@article {Ferdinandus191, author = {Justin Ferdinandus and Francesco Barbato and Michal Chodyla and Wolfgang P. Fendler and Lukas Kessler and Kelsey L. Pomykala and Martin Metzenmacher and Frederik Krefting and Thomas Hager and Lale Umutlu and Ken Herrmann and Daniel C. Christoph}, title = {Volumetric PET Response Assessment Outperforms Conventional Criteria in Patients Receiving High-Dose Pembrolizumab for Malignant Mesothelioma}, volume = {62}, number = {2}, pages = {191--194}, year = {2021}, doi = {10.2967/jnumed.120.245803}, publisher = {Society of Nuclear Medicine}, abstract = {Fixed-dose pembrolizumab (200 mg absolute, day 1, every 3 wk) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared with second-line chemotherapy. Because of lack of validated imaging response criteria, responder subgroups with potential survival benefit have not yet been identified. Here, we administered high-dose pembrolizumab (10 mg/kg, day 1, every 2 wk) considering the KEYNOTE-028 trial and assessed the prognostic value of PET metabolic response in patients with chemotherapy-resistant malignant mesothelioma of the pleura or peritoneum. Methods: Data from 27 patients with baseline and follow-up 18F-FDG PET/CT imaging were retrospectively analyzed. RECIST, version 1.1; modified RECIST; and PERCIST using both tumor lesion metabolic activity in a 1 cm3 spheric region of interest of up to 5 target lesions (PERCISTSULpeak) and metabolic tumor volume PERCIST (PERCISTMTV) were applied separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) were compared between responders and nonresponders using Kaplan{\textendash}Meier and log-rank analyses. Programmed cell death protein 1 ligand expression status was assessed, and its association with outcome was investigated. Results: Twenty-seven patients had 18F-FDG PET/CT imaging at baseline and after at least 4 cycles pembrolizumab. Median PFS and OS were 3.4 and 15.1 mo, respectively. Response rates were 7\%, 7\%, 30\%, and 30\% based on RECIST, modified RECIST, PERCISTSULpeak, and PERCISTMTV response criteria, respectively. Response according to PERCISTMTV predicted prolonged OS or PFS (P \< 0.01), whereas all other imaging criteria and programmed cell death protein 1 ligand expression did not. Conclusion: 18F-FDG PET metabolic volume response predicts survival in patients with malignant mesothelioma receiving high-dose pembrolizumab. These results should prompt inclusion of PET response assessment in future phase 3 clinical trials.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/62/2/191}, eprint = {https://jnm.snmjournals.org/content/62/2/191.full.pdf}, journal = {Journal of Nuclear Medicine} }