A model to predict the risk of lethal nasopharyngeal necrosis after re-irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients

Background:For patients with nasopharyngeal carcinoma(NPC) who undergo re-irradiation with intensity-modulated radiotherapy(IMRT),lethal nasopharyngeal necrosis(LNN) is a severe late adverse event.The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC.Methods:Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study.Clinical characteristics,including recurrent carcinoma conditions and dosimetric features,were evaluated as candidate risk factors for LNN.Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model.Results:Among 228 patients enrolled in this study,204 were at risk of developing LNN based on risk analysis.Of the 204 patients treated,31(15.2%) developed LNN.Logistic regression analysis showed that female sex(P = 0.008),necrosis before re-irradiation(P = 0.008),accumulated total prescription dose to the gross tumor volume(GTV) ≥ 145.5 Gy(P = 0.043),and recurrent tumor volume >25.38 cm3(P = 0.009) were independent risk factors for LNN.A model to predict LNN was then constructed that included these four independent risk factors.Conclusions:A model that includes sex,necrosis before re-irradiation,accumulated total prescription dose to GTV,and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

顺铂、氟尿嘧啶加或不加紫杉烷的诱导化疗对局部区域晚期鼻咽癌的影响:回顾性、倾向评分匹配分析

背景与目的比较局部区域晚期鼻咽癌(nasopharyngeal carcinoma,NPC)不同诱导化疗(induction chemotherapy,IC)方案的文献中缺乏可用数据。本研究旨在评价接受紫杉烷、顺铂和5-氟尿嘧啶(taxane,cisplatin and 5?fuorouracil,TPF)或顺铂和5-氟尿嘧啶(cisplatin and 5?fuorouracil,PF)方案的IC后进行同步放化疗(concurrent chemoradiotherapy,CCRT)的局部区域晚期鼻咽癌患者的结局。方法前瞻性维护数据库中共1879例接受了IC和CCRT治疗的局部区域晚期鼻咽癌患者被纳入此观察性研究。我们采用倾向评分法比较了总生存期(overall survival,OS)、疾病特异生存期(disease-specific survival,DSS)、无远处转移生存期(distant metastasis?free survival,DMFS)和无局部区域复发生存期。结果共1256例患者接受了TPF或PF作为IC方案。多因素分析中,TPF组比PF组表现出显著更好的OS[风险比(hazard ratio,HR)=0.660;95%置信区间(confdence interval,CI):0.442–0.986;P=0.042]、DSS(HR=0.624;95%CI:0.411–0.947;P=0.027)和DMFS(HR=0.589;95%CI:0.406–0.855;P=0.005)。倾向评分匹配在每个队列中确定了294例患者,并证实了TPF组比PF组表现出显著改善的5年OS率(88.1%vs. 80.7%;P=0.042)、DSS率(88.5%vs.80.7%;P=0.021)和DMFS率(87.9%vs. 78.6%;P=0.012)。匹配前后的局部区域无复发生存率无显著差异。结论在我们的研究中,与PF方案相比,TPF方案IC结合CCRT改善了局部区域晚期鼻咽癌患者的长期生存。然而,有必要进行前瞻性随机临床试验来验证这些发现。

Subtype distribution and long-term titer luctuation patterns of serum anti-Epstein–Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China:a cohort study

Background: Serum immunoglobulin A antibodies against Epstein–Barr virus(EBV), viral capsid antigen(VCA?Ig A) and early antigen(EA?Ig A), are used to screen for nasopharyngeal carcinoma(NPC) in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non?NPC participants.Methods: The distribution of baseline VCA?IgA was analyzed between sexes and across 10?year age groups in 18,286 non?NPC participants using Chi square tests. Fluctuations in the VCA?IgA level were assessed in 1056 non?NPC participants with at least two retests in the first 5?year period(1987–1992) after the initial screening using the Kaplan–Meier method.Results: The titers of VCA?Ig A increased with age(P < 0.001). Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non?NPC partici?pants with an initial VCA?Ig A?positive status and in 20.6% with an initial negative status during the 5?year follow?up. However, seroconversions were common; 85.2% of the participants with a VCA?Ig A?positive status at baseline con?verted to negative, and all VCA?Ig A?negative participants changed to positive at least once during the 5?year follow?up. The EA?Ig A status had a high seroconversion probability(100%) from positive to negative; however, it had a low probability(19.6%) from negative to positive.Conclusions: Age? and sex?specific cutoff titer values for serum anti?EBV antibodies as well as their specific titer fluc?tuation patterns should be considered when defining high NPC risk criteria for follow?up diagnostics and monitoring.

Effect of induction chemotherapy with cisplatin, fluorouracil, with or without taxane on locoregionally advanced nasopharyngeal carcinoma: a retrospective, propensity score-matched analysis

Background:Available data in the literature comparing different induction chemotherapy(IC)regimens on locoregionally advanced nasopharyngeal carcinoma(NPC)are scarce.The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane,cisplatin and 5-fluorouracil(TPF)or cisplatin and 5-fluorouracil(PF)as IC followed by concurrent chemoradiotherapy(CCRT).Methods:In total,1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study.We compared overall survival(OS),disease-specific survival(DSS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival,using the pro-pensity score method.Results:In total,1256 patients received TPF or PF as IC backbone.The TPF group showed significantly better OS(hazard ratio[HR],0.660;95%confidence interval[CI]0.442-0.986;P=0.042),DSS(HR,0.624;95%CI 0.411-0.947;P=0.027)and DMFS(HR,0.589;95%CI 0.406-0.855;P=0.005)compared with the PF group in multivariable analy-ses.Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS(88.1%vs.80.7%;P=0.042),DSS(88.5%vs.80.7%;P=0.021)and DMFS(87.9%vs.78.6%;P=0.012)rates compared with the PF group.There were no significant differences in locoregional relapse-free survival before or after matching.Conclusions:In our study,IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen.However,a prospective randomized clinical trial to validate these findings is necessary.

Decreased macrophage inflammatory protein (MIP)-1α and MIP-1β increase the risk of developing nasopharyngeal carcinoma

Background:The association of circulating inflammation markers with nasopharyngeal carcinoma(NPC)is still largely unclear.This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China.Methods:The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study(150 NPC patients and 150 controls)using multiplex assay platforms.Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection.Odds ratios(ORs)and 95%confidence intervals(CIs)relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models.The associations were validated in 60 patients with NPC and 120 con-trols in a subsequent nested case-control study within a NPC screening trial.Potential interactions between serum cytokines and Epstein-Barr virus(EBV)relating to the risk of NPC were assessed using a likelihood ratio test.Results:The levels of serum macrophage inflammatory protein(MIP)-1αand MIP-1βin the highest categories were associated with a decreased risk of NPC in both the case-control study(MIP-1α:OR=0.49,95%CI=0.26-0.95;MIP-1β:OR=0.47,95%CI=0.22-1.00)and the nested case-control study(MIP-1α:OR=0.13,95%CI=0.03-0.62;MIP-1β:OR=0.20,95%CI=0.04-0.94),compared with those in the lowest categories.Furthermore,individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study(MIP-1α:OR=16.28,95%CI=7.11-37.23;MIP-1β:OR=12.86,95%CI=5.9-28.05)and the nested case-control study(MIP-1α:OR=86.12,95%CI=10.58-701.03;MIP-1β:OR=115.44,95%CI=13.92-957.73).Conclusions:Decreased preclinical MIP-1αand MIP-1βlevels might be associated with a subsequently increased risk of NPC.More mechanistic studies are required to fully understand this finding.