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@ARTICLE{Placke:299520,
      author       = {J.-M. Placke$^*$ and L. S. Rajcsanyi and R. Herbst and P.
                      Terheyden and J. Utikal$^*$ and C. Pföhler and A. Kreuter
                      and P. Mohr and R. Gutzmer and M. Weichenthal and F. Meier
                      and C. Berking and U. Leiter and J. Seier and F. Krefting
                      and A. Tasdogan$^*$ and G. C. Lodde and E. Livingstone and
                      L. Zimmer and A. Roesch$^*$ and K. Griewank and D.
                      Schadendorf$^*$ and S. Ugurel$^*$},
      title        = {{P}resence of brain metastasis differentially impacts
                      long-term survival after first-line therapy in melanoma
                      depending on {BRAF} mutation status.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2025-00478},
      pages        = {1536642},
      year         = {2025},
      abstract     = {Modern therapeutic strategies have significantly improved
                      the prognosis of advanced melanoma patients. Predictive
                      factors of therapy response include serum LDH; however,
                      predictive markers for long-term survival are currently
                      largely lacking.Patients diagnosed with stage IV melanoma
                      (AJCCv8) of cutaneous origin or unknown primary were
                      identified from the prospective multicenter German
                      Dermatologic Cooperative Oncology Group (DeCOG) skin cancer
                      registry ADOREG. Baseline characteristics were compared
                      between patient groups with short-term versus long-term
                      survival. Statistical analysis included ROC analysis and
                      multinomial regression analysis.Of 3066 stage IV melanoma
                      patients entered into the ADOREG between 05/2014 and
                      06/2021, 395 were identified for this study, of whom 301
                      $(76.2\%)$ survived ≤1 year, and 94 $(23.8\%)$ survived
                      ≥5 years after stage IV diagnosis. The median follow-up
                      time was 6 months (range 0-129 months). Regarding the
                      baseline characteristics, only elevated serum LDH (P <0.001)
                      was found to be independently predicting survival ≤1 year.
                      Type of first-line therapy, immune checkpoint inhibition
                      (ICI) versus BRAF/MEK targeted therapy (TT), was not
                      predictive of long-term survival ≥5 years. For survival
                      ≤1 year, the presence of brain metastases at treatment
                      start was an independent predictor in BRAF-mutated patients
                      regardless if they received TT (N=113; P=0<0.001) or ICI
                      (N=69; P=0.015), but not in BRAF-wildtype patients who
                      received ICI (N=161; P=0.47).Low serum LDH independently
                      predicts long-term survival of stage IV melanoma patients in
                      every subgroup of treatment type and BRAF status. Brain
                      metastasis has a negative impact on long-term survival in
                      BRAF-mutated, but not in BRAF-wildtype patients.
                      Investigation of molecular features of brain metastases in
                      BRAF-mutated vs. BRAF-wildtype melanomas may lead to new
                      insights in tumor biology and may yield new therapeutic
                      approaches.},
      keywords     = {Humans / Proto-Oncogene Proteins B-raf: genetics /
                      Melanoma: genetics / Melanoma: mortality / Melanoma: drug
                      therapy / Male / Brain Neoplasms: secondary / Brain
                      Neoplasms: genetics / Brain Neoplasms: mortality / Female /
                      Middle Aged / Aged / Mutation / Adult / Skin Neoplasms:
                      genetics / Skin Neoplasms: mortality / Skin Neoplasms: drug
                      therapy / Skin Neoplasms: pathology / Prognosis / Neoplasm
                      Staging / Aged, 80 and over / Prospective Studies / Immune
                      Checkpoint Inhibitors: therapeutic use / Biomarkers, Tumor:
                      genetics / Registries / BRAF (Other) / brain metastases
                      (Other) / immune checkpoint inhibitor (ICI) (Other) /
                      long-term survival (Other) / melanoma (Other) / targeted
                      therapy (Other) / Proto-Oncogene Proteins B-raf (NLM
                      Chemicals) / BRAF protein, human (NLM Chemicals) / Immune
                      Checkpoint Inhibitors (NLM Chemicals) / Biomarkers, Tumor
                      (NLM Chemicals)},
      cin          = {ED01 / A370},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331 / I:(DE-He78)A370-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40028330},
      pmc          = {pmc:PMC11868123},
      doi          = {10.3389/fimmu.2025.1536642},
      url          = {https://inrepo02.dkfz.de/record/299520},
}