A comparative study of standardized quantitative and visual assessment for predicting tumor volume and outcome in newly diagnosed diffuse large B-cell lymphoma staged with 18F-FDG PET/CT

Lars C. Gormsen*, Mikkel H. Vendelbo, Mette Abildgaard Pedersen, Ate Haraldsen, Karin Hjorthaug, Trond Velde Bogsrud, Lars J. Petersen, Karen Juul Jensen, Rasmus Brøndum, Tarec C. El-Galaly

*Corresponding author for this work

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Abstract

Background: Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication. Materials and methods: Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV 2.5 (SUV 2.5 cut-off) and MTV 41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTV VAS ) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers. Results: In the quantitative analysis, a ROC-determined MTV 2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV 41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTV VAS and eMTV were not consistently correlated with the outcome. Conclusion: Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.

Original languageEnglish
Article number36
JournalEJNMMI Research
Volume9
Number of pages8
ISSN2191-219X
DOIs
Publication statusPublished - 3. May 2019

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Lymphoma, Large B-Cell, Diffuse
Fluorodeoxyglucose F18
Tumor Burden
Observer Variation
Nuclear Medicine
Visual Analog Scale
ROC Curve
Disease-Free Survival
Lymphoma

Keywords

  • 18F-FDG PET/CT
  • DLBCL
  • MTV
  • Prognosis

Cite this

Gormsen, Lars C. ; Vendelbo, Mikkel H. ; Pedersen, Mette Abildgaard ; Haraldsen, Ate ; Hjorthaug, Karin ; Bogsrud, Trond Velde ; Petersen, Lars J. ; Jensen, Karen Juul ; Brøndum, Rasmus ; El-Galaly, Tarec C. / A comparative study of standardized quantitative and visual assessment for predicting tumor volume and outcome in newly diagnosed diffuse large B-cell lymphoma staged with 18F-FDG PET/CT. In: EJNMMI Research. 2019 ; Vol. 9.
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abstract = "Background: Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication. Materials and methods: Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder{\circledR} to obtain MTV 2.5 (SUV 2.5 cut-off) and MTV 41 (41{\%} SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTV VAS ) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers. Results: In the quantitative analysis, a ROC-determined MTV 2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV 41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTV VAS and eMTV were not consistently correlated with the outcome. Conclusion: Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.",
keywords = "18F-FDG PET/CT, DLBCL, MTV, Prognosis",
author = "Gormsen, {Lars C.} and Vendelbo, {Mikkel H.} and Pedersen, {Mette Abildgaard} and Ate Haraldsen and Karin Hjorthaug and Bogsrud, {Trond Velde} and Petersen, {Lars J.} and Jensen, {Karen Juul} and Rasmus Br{\o}ndum and El-Galaly, {Tarec C.}",
year = "2019",
month = "5",
day = "3",
doi = "10.1186/s13550-019-0503-z",
language = "English",
volume = "9",
journal = "EJNMMI Research",
issn = "2191-219X",
publisher = "Springer",

}

A comparative study of standardized quantitative and visual assessment for predicting tumor volume and outcome in newly diagnosed diffuse large B-cell lymphoma staged with 18F-FDG PET/CT. / Gormsen, Lars C.; Vendelbo, Mikkel H.; Pedersen, Mette Abildgaard; Haraldsen, Ate; Hjorthaug, Karin; Bogsrud, Trond Velde; Petersen, Lars J.; Jensen, Karen Juul; Brøndum, Rasmus; El-Galaly, Tarec C.

In: EJNMMI Research, Vol. 9, 36, 03.05.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - A comparative study of standardized quantitative and visual assessment for predicting tumor volume and outcome in newly diagnosed diffuse large B-cell lymphoma staged with 18F-FDG PET/CT

AU - Gormsen, Lars C.

AU - Vendelbo, Mikkel H.

AU - Pedersen, Mette Abildgaard

AU - Haraldsen, Ate

AU - Hjorthaug, Karin

AU - Bogsrud, Trond Velde

AU - Petersen, Lars J.

AU - Jensen, Karen Juul

AU - Brøndum, Rasmus

AU - El-Galaly, Tarec C.

PY - 2019/5/3

Y1 - 2019/5/3

N2 - Background: Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication. Materials and methods: Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV 2.5 (SUV 2.5 cut-off) and MTV 41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTV VAS ) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers. Results: In the quantitative analysis, a ROC-determined MTV 2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV 41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTV VAS and eMTV were not consistently correlated with the outcome. Conclusion: Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.

AB - Background: Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication. Materials and methods: Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV 2.5 (SUV 2.5 cut-off) and MTV 41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTV VAS ) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers. Results: In the quantitative analysis, a ROC-determined MTV 2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV 41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTV VAS and eMTV were not consistently correlated with the outcome. Conclusion: Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.

KW - 18F-FDG PET/CT

KW - DLBCL

KW - MTV

KW - Prognosis

U2 - 10.1186/s13550-019-0503-z

DO - 10.1186/s13550-019-0503-z

M3 - Journal article

C2 - 31054023

AN - SCOPUS:85065332842

VL - 9

JO - EJNMMI Research

JF - EJNMMI Research

SN - 2191-219X

M1 - 36

ER -