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. 2022 Dec 17;14(24):6235.
doi: 10.3390/cancers14246235.

Quantitative Diffusion-Weighted Imaging Analyses to Predict Response to Neoadjuvant Immunotherapy in Patients with Locally Advanced Head and Neck Carcinoma

Hedda J van der Hulst  1   2 , Joris L Vos  3   4   5 , Renaud Tissier  6 , Laura A Smit  7 , Roland M Martens  8 , Regina G H Beets-Tan  1   2   9 , Michiel W M van den Brekel  3   10 , Charlotte L Zuur  3   10   11   12 , Jonas A Castelijns  1
Affiliations

Quantitative Diffusion-Weighted Imaging Analyses to Predict Response to Neoadjuvant Immunotherapy in Patients with Locally Advanced Head and Neck Carcinoma

Hedda J van der Hulst et al. Cancers (Basel). .

Abstract

Background: Neoadjuvant immune checkpoint blockade (ICB) prior to surgery may induce early pathological responses in head and neck squamous cell carcinoma (HNSCC) patients. Routine imaging parameters fail to diagnose these responses early on. Magnetic resonance (MR) diffusion-weighted imaging (DWI) has proven to be useful for detecting HNSCC tumor mass after (chemo)radiation therapy.

Methods: 32 patients with stage II-IV, resectable HNSCC, treated at a phase Ib/IIa IMCISION trial (NCT03003637), were retrospectively analyzed using MR-imaging before and after two doses of single agent nivolumab (anti-PD-1) (n = 6) or nivolumab with ipilimumab (anti-CTLA-4) ICB (n = 26). The primary tumors were delineated pre- and post-treatment. A total of 32 features were derived from the delineation and correlated with the tumor regression percentage in the surgical specimen.

Results: MR-DWI data was available for 24 of 32 patients. Smaller baseline tumor diameter (p = 0.01-0.04) and higher sphericity (p = 0.03) were predictive of having a good pathological response to ICB. Post-treatment skewness and the change in skewness between MRIs were negatively correlated with the tumor's regression (p = 0.04, p = 0.02).

Conclusion: Pre-treatment DWI tumor diameter and sphericity may be quantitative biomarkers for the prediction of an early pathological response to ICB. Furthermore, our data indicate that ADC skewness could be a marker for individual response evaluation.

Keywords: diffusion magnetic resonance imaging; immune checkpoint blockade; immunotherapy; magnetic resonance imaging; radiomics; squamous cell carcinoma of head and neck.

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Conflict of interest statement

C.L.Z. is linked to Investigator-initiated clinical trials in collaboration with Bristol Myers Squibb. This funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. All other authors have no conflicts of interest to declare.

Figures

Figure A1
Figure A1
ROC-curve using delta DWI parameters. Responders vs. non-responders. Accuracy: 81.82% (59.72–94.81%). Sensitivity: 100%, Specificity: 69.23%.
Figure 1
Figure 1
DWI and STIR imaging of 2 patients before and after immunotherapy treatment with different treatment outcomes. Pt39, with a primary cT3N0 HNSCC of the oral cavity, is depicted before ((a1) b1000; (a2) ADC-map; (a3) STIR) and after ((b1) b1000; (b2) ADC-map; (b3) S = TIR) immunotherapy; this patient had MPR to treatment. Pt37 with a primary cT3N0 HNSCC of the oral cavity is depicted before ((c1) b1000; (c2) ADC-map; (c3) STIR) and after ((d1) b1000; (d2) ADC-map; (d3) STIR) immunotherapy; this patient had NPR to treatment.
Figure 2
Figure 2
Flow diagram of the patient inclusion. MR-DW: magnetic resonance diffusion weighted, *: Some patients had both a large artefact and low DWI quality.
Figure 3
Figure 3
Boxplot overview of some correlations between responder and non-responder groups. (A) Sphericity or tumor roundness is significantly higher for responders at pre-treatment; this dissipates at post-treatment imaging. (B) Significantly lower levels of entropy can be seen for responders compared to non-responders, but only at pre-treatment imaging. (C) The maximum diameter measured using 3D dimensions is significantly lower at pre-treatment imaging for responders compared to non-responders. (D) No significance of ADC skewness can be seen between the two response groups at pre- or post-treatment. A near-significant result (p = 0.066) is observed for the delta of ADC skewness.
Figure 4
Figure 4
Two different patients illustrating possible tumor microenvironments on T1Wc imaging and on ADC. Figure 4a and b depict pre-immunotherapy imaging of a patient with a residual tumor (rT3N0) after previous CRT with a necrotic area (n) within the tumor region (t) on T1Wc (a), and as shown on ADC-map (b). On the T1Wc imaging, a possible infiltrate (i) could be included in the tumor area, marked by t(+i), as this is difficult to discern. This patient did not respond to treatment. Figure 4c and d depict post-treatment imaging of a cT4N1 primary tumor of the oral cavity, with possible immune infiltrate (i) surrounding the tumor (t), or, conceivably, within the tumor area (t(+i)) on T1wc (c) and ADC-map (d). This patient had a partial pathological response to treatment.
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