[ 18 F]FDG-PET accurately identifies pathological response early upon neoadjuvant immune checkpoint blockade in head and neck squamous cell carcinoma

Eur J Nucl Med Mol Imaging. 2022 May;49(6):2010-2022. doi: 10.1007/s00259-021-05610-x. Epub 2021 Dec 27.

Abstract

Purpose: To investigate the utility of [18F]FDG-PET as an imaging biomarker for pathological response early upon neoadjuvant immune checkpoint blockade (ICB) in patients with head and neck squamous cell carcinoma (HNSCC) before surgery.

Methods: In the IMCISION trial (NCT03003637), 32 patients with stage II‒IVb HNSCC were treated with neoadjuvant nivolumab with (n = 26) or without (n = 6) ipilimumab (weeks 1 and 3) before surgery (week 5). [18F]FDG-PET/CT scans were acquired at baseline and shortly before surgery in 21 patients. Images were analysed for SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Major and partial pathological responses (MPR and PPR, respectively) to immunotherapy were identified based on the residual viable tumour in the resected primary tumour specimen (≤ 10% and 11-50%, respectively). Pathological response in lymph node metastases was assessed separately. Response for the 2 [18F]FDG-PET-analysable patients who did not undergo surgery was determined clinically and per MR-RECIST v.1.1. A patient with a primary tumour MPR, PPR, or primary tumour MR-RECIST-based response upon immunotherapy was called a responder.

Results: Median ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG decreased in the 8 responders and were significantly lower compared to the 13 non-responders (P = 0.05, P = 0.002, P < 0.001, and P < 0.001). A ΔMTV or ΔTLG of at least - 12.5% detected a primary tumour response with 95% accuracy, compared to 86% for the EORTC criteria. None of the patients with a ΔTLG of - 12.5% or more at the primary tumour site developed a relapse (median FU 23.0 months since surgery). Lymph node metastases with a PPR or MPR (5 metastases in 3 patients) showed a significant decrease in SUVmax (median - 3.1, P = 0.04). However, a SUVmax increase (median + 2.1) was observed in 27 lymph nodes (in 11 patients), while only 13 lymph nodes (48%) contained metastases in the corresponding neck dissection specimen.

Conclusions: Primary tumour response assessment using [18F]FDG-PET-based ΔMTV and ΔTLG accurately identifies pathological responses early upon neoadjuvant ICB in HNSCC, outperforming the EORTC criteria, although pseudoprogression is seen in neck lymph nodes. [18F]FDG-PET could, upon validation, select HNSCC patients for response-driven treatment adaptation in future trials.

Trial registration: https://www.

Clinicaltrials: gov/ , NCT03003637, December 28, 2016.

Keywords: Head and neck squamous cell carcinoma; Metabolic response assessment; Neoadjuvant immune checkpoint blockade; [18F]FDG-PET.

Publication types

  • Clinical Trial

MeSH terms

  • Fluorodeoxyglucose F18*
  • Head and Neck Neoplasms* / diagnostic imaging
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Immune Checkpoint Inhibitors
  • Lymphatic Metastasis
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local
  • Positron Emission Tomography Computed Tomography / methods
  • Radiopharmaceuticals
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / diagnostic imaging
  • Squamous Cell Carcinoma of Head and Neck / therapy

Substances

  • Immune Checkpoint Inhibitors
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18

Associated data

  • ClinicalTrials.gov/NCT03003637