${}^{18}$fdg pet/ct in the early assessment of non-small cell lung cancer response to immunotherapy. frequency and clinical significance of atypical evolutive patterns

This prospective study aimed (1) to assess the non-small cell lung cancer (NSCLC) evolutive patterns to immunotherapy using FDG-PET and (2) to describe their association with clinical outcome. 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}$2 after an initial PD. If a second PERCIST PD was assessed on PET${}_{interi{m}^2}$, a homogeneous progression of lesions (termed immune homogeneous progressive-disease: iPD${}_{homogeneous}$) was distinguished from a heterogeneous evolution (termed immune dissociated-response: iDR). A durable clinical benefit (DCB) of immunotherapy was defined as treatment continuation over a 6-month period. The association between PET evolutive profiles and DCB was assessed. Using PERCIST on PETi${}_{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. 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.