Reply: Qualitative ¹⁸F-FDG PET/CT Response Evaluation After Chemotherapy or Radiotherapy for Head and Neck Squamous Cell Carcinoma: Is There an Equivocal Group?

REPLY: We agree that having an equivocal group is a challenging clinical issue in assessing patients with head and neck squamous cell carcinoma after chemoradiation therapy. The Hopkins criteria (1) are a simple, standardized, qualitative method of assessing therapy, or a “perceptual quantitation,” based on ¹⁸F-FDG uptake in the local blood pool (internal jugular vein) and liver and the intuition of the interpreter. Although we dichotomized the standardized interpretation as negative (scores of 1–3) and positive (scores of 4 and 5) for the purpose of clinical utility, statistical analysis for truth, and outcome prediction, the patients who were categorized as having a score of 3 were the equivocal group in which ¹⁸F-FDG uptake was diffuse in an irradiated area and the degree of uptake was greater than that of the liver. This we interpreted as more likely representing radiation-induced inflammation than residual tumor. There were 44 patients categorized into this group (score of 3), and 6 of these patients (13.6%) had disease recurrence by biopsy or within 6 mo of follow-up. There were 68 patients with a score of 1 and 52 patients with a score of 2. Among these patients, 4 (6%) and 5 (9.6%), respectively, had false-negative results, with recurrence within 6 mo as the reference standard. We believe the false-negative numbers in these groups are at the upper limit and conservative, as the reference standard we used was identification of recurrence within 6 mo rather than true residual disease at the time of the PET/CT studies. Hence, the true-negative predictive value for therapy assessment is likely higher than what we reported.

We acknowledge that distinguishing postradiation inflammation from residual tumor is challenging and that perceptual quantitation or standardized qualitative methods (such as recognition of pattern of uptake (2) and degree of uptake, using blood pool and liver ¹⁸F-FDG uptake as the reference standard) may be more valuable than numeric quantitation (such as maximum standardized uptake value and other parameters). This approach of perceptual quantitation incorporates the interpreter’s intuition and human intelligence in this difficult challenge with a standardized approach. We continue to evaluate patients categorized as being in an equivocal group (score of 3) to develop a systematic way of resolving postirradiation inflammation versus residual tumor.

We acknowledge that many investigators have used qualitative methods for clinical ¹⁸F-FDG PET/CT assessment of head and neck cancer therapy (3,4). However, the Hopkins criteria explicitly standardize the categorization reference as ¹⁸F-FDG uptake in the liver and in the background blood pool in the internal jugular vein. In addition, the Hopkins criteria have established that the method is reliable among multiple interpreters and is linked to outcomes in both human papillomavirus–positive and –negative head and neck cancer patients.

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