Mismatch Repair Deficiency Identifies Patients With High-Intermediate–Risk (HIR) Endometrioid Endometrial Cancer at the Highest Risk of Recurrence: A Prognostic Biomarker

Backes, Floor J.; Haag, Jennifer; Cosgrove, Casey; Suarez, Adrian A.; Cohn, David E.; Goodfellow, Paul J.

doi:10.1097/ogx.0000000000000668

Cited by 5 publications

(7 citation statements)

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“…Recurrent endometrial cancer (REC) is a great clinical challenge in the management of EC. Approximately 10-15% of patients with early-stage EC develop tumor recurrence after staged surgery, and among women with EC, there is a high incidence of tumor recurrence in the two to three years following systemic therapy [4][5][6]. Early EC can be screened out and cured at an early stage, but REC predicts poor prognosis [7].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Prognostic Factors and Treatment Modes of Patients with Recurrent Endometrial Carcinoma

Yang

2021

Evidence-Based Complementary and Alternative Medicine

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Objective. Recurrence of endometrial cancer after initial treatment can be complex and difficult to treat. The current main treatment modalities for patients with recurrent endometrial cancer (REC) include chemotherapy, radiotherapy, and surgery, which vary according to the individual patient. However, REC is often associated with a poor prognosis, and it is therefore important to investigate the risk factors affecting REC prognosis and to explore appropriate treatment modalities to improve the prognosis and treatment strategies for patients with REC. Methods. Totally, 100 patients with REC admitted to our hospital from January 2013 to January 2018 were chosen to be research objects. Their pathological data were analyzed, including age, disease-free interval (DFI), recurrence site, and treatment plan after relapse (definitive local therapy (DLT) and palliative chemotherapy (PC)). According to these parameters, univariate and multivariate factors affecting the prognosis of REC patients and the curative effect of PC were analyzed, and the 3-year overall survival (OS) curve and progression-free survival (PFS) curve were drawn. Results. After 3 years of follow-up, 30 patients had a poor prognosis and 70 had a good prognosis, according to which a single multifactorial analysis was performed for different prognoses, where the results of the single-factor analysis showed significant differences between patients with different prognoses in terms of pathomorphology, pathological grading, TFI, and treatment modality after relapse. Further multifactorial analysis showed that TFI and treatment modality after recurrence were independent factors affecting poor prognosis in REC patients. The 3-year OS and 3-year PFS of REC patients were 74.00% and 70.00%, respectively. Patients whose DFI was less than 12 months or treated with PC after relapse were notably associated with lower levels of 3-year OS and 3-year PFS. In addition, radiotherapy and chemotherapy, DFI, and chemotherapy plan after primary surgery were independent risk factors that affected the PC efficacy of REC patients. Conclusion. DFI and treatment mode after relapse are independent factors affecting the prognosis of REC patients. DLT can obviously improve the prognosis of REC patients. For patients who can only choose PC, chemoradiotherapy and DFI after primary surgery are helpful to predict the chemotherapy effect, and the combination of paclitaxel and platinum drugs should be the first choice for chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Analysis of Prognostic Factors and Treatment Modes of Patients with Recurrent Endometrial Carcinoma

Yang

2021

Evidence-Based Complementary and Alternative Medicine

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“…We found that EEC was FIGO grade 3 only in this study, the most patients received adjuvant therapy. In contrast, in the study by Backes et al [27], MSI was associated with a signi cantly worse recurrence-free survival, in which EEC was FIGO grade1-3, and patients receive adjuvant at a much lower rate. Therefore, We assume that more adjuvant therapy is an important in uencing factor on the prognostic value of MSI.…”

Section: Discussionmentioning

confidence: 73%

“…15 studies were retrospective cohort studies [8, 11, 13-19, 21, 23-27], and 2 studies were clinical trials [7,22]. 8 studies assessed MSI using quasimonomorphic mononucleotide markers [7,8,[15][16][17][18][19]21], and 9 studies assessed MSI using immunohistochemistry [11,13,14,[22][23][24][25][26][27]. The pooled HR for patients with EEC shown that MSI was signi cantly associated with shorter overall survival [HR = 1.37, 95% CI (1.00-1.86), p = 0.048].…”

Section: Study Characteristicsmentioning

confidence: 99%

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Microsatellite Instability as a Maker of Prognosis: a Systematic Review and Meta-analysis of Endometrioid Endometrial Cancer Survival Data

Xiao

Wang

Zhao

et al. 2022

Preprint

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Introduction To investigate whether microsatellite instability (MSI) is an important prognostic biomarker for endometrioid endometrial cancer (EEC).Methods The PubMed, EMBASE and the Cochrane Cooperative Library databases were searched from inception to July 2021. Overall survival, disease-free survival, progression-free survival, EEC-specific survival, recurrence-free survival and the recurrence rate were pooled to analyze the correlation between MSI and EEC. In addition, Egger’s regression analysis and Begg’s test were used to detect publication bias.Results 17 studies met the inclusion criteria and were included in our meta-analysis with a sample size of 4723, and the included patients with endometrioid cancer (EC) all were EEC. The pooled hazard ratios (HR) in patients with EEC shown that MSI was significantly associated with shorter overall survival [HR=1.37, 95% confidence interval (CI) (1.00-1.86), p=0.048, I2=60.6%], shorter disease-free survival [HR=1.99, 95% CI (1.31-3.01), p=0.000, I2=67.2%], shorter EEC-specific survival [HR=2.07, 95% CI (1.35-3.18), p=0.001, I2=31.6%] and a higher recurrence rate [Odds ratios (OR)=2.72, 95% CI (1.56-4.76), p=0.000, I2=0.0%]. In the early-stage EEC subgroup, MSI was significantly associated with shorter overall survival [HR=1.47, 95% CI (1.11-1.95), p=0.07], shorter disease-free survival [HR=4.17, 95% CI (2.37-7.41), p=0.000], and shorter progression-free survival [HR=2.41, 95% CI (1.05-5.54), p=0.039]. No significant heterogeneity was observed in overall survival (I2=20.9%), disease-free survival (I2=0.0%), or progression-free survival (I2=0.0%) in patients with early-stage EEC. Meanwhile, publication bias was not observed, and the p-value for Egger’s test of overall survival, disease-free survival, and EEC-specific survival were p=0.131, p=0.068 and p=0.987, respectively.Conclusion MSI is likely an important biomarker for poor prognosis in patients with EEC, and this correlation is even more certain in patients with early-stage EEC.

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“…Stage III/IV patients with dMMR had significantly decreased recurrence-free survival (47.4% vs. 3.4%) despite receiving similar adjuvant therapies. This relationship was further investigated in high-intermediate risk patients, with MMR defects being associated with worse recurrence rates (28% vs. 11%), with distant recurrences being particularly notable (14.1% vs. 3%) (35). This difference held even when excluding isolated vaginal recurrences (18.8% vs. 4.5%).…”

Section: Endometrial Cancermentioning

confidence: 97%

Combination radiation and immunotherapy in gynecologic malignancies—a comprehensive review

Ladbury¹,

Germino²,

Novák³

et al. 2021

Transl Cancer Res TCR

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Definitive and adjuvant radiation and chemoradiation have been mainstays in the management of multiple gynecologic malignancies for decades. However, despite these treatments, the prognosis of patients with locally advanced, recurrent, refractory, and metastatic disease continues to be poor. Over the last decade, immune checkpoint inhibitors have emerged as a promising therapeutic modality, but response rates to monotherapy are low. Mounting basic science and translational research suggests that immunotherapy and radiation may act synergistically with the potential to improve clinical outcomes across multiple disease sites relative to monotherapy with either radiation or immunotherapy alone. Results from early clinical trials in other disease sites, and burgeoning trials within the gynecologic malignancies space hold promise for combined modality treatment. With increasing clinical data supporting combined modality therapy, there is interest in reevaluating treatment paradigms in gynecologic malignancies to improve the current standards of care. In this review, current proposed mechanisms, rationale, and evidence for treatment of gynecologic malignancies with combined radiation and immunotherapy, specifically immune checkpoint inhibitors, will be discussed. Additionally, although currently early and limited, existing clinical data will be summarized as it applies to cervical, endometrial, ovarian, and vulvar cancers. The status of current clinical trials investigating the sequencing, dosing, and fractionation of combined radiation and immunotherapy in these disease sites will also be reviewed.

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Mismatch Repair Deficiency Identifies Patients With High-Intermediate–Risk (HIR) Endometrioid Endometrial Cancer at the Highest Risk of Recurrence: A Prognostic Biomarker

Cited by 5 publications

References 0 publications

Analysis of Prognostic Factors and Treatment Modes of Patients with Recurrent Endometrial Carcinoma

Analysis of Prognostic Factors and Treatment Modes of Patients with Recurrent Endometrial Carcinoma

Microsatellite Instability as a Maker of Prognosis: a Systematic Review and Meta-analysis of Endometrioid Endometrial Cancer Survival Data

Combination radiation and immunotherapy in gynecologic malignancies—a comprehensive review

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