Do microsatellite instability (MSI) and deficient mismatch repair (dMMR) affect the pathologic complete response (pCR) in patients with rectal cancer who received neoadjuvant treatment?

Acar, Turan; Acar, Nihan; Kamer, Erdinç; Tekindal, Mustafa Agâh; Cengız, Fevzi; Kar, Haldun; Atahan, Kemal; Hacıyanlı, Mehmet

doi:10.1007/s13304-019-00697-2

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…In addition, MSI has been consistently associated with decreased survival in rectal cancer. 14,15 Taken together, these data points could be used to direct further studies that would identify patients at high risk of non-response or progression and enable more personalized treatment plans.…”

Section: Discussionmentioning

confidence: 99%

Not All Patients With Locally Advanced Rectal Cancer Benefit From Neoadjuvant Therapy

Chang

Bliggenstorfer

Liu

et al. 2022

The American Surgeon™

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Background While neoadjuvant combined modality therapy (NA-CMT) is beneficial for most patients with locally advanced rectal cancer some patients may experience disease progression during treatment. The purpose of this study is to identify characteristics associated with progression during NA-CMT. Methods A single institution retrospective review of patients with stage II-III rectal cancer receiving NA-CMT was conducted from 2008-2019. Patients with incomplete or unknown NA-CMT treatment and those who received chemotherapy in addition to NA-CMT were excluded. Initial staging MRI was compared to post-operative pathology to determine progression. Definitions: responders (complete response or regression) and non-responders (stable disease or progression). Results 156 patients were included: 25 (16.1%) complete responders, 79 (50.6%) had evidence of regression, 34 (21.8%) were stable non-responders, and 18 (11.5%) were progressors. Those who progressed had worse overall survival. Factors associated with non-responders included black race (OR 4.5, 95% CI: 1.10-18.7) and increasing distance from the anal verge (OR 1.2, 95% CI: .2-2.9). Distance from the anal verge was determined via MRI. Recurrence was significantly more common among non-responders (15, 30.61%) when compared to responders (14, 13.46%), P = .012. Conclusion Patients who progress despite NA-CMT have overall worse survival compared to patients who do respond. While this study failed to identify modifiable or predictive risk factors for progression, the multivariate logistic regression model suggests that race and tumor biology may play a role in progression. Future studies should focus on early identification of patients who may not benefit from NA-CMT in an effort to develop alternative treatment algorithms.

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Section: Discussionmentioning

confidence: 99%

Not All Patients With Locally Advanced Rectal Cancer Benefit From Neoadjuvant Therapy

Chang

Bliggenstorfer

Liu

et al. 2022

The American Surgeon™

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“…The prognostic effect of MSI and inflammatory markers after CRT in rectal cancer is controversial. Previous studies about the difference in clinical outcomes, according to MSI, have shown conflicting results (19)(20)(21)(22). Also, only a limited number of studies have reported inconsistent data on the potential role of inflammatory markers as a predictive factor for survival (2,(23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…The small sample size of MSI-H was the major limitation of this study. However, the incidence of MSI-H is infrequent, only about 2-8% in rectal cancer (19)(20)(21)(22)29). Among the clinical studies dealing with this subject (19,21,22,29), our study included the largest number of MIS-H patients.…”

Section: Discussionmentioning

confidence: 99%

“…However, the incidence of MSI-H is infrequent, only about 2-8% in rectal cancer (19)(20)(21)(22)29). Among the clinical studies dealing with this subject (19,21,22,29), our study included the largest number of MIS-H patients. Although Hassan et al (20) have collected 636 MSI-positive patients through the National Cancer Database, they did not discriminate MSI-H against MSI-L, which is immunologically and clinically similar to MSS.…”

Section: Discussionmentioning

confidence: 99%

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Microsatellite Instability Correlated Inflammatory Markers and their Prognostic Value in the Rectal Cancer Following Neoadjuvant Chemoradiotherapy: A Hypothesis-generating Study

Lee

Kang

Song

et al. 2020

In Vivo

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Background/Aim: This study aimed to analyze the correlation between microsatellite instability (MSI) and inflammatory markers during neoadjuvant CRT in rectal cancer and its influence on prognosis. Patients and Methods: A total of 549 patients with locally advanced rectal cancer underwent neoadjuvant CRT. Complete blood counts before CRT, and 4-8 weeks after CRT were used to measure neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocyte ratio (PLR). Results: MSI was significantly associated with elevated NLR and PLR after CRT as well as with a change in NLR and PLR during CRT. Neither inflammatory markers nor MSI significantly related to survival. However, in patients with MSI, an increase in NLR and PLR before CRT was significantly correlated with poor overall survival and disease-free survival. Conclusion: There is correlation between inflammatory markers and MSI during CRT and it influences prognosis. Therefore, inflammatory markers might have a role in assessing the microenvironment related to MSI and the immunologic response in rectal cancer. Chemotherapy and radiotherapy have the potential to reprogram the tumor microenvironment and induce immunostimulatory effects, possibly by encouraging tumor antigen-specific immune response (1). In rectal cancer, neoadjuvant chemoradiotherapy (CRT) has been widely used in patients with locally advanced rectal cancer. We have previously reported that inflammatory markers including a neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocyte ratio (PLR) can be used as a predictive marker of treatment response after neoajduvant CRT (2). In previous studies, inflammatory markers have been shown to have a direct correlation with the intra-tumoral levels of granulocyte myeloid-derived suppressor cells and regulatory T cells (3, 4), which can suppress anti-tumor immune reaction (1). Furthermore, the inflammatory markers have been recently found to predict the response of immunotherapy (5, 6). Microsatellite instability (MSI) is one of the well-known immunologic markers in colorectal cancer, which tends to induce hyper-mutation and exhibit peri-tumoral immune cell infiltration/activation closely related to the change in tumor 2119 This article is freely accessible online.

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“…Acar et al (33), realizaron un trabajo cuyo objetivo fue examinar los factores clínicos que son predictivos de respuesta patológica completa tras el tratamiento neoadyuvante con quimiorradioterapia en cáncer de recto con la finalidad de ayudar a determinar un programa de tratamiento para el manejo de los pacientes afectos por esta enfermedad.…”

Section: Msi Y Mmr: Relación Con Respuesta Tras Neoadyuvanciaunclassified

Inestabilidad de microsatélites como factor pronóstico de respuesta al tratamiento neoadyuvante en cáncer de recto

Valls¹

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Background: Colorectal cancer is the third most diagnosed cancer and the second in cancer mortality in Europe. The proportion of rectal cancer cases ranges from 27-58%.In the locally advanced stages, treatment of choice consists of neoadjuvant therapy (radiotherapy with or without chemotherapy) after complete mesorectal excision.Complete pathological response to neoadjuvant treatment is considered a prognostic factor in these cases; however, it varies around 15% without being able to determine at present what predicts the good response in some patients and not in others, given the same clinical characteristics.Objective: To assess the usefulness of microsatellite instability (MSI) as a biomarker of response to neoadjuvant treatment in rectal cancer.Methods: An updated bibliographic review of the evidence for MSI as a biomarker of response to neoadjuvant treatment in rectal cancer is carried out. MEDLINE database search was performed using PubMed search engine. The combination of the following terms was used: (rectal cancer) AND (msi) AND (microsatellite instability).Results were restricted to the last 10 years. Results:In the reviewed literature, rectal cancer with microsatellite instability (MSI) shows a worse response to neoadjuvant treatment, observing a lower percentage of complete pathological responses. Although MSI is not directly related to overall survival (OS), it appears to have an impact on disease-free survival (DFS). Conclusion:It is important to recommend the determination of MSI in the initial pathological studies in rectal cancer to continue evaluating its role in the prognosis of patients, as well as its joint assessment with other biomarkers that allow adapting the treatment to the biomolecular characteristics of each case.

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Do microsatellite instability (MSI) and deficient mismatch repair (dMMR) affect the pathologic complete response (pCR) in patients with rectal cancer who received neoadjuvant treatment?

Cited by 10 publications

References 34 publications

Not All Patients With Locally Advanced Rectal Cancer Benefit From Neoadjuvant Therapy

Not All Patients With Locally Advanced Rectal Cancer Benefit From Neoadjuvant Therapy

Microsatellite Instability Correlated Inflammatory Markers and their Prognostic Value in the Rectal Cancer Following Neoadjuvant Chemoradiotherapy: A Hypothesis-generating Study

Inestabilidad de microsatélites como factor pronóstico de respuesta al tratamiento neoadyuvante en cáncer de recto

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