胰腺癌放疗剂量模式改变的研究进展

胰腺癌恶性程度高,预后差。放射治疗是胰腺癌的重要治疗手段,但常规剂量模式延长患者生存时间的疗效受到质疑。通过改变胰腺癌放疗剂量模式,国内外文献报道采用高剂量少分次模式可提高肿瘤局部控制率、缓解癌痛,并有进一步延长患者生存时间的趋势。尽管如此,在高剂量少分次放疗中剂量模式的选取、危及器官的保护、以及如何与手术联合等方面仍有待深入研究。     

塞来昔布对胰腺癌的放疗增敏作用及其机制研究

目的研究环氧合酶-2选择性抑制剂塞来昔布联合放射治疗对胰腺癌的作用，并探讨其作用机制。方法克隆形成实验和裸鼠移植瘤模型观察塞来昔布、放疗和两者联合对胰腺癌细胞SW1990体内外增殖的影响。Western印迹法检测细胞增殖相关蛋白表达。原位缺口末端标记法（TUNEL）研究胰腺癌细胞凋亡。RT-PCR检测凋亡相关基因表达的变化。体外血管生成和体外侵袭力测定方法检测塞来昔布、放疗及两者联合对胰腺癌细胞新生血管生成和细胞侵袭力的影响，RT-PCR、明胶酶谱和反式酶谱方法检测基质金属蛋白酶（MMP）-2、MMP-9及其组织抑制剂（TIMP）-1、TIMP-2的表达。结果塞来昔布在体内外均有放射增敏作用。胰腺癌细胞增殖细胞核抗原（PCNA）蛋白表达水平在塞来昔布组和联合放疗组均降低，联合组较塞来昔布组有进一步降低。塞来昔布诱导胰腺癌细胞凋亡，单独放疗并不能诱导SW1990细胞发生凋亡，两者联合凋亡细胞数明显增加。塞来昔布下调bel-2 mRNA表达，而放疗诱导bel-2 mRNA表达上调，联合组bel-2的表达最低。单剂量放疗时，裸鼠胰腺癌移植瘤的生长延迟时间为22d，联合塞来昔布为38d。单独放疗并不能抑制体外胰腺癌细胞的新生血管生成和侵袭，塞来昔布在体外抑制胰腺癌新生血管形成和侵袭，塞来昔布与放疗联合其抑制作用较单用塞来昔布无明显增强。塞来昔布抑制胰腺癌细胞合成、分泌和激活MMP-2、MMP-9，但对TIMP-1、TIMP-2的合成、分泌和激活无明显影响。结论COX-2选择性抑制剂塞来昔布对胰腺癌放疗有增敏作用，其机制涉及诱导细胞凋亡，并通过抑制胰腺癌细胞新生血管生成和细胞侵袭，间接对胰腺癌的放疗起增敏作用。     

《胰腺癌综合诊治中国专家共识(2014年版)》放射治疗部分的解读

<正>胰腺癌恶性程度高、预后差,目前没有特别有效的治疗手段,即使早期可接受手术的患者,5年生存率也不及10%。由于胰腺临近大血管、肿瘤发展迅速,初诊时80%的患者无法接受手术根治切除。作为肿瘤治疗三大手段之一的放射治疗,其肿瘤局部控制、止痛疗效显著,已应用到绝大多数胰腺癌患者治疗当中。但胰腺癌毗邻胃肠道组织,传统放疗技术难以提高局部肿瘤照射剂量,几十年来放疗在胰腺癌治疗方面一直停滞     

数字智能化诊疗技术在胰腺癌中的应用

随着数字智能化诊疗时代的到来,新技术的临床应用对提高胰腺癌的诊疗水平发挥了重要的推动作用。三维可视化仿真、3D打印、虚拟现实、增强现实手术导航、影像组学等数字智能化诊疗技术的飞速发展,以全新的角度展示了胰腺外科疾病诊疗的新方向,引领着数字化胰腺外科迈入数字智能化时代。结合国内外相关文献和笔者近年来应用数字智能化诊疗技术在胰腺癌诊治中的经验,对相关技术在胰腺癌中的应用现状进行了详细的阐述,介绍了上述技术在胰腺癌术前可切除性评估、个体化手术规划、可视化指导手术等方面的应用,展望数字智能化诊疗技术在提高胰腺癌临床诊断率、选择合理治疗方案和改善外科治疗效果等方面发挥的积极作用。     

青年胰腺癌TOMO高剂量少分次放疗的预后分析

[目的]分析采用螺旋断层放疗(TOMO)高剂量少分次放疗模式治疗青年胰腺癌的疗效及毒副反应。[方法]:回顾性收集年龄≤45岁胰腺癌的病例资料,所有患者接受TOMO按照高剂量少分次模式治疗。随访获取放疗后疗效及毒副反应。生存分析采用Kaplan-Meier法计算。[结果]共计27例患者,男女比例198,中位年龄41岁,最小年龄26岁,胰腺病灶体积中位值57.92cm3。放疗剂量模式主要采取胰腺病灶靶区剂量60~70Gy,15或20分次,胰腺病灶BED10中位值94.5Gy。中位生存时间7个月,1年OS是28.8%。至放疗结束疼痛缓解率90.1%(19/21)。血液学反应3级2例(7.4%),无2级以上消化道反应。[结论]采用TOMO设备按照高剂量少分次模式治疗青年胰腺癌方法可行。     

老年Ⅳ期胰腺癌高剂量少分次放疗的效果观察

目的评估高剂量少分次放疗模式治疗老年Ⅳ期胰腺癌的疗效及毒副反应。方法收集2011年9月-2015年5月于中国人民解放军空军总医院肿瘤放疗科就诊的胰腺癌伴远处转移患者的临床资料,所有患者接受螺旋断层放疗高剂量少分次模式治疗。通过随访获取疗效及毒副反应,依据NCI-CTCAE 4.02标准行不良反应评价。生存分析采用Kaplan-Meier法。结果共33例65岁以上患者接受高剂量少分次模式放疗,30例获得随访,获访率91.0%,其中位生存时间9个月,1年生存率为24.0%,疼痛缓解率80.0%(20/25)。17例患者可评价胰腺病灶治疗效果,其中部分缓解4例(23.5%),稳定12例(70.6%),进展1例(5.9%)。毒副反应中血液学反应3级占6.7%(2/30),无2级以上消化道反应。结论采用高剂量少分次模式治疗老年Ⅳ期胰腺癌,副反应可接受,可缓解患者癌痛,有延长生存时间的趋势。     

表皮生长因子受体抑制剂在胰腺癌治疗中的作用

胰腺癌是常见的消化道恶性肿瘤,传统的化疗和放疗效果均不甚理想。表皮生长因子受体(EGFR)信号转导通路在胰腺癌细胞的增殖、转移、血管形成等方面有重要作用,因此,针对EGFR信号通路的新型药物已陆续开发和应用。此文综述了EGFR的结构、功能以及EGFR抑制剂在胰腺癌治疗中的作用。     

原发性肝细胞癌体部立体定向放疗的疗效及安全性

近年来,随着肿瘤放疗技术进展,原发性肝细胞癌(hepatocellular carcinoma,HCC)的放疗引起越来越多的关注,越来越多的证据也表明其较好的疗效。其中,体部立体定向放疗(stereotactic body radiation therapy,SBRT)对于不适合一线手术或经皮射频消融技术的HCC患者,在提高局部控制率方面发挥了重要作用。SBRT的研究已经开展了很多,也获得了明确的疗效。但关于恰当治疗适应证,合理剂量分割等方面的研究仍有限。本文综述SBRT对于不可手术的HCC患者的有效性、安全性、适应证和剂量分割模式。     

局部晚期胰腺癌放疗并同期5-FU对比吉西他滨的疗效分析

目的 比较放疗联合5-氟尿嘧啶（5-FU）与放疗联合吉西他滨治疗局部晚期胰腺癌的疗效及放、化疗不良反应.方法 回顾性分析第四军医大学西京医院放疗科2007年1月到2011年1月收治的56例局部晚期不可手术切除的胰腺癌患者的资料.入组患者均采用三维适形或三维适形调强放疗并同期给予单药5-FU或吉西他滨化疗.放疗剂量每次1.8 ～2 Gy,每周5次,总剂量45 ～ 50.4 Gy,共25～ 28次.同期吉西他滨化疗组共30例,在放疗期间的第1、8、15、22天以500 mg/m2体表面积的剂量、10 mg· （m2）-1·min-1微量泵泵入给药;放疗结束后休息3周,再以800 mg· （m2）-1·d-1的剂量静脉滴注,每周1次,连用3～4周.同期5-FU化疗组共26例,放疗期间以500 mg· （m2）-1·d-l剂量静脉滴注,每周第1～5天给药,14 d一个周期;放疗结束后休息3周,按照800 mg·（m2）-1·d-1的剂量静脉滴注,每周第1～5天给药,14 d一个周期,连用3～4个周期.观察疗效和不良反应,并对患者进行随访,随访截止日为2013年6月,计算患者中位生存时间和l、2年生存率.结果 全组客观有效率（CR＋ PR）为73.2％,放疗联合5-FU组总有效率为65.3％,放疗联合吉西他滨组总有效率80.0％（P＜0.05）.全组1、2年生存率分别为48.2％和14.3％,中位生存期为15.2个月,其中放疗联合5-FU组分别为42.3％、11.5％、13.3个月,放疗联合吉西他滨组分别为53.3％、16.7％、16.6个月,两组患者生存率差异无统计学意义（P=0.071）.治疗结束后全组疼痛客观缓解率（VAS评分＜4分）为83.3％,放疗联合5-FU组为75％,放疗联合吉西他滨组为90％.放疗联合吉西他滨治疗组发生3～4级骨髓抑制率显著高于放疗联合5-FU组,差异具有统计学意义（20.0％比7.6％,P＜0.05）.结论 手术不能切除的局部晚期胰腺癌患者采用放疗联合吉西他滨化疗在长期生存、疼痛缓解方面较放疗联合5-FU具有优势,但骨髓抑制的不良反应较强.     

纳米刀消融术在不可切除胰腺癌治疗中的应用现状及展望

胰腺癌是常见的一种消化系恶性肿瘤,具有发病隐匿、进展迅速、预后极差等特点,近年来发病率呈明显上升趋势,居恶性肿瘤第4位.目前为止,胰腺癌的治疗手段主要包括手术切除、局部消融疗法、局部放疗、全身化疗、分子靶向治疗及生物治疗等.而根治性手术切除仍被认为是唯一有望治愈胰腺癌的方法,但胰腺癌确诊时多数已属晚期,只有约20%患者有手术切除机会.随着医疗技术的发展,基于不可逆性电穿孔(irreversible electroporation,IRE)原理的纳米刀消融术(nanoknife ablation)已进入人们的视野,逐渐应用于动物实验和临床治疗中,并取得了良好疗效.本文将从相关技术原理及应用现状等方面对纳米刀消融术在不可切除胰腺癌中的应用进展进行综述.     

Preliminary experience of helical tomotherapy for locally advanced pancreatic cancer

Radiotherapy for locally advanced pancreatic cancer is technically difficult and frequently associated with high- grade digestive toxicity. Helical tomotherapy （HT） is a new irradiation modality that combines megavoltage computed tomography imaging for patient positioning with intensity-modulated fan-beam radiotherapy. Its recent availability opens new fields of exploration for pancreatic radiotherapy as a result of its ability to tailor very well-defined dose distributions around the target volumes. Here, we report the use of HT in two patients with locally advanced pancreatic cancer. Doses to the bowel, kidneys and liver were reduced significantly, which allowed for excellent treatment tolerance without any high-grade adverse effects in either patient.     

肺癌脑转移治疗的新进展

脑转移瘤是颅内最常见的恶性肿瘤,其原发灶多来源于肺。肺癌患者一旦发生脑转移,预后差,病死率高。自然生存期约1~2个月,如经积极治疗,其中位生存期也仅有4~12个月。目前研究显示,脑转移肺癌患者的预后与影像学技术、放疗技术、手术方式等密切相关。近年来,随着放疗技术的提高、手术方式的改进、以及靶向药物的不断开发利用,患者的生存时间有了很大延长,生活质量也有了明显提高。本文从肺癌脑转移的放疗、化疗、手术治疗及小分子靶向治疗4个方面系统阐释肺癌脑转移治疗的研究进展。     

肿瘤生物化疗的研究进展

近年来随着科学技术的发展,恶性肿瘤的早期诊断率有所提高,但其治疗仍是一个难题.传统的手术、化疗、放疗并不能从根本上消灭肿瘤,大部分肿瘤患者的长期生存率较低.在生物和免疫学技术飞速发展的推动下,生物治疗的出现为人们对抗肿瘤带来了新的希望.生物治疗与化疗的结合--生物化疗更是为恶性肿瘤的治疗带来了新的理念,并且得到了较好的发展.     

Hyperfractionated and accelerated radiotherapy in non-small cell lung cancer

Radical radiotherapy plays a major role in the treatment of non-small cell lung cancer (NSCLC) due to the fact that many patients are medically or surgically inoperable. Advances in technology and radiotherapy delivery allow targeted treatment of the disease, whilst minimizing the dose to organs at risk. This in turn creates an opportunity for dose escalation and the prospect of tailoring radiotherapy treatment to each patient. This is especially important in patients deemed unsuitable for chemotherapy or surgery, where there is a need to increase the therapeutic gain from radical radiotherapy alone. Recent research into fractionation schedules, with hyperfractionated and accelerated radiotherapy regimes has been promising. How to combine these new fractionated schedules with dose escalation and chemotherapy remains open to debate and there is local, national and international variation in management with a lack of overall consensus. An overview of the current literature on hyperfractionated and accelerated radiotherapy in NSCLC is provided.KEYWORDS : Accelerated radiotherapy, hyperfractionated radiotherapy, non-small cell lung cancer (NSCLC)     

Intraoperative radiotherapy and bypass surgery for unresectable pancreatic cancer

BACKGROUND/AIMS: Conflicting results have been reported concerning the usefulness of radiotherapy for unresectable pancreatic cancer. We evaluated the clinical efficacy of intraoperative radiotherapy and/or external beam radiotherapy in combination with bypass surgery. METHODOLOGY: Twenty-six patients with unresectable pancreatic cancer (16 in Stage II-III and 10 in Stage IV) were treated with intraoperative radiotherapy plus external beam radiotherapy (16 patients) or intraoperative radiotherapy alone (10 patients). The dose of intraoperative radiotherapy was either 25 or 30 Gy and the external beam radiotherapy dose was 31-60 Gy. The feasibility and clinical outcome were analyzed. RESULTS: The median survival time for Stage II-III and Stage IV were 11.5 and 6.5 months, respectively. The difference between Stage II-III and Stage IV in survival patterns was statistically significant (P < 0.05). For Stage II-III patients, the survival curves between the groups of intraoperative radiotherapy plus external beam radiotherapy and intraoperative radiotherapy alone were not significantly different, and only performance status was a significant factor in the prognosis (P < 0.05). Gastrointestinal bleeding was noted in 8%, but did not occur in the patients treated with an external beam radiotherapy dose less than 50 Gy. Palliative radiation was successfully performed to relieve pain, jaundice and appetite-loss and to shorten the hospital stay. CONCLUSIONS: The combination therapy with intraoperative radiotherapy and bypass surgery is considered to be tolerable and effective for unresectable pancreatic cancer, and also may improve the quality of life of the patients.     

Radiation therapy in pancreatic cancer]

Radiotherapy has been offered to patients with pancreatic cancer, either in the adjuvant or definitive setting. However, the role of radiotherapy in pancreatic cancer is increasingly doubted, especially after the introduction of gemcitabine to both domains. Although contradictory data exist, combined chemoradiotherapy improves both quantity and quality of life for patients with locally advanced tumors compared with radiotherapy alone or chemotherapy alone. Recently, induction chemotherapy strategy is being evaluated for better selection of patients for optimal benefit from consolidative chemoradiotherapy. Much controversy has been suggested concerning the role of adjuvant radiotherapy, but quality assurance for radiotherapy was not considered in the previously reported studies. Combined chemoradiotherapy in the adjuvant setting is still considered as a viable option. Current phase III randomized on-going studies will provide better answers on the role of radiotherapy in the treatment of pancreatic cancer.     

Neoadjuvant and adjuvant radio- and radio-chemotherapy of rectal carcinomas

The objectives in treating rectal cancer are to achieve locoregional tumor control and to prolong overall survival. With surgery alone the reported local failure rates in recent decades have been unacceptably high, and this is associated with substantial morbidity and mortality. Perioperative radiotherapy with or without concomitant chemotherapy has been used extensively to reduce the high frequency of local recurrence. Adjuvant radiotherapy reduces the local recurrence rate dramatically if the dose is high enough and is administered preoperatively. Although a higher dose has been used in most postoperative radiotherapy trials, the reduction has not proven particularly pronounced. If the reduction were as great as that with preoperative radiotherapy, it would also have a positive effect on survival, which as yet has not been achieved with postoperative radiotherapy. However, postoperative irradiation combined with chemotherapy yields a survival benefit of the same magnitude as preoperative irradiation. Modern radiation techniques allow preoperative radiotherapy to be delivered without interfering substantially in the postoperative healing process; it does not increase mortality or morbidity and entails a low rate of late toxicity if the radiation technique is optimal. A major question today is whether radiotherapy is necessary if surgery is optimal. Control trials report an average local recurrence rate of 29% with standard surgery. With optimal surgery the figure reported from institutional series is about 10%. Other questions to be answered include whether to use superfractionation or standard fractionation in radiotherapy, and how chemotherapy should be given, concomitantly to radiotherapy or in the classical method of postoperative intravenous treatment. Accepted: 26 November 1999     

经内镜逆行胰胆管造影在小儿胰腺疾病中的应用

经内镜逆行胰胆管造影(ERCP)使成人胰腺疾病的治疗发生了革命性变化。经过多年的临床应用,目前成人治疗性ERCP技术已相当成熟。随着儿科内镜技术的发展,近年来,小儿治疗性ERCP技术已从研究阶段进入实际应用阶段,并逐渐成为小儿胰腺疾病的重要治疗手段。本文主要就ERCP在小儿胰腺疾病中的诊断、治疗及并发症等现状作一综述。     

The role of neoadjuvant chemoradiation in pancreatic cancer

Although complete surgical resection, when possible, leads to prolonged survival in pancreatic cancer, if used alone, its results remain sub-optimal. Neoadjuvant strategies are recent in pancreatic cancer: in primary resectable tumors, they ensure that all patients obtain additional treatment to complete surgery; in locally advanced tumors, they allow a better selection of candidates for curative resection. By delaying surgery, neoadjuvant strategies modify the initial diagnostic process and the symptomatic treatment of pancreatic cancer. Several recent phase I-II studies have confirmed the feasibility and efficacy of the association of chemotherapy and radiotherapy, which is well-tolerated and is associated with better local control and survival. Due to the aggressiveness of pancreatic cancers, most recent cytotoxic agents should be associated with modern radiation techniques. Neoadjuvant chemoradiation is under evaluation in pancreatic cancers, and no randomized phase III trials comparing neoadjuvant and adjuvant therapeutic sequences has been reported. Moreover, radiological and pathological evaluations, not only at diagnosis, but also after preoperative chemoradiation, must be standardized to improve the selection of patients who will benefit from this multi-modal treatment.