Diagnostic Accuracy of [68Ga]Ga Labeled Fibroblast-Activation Protein Inhibitors in Detecting Head and Neck Cancer Lesions Using Positron Emission Tomography: A Systematic Review and a Meta-Analysis

Abstract

Several studies have examined the use of positron emission tomography (PET) using [68Ga]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging. The present study incorporates original publications assessing the efficacy of this innovative molecular imaging test in both newly diagnosed and previously treated HNC patients. This systematic review examined eleven investigations, of which nine were deemed suitable for inclusion in the subsequent meta-analysis. The quantitative synthesis yielded a pooled detection rate of 99% for primary HNC lesions. Additionally, on a per patient-based analysis, the pooled sensitivity and specificity for regional lymph node metastases were found to be 90% and 84%, respectively. The analysis revealed a statistical heterogeneity among the studies for the detection rate of primary HNC lesions. The quantitative findings presented in this study indicate a favorable diagnostic performance of FAP-targeted PET imaging in detecting primary HNC tumors. In contrast, discordant results concerning the diagnostic accuracy of lymph node metastases were found. However, further multicentric trials are required to validate the efficacy of FAP-targeted PET in this specific group of patients.

Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications

“…A clear advantage of fibroblast-activating protein inhibitors (FAPi) over 18 F-FDG is their high tumor-to-background contrast that allows an exceptionally clear tumor delimitation in districts with high 18 F-FDG background uptake (e.g., brain, liver, spleen, bowel, and tonsils) [133]. As reported in a recent systematic review and meta-analysis [134], FAPi PET/CT is very useful for detecting unknown primary HN tumors in patients with cervical LN metastases, thanks to higher uptake than surrounding healthy tissue, and is better than 18 F-FDG in assessing skull-base invasion due to negligible brain uptake (superior performance than MRI in patients with nasopharyngeal carcinoma) [135]. Moreover, FAPi PET/CT is helpful for detecting cervical LN metastases from HN cancer, with acceptable sensitivity (80-90%, false-negative findings in lesions < 5 mm) and higher specificity than 18 F-FDG (93.3% vs. 81.3%) due to less inflammatory false-positive nodes [21,136].…”

Diagnostic yield of FAP-guided positron emission tomography in thyroid cancer: a systematic review

“…Nevertheless, the tumour microenvironment (TME), which includes tumour-associated stromal cells and the extracellular matrix, is also crucial in tumour invasion and metastases onset, promoting cell migration ( 17 – 19 ); for example, cancer-associated fibroblasts (CAFs) are a significant component of the tumour stroma. CAFs, also known as reactive fibroblasts or myofibroblasts, are found in a variety of malignant tumours, including head and neck malignancies other than TC ( 20 , 21 ). FAP expression may also variate according to the solid tumours’ grading, such as in prostate cancer ( 22 , 23 ).…”