The Additional Value of Ultrafast DCE-MRI to DWI-MRI and 18F-FDG-PET to Detect Occult Primary Head and Neck Squamous Cell Carcinoma

SIMPLE SUMMARY: Patients with cervical lymph node metastasis from squamous cell carcinoma undergo extensive irradiation or surgery of the head and neck with higher treatment morbidity, recurrence rate and lower overall survival than patients with overt primary tumor. In order to enhance treatment efficiency and morbidity reduction, the primary tumor detection accuracy was evaluated by using Ultrafast-Dynamic Contrast-Enhancement (DCE-)MRI in addition to Diffusion-Weighted (DW-)MRI and (18)F-FDG-PET/CT imaging. Ultrafast-DCE, with a temporal resolution of 4 s, enabled capturing lesions with increased neoangiogenesis or perfusion compared to normal tissue. The use of Ultra-fast DCE resulted in higher confidence for suspicious locations and high observer agreement. Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and (18)F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and (18)F-FDG-PET/CT yielded highest sensitivity. ABSTRACT: To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or (18)F-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 (18)F-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 (18)F-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 (18)F-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 (18)F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and (18)F-FDG-PET/CT yielded highest sensitivity.