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。     

立体定向放疗用于结直肠癌肝与肺寡转移的研究进展

寡转移是肿瘤从局部区域病变进展到远处广泛转移过程中存在的一种中间状态,通过局部治疗有获得长期生存的可能。体部立体定向放疗(SBRT)单次剂量高、分割次数少,是一种高精准的局部消融治疗手段。结直肠癌有近一半患者会发生转移,主要转移部位为肝和肺。本文主要阐述SBRT治疗结直肠癌肝、肺寡转移灶的安全性、近期疗效及其影响因素,同时也总结了SBRT具体实施的要点。SBRT在严格的呼吸运动管理和放疗质控下是治疗结直肠癌寡转移的有效手段。     

立体定向放射治疗肝脏转移瘤的临床疗效

目的探讨立体定向放射(stereotactic body radiation therapy,SBRT)治疗肝脏转移瘤的临床疗效。方法回顾性分析2016年12月至2020年5月同济大学附属东方医院收治的43例肝脏转移瘤患者的临床资料。所有患者均采用4D⁃CT或呼吸门控技术进行CT模拟定位,共58个病灶接受SBRT治疗,总剂量为36~70 Gy,分割次数为5~10次,1天1次,1周5次。结果43例患者均顺利完成全程放疗,中位随访时间为15.6个月(范围:2.0~31.9个月)。2年总生存率、局部控制率和无进展生存率分别为55.4%、86.0%和5.9%。常见的Ⅰ~Ⅱ级不良反应为食欲减退(6例)、疲劳(6例)、骨髓抑制(3例)和肝脏疼痛(1例),未发现Ⅲ级及以上不良反应。EQ⁃5D⁃5L生活质量量表的平均效用得分为0.848(标准差=0.277)。结论立体定向放射治疗肝脏转移瘤局部控制率良好且不良反应较少,其远期疗效和安全性值得开展随机对照研究进一步探索。     

SBRT联合免疫治疗的机制及研究进展

近年来,大量临床前和临床研究表明,SBRT除直接杀伤肿瘤细胞外,还能导致肿瘤细胞免疫原性死亡,释放大量肿瘤相关抗原(TAA)及危险相关模式分子(DAMPs)形成肿瘤原位疫苗。通过激活的抗原提呈细胞交叉致敏引流淋巴结内的CD8(+) T细胞。SBRT能介导肿瘤局部和全身系统性的抗肿瘤免疫反应,与免疫治疗结合,还可以引发远位效应。SBRT同时能改善肿瘤免疫抑制微环境,增加肿瘤对免疫治疗的敏感性。本文对SBRT联合肿瘤免疫治疗的协同作用机制的研究进展进行综述。     

转移性肾细胞癌分子靶向治疗进展

肾细胞癌是我国泌尿生殖系统最常见的肿瘤之一。约30%的肾细胞癌患者在就诊时或手术后可能出现转移,预后差。转移性肾细胞癌对放疗与化疗均不敏感。转移性肾癌的分子靶向治疗已经取得了显著进展。现将最新的相关进展进行总结。     

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.     

A rapid and systemic complete response to stereotactic body radiation therapy and pembrolizumab in a patient with metastatic renal cell carcinoma

Stereotactic body radiation therapy (SBRT) of local tumor would induce an abscopal effect that has been observed in several kinds of human cancers; one important mechanism may involve the improved activation of the host immune system. The immune checkpoint inhibitor can overcome immune tolerance and enhance the activation of antitumor T cells. The combined treatment of SBRT and checkpoint inhibitor may represent a new promising therapeutic approach. Herein, we reported a patient with metastatic renal cell carcinoma (RCC) treated with concurrent SBRT and anti-PD-1 antibody, pembrolizumab, by which the patient achieved an amazingly systemic complete response in only 2.2 months after starting treatment. This case report indicates that the advanced RCC may benefit from the combining treatment of local SBRT and PD-1 inhibitor and provide a useful paradigm worthy of establishing a clinical trial for patients with advanced renal cell carcinoma.     

立体定向放疗在治疗肝转移癌中的应用现状及研究进展

肝脏是大多数实体恶性肿瘤转移的常见部位，研究证实，对于合并肿瘤肝转移的患者，除积极针对原发病灶进行综合治疗外，对肝转移癌进行局部治疗亦可提高患者的生存潜能。立体定向放疗（SBRT）作为一种无创的肿瘤局部治疗方式，具有生物等效剂量(BED)高、正常组织反应轻、治疗时间短等优势。现有研究在应用人群、剂量和分割方式、临床疗效、安全性等方面均已积累了一定的研究证据。但尚缺乏统一定论及标准，仍需要开展更加广泛深入的前瞻性研究，进一步验证和优化现有的治疗策略。本文将针对目前SBRT在治疗肝转移癌中的应用现状作以介绍，探讨其在临床应用中的价值及发展方向。     

Use of stereotactic body radiation therapy for oligometastatic recurrent prostate cancer: A systematic review

The purpose of this study is to evaluate the effectiveness and safety of stereotactic body radiation therapy (SBRT) in the management of oligometastatic recurrent prostate cancer (PCa) by means of a systematic review. Six databases were searched (CENTRAL, Embase, LILACS, PubMed, Scopus and Web of Science). Additionally, hand‐searching and grey literature search were performed. The main outcomes were progression‐free survival (PFS) and toxicity rates. Androgen deprivation therapy‐free survival (ADT‐FS), local control, pattern of recurrence, cancer‐specific survival and overall survival were also assessed. Risk of bias and quality of evidence were judged with the aid of specific tools. Fourteen studies were included, involving 661 patients and 899 lesions (561 nodal, 336 bone, 2 liver). Median PFS and ADT‐FS were around 1 to 3 years. Local control rates varied from 82 to 100% among researches with low risk of bias. Acute and late grade 2 toxicity was observed in 2.4% and 1.1% of the patients, respectively. One case of acute and two cases of late grade 3 toxicity were registered. Only one randomized study addresses this topic. Although it does not meet all the eligibility criteria, it is useful for the discussion. A quantitative analysis was not possible, nor were subgroup analyses, due to the significant heterogeneity of the interventions and outcomes reported. Longer follow‐up period is required. SBRT seems to be a safe approach to metastatic lesions that might provide disease control and defer androgen deprivation therapy (ADT). Local control is better when higher radiation doses are employed.     

立体定向体部放疗联合靶向药物治疗转移性肾癌的研究进展

立体定向体部放疗(Stereotactic body radiotherapy, SBRT)是近年来放疗取得的一个突破性进展,具有分次剂量高、生物学效应高、分割次数少等优势,可显著提高肾癌的放疗敏感性。分子靶向治疗显著延长了部分患者的无进展生存期和总生存期,但在大多数情况下产生全身用药的耐药性仍不可避免。近年来,SBRT联合靶向药物治疗转移性肾癌初步显示了有效性和安全性,有可能成为一种更有效的治疗方案。本文针对SBRT联合靶向药物治疗转移性肾癌研究进展进行综述。     

Regorafenib-induced transverse myelopathy after stereotactic body radiation therapy

Stereotactic body radiation therapy (SBRT) delivers large doses of radiation with great accuracy, but is known to have deleterious effects on the vascular compartment of irradiated tissues. Combining SBRT with targeted anti-angiogenesis agents, while able to increase therapeutic efficacy, may unexpectedly precipitate vascular-based toxicities. In this report, we describe a patient with colon cancer who developed transverse myelopathy from regorafenib 2 years after receiving SBRT for three metastatic liver lesions. Regorafenib (Stivarga), formerly BAY 73-4506, (Bayer HealthCare Pharmaceuticals, Montville, NJ) is a multiple receptor tyrosine kinase inhibitor with anti-angiogenic effects used in metastatic colon cancer. Its most common side effects are fatigue, diarrhea and hypertension. However, severe neurologic toxicity has not been previously recognized. Here, we illustrate a case in which the patient developed hyperalgesia and radicular pain 2 weeks after starting regorafenib. Several studies report an increased neurological toxicity when angiogenesis inhibitors are given after radiation therapy, and we postulate that the angioinhibitory effects of regorafenib accelerated subclinical microvascular injury from SBRT. This unexpected toxicity may be clinically relevant when giving targeted angiogenesis inhibitors after SBRT.     

Guidelines for safe practice of stereotactic body (ablative) radiation therapy

The uptake of stereotactic ablative body radiation therapy (SABR)/stereotactic body radiation therapy (SBRT) worldwide has been rapid. The Australian and New Zealand Faculty of Radiation Oncology (FRO) assembled an expert panel of radiation oncologists, radiation oncology medical physicists and radiation therapists to establish guidelines for safe practice of SABR. Draft guidelines were reviewed by a number of international experts in the field and then distributed through the membership of the FRO. Members of the Australian Institute of Radiography and the Australasian College of Physical Scientists and Engineers in Medicine were also asked to comment on the draft. Evidence‐based recommendations (where applicable) address aspects of departmental staffing, procedures and equipment, quality assurance measures, as well as organisational considerations for delivery of SABR treatments. Central to the guidelines is a set of key recommendations for departments undertaking SABR. These guidelines were developed collaboratively to provide an educational guide and reference for radiation therapy service providers to ensure appropriate care of patients receiving SABR.     

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.     

MR加速器在肝脏肿瘤放疗中的临床应用北大核心CSCD

目的初步探讨MR加速器在肝脏肿瘤中的应用流程、疗效及安全性。方法回顾性分析2019—2021年15例采用MR加速器治疗的肝脏肿瘤患者的临床数据, 探讨肝脏肿瘤采用MR加速器治疗的流程, 分析患者肿瘤的图像识别率、疗效及不良反应。结果全组15例患者中肝细胞癌6例、结直肠癌肝转移8例、乳腺癌肝转移1例;肝内1个病灶10例、2个病灶4例、3个病灶1例;中位肿瘤最长径2.4 cm (0.8~9.8 cm)。MR加速器大体肿瘤体积(GTV)识别率达13/15, 2例患者GTV显示不清, 采用肿瘤周边大血管或胆管识别辅助仍可达精准配准。全组患者均接受体部立体定向放疗。肝细胞癌患者中位分割次数9次(5~10次), GTV或计划靶体积(PGTV)中位单次剂量6 Gy (5~10 Gy), 中位总剂量52 Gy (50~54 Gy), α/β=10的中位2 Gy等效剂量(EQD2Gy)为72 Gy (62.5~83.3 Gy)。肝转移瘤患者中位分割次数10次(5~10次), GTV或PGTV的中位单次剂量5 Gy (5~10 Gy), 中位总剂量50 Gy (40~50 Gy), α/β=5的中位EQD2Gy为71.4 Gy (71.4~107.1 Gy)。放疗后1个月野内总有效率8/13, 疾病控制率13/13, 放疗后3~6个月野内总有效率6/6。全组患者中位随访4.0个月(0.3~11.6个月), 4个月局部无进展生存、无进展生存和总生存分别为15/15、11/15和15/15。放疗不良反应轻微, 未见≥3级不良反应。结论 MR加速器对肝内肿瘤显示率高, 且可通过周边大血管或胆管的显示辅助精准配准, 在肝脏肿瘤的精准治疗上初步展现优势, 局部疗效肯定, 耐受性好。     

转移性肾癌术前D-二聚体对靶向治疗的预测意义

目的：回顾性分析减瘤性肾切除术（cytoreductive nephrectomy ,CN）术前各项临床指标对于联合靶向治疗的转移性肾癌（metastatic renal cell carcinoma,mRCC）患者预后的影响。方法：收集1996年1 月至2015年6 月40例天津医科大学肿瘤医院行CN且术后1 年内行靶向药物治疗mRCC 患者的临床病理学资料,采用Kaplan-Meier 法进行单因素分析,Cox 回归模型进行多因素分析。结果：单因素生存分析结果显示,碱性磷酸酶、血小板与淋巴细胞比值（platelet lymphocyte ratio ,PLR ）、中性粒细胞与淋巴细胞比值（neutrophil lymphocyte ratio ,NLR ）、D-二聚体、T 分期、肿瘤转移器官数目、MSKCC危险模型评分均为影响患者总生存期（overall survival,OS ）的危险因素（P < 0.005）,其中碱性磷酸酶、PLR 、NLR 、D-二聚体、肿瘤转移器官数目、MSKCC危险模型评分为影响无进展生存期（progression-free survival,PFS）的危险因素（P < 0.005）。 Cox 回归模型多因素分析结果显示,D-二聚体（P =0.033）是影响患者OS、PFS 的独立因素,同时碱性磷酸酶（P = 0.045）、MSKCC危险模型评分（P = 0.003）也是影响PFS 的独立因素。结论：术前D-二聚体水平是行CN联合靶向治疗mRCC 患者的独立预后危险因素。     

密集化疗联合靶向治疗在转移性乳腺癌患者中的疗效及安全性分析

目的探讨密集化疗联合靶向治疗治疗转移性乳腺癌的疗效及安全性。方法选择68例人类表皮生长因子受体2(HER2)阳性转移性乳腺癌患者作为研究对象,根据治疗方案的不同将患者分为A组(n=30)和B组(n=38)。A组患者接受表柔比星+环磷酰胺,序贯紫杉醇的剂量密集化疗方案,B组患者在此基础上联合采用曲妥珠单抗靶向治疗。出院后,对两组患者进行为期3年的随访。比较两组患者的不良反应发生率、临床疗效、生活质量及3年总生存率。HER2阳性转移性乳腺癌患者临床疗效的影响因素采用Logistic回归分析。结果 A组患者的不良反应总发生率为40.00%,B组患者的不良反应总发生率为50.00%,差异无统计学意义(P﹥0.05)。B组患者总缓解率、生活质量核心量表(QLQ-C30)评分均明显优于A组患者(P﹤0.01)。B组和A组患者的3年生存率分别为60.0%和30.6%,B组患者的生存情况优于A组(P﹤0.05)。Logistic回归分析显示,转移器官数量是转移性乳腺癌患者临床疗效的影响因素。结论密集化疗联合靶向治疗可提高转移性乳腺癌患者的肿瘤缓解率,延长患者的生存时间,提高患者的生活质量,且安全性较好。     

26例术后复发性胆管细胞癌射波刀SBRT疗效分析

目的 评价射波刀SBRT在复发性胆管细胞癌治疗中的效果及安全性。方法 回顾分析2010-2015年26例术后复发的胆管癌射波刀SBRT的患者,中位术后复发时间10个月,中位肿瘤直径为2.8 cm。中位处方剂量45 Gy,中位分割次数5次。基于增强CT或MRI评估肿瘤进展。采用Kaplan-Meier法计算OS、PFS及LC。使用CTCAE4.0版评估不良反应。结果 中位随访29.3个月,其中位OS和PFS分别为13.5个月和6.5个月,1、2年OS和PFS率分别为52%、21%和28%、15%。4例患者出现肿瘤原位进展。3例患者发生3级不良反应,包括1例胃肠道反应、1例肝功能减退、1例胆道感染;仅1例患者在晚期出现了≥4级消化道出血。结论 射波刀SBRT术后复发性胆管癌可获得较好的疗效且不良反应可耐受。     

A prospective trial of stereotactic body radiation therapy for unresectable pancreatic cancer testing ablative doses

BackgroundWe explored the safety and efficacy of ablative doses of stereotactic body radiation therapy (SBRT) for unresectable pancreatic cancer.MethodsThis phase I/II trial included patients with unresectable pancreatic cancer previously treated with any number of cycles of induction chemotherapy. Patients were enrolled according to a 3+3 dose escalation design at 10, 12.5, and 15 Gy ×3, with subsequent patients at the maximally tolerated dose (MTD). Treatment was delivered to gross tumor delineated with MRI fusion using image-guidance to fiducial markers. Dose-limiting toxicity (DLT) was defined as grade 3+ toxicity within 30 days. Secondary endpoints included late gastrointestinal (GI) toxicity, freedom from local failure (FFLF), and survival.ResultsFifteen patients received a median 10 cycles of chemotherapy. There were no DLTs, and the MTD was 15 Gy ×3. Thirty-day toxicity included grade 2 nausea (46%) and grade 2 diarrhea (7%). Median survival after SBRT was 12.8 months (23 months after diagnosis) and median relapse-free survival was 7 months. At 1-year, FFLF was 80%. Four patients had grade 3+ GI bleeding after 30 days (median 6 months). Grade 3+ GI bleeding was associated with tumor volume (P=0.01), heterogeneity of dose within the planning target volume (PTV) (V120, P=0.03), and duodenal dose (V26–30 Gy, P<0.2).ConclusionsThis aggressive SBRT regimen demonstrated limited 30-day morbidity, a moderate degree of local control, and a moderate risk for late GI bleeding. Further work is necessary to define the most appropriate hypofractionated radiation therapy (RT) regimen in the ablative dose range.