Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

Treatment of metastatic liver tumors using stereotactic ablative radiotherapy

The prognosis of patients with metastatic liver disease remains dismal with a median survival of only 6-12 mo. As 80%-90% of patients are not candidates for surgical therapy, there is a need for effective non-surgical therapies that would improve outcomes in these patients. The body of evidence related to the use of stereotactic ablative radiotherapy(SABR) in metastatic liver disease has substantially grown and evolved over the past decade. This review summarizes the current evidence supporting liver SABR with particular attention given to patient selection, target delineation, organ at risk dose volume constraints, response evaluation imaging and the various SABR techniques for delivering ablative radiotherapy to the liver. Even though it is unclear what dose-fractionation scheme, delivery system, concomitant therapy or patient selection strategy yields the optimum liver SABR outcomes, clear and growing evidence is available that SABR is a safe and effective therapy for the treatment of oligometastatic liver disease.

Single-fraction stereotactic ablative body radiation therapy for primary and metastasic lung tumor:A new paradigm?

Stereotactic ablative body radiotherapy(SABR)is an effective technique comparable to surgery in terms of local control and efficacy in early stages of non-small cell lung cancer(NSCLC)and pulmonary metastasis.Several fractionation schemes have proven to be safe and effective,including the single fraction(SF)scheme.SF is an option costeffectiveness,more convenience and comfortable for the patient and flexible in terms of its management combined with systemic treatments.The outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic has driven this not new but underutilized paradigm,recommending this option to minimize patients’visits to hospital.SF SABR already has a long experience,strong evidence and sufficient maturity to reliably evaluate outcomes in peripheral primary NSCLC and there are promising outcomes in pulmonary metastases,making it a valid treatment option;although its use in central locations,synchronous and recurrencies tumors requires more prospective safety and efficacy studies.The SABR radiobiology study,together with the combination with systemic therapies,(targeted therapies and immunotherapy)is a direction of research in both advanced disease and early stages whose future includes SF.

Stereotactic radiotherapy for prostate cancer:A review and future directions

Prostate cancer affects over 200000 men annually in the United States alone.The role of conventionally fractionated external beam radiation therapy (RT) is well established as a treatment option for eligible prostate cancer patients; however,the use of stereotactic body radiotherapy (SBRT) in this setting is less well defined.Within the past decade,there have been a number of studies investigating the feasibility of SBRT as a potential treatment option for prostate cancer patients.SBRT has been well studied in other disease sites,and the shortened treatment course would allow for greater convenience for patients.There may also be implications for toxicity as well as disease control.In this review we present a number of prospective and retrospective trials of SBRT in the treatment of prostate cancer.We focus on factors such as biochemical progression-free survival,prostate specific antigen (PSA) response,and toxicity in order to compare SBRT to established treatment modalities.We also discuss future steps that the clinical community can take to further explore this new treatment approach.We conclude that initial studies examining the use of SBRT in the treatment of prostate cancer have demonstrated impressive rates of biochemical recurrencefree survival and PSA response,while maintaining a relatively favorable acute toxicity profile,though long-term follow-up is needed.

Stereotactic radiotherapy for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(iCCA)is an aggressive malignancy with an increasing incidence worldwide and poor prognosis,despite several advances and continuous efforts to develop effective treatments.Complete surgical resection is the mainstay of treatment and offers a potentially curative option,but is only possible in less than a third of patients,owing to advanced disease.Chemotherapy is a well-established treatment in the adjuvant and palliative setting,however,confers limited benefit.Conventional radiotherapy is challenging due to local toxicity.With recent advances in stereotactic ablative radiotherapy(SABR),it is now possible to focus ablative beams of radiotherapy precisely aimed at tumours to minimise damage to surrounding viscera.This review details the history,technical background and application of SABR to iCCA,with directions for future research suggested.

Tumorigenic Responses of Cancer-Associated Stromal Fibroblasts after Ablative Radiotherapy: A Transcriptome-Profiling Study

Cancer-associated fibroblasts (CAFs) are key elements in the progression of cancer and thereby represent important targets for cancer therapies. Increased attention has been given to ablative radiotherapy in the clinics. Therefore, in this study we have aimed at identifying the transcriptional responses occurring in primary CAFs exposed to high-dose irradiation. Established primary CAFs obtained from non-small-cell lung cancer (NSCLC) patient material were irradiated with a single dose of 18 Gy and total RNA was isolated 24 hrs after treatment. Radiation-induced transcriptional alterations were investigated by gene expression analysis using genome-wide microarrays. Obtained results were verified by qRT-PCR of relevant genes. Confirmation of gene expression outcomes was achieved by diverse functional and expression assays including DNA damage response, measurements of reactive oxygen species (ROS) by flow cytometry and senescence-associated β-galactosidase. Irradiation resulted in differential expression of 680 genes of which 557 were up- and 127 down-regulated. Of those, 153 genes were differentially expressed with a fold-change greater than 1.0 and an adjusted p-value less than 0.05 across different comparisons (non-irradiated vs. irradiated). Expression patterns revealed profound changes in biological functions and processes involved in DNA repair, apoptosis, p53 pathway, autophagy, senescence, ROS production and immune response. CAFs display pro- and anti-tumorigenic effects after having received a single high-dose radiation. The measured effects will have an impact on the tumor microenvironment in respect to tumor growth and metastasis.

Stereotactic body radiation therapy for non-small cell lung cancer:A review

Stereotactic body radiation therapy(SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer(NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility,prescription dose and delivery, and follow up duration varied widely. Threeyears overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.

Oligometastases in prostate cancer:Ablative treatment

Technological advances in radiotherapy have led to the introduction of techniques such as stereotactic body radiation therapy(SBRT), allowing the administration of ablative doses. The hypothesis that oligometastatic disease may be cured through local eradication therapies has led to the increasing use of SBRT in patients with this type of disease. At the same time, scientific advances are being made to allow the confirmation of clinically suspected oligometastatic status at molecular level. There is growing interest in identifying patients with oligometastatic prostate cancer(PCa) who may benefit from curative intent metastasis-directed therapy, including SBRT. The aim is to complement, replace or delay the introduction of hormone therapy or other systemic therapies. The present review aims to compile the evidence from the main ongoing studies and results on SBRT in relation to oligometastatic PCa; examine aspects where gaps in knowledge or a lack of consensus persist(e.g., optimum schemes, response assessment, identification and diagnosis of oligometastatic patients); and document the lack of first-level evidence supporting the use of such techniques.

肺部恶性肿瘤立体定向放射治疗后影像学动态变化规律

目的 肺部恶性肿瘤立体定向放射治疗(stereotactic radiation therapy,SRT)后计算机断层扫描(computed tomography,CT)图像的动态变化是一个复杂而连续的过程,容易引起误诊。探讨SRT后肿瘤及其周边正常肺组织的CT图像动态变化的规律。方法 回顾性分析2018—2021年在南京医科大学附属肿瘤医院接受SRT的104例肺部恶性肿瘤患者的临床资料,根据纳入条件,由研究者诊断小组对每次CT图像进行评估和动态比较,记录SRT后肿瘤本身及周边正常肺组织形态学变化和时序特征。结果 104例患者共109个病变。94个(86.2%)病灶呈现残存病灶与周边放射性肺损伤融合形成肿块样实变,可分为3个阶段。发生期:治疗后3个月(范围为1~9个月),胸部CT呈病灶周围絮状渗出性改变。发展期:治疗后4.5个月(范围为1.5~15.5个月),呈密度更高的斑片条索影和/或纤维化实变影。影像稳定前期:治疗后13个月(范围为5.5~39个月),呈纤维化实变逐渐吸收、固结或收缩并与病灶融合形成最终的肿块样实变,伴或不伴随纤维化移动,最终趋于稳定。15例(14.4%)患者周围肺组织无明显改变,仅表现为病灶本身变化,达到影像学稳定的中位时间为治疗后10个月(范围为2.5~15.5个月)。65个(59.6%)病灶影像稳定期肿块样实变长径比初始病变增加了20%以上。进入发展期时间越短,影像稳定阶段肿块样实变长径可能越大(P=0.021)。结论 SRT后肿瘤本身及周边正常肺组织通常会出现连续动态影像学改变,最终多数患者残存病灶与周边肺组织纤维化融合形成肿块样实变。多数患者肿块样实变长径较SRT前增加20%以上。

3DCT联合4DCBCT在中下叶肺癌SABR放疗靶区外放边界中的应用研究

目的:利用四维锥形束CT(4DCBCT)扫描获取放疗靶区摆位误差和呼吸运动误差,计算肿瘤立体定向消融放射治疗(SABR)中计划靶区体积(PTV)外放边界大小。方法:回顾性分析19例中下叶肺癌SABR治疗患者,治疗前4DCBCT扫描,共72次扫描图像。根据4DCBCT与定位CT的配准结果,评估放疗靶区分次间摆位和呼吸运动误差,确定PTV外放边界大小。结果:放疗靶区摆位误差在左右、上下、前后3个方向上分别为(0.11±0.29)、(0.02±0.58)、(0.05±0.26)cm,放疗靶区呼吸运动误差在3个方向上分别为(-0.06±0.34)、(0.09±0.68)、(0.06±0.23)cm,利用ICRU83#报告公式计算PTV外放边界,在3个方向上分别为1.13、2.15、0.90 cm。结论:4DCBCT可有效评估放疗靶区摆位和呼吸运动误差,并确定中下叶肺癌SABR治疗中PTV外放边界大小。利用本方法计算的外放边界比原来RTOG提出的外放标准更加精确,可个体化评估放疗靶区外放边界。

立体定向消融放射治疗(SABR)医用直线加速器的相关剂量学研究

目的:研究ELEKTA Synergy加速器SABR临床治疗的相关剂量学特点。方法:根据IAEA TRS277报告(97年版)和《医用电子加速器验收和周期检验规程》(GB/T 19046-2003)相关内容测量ELEKTA Synergy加速器相关剂量指标。对ELEKTA Synergy加速器实施SABR治疗病人的临床治疗计划进行剂量分布验证。结果:ELEKTA Synergy的临床剂量学相关指标符合IAEA TRS277报告(97年版)和《医用电子加速器验收和周期检验规程》(2003年版)的指标要求;临床治疗计划剂量分布的验证满足SABR治疗的临床要求。结论:ELEKTA Synergy加速器剂量相关指标和临床治疗计划剂量分布数据的偏差范围可以满足SABR临床治疗的要求。

Technical advances in external radiotherapy for hepatocellular carcinoma

Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma(HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy(IMRT), stereotactic ablative body radiotherapy(SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy.

Precision radiotherapy for brain tumors A 10-year bibliometric analysis

OBJECTIVE： Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; （b） type of articles： original research articles and reviews; （c） year of publication： 2002-2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） Corrected papers or book chapters. MAIN OUTCOME MEASURES： （1） Annual publication output; （2） distribution according to country; （3） distribution according to institution; （4） top cited publications; （5） distribution according to journals; and （6） comparison of study results on precision radiotherapy for brain tumors. RESULTS： The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven are in the USA, three are in Germany, two are in France, and there is one institute in India. Research interests including urology and nephrology, clinical neurology, as well as rehabilitation are involved in precision radiotherapy for brain tumors studies. CONCLUSION： Precision radiotherapy for brain tumors remains a highly active area of research and development.

肿瘤立体定向消融放疗联合免疫治疗的研究进展

近年来,随着放疗技术的迅速发展,特别是影像技术和计算机技术的发展,肿瘤立体定向消融放疗(SABR)实现了精准地将非常高剂量的射线传递到肿瘤局部,而对周围正常组织的损伤降到最低。SABR除了对肿瘤的直接杀伤作用外,还具有免疫调节作用,SABR的作用相当于原位疫苗接种的效果,导致受照射局部肿瘤释放大量肿瘤相关抗原和损伤相关模式分子等,促进了机体抗肿瘤T细胞反应,使肿瘤的免疫原性细胞死亡增加,并可能诱发抗肿瘤的远端效应。然而,肿瘤周围微环境通常处于免疫抑制状态,单独SABR的免疫调节作用很难奏效,因此,在SABR的同时引入免疫调节剂的联合治疗方案非常具有说服力。免疫调节剂可解除肿瘤周围的免疫抑制状态,从而与SABR发挥协同作用,这种协同关系已在实验室模型中得到广泛证实,目前多项早期临床试验正在进行中。

基于CT或PET/CT的影像组学信息预测Ⅰ期非小细胞肺癌立体定向消融放疗疗效的初步研究

背景与目的:影像组学作为极具潜力的新领域,是指从影像图像中提取有价值的图像特征,并将这些特征数据定量化并转换成可挖掘的数据矿用以指导临床。该回顾性研究应用影像组学的方法初步探索PET/CT对比常规CT在Ⅰ期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者接受立体定向消融放疗(stereotactic ablative radiotherapy,SABR)后疗效预测方面的可行性。方法:回顾性收集经病理证实并在复旦大学附属肿瘤医院行SABR治疗的Ⅰ期NSCLC患者,提取治疗前PET/CT和定位CT图像,由放疗科医师勾画病灶,运用影像组学的方法进行特征值的提取、分析和总结,采用NMF聚类法(non-negative matrix factorization)分析这些特征值是否能够对有无局部进展的患者进行区分,所有统计学算法都在R平台(R Development Core Team)上实现。结果:16例患者纳入最终分析,在PET/CT的影像组学PET特征中发现两个差异有统计学意义的特征值(灰度共生矩阵最大相关系数和灰度游程共生矩阵长行程加重),可以用以区分患者是否出现局部进展,而在所有定位CT图像提取的特征值中并没有类似发现。结论:在经过SABR治疗后的Ⅰ期NSCLC患者中应用基线PET/CT及胸部定位CT提供的信息进行影像组学分析后,PET/CT似乎能够提供更具统计效能的PET特征值用以预测疗效,对比胸部定位CT提供的信息,PET/CT所提取的特征值可能更敏感、更全面甚至更具特征性。

结直肠癌肝转移立体定向消融放疗

全身治疗和转移灶局部治疗可以改善结直肠癌肝转移(CRLM)患者的生存。体部立体定向放射治疗,又称立体定向消融放疗(SABR),不仅是转移灶局部治疗的有效手段,还对全身免疫状态具有一定的影响。SABR可以直接杀伤肿瘤细胞,也通过对肿瘤细胞和非肿瘤细胞的影响改变肿瘤免疫微环境。SABR联合免疫治疗可能通过影响免疫应答的各个环节增加照射区域之外病灶远隔效应的发生率。立体定向近距离消融(SABT)是一种独立的微创治疗体系,具有疗程短、精确性高、疗效确切的特点。现就SABR和SABT在CRLM中的应用进行综述。

原发性肝癌立体定向消融放疗后CT影像学随访观察

目的观察原发性肝癌全身γ刀立体定向消融放疗（SABR）后的CT影像学表现。方法随机选取采用超级γ刀（SGS-I型）SABR的肝癌患者100例，将112个可评价病灶按肿瘤大小分为三组：A组，肿瘤最大径〈5cm；B组，肿瘤最大径5—10cm；C组，肿瘤最大径〉10cm。治疗后2—3个月及半年CT复查，分析不同类型和大小肿瘤治疗后的CT平扫及增强影像特点。结果肝癌γ刀治疗后2—3个月CT复查，与治疗前比较，A组病灶缩小不明显，无统计学差异（t=1．51，P〉0．05），B、C组病灶明显缩小，差异有统计学意义（t=10．07、8．56，P均〈0．05）。增强扫描，所有病灶边缘均与治疗靶区形状基本一致，清晰可见。其中27（24．11％）个病灶动脉期及门脉期均无明显强化，30（26．79％）个病灶边缘动脉期出现环形强化，门脉期强化仍可见，但减弱，55（49．11％）个病灶动脉期边缘强化，门脉期强化较动脉期明显，延迟期强化仍可见。治疗半年后所有边缘强化均减弱或消失，变得模糊。结论肝癌γ刀治疗后CT影像表现具有多样性，需结合临床，AFP检查方可作出客观评价。

Cyberknife治疗纵隔转移淋巴结的临床分析

目的:评价射波刀(Cyberknife)治疗纵隔转移淋巴结的临床价值。方法:分析射波刀治疗39例恶性肿瘤纵隔淋巴结转移患者的临床资料。病灶共计49个,直径1.5～4.3 cm。治疗剂量12～60 Gy,分割1～10次。结果:治疗后随访3～67个月(中位数20个月),胸闷、气短等症状缓解率83.3%。49个病灶CR、PR、SD分别为29、15、5个,有效率90%。1、2年局控率为100%、91%,1、2年生存率分别为84.6%、68.3%。急性期无反应者25例,1～2级、3～4级放疗反应分别为11例、3例。既往行胸部放疗、隆突下及气管食管沟病灶、放疗前后1个月行化疗者放疗不良反应发生率较高(P=0.014、0.007、0.039),反应组食管5 mL平均照射剂量30.62 Gy明显高于无反应组15.5 Gy(P=0.045)。结论:射波刀为纵隔淋巴结转移者提供了安全有效的治疗手段。

立体定向消融放疗挑战手术在早期非小细胞肺癌的治疗地位

单臂Ⅱ期临床研究及倾向性分析表明,可手术的Ⅰ期非小细胞肺癌（non-small cell lung cancer,NSCLC）立体定向消融放疗（stereotactic ablative radiotherapy,SABR）的疗效与手术相当[1-2],然而这一结论一直缺乏Ⅲ期临床研究结果的支持。

多原发性肺癌的诊治进展

多原发性肺癌的发病率和检出率逐年升高。目前临床上诊断多原发性肺癌(multiple primary lung cancer,MPLC)主要参照Martini-Melamed标准和美国胸科医师协会(American College of Chest Physicians,ACCP)标准,综合考虑临床表现、影像学特征、组织学类型和分子遗传学特征。组织学类型不同的MPLC诊断相对容易,而组织学类型相同的MPLC诊断仍相当困难。DNA倍体分析、基因突变检测、微卫星多态性分析等分子生物学技术为MPLC的正确诊断提供了新手段,可评估各病灶的克隆性关系,帮助鉴别MPLC与转移。MPLC的首选治疗方案为根治性手术,术式应考虑患者肺功能储备等因素,选择肺叶切除、肺段切除或楔形切除;对于不能根治性切除的病灶,可综合化疗、放疗、立体定向放疗(stereotactic ablative radiotherapy,SABR)、射频消融(radiofrequency ablation,RFA)、分子靶向治疗等。