Detection of cancer‐associated cachexia in lung cancer patients using whole‐body [18F]FDG‐PET/CT imaging: A multi‐centre study

Abstract Background Cancer‐associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non‐imaging criteria. Given the metabolic underpinnings of CAC and the ability of [18F]fluoro‐2‐deoxy‐D...

Full description

Saved in:
Bibliographic Details
Main Authors: Daria Ferrara, Elisabetta M. Abenavoli, Thomas Beyer, Stefan Gruenert, Marcus Hacker, Swen Hesse, Lukas Hofmann, Smilla Pusitz, Michael Rullmann, Osama Sabri, Roberto Sciagrà, Lalith Kumar Shiyam Sundar, Anke Tönjes, Hubert Wirtz, Josef Yu, Armin Frille
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Journal of Cachexia, Sarcopenia and Muscle
Subjects:
Online Access:https://doi.org/10.1002/jcsm.13571
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846127404474433536
author Daria Ferrara
Elisabetta M. Abenavoli
Thomas Beyer
Stefan Gruenert
Marcus Hacker
Swen Hesse
Lukas Hofmann
Smilla Pusitz
Michael Rullmann
Osama Sabri
Roberto Sciagrà
Lalith Kumar Shiyam Sundar
Anke Tönjes
Hubert Wirtz
Josef Yu
Armin Frille
author_facet Daria Ferrara
Elisabetta M. Abenavoli
Thomas Beyer
Stefan Gruenert
Marcus Hacker
Swen Hesse
Lukas Hofmann
Smilla Pusitz
Michael Rullmann
Osama Sabri
Roberto Sciagrà
Lalith Kumar Shiyam Sundar
Anke Tönjes
Hubert Wirtz
Josef Yu
Armin Frille
author_sort Daria Ferrara
collection DOAJ
description Abstract Background Cancer‐associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non‐imaging criteria. Given the metabolic underpinnings of CAC and the ability of [18F]fluoro‐2‐deoxy‐D‐glucose (FDG)‐positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole‐body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC. Methods This multi‐centre study included 345 LCP who underwent WB [18F]FDG‐PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into ‘No CAC’ (WLGS‐0/1 at baseline prior treatment and at first follow‐up: N = 158, 51F/107M), ‘Dev CAC’ (WLGS‐0/1 at baseline and WLGS‐3/4 at follow‐up: N = 90, 34F/56M), and ‘CAC’ (WLGS‐3/4 at baseline: N = 97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake (<SUVaorta>) and CT‐defined volumes were extracted for abdominal and visceral organs, muscles, and adipose‐tissue using automated image segmentation of baseline [18F]FDG‐PET/CT images. Imaging and non‐imaging parameters from laboratory tests were compared statistically. A machine‐learning (ML) model was then trained to classify LCP as ‘No CAC’, ‘Dev CAC’, and ‘CAC’ based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient. Results The three CAC categories displayed multi‐organ differences in <SUVaorta>. In all target organs, <SUVaorta> was higher in the ‘CAC’ cohort compared with ‘No CAC’ (P < 0.01), except for liver and kidneys, where <SUVaorta> in ‘CAC’ was reduced by 5%. The ‘Dev CAC’ cohort displayed a small but significant increase in <SUVaorta> of pancreas (+4%), skeletal‐muscle (+7%), subcutaneous adipose‐tissue (+11%), and visceral adipose‐tissue (+15%). In ‘CAC’ patients, a strong negative Spearman correlation (ρ = −0.8) was identified between <SUVaorta> and volumes of adipose‐tissue. The machine‐learning model identified ‘CAC’ at baseline with 81% of accuracy, highlighting <SUVaorta> of spleen, pancreas, liver, and adipose‐tissue as most relevant features. The model performance was suboptimal (54%) when classifying ‘Dev CAC’ versus ‘No CAC’. Conclusions WB [18F]FDG‐PET/CT imaging reveals groupwise differences in the multi‐organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients with CAC with good accuracy. However, its performance in patients developing CAC was suboptimal. A prospective, multi‐centre study has been initiated to address the limitations of the present retrospective analysis.
format Article
id doaj-art-bb14636f1c8346a4807b2f4b4bce05c3
institution Kabale University
issn 2190-5991
2190-6009
language English
publishDate 2024-12-01
publisher Wiley
record_format Article
series Journal of Cachexia, Sarcopenia and Muscle
spelling doaj-art-bb14636f1c8346a4807b2f4b4bce05c32024-12-12T02:31:37ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092024-12-011562375238610.1002/jcsm.13571Detection of cancer‐associated cachexia in lung cancer patients using whole‐body [18F]FDG‐PET/CT imaging: A multi‐centre studyDaria Ferrara0Elisabetta M. Abenavoli1Thomas Beyer2Stefan Gruenert3Marcus Hacker4Swen Hesse5Lukas Hofmann6Smilla Pusitz7Michael Rullmann8Osama Sabri9Roberto Sciagrà10Lalith Kumar Shiyam Sundar11Anke Tönjes12Hubert Wirtz13Josef Yu14Armin Frille15QIMP Team Medical University of Vienna Vienna AustriaDivision of Nuclear Medicine Azienda Ospedaliero Universitaria Careggi Florence ItalyQIMP Team Medical University of Vienna Vienna AustriaDivision of Nuclear Medicine Medical University of Vienna Vienna AustriaDivision of Nuclear Medicine Medical University of Vienna Vienna AustriaDepartment of Nuclear Medicine University Hospital Leipzig Leipzig GermanyDepartment of Nuclear Medicine University Hospital Leipzig Leipzig GermanyDivision of Nuclear Medicine Medical University of Vienna Vienna AustriaDepartment of Nuclear Medicine University Hospital Leipzig Leipzig GermanyDepartment of Nuclear Medicine University Hospital Leipzig Leipzig GermanyDivision of Nuclear Medicine Azienda Ospedaliero Universitaria Careggi Florence ItalyQIMP Team Medical University of Vienna Vienna AustriaDepartment of Endocrinology University Hospital Leipzig Leipzig GermanyDepartment of Respiratory Medicine University Hospital Leipzig Leipzig GermanyQIMP Team Medical University of Vienna Vienna AustriaDepartment of Nuclear Medicine University Hospital Leipzig Leipzig GermanyAbstract Background Cancer‐associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non‐imaging criteria. Given the metabolic underpinnings of CAC and the ability of [18F]fluoro‐2‐deoxy‐D‐glucose (FDG)‐positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole‐body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC. Methods This multi‐centre study included 345 LCP who underwent WB [18F]FDG‐PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into ‘No CAC’ (WLGS‐0/1 at baseline prior treatment and at first follow‐up: N = 158, 51F/107M), ‘Dev CAC’ (WLGS‐0/1 at baseline and WLGS‐3/4 at follow‐up: N = 90, 34F/56M), and ‘CAC’ (WLGS‐3/4 at baseline: N = 97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake (<SUVaorta>) and CT‐defined volumes were extracted for abdominal and visceral organs, muscles, and adipose‐tissue using automated image segmentation of baseline [18F]FDG‐PET/CT images. Imaging and non‐imaging parameters from laboratory tests were compared statistically. A machine‐learning (ML) model was then trained to classify LCP as ‘No CAC’, ‘Dev CAC’, and ‘CAC’ based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient. Results The three CAC categories displayed multi‐organ differences in <SUVaorta>. In all target organs, <SUVaorta> was higher in the ‘CAC’ cohort compared with ‘No CAC’ (P < 0.01), except for liver and kidneys, where <SUVaorta> in ‘CAC’ was reduced by 5%. The ‘Dev CAC’ cohort displayed a small but significant increase in <SUVaorta> of pancreas (+4%), skeletal‐muscle (+7%), subcutaneous adipose‐tissue (+11%), and visceral adipose‐tissue (+15%). In ‘CAC’ patients, a strong negative Spearman correlation (ρ = −0.8) was identified between <SUVaorta> and volumes of adipose‐tissue. The machine‐learning model identified ‘CAC’ at baseline with 81% of accuracy, highlighting <SUVaorta> of spleen, pancreas, liver, and adipose‐tissue as most relevant features. The model performance was suboptimal (54%) when classifying ‘Dev CAC’ versus ‘No CAC’. Conclusions WB [18F]FDG‐PET/CT imaging reveals groupwise differences in the multi‐organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients with CAC with good accuracy. However, its performance in patients developing CAC was suboptimal. A prospective, multi‐centre study has been initiated to address the limitations of the present retrospective analysis.https://doi.org/10.1002/jcsm.13571[18F]Fluoro‐2‐deoxy‐D‐glucoseCachexiaLung cancerMetabolismPET/CT
spellingShingle Daria Ferrara
Elisabetta M. Abenavoli
Thomas Beyer
Stefan Gruenert
Marcus Hacker
Swen Hesse
Lukas Hofmann
Smilla Pusitz
Michael Rullmann
Osama Sabri
Roberto Sciagrà
Lalith Kumar Shiyam Sundar
Anke Tönjes
Hubert Wirtz
Josef Yu
Armin Frille
Detection of cancer‐associated cachexia in lung cancer patients using whole‐body [18F]FDG‐PET/CT imaging: A multi‐centre study
Journal of Cachexia, Sarcopenia and Muscle
[18F]Fluoro‐2‐deoxy‐D‐glucose
Cachexia
Lung cancer
Metabolism
PET/CT
title Detection of cancer‐associated cachexia in lung cancer patients using whole‐body [18F]FDG‐PET/CT imaging: A multi‐centre study
title_full Detection of cancer‐associated cachexia in lung cancer patients using whole‐body [18F]FDG‐PET/CT imaging: A multi‐centre study
title_fullStr Detection of cancer‐associated cachexia in lung cancer patients using whole‐body [18F]FDG‐PET/CT imaging: A multi‐centre study
title_full_unstemmed Detection of cancer‐associated cachexia in lung cancer patients using whole‐body [18F]FDG‐PET/CT imaging: A multi‐centre study
title_short Detection of cancer‐associated cachexia in lung cancer patients using whole‐body [18F]FDG‐PET/CT imaging: A multi‐centre study
title_sort detection of cancer associated cachexia in lung cancer patients using whole body 18f fdg pet ct imaging a multi centre study
topic [18F]Fluoro‐2‐deoxy‐D‐glucose
Cachexia
Lung cancer
Metabolism
PET/CT
url https://doi.org/10.1002/jcsm.13571
work_keys_str_mv AT dariaferrara detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT elisabettamabenavoli detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT thomasbeyer detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT stefangruenert detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT marcushacker detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT swenhesse detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT lukashofmann detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT smillapusitz detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT michaelrullmann detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT osamasabri detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT robertosciagra detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT lalithkumarshiyamsundar detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT anketonjes detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT hubertwirtz detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT josefyu detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy
AT arminfrille detectionofcancerassociatedcachexiainlungcancerpatientsusingwholebody18ffdgpetctimagingamulticentrestudy