寡转移性乳腺癌的立体定向放疗研究进展

远处转移是乳腺癌患者死亡的主要原因,大多数晚期乳腺癌是不可治愈的。寡转移是介于局限期和广泛转移的一种中间状态。放疗在寡转移性乳腺癌的局部治疗中发挥着非常重要的作用。随着立体定向放疗(SBRT)技术的发展,可以予以根治剂量,同时保护周围的正常组织。既往研究证明SBRT是安全有效的,对乳腺癌的骨、肺、肝、脑、淋巴结等寡转移的局控率>80%。但是,如何筛选真正的寡转移还存在一定争议,进一步的随机临床研究证实放疗能否改善患者生存是至关重要的。     

结直肠癌肺转移的多学科综合诊疗现状

近年来,中国结直肠癌发病人数和死亡人数呈增长趋势,术后复发及转移是导致患者死亡的主要原因,肺是除肝以外结直肠癌转移最常见的好发部位。结直肠癌肺转移患者的治疗手段包括手术治疗、化疗、放疗、射频消融等多种方式。随着多学科诊疗的逐步发展和深入,结直肠癌肺转移患者的生存得到显著提高。     

肺寡转移瘤SBRT疗效及预后因素分析

目的 评价肺寡转移瘤行SBRT疗效和预后影响因素,进一步探讨行SBRT治疗的最佳人群。方法 对2012-2015年间51例肺寡转移患者76个肺转移结节行SBRT。原发肺肿瘤27例,肺外来源肿瘤24例。鳞癌7例,腺癌35例,其他9例。剂量50 Gy分5次、60 Gy分3次等。Kaplan-Meier法生存分析,Cox模型多因素分析。结果 1、2年LC率分别为86%(65/76)和80%(61/76),OS率分别为80%(41/51)和55%(28/51),中位OS为30(2~57)个月,中位PFS为8(1~32)个月。21例出现1级RP,1例出现2级RP。多因素分析表明肺转移结节数≤2、PFI及PS评分≤1分均影响OS (P<0.05)。结论 肺寡转移瘤行SBRT是安全、有效的,肺转移结节数、PFI及PS评分是影响OS因素,选择合适患者和适宜治疗时机是保证SBRT疗效的关键。     

立体定向放射技术治疗结直肠癌肝与肺寡转移的Ⅱ期临床研究

目的探讨立体定向放射治疗(SBRT)用于结直肠癌(CRC)寡转移的安全性和有效性。方法研究为前瞻性、单臂Ⅱ期临床研究。选取原发灶经组织病理学证实为CRC、肝或肺转移灶数目为1～5个、单个转移灶最大长径≤5 cm的患者。所有转移病灶均接受SBRT, 主要研究终点为3年局部控制率(LC), 次要研究终点为≥3级急性治疗相关不良反应, 1、3年生存率和无进展生存率。生存分析采用Kaplan-Meier法和Log rank检验。结果选取2016—2019年中国医学科学院肿瘤医院CRC患者48例, 共60个转移灶(37个肝转移灶和23个肺转移灶)接受了基于呼吸运动管理下的SBRT治疗。46例患者治疗了1～2个转移灶, 转移灶的中位长径为1.3 cm, 中位等效生物学剂量为100.0 Gy。全组患者的中位随访时间为19.5个月, 共25个转移病灶局部复发, 中位无局部复发生存时间为15个月, 1年LC、1年生存率和1年无进展生存率分别为70.2%(95%CI为63.7%～76.7%)、89.0%(95%CI为84.3%～93.7%)和40.4%(95%CI为33.0%～47.8%)。计划靶区体积和...     

SBRT治疗头颈部肿瘤肺寡转移初步结果

目的 初步研究体部立体定向放疗(SBRT)治疗头颈部肿瘤肺寡转移的疗效和安全性。方法 回顾性分析2014-2019年间在浙江省肿瘤医院行SBRT治疗头颈部肿瘤肺寡转移患者24例,采用Kaplan-Meier法生存分析。结果 24例患者中鼻咽来源12例,非鼻咽来源12例,共34个肺转移病灶行SBRT治疗。中位随访时间19.5个月,SBRT后出现新发病灶者13例,其中9例出现在SBRT治疗1年内。1年实际局控率为95%;中位无进展生存期15.2个月,1、2年无进展生存率分别为59%、46%;肺转移后2、3年总生存率分别为71%、51%。单因素分析显示原发灶位于鼻咽和原发灶治疗后无瘤间期>1年者有生存优势。全组SBRT后均未观察到>3级放射性损伤,轻度放射性损伤发生率为13%。结论 SBRT治疗头颈部肿瘤肺寡转移初步显示安全有效,原发肿瘤来源于鼻咽者可能有更好的疗效。     

寡转移瘤患者体部立体定向放疗的疗效及安全性

目的 探讨小体积寡转移瘤患者局部立体定向放疗（SBRT）的疗效及安全性。方法收集2011年6月至2016年12月85例转移灶≤5个、预计生存期＞3个月、一般状况良好的Ⅳ期寡转移瘤患者,采用3个剂量的SBRT,主要研究终点是局部控制率和毒性反应,次要研究终点是总生存期（OS）和无疾病进展生存期（PFS）。疗效评价采用RECIST 1.1版标准;毒副反应采用RTOG评价标准;Kaplan-Meier法计算生存,Log-rank检验生存差异。结果 85例患者共187处转移灶,中位随访时间为25个月,局部控制率为66.8％（125／187）,其中24、30、36 Gy剂量组局部控制率分别为39.0％、79.0％、84.0％,差异有统计学意义（P＜0.05）。全组中位PFS为7.8个月（1～25个月）,1、2、3年无进展生存率分别为33.3％、25.0％、23.0％;中位OS为25个月,1、2、3年生存率分别为80.5％、75.6％、70.6％。4例患者发生3级以上急性毒副反应,其中2例是肺部转移瘤,2个月后证实为放射性肺炎;另外1例是肝脏转移瘤,放疗时发生严重呕吐、转氨酶升高需入院治疗;还有1例肝、肺、骨多发转移患者发生4级骨髓抑制（白细胞减少为主）。结论 寡转移瘤患者在安全治疗范围内可以从局部SBRT放疗中获得较好的局部控制率,不良反应可耐受。     

非小细胞肺癌寡转移的立体定向放射治疗研究

非小细胞肺癌(Non-small cell lung cancer,NSCLC)是除小细胞肺癌以外所有类型的肺癌,脑、骨、肝及肾上腺为最常见的远处转移部位。在NSCLC远处转移患者中,并非都是多发的、广泛的,有近7%的患者表现为肺外孤立性转移。这种特殊形式的晚期肿瘤转移状态称之为NSCLC寡转移。寡转移的治疗以局部治疗为主,局部治疗主要措施包括立体定向放疗、手术切除、射频消融等。本文主要探讨立体定向放射治疗(Stereotactic radiotherapy,SRT)对NSCLC在常见远处转移脏器寡转移的作用。     

立体定向放疗联合或不联合经导管动脉化疗栓塞治疗不可切除结直肠癌肝转移的回顾性研究

目的:比较单纯立体定向放疗或经导管动脉栓塞化疗联合立体定向放疗治疗不可手术结直肠癌肝转移的疗效及安全性。 方法:回顾性分析23例不可手术结直肠癌肝转移患者资料,所有患者曾接受一线标准的全身化疗,化疗后肝脏病灶接受或者经导管动脉栓塞化疗。单纯接受立体定向治疗的13例患者为SBRT组,接受经导管动脉栓塞化疗和立体定向放疗的10例患者为TACE-SBRT组,比较两组患者的肝内病灶局部治疗后的疾病缓解率(RR)、疾病控制率(DCR)和疾病进展时间（TTP）,同时观察并发症发生情况,采用Kaplan-Meier、Log-rank检验,Cox回归模型分析中位无进展生存时间(mPFS)和总生存时间(mOS)。结果:SBRT组和TACE-SBRT组的局部治疗反应RR和DCR无统计学意义（P=0.685）;与SBRT组相比,TACE-SBRT组的无疾病进展时间延长,差异有统计学意义（11.77±1.56 vs 25.40±5.81,P=0.019）。TACE-SBRT的mPFS优于SBRT组,分别为17.4个月和15.1个月（P<0.05）,但是mOS两组之间无统计学意义。同时,仅有1例患者出现Ⅲ级肝功能损伤,治疗后恢复。Cox 回归比例风险模型分析确诊肝转移时CEA水平和同时性转移是无进展生存期和总生存期的预后不良因素(P<0.05)。结论:全身化疗后联合SBRT和TACE治疗不可切除的结直肠癌肝转移是一种安全有效的方法,是一种可接受的替代治疗方法,但仍需进一步研究。     

结直肠癌术后局部复发或转移的三维适形放疗

目的评价三维适形放疗对术后局部复发或转移的结直肠癌患者局部控制率和生存率的影响。方法23例术后局部复发或转移的结直肠癌患者采用三维适形放疗，5—7Gy／次，隔日1次，共6—8次，总剂量0140—45Gy。结果完全缓解率为35％(8／23)，部分缓解率为39％(9／23)，有效率为74％(17／23)。1、2、3年生存率分别为78％、52％、30％。结论三维适形放疗可提高术后局部复发或转移结直肠癌的控制率和生存率，改善其生存质量。     

体部立体定向放疗在寡转移NSCLC的临床应用和前景北大核心CSCD

免疫治疗及靶向治疗等药物的快速进展,为局部晚期非小细胞肺癌(NSCLC)带来了长期生存获益。尤其是针对转移病灶少的晚期肺癌,通过积极的局部治疗手段,可进一步提高患者的生存率,甚至达到临床治愈的可能。近年来,随着放射技术的进步,体部立体定向放射治疗(SBRT)实现了对小靶区肿瘤的精准高剂量放射治疗,目前已被广泛应用于不可手术的早期肺癌,而其在晚期肺癌患者中的应用价值和安全性也正被积极探索。本文就SBRT在晚期寡转移肺癌的研究现状、进展及未来发展方向进行讨论。     

Liver regeneration following repeat SBRT

Liver stereotactic body radiation therapy (SBRT) is an emerging treatment option for oligometastases and may confer a survival benefit in select patients. Herein, we document the first case of liver regeneration (LR) following repeat right hepatic lobe SBRT in a woman with breast cancer metastases. Retraction of the treated lobe was significant with a near 50% volume reduction. Compensatory contralateral lobe hypertrophy was noted with a 320% volume increase. The overall liver volume remained stable, within ±5% of baseline. This case indicates that repeat liver SBRT can be delivered safely to individual patients and that compensatory contralateral lobe hypertrophy is observed to maintain a functional liver volume.     

Emerging application of stereotactic body radiation therapy for gynecologic malignancies

Stereotactic body radiation therapy (SBRT) involves delivery of image-guided, ablative radiation doses to planning treatment volume(s) using sophisticated dosimetric planning and target localization. Early on, clinical investigators pursued SBRT for the treatment of early stage non-small-cell lung cancer, lung and liver oligometastases and spinal metastases. As a result of its clinical efficacy in these disease sites, SBRT has been explored in the management of persistent or recurrent gynecological cancers. This article will consider indications for SBRT application in gynecological cancer management, will reflect on outcomes from key SBRT clinical trials and will discuss new therapeutic roles of SBRT for gynecological cancers.     

Stereotactic body radiation therapy for metastasis to the adrenal glands

Many primary cancers can metastasize to the adrenal glands. Adrenalectomy via an open or laparoscopic approach is the current definitive treatment, but not all patients are eligible or wish to undergo surgery. There are only limited studies on the use of conventional radiation therapy for palliation of symptoms from adrenal metastasis. However, the advent of stereotactic body radiation therapy (SBRT) – also named stereotactic ablative radiotherapy for primary lung cancer, metastases to the lung, and metastases to the liver – have prompted some investigators to consider the use of SBRT for metastases to the adrenal glands. This review focuses on the emerging data on SBRT of metastasis to the adrenal glands, while also providing a brief discussion of the overall management of adrenal metastasis.     

2017第二届全国放疗靶区勾画学习班在北京成功举办

目的 评价SBRT肺部肿瘤的安全性及临床疗效。方法 回顾分析2012—2015年在浙江省肿瘤医院经SBRT的200例肺部肿瘤患者。早期原发性NSCLC 118例,肺孤立转移82例,80%等剂量线作为处方剂量覆盖95%PTV,100%等剂量线覆盖100%IGTV,4.0~18.0 Gy/次,每天或隔天1次,BED为40.0~151.2 Gy (中位数100 Gy)。结果 所有患者均完成治疗,随访率96.0%。原发瘤组CR率14.8%(17/115),PR率65.2%(75/115)。转移瘤组组CR率25%(19/77),PR率38%(29/77)。2、3级急性RP发生率分别为4.7%、3.1%。中位随访时间14.9个月,1、2年原发和转移瘤组LC率分别为95.7%、84.3%和92%、73%,OS率分别为94.5%、92.0%和85%、62%。结论 SBRT对早期原发性NSCLC和肺孤立转移瘤的1、2年LC、OS率较高且发症低,是一种安全有效的治疗手段。     

200例肺部肿瘤SBRT的经验和疗效

目的 评价SBRT肺部肿瘤的安全性及临床疗效。方法 回顾分析2012—2015年在浙江省肿瘤医院经SBRT的200例肺部肿瘤患者。早期原发性NSCLC 118例,肺孤立转移82例,80%等剂量线作为处方剂量覆盖95%PTV,100%等剂量线覆盖100%IGTV,4.0~18.0 Gy/次,每天或隔天1次,BED为40.0~151.2 Gy (中位数100 Gy)。结果 所有患者均完成治疗,随访率96.0%。原发瘤组CR率14.8%(17/115),PR率65.2%(75/115)。转移瘤组组CR率25%(19/77),PR率38%(29/77)。2、3级急性RP发生率分别为4.7%、3.1%。中位随访时间14.9个月,1、2年原发和转移瘤组LC率分别为95.7%、84.3%和92%、73%,OS率分别为94.5%、92.0%和85%、62%。结论 SBRT对早期原发性NSCLC和肺孤立转移瘤的1、2年LC、OS率较高且发症低,是一种安全有效的治疗手段。     

Dose as a function of liver volume and planning target volume in helical tomotherapy, intensity-modulated radiation therapy-based stereotactic body radiation therapy for hepatic metastasis

PURPOSE: Stereotactic body radiation therapy (SBRT) has been shown to be an effective, well-tolerated treatment for local control of tumors metastatic to the liver. Multi-institutional Phase II trials are examining 60 Gy in 3 fractions delivered by linac-based, 3D-conformal IMRT. HiArt Helical TomoTherapy is a treatment unit that delivers co-planar helical IMRT that is capable of image-guided SBRT. We hypothesized that the maximum tolerable dose (MTD) delivered to a lesion by Helical TomoTherapy-based SBRT could be predicted based on the planning target volume (PTV) and liver volume. METHODS AND MATERIALS: To test this, we performed inverse treatment planning and analyzed the dosimetry for multiple hypothetical liver gross tumor volumes (GTV) with conventional PTV expansions. Inverse planning was carried out to find the maximum tolerated SBRT dose up to 60 Gy to be delivered in 3 fractions based on the dose constraint that 700 cc of normal liver would receive less than 15 Gy. RESULTS: Regression analysis indicated a linear relationship between the MTD, the PTV and the liver volume, supporting our hypothesis. A predictive equation was generated, which was found to have an accuracy of +/-3 Gy. In addition, dose constraints based on proximity to other normal tissues were tested. Inverse planning for PTVs located at varying distances from the heart, small bowel, and spinal cord revealed a predictable decrease in the MTD as the PTV increased in size or approached normal organs. CONCLUSIONS: These data provide a framework for predicting the likely MTD for patients considered for Helical TomoTherapy liver SBRT.     

The expanding role of stereotactic body radiation therapy in oligometastatic solid tumors: What do we know and where are we going?

The spectrum hypothesis posits that there are distinct clinical states of metastatic progression. Early data suggest that aggressive treatment of more biologically indolent metastatic disease, characterized by metastases limited in number and destination organ, may offer an opportunity to alter the disease course, potentially allowing for longer survival, delay of systemic therapy, or even cure. The development of stereotactic body radiation therapy (SBRT) has opened new avenues for the treatment of oligometastatic disease. Early data support the use of SBRT for treating oligometastases in a number of organs, with promising rates of treated metastasis control and overall survival. Ongoing investigation is required to definitively establish benefit, determine the appropriate treatment regimen, refine patient selection, and incorporate SBRT with systemic therapies.     

Stereotactic Body Radiation Therapy for Extracranial Oligometastases: Does the Sword Have a Double Edge?

Understanding the acute and chronic toxicities of stereotactic body radiation therapy (SBRT) for extracranial oligometastases might reveal treatment parameters that can be modulated to enhance the therapeutic ratio. Therefore, we searched PubMed from 1995 to 2005 for reports on stereotactic body radiation therapy, with emphasis on treatment of metastatic lesions of the lung and/or liver. Reports of SBRT for primary tumors of these sites were included to increase the number of evaluable patients. The reports were categorized by organ system and evaluated based on number of patients, number of lesions treated, dose fractionation scheme, and local control. A total of 15 lung studies (including 683 patients) and 7 liver studies (including 156 patients) were identified. Overall grade 3 to 5 toxicity was seen in up to 15% of patients in the lung SBRT studies and up to 18% of patients in the liver SBRT studies. Only 3 deaths were reported after SBRT of the liver and 2 after SBRT of the lung for treatment related mortality rates of 2% and 0.3%, respectively. No definitive relationship was found between radiation dose and toxicity. Conversely, radiation treatment volume may be associated with the infrequent toxicities that occur. The literature supports SBRT as a safe and effective treatment for oligometastases of the liver and lung. Further studies are needed to define the optimal dose and fractionation schedule.     

靶向药物联合立体定向放疗治疗转移性肾癌初步临床观察

目的 初步评估靶向药物联合体部立体定向放疗(SBRT)治疗转移性肾癌的疗效和安全性。方法 回顾性分析2013-2018年间中山大学肿瘤防治中心接受靶向药物联合SBRT治疗的 58例转移性肾癌患者资料,79.3%患者根据国际转移性肾细胞癌联合数据库评分为中高危,中位生物有效剂量为147 Gy (67~238 Gy)。结果 分别有32、13、7、5、1例患者接受了1、2、3、4和6处共105个病灶的SBRT治疗,71%为骨转移灶,放疗期间未停用靶向药。SBRT治疗后中位随访9.4个月(2.7~40.1个月),18例患者死亡。1年局控率为97.4%,1年无进展生存率为50.3%,1、2年总生存率分别为72%、53%。85%患者放疗后疼痛减轻。放疗后肿瘤退缩患者 1年总生存优于放疗后疾病稳定或进展患者(83%∶48%,P=0.021)。全组患者共 6例发生3级不良反应,4例为3级骨髓抑制,1例为放射性神经炎,1例为放射性皮肤损伤。结论 初步显示靶向治疗基础上联合局部转移病灶的SBRT治疗晚期转移性肾癌安全有效。     

Preliminary clinical observation of efficacy and safety of stereotactic body radiation therapy in combination with targeted therapy for metastatic renal cell carcinoma

Objective To evaluate the preliminary clinical efficacy and safety of stereotactic body radiation therapy (SBRT) in combination with targeted therapy for metastatic renal cell carcinoma (mRCC). Methods Clinical data of 58 patients with mRCC who were treated with SBRT in combination with targeted therapy in Sun Yat-sen University Cancer Center from June 2013 to December 2018 were retrospectively analyzed. Among them, 79.3% patients were classified as intermediate or high risk according to International Metastatic Renal Cell Carcinoma Database Consortium Criteria. The median biologically equivalent dose (BED) was 147 Gy (67 to 238 Gy). Results Overall, 32, 13, 7, 5 and 1 patients received SBRT for 1, 2, 3, 4 and 6 metastatic sites (105 lesions) and 71.4% of them were bone lesions. Targeted therapy was continued during SBRT. With a median follow-up of 9.4 months (range 2.7 to 40.1 months), 18 patients died. The 1-year local control rate was 97.4%. The 1-year progression-free survival was 50.3%. The 1-and 2-year overall survival was 72% and 53%. Approximately 85% patients experienced pain relief after SBRT. Patients who achieved complete or partial response after SBRT obtained better overall survival than those with stable disease or disease progression (1-year overall survival:83% vs. 48%,P=0.021). In the whole cohort, 6 cases developed Grade Ⅲ adverse events, 4 of which were Grade Ⅲ myelosuppression, 1 case of Grade Ⅲ neuropathy and 1 case of radiation-induced skin injury. Conclusion Preliminary study reveals that combined use of targeted therapy and SBRT is an efficacious and safe treatment of advanced mRCC.