Radiomics Based Assessment of Tumor Infiltrating CD8 T-Cells Predicts Induction Systemic Therapy Response in HPV+ Oropharyngeal Cancer: Exploratory Analysis of Prospective Trials

Abstract

The adaptive immune system is increasingly recognized to be important for tumor control in HPV+ oropharyngeal cancer (HPV+OPC), and pre-clinical models suggest tumor specific T-cell priming occurs in draining lymph nodes. De-escalation strategies incorporating T-cell infiltration present a novel prognostic biomarker. The purpose of this study was to examine the utility of a validated radiomics model of CD8 T-cell infiltration within the framework of 2 prospective HPV+OPC response-adaptive de-escalation trials. We hypothesized that nodal radiomics scores (RS) would be correlated with response to induction systemic therapy. Patients enrolled on 2 prospective phase II response adapted de-escalation trials for low- and high-risk HPV+OPC were included in the analysis. Patients received induction chemotherapy and chemoimmunotherapy in trials 1 and 2, respectively. Primary tumors and nodes were retrospectively delineated on diagnostic CT scans before and after induction therapy to ascertain volumetric tumor burden & response. RS were generated on pre-induction scans for both primary tumors and nodes. RS and tumor response were dichotomized using a 50% threshold (high vs low, responder vs non-responder, respectively). Linear regression was used to evaluate the correlation between % volume change in tumor burden and RS. Fisher's exact test was used to evaluate concordance between RS and tumor response. A total of 87 patients (N = 47 Trial 1, N = 40 Trial 2) were evaluable. The mean post-induction therapy reduction in primary and nodal volumetry was 80.7% and 67% respectively. Primary and nodal RS were not associated with primary (T1/T2 vs T3/T4) or nodal stage (N1-N2b vs N2c-N, p > 0.10 both). Both primary and nodal RS were correlated with % volume change, r = 0.24 (p = 0.034) and r = 0.37 (p = 0.002), respectively. The mean difference in % volume change in primary and node, using the RS, was 11.13% (p = 0.015) and 17. 69% (p = 0.004). There was no association between primary tumor RS and total lesion responder status (p = 0.312). However, there was an association between high vs low nodal RS and total lesion responder status (p = 0.005). This is the first report of a validated radiomics score of CD8-T cell infiltration in HPV+OPC to predict response to systemic therapy. While radiomics scores in both the primary and nodes were associated with percent volume response, this association was stronger in nodes. Higher nodal radiomics scores were associated with improved volume reduction in total lesion burden. This effect however was not observed in the primary tumor. CD8-T cell infiltration in nodes, but not in the primary tumor, was associated with overall tumor response after systemic induction therapy in HPV+ oropharyngeal cancer.