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@ARTICLE{AvinentPrez:296075,
      author       = {M. Avinent-Pérez$^*$ and F. Westermann$^*$ and S. Navarro
                      and A. López-Carrasco and R. Noguera},
      title        = {{T}ackling {ALT}-positive neuroblastoma: is it time to
                      redefine risk classification systems? {A} systematic review
                      with {IPD} meta-analysis.},
      journal      = {Neoplasia},
      volume       = {60},
      issn         = {1522-8002},
      address      = {Basingstoke},
      publisher    = {Stockton Press},
      reportid     = {DKFZ-2025-00023},
      pages        = {101106},
      year         = {2025},
      note         = {#EA:B087#},
      abstract     = {The heterogeneous prognosis in neuroblastoma, shaped by
                      telomere maintenance mechanisms (TMMs), notably the
                      alternative lengthening of telomeres (ALT) pathway,
                      necessitates a refined risk classification for high-risk
                      patients. Current systems often lack precision, hindering
                      tailored treatment approaches. This individual participant
                      data (IPD) meta-analysis of survival among ALT-positive
                      patients aims to improve risk classification systems,
                      enhancing therapeutic strategies and patient
                      outcomes.Following PRISMA-IPD guidelines, we conducted a
                      comprehensive review of neuroblastoma patients retrieved
                      from PubMed, Scopus, and Embase databases until March-2024.
                      Patients were stratified into ALT-positive and TMM-negative
                      subgroups. Overall and event-free survival probabilities
                      were evaluated.In our cohort of 293 patients (156
                      ALT-positive, 137 TMM-negative) obtained from eight
                      different studies, ALT-positive individuals displayed lower
                      survival rates than TMM-negative patients. Non-stage 4
                      ALT-positive patients had reduced overall and event-free
                      survival probabilities compared to their TMM-negative
                      counterparts, indicating potential misclassification. Stage
                      4 ALT-positive patients similarly showed poorer survival
                      outcomes than non-stage 4 TMM-negative patients,
                      underscoring the significance of ALT in patient
                      prognosis.Our study highlights poorer outcomes in
                      ALT-positive neuroblastoma patients, emphasizing the need to
                      integrate TMM status into international risk classification
                      guidelines. Standardizing TMM assessment is key for refining
                      treatment strategies, considering the unique biology of
                      ALT-positive patients.},
      subtyp        = {Review Article},
      keywords     = {Childhood cancer (Other) / Prognosis biomarker (Other) /
                      Survival (Other) / Telomere maintenance mechanisms (Other) /
                      Therapeutic strategies (Other)},
      cin          = {B087},
      ddc          = {610},
      cid          = {I:(DE-He78)B087-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39733691},
      doi          = {10.1016/j.neo.2024.101106},
      url          = {https://inrepo02.dkfz.de/record/296075},
}