Metabolic Tumor Volume Changes Measured by18F-FDG-PET/CT After 1 Cycle of Induction Chemotherapy Is an Early Predictor of Radical Chemoradiation Therapy Outcome in Head and Neck Squamous Cell Carcinoma

Abstract

To assess the predictive value of 18F-FDG positron emission tomography/computed tomography (PET/CT) parameter changes during induction chemotherapy (IC) for response to radical chemoradiation therapy (CRT) in head and neck squamous cell carcinoma (HNSCC). This is an ongoing prospective, single-institution study in which patients underwent 18F-FDG-PET/CT with thermoplastic shell immobilization before and 2 weeks following each cycle of IC (first cycle, IC1; second cycle, IC2). Following IC, patients received radical CRT (65 Gy in 30 fractions) over 6 weeks with concomitant chemotherapy on days 1 and 29. Treatment response was assessed at 3 months from completion of CRT with clinical examination, magnetic resonance imaging, and 18F-FDG-PET/CT. Patients with evidence of residual or progressive disease were classed as nonresponders. Reductions in tumor SUVmax (maximum standard uptake value) and MTV (metabolic tumor volume with a pre-determined SUV threshold of 3.5) following IC were compared between responders versus non-responders with Mann-Whitney U test. The significance threshold was set at P<.05. Twenty patients with stage III-IVA HNSCC were included in this preliminary analysis. The median age was 63 years (47-69). All patients underwent 2 cycles of IC except 3 patients who stopped after 1 cycle due to poor tolerance. One patient did not receive concomitant chemotherapy due to persistent myelosuppression. In 17 evaluable patients, there was no significant difference in the changes from baseline between IC1 and IC2 for MTV (P=.80) and SUVmax (P=.10), indicating that most metabolic response to IC was observed early with little changes with subsequent cycle. There were 15 responders and 5 nonresponders (all had local failure with 2 also having distant metastases). Pretreatment MTV differed between the 2 groups (21.9±16.5 cm3 vs 56.7±24.6 cm3, P=.01) but not SUVmax (P=.17). Responders showed a significantly greater mean MTV reduction following IC1: 84.3±19.4% vs 29.6±55.8% than did nonresponders (P=.03). The SUVmax reduction was not discriminative between the 2 groups following IC1 (P=.12) but did reach statistical significance following IC2 (P=.01). A combination of pretreatment MTV<50 cm3 and MTV reduction >60% following IC1 gives a sensitivity, specificity, and positive and negative predictive value of 87%, 80%, 93%, and 67%, respectively in predicting complete response to CRT. Our preliminary data suggested that ascertaining MTV response (or lack of it) as early as IC1 could help to identify patients at risk of treatment failure in a timely way, which allows more scope to consider alternative treatment strategies such as radiation therapy dose escalation or surgery. On the other hand, SUVmax response to IC was more gradual and unsuitable for early assessment, that is, prior to IC2. This study will be further reported in the future with more patients and 2 years of disease-free survival.