To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or ¹⁸F-FDG-PET and the combination of modalities for the detection of unknown primary tumor (UPT) in patients presenting with cervical lymph node metastasis from squamous cell carcinoma (SCC). Between 2014–2019, patients with histologically proven cervical lymph node metastasis of UPT SCC were prospectively included and underwent DWI, ultrafast-DCE, and ¹⁸F-FDG-PET/CT. Qualitative assessment was performed by two observers per modality. Interobserver agreement was calculated using the proportion specific agreement. Diagnostic accuracy of combined use of DWI, ultrafast-DCE and ¹⁸F-FDG-PET/CT was assessed. Twenty-nine patients were included (20 males. [68%], median age 60 years). Nine (31%) primary tumors remained occult. Ultrafast-DCE added reader confidence for suspicious locations (one additional true positive (5%), 2 decisive true malignant (10%). The per-location analysis showed highest specific positive agreement for ultrafast-DCE (77.6%). The per-location rating showed highest sensitivity (95%, 95%CI = 75.1–99.9, YI = 0.814) when either one of all modalities was scored positive, and 97.4% (95%CI = 93.5–99.3, YI = 0.774) specificity when co-detected on all. The per-patient analysis showed highest sensitivity (100%) for ¹⁸F-FDG-PET/CT (YI = 0.222) and either DWI or PET (YI = 0.111). Despite highest trends, no significant differences were found. The per-patient analysis showed highest specific positive agreement when co-detected on all modalities (55.6%, 95%CI = 21.2–86.3, YI = 0.456). Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and ¹⁸F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and ¹⁸F-FDG-PET/CT yielded highest sensitivity.

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.

Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for nodal staging in head and neck squamous cell cancer (HNSCC). Peripheral vascularity is a described feature for node metastasis. Micro-flow imaging (MFI) is a new sensitive technique to evaluate micro-vascularization. Our goal is to assess the additional value of MFI to detect malignancy in lymph nodes. A total of 102 patients with HNSCC were included prospectively. USgFNAC was performed with the Philips eL18–4 transducer. Cytological results served as a reference standard to evaluate the prediction of cytological malignancy depending on ultrasound features such as resistive index (RI), absence of fatty hilum sign, and peripheral vascularization. Results were obtained for all US examinations and for the subgroup of clinically node-negative neck (cN0). USgFNAC was performed in 211 nodes. Peripheral vascularization had a positive predictive value (PPV) of 83% (cN0: 50%) and the absence of a fatty hilum had a PPV of 82% (cN0 50%) The combination of peripheral vascularization and absent fatty hilum had a PPV of 94% (cN0: 72%). RI (threshold: 0.705) had a PPV of 61% (cN0: RI-threshold 0.615, PPV 20%), whereas the PPV of short axis diameter (threshold of 6.5mm) was 59% for all patients and 19% in cN0 necks (threshold of 4 mm). Peripheral vascularization assessed by MFI and absent hilum has a high predictive value for cytological malignancy in neck metastases. Next to size, both features should be used as additional selection criteria for USgFNAC.

Magnetic resonance imaging (MRI) is an indispensable, routine technique that provides morphological and functional imaging sequences. MRI can potentially capture tumor biology and allow for longitudinal evaluation of head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis evaluates the ability of MRI to predict tumor biology in primary HNSCC. Studies were screened, selected, and assessed for quality using appropriate tools according to the PRISMA criteria. Fifty-eight articles were analyzed, examining the relationship between (functional) MRI parameters and biological features and genetics. Most studies focused on HPV status associations, revealing that HPV-positive tumors consistently exhibited lower ADC_mean (SMD: 0.82; p < 0.001) and ADC_minimum (SMD: 0.56; p < 0.001) values. On average, lower ADC_mean values are associated with high Ki-67 levels, linking this diffusion restriction to high cellularity. Several perfusion parameters of the vascular compartment were significantly associated with HIF-1α. Analysis of other biological factors (VEGF, EGFR, tumor cell count, p53, and MVD) yielded inconclusive results. Larger datasets with homogenous acquisition are required to develop and test radiomic-based prediction models capable of capturing different aspects of the underlying tumor biology. Overall, our study shows that rapid and non-invasive characterization of tumor biology via MRI is feasible and could enhance clinical outcome predictions and personalized patient management for HNSCC.

BACKGROUND AND PURPOSE: New imaging techniques such as hybrid imaging of ultrasound and FDG-PET/CT are available but not yet investigated for node staging. The aim of the study was to evaluate the feasibility and added diagnostic value of real-time image-fused ultrasound-guided fine-needle aspiration with FDG-PET/CT data for node staging. MATERIALS AND METHODS: Ninety-six patients who were referred for cervical lymph node staging with FDG-PET/CT before ultrasound were prospectively included. After routine ultrasound-guided fine-needle aspiration, all FDG-PET-positive nodes were marked on FDG-PET/CT, and real-time image fusing of ultrasound and FDG-PET/CT was performed using the electromagnetic navigation system PercuNav. Already-punctured nodes were confirmed to be PET-positive, and additional fused-ultrasound-guided fine-needle aspiration was performed in previously missed PET-positive nodes. RESULTS: Of 96 patients, 87 (91%) patients had suspicious nodes requiring fine-needle aspiration cytology. Ultrasound-guided fine-needle aspiration was performed in 175 nodes. Cytology was inconclusive in 9/175 (5%) nodes, and 85/166 (51%) nodes were malignant. Target planning was performed in 201 PET-positive nodes; 195/201 (97%) of those nodes were fused successfully. Twenty of 175 ultrasound-guided fine-needle aspiration nodes turned out to be FDG-PET-negative, and 149/175 (85%) of the fused ultrasound-guided fine-needle aspiration nodes were confirmed to be FDG-PET-positive. Of 201 PET-positive nodes, 46 (23%) were additionally identified, and fused ultrasound-guided fine-needle aspiration was performed. Cytology was inconclusive in 4/46 nodes (9%), and 13/42 (31%) nodes were malignant. CONCLUSIONS: Real-time ultrasound image fusion with FDG-PET-positive nodes is feasible in cervical lymph nodes, and fused ultrasound-guided fine-needle aspiration increases the number of malignant nodes detected.