Post-Treatment FDG-PET/CT Hopkins Criteria Predict Locoregional Recurrence After Definitive Radiotherapy for Oropharyngeal Squamous Cell Carcinoma

Abstract

Surveillance after definitive radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is critical to confirm clinical complete response, as a subset of patients develop locoregional recurrences (LRR). The Hopkins Criteria are a standardized qualitative system for assessing response using post-treatment PET/CT and are validated for overall (OS) and progression-free survival (PFS). We hypothesized that the Hopkins Criteria score is independently prognostic for LRR.We conducted an institutional retrospective study of adult patients with newly-diagnosed node-positive non-metastatic OPSCC treated with definitive (chemo)radiotherapy. Patients were eligible if they completed a pre- and post-radiotherapy PET/CT within 24 weeks after treatment. The primary outcome was the cumulative incidence of locoregional recurrence/persistence. A single board-certified nuclear medicine physician assigned Hopkins scores, which were considered either positive (scores 4-5) or negative (scores 1-3).Between 2004-2018, 259 patients were included in this analysis, while an additional 221 were excluded, most commonly due to lack of post-treatment PET/CT [37%] or N0 disease [22%]. Most patients were men (90%), 47% had never smoked, 86% had p16+/HPV+ tumors, and 39% had T3-4 tumors. Nearly all (98%) received concurrent chemotherapy, while 11% received induction chemotherapy. Median clinical follow-up was 40 months. Following radiotherapy, the first post-treatment PET/CT was positive (score 4-5) at the primary site in 32 patients (12%), cervical lymph nodes in 26 patients (10%), and either the primary site or neck in 50 patients (19%). This PET/CT was performed at a median of 3.3 months [range, 1.6-6.0] after radiotherapy. Thirty-four (13%) LRRs were observed. The sensitivity, specificity, negative predictive value, and overall accuracy of the Hopkins score for LRR were 68%, 88%, 95%, and 85%. The 36-month cumulative incidence of LRR was greater among patients with Hopkins scores 4-5 (45% vs. 5%, multivariable-adjusted HR 14.16, P < 0.001). Positive scores were similarly prognostic for 36-month OS (69% vs. 94%) and PFS (55% vs. 87%). LRR was similar among patients with scores of 3 relative to scores of 1-2. Performance was reduced when PET/CTs were obtained within 2.5 months of radiotherapy (accuracy: ≤2.5 months: 73%; 2.5-3.5 months: 85%; 3.5-6.0 months: 87%). Twenty-two negative biopsies or surgeries were performed among patients without LRR; negative biopsies/surgeries were more common after early PET/CT (≤2.5 months: 36%; 2.5-3.5 months: 9%; 3.5-6.0 months: 9%, P = 0.03).There is a lack of consensus reporting standards for response assessment after definitive radiotherapy for OPSCC. The Hopkins Criteria are an easily-implemented standard that appear to offer high accuracy for recurrence and death. These data support an initial PET/CT at least three months after radiotherapy to limit unnecessary diagnostic procedures.