with LACC were enrolled between 2017 and 2023, all receiving standard-of-care concurrent chemoradiation. Seventeen patients received an additional therapeutic HPV vaccine as part of a clinical trial (PDS0101; IMMUNOCERV). Patient plasma was collected at 1, 3, and 5-weeks. MRI scans were obtained pre-treatment and before brachytherapy, while CT scans were obtained at initial simulation and at first brachytherapy implant. Using IBS-GEC ESTRO-ABS 2021 guidelines, a CT-HRCTV was contoured based on cervix, tumor volume and physical exam to assess tumor response on CT. Radiographic reported MRI tumor volumes were used for comparison. MRI and CT responses were calculated as percent reductions in tumor measurements. Categorical features were summarized, survival outcomes were analyzed with Kaplan-Meier and Cox regression, and tumor measurements were assessed with correlation and linear regression, using R version 4.3.1.Results:
Baseline CT-HRCTV and MRI volumes were highly correlated (R = 0.74; p < 0.001). Median MRI and CT response were 88% (IQR 77% - 97%) and 59% (IQR 43% - 67%), respectively, and significantly associated (p = 0.02). Larger baseline CT-HRCTV and MRI tumor volumes were associated with higher week 3 cfDNA levels significantly (p = 0.046 and p < 0.001). CT response and MRI response were not associated significantly with week 3 cfDNA levels. Greater CT-HRCTV volumes at first brachytherapy were associated with worse recurrence free survival (RFS) and overall survival (OS) (HR = 1.014, p = 0.005, and HR = 1.016, p = 0.007). In a threshold-based analysis (where CT response = 55% and cfDNA levels = 16 at week 3 indicated optimal response), a non-significant trend favored optimal responders over non-optimal responders (estimated 2-year RFS: 100% vs 80%; p = 0.07). In contrast, when analyzed individually, survival analysis by optimal CT response and optimal cfDNA clearance were both non-significant (p > 0.5; estimated 2-year RFS: 80% vs 75% for CT response, 86% vs 81% for cfDNA).Conclusion:
Combining imaging and cfDNA may be more informative than single biomarkers alone, necessitating future research with larger, multinational datasets to validate these findings and optimize biomarker combinations. Identifying patients with optimal biomarker and imaging characteristics may help personalize treatment with regards to radiation dose and use of systemic therapies.