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@ARTICLE{Zschaeck:299012,
      author       = {S. Zschaeck$^*$ and M. Hajiyianni and P. Hausmann and P.
                      Nikulin and E. Kukuk and C. Furth and P. Cegla and E.
                      Lombardo and J. Kazmierska and A. Holzgreve and I. Strouthos
                      and C. Stromberger and C. Belka$^*$ and M. Baumann$^*$ and
                      M. Krause$^*$ and G. Landry and W. Cholewinski and J.
                      Kotzerke and D. Zips$^*$ and J. van den Hoff and F.
                      Hofheinz},
      title        = {{T}otal 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.},
      journal      = {Cancer imaging},
      volume       = {25},
      number       = {1},
      issn         = {1470-7330},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2025-00422},
      pages        = {18},
      year         = {2025},
      abstract     = {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.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.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.TLGall is a promising biomarker to
                      select OPC patients with high risk for metachronous distant
                      metastases.},
      keywords     = {Humans / Oropharyngeal Neoplasms: pathology / Oropharyngeal
                      Neoplasms: diagnostic imaging / Oropharyngeal Neoplasms:
                      mortality / Oropharyngeal Neoplasms: metabolism / Male /
                      Female / Retrospective Studies / Middle Aged / Glycolysis /
                      Aged / Fluorodeoxyglucose F18 / Positron-Emission
                      Tomography: methods / Radiopharmaceuticals / Prognosis /
                      Lymphatic Metastasis: diagnostic imaging / Lymph Nodes:
                      pathology / Lymph Nodes: diagnostic imaging / Adult / Aged,
                      80 and over / Neoplasm Metastasis / Tumor Burden /
                      Fluorodeoxyglucose positron emission tomography (Other) /
                      Head and neck squamous cell carcinoma (Other) / Oropharynx
                      cancer (Other) / Total lesion glycolysis (Other) /
                      Fluorodeoxyglucose F18 (NLM Chemicals) /
                      Radiopharmaceuticals (NLM Chemicals)},
      cin          = {DD01 / MU01 / E220 / BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331 / I:(DE-He78)MU01-20160331 /
                      I:(DE-He78)E220-20160331 / I:(DE-He78)BE01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39985091},
      pmc          = {pmc:PMC11844016},
      doi          = {10.1186/s40644-025-00836-6},
      url          = {https://inrepo02.dkfz.de/record/299012},
}