Background
The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs.
Methods
We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized.
Results
In local disease, CMS4 tumors were associated with worse overall survival (OS) compared to CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval= 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33 to 0.55; progression-free survival HR range = 0.53 to 0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16 to 0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome as compared to oxaliplatin (HR range = 0.31 to 0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-EGFR therapy improved outcome for KRAS wildtype CMS2 patients.
Conclusions
The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.
Chronic lymphocytic leukemia (CLL) is frequently complicated by cytopenias, either due to bone marrow infiltration or autoimmunity, resulting in autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia (PRCA), or autoimmune neutropenia (AIN). Morbidity due to autoimmune cytopenias (AIC) can be substantial; in addition, infection risk increases and pre-existing infections might deteriorate due to immunosuppressive medication. In the aging population, CLL occurs more frequently and AIC related to CLL represent a growing clinical challenge. Areas covered: This review summarizes current knowledge on pathophysiological mechanisms involved in AIC development and their prognostic significance. It provides diagnostic criteria and a treatment guideline for daily clinical practice, which includes the role of novel targeted agents. Expert commentary: The pathophysiology of AIC involves loss of self-tolerance, antigen presentation by malignant CLL cells, and autoantibody production through aberrant T- and B-cell function. The value of detecting autoantibodies via the direct antiglobulin test (DAT) is disputable, since a positive test does not imply overt hemolysis. Importantly, AIC should be distinguished from infiltrative cytopenias, because of prognostic and therapeutic consequences. Compared to chemotherapy, triggering AIC by targeted therapies is less common and, hence, these agents may be valuable as treatment for CLL-related immune cytopenias.
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