Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)-interreader reliability, accuracy, and survival outcomes

Abstract

There has been no established qualitative system of interpretation for therapy response assessment using PET/CT for head and neck cancers. The objective of this study was to validate the Hopkins interpretation system to assess therapy response and survival outcome in head and neck squamous cell cancer patients (HNSCC).

Methods: The study included 214 biopsy-proven HNSCC patients who underwent a posttherapy PET/CT study, between 5 and 24 wk after completion of treatment. The median follow-up was 27 mo. PET/CT studies were interpreted by 3 nuclear medicine physicians, independently. The studies were scored using a qualitative 5-point scale, for the primary tumor, for the right and left neck, and for overall assessment. Scores 1, 2, and 3 were considered negative for tumors, and scores 4 and 5 were considered positive for tumors. The Cohen κ coefficient (κ) was calculated to measure interreader agreement. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier plots with a Mantel-Cox log-rank test and Gehan Breslow Wilcoxon test for comparisons.

Results: Of the 214 patients, 175 were men and 39 were women. There was 85.98%, 95.33%, 93.46%, and 87.38% agreement between the readers for overall, left neck, right neck, and primary tumor site response scores, respectively. The corresponding κ coefficients for interreader agreement between readers were, 0.69-0.79, 0.68-0.83, 0.69-0.87, and 0.79-0.86 for overall, left neck, right neck, and primary tumor site response, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the therapy assessment were 68.1%, 92.2%, 71.1%, 91.1%, and 86.9%, respectively. Cox multivariate regression analysis showed human papillomavirus (HPV) status and PET/CT interpretation were the only factors associated with PFS and OS. Among the HPV-positive patients (n = 123), there was a significant difference in PFS (hazard ratio [HR], 0.14; 95% confidence interval, 0.03-0.57; P = 0.0063) and OS (HR, 0.01; 95% confidence interval, 0.00-0.13; P = 0.0006) between the patients who had a score negative for residual tumor versus positive for residual tumor. A similar significant difference was observed in PFS and OS for all patients. There was also a significant difference in the PFS of patients with PET-avid residual disease in one site versus multiple sites in the neck (HR, 0.23; log-rank P = 0.004).

Conclusion: The Hopkins 5-point qualitative therapy response interpretation criteria for head and neck PET/CT has substantial interreader agreement and excellent negative predictive value and predicts OS and PFS in patients with HPV-positive HNSCC.

Keywords: Hopkins PET interpretation criteria; head and neck; therapy assessment.

Conflict of interest statement

DISCLOSURE

No potential conflict of interest relevant to this article was reported.

© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Figures

FIGURE 1

Hopkins head and neck therapy assessment criteria: primary tumor—axial fused PET/CT images. (A) Score 1 demonstrates no evidence of increased 18F-FDG uptake within site of primary tumor, consistent with complete treatment response. (B) Score 2 demonstrates minimal activity at primary tumor site, consistent with likely complete treatment response. (C) Score 3 demonstrates diffuse 18F-FDG activity within oropharyngeal soft tissue, consistent with probable postradiation inflammatory changes. (D) Score 4 demonstrates moderate focal 18F-FDG uptake within oropharyngeal mass, consistent with likely residual disease. (E) Score 5 demonstrates large laryngeal mass with focal, intense 18F-FDG uptake, consistent with residual disease. Arrows point to where original primary tumor was before treatment and degree of 18F-FDG uptake in posttherapy scans.

FIGURE 2

Hopkins head and neck therapy assessment criteria: Neck node—axial fused PET/CT images. (A) Score 1 demonstrates no evidence of 18F-FDG–avid residual nodal disease in neck, consistent with complete metabolic response. (B) Score 2 demonstrates minimal 18F-FDG activity within left level IIA cervical lymph node, consistent with likely complete metabolic response. (C) Score 3 demonstrates mild 18F-FDG activity with right level-IIA cervical lymph node, consistent with probable postradiation inflammatory changes. (D) Score 4 demonstrates moderate, focal 18F-FDG activity within right level-IIB cervical lymph node, consistent with likely residual nodal neck disease. (E) Score 5 demonstrates intense, focal 18F-FDG activity within left level-III cervical lymph node, consistent with residual neck nodal disease. Arrows point to where original nodal metastasis was before treatment and degree of 18F-FDG uptake in posttherapy scans.

FIGURE 3

Kaplan–Meier survival curves for all patients. OS (A) and PFS (B) differed significantly between patients with negative PET result (score 1–3) and positive PET result (score 4 or 5) according to therapy assessment scoring system.

FIGURE 4

Kaplan–Meier survival curves for patients with 18F-FDG–avid lesions at single site (primary site or right neck or left neck) versus multiple sites. (A) OS did not show significant difference between the 2 groups. (B) PFS differed significantly between the 2 groups of patients.

FIGURE 5

Kaplan–Meier survival curves for HPV-positive patients. OS (A) and PFS (B) differed significantly between patients, with negative PET result (score 1–3) and positive PET result (score 4 or 5) according to therapy assessment scoring system.