分子靶向药物在胃肠道肿瘤综合治疗中的应用

分子靶向药物在晚期胃肠道肿瘤治疗中,被证实可提高患者的客观缓解率并延长总生存期.因此,其在局部进展期胃肠道肿瘤综合治疗中的价值被逐渐重视.曲妥珠单抗用于HER-2基因阳性的局部进展期胃癌新辅助化疗中的临床研究正在进行中,结果值得期待.大量研究证明,西妥昔单抗联合化疗对于KRAS基因野生型潜在可切除的结直肠癌肝转移患者,能提高手术切除率并延长总生存期;而贝伐珠单抗在KRAS基因突变型结直肠癌肝转移术前转化治疗中的作用正在评估中.对于可切除的结直肠癌肝转移,虽现有的证据显示,分子靶向药物在新辅助治疗中未能带来长期生存益处,但最终结论仍存议甚多.对于局部进展期直肠癌患者,新辅助化疗中的西妥昔单抗在二期临床研究中未能显示治疗获益,贝伐珠单抗的作用同样需要在三期临床研究后进一步证实.与晚期肿瘤单一治疗模式不同,在肿瘤综合治疗中,需要系统评估分子靶向药物与细胞毒药物、手术以及放疗之间可能的相互影响及协同作用,制定出科学并适用于临床实践的综合治疗模式.     

跨越曲妥珠单抗时代乳腺癌靶向治疗策略

乳腺癌是一个复杂的异质性疾病。随着分子生物学技术的进步,乳腺癌靶向治疗进展很快。从1997年美国食品与药物管理局（FDA）批准抗HER?2的分子靶向治疗药物--曲妥珠单抗治疗晚期乳腺癌,开创了乳癌分子靶向治疗的时代。以后有多靶点药物拉帕替尼、血管表皮生长因子抑制剂贝伐单抗相继用于临床治疗。还有很多批准用于其他恶性肿瘤的靶向药物如吉非替尼、索拉非尼等也有一些II期研究显示了在乳腺癌治疗中的活性。另外,T?DM1等新药也在进行II/III期临床研究。     

胃癌靶向治疗及免疫治疗

近年来,随着对胃癌分子生物学特点的不断认识,分子靶向治疗成为综合治疗的新方向。曲妥珠单抗和雷莫卢单抗已被用于治疗晚期胃癌,其他靶向药物也在不断的研发中。免疫治疗是一种新治疗方法,尤其在黑色素瘤领域取得了很大的成功,许多胃癌免疫治疗的研究也在不断扩大和深入。     

胃肠道肿瘤的分子标志物与个体化治疗

胃肠道肿瘤是我国的常见恶性肿瘤．严重影响中国人的健康。随着肿瘤分子标志物研究的深入和新型抗肿瘤药物的开发应用,胃肠道肿瘤的治疗模式正在不断发生着变化．越来越多的分子靶向药物如曲妥珠单抗、西妥昔单抗和贝伐单抗等开始应用于临床。基于肿瘤分子分型制定适合患者的个体化治疗策略必将使更多的患者从治疗中获得益处,是未来胃肠道肿瘤治疗的必然趋势。     

进一步优化胃癌综合治疗的方案与措施

全球胃癌发病率呈逐渐下降趋势,但我国人口众多,每年新发胃癌人数仍极庞大.国内多家诊疗中心已建立了胃癌多学科诊疗团队,但在外科手术、化疗、放疗乃至生物靶向治疗等具体策略方面,仍有进一步优化的空间.目前的研究热点包括:合理应用各种技术做精确的术前分期、局部进展期胃癌的围手术期化疗、微创外科技术在各期胃癌中的应用价值、临床研究与基础科研的合理转化以及胃癌的个体化治疗等.中西方胃癌的生物学行为及各类分子事件存在差异,期待有更多源自东方的临床研究证据,充实我国胃癌治疗临床实践.     

免疫联合靶向治疗在晚期肝癌转化治疗中的研究进展

随着肝细胞癌(HCC)发病机制研究的深入,晚期肝癌已经进入到了多种方式、多种药物联合使用的综合治疗时代,尤其是免疫治疗、免疫联合抗血管靶向治疗以及肝动脉灌注化疗等降期转化治疗取得了显著的疗效,给晚期肝癌患者带来了希望。目前免疫联合靶向药物治疗晚期肝癌已经成为了国内外研究的热点之一,阿特利珠单抗联合贝伐珠单抗(T+A)方案更是作为一线治疗方案正式写入了多个指南之中。本文就免疫联合靶向治疗研究进展、适用人群、疗效监测方面进行讨论。     

免疫联合靶向治疗在晚期肝癌转化治疗中的研究进展

随着肝细胞癌(HCC)发病机制研究的深入,晚期肝癌已经进入到了多种方式、多种药物联合使用的综合治疗时代,尤其是免疫治疗、免疫联合抗血管靶向治疗以及肝动脉灌注化疗等降期转化治疗取得了显著的疗效,给晚期肝癌患者带来了希望。目前免疫联合靶向药物治疗晚期肝癌已经成为了国内外研究的热点之一,阿特利珠单抗联合贝伐珠单抗(T+A)方案更是作为一线治疗方案正式写入了多个指南之中。本文就免疫联合靶向治疗研究进展、适用人群、疗效监测方面进行讨论。     

进一步认识和提高进展期胃癌综合治疗的理念

胃癌是我国最常见的恶性肿瘤之一,其发病率和死亡率一直居高不下.目前,根治性手术仍然是治疗进展期胃癌的重要基石,但已非唯一手段.为进一步改善预后,需要外科医师重视和提高综合治疗的理念：必须强调开展准确的术前TNM分期,以选择恰当的治疗模式;在规范化手术的基础上合理运用化疗、放疗和分子生物靶向治疗等综合手段,以较小的代价换取最佳的肿瘤预后;对晚期转移性患者不轻言放弃,制定个体化治疗方案以延长生存期并提高生活质量.此外,应充分认识到胃癌的异质性,科学看待东西方人种胃癌生物学行为的差异,在治疗上加强多学科协作,以实现规范化和个体化相融的综合治疗模式,使患者获益.     

直肠癌的靶向药物治疗

近些年,在晚期结直肠癌中靶向治疗明显延长了患者生存期.但是这些大规模的临床研究数据主要来自以结肠癌为主的欧美人群.在我国,直肠癌发病率高,约占全部结直肠癌50％[1].并且由于直肠的特殊解剖结构,易出现局部复发和血行转移（如肺转移）.同时,直肠癌术式的选择也直接影响着患者长期生存的生活质量.因此直肠癌的治疗较结肠癌而言要更复杂,更需要在多学科指导下进行综合治疗.针对直肠癌如何合理地应用抗血管生成类的靶向药物（如贝伐珠单抗）和抗EGFR单抗类的靶向药物（如西妥昔单抗和帕尼单抗）,是我们临床实践需要关注的重点之一.     

抗体偶联药物治疗转移性尿路上皮癌的临床研究进展

抗体偶联药物(ADC)是目前新型肿瘤药物研发的热点, 同时具有抗体药物选择性强和化疗药物活性高的特点, 目前已在多种实体瘤中得到广泛应用。全球范围内已有3种ADC药物获批治疗尿路上皮癌, 包括恩诺单抗(Nectin-4抗体-MMAE偶联物)、戈沙妥珠单抗(Trop-2抗体-SN-38偶联物)和维迪西妥单抗(HER2抗体-MMAE偶联物), 显著改善了晚期患者的预后, 改变了尿路上皮癌的治疗模式。此外, 一些ADC药物与靶向治疗、免疫检查点抑制剂联合应用的临床研究也正在开展。本文总结近年来ADC药物应用于尿路上皮癌治疗的临床研究进展。     

重视循证研究进展 规范胃癌综合治疗

循证医学是临床医学的新模式,正不断改变着临床医师的理念和实践。虽然针对胃癌治疗的临床研究已很深入,并发挥了重要的作用,但是其结论并不相同,也各有其局限性。临床医师在治疗胃癌病人过程中,应合理运用循证依据,并结合病人自身情况,制定个体化治疗方案。     

胰腺癌综合治疗的现状

胰腺癌是一种难治性消化系统恶性肿瘤,具有病程短、进展快、病死率高等特点.由于胰腺解剖位置特殊,且缺乏特异性症状及检查手段,导致胰腺癌早期诊断困难.胰腺癌生物学行为特殊,早期易发生胰内、外的转移和侵犯.手术切除率<15%,病程不到1年.即使手术切除肿瘤,胰腺癌局部复发率和远处转移率仍相当高,患者5年生存率<5%,预后极差<'[1-2]>.同时,胰腺癌的发病率呈明显上升趋势,近20年增加了1～5倍.我国胰腺癌的发病率已由第22位(20世纪60年代)上升到第5位(20世纪90年代),相应的病死率由第15位上升至第6位<'[3-4]>.临床流行病学调查进一步显示,上海市胰腺癌发病率正以每年2%的速度增加,且病死率和发病率非常接近<'[5]>.如何进行合理的胰腺癌综合治疗已成为当务之急.纵观胰腺癌综合治疗的现状,主要包括以下7个方面.     

围手术期胃癌放疗的相关问题

放疗作为胃癌综合治疗的组成部分,在近年来得到较多的关注和重视。可切除胃癌的术后辅助放化疔已在INT0116研究中得到证实．而且在实际治疗人群证实了术后辅助放化疗的获益。近期的ARTIST研究．在D,术后辅助放化疗的优势仅显示在淋巴结阳性患者中．而且另外两项ACT—GC和CLASSIC研究．报道的极低局部复发率．与实际临床的差异．使得这些研究结果在实际临床治疗的应用需要慎重。早期单纯放疗的新辅助治疗．在贲门癌中显示了疗效．随后的Ⅱ期新辅助放化疗研究均显示了较高的病理完全缓解率．但同期联合的化疗毒性较高．值得在降低不良反应同时,探索新辅助放化疗的作用。放疗新技术的应用对胃癌放疗提高肿瘤控制和减轻不良反应有重要价值。确立合适治疗人群、放疗敏感性筛选、联合化疗药物和靶向药物在胃癌放疗中的应用．是胃癌放疗的发展方向。     

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??Standardization of the treatment of gastric cancer with the advance of evidence based medicine QIN Xin-yu, LIU Feng-lin. Department of General Surgery, Zhongshan Hospital, Fudan University; Institute of General Surgery, Fudan University, Shanghai 200032,China
Corresponding author:QIN Xin-yu, E-mail:qin.xinyu@zs-hospital.sh.cn
Abstract Evidence based medicine has emerged as a new mode of clinical medicine, and changed the concepts and practice of doctors. Though some high-level clinical trials have been carried out, and their results made great progress in the field of treatment of gastric cancer, the protocols of the trials have some limitation and the results are not identical. During the treatment for patients with gastric cancer, doctors should properly apply the evidences and consider the conditions of such patients, then make individualized treatment regimen.     

精准医学在胃癌中的研究进展

得益于各种分子生物学技术以及基因测序等的进步,胃癌在发病机制研究、分子分型以及靶向治疗等方面有不小的突破.借助于最新的液体活检技术,在评判胃癌病人预后以及对药物或者治疗的反应性方面有了突飞猛进的发展.而光学和物理学的进步推动了内窥镜在胃癌早期诊断以及早期治疗中的发展,同时推动了腹腔镜在进展期胃癌中的广泛开展,高清3D腹...     

Magen- und Adenokarzinome des ?sophagogastralen ��bergangs

According to the current European and German S3 guidelines, neoadjuvant chemotherapy is now an integral part of the treatment of locally advanced gastric cancer and adenocarcinoma of the esophagogastric junction. Neoadjuvant therapy seeks to achieve downsizing of the primary tumor, lowering of the T and N categories and eradication of micrometastases. As the indications for neoadjuvant treatment are based on pretherapeutic information alone, a sophisticated clinical staging plays a central role. Despite all progress made in the field of diagnostic work-up, clinical staging often fails. Despite this fact, controlled randomized trials showed that neoadjuvant chemotherapy enhances the rate of curative (R0) resections and reduces the likelihood of systemic relapse. Overall, survival can be improved by neoadjuvant chemotherapy. The current research is focused on the molecular prediction of response and early response monitoring with functional imaging. New targeted drugs are being integrated into the peri-operative treatment.     

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??Strategies of diagnosis and treatment of gastric cancer in the era of big data and precision medicine JI Jia-fu, LI Zhe-min, XUE Kan, et al. Center of Gastrointestinal Tumors, Peking University School of Oncology, Beijing Cancer Hospital & Institute; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing 100142, China
Corresponding author: JI Jia-fu, E-mail??jiafuji@hotmail.com
Abstract The era of big data and precision medicine has brought new horizon for diagnosis and treatment of gastric cancer. The acquisition of clinical and personal biological data has made personalized treatment possible. Based on the precondition of precise diagnosis, patients with relatively early stage should avoid unnecessary injury, and patients with relatively late stage should be performed multi-disciplinary treatment according to indication for target therapy, chemotherapy and surgery accurately to improve the efficiency of treatment and overall survival. Through the establishing and exploring of the national data sharing and analysis platform, precision medicine program suitable for Chinese conditions should be proposed in the future.     

局部进展期胃癌围手术期治疗的现状与展望

在我国,每年新增的胃癌患者中,局部进展期胃癌（LAGC）占大宗。D 2根治性手术及其术后辅助化疗已取得了普遍的共识,该治疗策略明显改善了LAGC患者的预后,但是术后复发率仍然较高（50%~80%）,致使远期疗效难以进一步提高。围手术期治疗,特别是术前新辅助治疗（NAT）能否提高LAGC疗效,已受到越来越多的关...     

Adjuvant treatment strategies for pancreatic cancer

Pancreatic cancer is a difficult and unsolved surgical problem. It remains one of the top five causes of cancer-related deaths and has the lowest 5-year survival of any cancer, largely due to late diagnosis, low resection rates, and local recurrence. Clinical trials examining the optimal timing and delivery of adjuvant therapies for pancreatic cancer have yielded controversial results. Although most experts agree that the addition of chemotherapy has survival benefit in patients with resectable pancreatic cancer, there is no consensus regarding the optimal therapeutic agents, timing (neoadjuvant versus adjuvant), and the addition of radiation therapy to the treatment regimen. Multiple phase III trials are in progress in efforts to examine these issues. Additionally, exciting progress has been made with novel chemotherapeutic combinations, and alternative treatment modalities including interferon-α, immunotherapy, and pancreatic cancer stem cells. Given the high failure pattern after surgical resection, with more than half of patients developing locoregional recurrence, all patients undergoing pancreaticoduodenectomy are candidates for adjuvant therapy.     

Adjuvant therapy of cancers of the colon and rectum

Important advances have been made in our understanding of the role of adjuvant therapy for colorectal cancer. Current standard 5FU-based regimens have been convincingly shown to reduce the incidence of recurrences and to prolong overall survival in patients with resected stage III colon cancer. Colon cancer patients with stage II disease have a better-overall prognosis than those with stage III; however, the relative merits of adjuvant treatment in these patients remains controversial. Combined chemotherapy plus radiation therapy is currently the standard adjuvant approach for stage II and III rectal cancer patients. Despite the advances that have been made, far too many patients with resectable colorectal cancer ultimately relapse and die of their disease. There remains a pressing need for continued development of improved adjuvant treatments. Participation of eligible patients in clinical trials must continue to be actively encouraged. Only in this way will we be able to continue to build and expand on the progress that has been made thus far.