Purpose: To compare the diagnostic performance of two modalities commonly used for detecting distant metastasis in primary nasopharyngeal carcinoma (NPC): 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) and conventional work-ups (CWUs).Methods: All topic-related studies were comprehensively searched and included.We determined sensitivities and specificities across studies, calculated negative and positive likelihood ratios (LR-and LR+, respectively), and constructed summary receiver operating characteristic curves.Moreover, we compared the diagnostic performance of PET/CT and CWUs by analyzing studies that reported the results of these diagnostic methods on the same patients.Results: The pooled sensitivity and specificity were 85.7% and 98.1% for PET/CT (1474 patients), and 38.0% and 97.6% for CWUs (1329 patients).In the head-to-head comparison of PET/CT and CWUs (1029 patients), PET/CT showed a significantly higher sensitivity (83.7% vs. 40.1%,P < 0.001) and lower LR-(0.169vs. 0.633, P < 0.001) than CWUs on a per-patient basis; no significant difference was observed in pooled specificity (97.7% vs. 97.8%,P = 0.892) or LR+ (36.416 vs. 16.845,P = 0.149).The superiority of PET/CT over CWUs was due mainly to the better diagnostic performance on bone metastasis.However, suboptimal sensitivity of PET/CT was reported in the aspect of detection of liver metastasis.Sensitivity analyses showed relatively poor sensitivity and LR-of PET/CT compared to the original analysis.Conclusions: PET/CT was superior to CWUs in detecting distant metastasis in primary NPC.However, the efficacy of PET/CT in detecting liver metastasis still requires further optimization.
The objective of this study is to assess the prognostic value of ABO blood group in nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT).We retrospectively reviewed the data on 1397 patients with non-metastatic, newly diagnosed NPC treated using IMRT. Patient survival between different ABO blood groups were compared using log-rank test. Cox hazards model was adopted to establish independent prognostic factors.In our study, the distribution of the A, B, AB and O blood groups was 26.6% (372/1397), 26.2% (366/1397), 5.2% (73/1397) and 42.0% (586/1397), respectively. The cut-off value of pre-treatment Epstein-Barr virus (EBV) DNA based on disease-free survival (DFS) was 1355 copies/ml (area under curve [AUC], 0.649; sensitivity, 0.76; specificity, 0.496) for the whole cohort. Estimated four-year DFS, overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates were 81.7%, 89.2%, 89.4% and 92.3% for blood group A; 82.1%, 89.3%, 89.0% and 92.0% for group B; 83.3%, 88.1%, 86.2% and 95.5% for group AB, 80.9%, 90.7%, 88.4% and 90.2% for group O (P > 0.05 for all rates). Multivariate analysis revealed ABO blood group was not an independent prognostic factor for DFS, OS, DMFS or LRRFS (P > 0.05 for all rates) after adjusting for plasma EBV DNA in either the whole cohort or subgroup analysis by gender.The prognostic value of ABO blood group may be limited for patients with NPC in the era of IMRT, and no substantial correlation between ABO blood group and plasma EBV DNA was observed.
Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry.Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method.registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method.For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time.Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.
The value of adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. In our recent article entitled "Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial" published in the Lancet Oncology, we reported the results of a phase III, multicenter, randomized controlled trial comparing cisplatin, 5-fluorouracil, and docetaxel (TPF) IC plus CCRT versus CCRT alone in patients with T3-4N1/TxN2-3M0 NPC (ClinicalTrials.gov registration number NCT01245959). The IC-plus-CCRT group showed significantly higher 3-year failure-free survival, overall survival, and distant failure-free survival rates than the CCRT-alone group, with an acceptable toxicity profile. Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC. However, long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy, and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.
Abstract The prognostic value and staging category of parotid lymph node (PLN) metastasis in nasopharyngeal carcinoma (NPC) remain unknown. We retrospectively reviewed MRI scans and medical records for 1811 NPC patients who received intensity-modulated radiotherapy. The diagnosis of PLN metastasis was mainly based on MRI follow-up. Twenty-five positive PLNs in 21/1811 patients were identified; the incidence of PLN metastasis was 1.2%. PLN metastasis was significantly associated with advanced N-category and stage. Ten of the 21 patients received irradiation of the involved PLNs; the PLN recurrence rate was significantly higher for patients who received no irradiation; thus only patients with irradiated PLN were included in prognostic analyses. PLN metastasis was associated with significantly poorer progression-free survival, overall survival and distant metastasis-free survival (DMFS), but not regional or local relapse-free survival, in univariate analysis. In multivariate analysis, PLN metastasis was also significantly associated with poor DMFS. PLN involvement had a significantly higher hazard ratio (HR) for distant failure than N2 disease and similar HR to N3 disease. In conclusion, PLN metastasis is rare in NPC and was associated with similarly poor DMFS as N3 disease. PLN metastasis should be suspected in advanced nodal disease, but diagnosed with care before administering aggressive treatment.
To compare the survival outcomes and acute toxicities of concurrent chemoradiotherapy (CCRT), induction chemotherapy (IC) plus radiotherapy (RT), and IC plus CCRT in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiotherapy (IMRT).Patients with stage III-IVB NPC who were treated with IMRT between 2009 and 2012 at a single institution were retrospectively reviewed. The induction regimens included PF (cisplatin and fluorouracil) and TP (docetaxel and cisplatin) every 3 weeks for 2-3 cycles; the concurrent regimen was cisplatin every three weeks for 2-3 cycles. A propensity score matching method was used to match patients from each group in a 1:1:1 ratio.In total, 147 eligible patients were propensity-matched, with 49 patients in each treatment group. The median follow-up duration was 38.5 months (range, 4.5 - 56 months). The 3-year disease-free survival, overall survival, distant metastasis-free survival, and locoregional relapse-free survival rates were 82.1%, 92.8%, 87%, and 90.4% in the CCRT group; 86.3%, 91.0%, 91.6%, and 94.4% in the IC plus RT group; and 87.8%, 95.8%, 93.8%, and 93.9% in the IC plus CCRT group, respectively. No statistically significant survival differences were observed between the three treatment groups in either univariate or multivariate analyses. The incidence of grade 3-4 acute toxicities was similar among groups.This study suggests that CCRT, IC plus RT, and IC plus CCRT are similarly efficacious treatment strategies for patients with locoregionally advanced NPC treated using IMRT; however, long-term, large-scale randomized trials are required to confirm these findings.
Nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV). The current study investigated change in the plasma EBV DNA load in the first 3 months after treatment and its clinical significance in NPC.A total of 273 patients with non-metastatic, histologically-proven NPC treated with radiotherapy or chemoradiotherapy were retrospectively reviewed.EBV DNA was detectable in 19/273 (7.0%) patients at the end of therapy (end-DNA). Three months later, 16/273 (5.9%) patients had detectable EBV DNA (3-month-DNA). To investigate risk stratified by the pattern of change in post-treatment EBV-DNA, we divided patients into four subgroups: Group 1, undetectable end-DNA and 3-month-DNA (n = 244); Group 2, detectable end-DNA and undetectable 3-month-DNA (n = 13); Group 3, undetectable end-DNA and detectable 3-month-DNA (n = 7); and Group 4, detectable end-DNA and 3-month-DNA (n = 2). Patients with delayed remission of EBV DNA after treatment (Group 2) had significantly poorer 3-year DFS (48.6% vs. 89.7%, P < 0.001), DMFS (48.6% vs. 94.6%, P < 0.001) and OS (91.7% vs. 97.5%, P < 0.001) than those with persistently undetectable EBV DNA post-treatment (Group 1). Five of the seven patients with re-emergent EBV DNA (Group 3) and both patients with persistent EBV DNA post-treatment (Group 4) developed disease failure.Plasma EBV DNA load continues to change during the first 3 months after treatment. The pattern of change in EBV DNA load post-treatment could help identify patients with different prognoses.
The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV).Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC.Data on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared.EBV status was an independent prognostic factor for patients with stage III-IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients.
Abstract Background Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients. Methods BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154). Results BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P < 0.001) and poor overall survival (OS, P < 0.001) in the training set; these results were validated in the testing set and overall patient population. Cox regression analysis demonstrated that low BRMS1 expression was an independent prognostic factor for DMFS and OS in NPC. Conclusions Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients.
Purpose The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. Results Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel–cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. Conclusion Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC. Key words: Induction chemotherapy, Nasopharyngeal carcinoma, Neutropenia, Lymphocyte, Prognosis, Survival
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