Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA–N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy

This prospective, randomized, phase III trial shows that prophylactic cranial irradiation prolongs disease-free survival, decreases the rate of cerebral metastases and does not affect quality-of-life for patients with fully resected postoperative pathologically confirmed stage IIIA-N2 non-small-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.BackgroundThis study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA–N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy.Patients and methodsIn this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life.ResultsThis trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46–0.98;P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14–0.57;P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56–1.16;P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild.ConclusionIn patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.     

术后放疗在Ⅲ(pN2)期EGFR基因野生型肺腺癌辅助化疗患者中价值

目的:探讨Ⅲ(pN 2)期表皮生长因子受体(EGFR)基因野生型肺腺癌完全切除并辅助化疗患者术后放疗(PORT)的价值及预后影响因素。 方法:回顾性分析2009—2016年间郑州大学附属肿瘤医院完全切除的Ⅲ(pN 2)期EGFR基因野生型肺腺癌患者172例,均接受>4个周期含铂两药联合...     

Postoperative Chemotherapy Use and Outcomes From ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR-Mutated NSCLC

IntroductionAdjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA.MethodsPatients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB–IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage.ResultsOverall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10–0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13–0.40), regardless of disease stage.ConclusionsThese findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy.     

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma

Objective:No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma (ESCC).This is a study to explore the effect of postoperative paclitaxel (PTX) and cisplatin (DDP) in lymph node-positive,completely resected thoracic ESCC patients.Methods:We conducted a prospective phase Ⅱ trial.Patents had pathologically node-positive thoracic ESCC with negative margins.Outcomes of disease-free survival (DFS) and overall survival (OS) were compared with a matched historical control cohort.The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d.Results:Forty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy.The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time.Of the 43 patients with adjuvant chemotherapy,37 (86.0％) patients completed 4 to 6 cycles of chemotherapy.The 3-year DFS rates were 56.3％ in the adjuvant group and 34.6％ in the control group (P=0.006).The 3-year OS rates were 55.0％ in the adjuvant group and 37.5％ in the control group (P=0.013).Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS (P=0.005).Conclusions:Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive,curatively resected thoracic ESCC patients.These conclusions warrant further study in randomized phase Ⅲ clinical trials.     

Ⅲ期结直肠癌术后经肝动脉灌注联合静脉辅助化疗的临床观察

  目的  通过与静脉辅助化疗对照, 观察经肝动脉灌注联合静脉辅助化疗对Ⅲ期结直肠癌术后肝转移、无病生存期及总生存期的影响。   方法  2002年1月至2006年3月, 21例Ⅲ期结直肠癌患者作为治疗组, 术后给予肝动脉灌注FUDR联合静脉应用草酸铂化疗, 同期对照21例Ⅲ期结直肠癌患者, 术后给予草酸铂联合CF/5-FU静脉化疗。主要观察终点为肝转移率及DFS, 次要终点为OS和用药安全性。   结果  中位随访65(9~119)个月, 治疗组肝转移发生率较低(9.5%vs.28.6%, P=0.109), 肺转移发生率略高(28.6%vs.14.3%, P=0.256)。2组5年DFS(38.1%vs.42.9%, P=0.671)及OS(47.9%vs.45.0%, P=0.784)无统计学差异。化疗副反应多为Ⅰ~Ⅱ度血白细胞减少、恶心呕吐及感觉神经障碍。   结论  Ⅲ期结直肠癌术后给予经肝动脉联合静脉系统化疗, 与静脉化疗相比, 可能会降低肝转移的发生率, DFS及OS无统计学差异, 化疗副反应较轻, 可耐受。      

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01).This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.     

Feasibility and anti-tumor activity of postoperative adjuvant chemotherapy with gemcitabine for resected pancreatic cancer

The feasibility and anti-tumor activity of gemcitabine (GEM) as postoperative adjuvant chemotherapy were evaluated retrospectively. Between September 1998 and June 2007, patients with resected invasive pancreatic cancer (stage III, IVa, IVb) were given adjuvant chemotherapy with GEM (GEM group, n=10) or did not receive chemotherapy (n=11). Started the administration of GEM 38.5 days after surgery, and the mean duration was 15.4 months. Grade 3 or 4 adverse event was not observed in the GEM group. There was a significant difference in overall survival between the GEM group and the no-chemotherapy group (p=0.037), but there was no significant difference in disease-free survival between the two groups. Adjuvant chemotherapy with GEM was feasible and showed a benefit in patients with invasive pancreatic cancer.     

Prognostic Factors for Lymph Node Negative Stage I and IIA Non-small Cell Lung Cancer: Multicenter Experiences

Background: Surgery is the only curative treatment for operable non-small lung cancer (NSCLC) and theimportance of adjuvant chemotherapy for stage IB patients is unclear. Herein, we evaluated prognostic factorsfor survival and factors related with adjuvant treatment decisions for stage I and IIA NSCLC patients withoutlymph node metastasis. Materials and Methods: We retrospectively analyzed 302 patients who had undergonecurative surgery for prognostic factors regarding survival and clinicopathological factors related to adjuvantchemotherapy. Results: Nearly 90% of the patients underwent lobectomy or pneumonectomy with mediastinallymph node resection. For the others, wedge resection were performed. The patients were diagnosed as stageIA in 35%, IB in 49% and IIA in 17%. Histopathological type (p=0.02), tumor diameter (p=0.01) and stage(p<0.001) were found to be related to adjuvant chemotherapy decisions, while operation type, lypmhovascularinvasion (LVI), grade and the presence of recurrence were important factors in predicting overall survival (OS),and operation type, tumor size greater than 4 cm, T stage, LVI, and visceral pleural invasion were related withdisease free survival (DFS). Multivariate analysis showed operation type (p<0.001, hazard ratio (HR):1.91) andthe presence of recurrence (p<0.001, HR:0.007) were independent prognostic factors for OS, as well visceralpleural invasion (p=0.01, HR:0.57) and LVI (p=0.004, HR:0.57) for DFS. Conclusions: Although adjuvantchemotherapy is standard for early stage lymph node positive NSCLC, it has less clear importance in stage Iand IIA patients without lymph node metastasis.     

Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial

BACKGROUND: Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer (NSCLC) is not known. We aimed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC. METHODS: 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were randomly assigned to observation (n=433) or to 30 mg/m(2) vinorelbine plus 100 mg/m(2) cisplatin (n=407). Postoperative radiotherapy was not mandatory and was undertaken according to every centre's policy. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN95053737. FINDINGS: 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment. 301 (36%) patients had stage IB disease, 203 (24%) had stage II disease, and 325 (39%) had stage IIIA disease. Tolerance to chemotherapy mainly included neutropenia in 335 (92%) patients and febrile neutropenia in 34 (9%); seven (2%) toxic deaths were also recorded. Compliance was greater with cisplatin than with vinorelbine (median dose intensity 89% [range 17-108] vs 59% [17-100]). After a median follow-up of 76 months (range 43-116), median survival was 65.7 months (95% CI 47.9-88.5) in the chemotherapy group and 43.7 (35.7-52.3) months in the observation group. Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls (hazard ratio 0.80 [95% CI 0.66-0.96]; p=0.017). Overall survival at 5 years with chemotherapy improved by 8.6%, which was maintained at 7 years (8.4%). INTERPRETATION: Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC, better defining indication of adjuvant chemotherapy.     

Ⅱ期结肠癌根治术后奥沙利铂联合氟尿嘧啶类药物辅助化疗疗效和获益人群分析

  目的  对Ⅱ期结肠癌根治术后接受奥沙利铂联合氟尿嘧啶类药物辅助化疗疗效进行评价, 并对临床获益人群进行探索性分析。  方法  对中国医学科学院肿瘤医院2005年1月至2008年12月接受结肠癌根治术、术后分期为Ⅱ期患者回顾性分析, 比较单纯手术和术后奥沙利铂联合氟尿嘧啶类药物辅助化疗的无瘤生存率(Disease-Free Survive, DFS)和总生存率(Overall Sur vival, OS)差异。采用Kaplan-Merier进行生存分析, Log-rank检验进行组间差异比较, 亚组分析采用Cox风险比例模型。  结果  全组患者中位年龄62岁, 单纯手术患者111例, 术后采用奥沙利铂联合5-氟尿嘧啶(5-FU)或其衍生物的方案辅助治疗155例。全部患者中位随访时间为59(16~87)个月。单纯手术组和术后辅助治疗组5年无瘤生存率为86.5%和90.2%(HR=0.596, 95%CI: 0.295~1.208, P=0.152), 5年生存率分别为88.3%和92.9%(HR=0.576, 95%CI: 0.248~1.338, P=0.199), 两组间差异无统计学意义。亚组分析显示: T₄、低分化(包括印戒细胞癌)腺癌、具有2个及以上高危因素(高危因素包括肠梗阻穿孔、淋巴结清扫少于12枚、脉管瘤栓、神经侵犯)、CEA > 5ng/mL患者术后辅助治疗能明显提高无瘤生存(P均 < 0.05)。  结论  部分Ⅱ期结肠癌患者, 包括肿瘤浸润程度为T₄、低分化腺癌、具有2个及以上高危因素、术前CEA > 5 ng/mL可能从术后奥沙利铂联合氟尿嘧啶治疗中获益。      

The Rationale for Adjuvant Chemotherapy in Stage I Non-small Cell Lung Cancer

The past decade has witnessed renewed interest in studies exploring the benefits of adjuvant (postoperative) chemotherapy (± radiation therapy) in patients with resected non-small cell lung cancer (NSCLC). Recently completed adjuvant trials have included a heterogeneous group of patients with resected stages I to IIIA NSCLC. With rare exception, the published results of these studies indicate adjuvant chemotherapy imparts a significant overall survival advantage. Subset analyses suggest survival benefit occurs primarily in patients with resected stage II or IIIA and is less likely to occur in stage I patients. This apparent lack of survival benefit in stage I patients was seemingly validated in a prospective trial conducted by the Cancer and Leukemia Group B in which stage IB patients were randomized to observation or adjuvant carboplatin and paclitaxel. Survival at 5 -years was identical in the two arms of this trial. By contrast, two contemporary postoperative chemotherapy trials also conducted exclusively in stage I NSCLC patients yielded positive survival results. The divergent outcome of the prospective trials along with the negative subset analyses has created uncertainty as to the utility of postoperative adjuvant chemotherapy in stage I NSCLC. Herein we review the data underlying this controversy and offer a proposed algorithm to aid the clinician in selecting patients whom we believe may benefit from adjuvant chemotherapy. The treatment algorithm is based on currently available tumor- and host-related factors that affect prognosis.     

An individual patient data meta-analysis of adjuvant therapy with uracil-tegafur (UFT) in patients with curatively resected rectal cancer

Uracil-Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70-0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63-0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer.     

Patterns of failure in a randomized trial of adjuvant chemotherapy in postmenopausal patients with early breast cancer treated with tamoxifen.

BACKGROUND: We studied the effect of adjuvant anthracycline-based chemotherapy in postmenopausal patients with resected early breast cancer treated with adjuvant tamoxifen. PATIENTS AND METHODS: The trial included 835 patients with either axillary lymph node involvement, or tumors with histological grade II or III. They were randomized after local surgery to receive either tamoxifen (TAM group) or tamoxifen plus chemotherapy (TAM-CT group) consisting of six courses of 5-fluorouracil, doxorubicin and cyclophosphamide (FAC), or 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC). Radiotherapy was given after completion of adjuvant chemotherapy in the TAM-CT group and after surgery in the TAM group. RESULTS: The 5-year disease-free survival (DFS) rates were 73% in the TAM group and 79% in the TAM-CT group (log-rank test, P = 0.06). The 5-year overall survival rates were 82% and 87%, respectively (P = 0.06). The 5-year distant metastasis rates were 22% and 16% (P = 0.02), and the 5-year local recurrence rates were 6% and 4%, respectively (P = 0.23). There were no significant differences for contralateral breast cancer or other new primary malignancies. Chemotherapy tended to be more effective for patients who had tumors without estrogen receptors (trend test, P = 0.05). CONCLUSIONS: Anthracycline-based chemotherapy administered to postmenopausal patients receiving adjuvant tamoxifen gave a borderline significant benefit on overall and DFS, mainly by a reduction in distant metastases. Delaying radiotherapy after six courses of chemotherapy did not affect local control after up to 10 years of follow-up.     

Ⅲb及Ⅲc期结肠癌辅助化疗后行卡培他滨巩固化疗的临床研究

目的研究一组Ⅲb及Ⅲc期结肠癌术后患者,在辅助化疗后继续行卡培他滨巩固化疗,观察对无病生存率的影响。方法对入组的2005年6月至2008年9月我院收治的22例Ⅲb及Ⅲc结肠癌术后患者,行常规6个月辅助化疗,休息3～6个月之后给予6个周期卡培他滨口服巩固化疗,观察无病生存率及巩固化疗期间的相关不良反应,无病生存率的计算采用Life Tables分析法。结果使用卡培他滨作为Ⅲb及Ⅲc期结肠癌术后巩固化疗十分安全,初步观察复发转移率较低,无病生存率较高,不良反应轻微。结论Ⅲb及Ⅲc结肠癌术后患者接受卡培他滨巩固化疗可能改善无病生存率,值得进一步行大规模的临床研究。     

Stage IA non-small cell lung cancer: vessel invasion is a poor prognostic factor and a new target of adjuvant chemotherapy

This study reports the efficacy of adjuvant chemotherapy in stage IA non-small cell lung cancer (NSCLC) with vessel invasion (Vi). We sub-divided 322 patients with surgically resected pathological stage IA NSCLC into two groups according to Vi [non-Vi (n=237) and Vi (n=85)]. Both groups were compared with regard to age, gender, performance status, smoking habits, serum carcinoembryonic antigen level, extent of surgery, tumour size, histopathology, recurrence sites, and survival. The overall 5-year survival rates of non-Vi and Vi groups were 89.6% and 71.8% (P<0.001), respectively. Distant metastasis was observed more frequently in the Vi group (P<0.001, risk ratio: 9.06). Univariate and multivariable analyses identified poor performance status, squamous cell carcinoma, tumour size>or=15 mm and Vi as poor prognostic factors (P<0.05). The overall 5-year survival rate of stage IA Vi group nearly overlapped with that of patients with stage IB NSCLC. Retrospectively, oral uracil-tegafur chemotherapy increased the overall 5-year survival rate of stage IA Vi group by more than 25% (P=0.036). In conclusion, vessel invasion is a poor prognostic factor in patients with stage IA NSCLC. Prognosis of patients with Vi-stage IA NSCLC is similar to that of patients with stage IB NSCLC and is improved significantly by postoperative oral uracil-tegafur chemotherapy. Our preliminary study suggests that stage IA Vi group benefits from adjuvant chemotherapy.     

早期小细胞肺癌术后胸内放射治疗预后价值的Meta分析

目的:通过Meta分析探究术后辅助化疗联合胸内照射对于早期小细胞肺癌（small cell lung cancer,SCLC）的预后价值。方法:采用主题词和关键词相结合的检索方法,检索Pubmed、Embase、Cochrane Library、Web of Science、中国生物医学文献数据库、万方数据库和中国知网数据库从建库至2020年08月20日发表的比较SCLC术后辅助胸内放疗的文献。主要研究终点为总生存时间（overall survival,OS）,次要研究终点为无病生存时间（disease-free survival,DFS）;是否术后胸内照射同OS、DFS的相关性通过风险比(hazard ratio,HR)表达。文献质量评估采用纽卡斯尔-渥太华量表（Newcastle-Ottawa scale,NOS)文献质量评分;异质性检验采用Q检验和I2统计量,并通过亚组分析、敏感性分析以及Meta回归分析用来探讨异质性来源。发表偏倚评价采用剪补漏斗图。软件采用R语言 4.0.0版本meta包。结果:共纳入5篇文献,3 907例患者。Meta分析结果显示,早期SCLC患者术后接受辅助化疗联合术后胸内照射同单纯辅助化疗相比,在OS上差异无统计学意义（HR=0.99,95%CI:0.88~1.11）;但亚组分析中术后淋巴结阳性的患者OS可能获益,N1患者为（HR=0.73,95%CI:0.59~0.91）,N2患者为（HR=0.60,95%CI:0.49~0.74）。此外,DFS存在获益（HR=0.277,95%CI:0.160~0.480）。结论:术后胸内照射治疗不能改善早期SCLC患者的OS,但亚组分析中可以延长术后淋巴结阳性患者的OS;而且无论术后淋巴结状态,胸内照射都可以延长DFS。     

可手术的乳腺癌术前化疗的远期效果

目的探讨术前化疗对可手术的乳腺癌的远期疗效。方法可手术的乳腺癌患者５３７例,分为两组：术前化疗组（Ａ组）２５３例;术后辅助化疗组（Ｂ组）２８４例。Ａ组术前联合化疗,每周一次共４次,休２周行根治性手术。两组患者术后两周内开始化疗、化疗方案和完成化疗周期相同。结果（１）Ⅲ期患者,Ａ组５年总生存率（ＯＳ）５９％,无病存活率（ＤＦＳ）５４．９％,均明显高于Ｂ组２８．３％和２０．８％（Ｐ＜０．０５）。（２）Ⅱ期患者,Ａ组８年ＯＳ８１．４％,ＤＦＳ７６．３％,均高于Ｂ组６７．４％和６２．９％（Ｐ＜０．０５）。Ⅲ期患者,Ａ组８年ＯＳ４６．９％,ＤＦＳ４０．６％,也高于Ｂ组２０．７％和１３．３％（Ｐ＜０．０５）。（３）Ａ组Ｔ３、Ｔ４和转移淋巴结数≥４个的患者,５年、８年生存率均高于Ｂ组（Ｐ＜０．０５）。结论可手术的Ⅲ期乳腺癌,术前化疗可提高患者５年、８年生存率,明显改善Ⅱ期患者的远期疗效。     

A randomized phase II trial of adjuvant chemotherapy with uracil/tegafur and gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer

BACKGROUND: There have been few randomized studies of adjuvant chemotherapy using gemcitabine (GEM) in patients with resected pancreatic cancer. METHODS: Patients with invasive ductal pancreatic cancer who underwent radical surgery were enrolled and assigned to receive uracil/tegafur (UFT) and GEM together (GU) or GEM alone (G). GEM was administrated at a dosage of 1 g/m(2) intravenously weekly 3 of 4 weeks and UFT at a dosage of 200 mg/day orally continuously. Eligibility included resection status 0 or 1, and no previous chemo- or/and radiation therapy. The primary endpoint was disease-free survival (DFS), and secondary endpoints included overall survival (OS) and toxicity. RESULTS: Between 2002 and 2005, 100 patients were randomized into the 2 arms of the trial (50 patients to GU and 50 to G). One patient in the G group was found to be ineligible. Baseline characteristics were well balanced between the 2 groups. With a median observation period of 21 months, the 1- and 3-year DFS rates were 50.0% and 17.7% in the GU group and 49.0% and 21.6% in the G group, respectively. The median OS was 21.2 months in the GU group and 29.8 months in the G group. Toxicity was minor and acceptable, less than grade 4 in both groups. CONCLUSIONS: Postoperative GEM-based adjuvant chemotherapy was safe and well tolerated. However, addition of UFT with GEM did not improve DFS as compared with GEM alone. Further clinical trial resources for adjuvant chemotherapy should address other combinations and novel agents.     

DCR3 locus is a predictive marker for 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer

Adjuvant chemotherapy reduces the incidence of distant metastasis and increases survival of patients with colorectal cancer. However, predictive markers are needed to define subsets of patients with stage II and III disease that may benefit from adjuvant treatment. A secreted member of the TNF receptor superfamily, the decoy receptor 3 (DcR3), was reported to be amplified in colorectal cancer as a negative regulator of Fas-mediated apoptosis. We analyzed DcR3 gene copy number and protein expression in a large series of tumors from a randomized multicenter trial of 5-fluorouracil/mitomycin C (FU/MMC) adjuvant chemotherapy of the Swiss Group for Clinical Cancer Research (SAKK 40/81), using real-time quantitative PCR and immunohistochemistry on tumor microarrays. Results of gene status and protein expression of DcR3 were correlated with disease-free and overall survival of patients. We observed amplification of the DcR3 gene in 185/294 (63%) and overexpression of the DcR3 protein in 163/223 (73%) of colorectal tumors. Multivariate analysis showed no prognostic effect of DcR3 gene amplification and protein overexpression. However, adjuvant chemotherapy was significantly more beneficial in patients with normal DcR3 gene copy number than in patients with amplification (DFS: HR 2.84, 95% CI 1.16-6.98, p = 0.02; OS: HR 3.15, 95% CI 1.19-8.32, p = 0.02), whereas DcR3 protein overexpression did not influence the effect of adjuvant chemotherapy (DFS: HR 1.02, 95% CI 0.65-1.60, p = 0.95; OS: HR 0.95, 95% CI 0.61-1.49, p = 0.83). We conclude that amplification of the 20q13 locus is a predictive marker for adjuvant chemotherapy in colorectal cancer.     

Postoperative Adjuvant Systemic Therapy in Completely Resected Non–Small-Cell Lung Cancer: A Systematic Review

The purpose of the present review was to determine whether the use of postoperative adjuvant systemic therapy in patients with completely resected non–small-cell lung cancer (NSCLC) improves survival. Cancer Care Ontario's Program in Evidence-Based Care reviewed the evidence to update previously published recommendations for patients with completely resected NSCLC. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 2010 to 2016. All phase III randomized controlled trials (RCTs) and relevant systematic reviews were included. Data on overall survival (OS), disease-free survival, adverse events, and quality of life were extracted from each of the studies. Two relevant systematic reviews, 13 RCTs, and a series of pooled analyses by Lung Adjuvant Cisplatin Evaluation-Biomarker were included in the present review. Adjuvant chemotherapy statistically significantly improved OS for resected stage II-IIIA NSCLC and is recommended. For patients with stage IB NSCLC, no significant improvement was seen in OS; however, the results from subgroup analyses indicate that it would be reasonable to consider adjuvant chemotherapy for patients with larger tumors (≥ 4 cm). The present data do not support the use of adjuvant novel therapies (ie, epidermal growth factor receptor tyrosine kinase inhibitor, bevacizumab, and immunotherapy) either as an addition to, or instead of, cytotoxic chemotherapy. No predictive biomarkers are available to select patients more likely to benefit from adjuvant chemotherapy. Cytotoxic chemotherapy remains the standard of care as adjuvant therapy for patients with resected stage II-IIIA NSCLC. Additional clinical trials are needed to evaluate targeted agents in molecularly defined subgroups before these agents can be recommended in the adjuvant setting.