Monitoring anti-PD-1-based immunotherapy in non-small cell lung cancer with FDG PET: introduction of iPERCIST

Abstract

BackgroundImmunotherapy represents a new therapeutic approach in non-small cell lung carcinoma (NSCLC) with the potential for prolonged benefits. Because of the systemic nature and heterogeneity of tumoral diseases, as well as the immune restoration process induced by immunotherapy, the assessment of therapeutic efficacy is challenging, and the role of FDG PET is not well established. We evaluated the potential of FDG PET to monitor NSCLC patients treated with a checkpoint inhibitor.ResultsThis was a retrospective analysis of 28 NSCLC patients treated with nivolumab, a programmed cell death 1 (PD-1) blocker. All patients underwent a PET scan before treatment (SCAN-1) and another scan 2 months later (SCAN-2). Disease progression was assessed by immune PET Response Criteria in Solid Tumors (iPERCIST), which was adapted from PERCIST; and the immune Response Evaluation Criteria in Solid Tumors (iRECIST). iPERCIST is a dual-time-point evaluation of “unconfirmed progressive metabolic disease” (UPMD) status at SCAN-2. UPMD at SCAN-2 was re-evaluated after 4 weeks with SCAN-3 to confirm PMD. Patients with complete/partial metabolic response (CMR or PMR) or stable metabolic disease (SMD) at SCAN-2 or -3 were considered responders. Patients with UPMD confirmed at SCAN-3 were considered non-responders. The Kaplan-Meier method was used to estimate survival. At SCAN-2, we found 9/28 cases of PMR, 4/28 cases of SMD, 2/28 cases of CMR, and 13/28 cases of UPMD. Four of the 13 UPMD patients were classified as responders at SCAN-3 (PMR n = 1, SMD n = 3). The remaining nine UPMD patients were classified as non-responders due to clinical degradation, and treatment was stopped. The median follow-up was 16.7 months [3.6–32.2]. Responders continued treatment for a mean of 10.7 months [3.8–26.3]. Overall survival was longer for responders than that for non-responders (19.9 vs. 3.6 months, log rank p = 0.0003). The 1-year survival rates were 94% for responders and 11% for non-responders. A comparison with iRECIST showed reclassification in 39% (11/28) of patients with relevant additional prognostic information.ConclusionsiPERCIST dual-time-point evaluation might be a powerful tool for evaluating anti-PD-1-based immunotherapy, with the ability to identify patients who can benefit most from treatment. The prognostic value of iPERCIST criteria should be confirmed in large prospective multicentric studies.Electronic supplementary materialThe online version of this article (10.1186/s13550-019-0473-1) contains supplementary material, which is available to authorized users.

Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

“…Therefore, an effort has been made in nuclear medicine with modified scales proposed, including, for solid tumors, PECRIT (PET/CT Criteria for the early prediction of Response to Immune checkpoint inhibitor Therapy) (2017) [63], PERCIMT (PET Response Evaluation Criteria for Immunotherapy) (2018) [64], imPERCIST5 (immunotherapy-modified PERCIST up to five lesions) (2019) [65], and iPERCIST (immune PERCIST) (2019) [66]. Table 2 resumes the proposed criteria for therapeutic evaluation by 18 F-FDG PET of solid tumors treated by immune checkpoint inhibitor.…”

“…However, these nuclear medicine criteria are quite different, and therefore, standardization is needed [67]. It should be noticed that only iPERCIST introduces the need to confirm a progressive disease such as the updated radiological criteria [66]; however, such a control may limit the risk of a false positive PET scan. A dissociated response is also not considered in these scales, while it seems important as the patients experiencing these response patterns seems to have a clinical benefit of immunotherapy [58].…”

“…For lymphomas, modified Lugano criteria have been proposed with the establishment of lymphoma response to immunomodulatory therapy criteria (LYRIC) [69]. Comparable to the category "unconfirmed progressive disease" used for solid tumors by iRECIST and iPERCIST [7,66], LYRIC has introduced the category "indeterminate response" (IR) when an increase in tumor burden, new lesions, and/or increased 18 F-FDG uptake is observed with subsequent imaging within 12 weeks, which is recommended to confirm the true disease progression versus pseudoprogression [69]. However, concerning Hodgkin lymphoma, the contribution of LYRIC compared to the standard Lugano classification seems limited, because pseudoprogressions seem very rare in this disease.…”

ICOS Is an Indicator of T-cell–Mediated Response to Cancer Immunotherapy

“…The most classic PET radiotracer, 2-deoxy-2-( 18 F)fluoro-D-glucose( 18 F-FDG), has been widely used in lung cancer diagnosis and patient management in the clinic. Some have even proposed 18 F-FDG for monitoring immunotherapy response in clinical trials (13,14), but the biggest challenge is the lack of specificity. Since Author Manuscript Published OnlineFirst on March 10, 2020; DOI: 10.1158/0008-5472.…”

Evaluating response to immunotherapy with 18F-FDG PET/CT: where do we stand?

“…When it comes to 18 F-FDG PET/CT for therapy monitoring, the nuclear medicine community has been very active in the last decade, coming up with various response criteria [6,7] including the PERCIMT (PET Response Evaluation Criteria for Immunotherapy) [9], PECRIT (PET/CT Criteria for Early Prediction of Response to Immune Checkpoint Inhibitor Therapy) [10], iPERCIST [11], or other PERCIST (PET Response Criteria in Solid Tumors)-adapted criteria [12]. A good example is represented by imPERCIST5 [13], developed by the Memorial Sloan-Kettering Cancer Center group in patients receiving ipilimumab.…”