Use of Fluoro-[¹⁸F]-Deoxy-2-D-Glucose Positron Emission Tomography/Computed Tomography to Predict Immunotherapy Treatment Response in Patients With Squamous Cell Oral Cavity Cancers

Question  Can fluoro-[¹⁸F]-deoxy-2-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) predict response and immunological changes in patients receiving neoadjuvant immunotherapy for oral cavity squamous cell cancer (OCSCC)?

Findings  In this prospective phase 2 study of 27 patients with OCSCC, there were no correlations between changes in FDG uptake and pathologic primary tumor response or baseline CD8⁺ T-cell infiltrates. Patients developed new FDG-avid cervical lymph nodes after neoadjuvant immunotherapy and systemic immune responses on imaging were observed.

Meaning  Important early patterns of FDG uptake after neoadjuvant immunotherapy for OCSCC did not reflect progressive disease and suggest that surgical plans should not be altered in this setting.

Importance  Neoadjuvant immunotherapy is a novel approach with the potential to improve outcomes for patients with oral cavity squamous cell cancer (OCSCC). Adverse events of varying severity are reported with immunotherapy, and a biomarker to predict response would be clinically useful to avoid toxic effects in those unlikely to benefit.

Objective  To correlate changes on fluoro-[¹⁸F]-deoxy-2-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans with primary tumor pathologic response and immunologic biomarkers in patients with OCSCC receiving neoadjuvant immunotherapy.

Design, Setting, and Participants  This was a retrospective analysis of serial FDG-PET/CT scans obtained prospectively as part of a phase 2 open-label randomized clinical trial investigating neoadjuvant immunotherapy in patients with untreated OCSCC between 2016 and 2019. Included were a total of 29 patients from a single academic medical center with untreated OCSCC (≥T2, or clinically node positive) randomized 1:1 to receive neoadjuvant therapy with single agent nivolumab or combination nivolumab and ipilimumab followed by surgery and standard of care adjuvant therapy.

Interventions  The interventions in this study were FDG-PET/CT scans before (T0) and after (T1) preoperative immunotherapy.

Main Outcomes and Measures  Data collected from FDG-PET/CT scans included maximum standardized uptake value (SUVmax) of primary OCSCC and cervical lymph nodes (LNs) at T0 and T1 and new LN uptake and uptake consistent with radiologic immune-related adverse events (irAEs) at T1. Primary OCSCC pathologic response reported as percentages of viable vs nonviable tumor. The number of CD8⁺ cells/mm² was determined in the primary tumor biopsy specimen and at surgery.

Results  There was no correlation between pathologic response and change in SUVmax in the primary OCSCC between T0 and T1. Out of 27 total participants, 13 had newly FDG-avid ipsilateral LNs at T1, most negative on pathology. A total of 9 had radiologic irAEs, most commonly sarcoid-like LN (7 of 27). No correlations were found between primary OCSCC SUVmax at T0 and CD8⁺ T-cell number in the primary tumor biopsy, and no correlations were found between primary OCSCC SUVmax at T1 and CD8⁺ T-cell number in the primary tumor at surgery.

Conclusions and Relevance  There were no correlations between changes in FDG uptake after neoadjuvant immunotherapy and pathologic primary tumor response. Importantly, newly FDG-avid ipsilateral LNs following neoadjuvant immunotherapy were commonly observed but did not represent progressive disease or indicate pathologically disease positive nodes in most cases. These findings argue against altering surgical plans in this setting and suggest that the role of FDG-PET/CT may be limited as an early imaging biomarker for predicting pathologic response to preoperative immunotherapy for OCSCC.

Trial Registration  ClinicalTrials.gov Identifier: NCT02919683