Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systematic review was to assess the prognostic value of MCT1 immunoexpression in different malignancies. Study collection was performed by searching nine different databases (PubMed, EMBASE, ScienceDirect, Scopus, Cochrane Library, Web of Science, OVID, TRIP and PsycINFO), using the keywords “cancer”, “Monocarboxylate transporter 1”, “SLC16A1” and “prognosis”. Results showed that MCT1 is an indicator of poor prognosis and decreased survival for cancer patients in sixteen types of malignancies; associations between the transporter’s overexpression and larger tumour sizes, higher disease stage/grade and metastasis occurrence were also frequently observed. Yet, MCT1 overexpression correlated with better outcomes in colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer patients. These results support the applicability of MCT1 as a biomarker of prognosis, although larger cohorts would be necessary to validate the overall role of MCT1 as an outcome predictor.

Background  Colorectal cancer is one of the most common types of cancer and is associated with a high lethality rate. Treatment is multidisciplinary, and neoadjuvant chemoradiation is recommended in locally advanced rectal cancer. About 15% of patients answer favorably to neoadjuvant chemoradiation, so it is important to determine the predictors of response. Objective  To review the results of studies that analyzes the predictors of complete pathological response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Search methods  We searched for eligible articles in data bases Pubmed and Scopus, between the 12th and the 20th of March 2020. The following key words were used: “predictors of response”, “chemoradiation” and "locally advanced rectal cancer”. Selection criteria  Inclusion criteria: Studies including patients with locally advanced rectal cancer, patients receiving neoadjuvant chemoradiation as treatment, studies including predictors of response to neodjuvant chemoradiation, overall survival as an outcome and regarding language restrictions, only articles in English were accepted, only studies published until the 31st of December 2019 were accepted. Main results  Fourteen studies fulfilled the inclusion criteria. Thirteen are cohort studies and one is a clinical trial. Four groups of predictors were defined: blood markers, tumors, histopathological and patients’ characteristics. Author's conclusions  During the analysis of the articles, there were several predictors identified as potential candidates for clinical practice, such as high pre neoadjuvant chemoradiation Carcinoembryonic Antigen levels and small post neoadjuvant chemoradiation tumor size. Nevertheless, it is difficult to make definitive conclusions about the most reliable predictors. That is why it is crucial to initiate further studies with standardized cut-off values and a methodology homogenization.

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(IPCW) method and the Cox model using treatment as a time-dependent covariate were used as sensitivity analyses. RESULTS: Overall, 71% of patients randomized to dexamethasone crossed over to bortezomib. The primary analysis led to a hazard ratio of 0.59 (95%CI: [0.32,0.86]) for bortezomib versus dexamethasone, compared to 0.77 (95%CI: [0.61,0.97]) using the ITT approach. The results of the secondary analyses were consistent with the primary analysis. The IPCW provided results, which were very sensitive to the choice of the time interval. Lastly, the Cox model with treatment as a time-dependent variable resulted in a counter-intuitive higher hazard ratio than the ITT analysis, consistent with results from simulation studies indicating this approach is biased. CONCLUSIONS: Adjusting for crossover led to a decrease of the hazard ratio from 0.77 to 0.59, and resulted in wider confidence intervals than the ITT analysis. Additional analyses are required to assess the performance of the IPCW method compared to the IPE algorithm and the RPSFT model under different scenarios.

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