000290167 001__ 290167 000290167 005__ 20250820121506.0 000290167 0247_ $$2doi$$a10.1016/S2468-1253(24)00091-8 000290167 0247_ $$2pmid$$apmid:38734024 000290167 0247_ $$2ISSN$$a2468-1253 000290167 0247_ $$2ISSN$$a2468-1156 000290167 0247_ $$2altmetric$$aaltmetric:163222634 000290167 037__ $$aDKFZ-2024-01003 000290167 041__ $$aEnglish 000290167 082__ $$a610 000290167 1001_ $$0P:(DE-He78)b1b2f6c878545eac4cbd9729d8c10b7d$$aWankhede, Durgesh$$b0$$eFirst author$$udkfz 000290167 245__ $$aClinical significance of combined tumour-infiltrating lymphocytes and microsatellite instability status in colorectal cancer: a systematic review and network meta-analysis. 000290167 260__ $$aLondon$$bElsevier$$c2024 000290167 3367_ $$2DRIVER$$aarticle 000290167 3367_ $$2DataCite$$aOutput Types/Journal article 000290167 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1721829541_14726 000290167 3367_ $$2BibTeX$$aARTICLE 000290167 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000290167 3367_ $$00$$2EndNote$$aJournal Article 000290167 500__ $$a#EA:C070#LA:C070# / 2024 Jul;9(7):609-619 / HI-TRON 000290167 520__ $$aMicrosatellite 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). 000290167 536__ $$0G:(DE-HGF)POF4-313$$a313 - Krebsrisikofaktoren und Prävention (POF4-313)$$cPOF4-313$$fPOF IV$$x0 000290167 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000290167 7001_ $$0P:(DE-He78)b9e439a1aa1244925f92d547c0919349$$aYuan, Tanwei$$b1$$udkfz 000290167 7001_ $$0P:(DE-He78)028ee60cca729028708496826f077b58$$aKloor, Matthias$$b2$$udkfz 000290167 7001_ $$0P:(DE-He78)0a4053be7ffd6aa9bef69de28753a601$$aHalama, Niels$$b3$$udkfz 000290167 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b4$$udkfz 000290167 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b5$$eLast author$$udkfz 000290167 773__ $$0PERI:(DE-600)2874542-5$$a10.1016/S2468-1253(24)00091-8$$gp. 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