The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

“…36 , 37 Noteworthy, a significant part of studies regarding the prognostic impact of PD-L1 have not discriminated between its expression in tumour cells and tumour-infiltrating immune cells. The results from the present study, with immune cell-specific PD-L1 expression being an independent prognostic factor while its expression in tumour cells was not, are coherent with previous research 16 , 23-26 and demonstrate that PD-L1 expression in immune cells and tumour cells might carry different prognostic values and might be regulated by distinct mechanisms. Furthermore, although tumour cell-specific PD-L1 expression has been validated as a predictive marker for response to PD-1 or PD-L1 blockade in several cancers, 11 , 38 , 39 recent studies now suggest that PD-L1 expression in tumour-infiltrating myeloid and T cells also play a critical role in immunosuppression, 38 , 40-43 and should possibly be taken into account in assessment scoring for PD-1/PD-L1 blockade.…”

“…23 , 24 Right-sided tumours, often defined as proximal to the splenic flexure, are generally poorly differentiated, diagnosed in more advanced tumour stages, displaying different molecular patterns, and carrying a poorer prognosis than left-sided tumours. 24 , 25 Several studies also demonstrate the importance of taking PTL into account when evaluating treatment response, 26-28 and retrospective analyses from large phase III trials have demonstrated that patients with right-sided tumours have less benefit from the addition of EGFR-targeted therapy. 29 …”

S3-Leitlinie – Kolorektales Karzinom

“…Präklinische Analysen unterstützen die unterschiedlichen Muster der Genmutation und Genexpression bei rechts-und linksseitigen Tumoren [1113,1114]. Als Trennlinie wird in der Mehrzahl der Untersuchungen die splenische Flexur betrachtet [1051,1053]. Prinzipiell würde man die Trennlinie zwischen rechts-und linksseitigen Tumoren zwischen den proximalen zwei Dritteln und dem distalen Drittel des Colon transversum ziehen.…”

“…Prinzipiell würde man die Trennlinie zwischen rechts-und linksseitigen Tumoren zwischen den proximalen zwei Dritteln und dem distalen Drittel des Colon transversum ziehen. Angesichts der retrospektiven Evaluationen wurde jedoch in der Mehrzahl der Untersuchungen aus pragmatischen Gründen die splenische Flexur als Trennlinie betrachtet [1051,1053] …”

First-line therapy for mCRC — the influence of primary tumour location on the therapeutic algorithm

“…In this respect, subgroup analyses of six international, randomized, controlled trials in large cohorts of patients with RAS-wild-type mCRC were also reported in October 2016 , and the results showed clear differences in the efficacy of anti-EGFR therapy in patients with left-sided and rightsided primary tumours (Supplementary information S1 (table)). Overall, the addition of anti-EGFR antibodies to a chemotherapy doublet is associated with a significant overall survival benefit for patients with left-sided tumours (hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.58-0.83), which is essentially absent in those with right-sided tumours (HR 0.96, 95% CI 0.68-1.35; P interaction = 0.10) 10 . Consistent results were reported when comparing the addition of anti-EGFR antibodies versus bevacizumab to doublet chemotherapy according to tumour sidedness: a clear overall survival bene fit from the combination with anti-EGFR antibodies was evident for patients with left-sided tumours (HR 0.71, 95% CI 0.58-0.85), whereas doublet chemotherapy plus bevacizumab seems to provide better results in those with rightsided tumours (HR 1.30, 95% CI 0.97-1.74; P interaction <0.001) 10 .…”