Combined 5-fluorouracil (5-FU) and radiation therapy following resection of locally advanced gastric carcinoma

Twenty-five patients with locally advanced but resectable adenocarcinoma of the stomach were given concomitant postoperative radiotherapy to the tumor bed and chemotherapy with 5-Fluorouracil (5-FU). Twenty-two of the patients had regional lymph node involvement and seven had residual tumor in the surgical margins. Radiotherapy was delivered to a total dose of 5,000 rads in 7 weeks with a two-week split. 5-FU was given daily the first 3 days of each treatment period and was then continued weekly for a minimum of 1 year. At a median follow-up time of 19 months, 11 patients have relapsed, two locally and nine distally, and all have died. Thirteen patients remain alive, all but one disease-free, for a median of 21 months from diagnosis. One additional patient died of unrelated causes, free of tumor. The actuarial median survival for the whole group stands at 33 months with a projected 5-year survival of 40%. Treatment has been well tolerated.     

Effect of concomitant use of pentoxifylline and alpha-tocopherol with radiotherapy on the clinical outcome of patients with stage IIIB non-small cell lung cancer

We evaluated the effects of pentoxifylline (PTX) and alpha-tocopherol on the clinical outcome of 66 patients with stage IIIB non-small cell lung cancer in a randomized clinical trial. All patients received 46 Gy of external radiotherapy to the primary tumor and regional lymph, nodes with an additional 14-Gy dose to the primary tumor. Thirty-three of the 66 patients also received PTX (400 mg, three times daily) and alpha-tocopherol (300 mg, twide daily) during radiotherapy, followed by 400 mg of PTX and 300 mg of alpha-tocopherol daily for 3 mo after radiotherapy. The remaining 33 patients (control group) received radiotherapy only. After a mean follow-up time of 12 mo, 18 patients remained alive. During follow-up, there were local recurrences in 14 patients and distant metastases in 18 patients. In patients who received PXT and alpha-tocopherol, 1- and 2-yr overall survival rates were 55% and 30%, respectively, and median survival was 18 mo. In control patients, 1- and 2-yr overall survival rates were 40% and 14%, respectively, with a median survival of 10 mo. These differences were statistically significant (p=0.0175). In patients who received PXT and alpha-tocopherol, progression-free survival rates for 1 and 2 yr were 48% and 23%, respectively; median survival was 12 mo. In the control group, the corresponding rates were 24% and 18%; median survival was 8 mo (p=0.0223). We conclude that the use of PTX and alpha-tocopherol combined with radiotherapy offers a possible survival advantage in this patient population.     

Meta‐analysis comparing higher and lower dose radiotherapy for palliation in locally advanced lung cancer

The purpose of this meta‐analysis was to compare higher dose (≥30 Gy) and lower dose (<30 Gy) radiotherapy (RT) on palliation of symptoms and survival in patients with locally advanced lung cancer. A search of PubMed and Google Scholar was conducted on 10 June 2013 using combinations of the search terms: radiotherapy, non‐small‐cell lung carcinoma, palliative, supportive, symptom relief. Inclusion criteria were: (i) palliative thoracic RT; (ii) randomized controlled trial; (iii) English language; and (iv) compared outcomes between higher dose (≥30 Gy) and lower dose (<30 Gy) RT. The primary outcome was palliation of symptoms (cough, chest pain, hemoptysis), and 1‐ and 2‐year overall survival. Tests of heterogeneity, sensitivity, and publication bias were performed. Five randomized controlled trials with a total of 1730 patients with lung cancer were included in the meta‐analysis. There were 925 patients treated with a higher RT dose (≥30 Gy) and 805 treated with a lower RT dose (<30 Gy). The combined odds ratios (ORs) indicated no significant difference in palliation of cough, chest pain, and hemoptysis between the higher dose and lower dose RT groups (combined ORs = 0.88, 1.83, 1.39, respectively). The 1‐ and 2‐year OS rates were similar between the high and low dose RT groups (combined ORs = 1.09 and 1.38, respectively). This meta‐analysis indicates that high dose (≥30 Gy) and lower dose (<30 Gy) RT provide similar symptom palliation and 1‐ and 2‐year OS in patients with locally advanced lung cancer.     

局部晚期非小细胞肺癌放射治疗现状

局部晚期非小细胞肺癌患者占全部非小细胞肺癌的 4 0 %以上 ,其主要治疗方法为以放化疗为主的综合治疗。探寻更为合理有效的放射治疗策略是局部晚期非小细胞肺癌临床研究和治疗所关注的焦点 ,其中包括剂量分割模式的变更、照射剂量的递增、适形调强放疗、联合放化疗等各个方面。     

图像引导大分割调强放疗同步化疗治疗局部晚期非小细胞肺癌患者的疗效分析

目的探讨图像引导大分割调强放疗同步化疗治疗局部晚期非小细胞肺癌(NSCLC)的疗效。方法根据治疗方法不同将90例局部晚期NSCLC患者分为对照组(n=48)和研究组(n=42),对照组患者行常规分割的三维适形放疗同步化疗治疗,研究组患者行图像引导大分割调强放疗同步化疗治疗。对两组患者的临床疗效、治疗前后血清肿瘤标志物[血管内皮生长因子(VEGF)、癌胚抗原(CEA)]水平、不良反应发生情况及生存情况进行比较。结果研究组患者的治疗总有效率高于对照组(P﹤0.05);治疗前,两组患者的血清VEGF、CEA水平比较,差异均无统计学意义(P﹥0.05);治疗后,两组患者的血清VEGF、CEA水平均低于本组治疗前(P﹤0.05);治疗后,研究组患者的血清VEGF、CEA水平均低于对照组(P﹤0.05)。两组患者的总不良反应发生率比较,差异无统计学意义(P﹥0.05);研究组患者的1年生存率高于对照组(P﹤0.05)。结论图像引导大分割调强放疗同步化疗治疗局部晚期NSCLC患者的临床疗效明确,可以在有效调节患者肿瘤标志物水平的同时提高患者的1年生存率,且未增加药物不良反应。     

不可手术的局部晚期非小细胞肺癌患者胸部放疗后脑转移特征及危险因素分析

目的 探讨不可手术的局部晚期非小细胞肺癌患者胸部放疗后脑转移特征及其危险因素.方法 选取经组织病理学检查或免疫组化检查证实的不可手术的局部晚期非小细胞肺癌患者72例.根据患者各项资料,分析不可手术的局部晚期非小细胞肺癌患者放疗后脑转移特征,使用多因素Logistic回归分析影响不可手术的局部晚期非小细胞肺癌患者放疗后脑转移的危险因素.结果 72例患者中,15例(20.83%)患者出现脑转移,其中腺癌14例,鳞癌1例;单纯脑转移2例,脑转移合并其他部位转移13例.患者出现脑转移的中位时间为8.5个月,1年、3年累积脑转移率分别为16.31%、29.94%.单因素分析结果显示:患者的年龄、吸烟史、CA125、NSE、CEA与局部晚期非小细胞肺癌患者胸部放疗后脑转移存在一定关系(P﹤0.05).多因素Logistic回归分析结果显示:年龄﹥60岁、有吸烟史、CA125升高、NSE升高、非鳞状细胞癌是影响局部晚期非小细胞肺癌患者胸部放疗后脑转移的危险因素.结论 年龄﹥60岁、有吸烟史、CA125升高、NSE升高、非鳞状细胞癌的局部晚期非小细胞肺癌患者胸部放疗后出现脑转移的危险性高.     

吉西他滨联合替吉奥序贯替吉奥同步放化疗与联合化疗治疗局部晚期胰腺癌比较观察

目的探讨吉西他滨联合替吉奥序贯替吉奥同步放化疗与联合化疗在局部晚期胰腺癌治疗中的临床疗效和安全性。方法 39例诊断明确且无法手术的局部晚期胰腺癌患者在2种综合治疗方式后的生存状况,分为A、B组,其中A组20例,B组19例,A组采用吉西他滨联合替吉奥诱导化疗后序贯同步放化疗,以替吉奥为同步化疗药物;B组采用吉西他滨与替吉奥联合化疗。采用有效率、疾病控制率、临床受益反应来评价近期疗效;远期随访以无进展生存期和总生存期为观察终点,并对药物的安全性进行评估。结果 A组可评估患者16例,B组15例。在完成周期治疗的患者中,A组有效率、疾病控制率均优于B组(分别为31.2%vs 26.7%,81.3%vs 73.3%),差异有统计学意义(P=0.015、0.047)。A组患者总的临床受益反应率高于B组(80.6%vs 72.4%),差异有统计学意义(P=0.035);A组的疼痛评分降低及疼痛改善持续时间明显优于B组,差异有统计学意义(P<0.05);2组体质量增加及KPS评分升高差异无统计学意义(P>0.05)。A组的中位无进展生存期和中位总生存期均略高于B组(5.8个月vs 4.9个月,16.1个月vs 15.3个月),但差异无统计学意义(P=0.423、0.348)。A组的1 a生存率(70.2%)略高于B组(67.9%),但差异无统计学意义(P=0.315)。在血液学毒性反应方面,A组发生率低于B组,差异有统计学意义(P<0.05);在胃肠道反应及肝、肾功能不全方面,A组与B组差异均无统计学意义(P均>0.05)。结论吉西他滨联合替吉奥序贯替吉奥同步放化疗较联合化疗在肿瘤局部控制及疼痛控制方面上更优,但2种综合治疗在提高患者的生存方面效果相近;2种综合治疗的毒副反应均可耐受,其中吉西他滨联合替吉奥序贯替吉奥同步放化疗较联合化疗的血液学毒性稍低。     

Neoadjuvant chemotherapy in cervical cancer: an update

The role of neoadjuvant chemotherapy (NACT) has been investigated in order to improve prognosis of patients with locally advanced cervical cancer. According to a meta-analysis, NACT followed by radiotherapy may be detrimental with a low dose of cisplatin and longer cycle intervals. Some meta-analyses showed NACT followed by surgery resulted in a reduction in the risk of death by 35% with a gain of 14% in the 5-year survival compared with radiotherapy. In a Cochrane meta-analysis, overall survival and progression-free survival were significantly improved with NACT followed by surgery versus surgery alone (23% reduction in the risk of death). The platinum/paclitaxel combination is now the preferred regimen in the neoadjuvant setting and preliminary data indicate that dose-dense regimens are feasible and effective (overall response rate: 67.8–87%). A weekly regimen with carboplatin/paclitaxel before chemoradiation showed promising results and the INTERLACE ongoing trial will help to confirm whether additional short-course chemotherapy given weekly before chemoradiation will lead to an improvement in overall survival.     

MVP化疗联合放疗对晚期肺腺癌的疗效分析

目的　探讨化疗联合放疗对晚期肺腺癌预后的影响。方法　选择 80例晚期肺腺癌 ,其中 45例采用MVP方案 (丝裂霉素、长春花碱酰胺、顺铂 )化疗 1～ 2周期后给予局部放疗 ,放疗的同时或结束后再行化疗 2～ 4周期 ;35例单纯采用MVP方案化疗 4～ 6周期。结果　放化组总缓解率为 6 6 7% ,中位生存期 19 1个月 ,其 1、2、3年生存率分别为 6 4 4%、33 3 %、15 5 %。单化组总缓解率为34 3 % ,中位生存期 9 2个月 ,其 1、2、3年生存率分别为 40 %、11 4%、0 %。放化组疗效优于单化组 (P <0 0 5 )。两组的毒副作用无统计学差异 (P >0 0 5 )。结论　MVP化疗联合放疗能改善晚期肺腺癌患者生存质量 ,延长生存期 ,提高生存率。     

Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study

From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m(-2) and mesna 750 mg m(-2) two times a day, cisplatin 25 mg m(-2) and etoposide 100 mg m(-2), all administered intravenously (i.v.) on days 1-3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3-4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3-34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1-54+). Median OS for the entire group was 12.5 months (range 2-57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series.     

Clinical prognostic factors in patients with locally advanced (stage III) nonsmall cell lung cancer treated with hyperfractionated radiation therapy with and without concurrent chemotherapy: single-Institution Experience in 600 Patients

BACKGROUND:

Influence of potential clinical prognostic factors on overall survival (OS), local progression‐free survival (PFS), and distant metastasis‐free survival (MFS) in patients with locally advanced nonsmall cell lung cancer treated with hyperfractionated radiation therapy (HFX RT) with or without concurrent chemotherapy was investigated.

METHODS:

Three phase 3 and 2 phase 2 studies have been designed and executed with a total of 600 patients. HFX RT alone was given in 127 and HFX RT‐chemotherapy was given in 473 patients. HFX RT doses were either 64.8 grays (Gy) or 69.6 Gy using 1.2 Gy twice daily, or 67.6 Gy using 1.3 Gy twice daily. Chemotherapy consisted of concurrent carboplatin and etoposide in 409 patients and concurrent carboplatin and paclitaxel in 64 patients. Sex, age, Karnofsky performance score (KPS), weight loss (>5%), stage, histology, interfraction interval, and treatment (the addition of concurrent chemotherapy) were investigated as potential prognostic factors.

RESULTS:

The median OS, median local PFS, and median distant MFS times were 19, 21, and 23 months, respectively. Five‐year OS, local PFS, and distant MFS rates were 19%, 29%, and 35%, respectively. Univariate and multivariate analysis showed that only age did not influence OS and local PFS, whereas female sex, lower KPS, less pronounced weight loss, lower stage, squamous histology, shorter interfraction interval, and treatment independently predicted better OS and local PFS. Only age and treatment did not influence distant MFS, whereas histology was of borderline significance.

CONCLUSIONS:

This study identified independent prognosticators of treatment outcome. These results may have implications for future studies in this disease. Cancer 2011. © 2011 American Cancer Society.     

局部晚期乳腺癌的治疗体会

目的：观察85例III期乳腺癌患者治疗的疗效,寻找提高疗效的策略。方法：2003年6月至2005年12月85例III期乳腺癌患者接受了外科手术治疗,根据是否接受新辅助化疗分为手术组（41例）和新辅助化疗组（44例）,比较两组的手术性质及治疗结果。结果：新辅助化疗组的无病生存期为59.1个月,明显高于手术组的43.1个月（P〈0.05）,新辅助化疗组的5年无病生存率为36.16%,手术组为34.14%（P〉0.05）。结论：局部晚期乳腺癌患者接受新辅助化疗后手术可提高无病生存时间,值得临床推广。     

A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

Background:

We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin before radical chemoradiation (CRT) and assessed the response rate to such a regimen.

Methods:

CxII is a single-arm phase II trial of 46 patients, with locally advanced cervical cancer (stage Ib2-IVa). Patients received dose-dense carboplatin (AUC2) and paclitaxel (80 mg m⁻²) weekly for six cycles followed by CRT (40 mg m⁻² of weekly cisplatin, 50.4 Gy, 28 fractions plus brachytherapy). The primary end point was response rate 12 weeks post-CRT.

Results:

Baseline characteristics were: median age at diagnosis 43 years; 72% squamous, 22% adenocarcinoma and 7% adenosquamous histologies; FIGO stage IB2 (11%), II (50%), III (33%), IV (7%). Complete or partial response rate was 70% (95% CI: 54–82) post-NACT and 85% (95% CI: 71–94) post-CRT. The median follow-up was 39.1 months. Overall and progression-free survivals at 3 years were 67% (95% CI: 51–79) and 68% (95% CI: 51–79), respectively. Grade 3/4 toxicities were 20% during NACT (11% haematological, 9% non-haematological) and 52% during CRT (haematological: 41%, non-haematological: 22%).

Conclusion:

A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT. This treatment regimen is feasible as evidenced by the acceptable toxicity of NACT and by the high compliance to radiotherapy (98%).     

Definitive chemoradiation in the management of locally advanced esophageal cancer

A significant number of patients diagnosed with esophageal cancer will present with locally advanced disease. The appropriate management of these patients continues to be a matter of significant debate. Over the past 2 decades, concurrent chemoradiation has been widely recognized as a viable option for a majority of these patients. Although there have been no randomized trials comparing definitive chemoradiation with surgical resection, there is little doubt that nonoperative therapy offers comparative opportunity for cure with less intendent morbidity and mortality. The broad applicability of this treatment option has led investigators to study methods of maximizing the therapeutic gain associated with the combination of external beam radiation and systemic chemotherapy. The long-term survival results have compared favorably with surgical series, thus leading to clinical trials designed to define the role of surgery in future management strategies. The early evaluation of these recent trials fails to identify any significant advantage associated with the routine use of surgery for most patients. Recent advances in drug development in conjunction with the identification of specific molecular targets has provided new opportunities to improve on the outcomes achieved with standard chemoradiation combinations.     

局部晚期乳腺癌的治疗进展

新辅助化疗后再手术和（或）放疗已成为治疗局部晚期乳腺癌的治疗模式。本文综述新辅助化疗的依据、疗程方案、影响疗效及预后相关因素及其优缺点，同时介绍了局部晚期乳腺癌诊断，局部治疗及内分泌治疗等方面的进展。     

47例局部晚期为主直肠癌放化疗临床分析

目的 探讨局部晚期为主直肠癌单纯放化疗疗效与预后因素分析。方法 回顾分析2003—2010年收治的47例放化疗为主的局部晚期直肠癌患者资料,其中3例单纯放疗。Kaplan-Meier法计算OS、PFS、DMFS并Logrank检验和单因素预后分析,Cox模型多因素预后分析。结果 全组3、5年OS率分别为53%和33%,PFS率分别为37%和31%。局部进展15例(32%),PFS期1~60个月(中位数14个月);远处转移23例(49%),DMFS期2~60个月(中位数17个月)。中剂量和高剂量放疗的3、5年局部进展率分别为54%和11%、57%和11%(P=0.004)。放化疗后pCR 9例(19%),其3、5年OS和PFS均8例。单因素分析显示肿瘤距肛门距离(P=0.026)和是否cCR (P=0.000)均是影响预后因素,但多因素分析仅cCR是影响生存的因素(HR=12.24,95%CI=1.64~91.29,P=0.015)。结论 因各种原因放弃手术治疗或未能行手术切除的局部晚期直肠癌,放化疗或单纯放疗是一种安全有效方法。高剂量放疗可提高直肠癌LC率,放化疗的获得CR预示良好的预后。     

环磷酰胺节拍化疗联合塞来昔布治疗晚期乳腺癌临床观察

目的观察环磷酰胺节拍化疗联合塞来昔布治疗晚期乳腺癌的疗效和安全性。方法 19例晚期乳腺癌患者均接受环磷酰胺节拍化疗联合塞来昔布治疗。结果 19例患者总有效率5.3%,疾病控制率（CR＋PR＋SD）57.9%。全组中位无病生存期5.2个月,1 a生存率47.4%。主要毒副反应为轻度骨髓抑制和胃肠道反应。结论环磷酰胺节拍化疗联合塞来昔布治疗晚期乳腺癌安全有效。