A Bayesian network meta-analysis comparing concurrent chemoradiotherapy followed by adjuvant chemotherapy,concurrent chemoradiotherapy alone and radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma

BackgroundGiven the lack of studies, whether the addition of adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear. The main objective of this Bayesian network meta-analysis was to determine the efficacy of CCRT + AC when compared with CCRT alone.Patients and methodsWe systematically searched databases and extracted data from randomized, controlled trials involving NPC patients randomly assigned to receive CCRT + AC, CCRT, or radiotherapy (RT). Overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) with hazard ratios (HRs) were investigated. A Bayesian network for different outcomes was established to incorporate all evidence. Multiple treatment comparisons based on the network integrated the efficacy of CCRT + AC, CCRT, and RT.ResultsEight studies involving 2144 patients were analyzed. In the network meta-analysis, CCRT + AC and CCRT were both significantly better than RT alone for all outcomes, except that no significant difference was found between CCRT and RT for LRFS. Though ranking probabilities showed that CCRT + AC was ranked superior to CCRT for OS, LRFS, and DMFS, no significant differences were found between CCRT+AC and CCRT for all outcomes [OS: HR = 0.86, 95% credible interval (CrI) 0.60–1.16; LRFS: HR = 0.72, 95% CrI 0.43–1.15; DMFS: HR = 0.86, 95% CrI 0.62–1.16].ConclusionsNo significant improvement was found following CCRT + AC compared with CCRT alone. Whether the omission of additional AC can reduce toxic effects without adversely affecting survival in patients with locoregionally advanced NPC should be further explored, in addition to the precise patient status that would benefit from AC following CCRT.     

Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial

Aim of the studyPrevious results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC).MethodsPatients with stage III–IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m² weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m² and fluorouracil 800 mg/m²/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival.ResultsTwo hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64–1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3–4 toxicities (p = 0.14).ConclusionAdjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities.Registration numberNCT00677118.     

Concurrent chemoradiotherapy with or without adjuvant chemotherapy in intermediate and locoregionally advanced nasopharyngeal carcinoma

Concurrent chemoradiotherapy (CCRT) showed a significant improvement in disease control and clinical outcome in patients with intermediate and locoregionally advanced nasopharyngeal carcinoma (NPC) (stage II, III and IVA+B). However, there has been debate about the contribution and application of additional adjuvant chemotherapy (AC) to a CCRT regime. This study aims to evaluate the additional value of AC in the treatment of intermediate and locally advanced NPC with regard to toxicity and clinical outcomes. A total of 189 patients with American Joint Committee on Cancer (AJCC) stage II to stage IVB NPC were retrospectively identified. Patient characteristics, toxicity, compliance with treatment and clinical outcomes, including response to treatment, overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), freedom from local recurrence (FLR) and freedom from distant metastasis (FDM), were analyzed. The overall response rate of CCRT and CCRT/AC groups was 97.92 % and 97.83 %, respectively (P?=?0.643). The 5-year OS rate was 68.2 % in the CCRT group and 75.9 % in the CCRT/AC group (P?=?0.53). The 5-year PFS rate was 66.7 % and 71.4 % in CCRT and CCRT/AC groups, respectively (P?=?0.96). This study showed no evidence of an additional value of AC in CCRT treatment in disease control and clinical outcomes in patients with locally advanced NPC in endemic regions. Moreover, three additional cycles of AC after CCRT appeared to be poorly tolerated in patients. Therefore, AC should not be routinely used for treatment, although clinical trials may be justified.     

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

BackgroundThe role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC.MethodsPatients with stage III–IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m² cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² civ d1–5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints.ResultsFour hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77–0.87) than the control arm (74.1%, 95% CI = 0.68–0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3–4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3–4 toxicities (P < 0.001).ConclusionNACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.     

Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost

This study was to report the long-term outcomes and toxicities of nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). From 2009 to 2010, 869 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. With a median follow-up of 54.3 months, the 5-year estimated local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 89.7%, 94.5%, 85.6%, 76.3%, 84.0%, respectively. In locally advanced NPC, gender, T, N, total dose of cisplatin more than 300 mg/m² and radiation boost were independent prognostic factors for DMFS and DFS. Age, T, N and total dose of cisplatin were independent prognostic factors for OS. Radiation boost was an adverse factor for LRFS, RRFS, DMFS and DFS. Concurrent chemotherapy was not an independent prognostic factor for survival, despite marginally significant for DMFS in univariate analysis. Concurrent chemotherapy increased xerostomia and trismus, while higher total dose of cisplatin increased xerostomia and otologic toxicities. In conclusion, IMRT provided satisfactory long-term outcome for NPC, with acceptable late toxicities. Total dose of cisplatin was a prognostic factor for distant metastasis and overall survival. The role of concurrent chemotherapy and radiation boost in the setting of IMRT warrants further investigation.     

133例Ⅲ期鼻咽癌调强放疗的疗效及不良反应分析

背景与目的:调强放疗(intensity-modulated radiation therapy,IMRT)是最大限度提高肿瘤靶区照射剂量的同时明显减少周围正常组织的剂量的放疗技术,调强放疗联合化疗治疗局部晚期鼻咽癌取得了较好的疗效,如何在此基础上进一步提高疗效成为肿瘤学者共同关注的话题.鼻咽癌分期不同,疗效不同,同一分期各亚组间疗效有无差别,尚有待研究.通过回顾性分析临床Ⅲ期鼻咽癌各亚组间调强放疗联合化疗的疗效,探讨进一步提高疗效的方法.方法:对我院2003年1月-2006年6月期间收治的133例临床Ⅲ期鼻咽癌患者进行分析,根据AJCC 2002分期,其中T3N0 7例(5.3％),T3N1 39例(29.3％),T2N2 48例(36.1％),T3N2 39例(29.3％).所有患者均完成调强放疗,124例患者行诱导化疗,其中24例患者行同期化疗,33例患者行辅助化疗.结果:全组5年局部控制率、无远处转移生存率、无瘤生存率和总生存率分别为:90.9％、89.9％、82.5％和83.4％.T2、T3期患者5年局部控制率分别为93.1％、89.4％(x2=0.407,P=0.524),无远处转移生存率分别为91.2％、89.3％(x2=0.152,P=0.697),无瘤生存率分别为86.5％、80.0％(x2=0.899,P=0.343),总生存率分别为81.1％、84.7％(x2=0.311,P=0.577).N0-1、N2期患者5年局部控制率分别为91.1％、90.9％(x2=0.007,P=0.933),无远处转移生存率分别为97.8％、85.8％ (x2=4.69,P=0.030),无瘤生存率分别为88.9％、79.2％(x2=1.746,P=0.183 6),总生存率分别为93.5％、78.1％(x2=5.052,P=0.025).辅助化疗对IMRT Ⅲ期鼻咽癌未能获益,但3、4级毒性不良反应明显增加(48％ vs 27.6％,P＜0.005).结论:对临床Ⅲ期鼻咽癌患者,IMRT联合化疗可以取得较好的疗效,N0-1期较N2期患者有较高的总生存率和无远处转移生存率,进一步提高IMRT Ⅲ期鼻咽癌疗效还需寻找更有效的化疗药物、靶向药物及更合理的联合治疗方案.     

同期放化疗对比单纯放疗治疗非高发区T1~2N1M0期鼻咽癌远期疗效观察

目的:回顾性配对分析以适形调强放疗为基础的不同治疗模式对非高发区T1~2N1M0期鼻咽癌患者预后的影响。方法:回顾性分析2010年1月至2015年12月河南省肿瘤医院初治的行根治性放疗的T1~2N1M0期鼻咽癌患者,筛选出51对患者(单纯放疗组和同期放化疗组各51例)进行配对分析。比较两组患者各项生存率及急性不良反应。结果:全组5年总生存率、无局部复发生存率、无区域复发生存率、无远处转移生存率分别为94.1%、93.6%、96.7%、90.9%。单纯放疗组与同期放化疗组相比,5年总生存率(95.9%vs. 92.2%,P=0.894)、无局部复发生存率(94.1%vs. 93.3%,P=0.976)、无区域复发生存率(95.8%vs. 97.6%,P=0.572)、无远处转移生存率(91.4%vs. 90.2%,P=0.716),差异均无统计学意义。急性不良反应方面,与单纯放疗组相比,同期放化疗组呕吐、中性粒细胞减少、白细胞减少、血红蛋白减少和黏膜炎的发生率显著升高。结论:对于T1~2N1M0期鼻咽癌患者,同期化疗的加入并未明显改善患者预后,且急性不良反应增加。     

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。     

不同诱导化疗方案联合放疗治疗鼻咽癌疗效分析

  目的  分析诱导化疗后行调强放疗的鼻咽癌患者,对比不同诱导化疗方案的治疗疗效。  方法  回顾性分析2012年1月至2014年6月天津医科大学肿瘤医院初治170例Ⅱ~Ⅳb期鼻咽癌患者临床资料,其中男性126例,女性44例;Ⅱ期27例,Ⅲ期105例,Ⅳa~b期38例。  结果  全组中位随访时间34个月。3年总生存率、局部区域控制率、无病生存率和无远处转移生存率分别为82.8%、91.5%、76.7%和69.1%。多因素分析发现,含紫杉醇+顺铂的诱导化疗方案较顺铂+5-氟尿嘧啶疾病进展（HR:1.820,95%CI:1.013~3.271,P=0.045）及远处转移风险（HR:2.240,95%CI:1.017~4.090,P=0.045）显著降低。  结论  含紫杉醇+顺铂的诱导化疗方案较顺铂+5-氟尿嘧啶方案显著延长鼻咽癌患者无病生存率和无远处转移生存率。      

基于IMRT的Ⅱ期鼻咽癌同期放化疗与单纯放疗远期疗效比较

目的 评价以IMRT为基础的不同治疗模式对Ⅱ期鼻咽癌患者预后的影响。方法 回顾分析123例Ⅱ期鼻咽癌患者的临床资料,其中单纯放疗81例,同期放化疗42例。Kaplan-Meier计算生存率并Logrank检验。结果 全组5年OS、LRFS、DMFS、PFS分别为96.7%、94.7%、93.1%、87.8%。单纯放疗组与同期放化疗组相比,5年OS (98.7%:92.9%,P=0.569)、LRFS (94.8%:94.5%,P=0.770)、DMFS (94.5%:90.2%,P=0.408)、PFS (90.6%:82.2%,P=0.340)均无明显差异。T₂N₁期患者两组5年各项生存率仍无明显差异(P=0.929、0.967、0.917、0.492)。急性不良反应方面同期放化疗组中性粒细胞减少、白细胞减少、血红蛋白减少和放射性黏膜反应发生率明显升高(P=0.000、0.000、0.012、0.010),而两组晚期不良反应发生率相近(P=0.823、0.622、0.113)。结论 对Ⅱ期患者同期化疗的加入并未改善患者预后,但急性不良反应明显增加。     

Long-term follow-up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma

BackgroundPrevious results from our trial showed that adding oxaliplatin to radiotherapy (RT) increased survival in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term efficacy and late toxic effects.Patients and methodsBetween January 2001 and January 2003, 115 Patients with nonkeratinizing/undifferentiated locoregionally advanced NPC were randomly to receive either RT alone (n = 56) or plus concurrent oxaliplatin 70 mg/m² weekly for six cycles (n = 59).ResultsAfter a median follow-up of 114 months (range 18–139 months), the 5-year overall survival (OS) and metastasis-free survival (MFS) rates in the concurrent chemoradiotherapy (CCRT) group were significantly higher than those observed in the RT-alone group (OS, 73.2% versus 60.2%, P = 0.028; MFS, 74.7% versus 63.0%, P = 0.027). However, CCRT did not improve locoregional failure-free survival significantly. Subgroup analyses showed that the superiorities of CCRT mainly existed in the T3-4N0-1 stage subgroup (OS: HR = 0.394, P = 0.034). The grade 3/4 late toxic effects were similar in the two groups.Conclusion(s)The long-term follow-up data confirms the role of CCRT as a treatment of locoregionally advanced NPC. Oxaliplatin can be considered as an alternative optional therapeutic regimen for these patients due to its high efficiency and low toxic effect.     

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.     

Neoadjuvant chemotherapy plusintensity-modulated radiotherapy versusconcurrent chemoradiotherapy plusadjuvant chemotherapy forthe treatment oflocoregionally advanced nasopharyngeal carcinoma：a retrospective controlled study

Background:In the era of intensity?modulated radiotherapy (IMRT), the role of neoadjuvant chemotherapy (NAC) for locoregionally advanced nasopharyngeal carcinoma (NPC) is under?evaluated. The aim of this study was to com?pare the effcacy of NAC plus IMRT and concurrent chemoradiotherapy (CCRT) plus adjuvant chemotherapy (AC) on locoregionally advanced NPC.
Methods:Between January 2004 and December 2008, 240 cases of locoregionally advanced NPC conifrmed by pathologic assessment in Sun Yat?sen University Cancer Center were reviewed. Of the 240 patients, 117 received NAC followed by IMRT, and 123 were treated with CCRT plus AC. The NAC+IMRT group received a regimen that included cisplatin and 5?lfuorouracil (5?FU). The CCRT+AC group received cisplatin concurrently with radiotherapy, and subsequently received adjuvant cisplatin and 5?FU. 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 overall survival (OS), locoregional relapse?free survival (LRRFS), distant metastasis?free survival (DMFS), and disease?free survival (DFS) were 78.0, 87.9, 79.0, and 69.8%, respectively, for the NAC+IMRT group and 78.7, 84.8, 76.2, and 65.6%, respectively, for the CCRT+AC group. There were no signiifcant differences in survival between the two groups. In multivariate analysis, age (<50years vs.≥50years) and overall stage (III vs. IV) were found to be independent predictors for OS and DFS; furthermore, the overall stage was a signiifcant prognostic factor for DMFS. Compared with the CCRT+AC protocol, the NAC+IMRT protocol signiifcantly reduced the occurrence rates of grade 3–4 nausea–vomiting (6.5 vs. 1.5%,P=0.023) and leukopenia (9.7 vs. 0.8%,P=0.006).
Conclusions:The treatment outcomes of the NAC+IMRT and CCRT+AC groups were similar. Distant metastasis remained the predominant mode of treatment failure.     

A comparison of carboplatin and paclitaxel with cisplatinum and 5-fluorouracil in definitive chemoradiation in esophageal cancer patients

BackgroundIn esophageal cancer (EC) patients who are not eligible for surgery, definitive chemoradiation (dCRT) with curative intent using cisplatinum with 5-fluorouracil (5-FU) is the standard chemotherapy regimen. Nowadays carboplatin/paclitaxel is also often used. In this study, we compared survival and toxicity rates between both regimens.Patients and methodsThis multicenter study included 102 patients treated in five centers in the Northeast Netherlands from 1996 till 2008. Forty-seven patients received cisplatinum/5-FU (75 mg/m² and 1 g/m²) and 55 patients carboplatin/paclitaxel (AUC2 and 50 mg/m²).ResultsOverall survival (OS) was not different between the cisplatinum/5-FU and carboplatin/paclitaxel group {[P = 0.879, hazard ratio (HR) 0.97 [confidence interval (CI) 0.62–1.51]}, with a median survival of 16.1 (CI 11.8–20.5) and 13.8 months (CI 10.8–16.9). Median disease-free survival (DFS) was comparable [P = 0.760, HR 0.93 (CI 0.60–1.45)] between the cisplatinum/5-FU group [11.1 months (CI 6.9–15.3)] and the carboplatin/paclitaxel group [9.7 months (CI 5.1–14.4)]. Groups were comparable except clinical T stage was higher in the carboplatin/paclitaxel group (P = 0.008). High clinical T stage (cT4) was not related to OS and DFS in a univariate analysis (P = 0.250 and P = 0.201). A higher percentage of patients completed the carboplatin/paclitaxel regimen (82% versus 57%, P = 0.010). Hematological and nonhematological toxicity (≥grade 3) in the carboplatin/paclitaxel group (4% and 18%) was significantly lower than in the cisplatinum/5-FU (19% and 38%, P = 0.001).ConclusionsIn this study, we showed comparable outcome, in terms of DFS and OS for carboplatin/paclitaxel compared with cisplatinum/5-FU as dCRT treatment in EC patients. Toxicity rates were lower in the carboplatin/paclitaxel group together with higher treatment compliance. Carboplatin/paclitaxel as an alternative treatment of cisplatinum/5-FU is a good candidate regimen for further evaluation.     

N晚期鼻咽癌调强放疗远期疗效评价

目的 评价N晚期鼻咽癌根治性调强放疗(IMRT)的远期疗效及IMRT联合不同化疗模式对N晚期鼻咽癌患者预后影响。
方法 回顾分析2001-2008年间收治的179例N晚期鼻咽癌患者临床资料,其中单纯IMRT 33例,放化疗146例(同期放化疗71例、诱导化疗加同期放化疗66例,同期放化疗加辅助化疗9例)。
结果 随访率96.5%,随访时间满5年者133例。全组5年总生存率为69.0%。单纯IMRT和放化疗的5年总生存率、无远处转移生存率、无复发生存率、无进展生存率分别为47.7%和73.7%(χ²=13.91,P=0.000)、49.2%和68.3%(χ²=4.97,P=0.026)、74.5%和92.4%(χ²=9.87,P=0.002)、37.5%和65.1%(χ²=11.65,P=0.001),放化疗中同期放化疗、诱导化疗加同期放化疗、同期放化疗加辅助化疗的生存率相似,但诱导化疗加同期放化疗的无远处转移生存率比单纯IMRT的高(χ²=4.65,P=0.031)。
结论 N晚期鼻咽癌患者单纯IMRT后远处转移率仍较高,诱导化疗加IMRT联合同期化疗也许是较为合理的治疗手段。     

Adjuvant treatment with pegylated interferon α-2a versus low-dose interferon α-2a in patients with high-risk melanoma: a randomized phase III DeCOG trial

BackgroundAdjuvant treatment with interferon (IFN)-α-2a improved disease-free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis-free survival (DMFS), DFS and OS.Patients and methodsIn this multicenter, open-label, prospective randomized phase III trial, patients with resected cutaneous melanoma stage IIA(T3a)–IIIB (AJCC 2002) were randomized to receive PEG-IFN (180 μg subcutaneously 1×/week; 24 months) or IFN α-2a (3MIU subcutaneously 3×/week; 24 months). Randomization was stratified for stage, number of metastatic nodes, age and previous IFN treatment. The primary end point was DMFS; secondary end points were OS, DFS, quality of life (QoL) and tolerability.ResultsA total of 909 patients were enrolled (451 PEG-IFN versus 458 IFN). Neither 5-year DMFS [PEG-IFN 61.0% versus IFN 67.3%; hazard ratio (HR) 1.16, P = 0.21] nor 5-year OS (PEG-IFN 73.2% versus IFN 75.2%; HR 1.05, P = 0.70) nor 5-year DFS (PEG-IFN 57.3% versus IFN 60.9%; HR 1.09, P = 0.40) showed significant differences. Subgroup analyses in patients ± ulcerated primaries and of different tumor stages did not find differences in DMFS, OS or DFS between the treatment groups. One hundred and eighteen patients (26.2%) in the PEG-IFN and 61 patients (13.3%) in the IFN population did not receive the full dosage and length of treatment due to adverse events (P < 0.001). Leukopenia and elevation of liver enzymes were more common in the PEG-IFN arm (56% versus 23.5% LCP; 19.1% versus 9.4% AST; 33.0% versus 16.5% ALT). QoL was identical for nearly all domains.ConclusionPEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity.Clinical Trials.gov IdentifierNCT00204529.     

鼻咽癌IMRT同期EGFR单抗和同期化疗与单纯IMRT的回顾对照研究

目的 回顾性对比IMRT同期EGFR单抗、同期化疗和单纯IMRT治疗鼻咽癌的疗效及不良反应。方法 将2008—2012年间收治的68例接受IMRT同期EGFR单抗的Ⅱ—Ⅳ_b期初治鼻咽癌患者纳入BRT组,应用SAS软件进行1∶2配对形成单纯IMRT (IMRT)组136例及同期放化疗(CCRT)组136例,共340例。Kaplan-Meier法计算生存率并Logrank检验,Cox模型分析预后因素。结果 BRT、IMRT、CCRT组3年样本数分别为14、69、47例。全组3年OS、DFS、LRC、DMFS分别为91.2%、80.2%、93.1%、87.2%。BRT、IMRT、CCRT组的3年OS分别为91.9%、 92.1%、89.9%(P=0.379),3年DFS分别为82.1%、77.9%、81.6%(P=0.594),3年LRCR分别为98.2%、90.6%、93.0%(P=0.249),3年DMFS分别为85.2%、85.2%、90.3%(P=0.383)。多因素分析提示T分期及同期EGFR单抗是LRC的影响因素(P=0.034、0.032)。结论 鼻咽癌单纯IMRT即可达较好疗效。三组之间整体疗效相近,但BRT组有提高LRC的趋势。     

Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up

BackgroundTo evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up.MethodsWe retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011.ResultsOf the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5 years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p < 0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p = 0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p = 0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS.ConclusionsIMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used.     

635例非高发区局部晚期鼻咽癌调强放疗的长期随访观察

目的 探讨江苏省初治局部晚期（Ⅲ、ⅣA、ⅣB期）鼻咽癌患者调强放疗联合化疗治疗后长期生存情况及预后影响因素。方法 收集江苏省肿瘤医院放疗科2009年1月至2013年12月收治的局部晚期鼻咽癌635例进行回顾性分析。所有患者均接受调强放疗,其中604例患者接受了含铂方案为主的化疗。采用Kaplan-Meier法进行生存分析,用Log-rank检验和Cox比例风险回归模型分析局部晚期鼻咽癌患者的预后相关因素。结果 随访5～92个月,中位随访时间63.5个月。全组患者的5年局部无复发生存（LRFS）、 区域无复发生存（RRFS）、无远处转移生存（DMFS）、无进展生存（DFS）、总生存（OS）率分别为88.4％、94.2％、79.2％、71.9％和76.3％。175例（27.6％）治疗失败,其中远处转移（131例,74.9％）是主要的治疗失败形式。T分期是LRFS的独立预后因素,临床分期、N分期和化疗是RRFS、DMFS、DFS及OS的独立预后因素。结论 调强放疗提高了鼻咽癌患者的远期疗效。除了T、N分期是影响预后的重要因素外,化疗对预后也起到一定的作用。