直肠癌的新辅助治疗

近年来,直肠癌发病率逐年上升,随着新辅助治疗的提出与应用,直肠癌的疗效得到提升,引起国内外学者的关注。新辅助治疗包括术前放疗、术前化疗和术前同步放化疗。其中术前放疗方式可分为短程放疗和常规放疗,通过比较T降期率、保肛率、完全缓解率等指标,对两种方式的临床效果进行了评价。尽管单纯术前化疗的经验还不够丰富,但其仍在降低肿瘤分期等方面具有优势。目前,临床应用最多的为术前同步放化疗,且国内外学者均认为该方式在治疗直肠癌时具有明显优势,同时,三维放疗技术可使靶区分布更为均匀,对病灶治疗更为精准。但直肠癌的新辅助治疗在国内却尚未广泛应用于临床,对其临床效果的确定仍需进一步的理论支持,本文就直肠癌的新辅助治疗做一综述。     

直肠癌新辅助放化疗研究进展

近年来,随着生活水平提高,饮食习惯改变等原因,我国直肠癌的发病率呈上升趋势。外科手术切除是直肠癌的最主要治疗手段,早期直肠癌通过单纯手术即可治愈。但多数直肠癌患者就诊时即为局部晚期,术后局部复发率高,治疗困难。新辅助     

直肠癌新辅助放疗研究进展

在过去的近40年里,直肠癌的治疗方案逐渐标准化。大多数早期直肠癌患者仅通过手术即可得到充分的治疗。然而,相当比例的直肠癌患者处于局部进展期,此类患者需要行新辅助治疗。直肠癌的新辅助放射治疗已被证明能有效地降低患者术前肿瘤分期、改善患者生存以及降低直肠癌局部复发率等,随之而来的是患者放疗后出现的不同程度的放疗不良反应,但随着放射治疗规范化、放射治疗技术及设备的改进,放疗不良反应严重程度在逐渐降低。本文就新辅助放疗中的放疗方案的选择、放射治疗技术、放疗不良反应、放疗后的手术时间以及放疗后的观察与等待等问题的最新研究进展进行了系统性的综述,从而为临床直肠癌新辅助治疗提供有力依据。     

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…     

直肠癌新辅助放化疗

根治性手术结合术后放、化疗一度被作为国际公认的Ⅱ及Ⅲ期直肠癌的标准疗法。近年,新辅助放化疗逐渐得到广泛的关注。大量研究表明,与术后放化疗相比,新辅助放化疗结合根治性手术的多模式联合治疗在降低直肠癌的局部复发率、延长生存时间等方面均显示出更好的效果,特别是在提高保肛率方面具有突出的优势。目前认为,新辅助放化疗适用于局部进展期(T3~4)或有系膜内淋巴结转移的低位直肠癌患者(Ⅱ~Ⅲ期)。随着先进的诊断技术、更优化的放疗模式,以及更多有效的药物及新配伍方案的引入,对直肠癌患者采取个体化的术前新辅助治疗,将使直肠癌的治疗效果得到进一步提高。     

直肠癌新辅助治疗进展

近年来新辅助治疗已成为局部晚期中低位直肠癌的标准治疗,目前常用的方案为长程同步放化疗与短程放疗。全新辅助治疗也是可行的新辅助治疗方案,临床完全缓解后等待观察的临床研究也在进行中。本文就直肠癌新辅助治疗的现状与研究进展进行综述。     

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。     

新辅助治疗——对直肠癌现有治疗模式的挑战?

近年来,新辅助治疗对于直肠癌的疗效得到进一步的肯定,已被公认为进展期直肠癌的标准治疗方法。一些研究甚至开始探讨新辅助治疗是否可以取代根治性手术成为主导治疗方式。放化疗后临床分期的准确度以及T分期与淋巴结阳性率的相关性这两个方面从理论上决定非根治性手术的可行性。尽管目前不乏新辅助治疗后不手术或行局部切除术结果满意的报告,但由于缺乏前瞻性研究,关于新辅助治疗在进展期直肠癌治疗中的地位仍存在争议。     

结直肠癌辅助治疗现状

在过去的20年结直肠癌辅助治疗有很大改进。辅助性放化疗已成为结直肠癌综合治疗的重要组成部分。本文综述了结直肠癌术后辅助化疗、术前、术后辅助放疗、免疫治疗、局部门静脉灌注化疗的现状。     

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.     

胃癌的新辅助治疗

胃癌的预后极差,其死亡率居于所有癌症的第二位。尽管手术切除肿瘤是首选治疗方案,但术后死亡率仍高达60％以上。为了提高治愈性（RO）切除率,降低术后死亡率,延长生存期,提高生活质量,各国医学工作者进行了大量的研究。本文将对近年来胃癌新辅助治疗进展作一综述。     

Intensified concurrent chemoradiotherapy with 5-fluorouracil and irinotecan as neoadjuvant treatment in patients with locally advanced rectal cancer

This study aimed to evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy intensified with irinotecan in patients with locally advanced rectal cancer. Eligible patients had nonmetastatic disease at a locally advanced stage that made R0 resection and sphincter preservation uncertain. They received preoperative radiation over 6 weeks to 45 Gy and boost of 5.4 Gy and concurrent continuous infusion 5-fluorouracil 250 mg m(-2) day(-1) and weekly irinotecan 40 mg m(-2). In all, 37 patients entered the study. T stage at baseline as determined by ultrasound was T2/T3/T4 in 2/19/16 patients; 31 patients had lymph node involvement. The predominant toxicity was diarrhoea (grade 3/4 in 10/2 patients). Haematologic toxicity and surgical complications were moderate. Among 36 patients undergoing surgery, 32 (89%) had R0 resection and 23 (64%) sphincter preservation. Pathologic complete response (pCR) was achieved in eight (22%) of 36 patients, and 10 patients (28%) had only microscopic residual disease. At 4 years, overall survival was 66%, disease-free survival 73%, local relapse rate 7%, and distant failure rate 24%. Extent of resection and postoperative nodal status were significant predictors of overall and disease-free survival. Intensified neoadjuvant chemoradiotherapy with irinotecan can be safely administered and results in a high pCR rate.     

直肠癌新辅助放化疗临床效果的评估

直肠癌是常见的恶性肿瘤,直肠癌发病率近年有上升趋势。全直肠系膜切除术（total mesorectal excision ,TME ）是直肠癌的最主要治疗手段,但局部进展期直肠癌患者术后局部复发率高、保肛率低,新辅助放化疗成为局部晚期直肠癌的优选治疗手段。直肠癌新辅助治疗后的临床效果是临床医生关注的焦点。直肠癌新辅助治疗效果的预测及评估关系到后续治疗方案的选择,影响患者的生存期及生活质量。     

局部晚期直肠癌术前调强放疗同步化疗的疗效评价及预后因素分析

目的:观察并分析术前调强放疗同步化疗治疗局部晚期直肠癌的病理降期情况、临床疗效和预后因素.方法:回顾性分析2010年1月1日至2013年7月31日间接受术前同步放化疗随后行根治性手术的60例初治Ⅱ、Ⅲ期直肠癌患者的临床资料.全部患者接受调强放射治疗,总剂量为50Gy/25次,同期行氟尿嘧啶为基础的化疗,放化疗结束后间隔4~8周行手术治疗.结果:肿瘤病理退缩分级(tumor regression grading,TRG)0级为8例、1级为 12例、2级 为11例、3级为 20例、4级即病理完全缓解(complete responce rate,pCR)为9例,pCR率为15%,病理有效率为86.7%,T分期降期55%,N分期降期51.9%.手术并发症发生率为25.0%.3年总生存率(OS)为88.3%,3年无瘤生存率(DFS)为85.5%,3年局部复发率(LRR)为11.6%,3年远处转移率(DMR)为13.3%,3年无局部复发生存率(LRFS)为88.3%,3年无远处转移生存率(DRFS)为 86.7%.Kaplan-Meier分析及COX回归分析均表明TRG分级对患者总生存期的影响具有统计学意义.结论:局部晚期直肠癌术前调强放疗同期化疗能使肿瘤降期,提高手术切除率和生存率,3年局部控制好.pCR 和接近pCR 患者有更好的生存期.     

Wait-and-see or radical surgery for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy: a cohort study

A wait-and-see policy might be considered instead of surgery for rectal cancer patients with no residual tumor or involved lymph nodes on imaging or endoscopy after neoadjuvant chemoradiotherapy (clinical complete response, cCR). In this cohort study, we compared the oncologic outcomes of rectal cancer patients with a cCR who were managed according to a wait-and-see policy (observation group) or with surgery (surgery group). In the observation group, follow-up was performed every 3 months for the first year and consisted of MRI, endoscopy with biopsy, computed tomography and transrectal ultrasonography. In the surgery group, patients received radical surgery. Long-term oncologic outcomes were estimated using Kaplan-Meier curves. Thirty patients were enrolled in the observation group (median follow-up, 60 months; range, 18-100 months), and 92 patients were enrolled in the surgery group (median follow-up, 58 months; range, 18-109 months). The 5-year disease free survival and overall survival rates were similar in the two groups: 90.0% vs. 94.3% (P = 0.932) and 100.0% vs. 95.6% (P = 0.912), respectively. We conclude that for rectal cancer patients with a cCR after neoadjuvant chemoradiotherapy, a wait-and-see policy with strict selection criteria, follow-up and salvage treatments achieves outcomes at least as good as radical surgery. Additionally, we declare that the pCR (pathologic complete regression) and non-pCR subgroups of patients with a cCR have similar long-term failure (local recurrence and/or distant metastasis) rate.     

Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study

The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients with rectal cancer. Conventional radiation was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 55.8 (50.4 + 5.4) Gy. Concurrently, irinotecan 40 mg m(-2) once weekly and capecitabine continuously at dose levels of 500, 650, 750 and 825 mg m(-2) twice daily were administered. Surgery was performed 4-6 weeks following completion of chemoradiation. A total of 28 patients (3 UICC II, 25 UICC III) were enrolled and all received treatment. Dose-limiting toxicity was diarrhoea grade IV and hand-foot syndrome at the 825 mg m(-2) dose level. The maximum tolerated dose of capecitabine was 750 mg m(-2). Diarrhoea was the most common toxicity: grade III in nine patients. Two patients died, one due to pneumonia and one due to sudden cardiac death. A complete response and only microfocal residual tumour disease was achieved in four and three patients (27%). In all, 25 of 28 patients undergoing surgery, 24 (96%) had R0 resection. Preoperative chemoradiation based on continuous daily capecitabine and weekly irinotecan appears to tolerated and effective in patients with rectal cancer.     

Prognostic role of EGFR gene copy number and KRAS mutation in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy

Background:

Epidermal growth factor receptor (EGFR), evaluated by immunohistochemistry, has been shown to have prognostic significance in patients with colorectal cancer. Gene copy number (GCN) of EGFR and KRAS status predict response and outcome in patients treated with anti-EGFR therapy, but their prognostic significance in colorectal cancer patients is still unclear.

Methods:

We have retrospectively reviewed the baseline EGFR GCN, KRAS status and clinical outcome of 146 locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiotherapy. Pathological response evaluated by Dworak''s tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS) were analysed.

Results:

Tumour regression grade 4 and TRG3–4 were achieved in 14.4 and 30.8% of the patients respectively. Twenty-nine (19.9%) and 33 patients (19.2%) had an EGFR/nuclei ratio >2.9 and CEP7 polisomy >50% respectively; 28 patients (19.2%) had a KRAS mutation. Neither EGFR GCN nor KRAS status was statistically correlated to TRG. 5-year DFS and OS were 63.3 and 71.5%, respectively, and no significant relation with EGFR GCN or KRAS status was found.

Conclusion:

Our data show that EGFR GCN and KRAS status are not prognostic factors in LARC treated with preoperative chemoradiation.