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18FDG PET/CT in the early assessment of non-small cell lung cancer response to immunotherapy: frequency and clinical significance of atypical evolutive patterns

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

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.

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 (PETinterim1) 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 (PETinterim2) was performed at 3 months of treatment. Pseudo-progression (PsPD) was defined as a PERCIST response/stability on PETinterim2 after an initial PD. If a second PERCIST PD was assessed on PETinterim2, a homogeneous progression of lesions (termed immune homogeneous progressive-disease: iPDhomogeneous) 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 PETinterim1, 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 PETinterim1 criteria could accurately distinguished responding from non-responding patients. Treatment was continued in 19/29 of patients with a first PERCIST PD; the subsequent PETinterim2 demonstrated iPDhomogeneous, iDR and PsPD in 42% (8/19), 26% (5/19), and 32% (6/19), respectively. Whereas no patients with iPDhomogeneous 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.

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Acknowledgements

The authors would like to thank Colin Debaigt for protocol submission to regulatory agencies.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Centre Antoine-Lacassagne, Université Côte d’Azur (UCA), 33 Avenue de Valombrose, 06189, Nice, France

    O. Humbert, N. Cadour, M. Paquet, D. Chardin, D. Benisvy, M. J. Ouvrier, C. Zwarthoed, A. Schiazza, P. M. Koulibaly & J. Darcourt

  2. Laboratory Transporter in Imaging and Radiotherapy in Oncology (TIRO), UMR E 4320, CEA, UCA, Nice, France

    O. Humbert, D. Chardin & J. Darcourt

  3. Department of Biostatistics, Centre Antoine-Lacassagne, UCA, Nice, France

    R. Schiappa

  4. Department of Medical Oncology, Centre Antoine-Lacassagne, UCA, Nice, France

    M. Poudenx, D. Borchiellini, H. Ghalloussi & J. Otto

  5. Clinical Research and Innovation Office, Centre Antoine-Lacassagne, UCA, Nice, France

    D. Borchiellini

  6. Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Nice Hospital University, FHU OncoAge, UCA, Nice, France

    M. Ilie

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  1. O. Humbert
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  2. N. Cadour
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Corresponding author

Correspondence to O. Humbert.

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Conflict of interest

O. Humbert, N. Cadour, M. Paquet, R. Schiappa, M. Poudenx, D. Chardin, D. Borchiellini, D. Benisvy, M.J. Ouvrier, C. Zwarthoed, A. Schiazza, H. Ghalloussi, P.M. Koulibaly, J. Darcourt, and J. Otto declare that they have no conflict of interest. M. Ilie reports personal fees from AstraZeneca, Bristol-Myers Squibb, Roche, Boehringer-Ingelheim, and Merck & Co outside the submitted work.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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This article is part of the Topical Collection on Oncology – Chest

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Humbert, O., Cadour, N., Paquet, M. et al. 18FDG PET/CT in the early assessment of non-small cell lung cancer response to immunotherapy: frequency and clinical significance of atypical evolutive patterns. Eur J Nucl Med Mol Imaging 47, 1158–1167 (2020). https://doi.org/10.1007/s00259-019-04573-4

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