ORIGINAL ARTICLE 18 FDG PET/CT in the early assessment of non-small cell lung cancer response to immunotherapy: frequency and clinical significance of atypical evolutive patterns O. Humbert 1,2 & N. Cadour 1 & M. Paquet 1 & R. Schiappa 3 & M. Poudenx 4 & D. Chardin 1,2 & D. Borchiellini 4,5 & D. Benisvy 1 & M. J. Ouvrier 1 & C. Zwarthoed 1 & A. Schiazza 1 & M. Ilie 6 & H. Ghalloussi 4 & P. M. Koulibaly 1 & J. Darcourt 1,2 & J. Otto 4 Received: 2 May 2019 /Accepted: 10 October 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Purpose This prospective study aimed (1) to assess the non-small cell lung cancer (NSCLC) evolutive patterns to immunother- apy using FDG-PET and (2) to describe their association with clinical outcome. Design Fifty patients with metastatic NSCLC were included before pembrolizumab or nivolumab initiation. FDG-PET scan was performed at baseline and after 7 weeks of treatment (PET interim 1) and different criteria/parameters of tumor response were assessed, including PET response criteria in solid tumors (PERCIST). If a first PERCIST progressive disease (PD) without clinical worsening was observed, treatment was continued and a subsequent FDG-PET (PET interim 2) was performed at 3 months of treatment. Pseudo-progression (PsPD) was defined as a PERCIST response/stability on PET interim 2 after an initial PD. If a second PERCIST PD was assessed on PET interim 2, a homo- geneous progression of lesions (termed immune homogeneous progressive-disease: iPD homogeneous ) was distinguished from a heterogeneous evolution (termed immune dissociated-response: iDR). A durable clinical benefit (DCB) of immunotherapy was defined as treatment continuation over a 6-month period. The association between PET evolutive profiles and DCB was assessed. Results Using PERCIST on PET interim 1, 42% (21/50) of patients showed a response or stable disease, most of them (18/21) reached a DCB. In contrast, 58% (29/50) showed a PD, but more than one-third (11/29) were misclassified as they finally reached a DCB. No standard PET interim 1 criteria could accurately distinguished responding from non- responding patients. Treatment was continued in 19/29 of patients with a first PERCIST PD; the subsequent PET interim 2 demonstrated iPD homogeneous , iDR and PsPD in 42% (8/19), 26% (5/19), and 32% (6/19), respectively. Whereas no patients with iPD homogeneous experienced a DCB, all patients with iDR and PsPD reached a clinical benefit to immunotherapy. Conclusion In patients with a first PD on PERCIST and treatment continuation, a subsequent PET identifies more than half of them with iDR and PsPD, both patterns being strongly associated with a clinical benefit of immunotherapy. Keywords FDG PET . Immunotherapy . Lung cancer . Monitoring . Response This article is part of the Topical Collection on Oncology – Chest * O. Humbert olivier.humbert@univ-cotedazur.fr 1 Department of Nuclear Medicine, Centre Antoine-Lacassagne, Université Côte d’Azur (UCA), 33 Avenue de Valombrose, 06189 Nice, France 2 Laboratory Transporter in Imaging and Radiotherapy in Oncology (TIRO), UMR E 4320, CEA, UCA, Nice, France 3 Department of Biostatistics, Centre Antoine-Lacassagne, UCA, Nice, France 4 Department of Medical Oncology, Centre Antoine-Lacassagne, UCA, Nice, France 5 Clinical Research and Innovation Office, Centre Antoine-Lacassagne, UCA, Nice, France 6 Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Nice Hospital University, FHU OncoAge, UCA, Nice, France European Journal of Nuclear Medicine and Molecular Imaging https://doi.org/10.1007/s00259-019-04573-4