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@ARTICLE{Sachpekidis:277731,
      author       = {C. Sachpekidis$^*$ and C. K. Stein-Thoeringer and A.
                      Kopp-Schneider$^*$ and V. Weru$^*$ and A.
                      Dimitrakopoulou-Strauss$^*$ and J. C. Hassel},
      title        = {{C}an physiologic colonic [18{F}]{FDG} uptake in {PET}/{CT}
                      imaging predict response to immunotherapy in metastatic
                      melanoma?},
      journal      = {European journal of nuclear medicine and molecular imaging},
      volume       = {50},
      number       = {12},
      issn         = {1619-7070},
      address      = {Heidelberg [u.a.]},
      publisher    = {Springer-Verl.},
      reportid     = {DKFZ-2023-01448},
      pages        = {3709-3722},
      year         = {2023},
      note         = {#EA:E060#LA:E060# / 2023 Oct;50(12):3709-3722},
      abstract     = {The development of biomarkers that can reliably and early
                      predict response to immune checkpoint inhibitors (ICIs) is
                      crucial in melanoma. In recent years, the gut microbiome has
                      emerged as an important regulator of immunotherapy response,
                      which may, moreover, serve as a surrogate marker and
                      prognosticator in oncological patients under immunotherapy.
                      Aim of the present study is to investigate if physiologic
                      colonic [18F]FDG uptake in PET/CT before start of ICIs
                      correlates with clinical outcome of metastatic melanoma
                      patients. The relation between [18F]FDG uptake in lymphoid
                      cell-rich organs and long-term patient outcome is also
                      assessed.One hundred nineteen stage IV melanoma patients
                      scheduled for immunotherapy with ipilimumab, applied either
                      as monotherapy or in combination with nivolumab, underwent
                      baseline [18F]FDG PET/CT. PET/CT data analysis consisted of
                      standardized uptake value (SUV), metabolic tumor volume
                      (MTV), and total lesion glycolysis (TLG) calculations in the
                      colon as well as measurements of the colon-to-liver SUV
                      ratios (CLRmean, CLRmax). Visual grading of colon uptake
                      based on a four-point scale was also performed. Moreover,
                      the spleen-to-liver SUV ratios (SLRmean, SLRmax) and the
                      bone marrow-to-liver SUV ratios (BLRmean, BLRmax) were
                      calculated. We also measured serum lipopolysaccharide (LPS)
                      levels as a marker for bacterial translocation and surrogate
                      for mucosal defense homeostasis. The results were correlated
                      with patients' best clinical response, progression-free
                      survival (PFS), and overall survival (OS) as well as
                      clinical signs of colitis.Median follow-up $[95\%CI]$ from
                      the beginning of immunotherapy was 64.6 months [61.0-68.6
                      months]. Best response to treatment was progressive disease
                      (PD) for 60 patients, stable disease (SD) for 37 patients,
                      partial response (PR) for 18 patients, and complete response
                      (CR) for 4 patients. Kaplan-Meier curves demonstrated a
                      trend for longer PFS and OS in patients with lower colonic
                      SUV and CLR values; however, no statistical significance for
                      these parameters as prognostic factors was demonstrated. On
                      the other hand, patients showing disease control as best
                      response to treatment (SD, PR, CR) had significantly lower
                      colonic MTV and TLG than those showing PD. With regard to
                      lymphoid cell-rich organs, significantly lower baseline
                      SLRmax and BLRmax were observed in patients responding with
                      disease control than progression to treatment. Furthermore,
                      patients with lower SLRmax and BLRmax values had a
                      significantly longer OS when dichotomized at their median.
                      In multivariate analysis, PET parameters that were found to
                      significantly adversely correlate with patient survival were
                      colonic MTV for PFS, colonic TLG for PFS, and BLRmax for PFS
                      and OS.Physiologic colonic [18F]FDG uptake in PET/CT, as
                      assessed by means of SUV, before start of ipilimumab-based
                      treatment does not seem to independently predict patient
                      survival of metastatic melanoma. On the other hand,
                      volumetric PET parameters, such as MTV and TLG, derived from
                      the normal gut may identify patients showing disease control
                      to immunotherapy and significantly correlate with PFS.
                      Moreover, the investigation of glucose metabolism in the
                      spleen and the bone marrow may offer prognostic
                      information.},
      keywords     = {Gut microbiome (Other) / Immunotherapy (Other) /
                      Lipopolysaccharide (LPS) (Other) / MTV (Other) / Metastatic
                      melanoma (Other) / PET/CT (Other) / SUV (Other) / TLG
                      (Other) / [18F]FDG colonic uptake (Other)},
      cin          = {E060 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)E060-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37452874},
      doi          = {10.1007/s00259-023-06327-9},
      url          = {https://inrepo02.dkfz.de/record/277731},
}