Can benign lymphoid tissue changes in 18F-FDG PET/CT predict response to immunotherapy in metastatic melanoma?
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An association between immune-related adverse events (irAEs) caused by immunotherapeutic agents and the clinical benefit of immunotherapy has been suggested. We retrospectively evaluated by means of 18F-FDG PET/CT lymphoid tissue changes in the mediastinal/hilar lymph nodes and the spleen in response to ipilimumab administration in metastatic melanoma.
A total of 41 patients with unresectable metastatic melanoma underwent 18F-FDG PET/CT before the start of ipilimumab (baseline PET/CT), after two cycles (interim PET/CT) and at the end of treatment (late PET/CT). Data analysis was focused on the mediastinal/hilar lymph nodes and the spleen. The patients’ best clinical response (BCR) was used as reference.
According to the BCR reference, 31 patients showed disease control (DC) and 10 patients showed progressive disease (PD). Mediastinal/hilar lymph node evaluation revealed that in total 4 patients in the interim or late PET/CT (10%) demonstrated a ‘sarcoid-like lymphadenopathy’ as response to treatment (LN-positive). All LN-positive patients responded to ipilimumab with DC. On the other hand, no significant differences between the DC and PD groups regarding both semi-quantitative and quantitative 18F-FDG PET spleen-related parameters at baseline and as response to treatment were detected.
Based on our findings, 10% patients in the interim or late PET/CT showed ‘sarcoid-like lymphadenopathy’ as response to treatment. All these patients showed disease control, implying a relation between the appearance of sarcoid-like lymphadenopathy and the clinical benefit of anti-CTLA-4 therapy. On the other hand, quantitative 18F-FDG PET analysis of the spleen showed a poor performance in predicting clinical benefit to ipilimumab.
KeywordsMetastatic melanoma Ipilimumab ‘Sarcoid-like lymphadenopathy’ Spleen glucose metabolism 18F-FDG PET/CT
Best clinical response
Dynamic positron emission tomography/computed tomography
Immune-related adverse events
Negative mediastinal/hilar lymph nodes
Positive mediastinal/hilar lymph nodes
Positron emission tomography
Positron emission tomography/computed tomography
Standardized uptake value
Volume of interest
CS performed the PET/CT studies, carried out the PET/CT data analysis, drafted and performed final editing of the manuscript. LL contributed to the conception of the study and co-drafted the manuscript. AK-S was responsible for the statistical analysis of the study. JCH was responsible for the selection of the patients who received the ipilimumab therapy and co-drafted the manuscript. AD-S was responsible for the PET-CT study design and the data evaluation and coordinated the project.
This study was supported in part by the German Cancer Aid under the project with the title ‘Therapy monitoring of ipilimumab based on the quantification of F-18-FDG kinetics with 4D PET/CT (dPET-CT) in patients with melanoma (stage 4)’. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.
Compliance with ethical standards
Conflict of interest
Jessica C. Hassel received honoraria for talks and travel expenses from Bristol-Myers Squibb (BMS), Merck, Sharp & Dohm (MSD), Roche, Novartis, Pfizer and is a member of an advisory board for MSD and Amgen. The other authors declare that they have no conflict of interest.
The presented results are part of the study entitled “Quantification of 18F-FDG kinetics with 4D PET-CT in patients with melanoma stage IV”, which was approved by the Ethical Committee of the University of Heidelberg (Ethikvotum: S-107 /2012—Ethical Committee 1 of the University of Heidelberg) and the Federal Office for Radiation Protection (Bundesamt für Strahlenschutz; BfS: Z5- 22463 / 2 2012a-016). This study does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study. The patient presented in Fig. 1 agreed to the publication of this figure.
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