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Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

ABSTRACT: This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-?) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-? H score.

SUBMITTER: Lin YC

PROVIDER: S-EPMC7312424 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

Lin Ying-Chun YC Chen Yu-Chia YC Chen Rui-Yun RY Huang Yi-Xuan YX Tu Siang-Jyun SJ Liang Ji-An JA Hung Yao-Ching YC Yeh Lian-Shung LS Chang Wei-Chun WC Lin Wu-Chou WC Chang Yin-Yi YY Chen Shang-Wen SW Chang Jan-Gowth JG

International journal of molecular sciences 20200609 11

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue mic ...[more]

PMID: 32527042

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Project description:BackgroundThe present study aimed to construct a prognostic nomogram including Epstein-Barr virus DNA (EBV-DNA) and sarcopenia in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT).MethodsIn this retrospective analysis, we studied 1,045 patients with NPC who had been treated with CCRT between 2010 and 2014. Sarcopenia was determined using routine pre-radiotherapy computed tomography scans of the third cervical vertebrae. A new S-E grade was constructed using a receiver-operating characteristic (ROC) curve analyses determined cutoff values of sarcopenia and plasma EBV-DNA. The nomogram was developed base on the sarcopenia-EBV (S-E) grade and traditional prognostic factors. A calibration curve, time-dependent ROC, decision curve analysis, and the concordance index (C-index) determined the accuracy of prediction and discrimination of the nomogram, and were compared with TNM staging system and a traditional nomogram.ResultsPatient survival was significantly different when sarcopenia (P < 0.001) or EBV-DNA (P = 0.001) were used and they continued to be independent prognostic factors for survival upon univariate (P < 0.001, P = 0.002, respectively) and multivariate (P < 0.001, P = 0.015, respectively) analyses. Predicting overall survival (OS) was more accurate using the S-E grade than using TNM staging and sarcopenia or EBV-DNA alone. Nomogram B (model with sarcopenia) or nomogram A (model without sarcopenia) were then developed based on the identified independent prognostic factors. Comparing nomogram prediction with actual observation showed good agreement among the calibration curves for probability of 1-, 3-, and 5-year OS. Predicted survival (C-index = 0.77) of nomogram B was statistically higher than that of nomogram A (0.676, P = 0.020) and TNM staging (0.604, P < 0.001). Risk group stratification could distinguish between survival curves within respective TNM stages (all stages, P < 0.001; stage III, P < 0.001; stage IV, P = 0.002).ConclusionsThe sarcopenia-EBV DNA nomogram allowed more accurate prediction of prognosis for patients with NPC receiving CCRT.

Dataset Information

Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

Publications

Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

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