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

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.

Case report: Patient specific combination of surgery and immunotherapy in advanced squamous cell carcinoma of the head and neck – a case series and review of literature

“…A recent study by Vos et al. proposes [18F] FDG-PET for pathological response assessment in early neoadjuvant ICI, however radiological flare is also present in PET-CT ( 45 ). Regardless, it should be considered that ICI’s effect on the primary tumor site and on potential lymph node metastases may differ ( 46 ).…”

Neoadjuvante Immuntherapie bei Kopf-Hals- Plattenepithelkarzinomen

“…The test validity criteria for MRI in detecting major pathological response were evaluated in one study, showing a high specificity of 100 % but a low sensitivity of 29 % [104]. Conversely, in the same cohort, a metabolic tumor volume or total lesion glycolysis decrease pre-and post-immunotherapy was identified as a potential marker to identify response [120]. Taken together these studies suggest that though hybrid imaging might be able to identify responders, conventional imaging using MRT or CT is unable to differentiate stable or progressive disease from a successful anti-tumor immune response.…”

Imaging glucose metabolism to reveal tumor progression

“…To differentiate between those who will respond to treatment and those who will not, non-invasive in vivo 18F-FDG-PET/CT imaging of glucose metabolism in lymphatic organs might be a valuable preclinical and clinical technique ( Schwenck et al, 2020 ). Vos et al (2022) discovered 18F-FDG-PET-based DeltaMTV and DeltaTLG reliably identified pathological responses to neoadjuvant immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC) before surgery, surpassing the European Organisation For Research And Treatment Of Cancer (EORTC) criteria. However, neck lymph nodes exhibited pseudoprogression.…”

“…MPM may be a condition in which FDG uptake by each cell and its proliferation vary simultaneously. Additional clinical data are listed in Table 2 ( Kahraman et al, 2012 ; Lee et al, 2013 ; Maharjan et al, 2013 ; Usmanij et al, 2013 ; Bhoil et al, 2014 ; Boers-Sonderen et al, 2014 ; Choi et al, 2014 ; Soussan et al, 2014 ; Elimova et al, 2015 ; Tateishi et al, 2015 ; Wong et al, 2016 ; Xie et al, 2016 ; Lim et al, 2017 ; Liu et al, 2017 ; Park et al, 2017 ; Salavati et al, 2017 ; Calandriello et al, 2018 ; Kaira et al, 2018 ; Lovinfosse et al, 2018 ; Wang et al, 2018 ; Avallone et al, 2019 ; Carpenter et al, 2019 ; Dag et al, 2019 ; Mayerhoefer et al, 2019 ; van Berkel et al, 2019 ; Wang L. et al, 2020 ; Deckers et al, 2020 ; Fiore et al, 2020 ; Mathew et al, 2020 ; Mitchell et al, 2020 ; Pan et al, 2020 ; Dunet et al, 2021 ; Vos et al, 2022 ).…”