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FDG PET/CT for tumoral and systemic immune response monitoring of advanced melanoma during first-line combination ipilimumab and nivolumab treatment

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Abstract

Purpose

We aimed to investigate the role of FDG-PET/CT in monitoring of response and immune-related adverse events (irAEs) following first-line combination-immune checkpoint inhibitor (combination-ICI) therapy for advanced melanoma.

Methods

We retrospectively reviewed outcomes in patients who had (1) first-line nivolumab plus ipilimumab; (2) pre- and post-treatment FDG-PET/CT scans (pre-FDG-PET/CT and post-FDG-PET/CT) within 2 and 4 months of starting ICI, respectively; and (3) at least one lesion assessable by PET response criteria in solid tumors (PERCIST). Extracranial response was monitored by 3 monthly FDG-PET/CT. Whole-body metabolic tumor volume (wbMTV) was measured pre- and post-treatment and correlated with outcome. FDG-PET/CT manifestations of irAE were defined as new increased non-tumoral uptake on post-FDG-PET/CT and were correlated with clinical presentation.

Results

Thirty-one consecutive patients, median age 60 years (range, 30–78), were identified from 2016 to 2018. The median number of combination-ICI cycles to the first post-FDG-PET/CT response assessment was 3 (interquartile range (IQR), 2–4). The best-overall responses were complete metabolic response (CMR) in 25 (80%), partial metabolic response (PMR) in 3 (10%), and progressive metabolic disease (PMD) in 3 (10%) patients. Patients with PMD had significantly higher pre-treatment wbMTV (p = 0.009). At a median follow-up of 21.5 months, 26 (84%) patients were alive with median progression-free and overall survival not reached. Secondary progression occurred in 9/31 (29%) patients at a median of 8.2 months (IQR, 6.9–15.5), of those majority (78%) was detected by FDG-PET/CT. Of 36 findings on post-FDG-PET/CT suggestive of irAE, 29 (80%) had clinical confirmation. In 3 (7%), the FDG-PET/CT findings preceded clinical presentation. The most common FDG-PET/CT detectable irAEs were endocrinopathies (36%) and enterocolitis (35%).

Conclusion

FDG-PET/CT response evaluation predicts the long-term outcome of patients treated with first-line combination-ICIs. Long-term treatment response monitoring for detection of extracranial secondary progression is feasible by FDG-PET/CT. Beyond response assessment, FDG-PET/CT frequently detects clinically relevant irAEs, which may involve multiple systems contemporaneously or at various time-points and may precede clinical diagnosis.

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Availability of data and material

The collected data is available for further analysis if required.

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Funding

This research was partially supported by the Victorian Cancer Agency.

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Authors and Affiliations

  1. Cancer Imaging, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia

    Amir Iravani, Arian Lasocki, Tim Akhurst, Michael S. Hofman & Rodney J. Hicks

  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia

    Amir Iravani, Arian Lasocki, Tim Akhurst, Michael S. Hofman, Peter K. H. Lau, Damien Kee, George Au-Yeung, Shahneen Sandhu & Rodney J. Hicks

  3. Division of Nuclear Medicine, Department of Radiology, Saint Louis University Hospital, St. Louis, MO, USA

    Medhat M. Osman

  4. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Alison M. Weppler, Roslyn Wallace, Anna Galligan, Damien Kee, George Au-Yeung & Shahneen Sandhu

  5. Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Morgan O. Hunter

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  1. Amir Iravani
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by AI, MMS, AMW, RW, AG, AL, and MOH. The first draft of the manuscript was written by AI and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Amir Iravani.

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Conflict of interest

Professor Rodney Hicks is the recipient of a National Health and Medical Research Foundation Practitioner Fellowship (APP1108050). All other authors declare no conflict of interest.

Ethics approval

This retrospective study was approved by Peter MacCallum Cancer Center Ethics Committee (approval number: 17/231R). Authors certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.

Consent to participate and consent to publication

Due to the retrospective nature of the study, informed consent was waived by the Peter MacCallum Cancer Center Ethics Committee (approval number: 17/231R). Ethics committee allowed the publication of this study.

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Iravani, A., Osman, M.M., Weppler, A.M. et al. FDG PET/CT for tumoral and systemic immune response monitoring of advanced melanoma during first-line combination ipilimumab and nivolumab treatment. Eur J Nucl Med Mol Imaging 47, 2776–2786 (2020). https://doi.org/10.1007/s00259-020-04815-w

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