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PET-detected pneumonitis following curative-intent chemoradiation in non-small cell lung cancer (NSCLC): recognizing patterns and assessing the impact on the predictive ability of FDG-PET/CT response assessment

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Inflammatory FDG uptake in the lung (PET-pneumonitis) following curative-intent radiotherapy (RT)/chemo-RT (CRT) in non-small cell lung cancer (NSCLC) can pose a challenge in FDG-PET/CT response assessment. The aim of this study is to describe different patterns of PET-pneumonitis to guide the interpretation of FDG-PET/CT and investigate its association with tumor response and overall survival (OS).

Methods

Retrospective analysis was performed on 87 NSCLC patients in three prospective trials who were treated with radical RT (n = 7) or CRT (n = 80), with baseline and post-treatment FDG-PET/CT. Visual criteria were performed for post-treatment FDG-PET/CT response assessment. The grading of PET-pneumonitis was based on relative lung uptake intensity compared to organs of reference and classified as per Deauville score from grade 1–5. Distribution patterns of PET-pneumonitis were defined as follows: A) patchy/sub-pleural; B) diffuse (involving more than a segment); and C) peripheral (diffusely surrounding a photopenic region).

Results

Follow-up FDG-PET/CT scans were performed approximately 3 months (median, 89 days; interquartile range, 79–93) after RT. Overall, PET-pneumonitis was present in 62/87 (71%) of patients, with Deauville 2 or 3 in 12/62 (19%) and 4 or 5 in 50/62 (81%) of patients. The frequency of patterns A, B and C of PET-pneumonitis was 19/62 (31%), 20/62 (32%) and 23/62 (37%), respectively. No association was found between grade or pattern of PET-pneumonitis and overall response at follow-up PET/CT (p = 0.27 and p = 0.56, respectively). There was also no significant association between PET-pneumonitis and OS (hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.6–2.5; p = 0.45). Early FDG-PET/CT response assessment, however, was prognostic for OS (HR, 1.7; 95% CI, 1.2–2.2; p < 0.001).

Conclusion

PET-pneumonitis is common in early post-CRT/RT, but pattern recognition may assist in response assessment by FDG-PET/CT. While FDG-PET/CT is a powerful tool for response assessment and prognostication, PET-pneumonitis does not appear to confound early response assessment or to independently predict OS.

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Funding

No funding was received for this study. However, the 18F-FLT/18F-FDG study (Australian Clinical Trials Registry: ACTRN12611001283965) work was supported by the National Health and Medical Research Council (NHMRC) (grant number APP1003895) and the Victorian Cancer Agency. The 68Ga-Ventilation/perfusion PET (Universal Trial Number: U1111-1138-4421) study was supported by funding from the NHMRC (grant number APP1038399) and from the Cancer Australia Priority-driven Collaborative Cancer Research Scheme (Project No. 1060919). Professor Hicks is supported by an NHMRC Practitioner Fellowship (APP1108050).

Author information

Authors and Affiliations

  1. Cancer Imaging, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia

    Amir Iravani, Tim Akhurst, Jason W. Callahan, Michael S. Hofman & Rodney J. Hicks

  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia

    Amir Iravani, Sarah J. Everitt, Shankar Siva, Rodney J. Hicks, David L. Ball & Michael P. Mac Manus

  3. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Guy-Anne Turgeon, Shankar Siva, David L. Ball & Michael P. Mac Manus

  4. Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Mathias Bressel

  5. Radiation Therapy, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Sarah J. Everitt

  6. Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Dentistry, Monash University, Clayton, VIC, Australia

    Sarah J. Everitt

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  1. Amir Iravani
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Corresponding author

Correspondence to Amir Iravani.

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Conflict of interest

We wish to confirm that there are no known conflicts of interest associated with this publication. A Iravani, GA Turgeon, T Akhurst, JW Callahan, M Bressel, SJ Everitt and MP Mac Manus have no disclosure. Through his institution, DL Ball has an advisory role for Pfizer Australia. RJ Hicks has ownership interest in Telix Radiopharmaceuticals. Through his institution, S Siva has an advisory role for Astellas Pharmaceuticals and Janssen Pharmaceuticals and receives research funding from Varian Medical Systems and Merck Sharp & Dohme Pharmaceuticals. S Siva received speakers’ bureau, travel/accommodations/expenses from Bristol-Myers Squibb Pharmaceuticals as well as travel/accommodation/expenses from Astellas Pharmaceuticals.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

The registration number for the prospective studies were as follows, PET-planning study: Peter Mac protocol 03/55; the 18F-FLT/18F-FDG study: Australian Clinical Trials Registry no. ACTRN12611001283965; and the 68Ga-ventilation/perfusion PET study: universal trial number U1111-1138-4421. The Peter MacCallum Cancer Clinical Research and Ethics Committee approved this retrospective study and waived the requirement to obtain informed consent (approval number: PMCC 17/43R). All patients had previously provided written informed consent to undergo their respective prospective studies.

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Iravani, A., Turgeon, GA., Akhurst, T. et al. PET-detected pneumonitis following curative-intent chemoradiation in non-small cell lung cancer (NSCLC): recognizing patterns and assessing the impact on the predictive ability of FDG-PET/CT response assessment. Eur J Nucl Med Mol Imaging 46, 1869–1877 (2019). https://doi.org/10.1007/s00259-019-04388-3

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