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@ARTICLE{Wankhede:290167,
      author       = {D. Wankhede$^*$ and T. Yuan$^*$ and M. Kloor$^*$ and N.
                      Halama$^*$ and H. Brenner$^*$ and M. Hoffmeister$^*$},
      title        = {{C}linical significance of combined tumour-infiltrating
                      lymphocytes and microsatellite instability status in
                      colorectal cancer: a systematic review and network
                      meta-analysis.},
      journal      = {The lancet / Gastroenterology $\&$ Hepatology},
      volume       = {9},
      number       = {7},
      issn         = {2468-1253},
      address      = {London},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2024-01003},
      pages        = {609-619},
      year         = {2024},
      note         = {#EA:C070#LA:C070# / 2024 Jul;9(7):609-619 / HI-TRON},
      abstract     = {Microsatellite instability (MSI) status and
                      tumour-infiltrating lymphocytes (TIL) are established
                      prognostic factors in colorectal cancer. Previous studies
                      evaluating the combination of TIL and MSI status identified
                      distinct colorectal cancer subtypes with unique prognostic
                      associations. However, these studies were often limited by
                      sample size, particularly for MSI-high (MSI-H) tumours, and
                      there is no comprehensive summary of the available evidence.
                      We aimed to review the literature to compare the survival
                      outcomes associated with the subtypes derived from the
                      integrated MSI-TIL classification in patients with
                      colorectal cancer.In this systematic review and network
                      meta-analysis, we searched PubMed, Embase, Scopus, and the
                      Cochrane Library without language restrictions, for articles
                      published between Jan 1, 1990, and March 13, 2024. Patient
                      cohorts comparing different combinations of TIL (high or
                      low) and MSI status (MSI or microsatellite stable [MSS]) in
                      patients with surgically resected colorectal cancer were
                      included. Studies were excluded if they focused on
                      neoadjuvant therapy or on other immune markers such as B
                      cells or macrophages. Methodological quality assessment was
                      done with the Newcastle-Ottawa scale; data appraisal and
                      extraction was done independently by two reviewers. Summary
                      estimates were extracted from published reports. The primary
                      outcomes were overall survival, disease-free survival, and
                      cancer-specific survival. A frequentist network
                      meta-analysis was done to compare hazard ratios (HRs) and
                      $95\%$ CI for each outcome. The MSI-TIL subgroups were
                      prognostically ranked based on P-score, bias, magnitude, and
                      precision of associations with each outcome. The protocol is
                      registered with PROSPERO (CRD42023461108).Of 302 studies
                      initially identified, 21 studies (comprising 14 028
                      patients) were included in the systematic review and 19 (13
                      029 patients) in the meta-analysis. Nine studies were
                      identified with a low risk of bias and the remaining ten had
                      a moderate risk of bias. The MSI-TIL-high (MSI-TIL-H)
                      subtype exhibited longer overall survival (HR 0·45, $95\%$
                      CI 0·34-0·61; $I2=77·7\%),$ disease-free survival (0·43,
                      0·32-0·58; $I2=61·6\%),$ and cancer-specific survival
                      (0·53, 0·43-0·66; $I2=0\%),$ followed by the MSS-TIL-H
                      subtype for overall survival (HR 0·53, 0·41-0·69;
                      $I2=77·7\%),$ disease-free survival (0·52, 0·41-0·64;
                      $I2=61·6\%),$ and cancer-specific survival (0·55,
                      0·47-0·64; $I2=0\%)$ than did patients with MSS-TIL-low
                      tumours (MSS-TIL-L). Patients with the MSI-TIL-L subtype had
                      similar overall survival (0·88, 0·66-1·18; $I2=77·7\%)$
                      and disease-free survival (0·93, 0·69-1·26;
                      $I2=61·6\%),$ but a modestly longer cancer-specific
                      survival (0·72, 0·57-0·90; $I2=0\%)$ than did the
                      MSS-TIL-L subtype. Results from the direct and indirect
                      evidence were strongly congruous.The findings from this
                      network meta-analysis suggest that better survival was only
                      observed among patients with TIL-H colorectal cancer,
                      regardless of MSI or MSS status. The integrated MSI-TIL
                      classification should be further explored as a predictive
                      tool for clinical decision-making in early-stage colorectal
                      cancer.German Research Council (HO 5117/2-2).},
      cin          = {C070 / D470 / D196 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)D470-20160331 /
                      I:(DE-He78)D196-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38734024},
      doi          = {10.1016/S2468-1253(24)00091-8},
      url          = {https://inrepo02.dkfz.de/record/290167},
}