Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT

Our plain-English summary of Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT, by R.J. Francis, T. Segard, L. Morandeau, et al (Lung Cancer, 2015).

The study

• Authors: R.J. Francis, T. Segard, L. Morandeau, Y.C. Lee, M.J. Millward, A. Segal, A.K. Nowak
• Journal: Lung Cancer
• Published: 2015;90(1):55-60
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Malignant pleural mesothelioma (MPM) is a chemotherapy resistant tumor with a poor prognosis. Hypoxia is increasingly recognized as an important factor in tumor aggressiveness and cellular resistance to chemotherapy and radiation treatment. This prospective pilot study was performed with [F-18] fluoromisonidazole (FMISO) PET-CT to characterize hypoxia in patients with MPM.

Materials And Methods: Twenty prospectively recruited patients with histologically or cytologically confirmed MPM not currently receiving systemic or local treatment underwent both FMISO and fluorodeoxyglucose (FDG) PET-CT scans within 2 weeks. FMISO and FDG PET-CT scans were independently analyzed visually and semi-quantitatively using SUVmax and tumor to background ratio (TBR) in order to assess tumor hypoxia and metabolic activity. Lesion by lesion analysis was performed in sites of measurable pleural masses.

Results: Visual analysis demonstrated tumor FMISO activity in 17 of 20 patients, and tumor FDG activity in 19 of 20 patients. Focal areas of bulky tumor were most likely to demonstrate hypoxia. In 19 patients suitable for semi-quantitative analysis the median FDG SUVmax was 6.4 (range 1.9-19.1), median FMISO SUVmax was 2.5 (range 1.4-3.7) and median FMISO TBR was 1.8 (1.1-2.5). There was a positive correlation between intensity of metabolic activity and hypoxia (r=0.72, p=0.001). Lesion by lesion analysis demonstrated a positive correlation between tumor thickness and FMISO activity (r=0.77, p<0.001).

Conclusion: This pilot study confirms that MPM is a tumor with significant areas of hypoxia, particularly in dominant tumor masses. The relationship of tumor hypoxia to effectiveness of chemotherapy and/or radiation therapy warrants prospective assessment.

Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

In plain English

This pilot study, by authors based at Sir Charles Gairdner Hospital in Western Australia, used PET-CT scans to look for hypoxia (areas of low oxygen) in malignant pleural mesothelioma. Twenty patients (19 men, 1 woman) who had not had chemotherapy, immunotherapy or radiation therapy in the previous 6 weeks each had two scans within 2 weeks. One used FMISO, a tracer that collects in low-oxygen tumor cells. The other used FDG, which shows metabolic activity. Sixteen of the 20 had known asbestos exposure; the article gives no fiber types or jobs. On visual review, FMISO activity was seen in tumor in 17 of 20 patients, but it was mildly or markedly above muscle in only 7 of 20. In the 19 patients measured, FDG and FMISO uptake were correlated (r = 0.72, p = 0.001). Across 28 tumor lesions in 16 patients, thicker lesions showed more FMISO uptake (r = 0.77, p less than 0.001). FMISO measures showed no significant relationship with survival, but the authors state the study was not designed or powered for survival analysis. The authors concluded that hypoxia imaging in mesothelioma is feasible and that further studies are warranted.

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 pilot imaging study comparing FMISO PET-CT (hypoxia) with FDG PET-CT (metabolic activity) in the same patients
• Who was studied: 20 patients (19 male, 1 female; median age 64, range 48 to 85) with histologically or cytologically confirmed malignant pleural mesothelioma, not on active chemotherapy, immunotherapy or radiation therapy currently or in the previous 6 weeks. 18 had epithelioid and 2 sarcomatoid histology. The authors are based at Sir Charles Gairdner Hospital, Western Australia. Recruitment dates are not given.
• Exposure: The study measured tumor hypoxia with FMISO PET-CT and metabolic activity with FDG PET-CT. Asbestos exposure was recorded only as a background characteristic: 16 of 20 patients (80%) had known asbestos exposure. No fiber types, products or jobs are reported.
• Main results:
  • On visual assessment, 17 of 20 patients had FMISO (hypoxia) activity in tumor and 19 of 20 had FDG activity in tumor.
  • FMISO activity was mildly or markedly increased compared to muscle in only 7 of 20 patients. FDG activity was mildly or markedly increased in 18 of 20.
  • In the 19 patients with semi-quantitative analysis, median FDG SUVmax in tumor was 6.4 (range 1.9 to 19.1). FMISO SUVmax was 2.5 (range 1.4 to 3.7) and FMISO tumor to background ratio was 1.8 (1.1 to 2.5). The article text calls the FMISO figure a mean; the abstract calls it a median.
  • In the 19 patients, FDG SUVmax and FMISO SUVmax were correlated (r = 0.72, p = 0.001).
  • 28 discrete lesions were identified in 16 patients, with a median tumor thickness of 25 mm (range 7 to 56 mm).
  • Across these lesions, greater pleural thickness was correlated with higher FMISO SUVmax (r = 0.77, p less than 0.001).
  • On visual review, the most intense FMISO activity appeared to correspond to bulky pleural masses.
  • Of 15 patients who later received chemotherapy, 4 had a partial response, 6 had stable disease and 5 had progressive disease. The authors state these results cannot be related to hypoxia.
  • At analysis, 13 patients had died and 7 were alive. No significant relationship was found between FMISO SUVmax or tumor to background ratio and survival.
• The authors' conclusion: The authors concluded that the study shows hypoxia imaging is feasible in mesothelioma and likely has a role distinct from FDG-PET in showing differing hypoxia within tumor areas. They called for further FMISO PET-CT studies, giving highest priority to the link between hypoxia and radiotherapy response in bulky symptomatic lesions.
• Limitations the authors state:
  • The study was not powered or designed for survival analysis. Patients were recruited at different points in their disease and treated in different ways.
  • Variable time intervals between imaging and treatment prevented any interpretation of a relationship between hypoxia and treatment response.
  • Partial volume effects (a technical imaging effect) may contribute to the correlation between tumor thickness and FMISO uptake.
  • Hypoxia imaging with FMISO PET has relatively poor sensitivity, and hypoxia can vary over time and within tumors.
  • Patients joined a median of 58 weeks after diagnosis. The authors say this means the group likely had a better prognosis than is usual for this disease.

Topics

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

Medical terms in this study, explained in our Lexicon: Hypoxia, Pleural Mesothelioma, PET-CT, Chemotherapy, Prognosis.

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