Dataset Information

Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients.

ABSTRACT: The relevance of the transcription factor p53 in cancer is inarguable, and numerous lncRNAs are involved in the p53 regulatory network as either regulators or effectors, triggering a transcriptional response that causes either cell arrest or apoptosis following DNA damage in a p53-dependent manner. Despite the fact that the therapeutic response is improved in NPC, heterogeneity among people remains with regard to the susceptibility of adverse effects and the efficacy of treatments. Therefore, we analysed eight potentially functional SNPs of five genes in the lncRNA-p53 regulatory network in a discovery cohort of 505 NPC patients. By performing multivariate logistic regression, the impact of genetic variations on the efficacy and risk of CRT-induced toxicities was investigated. The most dramatic finding was that the MEG3 rs10132552 CC genotype had a greater than three-fold increased risk of developing grade 3-4 anaemia (OR?=?3.001, 95%CI?=?1.355-6.646, P?=?0.007). Furthermore, the rs10132552 CT genotype had a better response to treatment (OR?=?0.261, 95%CI?=?0.089-0.770, P?=?0.015). Individuals carrying LINC-ROR rs2027701 with one or two variant alleles had significant associations with a reduced risk of neutropaenia (OR?=?0.503, 95%CI?=?0.303-0.835, P?=?0.008). In conclusion, our results suggested that genetic polymorphisms of the lncRNA-p53 regulatory network could play a potential role in reducing treatment-related toxicities and improving outcomes for NPC patients.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5559481 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients.

Wang Youhong Y Guo Zhen Z Zhao Yu Y Jin Yi Y An Liang L Wu Bin B Liu Zhaoqian Z Chen Xiaoping X Chen Xiang X Zhou Honghao H Wang Hui H Zhang Wei W

Scientific reports 20170816 1

The relevance of the transcription factor p53 in cancer is inarguable, and numerous lncRNAs are involved in the p53 regulatory network as either regulators or effectors, triggering a transcriptional response that causes either cell arrest or apoptosis following DNA damage in a p53-dependent manner. Despite the fact that the therapeutic response is improved in NPC, heterogeneity among people remains with regard to the susceptibility of adverse effects and the efficacy of treatments. Therefore, we ...[more]

PMID: 28814798

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Project description:PurposeInduction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma.MethodsWe thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1.ResultsSeven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively).ConclusionsInduction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

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:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Project description:Objective This study investigated the curative effect of adding nimotuzumab (NTZ) in patients with locally advanced nasopharyngeal carcinoma (NPC) who were treated with concurrent chemoradiotherapy (CCRT) and explored significant prognostic factors of NPC. Materials and methods The clinical data of 307 patients with NPC treated in the First Affiliated Hospital of Soochow University from January 2013 to December 2018 were retrospectively analyzed. The patients were divided into the NTZ-CCRT group and the CCRT group according to whether they were associated with NTZ. We applied propensity score matching to reduce the interference of biases and compared the short-term efficacy and long-term survival rate of the two groups. Moreover, univariate and multivariate analyses were performed for all patients, and subgroup analysis was used to compare the efficacy of therapy combined with NTZ in different subgroups. Results In primary nasopharyngeal tumors, the objective response rates in the NTZ-CCRT group and CCRT group were 95.8% and 85.7%, respectively (P =0.007). In cervical positive lymph nodes, the objective response rates in the NTZ-CCRT group and CCRT group were 98.3% and 87.4%, respectively (P =0.001). Compared with CCRT alone, the addition of NTZ significantly improved the 5-year OS (94.1% vs. 81.8%, P=0.014) and the 5-year DFS (84.2% vs. 75.5%, P=0.031) of NPC patients; however, the addition of NTZ was accompanied by more severe hematologic toxicity and acute oral mucositis. Multivariate analysis demonstrated that the addition of NTZ was an important prognostic factor for OS and DFS (HR 0.367, 95% CI 0.167-0.808, P=0.013 for OS and HR 0.536, 95% CI 0.312-0.919, P=0.023 for DFS) and the level of pretreatment LDH (HR 5.170, 95% CI 2.125-12.580, P<0.001 for OS and HR 2.421, 95% CI 1.027-5.707, P=0.043 for DFS). Moreover, patients with high levels of hsCRP before treatment (HR 0.389, 95% CI 0.177-0.853, P=0.018) may gain more benefits from combined treatment with NTZ. Conclusions For locally advanced NPC patients treated with concurrent chemoradiotherapy, the addition of NTZ can significantly improve their survival outcome. However, it is necessary to guard against the associated increase in hematological toxicity and acute oral mucositis.

Dataset Information

Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients.

Publications

Genetic polymorphisms of lncRNA-p53 regulatory network genes are associated with concurrent chemoradiotherapy toxicities and efficacy in nasopharyngeal carcinoma patients.

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