Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial

Cao, Su Mei; Yang, Qi; Guo, Lanwei; Qiang, Hai; Mo, Hao Yuan; Cao, Ke; Qian, Chao Nan; Zhao, Chong; Xiang, Yan; Zhang, Xiu Ping; Lin, Zhi Xiong; Li, Wei Xiong; Liu, Qing; Qiu, Fang; Sun, Rui; Chen, Qiu Yan; Huang, Pei Yu; Luo, Dong Hua; Hua, Yi; Wu, Yu Chun; Lv, Xing; Wang, Lin; Xia, Wei; Ye, Yan Fang; Chen, Ming Yuan; Guo, Xiang; Hong, Ming

doi:10.1016/j.ejca.2016.12.039

Cited by 233 publications

(248 citation statements)

References 32 publications

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“…However, IC did not reduce distant metastasis or prolong survival in previous clinical trials (3)(4)(5)(6)(7). We previously demonstrated that IC plus CCRT increased the distant metastasis-free survival (DMFS) in LA-NPC, but the extent of the improvement was only 4%, with most patients being overtreated (8). It is possible that a better patient stratification can efficiently identify patients at highrisk of metastasis for additional IC.…”

Section: Introductionmentioning

confidence: 93%

A Prognostic Bio-Model Based on SQSTM1 and N-Stage Identifies Nasopharyngeal Carcinoma Patients at High Risk of Metastasis for Additional Induction Chemotherapy

Yang

Zhang

Zou

et al. 2018

Clinical Cancer Research

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Purpose: Metastasis is one of the most important causes of treatment failure in nasopharyngeal carcinoma (NPC). In T4 or N2-3 patients at high-risk of metastasis, concurrent chemoradiotherapy (CCRT) is inadequate and additional induction chemotherapy (IC) is controversial. There is a critical need to develop a better patient stratification to efficiently identify patients at highrisk of metastasis for additional IC. Recently, Sequestosome 1 (SQSTM1)/p62, an autophagy adaptor protein, was identified as one of the metastasis-related proteins in NPC. However, the mechanism by which SQSTM1 is involved in NPC metastasis was not investigated.Experimental Design: The effect of SQSTM1 on cell migration and invasion was examined in vitro and in vivo. SQSTM1 expression was analyzed in clinical NPC samples using IHC. Luciferase reporter analyses were conducted to identify the effects of SQSTM1 on NF-kB transcriptional activity. A prediction biomodel was constructed by Cox analysis. Retrospective and prospective randomized clinical data were adopted to build and test the model, respectively.Results: SQSTM1 mediated epithelial to mesenchymal transition (EMT) through the NF-kB pathway to promote NPC metastasis. Inhibiting SQSTM1 enhanced sensitivity to cisplatin in NPC cells. In NPC patients, high SQSTM1 expression was associated with increased risk of distant metastasis. Furthermore, we propose a prognostic bio-model based on SQSTM1 and N-stage to predict NPC metastasis. Most importantly, our prospective randomized study suggested that IC is beneficial for NPC patients with high metastasis risk.Conclusions: The prognostic bio-model identifies NPC patients at high-risk of metastasis for additional IC. Clin Cancer Res; 24(3); 648-58. Ó2017 AACR.

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Section: Introductionmentioning

confidence: 93%

A Prognostic Bio-Model Based on SQSTM1 and N-Stage Identifies Nasopharyngeal Carcinoma Patients at High Risk of Metastasis for Additional Induction Chemotherapy

Yang

Zhang

Zou

et al. 2018

Clinical Cancer Research

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“…Subsequently, these patients have a high risk of distant metastasis and mortality [2, 3] even if treated with concurrent chemoradiotherapy. Accordingly, induction chemotherapy is commonly administered before radiotherapy in clinical practice although randomized controlled trials have not yet contributed to a consensus about its survival benefit [4–8]. In addition, there are no effective adjuvant chemotherapy regimens that have been identified for these patients after radiotherapy [9–13].…”

Section: Introductionmentioning

confidence: 99%

External validity of a prognostic nomogram for locoregionally advanced nasopharyngeal carcinoma based on the 8th edition of the AJCC/UICC staging system: a retrospective cohort study

OuYang

You

Zhang

et al. 2018

Cancer Communications

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BackgroundThe tumor–node–metastasis (TNM) staging system does not perform well for guiding individualized induction or adjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We attempted to externally validate the Pan’s nomogram, developed based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system, for patients with locoregionally advanced disease. In addition, we investigated the reliability of Pan’s nomogram for selection of participants in future clinical trials.MethodsThis study included 535 patients with locoregionally advanced NPC who were treated between March 2007 and January 2012. The 5-year overall survival (OS) rates were calculated using the Kaplan–Meier method and compared with predicted outcomes. The calibration was tested using calibration plots and the Hosmer–Lemeshow test. Discrimination ability, which was assessed using the concordance index, as compared with other predictors.ResultsPan’s nomogram was observed to underestimate the 5-year OS of the entire cohort by 8.65% [95% confidence interval (CI) − 9.70 to − 7.60%, P < 0.001] and underestimated the 5-year OS of each risk group. The differences between the predicted and observed 5-year OS rates were smallest among low-risk patients (< 135 points calculated using Pan’s nomogram; which predicted minus observed OS, − 6.41%, 95% CI − 6.75 to − 6.07%, P < 0.001) and were largest among high-risk patients (≥ 160 points) (− 13.56%, 95% CI − 15.48 to − 11.63%, P < 0.001). The Hosmer–Lemeshow test suggested that the predicted and observed 5-year OS rates had no ideal relationship (P < 0.001). Pan’s nomogram had better discriminatory ability compared with the levels of Epstein–Barr virus DNA acid (EBV DNA) and the 7th or 8th AJCC/UICC staging system, although not better compared with the combination of EBV DNA and the 8th staging system. Additionally, Pan’s nomogram was marginally inferior to our predictive model, which included the 8th AJCC/UICC N-classification, age, gross primary tumor volume, lactate dehydrogenase, and body mass index.ConclusionsPan’s nomogram underestimated the 5-year OS of patients with locoregionally advanced NPC at our cancer center, and may not be a precise tool for selecting participants for clinical trials.

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“…Neoadjuvant chemotherapy (NAC) followed by intensity‐modulated radiotherapy (IMRT) has currently been widely accepted as an attractive approach in lieu of establishing concurrent chemoradiation therapy (CCRT) in nasopharyngeal carcinoma (NPC) . CCRT is frequently accompanied by acute and late dose‐limiting toxicities, hindering its common use .…”

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confidence: 99%

Integrating dynamic contrast‐enhanced magnetic resonance imaging and diffusion kurtosis imaging for neoadjuvant chemotherapy assessment of nasopharyngeal carcinoma

Zheng

Lai

Chen

et al. 2018

Magnetic Resonance Imaging

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Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial

Cited by 233 publications

References 32 publications

A Prognostic Bio-Model Based on SQSTM1 and N-Stage Identifies Nasopharyngeal Carcinoma Patients at High Risk of Metastasis for Additional Induction Chemotherapy

A Prognostic Bio-Model Based on SQSTM1 and N-Stage Identifies Nasopharyngeal Carcinoma Patients at High Risk of Metastasis for Additional Induction Chemotherapy

External validity of a prognostic nomogram for locoregionally advanced nasopharyngeal carcinoma based on the 8th edition of the AJCC/UICC staging system: a retrospective cohort study

Integrating dynamic contrast‐enhanced magnetic resonance imaging and diffusion kurtosis imaging for neoadjuvant chemotherapy assessment of nasopharyngeal carcinoma

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