Dataset Information

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

ABSTRACT: BACKGROUND:Epidermal growth factor (EGF) and its receptor (EGFR) are part of an important signaling pathway that is involved in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that EGF/EGFR genetic polymorphisms might have a prognostic impact on disease-free survival and overall survival (OS) in locally advanced SCCHN. MATERIALS AND METHODS:The patient group included a consecutive cohort of 180 patients with locally advanced SCCHN who underwent postoperative concurrent chemoradiotherapy between 2002 and 2010. DNA from formalin-fixed, paraffin-embedded tumor tissues was genotyped for the single nucleotide polymorphism (SNP) of EGF A61G A>G, EGFR R521K G>A and G-216T. The log-rank test was applied to evaluate the impact of SNPs on the outcomes. Survival was estimated using the Kaplan-Meier statistical method. RESULTS:We demonstrated that EGF/EGFR SNPs might predict prognosis in patients with primary pharyngolaryngeal tumors, but not in those with oral cavity tumors. In pharyngolaryngeal tumor subgroup, EGF61 G/G genotype led to worse 5 year OS rate when compared to G/A or A/A genotypes (13.3% versus 34.3% versus 50.0%, P=0.017). The 5 year OS of patients with EGFR R521K G/G (11.1%) and G/A (15.9%) were lower than the A/A (62.5%) genotype (P=0.054). Patients carrying one or two unfavorable alleles had worse 5 year OS than those without unfavorable allele (not available versus 20% versus 71.4%, P=0.002). Multivariate analysis revealed that the highest risk of death was associated with the coexistence of two unfavorable genotypes (hazard ratio 25.7, 95% confidence interval =3.4-193.4; P=0.002). CONCLUSION:In this study, we were able to demonstrate that the EGF A61G and EGFR R521K genetic polymorphisms might be important prognostic factors in patients with locally advanced primary pharyngolaryngeal squamous cell carcinoma who underwent postoperative concurrent chemoradiotherapy.

SUBMITTER: Su NW

PROVIDER: S-EPMC4259259 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

Su Nai-Wen NW Leu Yi-Shing YS Lee Jehn-Chuan JC Liu Chung-Ji CJ Cheng Chieh-Yuan CY Lin Jiun-Sheng JS Chen Yu-Jen YJ Chen Chi-Kuan CK Fang I-Chih IC Hsieh Ruey-Kuen RK Chang Yi-Fang YF

OncoTargets and therapy 20141128

<h4>Background</h4>Epidermal growth factor (EGF) and its receptor (EGFR) are part of an important signaling pathway that is involved in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that EGF/EGFR genetic polymorphisms might have a prognostic impact on disease-free survival and overall survival (OS) in locally advanced SCCHN.<h4>Materials and methods</h4>The patient group included a consecutive cohort of 180 patients with locally advanced SCCHN who unde ...[more]

PMID: 25506224

Similar Datasets

Project description:BackgroundThis study aims to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) covering partial regional lymph node areas combined with chemotherapy for locally advanced thoracic esophageal squamous cell carcinoma patients.MethodsThis was a single-center, single-arm phase II clinical trial that began in 2014. Patients who underwent radical transthoracic resection within 3 months and were histologically confirmed esophageal squamous cell carcinoma (pT3-4 or N+, M0 determined according to AJCC Guidelines, Edition 7) were recruited. Postoperative radiotherapy was performed with a total dose of 50.4Gy in 28 fractions using IMRT. Clinical target volumes (CTVs) included tumor bed, anastomosis, bilateral supraclavicular region, and superior mediastinal lymph nodes. Synchronous chemotherapy for 2 cycles (paclitaxel 150mg/m2, day1; Cisplatin 25mg/m2, day1-3; every 4 weeks), followed by 2 cycles of consolidation chemotherapy with the same regimen. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival (OS) and adverse events (AEs).ResultsA total of 75 eligible patients were included from 2014 to 2017. The 2-year LRFS rate, as the primary endpoint, was 73.3%. The 1-year and 3-year OS rates were 88.0% and 68.0%, respectively. Local recurrence occurred in 13/75 (17.4%) patients, of which 2.7% (2/75) were extra-target lymph nodes. Grade 4 adverse events reported in this study included 10 cases (13.3%) of neutropenia, 1 case (1.3%) of anemia, and 2 cases (2.7%) of thrombocytopenia, without toxic-related deaths. Almost all (96%) patients completed the entire postoperative radiotherapy course, and 62 (82.7%) patients completed at least 2 cycles of chemotherapy.ConclusionPostoperative IMRT (clinical target volume including tumor bed, anastomosis, bilateral supraclavicular region, and superior mediastinal lymph nodes) combined with synchronous chemotherapy in patients with locally advanced thoracic esophageal squamous cell carcinoma was well tolerated, with a high local control rate and a low probability of recurrence outside the irradiation field.Clinical trial registrationhttps://clinicaltrials.gov/ChiCTR1900022689.

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: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.

Dataset Information

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

Publications

EGF and EGFR genetic polymorphisms predict prognosis in locally advanced pharyngolaryngeal squamous cell carcinoma patients receiving postoperative concurrent chemoradiotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure