Continued pemetrexed and platin-based chemotherapy in patients with malignant pleural mesothelioma (MPM): value of 18F-FDG-PET/CT

Our plain-English summary of Continued pemetrexed and platin-based chemotherapy in patients with malignant pleural mesothelioma (MPM): value of 18F-FDG-PET/CT, by N.G. Schaefer, P. Veit-Haibach, J.D. Soyka, et al (European Journal of Radiology, 2012).

The study

• Authors: N.G. Schaefer, P. Veit-Haibach, J.D. Soyka, H.C. Steinert, R.A. Stahel
• Journal: European Journal of Radiology
• Published: 2012;81(1):e19-25
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: To prospectively analyze different FDG-PET/CT-parameters (modified RECIST, SUVmax, TLG, PETvol) in patients with malignant pleural mesothelioma (MPM) under continued pemetrexed and platin based treatment.

Methods: Patients with biopsy proven MPM undergoing treatment with pemetrexed and platin based treatment were prospectively included in the study. Integrated FDG-PET/CT imaging was performed within 2 weeks before therapy and after every three consecutive cycles of combined chemotherapy. All CT-images were evaluated according to the modified RECIST (modRECIST) criteria. All FDG-PET/CT images were analyzed using SUVmax (maximum Standard Uptake Value) according to the EORTC criteria, change in Total Lesion Glycolysis (TLG) and FDG volume (PETvol). Percent change in all parameters compared to the initial, pre-therapeutic and the previous FDG-PET/CT scan. ModRECIST, EORTC guidelines, increase or decrease in TLG and PETvol was correlated with overall survival (OS) using the Log Rank Test.

Results: 41 patients with MPM were prospectively included in this study. The median OS of the study population is 439 days (111-1128). 41 patients had initial staging, 41 patients completed 3 cycles, 28 patients completed 6 cycles, 19 patients completed 9 cycles, 11 patients completed 12 cycles, 5 patients completed 15 cycles, 4 patients completed 18 cycles and 1 patient completed 21 cycles of chemotherapy. Chemotherapy was well tolerated up to 21 cycles. SUVmax showed a high variance over time for individual patients and change in SUVmax using EORTC guidelines did not predict OS at any time point. Ongoing morphological response in CT using modRECIST had highest correlation with OS and predicted survival up to the 15th cycle of continued permetrexed and platin based treatment. The correlations of response of the volume based PET parameters (TLG and PETvol) and OS are inferior to the morphological modRECIST parameter.

Conclusion: Permetrexed and platin based treatment in MPM patients can be given over a prolonged time with good tolerance. Therapy response should be assessed by modRECIST in CT but not with SUVmax in FDG-PET. Long term permetrexed and platin therapy should be considered in MPM patients with good tolerance of treatment and ongoing morphological response in CT.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

In plain English

This prospective study followed 41 patients with malignant pleural mesothelioma treated in Zurich, December 2002 to June 2004, with pemetrexed plus cisplatin or carboplatin. Patients had FDG-PET/CT scans before treatment and after every three cycles. The authors compared tumor thickness on CT (modified RECIST) with three PET measures: SUVmax, total lesion glycolysis and PET volume. Median overall survival was 439 days (range 111 to 1128). All 41 completed 3 cycles, 11 completed 12, and one completed 21. Partial response on CT, versus the first scan, was associated with longer survival up to 15 cycles. Decreases in the two volume-based PET measures were associated with longer survival up to 6 cycles versus the first scan, and after the third cycle versus the previous scan. After 12 cycles (11 patients), Table 3 marks decreases versus the previous scan as inversely correlated, with shorter mean survival. SUVmax response was not associated with survival at any time point. The authors concluded that this chemotherapy can be given over a prolonged time with good tolerance, and that response should be judged by modified RECIST on CT, not SUVmax.

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 study of serial FDG-PET/CT imaging during chemotherapy, with overall survival as the reference
• Who was studied: 41 patients with biopsy-proven malignant pleural mesothelioma treated at the University Hospital of Zürich, Switzerland, December 2002 to June 2004. Of these, 34 had primary chemotherapy and 7 had chemotherapy after recurrence. Histology was 32 epithelial, 3 sarcomatoid and 6 biphasic. Patients with abdominal mesothelioma and patients planned for radical surgery were excluded.
• Exposure: Chemotherapy: pemetrexed 500 mg/m2 with cisplatin 75 mg/m2 or carboplatin AUC 5, given every three weeks and continued until untoward toxicity. FDG-PET/CT scans were done before therapy and after every three cycles. Asbestos exposure was not studied.
• Main results:
  • Median overall survival of the 41 patients was 439 days (range 111 to 1128).
  • Number of patients completing each stage of chemotherapy: 41 completed 3 cycles, 28 completed 6, 19 completed 9, 11 completed 12, 5 completed 15, 4 completed 18 and 1 completed 21. The chemotherapy was tolerated up to 21 cycles.
  • Partial response by modified RECIST on CT, compared with the pre-treatment scan, was significantly associated with overall survival up to 15 cycles. Figure 2 gives p = 0.02 after three, p less than 0.001 after six, p = 0.019 after nine and p = 0.034 after twelve cycles.
  • Partial response by modified RECIST compared with the previous scan correlated with overall survival only after the third cycle.
  • Partial response by SUVmax (EORTC criteria) did not correlate with overall survival, whether compared with the previous or the initial scan. Versus the initial scan: p = 0.817, 0.780, 0.885 and 0.387 after 3, 6, 9 and 12 cycles.
  • Decreases in total lesion glycolysis or PET volume, compared with the initial scan, correlated with overall survival up to 6 cycles.
  • Compared with the previous scan, decreases in total lesion glycolysis or PET volume showed a positive correlation with overall survival only after the third cycle (Table 3: p = 0.029 for TLG, p = 0.036 for PET volume).
  • After 12 cycles (11 patients), Table 3 marks the results versus the previous scan as inversely correlated. For PET volume, p = 0.021 and mean overall survival was 660 days with an increase and 510 days with a decrease. For TLG, p = 0.006, with 651 days with an increase and 484 days with a decrease. The article's text does not discuss these results.
  • Late partial responders (partial response after earlier stable or progressive disease) were mainly seen with SUVmax: 17.85% after 6 cycles and 21.05% after 9 cycles. Modified RECIST showed only 1 (9.09%) late partial responder, after the 12th cycle.
• The authors' conclusion: The authors concluded that pemetrexed and platin-based treatment in malignant pleural mesothelioma can be given over a prolonged time with good tolerance. They also concluded that modified RECIST remains the best standard for response assessment, and that stopping therapy should be based on progression on CT by modified RECIST, not on SUVmax in FDG-PET.
• Limitations the authors state:
  • The authors note that the high variance of SUVmax values in individual patients over time limits the relevance of the late-responder observations made with SUVmax.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Chemotherapy, Pleural Mesothelioma, Modified RECIST (mRECIST), Biopsy, CT Scan, Overall Survival, Staging.

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