Abstract
Introduction: Immunotherapy-modified Positron Emission Tomography Response Criteria in Solid Tumors (imPERCIST) using FDG-PET/CT and immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) using CT were compared for evaluation of response, prognosis prediction, and effect on patient management in non-small-cell lung cancer (NSCLC) patients treated with first-line immunotherapy, or immunotherapy and chemotherapy combined. Methods: Thirty-three patients (26 males, median 68.0 years old) with histologically NSCLC without EGFR/ALK/KRAS alterations underwent pembrolizumab treatment only or immunotherapy combined with chemotherapy. FDG-PET/CT and diagnostic CT scanning was performed at the baseline and after two to four cycles (2 in 8, 3 in 12, 4 in 13 patients). Findings for therapeutic response obtained with imPERCIST and irRECIST were compared. Progression-free survival (PFS) and overall survival (OS) were examined using log-rank and Cox methods. Results: imPERCIST indicated that 10 patients had complete metabolic response (CMR), eight partial metabolic response (PMR), three stable metabolic disease (SMD), and 12 progressive metabolic disease (PMD), while irRECIST showed that two had complete response (CR), 14 PR, nine SD, and eight PD, indicating substantial concordance (κ = 0.615). Twenty-eight patients showed progression and 18 died from NSCLC after a median 16.2 months. Patients showing response based on imPERCIST and irRECIST (CMR/PMR, CR/PR, respectively) showed significantly longer PFS and OS than nonresponders (SMD/PMD, SD/PD, respectively) (imPERCIST: p < 0.0001 and p = 0.0001, respectively; irRECIST: p = 0.0018 and p = 0.011, respectively). imPERCIST resulted in a change of management in 12 of the 33 patients (36.3%) with an additional effect on patient management in 4 patients (12.1%) evaluated by irRECIST. Conclusion: For evaluation of NSCLC patients for tumor response and patient management following first-line immunotherapy or that combined with chemotherapy, and predicting prognosis, both FDG-PET/CT and CT findings are accurate, with FDG-PET/CT being superior.
Plain Language Summary
Immunotherapy with antibodies that prevent the interaction of the programmed death ligand-1 (PD-L1) with the programmed cell death-1 (PD-1) receptor, thus releasing T cells to eliminate tumor cells, has led to significantly improved survival in patients with NSCLC. The assessment of ICI therapeutic efficacy is challenging and not well established. We have compared FDG-PET criteria, immunotherapy-modified Positron Emission Tomography Response Criteria in Solid Tumors (imPERCIST) with morphological CT criteria, immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) to evaluate response to treatment and effect on patient management and predict prognosis in patients with untreated metastatic NSCLC without EGFR/ALK/KRAS alterations undergoing pembrolizumab only or combined immuno-chemotherapy as first-line therapy. Thirty-three patients with histologically NSCLC without EGFR/ALK/KRAS alterations underwent pembrolizumab only or combined immunotherapy and chemotherapy. FDG-PET/CT and diagnostic CT scans were performed at baseline and after 2∼4 cycles (2 cycles in 8 patients, 3 cycles in 12 patients, and 4 cycles in 13 patients). Therapeutic response was evaluated according to imPERCIST and irRECIST and compared. PFS and OS was examined using log-rank and Cox methods. With imPERCIST, 10 patients had CMR, 8 PMR, 3 SMD, and 12 PMD, while using irRECIST, 2 had CR, 14 PR, 9 SD, and 8 PD. There was substantial concordance between imPERCIST and irRECIST (κ = 0.615). After a median of 16.2 months, 28 patients showed progression and 18 had died from NSCLC. According to imPERCIST and irRECIST, patients with responder (CMR/PMR and CR/PR) showed significantly longer PFS and OS than nonresponder (SMD/PMD and SD/PD) patients, respectively (imPERCIST: p < 0.0001 and p = 0.0001, respectively; irRECIST: p = 0.0018 and p = 0.011, respectively). imPERCIST resulted in a change of management in 12 of the 33 patients (36.3%) with an additional effect on patient management in 4 patients (12.1%) evaluated by irRECIST. Both FDG-PET/CT and CT, especially FDG-PET/CT, are accurate for evaluation of tumor response and patient management to first-line immunotherapy or combined immunotherapy and chemotherapy and predicting prognosis in NSCLC patients.
