Adjuvant chemoradiation associated with improved outcomes in patients with microsatellite instability-high advanced endometrial carcinoma

McEachron, Jennifer; Zhou, Nancy; Spencer, Christina; Chatterton, Carolyn; Shanahan, Lisa; Katz, Julian; Naegele, Saskia; Singhal, Pankaj; Lee, Yi-Chun

doi:10.1136/ijgc-2020-001709

Cited by 15 publications

(8 citation statements)

References 35 publications

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“…There have been reports showing that the MSS phenomenon in tissues without MLH1 and PMS2 protein expression is associated with hypermethylation of the MLH1 promoter (35). Another possible explanation is that there are excessive numbers of nuclei (particularly in the normal endometrium and a large number of tumorinfiltrating lymphocytes) that allow the MSI or protein expression of MMR to be used to indicate if patients with EC can benefit from immune checkpoint inhibitor therapy or radiotherapy (36). In addition, the result that MSI or protein expression of MMR is also a referring indicator for the diagnosis of Lynch syndrome.…”

Section: Discussionmentioning

confidence: 99%

A new strategy in molecular typing: the accuracy of an NGS panel for the molecular classification of endometrial cancers

Li¹,

Feng²,

Zhao³

et al. 2022

Ann Transl Med

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Background: Multiplatform molecular subtyping has been put into clinical practice as an alternative for The Cancer Genome Atlas (TCGA)-based classification for endometrial cancer (EC), which proved a tool for predicting prognosis and guiding treatment. The traditional methods for the molecular classification of EC only based on pathological indicators are not accurate. The present study aimed to classify EC on a molecular level and explored the possibility of a one-time solution to guide clinical treatment and prognosis determination by utilizing data from a next-generation sequencing (NGS) panel. The ultimate aim was to utilize multiplatform testing to overcome disadvantages of long detection periods and limitations in the information regarding genetic variation.Methods: An NGS-panel was produced using FFPE samples isolated from 86 patients pathologically diagnosed with EC, and molecular subtyping was performed according to the recommended criteria. In addition, 45 matched samples from 86 patients were randomly selected for immunohistochemical (IHC) staining of P53, MLH1, MSH2, PMS2, and MSH6. Another 41 samples were not analyzed due to incomplete IHC staining results. SPSS (V26.0; IBM Corp., Armonk, NY, USA) was used for receiver operating characteristic (ROC) curve analysis. Results:The molecular typing ratio of the 86 cases of endometrial carcinoma was calculated to be 16.28% for POLE type, 17.44% for MSI-H type, 47.67% for CN-L type, 12.79% for CN-H type, 5.81% for unclassified case. A comparison between IHC ProMisE-based subtyping and NGS-based subtyping of the 45 cases revealed that 3 cases were classified as MSI-H by IHC but as MSS by NGS. Among these cases, 1 case was deficient in MLH1 expression and PMS2 protein expression but had wild-type P53 protein, and the P53 sequencing data of this sample showed a missense mutation. Good overall consistency between the 2 determination methods was shown. Receiver operating characteristic (ROC) analysis showed that NGS had particularly high specificity and sensitivity for detecting the MSI and CN subtypes [area under the curve (AUC) =0.893>0.5, P=0.000029<0.01]. Conclusions:The present study suggested that NGS-based subtyping could serve as an effective approach for the molecular typing of EC. Both NGS and IHC bear their own unique advantages and challenges in clinical practice.

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Section: Discussionmentioning

confidence: 99%

A new strategy in molecular typing: the accuracy of an NGS panel for the molecular classification of endometrial cancers

Li¹,

Feng²,

Zhao³

et al. 2022

Ann Transl Med

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“…It also indicated a potential lack of benefit of perioperative or adjuvant chemotherapy for patients with high-MSI disease (HR 1.50, 95% CI 0.55–4.12 for OS; HR 1.27, 95% CI 0.53–3.04 for DFS), while patients with low-MSI or microsatellite-stable disease benefited from chemotherapy in terms of OS and DFS (HR 0.75, 95% CI 0.60–0.94; and HR 0.65, 95% CI 0.53–0.79, respectively). Although it was a study on advanced endometrial cancer, patients with high-MSI disease had an improved 2-year progression-free survival with adjuvant CCRT compared with that of chemotherapy alone (40.0% versus 29.5%, p = 0.04) [ 31 ]. The authors believed that the deficiency in mismatch repair could enhance the response to radiation-induced DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Preoperative Hematological Parameters in Patients with D2-Resected, Node-Positive Stomach Cancer

Park

Lim

et al. 2022

Biomedicines

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The purpose of the present study was to investigate the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer, and to explore who might benefit from adjuvant concurrent chemoradiotherapy (CCRT) compared to chemotherapy alone. Among 1032 patients with node-positive stomach cancer who had a confirmed diagnosis after complete D2 resection, and who received adjuvant chemotherapy alone or CCRT, a total of 692 patients was selected using propensity score matching. Among absolute neutrophil count, absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, AMC was the most relevant prognostic factor for overall survival and recurrence-free survival (hazard ratio (HR) 1.674, 95% confidence interval (CI) 1.180–2.376; HR 1.908, 95% CI 1.650–2.695, respectively). In a subgroup with a high ALC, patients treated with adjuvant CCRT had a favorable recurrence-free survival (HR 0.620, 95% CI 0.393–0.980) compared to those treated with chemotherapy alone. Further study is needed to confirm our findings and to develop tailored adjuvant treatment.

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“… 30 A more recent study compared adjuvant chemotherapy and radiation with chemotherapy alone in advanced MSI-high EC, and found an improved progression-free survival with the addition of radiation. 31 This evidence suggesting MMRd EC may have an increased sensitivity to radiation needs to be validated in prospective studies.…”

Section: Mmrd Endometrial Cancermentioning

confidence: 99%

The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer

2021

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Following the discovery of the four molecular subtypes of endometrial cancer (EC) by The Cancer Genome Atlas (TCGA) in 2013, subsequent studies used surrogate markers to develop and validate a clinically relevant EC classification tool to recapitulate TCGA subtypes. Molecular classification combines focused sequencing ( POLE) and immunohistochemistry (mismatch repair and p53 proteins) to assign patients with EC to one of four molecular subtypes: POLEmut, MMRd, p53abn and NSMP (no specific molecular profile). Unlike histopathological evaluation, the molecular subtyping of EC offers an objective and reproducible classification system that has been shown to have prognostic value and therapeutic implications. It is an exciting time in EC care where we have moved beyond treatment based on histomorphology alone, and molecular classification will now finally allow assessment of treatment efficacy within biologically similar tumours. It is now recommended that molecular classification should be considered for all ECs, and should be performed routinely in all high grade tumours. It is also recommended to incorporate molecular classification into standard pathology reporting and treatment decision-making algorithms. In this review, we will discuss how the molecular classification of EC can be used to guide both conventional and targeted therapy in this new molecular era.

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Adjuvant chemoradiation associated with improved outcomes in patients with microsatellite instability-high advanced endometrial carcinoma

Cited by 15 publications

References 35 publications

A new strategy in molecular typing: the accuracy of an NGS panel for the molecular classification of endometrial cancers

A new strategy in molecular typing: the accuracy of an NGS panel for the molecular classification of endometrial cancers

Clinical Significance of Preoperative Hematological Parameters in Patients with D2-Resected, Node-Positive Stomach Cancer

The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer

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