Total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesions
Abstract Background Oropharyngeal carcinomas are characterized by an increasing incidence and a relatively good prognosis. Nonetheless, a considerable number of patients develops metachronous distant metastases; identification of these patients is an urgent medical need. Methods This is a retrospect...
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2025-02-01
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| Online Access: | https://doi.org/10.1186/s40644-025-00836-6 |
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| author | Sebastian Zschaeck Marina Hajiyianni Patrick Hausmann Pavel Nikulin Emily Kukuk Christian Furth Paulina Cegla Elia Lombardo Joanna Kazmierska Adrien Holzgreve Iosif Strouthos Carmen Stromberger Claus Belka Michael Baumann Mechthild Krause Guillaume Landry Witold Cholewinski Jorg Kotzerke Daniel Zips Jörg van den Hoff Frank Hofheinz |
| author_facet | Sebastian Zschaeck Marina Hajiyianni Patrick Hausmann Pavel Nikulin Emily Kukuk Christian Furth Paulina Cegla Elia Lombardo Joanna Kazmierska Adrien Holzgreve Iosif Strouthos Carmen Stromberger Claus Belka Michael Baumann Mechthild Krause Guillaume Landry Witold Cholewinski Jorg Kotzerke Daniel Zips Jörg van den Hoff Frank Hofheinz |
| author_sort | Sebastian Zschaeck |
| collection | DOAJ |
| description | Abstract Background Oropharyngeal carcinomas are characterized by an increasing incidence and a relatively good prognosis. Nonetheless, a considerable number of patients develops metachronous distant metastases; identification of these patients is an urgent medical need. Methods This is a retrospective multicenter evaluation of 431 patients. All patients underwent [18F]-FDG positron emission tomography (PET). The cohort was split into an explorative group (n = 366) and a validation group (n = 65). Lesions were manually delineated in the explorative group and automatically delineated by a convolutional neuronal network (CNN) in the validation group. Quantitative PET parameters standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated for primary tumors (prim) and tumor plus lymphnodes (all). Association of parameters with freedom from distant metastases (FFDM) and overall survival (OS) was tested by cox regression analyses. Results In the explorative group, univariate analyses revealed an association of metric MTVprim (p = 0.022), MTVall (p < 0.001) and TLGall (p < 0.001) with FFDM, binarized parameters were also associated with FFDM (p < 0.001 and p = 0.002). Bootstrap analyses revealed a significantly better association of TLGall compared to TLGprim with FFDM (p = 0.02). MTVall and TLGall remained significantly associated with FFDM upon multivariate testing (p = 0.002, p = 0.031, respectively). In the validation group, the cutoff value for TLGall but not for TLGprim was significantly associated with FFDM (HR = 3.1, p = 0.045). Additional analyses with manually delineated contours of the validation cohort revealed a similar effect (HR = 3.47, p = 0.026). No considerable differences between HPV positive and negative disease were observed. Conclusions TLGall is a promising biomarker to select OPC patients with high risk for metachronous distant metastases. |
| format | Article |
| id | doaj-art-f309d4b5281b49d1941eedae449082ce |
| institution | DOAJ |
| issn | 1470-7330 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Cancer Imaging |
| spelling | doaj-art-f309d4b5281b49d1941eedae449082ce2025-08-20T03:06:50ZengBMCCancer Imaging1470-73302025-02-012511810.1186/s40644-025-00836-6Total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesionsSebastian Zschaeck0Marina Hajiyianni1Patrick Hausmann2Pavel Nikulin3Emily Kukuk4Christian Furth5Paulina Cegla6Elia Lombardo7Joanna Kazmierska8Adrien Holzgreve9Iosif Strouthos10Carmen Stromberger11Claus Belka12Michael Baumann13Mechthild Krause14Guillaume Landry15Witold Cholewinski16Jorg Kotzerke17Daniel Zips18Jörg van den Hoff19Frank Hofheinz20Department of Radiation Oncology, Charité– Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthDepartment of Radiation Oncology, Charité– Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthDepartment of Radiation Oncology, Charité– Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthInstitute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-RossendorfDepartment of Radiation Oncology, Charité– Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthDepartment of Nuclear Medicine, Charité Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin Institute of HealthDepartment of Nuclear Medicine, Greater Poland Cancer CentreDepartment of Radiation Oncology, LMU University Hospital, LMU MunichElectroradiology Department, University of Medical SciencesDepartment of Nuclear Medicine, LMU University Hospital, LMU MunichDepartment of Radiation Oncology, German Oncology Center, European University CyprusDepartment of Radiation Oncology, Charité– Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthDepartment of Radiation Oncology, LMU University Hospital, LMU MunichOncoRay– National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden– RossendorfDepartment of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Radiation Oncology, LMU University Hospital, LMU MunichDepartment of Nuclear Medicine, Greater Poland Cancer CentreDepartment of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Radiation Oncology, Charité– Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthInstitute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-RossendorfInstitute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-RossendorfAbstract Background Oropharyngeal carcinomas are characterized by an increasing incidence and a relatively good prognosis. Nonetheless, a considerable number of patients develops metachronous distant metastases; identification of these patients is an urgent medical need. Methods This is a retrospective multicenter evaluation of 431 patients. All patients underwent [18F]-FDG positron emission tomography (PET). The cohort was split into an explorative group (n = 366) and a validation group (n = 65). Lesions were manually delineated in the explorative group and automatically delineated by a convolutional neuronal network (CNN) in the validation group. Quantitative PET parameters standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated for primary tumors (prim) and tumor plus lymphnodes (all). Association of parameters with freedom from distant metastases (FFDM) and overall survival (OS) was tested by cox regression analyses. Results In the explorative group, univariate analyses revealed an association of metric MTVprim (p = 0.022), MTVall (p < 0.001) and TLGall (p < 0.001) with FFDM, binarized parameters were also associated with FFDM (p < 0.001 and p = 0.002). Bootstrap analyses revealed a significantly better association of TLGall compared to TLGprim with FFDM (p = 0.02). MTVall and TLGall remained significantly associated with FFDM upon multivariate testing (p = 0.002, p = 0.031, respectively). In the validation group, the cutoff value for TLGall but not for TLGprim was significantly associated with FFDM (HR = 3.1, p = 0.045). Additional analyses with manually delineated contours of the validation cohort revealed a similar effect (HR = 3.47, p = 0.026). No considerable differences between HPV positive and negative disease were observed. Conclusions TLGall is a promising biomarker to select OPC patients with high risk for metachronous distant metastases.https://doi.org/10.1186/s40644-025-00836-6Head and neck squamous cell carcinomaFluorodeoxyglucose positron emission tomographyOropharynx cancerTotal lesion glycolysis |
| spellingShingle | Sebastian Zschaeck Marina Hajiyianni Patrick Hausmann Pavel Nikulin Emily Kukuk Christian Furth Paulina Cegla Elia Lombardo Joanna Kazmierska Adrien Holzgreve Iosif Strouthos Carmen Stromberger Claus Belka Michael Baumann Mechthild Krause Guillaume Landry Witold Cholewinski Jorg Kotzerke Daniel Zips Jörg van den Hoff Frank Hofheinz Total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesions Cancer Imaging Head and neck squamous cell carcinoma Fluorodeoxyglucose positron emission tomography Oropharynx cancer Total lesion glycolysis |
| title | Total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesions |
| title_full | Total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesions |
| title_fullStr | Total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesions |
| title_full_unstemmed | Total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesions |
| title_short | Total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesions |
| title_sort | total lesion glycolysis of primary tumor and lymphnodes is a strong predictor for development of distant metastases in oropharyngeal carcinoma patients with independent validation in automatically delineated lesions |
| topic | Head and neck squamous cell carcinoma Fluorodeoxyglucose positron emission tomography Oropharynx cancer Total lesion glycolysis |
| url | https://doi.org/10.1186/s40644-025-00836-6 |
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