Predictive Values of MRI and PET Derived Quantitative Parameters for Patterns of Failure in Both p16+ and p16- High Risk Head and Neck Cancer.

Yue Cao,Pin Li,Keith Casper,Paul Swiecicki,Francis Worden,Avraham Eisbruch,Aleksandar F Dragovic,Madhava Aryal,Matthew Schipper,Michelle Mierzwa,Peter G Hawkins,Choonik Lee,Theodore S Lawrence,Christina Chapman,Dawn Owen

doi:10.3389/fonc.2019.01118

Yue Cao, Pin Li + Show 13 more

Open Access

https://doi.org/10.3389/fonc.2019.01118

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Abstract

Purpose: FDG-PET adds to clinical factors, such tumor stage and p16 status, in predicting local (LF), regional (RF), and distant failure (DF) in poor prognosis locally advanced head and neck cancer (HNC) treated with chemoradiation. We hypothesized that MRI-based quantitative imaging (QI) metrics could add to clinical predictors of treatment failure more significantly than FDG-PET metrics.Materials and methods: Fifty four patients with poor prognosis HNCs who were enrolled in an IRB approved prospective adaptive chemoradiotherapy trial were analyzed. MRI-derived gross tumor volume (GTV), blood volume (BV), and apparent diffusion coefficient (ADC) pre-treatment and mid-treatment (fraction 10), as well as pre-treatment FDG PET metrics, were analyzed in primary and individual nodal tumors. Cox proportional hazards models for prediction of LRF and DF free survival were used to test the additional value of QI metrics over dominant clinical predictors.Results: The mean ADC pre-RT and its change rate mid-treatment were significantly higher and lower in p16– than p16+ primary tumors, respectively. A Cox model identified that high mean ADC pre-RT had a high hazard for LF and RF in p16– but not p16+ tumors (p = 0.015). Most interesting, persisting subvolumes of low BV (TVbv) in primary and nodal tumors mid-treatment had high-risk for DF (p < 0.05). Also, total nodal GTV mid-treatment, mean/max SUV of FDG in all nodal tumors, and total nodal TLG were predictive for DF (p < 0.05). When including clinical stage (T4/N3) and total nodal GTV in the model, all nodal PET parameters had a p-value of >0.3, and only TVbv of primary tumors had a p-value of 0.06.Conclusion: MRI-defined biomarkers, especially persisting subvolumes of low BV, add predictive value to clinical variables and compare favorably with FDG-PET imaging markers. MRI could be well-integrated into the radiation therapy workflow for treatment planning, response assessment, and adaptive therapy.

Highlights

Locoregional failure (LRF) remains a clinical challenge for poor prognosis locally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with definitive chemoradiation therapy (CRT) [1]
We report for the first time that the persistent low Blood volume (BV) in primary and nodal tumors during the early course of CRT is associated with high-risk for distant failure
PET is a part of standard care, MRI could play an important role from treatment planning, to early response assessment, and boost target definition

Summary

Introduction

Locoregional failure (LRF) remains a clinical challenge for poor prognosis locally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with definitive chemoradiation therapy (CRT) [1]. We and others have been developing prognostic and predictive imaging markers of PET and MRI for LRF, distant metastases, progression free survival (PFS), and overall survival (OS) [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. Retrospective studies of pre-treatment FDGPET that quantify cellular glucose metabolism have identified metabolic tumor volume (MTV), total lesion glycolysis (TLG), and mean/max standard uptake value (SUV) in MTV as prognostic for LRF, PFS, and OS in HNSCC [2,3,4,5,6]. Functional MRI incorporating diffusion and perfusion parameters is an emerging advanced imaging modality in HNSCC. Perfused and low oxygenation tumors have been shown to be associated with LRF and worse survival outcomes [12,13,14,15,16,17,18]

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