Importance of Radiographic Tumor Regression during Radiotherapy in Squamous Cell vs. Adenocarcinoma of the Uterine Cervix as Assessed by MRI, CT and Conebeam CT

Abstract

<h3>Purpose/Objective(s)</h3> The purpose of this study was to evaluate the kinetics of tumor regression in cervical SCC and AC across the different imaging modalities used for patients undergoing radiotherapy, and to evaluate locoregional relapse (LRR), progression-free survival (PFS) and overall survival (OS) of each cohort and correlate these data with rate of regression of the primary tumor during treatment, and the percent of residual tumor after external beam. <h3>Materials/Methods</h3> Thirty-two patients with stage IB2-IVA cervical cancer were selected with all 3 imaging modalities from an institutional database with a 2:1 ratio of squamous cell carcinoma to adenocarcinoma. All available CT (113 scans), on-treatment weekly conebeam CT (CBCT; 100 scans) and MRIs (MRI₁ at diagnosis and MRI₂ prior to brachytherapy; 48 scans) were imported into planning software and tumor GTV volumes contoured (CT and MRI), or largest two-dimensional area of tumor delineated (CBCT). Volume regression over time curves were generated, and size and rate of regression, and the percent of residual tumor were correlated to disease progression and disease-specific survival (DSS), with receiver-operator curves and machine learning algorithms used to identify thresholds. Kaplan-Meier estimators were used for survival analysis. Fine-Grey analysis was used to estimate cumulative incidence of progression, using a competing risk of death. <h3>Results</h3> With a median follow-up of 2.9 years (yrs), 32 patients were included, 22 (69%) with SCC and 10 (31%) with AC. All were treated with concurrent chemoradiation with 45 Gy in 25 fractions with weekly cisplatin, followed by brachytherapy. The majority received 5 brachytherapy fractions (59%). 2/22 (9%) with SCC and 1/10 (10%) with AC had local progression. The 1- and 2-yr cumulative incidence (CI) of local progression for both SCC and AC was 10% at both time points. Distant progression was higher in AC (60%, 6/10) compared with SCC (9%, 2/22) For SCC vs AC, the 2-yr CI of distant progression was 9% vs 57% (p=0.02). Ten of 32 patients died (31%), 3/22 (14%) with SCC and 7/10 (70%) with AC. For SCC patients, 2-yr DSS was 90%, versus 60 % for AC. Extent and rate of regression on CT and CBCT data were not correlated with progression or survival in this cohort; however, these data showed consistent rates of tumor regression. A threshold of >20% residual on MRI₂ was identified and was correlated with worse 2-yr PFS (50% vs 90%, p=0.013) and 1-yr DSS (83% vs 100%, p<0.001). Median residual volume on MRI₂ trended toward significant between SCC and AC (55% vs 16%, p=0.052). <h3>Conclusion</h3> This study showed cervical AC is associated with higher rates of distant progression and worse overall survival than SCC. Cervical AC tends to have a higher residual tumor burden. Our identified threshold of >20% residual tumor on MRI₂ correlating with worse PFS and distant progression may help identify escalation of systemic therapy in select patients.