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Serum miRNAs, a potential prognosis marker of loco-regionally advanced nasopharyngeal carcinoma patients treated with CCRT.

ABSTRACT: BACKGROUND:Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT. METHODS:This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG),who were treated with CCRT within 5?years. The paired serum was collected before and after treatment and biomarkers were discovered by LNA-TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. Using the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. RESULTS:Using fold change?2.0 or???0.5 and p ??0.05 as cutoff levels, we identified 1 up-regulated and 6 down-regulated miRNAs, 1 up-regulated and 9 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After these down-regulated miRNAs were dealed with bioinformatics analysis and normalization, only 5 different miRNAs were significantly reduced, which there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT in the serum samples of 48 NPC patients. Based on this, we calculated a risk score with the expression of miRNA-26b?miRNA-29a?miRNA-125b?miRNA-29b?miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR?=?3.149, 95%CI:1.018-9.115, p =?0.034), whereas combining the former two is independent for OS (HR?=?5.146, 95%CI:1.674-15.817, p =?0.04). CONCLUSIONS:For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs, such as miRNA-29a, miRNA-125b and miRNA-26b etc., play an important role in predicting prognosis factors of PFS and OS, which will contribute to the strategic direction for future research.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC7057605 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Serum miRNAs, a potential prognosis marker of loco-regionally advanced nasopharyngeal carcinoma patients treated with CCRT.

Zhang Zhimin Z Huang Jiangbiao J Wang Ge G Jin Feng F Zheng Jijun J Xiao He H Lei Lin L Luo Jia J Chen Chuan C

BMC cancer 20200304 1

<h4>Background</h4>Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT.<h4>Methods</h4>This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG),who were treated with CCRT within 5 years. The paired serum was collected before and after tr ...[more]

PMID: 32131777

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Project description:BackgroundTo analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients.MethodsConsecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05.ResultsA total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 - 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3-4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%).ConclusionsOur classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials.

Project description:Objective: Radiotherapy or chemoradiotherapy has been preferred as the clinical therapeutic modalities to combat locally advanced esophageal squamous cell carcinoma (ESCC). The aim of this retrospective study is to ascertain combinatorial efficacy of anlotinib with concurrent radiotherapy (CCRT) rather than CCRT alone. Methods: Locally advanced ESCC patients registered between August 2018 to April 2019 in the third People's hospital of Zhengzhou, the First affiliated hospital of Zhengzhou University, Anyang Cancer Hospital, the Affiliated Hospital of Qingdao University were selected for this retrospective study; and these patients segregated into two groups subsequently who received combinatorial regimen with CCRT and anlotinib compared for treatment-related toxicity, response rates, safety, survival outcomes, than CCRT alone. Results: Progression free survival (PFS) was 0.577 (95% CI, 0.333-0.902, P = 0.014); the median overall survival time was 5 months (95% CI, 4.1-7.5) for the CCRT group, whereas 9 months (95% CI, 7.3-18.0) for the group received 'anlotinib with CCRT' (HR = 0.578, 95% CI, 0.337-0.924, P = 0.021). Overall objective response rates were considerable with a statistical difference between the two groups at 6 months (P1 = 0.027, P2 = 0.015) and 12 months (P1 = 0.012, P2 = 0.027). Overall adverse events are mitigated in combinatorial regimen than CCRT alone except the incidence of hypertension, which was higher in 'anlotinib with CCRT' group than CCRT group (P = 0.023). Total 13 patients exhibited hand-foot skin reactions in the group that received anlotinib in combination with CCRT. Anlotinib in combination with CCRT enhanced the overall survival (OS) rates, whereas incidence of treatment-related toxicity is minimized than CCRT alone. Conclusion: Combinatorial regimen of anlotinib with CCRT significantly enhanced clinical efficacy, safety and may benefit for treating the locally advanced ESCC patients.

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Serum miRNAs, a potential prognosis marker of loco-regionally advanced nasopharyngeal carcinoma patients treated with CCRT.

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Serum miRNAs, a potential prognosis marker of loco-regionally advanced nasopharyngeal carcinoma patients treated with CCRT.

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