Prognostic significance of a combined and controlled nutritional status score and EBV-DNA in patients with advanced nasopharyngeal carcinoma: a long-term follow-up study

Objective: Several studies have reported that the controlling nutritional status(CONUT) score is a prognostic predictor for survival among patients with different types of cancer. We assessed the prognostic value of changes in the CONUT score during treatment and the ΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods: We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011; the patients underwent...     

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.     

Two-year outcome of concurrent chemoradiation with carboplatin with or without adjuvant carboplatin/fluorouracil in nasopharyngeal cancer: A multicenter randomized trial

BackgroundAccording to the noninferiority result of chemoradiation with carboplatin in our previous nasopharyngeal carcinoma (NPC) study along with the inconclusive data on the efficacy of adjuvant chemotherapy (AC) following concurrent chemoradiotherapy (CCRT), we designed to assess the role of adjuvant carboplatin/fluorouracil following CCRT with carboplatin in locoregionally advanced NPC.Materials and MethodsA multicenter randomized trial was conducted at 5 cancer centers in Thailand. We enrolled in stage T2N0M0-T4N2M0 (American Joint Cancer Committee 7th edition) WHO Type 2 NPC patients. N3 or metastatic disease patients were excluded. Participants were randomized into 2 groups: CCRT plus AC group vs the CCRT alone group. Patients in both groups received weekly carboplatin 100 mg/m² for 6 cycles concurrently with radiotherapy 69.96-70 Gy. Patients in the AC group subsequently received 3 cycles of carboplatin area under curve-5 plus 1000 mg/m²/day of fluorouracil infusion within 96 hours every 3 weeks. We report the 2-year overall survival (OS), disease-free survival (DFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Treatment-related toxicities and compliance were also explored.ResultsOf 175 patients, 82 (46.9%) were assigned to the AC group, and 93 (53.1%) to the CCRT group. The compliance rate during CCRT was 90% and 86% in the AC and CCRT group, whereas 81.7% during adjuvant treatment in the AC group. With a median follow-up time of 24.4 months (interquartile range 17.9-24.4), the 2-year OS rate was 89.6% in the AC group and 81.8% in the CCRT group (P= 0.167). The 2-year DFS rate was 86.8% in the AC group and 74.6% in the CCRT group (P = 0.042). The 2-year LRFS rate was 91.5% in the AC group and 88.2% in the CCRT group (P = 0.443). The 2-year DMFS rate was 85.4% in the AC group and 79.6% in the CCRT group (P = 0.294). The most frequent serious (grade 3/4) nonhematologic toxicity was acute mucositis, which occurred 5% in the AC group vs 4% in the CCRT group (P = 0.498). For hematologic toxicity, grade 3-4 leukopenia were found 10% and 5% in the adjuvant and CCRT groups, respectively (P = 0.003). Multivariate analyses determined stage N2 disease was an adverse prognostic factor associated with shorter OS, DFS, and DMFS. And the adjuvant treatment was a significant protective factor for only DFS.ConclusionsThe addition of adjuvant carboplatin/fluorouracil following CCRT with carboplatin significantly improved 2-year DFS in stage T2N0M0-T4N2M0 NPC albeit there was a nonsignificant trend in favor of a higher 2-year OS, LRFS, and DMFS. Long-term efficacy and late toxicities of AC still require exploration.     

调强放疗结合诱导化疗或同期加辅助化疗治疗局部晚期鼻咽癌的疗效比较

目的:比较诱导化疗加调强放疗和同期放化疗加辅助化疗治疗局部晚期鼻咽癌的疗效。方法:收集2004年1 月至2008年12月中山大学肿瘤医院收治的经病理证实的局部晚期鼻咽癌240 例,其中采用顺铂+ 5-FU 诱导化疗加调强放疗（诱导组）117 例,采用顺铂、调强放疗同期放化疗加顺铂+ 5-FU 辅助化疗（同期组）123 例。应用Kaplan-Meier 和Log-rank 法计算和比较两组患者的生存率。结果:诱导组和同期组的5 年总生存率、无瘤生存率、无转移生存率、无鼻咽复发生存率和无颈部复发生存率分别为78.0% 和78.7% 、68.9% 和67.5% 、79.0% 和77.0% 、91.6% 和91.0% 、95.3% 和93.7% ,两组比较差异无统计学意义（P>0.05）。 同期组Ⅲ、Ⅳ级恶心呕吐和白细胞减少的发生率明显高于诱导组。多因素分析结果显示N 分期和年龄是影响局部晚期鼻咽癌患者总生存的预后独立因素。结论:诱导化疗加调强放疗治疗局部晚期鼻咽癌的疗效达到同期放化疗加辅助化疗的水平,远处转移是局部晚期鼻咽癌治疗失败的主要原因。      

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。     

Effect of adaptive replanning in patients with locally advanced nasopharyngeal carcinoma treated by intensity-modulated radiotherapy: a propensity score matched analysis

Purpose

Limited data have been published regarding the effect of adaptive radiotherapy (ART) on clinical outcome in patients with nasopharyngeal carcinoma (NPC). We compared the long-term outcomes in patients with locally advanced NPC treated by adaptive intensity-modulated radiotherapy (IMRT) replanning versus IMRT.

Methods

200 NPC patients with stage T3/T4 were included between October 2004 and November 2010. Patients in both treatment groups were matched using propensity score matching method at the ratio of 1:1. Clinical outcomes were analyzed with Kaplan–Meier method, log-rank test and Cox regression.

Results

After matching, 132 patients (66 patients in each group) were included for analysis. The median follow-up for the IMRT replanning group was 70 months, while the IMRT group was 69 months. The 5-year local–regional recurrence-free survival (LRFS) rate was higher in IMRT replanning group (96.7 vs. 88.1 %, P = 0.022). No significant differences in distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were observed between the two groups. 21.2 % patients in IMRT replanning group and 28.8 % patients in IMRT group had distant metastasis. In multivariable analysis, IMRT replanning was identified as an independent prognostic factor for LRFS (hazard ratio 0.229; 95 % CI 0.062–0.854; P = 0.028), but not for DMFS, PFS and OS.

Conclusions

IMRT replanning provides an improved LRFS for stage T3/T4 NPC patients compared with IMRT. Distant metastasis remains the main pattern of treatment failure. No significant advantage was observed in DMFS, PFS and OS when adaptive replanning was used.

     

Prognostic factors in elderly patients with non-small cell lung cancer: a two-center experience

Non-small cell lung cancer (NSCLC) is usually at advanced stage when it is diagnosed. There is no consensus about the standard treatment in elderly patients with advanced NSCLC. Generally, data regarding elderly patients with NSCLC are withdrawn from general NSCLC studies based on subgroup analyses and suggestions. We evaluated prognostic factors in elderly patients with advanced NSCLC. We reviewed retrospectively 338 patients from August 2005 to July 2009 in two centers in Turkey. Medical records of the patients ≥65 years with advanced NSCLC were collected. Collected data included demographic informations, clinical assessments and information on treatment, toxicities and outcomes. Survival was estimated by using Kaplan–Meier method and prognostic factors were evaluated with log-rank and Cox regression tests. The median overall survival (OS) for the entire group was 15.4 months (95% CI: 12.7–18.0). In univariate analysis, weight loss, stage, combination therapy, second-line chemotherapy and tumor response (P < 0.01) and performance status significantly affected OS (P < 0.05). The median progression-free survival (PFS) was 10 months (95% CI: 8.4–11.6). In univariate analysis, there was only a significant association between tumor response and PFS (14.6 vs. 8.5 months; P < 0.001). Multivariate analysis showed that only response to therapy was an important prognostic factor for OS (P < 0.001). Survival of elderly patients with advanced NSCLC is significantly influenced by performance status, weight loss, stage, combination therapy, second-line chemotherapy and response to therapy. Not only age but also these factors may be kept in mind in the treatment planning of the elderly patients with NSCLC. These results may be of benefit in changing clinical practice in elderly patients with NSCLC who are often undertreated.     

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.     

Clinical efficacy of nedaplatin-based concurrent chemoradiotherapy for uterine cervical cancer: a Tohoku Gynecologic Cancer Unit Study

Objective

The aim of this study was to compare the efficacy of nedaplatin-based concurrent chemoradiotherapy (CCRT) with that of cisplatin-based CCRT in patients with cervical cancer.

Methods

The medical records of patients with cervical cancer who had undergone CCRT between 2003 and 2007 were retrospectively reviewed. Of these, 129 patients were treated postoperatively with CCRT (n = 52) or primary CCRT (n = 77). A total of 29 patients were treated with nedaplatin-based postoperative CCRT and 23 patients were treated with cisplatin-based postoperative CCRT. A total of 28 patients were treated with nedaplatin-based postoperative CCRT, and 49 patients were treated with cisplatin-based postoperative CCRT. Progression-free survival (PFS) and overall survival (OS) were compared between the treatment groups.

Results

With postoperative CCRT, there were no significant differences in recurrence rate (P = 1.0000), PFS (log-rank: P = 0.8503), and OS (log-rank: P = 0.8926) between the two treatment groups. With primary CCRT, there were no significant differences in PFS (log-rank: P = 0.7845) and OS (log-rank: P = 0.3659). The frequency of acute toxicity was not significantly different between the cisplatin-based postoperative CCRT group and the nedaplatin-based postoperative CCRT group.

Conclusions

Nedaplatin-based postoperative CCRT is an effective and well-tolerated regimen for both early-stage and advanced-stage cervical cancer patients.

     

Positive effect of high RKIP expression on reduced distant metastasis by chemotherapy when combined with radiotherapy in locoregionally advanced nasopharyngeal carcinoma: a prospective study

The purpose of this prospective study is to investigate the predictive and prognostic significance of the Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC). Immunohistochemical assays were performed to detect the RKIP protein expression of samples from 212 patients with locoregionally advanced NPC. All patients were assigned randomly into the inductive chemotherapy plus radiation therapy (IC + RT) group, the concurrent chemoradiotherapy (CCRT) group, the inductive chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) group, and the radiation therapy alone (RT) group. The patients in the IC + RT group were treated with IC using 2?C3 cycles of cisplatin (80 mg/m²) and fluorouracil (500 mg/m²), repeated every 3 weeks, followed by radiotherapy. Those in the CCRT group were treated with weekly cisplatin (40 mg/m²) for 6?C7 cycles during radiotherapy. In the IC + CCRT group, the chemotherapy prior to radiation was similar to the cisplatin?Cfluorouracil regimen in the IC + RT group, whereas it cisplatin regimen was identical to that in the CCRT group. The results show that RKIP is an independent prognostic factor for 5-year distant metastasis?Cfree survival (DMFS), overall survival (OS), and progression-free survival (PFS). Patients with high RKIP expression benefited more from reduced metastasis in the IC + RT and the IC + CCRT group, with improved OS and PFS in each treatment group compared with that among patients with low RKIP expression. In the high RKIP expression subgroup, chemotherapy combined with radiotherapy improved the DMFS when compared with the RT group, but this effect was not observed in the low RKIP expression subgroup. RKIP was predictive of distant metastasis with good sensitivity and specificity. Clinically, high RKIP expression inhibited distant metastasis in advanced NPC, and its detection might be used to predict distant metastasis with good sensitivity and specificity. The effect of chemotherapy on distant metastasis in combined chemoradiotherapy might be related to the RKIP expression level. Patients with high RKIP expression showed more improved OS and PFS than their low RKIP expression counterparts. Higher RKIP expression improves the DMFS of patients who receive inductive high-dose cisplatin-based chemoradiotherapy, with or without concurrent cisplatin. Low RKIP expression is also a predictive marker for cancer progression and metastasis, which could be used to stratify patients with high risk of metastasis and death.     

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.     

XRCC1 and XPD genetic polymorphisms and clinical outcomes of gastric cancer patients treated with oxaliplatin-based chemotherapy: a meta-analysis

This meta-analysis aimed to obtain a comprehensive and reliable assessment of the relationships between XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms and the clinical outcomes of gastric cancer (GC) patients treated with oxaliplatin-based chemotherapy. The PubMed, CINAHL, Web of Science, CISCOM, EBSCO, Google Scholar, Cochrane Library, and CBM databases were searched for relevant articles published before September 1, 2013 without language restrictions. Crude odd ratios (ORs) or hazard risk (HR) [95 % confidence intervals (CI)] were calculated. Twelve clinical cohort studies were assessed with a total 1,024 GC patients treated with oxaliplatin-based chemotherapy. Our meta-analysis findings revealed that GC patients with the GA?+?AA (A carrier) genotypes of XRCC1 Arg399Gln showed a lower effective clinical response (CR?+?PR) than those with the GG (A non-carrier) genotype (OR?=?0.41, 95 % CI 0.20～0.82, P?=?0.012). However, there was no statistically significant difference in effective clinical response between those with XPD AC?+?CC (C carrier) genotypes and CC (C non-carrier) genotype (OR?=?0.55, 95 % CI 0.28～1.07, P?=?0.076). Furthermore, the GA?+?AA genotypes of XRCC1 Arg399Gln was associated with a worse progression-free survival (PFS) and overall survival (OS) compared with the CC genotype (PFS, HR?=?1.90, 95 % CI 1.12～2.69, P?<?0.001; OS, HR?=?2.13, 95 % CI 0.79～3.47, P?=?0.002, respectively). No relationships were found between XPD Lys751Gln polymorphism and both PFS and OS (all P?>?0.05). No publication bias was detected in this meta-analysis. Results from the current meta-analysis indicate that XRCC1 Arg399Gln polymorphism may be associated with poor clinical outcomes in GC patients treated with oxaliplatin-based chemotherapy.     

Is there any predictor for clinical outcome in EGFR mutant NSCLC patients treated with EGFR TKIs?

Background

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have demonstrated some dramatic response rate and prolonged progression-free survival (PFS) in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, PFS and overall survival (OS) among those patients who were treated with EGFR TKIs are inconsistent and unpredictable. In this study, we evaluated predictors of clinical outcome in EGFR mutant NSCLC patients treated with EGFR TKIs.

Methods

A total of 148 patients who had metastatic or recurrent NSCLC with activating EGFR mutation treated with either erlotinib or gefitinib as a first-line (n = 10) and a second-line or more treatment (n = 138) were retrospectively reviewed.

Results

The median follow-up duration was 21.9 months (range, 1.1–62.5). The median PFS and OS for a total 148 patients were 10.6 months (95 % CI 9.0–12.2) and 21.8 months (95 % CI 18.5–25.1), respectively. The survival outcomes were similar between the first-line and second-line or more line of treatment of EGFR TKIs (P = 0.512 for PFS, P = 0.699 for OS). Although a high number of metastasis sites (3–6 vs. 1–2) were associated with shorter PFS and OS (median PFS 9.9 vs. 11.9 months, P = 0.019; median OS 16.4 vs. 22.2 months, P = 0.021, respectively) in univariate analysis, but not in multivariate analysis. According to the clinical and molecular markers by multivariate analysis, there were no significant differences in PFS. When PFS was dichotomized by median 11 months for 105 patients treated with EGFR TKIs as second-line therapy, no significant differences in any clinical or molecular features were found between longer PFS and shorter PFS groups.

Conclusions

Despite the inconsistencies in PFS among EGFR mutant patients treated with EGFR TKIs, no significant differences of clinical features were noted, thereby suggesting a need for more understanding of the heterogeneity of underlying biology.     

S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis

This study aimed to derive a more precise estimate of the prognostic significance of S-1-based therapy over S-1 monotherapy in patients with advanced gastric cancer (AGC), including overall survival (OS) time, progression-free survival (PFS) time, objective response rate (ORR), and adverse events (AEs). Studies stratifying OS, PFS, ORR, and AEs in AGC patients in an S-1-based therapy versus an S-1 monotherapy setting were eligible for analysis by systematic computerized PubMed, Embase and Cochrane Library searches. Data from these studies were pooled using STATA package version 11.0. Six studies that investigated outcomes in a total of 913 AGC cases, of which 443 (48.5 %) received S-1-based therapy and 470 (51.5 %) received S-1 monotherapy, were included in the meta-analysis. Median OS and median PFS were significantly prolonged in AGC patients receiving S-1-based therapy compared with those receiving S-1 monotherapy (hazard ratio [HR] 0.83, 95 % confidence interval [CI] 0.71–0.96, P?=?0.015, and HR 0.69, 95 % CI 0.60–0.80, P?=?0.000, respectively). The ORR favored patients with S-1-based therapy (OR 1.65, 95 % CI 1.34–2.06, P?=?0.000). Higher incidence of grade 3/4 neutropenia was found in patients with S-1-based therapy (P?=?0.000). For the Asian population, S-1-based therapy significantly improved OS and PFS and enhanced ORR in comparison to S-1 monotherapy. The safety profile was poorer in patients with S-1-based therapy, but could be considerable between the S-1-based therapy and S-1 monotherapy group. Our conclusion needs to be confirmed via high-quality trials and the results need to be reproduced in other regions and populations.     

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.     

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。     

Three prognostic factors influence clinical outcomes of primary testicular lymphoma

The standard treatment of primary testicular lymphoma (PTL) has not been well established. Our study aimed to evaluate the relationship between the prognostic factors and clinical outcomes of PTL. We retrospectively reviewed the clinical records of 43 PTL patients and included the 39 patients who were diagnosed with primary testicular diffuse large B cell lymphoma (DLBCL) for analysis of prognostic factors and assessment of treatment modalities. Cox regression analysis showed that poor ECOG performance status (PS, ≥2), infiltration of adjacent tissues (spermatic cord, epididymis, or scrotum), and bulky disease (tumor mass, >9 cm) were independent predictors of worse overall survival (OS) for primary testicular DLBCL. According to these three factors, the patients were divided into two groups. Rituximab was found to significantly prolong progression-free survival (PFS) in the low-risk group (P?=?0.044) but not in the high-risk group (P?=?0.748). And the combination therapy for CNS prophylaxis significantly prolonged the survival in the high-risk group (P?=?0.005 for OS; P?=?0.004 for PFS), but not in the low-risk group (P?=?0.092 for OS; P?=?0.191 for PFS). ECOG performance status, infiltration of adjacent tissues, and bulky disease are practical prognostic factors of survival in patients with primary testicular DLBCL. The addition of rituximab is more important for the patients without the prognostics factors, and the combination CNS prophylaxis is more significant for the patients with the prognostics factors.     

The efficacy of bevacizumab plus paclitaxel as first-line treatment for HER2-negative metastatic breast cancer: a meta-analysis of randomized controlled trials

Although both bevacizumab and paclitaxel significantly improve the efficacy of chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative patients with metastatic breast cancer (MBC), little have changed with overall survival rates when they have been used alone or combined with other chemotherapy. Thus, a meta-analysis was conducted to evaluate the efficacy of bevacizumab combined with paclitaxel in HER2-negative MBC patients. Pubmed and Embase were systematically reviewed for studies published up to September 2013 in which bevacizumab plus paclitaxel were compared with other chemotherapy. Primary outcomes comprised overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Eight phase II/III clinical trials met the inclusion criteria, with a total of 3,758 patients. The pooled results showed that combination of bevacizumab and paclitaxel significantly improved the PFS (HR?=?0.63, 95 % CI, 0.55–0.73, P?=?0.011), ORR (RR?=?1.28, 95 % CI, 0.96–1.70, P?=?0.0), but had no effect on OS (HR?=?0.91, 95 % CI, 0.81–1.01, P?=?0.855). The meta-analysis confirms the benefits of bevacizumab–paclitaxel combination therapy in HER2 negative metastatic breast cancer, with an improvement in both progression free survival and objective response rate. However, no significant OS benefit was observed.     

The use of neoadjuvant platinum-based chemotherapy in locally advanced breast cancer that is triple negative: retrospective analysis of 144 patients

Triple-negative breast cancers comprise about 20 % of breast cancers. They have poor prognosis and have no standard therapy. The aim of this study was to evaluate pathologic complete response (pCR), progression-free survival (PFS), and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based chemotherapy. This is a retrospective study of one hundred and forty-four women with TNBC treated with neoadjuvant platinum-containing chemotherapy for locally advanced breast cancer at the University of Miami between January 1, 1999, and January 1, 2011. The medical record was reviewed to obtain data on clinical characteristics, including ethnicity, race, age, clinical stage, treatment regimen, and vital status. This study was approved by the University of Miami IRB. All patients had locally advanced breast cancer with at least one of the following features at presentation: T3, T4, N2, and N3. The mean tumor size by palpation was 9.4 cm. The clinical T-stage at presentation was 1.4 % T1, 8.3 % T2, 52.8 % T3, and 37.5 % T4 (19.4 % T4d). The nodal status by physical exam at presentation was 23 % N0, 37.5 % N1, 34 % N2, and 5.5 % N3. pCR in breast and axilla was seen in 31 %. PFS and OS were 55 and 59 %, respectively, at 7 years. Cisplatin offered a survival advantage over carboplatin in both PFS (P = 0.007) and OS (P = 0.018). Node positivity was the most important predictor of survival. Cisplatin/docetaxel neoadjuvant therapy was well tolerated and an effective therapy in locally advanced TNB.