Abstract
Introduction/Aim: Immunotherapy with immune checkpoint inhibitors (ICIs) has positively changed the history of several malignant tumors. In parallel, new challenges have emerged in the evaluation of treatment response as a result of their peculiar anticancer effect. In the current study, we aimed to compare different response criteria, both morphological and metabolic, for assessing response and outcome in patients with advanced non-small cell lung cancer (NSCLC) treated with ICI.Materials and Methods: Overall, 52 patients with advanced NSCLC candidate to ICI were prospectively evaluated. Inclusion criteria comprised whole-body contrast-enhanced CT and 18F-FDG PET/CT at baseline and at the first response evaluation 3 or 4 cycles after ICI. Response assessment on CT was performed according to RECIST 1.1 and imRECIST criteria, whereas metabolic response on PET was computed by EORTC, PERCIST, imPERCIST, and PERCIMT criteria. The concordance between the different tumor response criteria and the performance of each criterion to predict progression-free survival (PFS) and overall survival (OS) were calculated.Results: Inclusion criteria were fulfilled in 35 out of 52 patients. We observed a low agreement between imRECIST and imPERCIST (κ = 0.143) with discordant response in 20 patients, particularly regarding stable disease and progressive disease groups. Fair agreement between imRECIST and EORTC (κ = 0.340), and PERCIST (κ = 0.342), and moderate for PERCIMT (κ = 0.413) were detected. All criteria were significantly associated with PFS, while only PERCIMT and imPERCIST were associated with OS. Of note, in patients classified as immune stable disease (iSD), imPERCIST, and PERCIMT well-differentiated those with longer PFS (p < 0.001, p = 0.009) and OS (p = 0.001, p = 0.002). In the multivariate analysis, performance status [hazard ratio (HR) = 0.278, p = 0.015], imRECIST (HR = 3.799, p = 0.026), and imPERCIST (HR = 4.064, p = 0.014) were predictive factors for PFS, while only performance status (HR = 0.327, p = 0.035) and imPERCIST (HR = 3.247, p = 0.007) were predictive for OS.Conclusions: At the first evaluation during treatment with ICI, imPERCIST criteria correctly evaluated treatment response and appeared able to predict survival. Moreover, in patients with iSD on CT, imPERCIST were able to discriminate those with longer survival. This advantage might allow for earlier therapy modification based on metabolic response.
Highlights
Several clinical studies have demonstrated the successful therapeutic approach of immune checkpoint inhibitors (ICIs) in patients affected by different malignancies when compared with chemotherapy
The main peculiarity of the new morphological criteria developed in the ICI era, such as immune-related response criteria and immune-modifiedRECIST, is that the appearance of new lesions is not always synonymous with progression of disease, but requires confirmation at least after 4–8 weeks [9, 10]
New lesions are considered a sign of progression according to their number and size or if metabolic activity is greater than a determined cut-off, as proposed by PET Response Evaluation Criteria for Immunotherapy (PERCIMT) and Immunotherapy-modified PET Response Criteria in Solid Tumors criteria, respectively [11, 12]
Summary
Several clinical studies have demonstrated the successful therapeutic approach of immune checkpoint inhibitors (ICIs) in patients affected by different malignancies when compared with chemotherapy. Because of tumor inflammation, malignant lesions might appear stable, or even larger either in size or in metabolic activity before effective shrinkage occurs, making it difficult to discriminate between true progression from the so-called pseudo-progression [4–7]. To overcome these limitations, numerous response criteria have been proposed, starting with the traditional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [8]. New lesions are considered a sign of progression according to their number and size or if metabolic activity is greater than a determined cut-off, as proposed by PET Response Evaluation Criteria for Immunotherapy (PERCIMT) and Immunotherapy-modified PET Response Criteria in Solid Tumors (imPERCIST) criteria, respectively [11, 12]
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