학술논문
Prognostic value of baseline [18F]-fluorodeoxyglucose positron emission tomography parameters MTV, TLG and asphericity in an international multicenter cohort of nasopharyngeal carcinoma patients.
Document Type
Academic Journal
Author
Zschaeck S; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Berlin Institute of Health (BIH), Berlin, Germany.; Li Y; Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.; Lin Q; Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.; Beck M; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Amthauer H; Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.; Bauersachs L; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Hajiyianni M; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Rogasch J; Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.; Ehrhardt VH; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Kalinauskaite G; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Weingärtner J; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Hartmann V; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; van den Hoff J; Department of Positron Emission Tomography, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.; Budach V; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Stromberger C; Charité -Universitätsmedizin Berlin, Berlin, Germany.; Freie Universität Berlin, Berlin, Germany.; Humboldt-Universität zu Berlin, Berlin, Germany.; Department of Radiation Oncology, Berlin Institute of Health, Berlin, Germany.; Hofheinz F; Department of Positron Emission Tomography, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
Source
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters have shown prognostic value in nasopharyngeal carcinomas (NPC), mostly in monocenter studies. The aim of this study was to assess the prognostic impact of standard and novel PET parameters in a multicenter cohort of patients.
Methods: The established PET parameters metabolic tumor volume (MTV), total lesion glycolysis (TLG) and maximal standardized uptake value (SUVmax) as well as the novel parameter tumor asphericity (ASP) were evaluated in a retrospective multicenter cohort of 114 NPC patients with FDG-PET staging, treated with (chemo)radiation at 8 international institutions. Uni- and multivariable Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), event-free survival (EFS), distant metastases-free survival (FFDM), and locoregional control (LRC) was performed for clinical and PET parameters.
Results: When analyzing metric PET parameters, ASP showed a significant association with EFS (p = 0.035) and a trend for OS (p = 0.058). MTV was significantly associated with EFS (p = 0.026), OS (p = 0.008) and LRC (p = 0.012) and TLG with LRC (p = 0.019). TLG and MTV showed a very high correlation (Spearman's rho = 0.95), therefore TLG was subesequently not further analysed. Optimal cutoff values for defining high and low risk groups were determined by maximization of the p-value in univariate Cox regression considering all possible cutoff values. Generation of stable cutoff values was feasible for MTV (p<0.001), ASP (p = 0.023) and combination of both (MTV+ASP = occurrence of one or both risk factors, p<0.001) for OS and for MTV regarding the endpoints OS (p<0.001) and LRC (p<0.001). In multivariable Cox (age >55 years + one binarized PET parameter), MTV >11.1ml (hazard ratio (HR): 3.57, p<0.001) and ASP > 14.4% (HR: 3.2, p = 0.031) remained prognostic for OS. MTV additionally remained prognostic for LRC (HR: 4.86 p<0.001) and EFS (HR: 2.51 p = 0.004). Bootstrapping analyses showed that a combination of high MTV and ASP improved prognostic value for OS compared to each single variable significantly (p = 0.005 and p = 0.04, respectively). When using the cohort from China (n = 57 patients) for establishment of prognostic parameters and all other patients for validation (n = 57 patients), MTV could be successfully validated as prognostic parameter regarding OS, EFS and LRC (all p-values <0.05 for both cohorts).
Conclusions: In this analysis, PET parameters were associated with outcome of NPC patients. MTV showed a robust association with OS, EFS and LRC. Our data suggest that combination of MTV and ASP may potentially further improve the risk stratification of NPC patients.
Competing Interests: Dr. Amthauer reports personal fees from SIRTEX Medical Europe, grants from GE Healthcare, grants and personal fees from Novartis, outside the submitted work; All other authors have declared that no competing interests exist. We ensure that Dr Amthauer´s fees and grants do not alter our adherence to PLOS ONE policies on sharing data and materials.
Methods: The established PET parameters metabolic tumor volume (MTV), total lesion glycolysis (TLG) and maximal standardized uptake value (SUVmax) as well as the novel parameter tumor asphericity (ASP) were evaluated in a retrospective multicenter cohort of 114 NPC patients with FDG-PET staging, treated with (chemo)radiation at 8 international institutions. Uni- and multivariable Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), event-free survival (EFS), distant metastases-free survival (FFDM), and locoregional control (LRC) was performed for clinical and PET parameters.
Results: When analyzing metric PET parameters, ASP showed a significant association with EFS (p = 0.035) and a trend for OS (p = 0.058). MTV was significantly associated with EFS (p = 0.026), OS (p = 0.008) and LRC (p = 0.012) and TLG with LRC (p = 0.019). TLG and MTV showed a very high correlation (Spearman's rho = 0.95), therefore TLG was subesequently not further analysed. Optimal cutoff values for defining high and low risk groups were determined by maximization of the p-value in univariate Cox regression considering all possible cutoff values. Generation of stable cutoff values was feasible for MTV (p<0.001), ASP (p = 0.023) and combination of both (MTV+ASP = occurrence of one or both risk factors, p<0.001) for OS and for MTV regarding the endpoints OS (p<0.001) and LRC (p<0.001). In multivariable Cox (age >55 years + one binarized PET parameter), MTV >11.1ml (hazard ratio (HR): 3.57, p<0.001) and ASP > 14.4% (HR: 3.2, p = 0.031) remained prognostic for OS. MTV additionally remained prognostic for LRC (HR: 4.86 p<0.001) and EFS (HR: 2.51 p = 0.004). Bootstrapping analyses showed that a combination of high MTV and ASP improved prognostic value for OS compared to each single variable significantly (p = 0.005 and p = 0.04, respectively). When using the cohort from China (n = 57 patients) for establishment of prognostic parameters and all other patients for validation (n = 57 patients), MTV could be successfully validated as prognostic parameter regarding OS, EFS and LRC (all p-values <0.05 for both cohorts).
Conclusions: In this analysis, PET parameters were associated with outcome of NPC patients. MTV showed a robust association with OS, EFS and LRC. Our data suggest that combination of MTV and ASP may potentially further improve the risk stratification of NPC patients.
Competing Interests: Dr. Amthauer reports personal fees from SIRTEX Medical Europe, grants from GE Healthcare, grants and personal fees from Novartis, outside the submitted work; All other authors have declared that no competing interests exist. We ensure that Dr Amthauer´s fees and grants do not alter our adherence to PLOS ONE policies on sharing data and materials.