F18-FDG PET/CT imaging early predicts pathologic complete response to induction chemoimmunotherapy of locally advanced head and neck cancer: preliminary single-center analysis of the checkrad-cd8 trial

Abstract

Aim: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy.

Methods: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3-14 days before (pre-ICIT) and 21-28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu).

Results: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value.

Conclusion: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value.

Trial registry: ClinicalTrials.gov identifier: NCT03426657.

Keywords: FDG-PET/CT; HNSCC; Head neck cancer; Immunotherapy; Induction therapy.

Conflict of interest statement

M.B. conflict of interest with Novartis (travel expenses); Bayer (advisory role, honoraria); SIRTEX (travel expenses). J.H. has no conflict of interest. M.E. conflict of interest with Diaceutics (employment, honoraria, advisory role, speakers’ bureau, travel expenses); AstraZeneca (honoraria, advisory role, speakers’ bureau, travel expenses); Roche (honoraria, travel expenses); MSD (honoraria, speakers’ bureau); GenomicHealth (honoraria, advisory role, speakers bureau, travel expenses); Astellas (honoraria, speakers’ bureau); Janssen-Cilag (honoraria, advisory role, research funding, travel expenses); Stratifyer (research funding, patents). D.S. has no conflict of interest. A.O.G. has no conflict of interest. S.M. has no conflict of interest. S.R. conflict of interest with AstraZeneca (research funding); MSD (research funding). U.S.G. conflict of interest with AstraZeneca (advisory role, research funding); BMS (advisory role); MSD (research funding); Sennewald Medizintechnik (travel expenses). J.G. has no conflict of interest. I.T. has no conflict of interest. M.G.H. conflict of interest with Roche (stock, honoraria); Varian (stock); Sanofi (honoraria); AstraZeneca (honoraria, travel expenses); BMS (honoraria, advisory role); MSD (honoraria, advisory role); Merck Serono (honoraria); Celgene (honoraria). G.K. conflict of interest with BMS (advisory role); Lilly (advisory role); Roche (advisory role). J.D. has no conflict of interest. B.T. conflict of interest with BMS (honoraria, advisory role, travel expenses); Merck Serono (honoraria, advisory role); MSD (travel expenses). A.H. conflict of interest with BMS (honoraria, advisory role); MSD (honoraria, advisory role); Roche (honoraria, advisory role, research funding); AstraZeneca (honoraria, advisory role, research funding); Boehringer Ingelheim (honoraria); Abbvie (honoraria); Cepheid (advisory role, research funding); Quiagen (advisory role); Janssen-Cilag (honoraria, advisory role, research funding); Ipsen (honoraria, advisory role); NanoString Technologies (advisory role, research funding, expert testimony); Illumina (advisory role); 3DHistech (advisory role); Diaceutics (advisory role); BioNTech (research funding). H.I. has no conflict of interest. T.K. conflict of interest with Siemens Healthineers (advisory role, honoraria, speakers’ bureau, travel expenses, research funding). R.F. conflict of interest with MSD (honoraria, advisory role, research funding, travel expenses); Fresenius (honoraria); BrainLab (honoraria); AstraZeneca (honoraria, advisory role, research funding, travel expenses); Merck Serono (advisory role, research funding, travel expenses); Novocure (advisory role, speakers’ bureau, research funding); Sennewald (speakers’ bureau, travel expenses). The other authors declare no conflicts of interest. M.H. conflict of interest with Merck Serono (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); MSD (advisory role, speakers’ bureau, travel expenses, research funding); AstraZeneca (research funding); Novartis (research funding); BMS (advisory role, honoraria, speakers’ bureau); Teva (travel expenses). S.S. conflict of interest with Strycker (stock); Varian (stock); Abbot (stock); Crispr Techn. (stock); Pfitzer (stock); Merck Serono (stock); Symrise (stock); Ortho (honoraria, advisory role, speakers’ bureau, research funding, travel expenses); PharmaMar (speakers’ bureau, travel expenses); Haema (speakers’ bureau).

© 2022. The Author(s).

Figures

Fig. 1

Flowchart of the CheckRad CD-8 trial design BSA body surface area, pCR pathological complete remission; ReTu residual tumor

Fig. 2

Upper row: Representative patient with (A) cT2 cN2c HNSCC of hypopharynx prior to induction chemoimmunotherapy. FDG-PET/CT records a high baseline metabolic activity high (SUVmax, 19.8). Histology shows a moderately to poorly differentiated non-keratinizing squamous cell carcinoma (B) HE staining with a low levels of stromal and intratumoral infiltration with cytotoxic T-Cells (CD8 immunohistochemistry) (C). Lower row: Same patient after ICIT: (D) marked decline in uptake by primary tumor (SUVmax, 2.8; ΔSUVpeak, 85.9%). Histology shows a densely packed lymphoid stroma in the HE stain (E) with CD8 positive lymphocytes after immunolabeling (D) but without evidence of viable tumor cells (F). PT primary tumor, SUV standardized uptake value, HE stain hematoxylin and eosin stain

Fig. 3

Receiver operating characteristic (ROC) curve plotted for complete remission in subset of patients with nodal metastasis (n = 25)