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

Lucas Goldfarb, Boris Duchemann, Kader Chouahnia, Laurent Zelek, Michael Soussan, Lucas Goldfarb, Boris Duchemann, Kader Chouahnia, Laurent Zelek, Michael Soussan

Abstract

Background: Immunotherapy 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.

Results: This 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.

Conclusions: iPERCIST 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.

Keywords: Fluorodeoxyglucose; Nivolumab; Non-small cell lung cancer; PET; iPERCIST.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of the screened population
Fig. 2
Fig. 2
A 64-year-old patient with metastatic lung adenocarcinoma was treated with a second line of nivolumab. SCAN-1 shows lung nodules with adrenal metastases (a, maximum intensity projection (MIP) image, arrows; b, e axial fusion). SCAN-2 at 8 weeks of treatment (4 cycles) showing partial metabolic response (PMR): complete metabolic response on the lungs and left adrenal lesions (c MIP, d axial fusion) but persistent and significant FDG uptake on the right adrenal lesion (f arrow). The classification was PMR according to iPERCIST. Nivolumab treatment was maintained for 10 months, and at the last follow-up, the patient was still alive (survival of 23.8 months)
Fig. 3
Fig. 3
A 45-year-old women with metastatic lymphoepithelioma-like lung carcinoma treated with a second line of nivolumab. SCAN-1 showed left lung carcinoma with liver metastases (a maximum intensity projection image, MIP, arrows). SCAN-2 at 8 weeks of treatment (4 cycles) showed UPMD: increase in size of the primary lesion and appearance of numerous liver lesions (b MIP). SCAN-3 after two more cycles of nivolumab showed the disappearance of most liver lesions and a persistent large lung mass (c MIP). See Additional file 1: Figure S1 for axial views. Pseudo-progression was retrospectively diagnosed, and the classification was PMR according to iPERCIST. Nivolumab treatment was maintained for 7.1 months, and survival was 13.8 months
Fig. 4
Fig. 4
Category of imaging response according to iPERCIST
Fig. 5
Fig. 5
Kaplan-Meier curves for overall survival for metabolic responders vs non-responders (p = 0.0003)

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