Optimal Treatment Strategies for Localized and Advanced Microsatellite Instability–High Colorectal Cancer

2012 ◽  
Vol 8 (1) ◽  
pp. 36-41
Author(s):  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Treatment Strategies ◽  
Optimal Treatment

scholarly journals Cost-Effectiveness of First-Line Versus Second-Line Pembrolizumab or Chemotherapy in Patients With Microsatellite-Instability-High/Mismatch Repair-Deficient Advanced Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Tan Chongqing ◽  
Li Sini ◽  
Zeng Xiaohui ◽  
Peng Liubao ◽  
Peng Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Advanced Colorectal Cancer ◽  
Treatment Strategies ◽  
Cost Effective ◽  
Second Line ◽  
First Line ◽  
Life Years ◽  
Line Setting

Background: Pembrolizumab is a guideline-recommended, both first- and second-line treatment option for microsatellite-instability-high (MSI-H)/mismatch repair-deficient (dMMR)advanced colorectal cancer patients. The aim of the present study is to investigates the health and economic outcomes of three treatment strategies with or without pembrolizumab in MSI-H/dMMR advanced colorectal cancer to define the best treatment strategy from the perspective of the US payer.Methods: A microsimulation model was developed to estimate the cost and effectiveness of three treatment strategies: 1) pembrolizumab used as first-line, 2) pembrolizumab used as second-line and, 3) chemotherapy. Life years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated.Results: The model projected that patients receiving pembrolizumab in the first-line setting gained 5.579 QALYs; this value was 1.501 and 3.941 QALYs more than that for patients receiving pembrolizumab in the second-line setting and chemotherapy, respectively. First-line pembrolizumab strategy dominated second-line pembrolizumab strategy. Compared with chemotherapy, first-line pembrolizumab strategy yielded an incremental cost of $50613.7, which resulted in an ICER of $13441 per QALY.Conclusion: For patients with MSI-H/dMMR advanced colorectal cancer, reserving pembrolizumab for second-line line use is dominated by its first-line use, and first-line use of pembrolizumab is cost-effective compared with chemotherapy.

scholarly journals Expanding the Scope of Immunotherapy in Colorectal Cancer: Current Clinical Approaches and Future Directions

2020 ◽  
Vol 2020 ◽  
pp. 1-24 ◽  
Author(s):  
Malek Kreidieh ◽  
Deborah Mukherji ◽  
Sally Temraz ◽  
Ali Shamseddine
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Adoptive Cell Transfer ◽  
Durable Response ◽  
Novel Treatment Strategies ◽  
Tumor Types

The success of immune checkpoint inhibitors (ICIs) in an increasing range of heavily mutated tumor types such as melanoma has culminated in their exploration in different subsets of patients with metastatic colorectal cancer (mCRC). As a result of their dramatic and durable response rates in patients with chemorefractory, mismatch repair-deficient-microsatellite instability-high (dMMR-MSI-H) mCRC, ICIs have become potential alternatives to classical systemic therapies. The anti-programmed death-1 (PD-1) agents, Pembrolizumab and Nivolumab, have been granted FDA approval for this subset of patients. Unfortunately, however, not all CRC cases with the dMMR-MSI-H phenotype respond well to ICIs, and ongoing studies are currently exploring biomarkers that can predict good response to them. Another challenge lies in developing novel treatment strategies for the subset of patients with the mismatch repair-proficient-microsatellite instability-low (pMMR-MSI-L) phenotype that comprises 95% of all mCRC cases in whom treatment with currently approved ICIs has been largely unsuccessful. Approaches aiming at overcoming the resistance of tumors in this subset of patients are being developed including combining different checkpoint inhibitors with either chemotherapy, anti-angiogenic agents, cancer vaccines, adoptive cell transfer (ACT), or bispecific T-cell (BTC) antibodies. This review describes the rationale behind using immunotherapeutics in CRC. It sheds light on the progress made in the use of immunotherapy in the treatment of patients with dMMR-MSI-H CRC. It also discusses emerging approaches and proposes potential strategies for targeting the immune microenvironment in patients with pMMR-MSI-L CRC tumors in an attempt to complement immune checkpoint inhibition.

scholarly journals Prognostic value of microsatellite instability in adjuvant treatment of colorectal cancer

2018 ◽  
Vol 72 ◽  
pp. 540-546
Author(s):  
Oleksii A. Potapov ◽  
Anastasia Y. Glagolieva ◽  
Dmytro E. Makhmudov ◽  
Andrzej L. Komorowski
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Adjuvant Treatment ◽  
Prognostic Value ◽  
Treatment Strategies ◽  
Current Status ◽  
Molecular Profile ◽  
Repair System ◽  
Dna Mismatch Repair System ◽  
Analytic Review

The dynamics of morbidity and mortality in colorectal cancer (CRC) has changed little in recent years and consistently remains at a high level. The carcinogenesis of this type of tumors includes a large number of genetic disorders and epigenetic changes, which show a number of features specific for this nosology, providing the basis for the first consensus classification of molecular subtypes for colorectal cancer. One of the main mechanisms chosen as crucial for this classification is the microsatellite instability (MSI) caused by defects in the DNA Mismatch Repair System (MMR). The clinical significance of this CRC molecular profile parameter is hard to overestimate. Over the past three decades, the MSI and MMR have been actively studied for prognosis evaluation, determination of need and selection of appropriate adjuvant chemotherapy scheme for CRC. Despite the significant accumulation of clinical and experimental study data, currently the prognostic value of this parameter is still not well defined with reference to CRC adjuvant treatment strategies, and the released data remain controversial. The purpose of this analytic review is to analyze the current status of MSI and MMR in the setting of adjuvant treatment of CRC patients from a perspective of evidence-based medicine.

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

Genetic Abnormalities and Microsatellite Instability in Colorectal Cancer

1998 ◽  
Vol 22 (5) ◽  
pp. 383-395 ◽  
Author(s):  
Pilar Iniesta ◽  
Carmen de Juan ◽  
Trinidad Caldes ◽  
Francisco-Jose Vega ◽  
Maria-Jose Massa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Genetic Abnormalities

scholarly journals The Role of the CpG Island Methylator Phenotype in Colorectal Cancer Prognosis Depends on Microsatellite Instability Screening Status

2010 ◽  
Vol 16 (6) ◽  
pp. 1845-1855 ◽  
Author(s):  
Anna M. Dahlin ◽  
Richard Palmqvist ◽  
Maria L. Henriksson ◽  
Maria Jacobsson ◽  
Vincy Eklöf ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Cancer Prognosis ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

Decreased mean platelet volume is associated with microsatellite instability in colorectal cancer: A propensity score-matched analysis

2021 ◽  
pp. 1-9
Author(s):  
Wen Wang ◽  
Guangyu Wang ◽  
Shuang Fu ◽  
Beibei Zhang ◽  
Zengyao Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Propensity Score ◽  
Microsatellite Instability ◽  
Propensity Score Matching ◽  
Mean Platelet Volume ◽  
Innate Immune ◽  
Platelet Volume ◽  
Activated Platelets ◽  
Medical University ◽  
Potential Parameters

BACKGROUND: Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis and a more effective immune response than patients with microsatellite stable (MSS) CRC. Moreover, activated platelets play a crucial role in modulating innate immune cells. Mean platelet volume (MPV) is an indicator of platelet activation. This study is to examine the association between MPV and MSI status in CRC. METHODS: We collected the clinical and pathological variables of 424 CRC patients diagnosed at the Harbin Medical University Cancer Hospital from January 2018 to December 2018. Associations between MPV levels and MSI status were examined. Propensity score matching (PSM) was performed to reduce the possibility of selection bias. RESULTS: 424 CRC patients were divided into low-MPV group and high-MPV group according to the optimal cut-off value of MPV. 131 high-MPV patients were matched to low-MPV counterparts in a 1:1 ratio by propensity score matching. As MPV levels increased, the percentage of patients with MSI-H reduced. Furthermore, compared with MSS group, the MSI-H group had a significantly lower MPV levels (p= 0.003 after matching). In addition, logistic regression analysis identified reduced MPV as an independent risk factor for MSI-H in CRC patients after controlling for other potential parameters. CONCLUSION: Lower MPV is associated with MSI-H subtype of CRC. Further study on MPV in MSI-H CRC is warranted.

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