Assessment of Tumor Burden and Response by RECIST vs. Volume Change in HPV+ Oropharyngeal Cancer – An Exploratory Analysis of Prospective Trials

Abstract

<h3>Purpose/Objective(s)</h3> Tumor burden and response to therapy are commonly assessed using RECIST, however, unidimensional evaluation may not fully characterize disease dynamics. Using HPV+ oropharyngeal carcinoma as a tumor model, here we report a comparison of RECIST and volumetric measurements from 2 consecutive prospective trials of response-adaptive de-escalation of therapy. <h3>Materials/Methods</h3> Patients enrolled on 2 prospective phase II response adapted de-escalation trials for low- and high-risk HPV+ oropharynx cancer were included in the analysis. Patients received induction chemotherapy in trial 1 and induction chemoimmunotherapy in trial 2. Target lesions were initially assessed using RECIST 1.1 at baseline and post-induction therapy; patients with ≥ 50% response by RECIST received de-escalated radiation dose and treatment volume per protocol. Primary tumors and nodes were retrospectively delineated on diagnostic scans before and after induction therapy to ascertain volumetric tumor burden and response. Mean differences in RECIST and volume were evaluated with paired t-tests. Linear regression and chi-squared analysis were used to evaluate the correlation between percent change in tumor burden as well as de-escalation-concordance. Outcomes were overall excellent with use of 50% response by RECIST to guide de-escalation as reported previously. Analysis was thus done to identify proportion that responded 50% by volume. <h3>Results</h3> 104 patients (N=54 Trial 1, N=50 Trial 2) were evaluable. The mean post-induction therapy reduction in RECIST and volumetry was 3.13 cm and 25.18 cm³ respectively (<i>p</i><0.001). Primary tumor response to induction was greater than nodal response for both RECIST and volumetry. The mean percent difference in size post induction was 27.3% and 14.8% for RECIST and volumetry. Percent change in RECIST was correlated with volume change, <i>r</i> = 0.687 (<i>p</i><0.001). An increased proportion (<i>p</i>=0.008) of patients would be eligible for de-escalation based on response assessment (72% de-escalated by RECIST vs 89% by volumetry), and 4% (N=4) of patients who were de-escalated by RECIST would not meet criteria for de-escalation by volumetry. 2 of these 4 patients developed a local failure. <h3>Conclusion</h3> Here we report on volumetry as a novel response assessment tool. While volumetry was correlated with RECIST, a large proportion of variance in volume-based measurements was not accounted for by RECIST. Furthermore, volumetry-based assessment of tumor burden and response provided a more robust assessment of tumor response and subsequent decision to de-escalate therapy. Patients that responded by RECIST but not volume had higher rates of local failure. In addition, a higher proportion of patients met response criteria by volume and could have been considered for de-escalation.