Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Treatment outcomes of a prospective, multicentric clinical study

Wu, Fang; Wang, Rensheng; Lu, Hongsheng; Wei, Bo; Feng, Guosheng; Li, Guisheng; Liu, Meilian; Yan, Haolin; Jin, Zhu; Zhang, Yong; Hu, Kai

doi:10.1016/j.radonc.2014.05.005

Cited by 112 publications

(76 citation statements)

References 33 publications

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“…In addition, it was supposed that most local recurrence occurred in the tumor areas that exhibited late responses, and that isolated recurrences in marginal areas were minimal even with suboptimal dose coverage. Wu et al18 reported 29 local recurrences in NPC patients treated with radiotherapy, and all of the recurrences were located inside the boost areas. In this study, the 10 local recurrences were all within the PTV-G, further confirmed the safety of reduced GTV delineation.…”

Section: Discussionmentioning

confidence: 99%

Induction chemotherapy followed by intensity-modulated radiotherapy with reduced gross tumor volume delineation for stage T3-4 nasopharyngeal carcinoma

Xue¹,

Hu²,

He³

2017

OTT

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PurposeA common problem in stage T3–4 nasopharyngeal carcinoma (NPC) is the narrow gap between the primary tumor and neurological structures, which makes dose optimization difficult. Considering that significant tumor shrinkage may occur during induction chemotherapy (IC), this study explored the efficacy of intensity-modulated radiotherapy (IMRT) using reduced gross tumor volume (GTV) in the treatment of T3–4 NPC.Patients and methodsBetween January 2009 and April 2014, 103 patients with non-metastatic stage T3–4 NPC were prospectively recruited. They were assigned to accept IC, followed by reduced-volume IMRT and adjuvant chemotherapy. GTV was based on the post-IC volume of intracavity tumors and lymph nodes, and the pre-IC volume of the remaining involved structures.ResultsFor all treated patients, the 3-year local failure-free survival (LFFS) was 91.9%. After IC, 91 (88.3%) patients achieved local objective response (OR), and their 3-year LFFS rates were significantly better than in patients who failed to achieve local OR (94.1% vs 75.0%, P=0.023). A multivariate analysis demonstrated the prognostic value of tumor response to IC for LFFS. Dosimetric analysis showed good homogeneity, and the dose constraints were stringent. Asymptomatic temporal lobe necrosis in the ipsilateral side of tumor occurred in one patient.ConclusionIMRT using a reduced GTV delineation delivered satisfactory doses to the target volumes and avoided overdosing of critical neurological structures. Results showed satisfactory survival outcomes with few treatment-related toxicities. Tumor response to IC could facilitate selection of patients with stage T3–4 NPC eligible for treatment with this method.

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Section: Discussionmentioning

confidence: 99%

Induction chemotherapy followed by intensity-modulated radiotherapy with reduced gross tumor volume delineation for stage T3-4 nasopharyngeal carcinoma

Xue¹,

Hu²,

He³

2017

OTT

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“…The non-specificity of nasal and aural symptoms accounts for locoregionally advanced disease in 70% of patients upon initial diagnosis [1]. 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].…”

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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“…NPC has the highest metastasis features among head and neck cancers, with approximately 75–85% of patients have regional lymph node metastasis, and 15-19% of patients develop distant metastasis [4, 5]. Although NPC is sensitive to radiotherapy (RT) and the addition of chemotherapy to RT works effectively, treatment failure for NPC remains quite frequent, with rate of approximately 20% for distant metastasis [6, 7]. Over the past decades, the prognosis for NPC is still poor with a 5-year survival rate range from 50% to 70% for patients in advanced stage [8].…”

Section: Introductionmentioning

confidence: 99%

BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway

Wang

Zhou

Zhang

et al. 2017

Aging

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Bone morphogenetic protein-2 (BMP2) is a secreted protein that highly expressed in a variety of cancers and contributes to cell proliferation, migration, invasiveness, mobility, metastasis and EMT. However, its clinical significance and biological function in nasopharyngeal carcinoma (NPC) remain unknown up to now. Up-regulation of BMP2 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. In this study, BMP2 mRNA was detected by qRT-PCR and data showed that it was upregulated in NPC compared with non-cancerous nasopharynx samples. Immunohistochemistry (IHC) analysis in NPC specimens revealed that high BMP2 expression was significantly associated with clinical stage, distant metastasis and shorter survival of NPC patients. Moreover, overexpression of BMP2 in NPC cells promoted cell proliferation, migration, invasiveness and epithelial-mesenchymal transition (EMT). Mechanistically, BMP2 overexpression increase phosphorylated protein level of mTOR, S6K and 4EBP1. Correspondingly, mTORC1 inhibitor rapamycin blocked the effect of BMP2 on NPC cell proliferation and invasion. In conclusion, our results suggest that BMP2 overexpression in NPC enhances proliferation, invasion and EMT of tumor cells through the mTORC1 signaling pathway.

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Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Treatment outcomes of a prospective, multicentric clinical study

Cited by 112 publications

References 33 publications

Induction chemotherapy followed by intensity-modulated radiotherapy with reduced gross tumor volume delineation for stage T3-4 nasopharyngeal carcinoma

Induction chemotherapy followed by intensity-modulated radiotherapy with reduced gross tumor volume delineation for stage T3-4 nasopharyngeal carcinoma

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

BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway

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