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. 2021 Dec 27;49(6):2010–2022. doi: 10.1007/s00259-021-05610-x

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — SUV_max waterfall plot and two cases illustrating the EORTC criteria’s relative inaccuracy to determine pathologic response at the primary tumour site early upon neoadjuvant ICB in HNSCC. a Waterfall plot presenting the percentage change in primary tumour SUV_max from baseline to on-treatment per individual patient. Green bars represent pathological responders, red bars non-responders. Patients in whom response was assessed per MR-RECIST are marked with an asterisk. Dotted grey lines at 25% and − 25% represent the EORTC criteria for progressive metabolic disease (PMD) and partial metabolic response (PMR), respectively; patients in between both lines had stable metabolic disease SMD. Two patients visually had a complete metabolic response (marked CMR), though the SUV_max did not become 0. Patients marked with b and c are further illustrated under b and c, respectively. b A patient with clinically rT2N0 carcinoma of the left cheek mucosa demonstrated primary tumour PMD after 2 cycles of nivolumab + ipilimumab, with a SUV_max increase from 5.4 to 11.7 (117%). Evaluation of the surgically resected specimen (right panel) revealed a major (near-complete) pathological response, with some viable residual tumour (‘T’) surrounded by a dense infiltrate of immune cells (‘IC’). c A patient with cT4aN2b HNSCC of the floor of the mouth shows a SUV_max increase from 15.9 to 17.5 (10%). Correlative histopathology shows a partial pathological response: 69% of the histologically identifiable tumour bed is taken up by keratinous debris (KD) under apparent clearance of multinucleated giant cells and foamy macrophages (arrows)