结直肠癌辅助治疗现状

结直肠癌是最常见恶性肿瘤之一,近年来国内外发病率逐年上升.尽管确诊时70%～80%的患者可以进行根治性手术切除,但总体的5年生存率仍只有50%～60%.约2/3接受过根治手术的患者会发生复发或远处转移,85%的复发转移发生在术后2年半之内,这些复发转移的发生可能与确诊时已存在微转移灶有关,而目前的检查手段还无法发现这种微转移.在无辅助化疗之前,Ⅲ期结直肠癌术后3年无病生存率(disease-free survival,DFS)约为44%～52%,而术后辅助治疗的目的在于预防根治性切除术后肿瘤的局部复发和远处转移,从而延长患者的生存时间.     

直肠癌围手术期的辅助治疗

直肠癌发病率和死亡率仍不断上升，而外科治疗效果近30年提高并不显著，加上患者多要求保肛，单靠手术难以进一步提高生存率和生活质量，只能谋求多学科综合治疗。现结合国内外有关文献，介绍直肠癌围手术期的辅助治疗，即术前放疗、术中放疗、术后放疗和术后放化疗；术后化疗和术中化疗。     

结直肠癌内科治疗进展

结直肠癌是最常见的恶性肿瘤之一.新的化疗药物和分子靶向药物的问世,使晚期结直肠癌病人中位生存期延长,根治术后的辅助治疗使Ⅲ期结肠癌病人复发和死亡风险进一步降低.本文综述结直肠癌内科治疗最新进展.     

结直肠癌的辅助和新辅助治疗

结直肠癌正成为我国常见的恶性肿瘤之一,尤其是在大中城市,由于人们生活水平的提高和膳食结构的改变,结直肠癌发病率的上升趋势更加明显。随着医学生物学技术的进展,虽然结直肠癌的手术、放疗和化疗有了长足的进步,但是,仍然有近半数的患者预后很差。影响结直肠癌患者预后的因素较多。主要有:(1)术后TNM分期:文献报道,按美国AJCC临床分期从Ⅰ期到Ⅳ期的患者,其5年生存率则从大于90%降至小于10%[1,2]。(2)病理和临床特性:如分化差、淋巴管受侵、神经受侵、T4的肿瘤、有肠梗阻或肠穿孔、或术前CEA较高等[3,4]。(3)肿瘤的分子特征:如结肠…     

结直肠癌化疗进展

在过去的20年中,无论是针对术后结直肠癌的辅助化疗或是转移性结直肠癌的化疗均取得了令人鼓舞的进展。在20世纪80年代末,仅有5-Fu一种化疗药物可选用,现在已经有了奥沙利铂、伊立替康、卡培他滨、贝伐单抗、西妥昔单抗等多种药物组成联合化疗方案供选择。通过目前的化疗方案治疗,75%的结直肠癌患者术后3年无复发,50%晚期结直肠癌患者生存期达2年。文章重点对化疗在辅助治疗与转移结直肠癌治疗中的作用进行了综述。     

结直肠癌肝转移新辅助治疗的研究进展

结直肠癌具有较高发病率和病死率,辅助化疗的效果差强人意,超过50%的患者病程中会出现肝转移.手术切除可延长患者生存时间,术后5年生存率在50%以上,但是仅小部分患者有手术切除的机会.新辅助治疗的应用降低肿瘤分期,提高结直肠癌肝转移患者手术切除率,展现出较大临床应用价值,但其对生存获益,目前尚无统一结论 .本文就结直肠癌肝转移新辅助治疗进展进行综述.     

直肠癌的新辅助治疗

为了保留肛门、减少复发、延长生存,新辅助化放疗已成为直肠癌治疗的重要组成部分.本文详细论述了直肠癌新辅助治疗的发展和现状.探讨了新辅助放疗、新辅助放化疗与单纯手术及辅助化放疗相比的优劣.     

结直肠癌根治术患者术后辅助化疗依从性的影响因素分析

目的 探讨结直肠癌根治术患者术后辅助化疗依从性的影响因素.方法 收集130例结直肠癌根治术患者的病历资料,分析患者术后辅助化疗依从性的影响因素.结果 客观性影响因素的单因素分析结果显示,不同年龄、性别、术后并发症、体重指数(BMI)、体表面积(BSA)结直肠癌根治术患者术后辅助化疗依从性比较,差异均有统计学意义(P﹤0.05);不同肿瘤位置、病理类型结直肠癌根治术患者术后辅助化疗依从性比较,差异均无统计学意义(P﹥0.05).进一步行多因素Logistic回归分析,结果显示,年龄≥65岁、女性、术后出现并发症、BMI﹤22 kg/m2、BSA﹤1.6 m2是影响结直肠癌根治术患者术后辅助化疗依从性的客观性独立危险因素(P﹤0.05).主观性影响因素的单因素分析结果显示,不同对生命的态度、家庭经济情况、病情保密、家庭支持、不良反应结直肠癌根治术患者术后辅助化疗依从性比较,差异均有统计学意义(P﹤0.05);就医困难结直肠癌根治术患者术后辅助化疗依从性比较,差异无统计学意义(P﹥0.05).进一步行多因素Logistic回归分析,结果显示,对生命绝望、家庭经济困难、不对病情保密、无家庭支持、无法耐受不良反应是影响术后辅助化疗依从性的主观性独立危险因素(P﹤0.05).接受化疗患者病死率为2.78％(2/72),低于拒绝化疗患者的12.07％(7/58),差异有统计学意义(χ2=4.303,P=0.038).结论 结直肠癌根治术患者术后辅助化疗依从性的主观性及客观性影响因素较多,临床医护人员可根据具体的影响因素采取有效的干预措施,从而提高患者术后辅助化疗治疗依从性,改善患者预后.     

直肠癌围手术期的辅助治疗

直肠癌发病率和死亡率仍不断上升,而外科治疗效果近30年提高并不显著,加上患者多要求保肛,单靠手术难以进一步提高生存率和生活质量,只能谋求多学科综合治疗.现结合国内外有关文献,介绍直肠癌围手术期的辅助治疗,即术前放疗、术中放疗、术后放疗和术后放化疗;术后化疗和术中化疗.     

乳癌术后辅助放化治疗对远期生存的影响

本文回顾总结我院内科１９７７至１９８７年收治９８例Ⅱ、Ⅲ期乳癌术后病人辅助化疗及辅助放化治疗的远期疗效，该组５、１０年生存率７１．４％与４２．９％，较同期手术组Ⅱ、Ⅲ期病人５、１０年生存率６６．４％与２９．６％提高。在Ⅱ期病人中辅助化疗组５、１０年生存率９４．１％与７３．５％明显高于Ⅱ期放化治疗组５、１０年生存率６９．６％与２６．１％。Ⅲ期病人辅助化疗组与辅助放化组生存率相近似。     

Adjuvant chemotherapy for non-small cell lung cancer

Nearly half of all patients who undergo surgical resection of localized non-small cell lung cancer (NSCLC) will develop and ultimately die of recurrent disease. The postoperative radiotherapy (PORT) meta-analysis showed adjuvant thoracic radiotherapy to have a detrimental effect on survival in this patient population. A meta-analysis of early trials of adjuvant chemotherapy by the Non-Small Cell Lung Cancer Collaborative Group showed that while chemotherapy with alkylating agents was also detrimental, chemotherapy with cisplatin-based adjuvant chemotherapy was associated with an improved hazard ratio for death (HR = 0.87), equating to a 5 percent survival benefit at 5 years. However, the result was not statistically significant (p = 0.08). Recently, results have been reported for several large Phase III trials of adjuvant chemotherapy which differed with respect to the stage of resected disease included, the type of chemotherapy used and the use of post-operative radiotherapy. Three trials (IALT, JBR 10, and ANITA) that utilized cisplatin-based doublets showed a significantly positive survival benefit of adjuvant chemotherapy in patients with Stage II-IIIA NSCLC. The magnitude of this benefit, which was suggested to be 4-5 percent at 5 years in the meta-analysis and by the IALT study, may be as large as 8-15 percent as indicated by more recent studies with modern platinum-based doublet chemotherapy. These data indicate that medically fit patients with resected Stage II-IIIA NSCLC should be offered adjuvant chemotherapy with a modern cisplatin-based doublet.     

Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial

Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m(-2)), doxorubicin (45 mg m(-2)), cyclophosphamide (600 mg m(-2)) every 28 days for five cycles, or external RT (45-50 Gy on a 5 days week(-1) schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66-1.36; P = 0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63-1.23; P = 0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited.     

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.     

胰腺癌:辅助治疗

Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%-15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation （with or without maintenance chemotherapy） has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level I evidence （from the ESPAC-1 trial） is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.     

Adjuvant therapy for Dukes C adenocarcinoma of colon

Forty-two patients with adenocarcinoma of the colon, who received surgery between 1975 and 1978 and were to found to have pericolonic fat infiltration and lymph node metastases, were analyzed for disease free period and overall survival. Twenty-one patients had received post-operative X ray therapy, and post-X ray therapy intravenous 5-Fluorouracil adjuvant therapy. Twenty-one patients, matched by age, sex, ethnic origin and site of disease were untreated. The 5 year survival rate for the treated group was 65% compared with 36% for the control group (P greater than 0.2). At 5 years 55% of the treated group were disease free but only 12% of the control group remained disease free (P = 0.04). The significance of this work needs to be established by a randomized and prospectively controlled clinical trial.     

Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis

Introduction: Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer.

Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer.

Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.     

Adjuvant chemoimmunotherapy following regional therapy for isolated recurrences of breast cancer (stage IV NED).

A combination of 5-fluorouracil, Adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in breast cancer patients following surgical excision and/or radiation of first site of recurrent disease. In a group of 68 patients treated with FAC-BCG, the estimated proportion remaining free of disease at 2 years from first recurrence was 69%, compared to 24% in 60 historical control patients (P less than 0.01). Estimated 2-year survival rate from first recurrence was 85% for the FAC-BCG patients and 78% for the controls (P = 0.07). This regimen has significantly prolonged the disease-free interval from the first recurrence, but additional follow-up is needed to determine its effect on long-term survival.     

Adjuvant therapy for colorectal carcinoma

Adjuvant therapy for colorectal carcinoma has been developed over the last two decades. We have reviewed the history of adjuvant chemotherapy for colorectal carcinoma in the United States, Europe and Japan with regard to the rationale of the chemotherapy regimen and the survival benefit for the establishment of a standard regimen. Treatment with 5-fluorouracil (5-FU) and leucovorin (LV) for postoperative adjuvant chemotherapy had an overall survival benefit, compared with surgery alone, in randomized controlled trials in the United States and Europe for Dukes' C colon carcinoma. In contrast, the survival benefit of adjuvant chemotherapy for Dukes' B colon carcinoma and for rectal carcinoma has not yet been established. In Japan, randomized controlled trials have examined combination treatment with mitomycin (MMC) and oral fluoropyrimidines for colorectal carcinoma compared with surgery alone. A meta-analysis indicated that combination treatment with MMC and oral fluoropyrimidines had a survival benefit for colorectal carcinoma. The survival benefit of combination treatment with irinotecan (CPT-11) + 5-FU + LV or uracil + tegaful (UFT) + LV (Orzel) for adjuvant chemotherapy are currently being compared with 5-FU + LV. Meta-analysis revealed a survival benefit at 2-years in the prevention of liver metastasis following intraportal or intraarterial infusion of 5-FU. The survival benefit of preoperative radiotherapy was superior to postoperative radiotherapy for advanced rectal carcinoma in association with the prevention of local recurrence. Clinical trial data suggest that the current standard regimen of adjuvant chemotherapy is a combination of 5-FU and LV for Dukes' C colon carcinoma and that radiotherapy for local control of rectal carcinoma has a survival benefit.     

Adjuvant therapy for high-risk endometrial cancer: recent evidence and future directions

Introduction: Although the majority of women with endometrial cancer have a favorable prognosis due to early symptoms, 15–20% have high-risk disease features and are at increased risk of recurrence. In order to improve prognosis for these patients, several trials have compared chemotherapy (CT), radiotherapy (RT) or the combination of CTRT.

Areas covered: This review focuses on the current evidence on adjuvant treatment for women with high-risk endometrial cancer and future perspectives.

Expert commentary: For stage I-II high-risk endometrial cancer, external beam radiotherapy ensured good local control and no significant benefit in progression-free or overall survival was found with the addition of chemotherapy in 2 recent randomized trials. For women with stage III disease, the combination of chemotherapy and radiotherapy improved progression-free survival with a non-significant improvement of overall survival. Adjuvant chemotherapy alone resulted in higher rates of pelvic and para-aortic recurrence. More toxicity and reduced quality of life were found during and after adjuvant CTRT. It is essential to discuss the benefits and disadvantages of chemotherapy and radiotherapy with individual patients for shared decision-making. Translational research is ongoing to further characterize individual tumors, identify sensitivity to (immuno)therapies and find new treatment targets to improve outcomes.