Prospective Imaging Assessment of Mortality Risk After Head-and-Neck Radiotherapy

Purpose

The optimal roles for imaging-based biomarkers in the management of head-and-neck cancer remain undefined. Unresolved questions include whether functional or anatomic imaging might improve mortality risk assessment for this disease. We addressed these issues in a prospective institutional trial.

Methods and Materials

Ninety-eight patients with locally advanced pharyngolaryngeal squamous cell cancer were enrolled. Each underwent pre- and post-chemoradiotherapy contrast-enhanced computed tomography (CT) and ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT imaging. Imaging parameters were correlated with survival outcomes.

Results

Low post-radiation primary tumor FDG avidity correlated with improved survival on multivariate analysis; so too did complete primary tumor response by CT alone. Although both imaging modalities lacked sensitivity, each had high specificity and negative predictive value for disease-specific mortality risk assessment. Kaplan-Meier estimates confirmed that both CT and FDG-PET/CT stratify patients into distinct high- and low-probability survivorship groups on the basis of primary tumor response to radiotherapy. Subset analyses demonstrated that the prognostic value for each imaging modality was primarily derived from patients at high risk for local treatment failure (human papillomavirus [HPV]-negative disease, nonoropharyngeal primary disease, or tobacco use).

Conclusions

CT alone and FDG-PET/CT are potentially useful tools in head-and-neck cancer–specific mortality risk assessment after radiotherapy, particularly for selective use in cases of high-risk HPV-unrelated disease. Focus should be placed on corroboration and refinement of patient selection for imaging-based biomarkers in future studies.

Introduction

Long-term survival rates of approximately 50% on recent Phase III trials for squamous cell carcinomas of the head and neck (HNSCC) highlight the continued need to reduce mortality from this disease 1, 2, 3. Multiple retrospective series suggest that the metabolic response of HNSCC to chemoradiotherapy correlates directly with overall survival, raising the possibility that outcomes might be improved by using ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) to triage nonresponding patients to further therapy 4, 5, 6. However, these data are limited by the biases inherent in conducting retrospective studies. They have also largely ignored the important issues of comparing the utility of PET to more affordable imaging alternatives, such as computed tomography (CT) imaging alone. As a result, the appropriate role of imaging in predicting survival outcomes for HNSCC patients remains undefined.

We previously reported the results of a prospective clinical trial comparing radiation response assessment with FDG-PET/CT and contrast-enhanced CT, demonstrating equivalent accuracies for the general population and superiority of FDG-PET/CT for a subset of patients at high risk for local treatment failure (7). We now present a formal survival outcome analysis from this trial to address the potential roles of CT- and FDG-PET/CT as imaging-based biomarkers for mortality risk in head-and-neck radiotherapy patients.