高危因素联合分层法在预测N2-3M0期鼻咽癌预后的临床价值分析

目的 分析高危因素联合分层法在预测N2-3M0期鼻咽癌预后的临床价值。方法 2013-2015年间226例N2-3M0期首程鼻咽癌病例被纳入研究,分析肿瘤体积、颈部转移淋巴结特征(坏死、融合)和T、N分期等与生存的关系,分析影响生存的高危因素,探讨高危因素联合分层法在预测预后的价值。结果 N3期、Vn≥47.15cm³和淋巴结融合是N2-3M0期鼻咽癌患者远处转移的高危因素,根据高危因素分为低危、中危、高危、极高危组。生存分析显示低危、中危、高危、极高危组3年总生存率分别为84.2%、76.7%、58.7%、36.4%(P<0.001),无远处转移生存率分别为87.3%、85.2%、54.5%、12.1%(P<0.001),无进展生存率分别为76.8%、74.3%、49.2%、12.1%(P<0.001),无局部区域复发生存率分别为89.2%、88.5%、91.5%、88.3%(P=0.914)。比较N分期、Vn分组、淋巴结融合分组和高危因素联合分层法的无远处转移生存曲线发现:高危因素联合分层法将组间曲线分离的更开,明显优于其他三组(P<0.05)。结论 高危因素联合分层法在预测N2-3M0期鼻咽癌患者预后的临床价值更高。     

淋巴结阳性鼻咽癌患者与IMRT后发生远处转移相关性研究

目的 评价颈部转移性淋巴结与鼻咽癌IMRT后发生远处转移之间关系。方法 回顾分析2010—2012年接受IMRT的474例初治无远处转移鼻咽癌患者资料,采用Kaplan-Meier法计算各种生存率并Logrank检验和单因素预后分析,采用进入法进行Cox模型多因素分析。结果 474例患者中400例发生颈部淋巴结转移,122例经IMRT后存在颈部淋巴结残留。4年累计远处转移率13.7%(65/474),4年OS、DFS、LRFS、DMFS分别为82.9%、81.4%、93.5%、86.3%。单因素及多因素分析显示治疗方式、下颈Ⅳ/Ⅴb/Ⅴc区淋巴结转移、颈部转移淋巴结最大直径、残留淋巴结大小、淋巴结消退时间是DMFS的影响因素(P均<0.05)。结论 放化疗能降低鼻咽癌IMRT后远处转移发生率。颈部淋巴结越大,越容易发生残留,残留淋巴结越大,发生远处转移风险越高。颈部大淋巴结(≥6 cm)、残留淋巴结>1 cm及在放疗3个月后仍有淋巴结残留为鼻咽癌IMRT后DMFS的不利预后因素,需探讨更合理的干预治疗方式。     

鼻咽癌腮腺淋巴结转移危险因素及高危患者腮腺局部调强放疗的探讨

目的 探讨鼻咽癌腮腺淋巴结转移的高危因素,评价高危者腮腺放疗的可行性。方法 收集2011-2017年江苏省肿瘤医院放疗科收治的440例初诊鼻咽癌患者的临床资料,回顾性分析腮腺淋巴结转移相关的影像特点、治疗及预后。全组采用调强放疗技术,全腮腺或部分腮腺照射、选择性PLN照射,X线和(或)电子线补量,剂量45~60 Gy。χ²检验或Fisher's精确概率法检验和单因素分析,Logistic回归模型多因素分析。Kaplan-Meier法生存分析,Logrank检验差异。结果 腮腺区影像学可见淋巴结者共230例。确诊腮腺转移11例(占2.5%,11/440),其中腮腺淋巴结最大径≥5 mm者占81.8%(9/11)。多因素分析显示Ⅱ区淋巴结包膜外侵为其转移的独立危险因素。将腮腺区淋巴结最大径≥5 mm、Ⅱ区淋巴结包膜外侵者筛选为腮腺淋巴结转移高危组,根据腮腺区是否放疗分为放疗组及未放疗组。生存分析发现,在230例患者中,高危组腮腺区放疗者与未放疗者无局部复发生存率不同(P<0.05),总生存、无远处转移生存、无进展生存均相近(P>0.05)。结论 鼻咽癌腮腺淋巴结转移率低,Ⅱ区淋巴结包膜外侵为其独立高危因素。对于腮腺淋巴结最大径≥5 mm,或腮腺区存在影像学可见淋巴结,即使其最大径<5 mm,但若合并Ⅱ区淋巴结包膜外侵,建议行腮腺区放疗。     

不同诱导化疗疗效对非高发区局部晚期鼻咽癌调强放疗同期化疗预后影响

目的 评价不同诱导化疗疗效对非高发区局部晚期鼻咽癌患者调强放疗同期化疗疗效及预后影响因素。方法 回顾分析2012—2017年间初治的 210例Ⅲ-ⅣB期(排除T3-4N0M0期)鼻咽癌患者资料,根据不同诱导化疗疗效分为有效组(完全缓解 14例+部分缓解 165例)和无效组(稳定 31例+0例进展)。Kaplan-Meier法生存分析,Cox模型多因素分析。结果 与无效组相比,有效组 3年总生存率较高(89.2%∶74.2%,P=0.005),3年无复发生存率较高(93.0%∶81.9%,P=0.010),3年无进展生存率较高(80.2%∶58.1%,P=0.005),但无远处转移生存相近(84.1%∶69.7%,P=0.070)。多因素分析显示诱导化疗疗效是影响总生存、无复发生存、无进展生存的独立预后因素。结论 诱导化疗疗效可预测非高发区局部晚期鼻咽癌患者的预后,诱导化疗后无效患者预后更差,或许需要对这些患者采用更高强度的治疗方案以及更密切的随访。     

精确放疗时代T1期鼻咽癌不同N/M分期的预后分析

目的 探讨精确放疗时代T1期伴不同颈淋巴结转移状态的鼻咽癌患者生存预后,为优化治疗方案提供参考。方法 回顾性分析复旦大学附属眼耳鼻喉科医院放疗科2014—2019年间进行单纯放疗或放化疗的413例局部早期鼻咽癌患者(T1N0-3M0-1期)资料。Kaplan-Meier法生存分析并log-rank法检验。结果 全部病例中男291例、女122例,中位年龄51岁(9~78岁)。病理类型均为鼻咽非角化性癌、未分化型。T1N0M0期(Ⅰ期)48例(11.6%),T1N1M0期(Ⅱ期)158例(38.3%),T1N2M0期(Ⅲ期)162例(39.2%),T1N3M0/T1NxM1期(ⅣA-ⅣB期)45例(10.9%);初治发生转移的ⅣB期患者8例(1.9%)。所有患者总体淋巴结转移率高达88.1%。接受三维适形放疗7例,调强放疗371例,容积调强弧形治疗35例。5年总生存率为(95.9±1.2)%,其中T1N0M0期为100%,T1N1M0期为(99.2±0.8)%,T1N2M0期为(95.1±2.2)%,T1N3M0期为(87.9±6.6)%;初治转移及N3期与患者远期预后显著相关(P<0.05)。放疗远期不良反应中口干不适最常见,发生率为18.6%,其中17.9%为1级不良反应;其次为听觉损伤及牙齿不适等;仅2例发生3级不良反应,表现为听力完全丧失。结论 T1期鼻咽癌患者虽颈淋巴结转移率高,但放疗效果好,精确放疗技术下远期放疗不良反应并未对患者的生存质量产生严重影响。     

99例Ⅳa期鼻咽癌的预后分析

[目的]分析Ⅳa期鼻咽癌患者的预后及影响预后的因素。[方法]将99例Ⅳa期鼻咽癌纳入分析。Kaplan-Meier法计算生存数据,并对Ⅳa期鼻咽癌的预后相关因素行单因素和多因素分析。[结果]全组病例3年局部控制率、无远处转移生存率、无进展生存率、疾病相关总生存率分别为87.3%、75.8%、69.3%及77.9%,远处转移是治疗失败主要原因。单因素分析提示N分期较晚患者(N2～3)其生存显著低于N分期较早者(P<0.05)。多因素分析提示N分期较晚影响Ⅳa期病例远处转移发生,但无统计学差异(N0～1vs.N2～3,HR=0.396,95%CI:0.144～1.086,P=0.072)。N2～3的Ⅳa期患者其无远处转移生存和无进展生存率显著低于N0～1的Ⅳa期患者(P=0.023,P=0.011),局部控制率则无显著差异(P=0.432)。[结论]中国鼻咽癌2008分期中Ⅳa期病例预后具有很大的不一致性,主要由颈部淋巴结分期的早晚决定。     

初诊 ⅣB期胸段食管鳞癌综合放疗长期生存获益研究

目的 探讨综合放疗用于初诊 ⅣB期胸段食管鳞癌患者的价值。方法 选取2010—2016年间于河北医科大学第四医院初诊并经胃镜/食管镜或转移灶活检证实为 ⅣB的原发胸段食管鳞癌患者 199例。单纯远处淋巴结转移者 130例(65.3%),单纯实质脏器转移 51例(25.6%),实质脏器合并远处淋巴结转移者 18例(9.0%)。单纯化疗 16例(8.0%),单纯放疗 50例(25.1%),放化疗 133例(66.8%)(同期放化疗 81例、序贯放化疗 52例)。使用Kaplan-Meier法计算生存率并行log-rank检验差异,采用Cox模型行多因素预后分析。结果 全组中位总生存期为12.3个月(95%CI为 10.6~15.4个月),1、2、3、5年总生存率分别为52.1%、25.2%、19.1%、11.5%。多因素分析显示病变长度、转移器官数目、治疗模式是总生存的独立影响因素。同期放化疗对比序贯放化疗总生存相近(P=0.955)。放疗剂量≥6000 cGy组患者总生存明显高于 4500~5039 cGy组和 5040~6000 cGy组(均为 P<0.001)。结论 对于初诊 ⅣB期胸段食管鳞癌患者,原发病变长度≤3cm、单器官转移、放化疗模式有相对更长的总生存。对于体质较好的患者可考虑在全身化疗基础上将放疗参与到Ⅳ期食管癌的综合治疗中,个体化选择序贯或同期放化疗模式。在患者能够耐受基础上,建议给予原发灶或非区域转移淋巴结等部位进行放化疗,以达到延长患者生存的目的。     

调强放疗联合化疗在T1-2N1M0期鼻咽癌患者中的作用回顾性研究

目的 探索调强放疗(IMRT)联合化疗在治疗T1-2N1M0期鼻咽癌患者中的作用。方法 收集2008—2016年间浙江省肿瘤医院和中山大学肿瘤防治中心接受根治性治疗的T1-2N1M0期鼻咽癌患者343例。所有患者均接受IMRT,分为单纯放疗组(RT组)和放化疗组(CRT组),后者又分为同步放化疗组(CCRT组)、诱导化疗+同步放化疗组(IC+CCRT组)和同步放化疗+辅助化疗组(CCRT+AC组)。采用Kaplan-Meier法评价局部区域无复发生存率(LRFFS)、远处无转移生存率(DMFS)、无进展生存率(PFS)、肿瘤特异生存率(CSS)和总生存率(OS)。Cox模型多因素预后分析。结果 303例存活患者的中位随访时间为91个月(49~138个月)。CRT组∶RT组的5年OS、CSS、PFS、LRFFS、DMFS均相近(93.7%∶93.9%、93.7%∶93.9%、89.0%∶87.7%、93.8%∶92.8%、93.8%∶91.2%,均P>0.05)。T1N1期和T2N1期亚组分析也显示CRT组与RT组的治疗结果均相近(均P>0.05)。多因素分析显示只有年龄是OS、PFS、CSS和DMFS的独立预后因素,随年龄增长与上述结局呈负相关。CCRT组、IC+CCRT组、CCRT+AC组与RT组的治疗结局均未给患者带来生存获益,且上述3种联合治疗方式之间的疗效也相近(均P>0.05)。结论 T1-2N1M0期鼻咽癌患者接受单纯IMRT获得了满意的治疗效果,预后与联合化疗相当。但未来是否可在T1-2N1M0期人群中取消化疗仍需要前瞻性随机对照临床试验的进一步证实。     

初治寡转移鼻咽癌患者原发灶根治性放疗疗效分析

目的 初诊寡转移鼻咽癌患者原发灶根治性放疗预后因素分析。方法 2008—2011年39例初诊寡转移鼻咽癌患者接受1~6周期化疗及原发灶根治性放疗,其中10例常规放疗,26例IMRT。Kaplan-Meier法计算生存率,Logrank单因素预后分析,Cox模型多因素预后分析。结果 中位随访时间38个月,1、2、3年OS和PFS分别为97%及87%、87%及65%、70%及59%。年龄、转移灶数目、诱导化疗方案、是否同步化疗均是影响生存的因素,其中≤3个转移灶患者生存率更高(P=0.023),诱导化疗包含比不含多西他赛方案生存率明显提高(P=0.041)。结论 初治寡转移鼻咽癌患者接受诱导化疗及原发灶根治性放疗后仍可获得长期生存,尤其是年龄小及转移灶数目≤3个患者。含多西紫杉醇的方案或能使患者得到更大生存获益。     

非手术食管鳞癌病变长度对临床分期影响——Ⅱ/Ⅲ期根治性放疗患者多中心回顾性分析(3JECROG R-01D)

目的 回顾性分析接受根治性放疗Ⅱ、Ⅲ期食管鳞癌患者病变长度对预后的影响和在临床分期中的作用。方法 回顾分析2002-2016年全国10所医疗中心(泛京津冀食管癌协作组)符合纳入标准的2086例不宜手术或拒绝手术而接受根治性放疗的Ⅱ、Ⅲ期食管鳞癌患者的临床及随访资料。分析中位病变长度与总生存、无进展生存的关系,进一步分层分析病变长度对临床分期的影响。结果 全组中位生存时间和中位无进展生存时间分别为25.6个月和18.2个月。Cox多因素生存分析显示治疗方式、年龄、临床分期、病变长度为预后影响因素。≤5 cm组中位生存时间28.9个月,1、3、5年生存率为77.3%、45.0%、36.3%。全组>5 cm组中位生存时间21.9个月,1、3、5年生存率为69.9%、37.9%、28.1%(P<0.05)。Ⅱ期患者≤5 cm组和>5 cm组中位生存时间分别为42.1个月和38.9个月(P=0.303),Ⅲ期患者的分别为23.9个月和19.3个月(P<0.001),N1期患者的分别为24.1个月和18.4个月(P<0.001)。结论 Ⅱ、Ⅲ期食管癌患者病变长度与放疗预后相关,可能对目前临床分期具有补充作用,≤5 cm长度对Ⅲ期、N1期患者能更好的预测生存。     

基于鼻咽癌临床Ⅲ期探讨第8版AJCC/UICC分期系统

目的 基于调强放疗临床Ⅲ期鼻咽癌的生存分析中探讨第8版AJCC/UICC鼻咽癌分期系统。方法 2008-2014年在汕头大学医学院附属肿瘤医院首次治疗的 1351例鼻咽癌患者中按第7、8版标准重新分期,确定Ⅲ期患者分别为742、784例,将其各自分为3个亚组:T3N0-1期为 G1(226、245例),T1-2N2期为 G2(180、187例),T3N2期为G3(336、352例)。Kaplan-Meier法分别计算3个组 5年总生存(OS)、无进展生存(PFS)、无远处转移生存(DMFS)、无局部区域复发生存(LRRFS),并log-rank检验组间差异。结果 第8版病例中93.6%与第7版的相同。第8版与第7版总体的OS、PFS、DMFS、LRRFS分别为84.8%与85.4%、76.2%与77.0%、80.4%与81.3%、89.8%与90.6%(P均>0.05)。第8版分期3个亚组的OS、PFS和DMFS均不同(P均<0.001);G1与 G2、G1与G3也不同(P均<0.05),G2与G3间相近(P=0.183、0.310、0.248)。结论 第8版AJCC/UICC分期系统对临床Ⅲ期病例的分布特点及临床终点相对于第7版变化不大,亚组间仍有明显的组内生存风险分布差异,其中N2对Ⅲ期患者的生存风险评估起到主要作用。可能在IMRT联合化疗时代局部肿瘤对预后的影响已经减弱,第8版分期系统仍然有改进的空间。     

鼻咽癌患者血浆EBV-DNA检测的临床价值

目的 EB病毒与鼻咽癌的发生发展明确相关,多个研究显示血浆EBV-DNA对于鼻咽癌的诊断分期及预后判断有重要意义,因此对我院患者进行了血浆EBV-DNA的检测并分析其临床价值。方法 2013—2016年连续性鼻咽癌患者471例,分析其治疗前EBV-DNA水平与分期、肿瘤负荷的相关性,并对治疗前、治疗末EBV-DNA进行生存相关分析。结果 患者治疗前血浆EBV-DNA中位数137 copies/ml (0~494000),与T分期、N分期、M分期、总的临床分期、肿瘤负荷均有明显统计学相关性。生存分析显示治疗前血浆EBV-DNA拷贝数≤1300组比>1300组的患者有更好OS (P=0.007)、PFS (P=0.011)、DMFS (P=0.003)。治疗末血浆EBV-DNA不可检测到的患者有更好OS (P=0.016)、PFS (P=0.000)、DMFS (P=0.000)。Cox多因素分析T分期、治疗末是否可检测到EBV-DNA为OS (P=0.030、0.012)的预后因素,N分期(P=0.037、0.017)、放疗末是否可检测到EBV-DNA (P=0.006、0.001)为PFS及DMFS的预后因素。结论 鼻咽癌患者治疗前血浆EBV-DNA水平与分期及肿瘤负荷有明显相关性,治疗前EBV-DNA水平更高的患者可能治疗后的预后更差。治疗末血浆EBV-DNA是否可检测到对于OS、PFS、DMFS有较好的预测价值。     

Discussion of the 8th edition of AJCC/UICC staging system from the clinical stage Ⅲ nasopharyngeal carcinoma

Objective To evaluate the 8^th edition of AJCC/UICC staging system for stage Ⅲ nasopharyngeal carcinoma (NPC) by the survival analysis. All patients were treated with intensity-modulated radiotherapy (IMRT). Methods Among 1351 treatment-naïve NPC patients who received radiotherapy/chemoradiotherapy in our hospital from December 2008 to October 2014, 742 and 784 cases were classified as clinical stage Ⅲ based on the criteria of the 7^th and 8^th edition of AJCC/UICC staging systems, respectively. These patients were classified into three subgroups according to the 7^th and 8^th edition of AJCC/UICC staging systems:T3N0-1 as G1(n=226, n=245), T1-2N2 as G2(n=180, n=187) and T3N2 as G3(n=336, n=352). The 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and local-regional recurrence-free survival (LRRFS) were analyzed with Kaplan-Meier method. The differences among different groups were evaluated by log-rank test. Results There were 93.6% patients evaluated by the 8^th AJCC/UICC staging system remained the same cohort with those by the 7^th AJCC/UICC staging system. The 5-year OS, PFS, DMFS and LRRFS of the 8^th and 7^th staging systems were 84.8% and 85.4%, 76.2% and 77.0%, 80.4% and 81.3%, 89.8% and 90.6%, respectively (all P>0.05). The OS, PFS or DMFS significantly differed among three subgroups classified by the 8^th staging system (all P<0.001). In addition, statistical significance was observed between G1 and G2, and between G1 and G3(both P<0.05), whereas no statistical significance was noted between G2 and G3(P=0.183, 0.310, 0.248). Conclusions The distribution features and clinical endpoints of clinical stage Ⅲ defined by the 8^th AJCC/UICC staging system are similar to those defined by the 7^th AJCC/UICC staging system. The distribution of survival risk significantly differs among different subgroups. N2 plays a major role in assessing the survival risk of patients with stage Ⅲ NPC. In the era of IMRT plus chemotherapy, the effect of local tumors on clinical prognosis has been diminished. The 8^th AJCC/UICC staging system remains to be further improved.     

IMRT同期化疗在Ⅲ期鼻咽癌中作用分析

目的 探讨IMRT同期化疗对Ⅲ期鼻咽癌患者预后的影响和作用。方法 回顾性分析2001-2008年间中山大学肿瘤防治中心接受单纯IMRT和IMRT同期铂类药物化疗的 251例Ⅲ期鼻咽癌患者,分析相关预后因子和探讨IMRT同期化疗作用。采用Kaplan-Meier法计算生存率,组间差异比较采用log-rank检验,Cox模型预后因素分析。结果 全组 10年无局部区域复发生存(LRFS)、无远处转移生存(DMFS)、无进展生存(PFS)和总生存(OS)率分别为88.6%、81.1%、68.8%和75.1%。单因素和多因素分析显示N分期和鼻咽肿瘤体积是最重要的预后影响因素,同期化疗有助于改善患者PFS和OS (均 P<0.05)。T3N0-1期患者单纯放疗组和同期放化疗组各生存指标均相近(10年LRFS为93.8%∶93.2%,P=0.933;10年DMFS为80.9%∶86.8%,P=0.385;10年PFS为70.6%∶77.7%,P=0.513;10年OS为71.8%∶83.6%,P=0.207);T1-3N2期患者同期放化疗的LRFS、PFS和OS优于单纯放疗(10年LRFS为87.3%∶66.7%,P=0.016;10年PFS为70.2%∶41.0%,P=0.003;10年OS为78.5%∶51.7%,P=0.008),DMFS有提高趋势(10年DMFS为80.3%∶66.4%,P=0.103)。结论 IMRT中同期化疗的加入有助于改善Ⅲ期鼻咽癌患者预后,在N2期组获益较为明显,需要根据患者治疗失败风险予以个体化治疗方案。     

The role of concurrent chemotherapy in intensity-modulated radiotherapy for patients with stage Ⅲ nasopharyngeal carcinoma

Objective To investigate the clinical efficacy of concurrent chemotherapy in intensity-modulated radiotherapy (IMRT) for patients with stage Ⅲ nasopharyngeal carcinoma (NPC). Methods Clinical data of 251 patients with stage Ⅲ NPC treated with IMRT alone or concurrent chemoradiotherapy (CCRT) at Sun Yat-sen University Cancer Center from February 2001 to December 2008 were retrospectively analyzed. The prognostic factors of NPC were analyzed and the efficacy of CCRT was assessed. The survival rate was calculated by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. The prognostic factors were analyzed by Cox model. Results The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for NPC patients were 88.6%, 81.1%, 68.8% and 75.1%, respectively. Univariate and multivariate analyses demonstrated that N staging and nasopharyngeal tumor volume were the most important prognostic factors, and concurrent chemotherapy significantly improved PFS and OS (both P<0.05). In T3N0-1 patients, there was no significant difference in survival indexes between IMRT alone and CCRT (10y-LRFS:93.8% vs. 93.2%, P=0.933;10y-DMFS:80.9% vs. 86.8%, P=0.385;10y-PFS:70.6% vs. 77.7%, P=0.513;10y-OS:71.8% vs. 83.6%, P=0.207). For T1-3N2 patients, CCRT was significantly better than radiotherapy alone in LRFS, PFS, and OS (10y-LRFS:87.3% vs. 66.7%, P=0.016;10y-PFS:70.2% vs. 41.0%, P=0.003;10y-OS:78.5% vs. 51.7%, P=0.008), whereas there was an increasing trend in DMFS (10y-DMFS:80.3% vs. 66.4%, P=0.103). Conclusions Concurrent chemotherapy can improve clinical prognosis of stage Ⅲ NPC patients, and the most survival benefits are obtained in the N2 group. Individualized treatment options should be delivered based on the risk of treatment failure.     

Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma

Background

We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC).

Patients and methods

We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I.

Results

The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis.

Conclusion

Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC.     

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein–Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma

Background: According to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system, over 50% of patients with nasopharyngeal carcinoma (NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node (GTVnd) and pretreatment serum copy number of Epstein–Barr virus (EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients. Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were ana-lyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood sam-ples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic (ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model. Results: The 5-year distant metastasis-free survival (DMFS) rates for patients with GTVnd > 18.9 vs. ≤ 18.9 mL were 82.2% vs. 93.2% (P < 0.001), and for patients with EBV DNA copy number > 4000 vs. ≤ 4000 copies/mL were 83.5% vs. 93.9% (P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-, moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1, 87.4, and 73.8%, respectively (P < 0.001). Multi-variate analysis confirmed the prognostic value of this model for distant metastatic risk stratification (hazard ratio [HR], 4.17; 95% confidence interval [CI] 2.34–7.59; P < 0.001). Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.