Response to Immune Checkpoint Inhibitor Therapy in Patients with Unresectable Recurrent Malignant Pleural Mesothelioma Shown by FDG-PET and CT

Our plain-English summary of Response to Immune Checkpoint Inhibitor Therapy in Patients with Unresectable Recurrent Malignant Pleural Mesothelioma Shown by FDG-PET and CT, by K. Kitajima, M. Maruyama, H. Yokoyama, et al (Cancers, 2021).

The study

• Authors: K. Kitajima, M. Maruyama, H. Yokoyama, T. Minami, T. Yokoi, A. Nakamura, M. Hashimoto, N. Kondo, K. Kuribayashi, T. Kijima, S. Hasegawa, K. Yamakado
• Journal: Cancers
• Published: 2021;13(5)
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: To compare three FDG-PET criteria (EORTC, PERCIST, imPERCIST) with CT criteria (combined modified RECIST and RECIST 1.1) for response evaluation and prognosis prediction in patients with recurrent MPM treated with ICI monotherapy.

Methods: Thirty MPM patients underwent FDG-PET/CT and contrast-enhanced CT at the baseline and during nivolumab therapy (median 10 cycles). Therapeutic response was evaluated according to EORTC, PERCIST, imPERCIST, and CT criteria. PFS and OS were examined using log-rank and Cox methods.

Results: CMR/PMR/SMD/PMD numbered 5/3/4/18 for EORTC, 5/1/7/17 for PERCIST, and 5/3/9/13 for imPERCIST. With CT, CR/PR/SD/PD numbered 0/6/10/14. There was high concordance between EORTC and PERCIST (κ = 0.911), and PERCIST and imPERCIST (κ = 0.826), while that between EORTC and imPERCIST (κ = 0.746) was substantial, and between CT and the three PET criteria moderate (κ = 0.516-0.544). After median 14.9 months, 26 patients showed progression and nine died. According to both PET and CT findings, patients with no progression (CMR/PMR/SMD or CR/PR/SD) showed significantly longer PFS and somewhat longer OS than PMD and PD patients (EORTC p = 0.0004 and p = 0.055, respectively; PERCIST p = 0.0003 and p = 0.052; imPERCIST p < 0.0001 and p = 0.089; CT criteria p = 0.0015 and p = 0.056).

Conclusions: Both FDG-PET and CT criteria are accurate for response evaluation of ICI therapy and prediction of MPM prognosis. In comparison with CT, all three FDG-PET/CT criteria judged a greater percentage of patients (16.7%) as CMR, while two (EORTC, PERCIST) judged a greater percentage (10-13.3%) as PMD. For predicting PFS, the three FDG-PET criteria were superior to the CT criteria, and imPERCIST demonstrated the highest rate of accurate prediction.

In plain English

This retrospective study from Hyogo College of Medicine in Japan looked at 30 patients with unresectable recurrent malignant pleural mesothelioma. They were treated with the immunotherapy drug nivolumab between June 2018 and December 2019. The article does not report on asbestos exposure. Each patient had FDG-PET/CT and contrast-enhanced CT scans before treatment and again during treatment. The authors compared how three PET-based scoring systems (EORTC, PERCIST, imPERCIST) and one combined CT system (modified RECIST and RECIST 1.1) rated tumor response. All three PET systems judged 5 of 30 patients (16.7%) to have a complete metabolic response, while CT judged none to have a complete response. Agreement between CT and the PET systems was moderate. Twenty-six of the 30 patients had disease progression, and nine died from mesothelioma. Under every system, patients rated as not progressing had significantly longer progression-free survival. Differences in overall survival were not statistically significant. The authors concluded that the PET criteria were superior to CT for predicting progression-free survival. They noted that the study was small, retrospective and at a single center, and that scan timing varied.

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: Retrospective single-institution imaging study comparing PET-based and CT-based response criteria
• Who was studied: 30 patients (24 men, 6 women; mean age 68.1, range 46 to 77) with unresectable recurrent malignant pleural mesothelioma treated with nivolumab monotherapy at Hyogo College of Medicine, Japan, between June 2018 and December 2019. Histology: 24 epithelial, 4 sarcomatoid, 2 biphasic.
• Exposure: Asbestos or other fiber exposure is not reported. The treatment studied was intravenous nivolumab, 3 mg/kg every two weeks. The second scans were done after 4 to 21 cycles (median 10).
• Main results:
  • EORTC criteria (PET), all 30 patients: complete metabolic response in 5 (16.7%), partial metabolic response in 3 (10.0%), stable metabolic disease in 4 (13.3%), progressive metabolic disease in 18 (60.0%)
  • PERCIST criteria (PET): complete metabolic response in 5 (16.7%), partial in 1 (3.3%), stable in 7 (23.3%), progressive in 17 (56.7%)
  • imPERCIST criteria (PET): complete metabolic response in 5 (16.7%), partial in 3 (10.0%), stable in 9 (30.0%), progressive in 13 (43.3%)
  • Combined modified RECIST and RECIST 1.1 (CT): complete response in 0 (0%), partial response in 6 (20.0%), stable disease in 10 (33.3%), progressive disease in 14 (46.7%)
  • Agreement between EORTC and PERCIST was nearly perfect (kappa 0.911). Agreement between PERCIST and imPERCIST was kappa 0.826, and between EORTC and imPERCIST kappa 0.746.
  • Agreement between the CT criteria and the three PET criteria was moderate (kappa 0.516 with EORTC, 0.529 with PERCIST, 0.544 with imPERCIST)
  • Five of 30 patients (16.7%) were classified as complete metabolic response by all three PET criteria, a classification not given by the CT criteria
  • The second PET/CT found new lesions in 8 patients. The CT reader did not detect the new lesions in 3 of these 8.
  • 26 of 30 patients (86.7%) had progressive disease, after a median of 8.0 months (range 3.3 to 22.4 months)
  • Under all four criteria, patients without progression had significantly longer progression-free survival than patients with progression (EORTC p = 0.0004, PERCIST p = 0.0003, imPERCIST p less than 0.0001, CT p = 0.0015)
  • Responders by PET criteria had significantly longer progression-free survival than non-responders (EORTC p = 0.0064, PERCIST p = 0.0007, imPERCIST p = 0.0005). By CT criteria, responders showed a tendency toward longer progression-free survival that was not statistically significant (p = 0.074).
  • 9 of 30 patients (30.0%) died from malignant pleural mesothelioma, after a median of 14.9 months (range 5.8 to 25.6 months)
  • Patients without progression tended toward longer overall survival under all criteria, but the differences were not statistically significant (EORTC p = 0.055, PERCIST p = 0.052, imPERCIST p = 0.089, CT p = 0.056)
  • Pseudoprogression (a temporary apparent worsening caused by the immune response) was not observed in any of the 30 patients. The authors attributed this probably to the late timing of response assessment (4 or more cycles).
• The authors' conclusion: The authors concluded that, for predicting progression-free survival, the three FDG-PET criteria were superior to the CT criteria, and that imPERCIST had the highest rate of accurate prediction. They also called for further validation in a larger prospective study.
• Limitations the authors state:
  • Retrospective design, single center and small sample size, so the findings have limited generalizability and statistical errors are possible
  • The cohort was heterogeneous because the second PET/CT was done after anywhere from 4 to 21 cycles, so confounding factors were likely introduced
  • The study could not assess the early value of PET/CT because the follow-up scan timing varied widely and was relatively late
  • Other immunotherapy response criteria (irRC, irRECIST, iRECIST, iPERCIST) were not evaluated because regular follow-up scans were not done in every case
  • The authors stated that a significant and apparent superiority of FDG-PET/CT was not observed in their series. They suggested possible reasons: biological differences from melanoma, late assessment, or small sample size.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Unresectable, Pleural Mesothelioma, Modified RECIST (mRECIST), Prognosis, Nivolumab (Opdivo).

Related studies

• Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma — K. Kitajima, K. Kuribayashi, et al. (2024)
• Double immune checkpoint inhibitor therapy for unresectable pleural mesothelioma rarely induces hyperprogressive disease: a case report — G. Naulleau, I. Monnet, et al. (2024)
• Comparison of modified Response Evaluation Criteria in Solid Tumors, European Organization for Research and Treatment of Cancer criteria, and PET Response Criteria in Solid Tumors for evaluation of tumor response to chemotherapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma — K. Kitajima, M. Maruyama, et al. (2020)
• In-depth profiling of tumor tissue derived from malignant pleural mesothelioma patients identifies potential biomarkers predicting response to immune-checkpoint inhibitor therapy — D. Shek, B. Gao, et al. (2024)
• Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma — K. Hotta, N. Fujimoto (2020)
• Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors-Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment — Y. Yoshikawa, K. Kuribayashi, et al. (2020)

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