乳腺癌放疗联合PD-1/PD-L1抑制剂研究进展

放疗可以增强肿瘤特异性免疫反应,同时为免疫药物提供作用靶点,以PD-1/PD-L1为代表的免疫检查点阻断剂联合放疗增强抗肿瘤活性,并且具有远隔效应。本文就放疗联合PD-1/PD-L1抑制剂治疗乳腺癌的基础研究、临床研究进展及面临的挑战做一综述。     

放疗对机体抗肿瘤免疫效应机制的影响

放疗主要通过对放射野内肿瘤细胞的杀伤使靶区内肿瘤得到控制、可以作用于远处转移灶并能够激活机体抗肿瘤免疫应答。越来越多的研究表明合理的放疗剂量和分割模式能够改善肿瘤微环境,诱导特异性 T 细胞免疫应答,形成原位疫苗并激活机体的抗肿瘤免疫效应。本文重点阐述放疗对机体抗肿瘤免疫效应机制的影响,以及放疗在免疫治疗的辅助下如何发挥抗肿瘤的作用,为恶性肿瘤治疗提供新思路。     

大剂量分割放疗与肿瘤免疫——新概念与新结合

现代免疫学认为肿瘤的逃逸机制与肿瘤特异抗原(TSA)和肿瘤相关抗原(TAA)的隐藏、丢失,肿瘤自身分泌一些免疫抑制因子抑制免疫杀伤和抗原呈递细胞(APC)有关。肿瘤微环境的变化对肿瘤免疫变化及肿瘤治疗的转归也有影响。在肿瘤局部,尽管抗原呈递细胞(APC)和免疫效应细胞CTL都存在,但是,免疫作用效果却取决于T细胞受体(TCR)和其他共调节受体(CD₂₈、CD₈₀/ CD₈₆、CTLA-4)的活化或抑制。近年来研究发现,放疗不仅能造成肿瘤细胞DNA损伤,还能引起肿瘤细胞的免疫原性。无论常规分割照射还是大剂量分割照射都可以产生肿瘤的至免疫原性(Immunogenesis)。至免疫性细胞调节能使受照射细胞表达多种抗原,使细胞易于免疫识别和杀伤;至免疫原性细胞死亡所释放的细胞内容物(如DNA、HMGB1等)能够刺激免疫反应,产生“原位疫苗”作用,进而产生放疗的远隔效应。许多抗肿瘤免疫治疗方法没能达到令人满意的效果,如何利用放疗,特别是SBRT方法与抗肿瘤免疫治疗结合成为近年来的研究新课题。     

放疗联合免疫治疗癌症的研究进展

放疗不仅是肿瘤局部治疗的重要手段,同时也对免疫功能有重要的调节作用。放疗可通过产生新抗原、调节细胞因子释放、提高肿瘤对免疫细胞杀伤作用敏感性等方式调节机体抗肿瘤免疫应答。近年来部分研究和临床实践发现,放疗联合免疫治疗在部分病例中出现“远位效应”,照射野范围外的转移性病灶有部分或完全缓解,显示放疗联合免疫治疗的良好前景;但相关机制以及放疗剂量、分割方式等因素对免疫的影响仍有待进一步研究。本文综述了放疗影响免疫的机制以及放疗联合免疫治疗的研究进展。     

放疗联合免疫治疗的相关机制及研究进展

近年来,恶性肿瘤的发病率越来越高,而肿瘤的各种治疗技术也在不断提高,治疗方案不断完善。放疗主要是通过放射线对局部肿瘤细胞的杀伤来达到治疗效果,而在放疗过程中,可以诱导或提高抗肿瘤免疫反应。合适的放疗剂量、分割模式联合一定的免疫治疗在肿瘤的治疗中越来越起到重要的作用。本文综述了放疗增强抗肿瘤免疫反应的相关机制及放疗联合免疫治疗研究现状和发展前景。     

肿瘤抗血管内皮生长因子与放射及免疫联合治疗研究进展

目前的很多基础研究和临床研究,都在探讨血管内皮生长因子(VEGF)抑制剂与放疗、免疫治疗相结合的作用机制、联合方案、治疗疗效和不良反应等,现有研究证实抗VEGF治疗可以提高放疗对肿瘤的控制,但怎样在疗效最大化、伤害最小化的基础上将这3种治疗手段合理运用,仍有待进一步探索。本文将对抗VEGF治疗与放疗、免疫治疗联合抗肿瘤的相关机制及研究进展作一综述。     

调节性T细胞对肿瘤放疗的影响及其机制研究进展

放疗不仅对肿瘤细胞有直接杀伤作用,还能通过影响系统和局部抗肿瘤免疫反应促进肿瘤消退。调节性T细胞(Treg)是一类具有免疫抑制功能的T细胞亚群,因此Treg细胞成为抗肿瘤治疗的靶点之一。近年来,放疗联合抗Treg细胞治疗越来越受到人们的重视。这篇文章将对Treg细胞的生物学特性及Treg细胞与放疗的相互作用进行综述。     

微波抗肿瘤研究现状及展望

微波治疗人类恶性肿瘤之潜在效益久为人们所认识,它既能单独抗肿瘤,又能和放疗或化疗联合应用,增强抗肿瘤作用,减轻放疗、化疗的毒副作用;愈来愈受到肿瘤研究者的重视。微波产生的高热具有以下抗肿瘤特点:1.更易杀伤S期肿瘤细胞,与电离辐射有协同作用。2.可杀伤对电离辐射及某些抗癌药不敏感的肿瘤内乏氧细胞。3.对低pH的细胞(见于某些肿瘤)有更大的杀伤作用。4.局部高热可增强宿主抗肿瘤免疫。近来,由于利用组织培养、细胞电生理、放射性同位素标记等现代生物技术以及数学、     

肿瘤热疗研究进展

肿瘤疾病的热疗安全有效、不良反应低,且与其他治疗方法如放疗、化疗等有协同作用,近年来已成为继手术、放化疗和生物治疗后的一种抗肿瘤治疗的重要辅助手段。热疗主要通过直接对肿瘤细胞产生抑制作用和热诱导的放射增敏效应来发挥提高放化疗效果的作用,故现在热疗正逐渐应用于肿瘤的综合治疗中。本文主要对肿瘤热疗在联合传统化疗、放疗、免疫治疗以及新材料中的应用和研究进展等内容进行综述。     

放疗协同免疫检查点阻滞剂治疗肿瘤的机制

随着对肿瘤免疫机制的深入研究,学者们注意到了放疗激活机体产生全身免疫效应的现象,改变了放疗是“免疫抑制性”的片面认识.然而,放疗虽能增强机体的抗肿瘤免疫,在临床上,接受放疗的患者仍避免不了复发、转移.研究表明,这与肿瘤微环境诱导的免疫检查点通路异常激活密切相关.因此,将放疗与免疫检查点阻滞剂联合应用,改善肿瘤微环境,能提高肿瘤治疗效果.     

Radiotherapy combined with chemotherapy increases the risk of herpes zoster in patients with gynecological cancers: a nationwide cohort study

ObjectiveThis study aimed to determine the effect of radiotherapy (RT) on the risk of herpes zoster (HZ) in patients with gynecological cancers via a nationwide population-based study.MethodsBased on patient data obtained from the National Health Insurance Research Database, 1928 gynecological cancer patients were identified with 1:1 matching for RT and non-RT cohorts by age, index date, and cancer type. Another cohort consisting of 964 non-cancer individuals matched was used as normal control. The incidence of HZ was compared between cancer patients with and without RT. Age, comorbidities, cancer-related surgery and chemotherapy (CT), and cancer type were adjusted as confounders.ResultsThe risk of HZ in cancer patients was higher than that of non-cancer individuals (14.23 versus 8.34 per 1,000 person-years [PY], the adjusted hazard ratio [aHR]=1.38, p=0.044). In the cancer population, the incidence of HZ for the RT and non-RT cohorts was 20.55 versus 10.23 per 1,000 PY, respectively (aHR=1.68, p=0.009). Age >50 years was an independent factor for developing HZ. The 5-year actuarial incidence for patients receiving neither RT nor CT, RT alone, CT alone, and combined modalities was 5.4%, 6.9%, 3.7%, and 9.9%, respectively (p<0.001). In the RT cohort, the risk rose rapidly in the first year, becoming steady thereafter.ConclusionThis population-based study showed that gynecological cancer patients receiving RT combined with CT had the highest cumulative risk of HZ. Health care professionals should be aware of the potential toxicities.     

Analysis of residual disease following preoperative radiotherapy versus initial surgery in endometrial carcinoma

A clinicopathologic study of residual disease following pre-operative radiotherapy (RT) in 67 patients and initial surgery in 40 patients with early invasive endometrial carcinoma is presented. In 10%, extrauterine spread was found at operation. In 10% of patients, the histologic type, and in 19% the grade of tumor, differed between the curettage and hysterectomy specimens. Pre-op RT altered the depth of myometrial invasion and frequency of vascular invasion, but there was no evidence that irradiation itself affected the histologic type or grade of tumor. The patients with residual tumor after pre-op RT had significantly more cancer-related deaths than those without residual disease. The high risk factors were deep myometrial invasion and residual disease outside the uterus. Vascular invasion did not affect the prognosis in this series. The importance of surgical-pathologic staging by initial surgery is discussed.     

Irradiation and immunotherapy: From concept to the clinic

In recent years, an increased understanding of T‐cell–regulatory mechanisms has led to the development of a novel class of immune‐checkpoint inhibitors that have robust clinical activity against a broad array of malignancies—even those that historically were not believed to be sensitive to immune therapy. With this, there has been renewed interest in the potential for synergy with more traditional forms of anticancer therapy like radiation therapy (RT). The role of RT in palliation or as definitive treatment for certain malignancies has been well established. Yet, in recent years, the concept has come to light that RT could be an attractive partner for use in combination with other immunotherapies. The effects of RT include not only control of an irradiated tumor but also multiple immunomodulatory effects on both the tumor and the microenvironment, priming tumors for an immune‐mediated response. Herein, the authors summarize relevant preclinical data and rationale supporting the synergy of combined RT and immunotherapy and highlight recent clinical work on promising combination strategies. Cancer 2016;122:1659‐71 . © 2016 American Cancer Society.     

不同治疗方式对术后伴中危因素Ⅰ-ⅡA期宫颈癌预后影响

目的 比较不同治疗方式对伴中危因素的Ⅰ-ⅡA期宫颈癌患者的生存差异,探讨早期宫颈癌术后伴中危因素患者的最佳治疗模式。方法 回顾分析2007-2016年间收治的包含中危因素的323例宫颈癌术后患者,比较观察(NT)、单纯化疗(CT)、放疗(RT)及同步放化疗(CCRT)方式对生存的影响。Kaplan-Meier法生存分析,Logrank检验差异,Cox模型行预后因素分析。结果 全组的5年PFS、OS为79.0%、84.8%。单因素及多因素分析肿瘤大小>4 cm、治疗方式是影响PFS的因素(P=0.017、0.002),危险因素个数、治疗方式是影响OS的因素(P=0.042、0.000)。全组中RT及CCRT均可改善患者预后(P=0.007、0.000)。亚组分析中任意1个中危因素(低危组),CT能够延长5年PFS (P=0.026),在改善5年OS上相近(P=0.692);与NT及CT相比,RT及CCRT均能改善患者预后(P=0.006、0.000),但RT与CCRT相近(P=0.820、0.426)。≥2个中危因素(高危组)中,与CT相比,CCRT能提高患者的5年PFS (P=0.006),但不能延长患者5年OS (P=0.107);RT与CCRT比较,CCRT均可改善患者的预后(P=0.028、0.039)。结论 仅有1个中危因素时,RT也能改善预后;伴有≥2个中危因素时,CCRT更能改善患者的预后。     

常见恶性肿瘤新鲜组织中原发性多药耐药基因表达的初步研究

目的从基因水平探讨临床常见恶性肿瘤细胞中原发性多药耐药基因（ｍｄｒ－１）的表达规律,指导临床实践。方法取安阳市肿瘤医院１９９４年１１月～１９９５年９月术前未做治疗的恶性肿瘤切除标本１５１份,以反转录多聚酶链反应法（ＲＴ－ＰＣＲ）检测其ｍｄｒ－１基因的表达情况,并做比较研究。结果１５１例均经病理检查证实为恶性肿瘤,包括胃及贲门癌５１例,食管癌４６例,大肠癌１６例,乳腺癌１５例,甲状腺癌１０例,肺癌９例,宫颈癌４例。ｍｄｒ－１基因在上述肿瘤中的阳性表达率依次分别为３３．３％、３７．０％、３１．３％、１３．２％、４０．０％、５５．５％、０。结论ＲＴ－ＰＣＲ检测肿瘤组织中ｍｄｒ－１基因的表达简单方便、可靠准确。ｍｄｒ－１基因在临床常见恶性实体肿瘤组织中有较高的原发性表达,提示化疗时要区别对待,合理选药。     

诱导性同步放化疗治疗侵袭性肺上沟瘤

目的分析同步放化疗(CRT)在NSCLC外科治疗的地位.方法回顾性总结1987～1996年外科手术的30例累及胸顶部的NSCLC,单纯手术组10例,手术+放疗组(RT)9例,含铂方案化疗+放疗组(CRT)11例.结果单纯手术组2、4年生存率分别为30%和20%, RT组为22% 和11%,CRT组为73% 和53%.单因素分析根治性(是与否比较,P=0.027)和诱导性治疗(单纯手术和RT与CRT比较,P=0.0173)是有意义的预后因素.多因素分析仅诱导性治疗,P=0.023 8,是有意义的预后因素.结论与诱导性放疗和单纯手术相比,CRT可提高累及胸顶部的NSCLC患者的生存率.     

Details of recurrence sites after definitive radiation therapy for cervical cancer

Objective

This is a retrospective study aimed at clarifying the details of recurrence patterns and sites in patients with cervical cancer treated with definitive radiation therapy (RT).

Methods

Data were analyzed from consecutive patients, admitted to the University of Tokyo Hospital (Tokyo, Japan) between 2001 and 2013, who had received definitive RT, with or without chemotherapy, for International Federation of Gynecology and Obstetrics stages IB–IVA cervical cancer.

Results

One hundred and thirty-seven patients formed the patient cohort. The median follow-up period for surviving patients was 57.0 months. A complete response was achieved in 121 patients (88%). Of these, 36 (30%) developed a cancer recurrence during follow-up. The first sites of recurrence were located in intra-RT fields in nine, outside RT fields in 20, and both in seven patients. In the intra-RT field group, all patients showed a local recurrence, while no one experienced an isolated pelvic lymph node (PLN) recurrence. In the outside RT field group, the most frequent site of recurrence was lung (60%), and three-quarters of patients were free from intra-RT field recurrence until the last follow-up. Of the entire cohort, including 48 PLN-positive patients, only seven patients (5.1%) developed PLN persistence or recurrence, all in the common iliac, internal iliac, and/or obturator nodes, and all with another synchronous relapse.

Conclusion

Local disease was a major type of intra-RT field recurrence, while PLN control was favorable even in initially PLN-positive patients. The predominance of outside RT field recurrence alone highlights issues concerning distant control, including the intensity enhancement of systematic therapy.     

前列腺癌重碳离子放疗计划与调强放疗计划的比较

目的比较前列腺癌重碳离子放疗（C-ion RT）与调强放疗（IMRT）在剂量学方面的差异。方法随机选取5例前列腺癌患者,分别设计4野共面的C-ion RT计划和7野共面的IMRT计划。剂量均采用百分剂量,95％的等剂量面必须包括100％的计划靶体积（PTV）。比较靶区剂量分布的适形度指数（CI）和异质性指数（IC）,根据剂量体积直方图（DVH）,比较相同剂量水平下C-ion RT计划与IMRT计划中周围器官及非靶区正常组织的照射体积。结果在C—-ion RT计划中,CI50%、CI94%、IC分别为3．36、1．20和0．03,与IMRT计划比较差异有统计学意义（P均〈0．01）,靶区剂量分布的CI和IC均优于IMRT计划。除了95％的剂量水平外,在10％、30％、50％、70％和90％剂量水平,采用C—ion RT均可明显减少直肠的受照射体积（P均〈0．05）,同时完全保护直肠的后壁;在任何剂量水平,C—ion RT可明显减少膀胱和非靶区正常组织的受照射体积（P均〈0．05）;在10％、20％、30％和40％剂量水平,C—ion RT可明显减少双侧股骨头的受照射体积（P均〈0．05）。结论在前列腺癌的放射治疗中,与IMRT计划相比,C—ion RT计划在剂量学方面有明显优势,C—ion RT的这些优势将能够进一步提高前列腺癌的局部控制率,减少放疗引起的并发症。