Dual-time-point \[18F\]FDG-PET/CT as a prognostic biomarker in patients with pleural mesothelioma undergoing immunotherapy

Our plain-English summary of Dual-time-point [18F]FDG-PET/CT as a prognostic biomarker in patients with pleural mesothelioma undergoing immunotherapy, by S. Thunold, E. Hernes, L.T. Gyland Mikalsen, et al (EJNMMI Research, 2026).

The study

• Authors: S. Thunold, E. Hernes, L.T. Gyland Mikalsen, S. Farooqi, Å.K. Öjlert, R.J. Francis, A.K. Nowak, W.M. Szejniuk, S.S. Nielsen, S. Cedres, M.S. Perdigo, J.B. Sørensen, C. Meltzer, Å. Helland, E. Malinen, V.D. Haakensen
• Journal: EJNMMI Research
• Published: 2026;16(1)
• Read it: PubMed · Publisher · Free full text

Abstract

Background: [18F]FDG PET/CT provides a non-invasive assessment of tumour glucose metabolism. While conventional PET/CT captures a single time point, dual-time-point PET/CT (DTP-PET) evaluates metabolic dynamics by acquiring images at two defined times after injection. This study investigated whether the change in [18F]FDG uptake between 60 and 120 min-retention index (RI)-predicts clinical outcomes in patients with pleural mesothelioma (PM) receiving immunotherapy. Patients from the NIPU trial (NCT04300244) underwent DTP-PET at baseline (n = 50) and/or week-5 (n = 45), with 42 completing both. Peak SUV was measured in a 2-cm spherical volume of interest centred on the most avid lesion at 60 and 120 min, and RI was calculated as the percentage change between the two. Survival (OS, PFS) was analysed using Kaplan-Meier curves and Cox proportional hazards models based on tertiles of RI and SUV60min. Objective response and disease control were defined by mRECIST and iRECIST. Group comparisons used the Wilcoxon rank-sum test.

Results: At week-5, RI tertiles showed stepwise separation for both OS (p = 0.038) and PFS (p = 0.031), with the lowest tertile associated with the most favourable outcomes. SUV60min tertiles were also significantly associated with OS (p = 0.042) and PFS (p = 0.043), though OS exhibited a non-monotonic pattern in which the middle tertile had the poorest survival. Objective responders displayed significantly lower RI and SUV60min at week-5. Baseline RI tertiles were not associated with OS or PFS.

Conclusions: Week-5 [18F]FDG DTP-PET suggests prognostic value in PM patients receiving immunotherapy. Both RI and SUV60min were associated with objective response. RI showed a consistent stepwise association with survival, whereas SUV60min showed a non-monotonic relationship for OS. These findings are exploratory and require validation in larger cohorts. Further studies are warranted to explore underlying biological mechanisms.

Trial Registration: ClinicalTrials.gov NCT04300244. Registered 2020-03-09. https://clinicaltrials.gov/study/NCT04300244.

© 2026. The Author(s).

In plain English

This study tested whether PET/CT scans taken 60 and 120 minutes after tracer injection could predict outcomes in pleural mesothelioma patients receiving nivolumab and ipilimumab, with or without the UV1 vaccine, in the NIPU trial. The article does not discuss asbestos exposure. Of 53 eligible patients, 50 were scanned before treatment, 45 at week 5, and 42 at both. The main measure, the retention index (RI), was the percentage change in uptake between scans. At week 5, median overall survival was 23.6 months (95% confidence interval 6.5 to 30.5) in the lowest third of RI, 13.6 (4.2 to 17.7) in the middle third and 7.2 (5.3 to 14.8) in the highest third (p = 0.038 across all three). Uptake at 60 minutes was also linked to survival, but the middle third had the shortest overall survival. Patients whose tumours responded had lower week-5 values. Before treatment, RI was not significantly associated with survival; the authors noted limited statistical power. The authors concluded that week-5 scans may provide prognostic information, and called all analyses exploratory.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective imaging sub-study within a randomised trial (NIPU), using dual-time-point [18F]FDG PET/CT
• Who was studied: 53 eligible patients with pleural mesothelioma from the Oslo and Aalborg centres of the NIPU trial. 50 had dual-time-point scans at baseline, 45 at week 5 and 42 at both. The baseline group was 84% male, with a median age of 71 years and 82% epithelioid histology.
• Exposure: No asbestos exposure is reported. Patients received second-line nivolumab and ipilimumab, with or without the UV1 telomerase peptide vaccine. The measure studied was FDG uptake at 60 and 120 minutes after injection, and the retention index (percentage change between the two).
• Main results:
  • Week-5 RI thirds were associated with overall survival (p = 0.038) and progression-free survival (p = 0.031). These p-values compare all three thirds together.
  • Week-5 median overall survival by RI third: 23.6 months (95% CI 6.5 to 30.5) in the low third, 13.6 (4.2 to 17.7) in the intermediate third, and 7.2 (5.3 to 14.8) in the high third.
  • Week-5 median progression-free survival by RI third: 7.0 months (1.7 to 15.4) in the low third, 2.9 (1.6 to 7.1) in the intermediate third, and 3.9 (1.4 to 5.4) in the high third.
  • Week-5 thirds of uptake at 60 minutes were associated with overall survival (p = 0.042) and progression-free survival (p = 0.043). Median overall survival was 20.2 months in the low third, 6.9 in the intermediate third and 17.3 in the high third, so the middle third did worst.
  • At week 5, patients with an objective response had significantly lower RI (p = 0.0077) and lower 60-minute uptake (p = 0.0015) than non-responders.
  • Of 9 objective responders at week 5, 7 were in the lowest third of 60-minute uptake and 6 were in the lowest third of RI.
  • RI thirds measured at baseline were not significantly associated with overall survival (p = 0.47) or progression-free survival (p = 0.67).
  • The authors noted a numerical separation in overall survival across baseline RI thirds that did not reach statistical significance, likely reflecting limited power.
• The authors' conclusion: The authors concluded that week-5 dual-time-point FDG PET may provide prognostic information in patients with pleural mesothelioma undergoing immunotherapy, and that on-treatment scans appeared more prognostic than baseline scans.
• Limitations the authors state:
  • The small sample size and limited number of events reduced statistical power and generalisability.
  • The authors state that all analyses should be considered exploratory and hypothesis-generating.
  • Splitting patients into thirds (tertiles) has inherent limitations.
  • No multivariable adjustment was performed.
  • Only one lesion per patient was measured, which may be hard to reproduce and misses differences between lesions.
  • The biological meaning of RI is speculative because tumour tissue was not analysed.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Immunotherapy, Kaplan-Meier Curve.

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