Comparison of early response assessment with Ga-68 FAPI PET/CT and F-18 FDG PET/CT in Non-small cell lung cancer

Introduction: Lung cancer contributes significantly to cancer-related deaths worldwide. Therapeutic response assessment is crucial for personalized treatment planning and treatment outcomes. An accurate response assessment can help the treating physicians and improve the patient's survival. FDG PET/CT provides an early and more precise therapeutic response than the CT scan. Ga-68 FAPI PET/CT has emerged as a promising modality for evaluating NSCLC. In the present study, we aimed to compare the role of F-18 FDG PET/CT and Ga-68 FAPI PET/CT for early response assessment in NSCLC after 3 cycles of standard chemotherapy.Lung cancer contributes significantly to cancer-related deaths worldwide. Therapeutic response assessment is crucial for personalized treatment planning and treatment outcomes. An accurate response assessment can help the treating physicians and improve the patient's survival. FDG PET/CT provides an early and more precise therapeutic response than the CT scan. Ga-68 FAPI PET/CT has emerged as a promising modality for evaluating NSCLC. In the present study, we aimed to compare the role of F-18 FDG PET/CT and Ga-68 FAPI PET/CT for early response assessment in NSCLC after 3 cycles of standard chemotherapy.

Methods: This prospective study included newly diagnosed patients of NSCLC and all underwent F-18 FDG PET/CT and Ga-68 FAPI PET/CT within seven to ten days at baseline and after three cycles of chemotherapy for response evaluation. FDG and FAPI PET/CT images were analyzed quantitatively by measuring the molecular matrices of the lesions. Pre-therapy and post-therapy imaging parameters were compared. PERCIST 1.0 was used for response evaluation with F-18 FDG PET/CT. PERCIST 1.0 was modified for Ga-68 FAPI-PET/CT as adapted PET Response Criteria in Solid Tumors (aPERCIST 1.0). Molecular parameters of the hottest single lesion and background activity of the liver in 18F-FDG PET/CT and aorta in Ga-68 FAPI PET/CT were measured. Background data helped to establish proper PET acquisition and appropriate threshold for standardized uptake value corrected for lean body mass. As per PERCIST 1.0, patients were classified into four categories: progressive metabolic disease (PMD), stable metabolic disease (SMD), partial metabolic response (PMR), and complete metabolic response (CMR) based upon SULpeak values. PMR and CMR were considered responding diseases, while PMD and SMD were classified as non-responders.

Results: Fifteen participants (nine men; mean age 48±7) with NSCLC (11 adenocarcinoma and four squamous cell carcinoma) were recruited prospectively. Percentage change in SULpeak was measured for each patient on FDG and FAPI PET. Based on PERCIST 1.0 on F-18 FDG PET/CT, nine patients showed PMR, five SMD, one PMD, and none CMR. Ga-68 FAPI PET/CT demonstrated PMR in six patients, SMD in seven, PMD in two, and CMR in none. Discordant results were seen in four patients. Three patients with PMR on FDG had stable disease on FAPI PET, while one showed SMD on FDG had PMD on FAPI. FDG PET/CT and FAPI PET/CT showed a moderate agreement (kappa = 0.552, p< 0.05) for response grading. FDG PET identified responding disease in 60% (9/15) of participants, while FAPI PET showed responders in 40% (6/15). FDG PET/CT and FAPI PET/CT showed substantial agreement (kappa = 0.615, p< 0.05) in categorizing patients as responders and non-responders.

Conclusions: F-18 FDG PET/CT has a proven role in response assessment in NSCLC. However, Ga-68 FAPI PET/CT has shown a substantial degree of agreement with F-18 FDG PET/CT and, hence, can be used in place of F-18 FDG PET/CT. The prognostic significance of these assessments is yet to be determined in subsequent follow-ups for overall survival evaluation in a large population.