Progress in image-guided radiotherapy for the treatment of non-small cell lung cancer

Lung cancer is one of the most common malignant tumors. It has the highest incidence and mortality rate of all cancers worldwide. Late diagnosis of nonsmall cell lung cancer(NSCLC) is very common in clinical practice, and most patients miss the chance for radical surgery. Thus, radiotherapy plays an indispensable role in the treatment of NSCLC. Radiotherapy technology has evolved from the classic two-dimensional approach to three-dimensional conformal and intensity-modulated radiotherapy. However, how to ensure delivery of an accurate dose to the tumor while minimizing the irradiation of normal tissues remains a huge challenge for radiation oncologists, especially due to the positioning error between fractions and the autonomous movement of organs. In recent years, image-guided radiotherapy(IGRT) has greatly increased the accuracy of tumor irradiation while reducing the irradiation dose delivered to healthy tissues and organs. This paper presents a brief review of the definition of IGRT and the various technologies and applications of IGRT. IGRT can help ensure accurate dosing of the target area and reduce radiation damage to the surrounding normal tissue. IGRT may increase the local control rate of tumors and reduce the incidence of radio-therapeutic complications.

Biological effects of human lung cells MRC-5 in CBCT positioning for image-guided radiotherapy

Image-guided radiotherapy(IGRT) provides precise positioning for the tumor target, but it may bring extra irradiation dose in the target positioning with a cone beam CT(CBCT) which has been increasingly used in IGRT. In this work, we focused on biological effects of the low-dose irradiation in IGRT, which have not been considered so far. Primary human fibroblasts cells from the lung and MRC-5 were irradiated by a CBCT. DNA doublestrand breaks(c-H2 AX foci) and micronucleus frequency of the irradiated samples were analyzed. Compared to the control, the c-H2 AX foci yields of the samples irradiated to 16 m Gy increased significantly, and the micronuclei rate of the samples irradiated for 3 days increased notably. The dose by imaging guidance device can be genotoxic to normal tissue cells, suggesting a potential risk of a secondary cancer. The effects, if confirmed by clinical studies,should be considered prudentially in designing IGRT treatment plans for the radiosensitive population, especially for children.

Long-term clinical outcomes of lipiodol marking using standard gastroscopy for image-guided radiotherapy of upper gastrointestinal cancers

BACKGROUND Image-guided radiotherapy(IGRT)has significantly improved the precision in which radiotherapy is delivered in cancer treatment.Typically,IGRT uses bony landmarks and key anatomical structures to locate the tumor.Recent studies have demonstrated the feasibility of peri-tumor fiducials in enabling even more accurate delineation of target and normal tissue.The use of gold coils as fiducials in gastrointestinal tumors has been extensively studied.However,placement requires expertise and specialized endoscopic ultrasound equipment.This article reports the long-term outcomes of using a standard gastroscopy to inject liquid fiducials for the treatment of oesophageal and gastric tumors with IGRT.AIM To assess the long-term outcomes of liquid fiducial-guided IGRT in a cohort of oesophageal and gastric cancer patients.METHODS A retrospective cohort study of consecutive adults with Oesophagogastric cancers referred for liquid fiducial placement before definitive/neo-adjuvant or palliative IGRT between 2013 and 2021 at a tertiary hospital in Melbourne,Australia was conducted.Up to four liquid fiducials were inserted per patient,each injection consisting of 0.2-0.5mL of a 1:1 mixture of iodized oil(Lipiodol;Aspen Pharmacare)and n-butyl 2-cyanoacrylate(Histoacryl®;B.Braun).A 23-gauge injector(Cook Medical)was used for the injection.All procedures were performed by or under the supervision of a gastroenterologist.Liquid fiducial-based IGRT(LF-IGRT)consisted of computer-assisted direct matching of the fiducial region on cone-beam computerised tomography at the time of radiotherapy.Patients received standard-IGRT(S-IGRT)if fiducial visibility was insufficient,consisting of bone match as a surrogate for tumor position.Radiotherapy was delivered to 54Gy in 30 fractions for curative patients and up to 45Gy in 15 fractions for palliative treatments.RESULTS 52 patients were referred for liquid fiducial placement within the study period.A total of 51 patients underwent liquid fiducial implantation.Of these a total of 31 patients received radiotherapy.Among these,the median age was 77.4 years with a range between 57.5 and 88.8,and 64.5%were male.Twenty-seven out of the 31 patients were able to have LF-IGRT while four had S-IGRT.There were no complications after endoscopic implantation of liquid fiducials in our cohort.The cohort overall survival(OS)post-radiotherapy was 19 mo(range 0 to 87 mo).Whilst the progression-free survival(PFS)post-radiotherapy was 13 mo(range 0 to 74 mo).For those treated with curative intent,the median OS was 22.0 mo(range 0 to 87 mo)with a PFS median of 14.0 mo(range 0 to 74 mo).Grade 3 complication rate post-radiotherapy was 29%.CONCLUSION LF-IGRT is feasible in 87.1%of patients undergoing liquid fiducial placement through standard gastroscopy injection technique.Our cohort has an overall survival of 19 mo and PFS of 13 mo.Further studies are warranted to determine the long-term outcomes of liquid-fiducial based IGRT.

食管癌图形引导的放射治疗(IGRT)6个自由度摆位误差研究

目的肿瘤患者在接受放射治疗的过程中,会因各种原因引起摆位误差,影响放射治疗的准确性。因此有必要利用锥形束CT在线研究食管癌六个自由度的摆位误差,为临床提供数据。方法采用图像引导的放射治疗(imageguidedr adiotherapy,IGRT)的锥形束CT(cone—beam computedtomography,CBCT)影像技术获得患者左右(X)、头脚(Y)、前后(Z)3个方向的线性摆位误差以及分别以X、Y、Z轴旋转形成相应的U、V、W旋转摆位误差。对食管癌患者146次治疗前摆位后、摆位误差调整后及治疗后获取348个CBCT信息,通过系统配有的匹配功能,获取的CBCT图像与计划CT图像相匹配,获取线性误差和旋转误差,分析其摆位误差。结果将计划CT作为参考标准,治疗前摆位后的摆位误差呈近似正态分布,系统误差(均数)±随机误差(标准差)在X、Y、Z、U、V、W6个自由度分别为(0.85±3.56)mm、(1.82±4.00)mm、(-2.31±2.10)mm、(0.59±0.85)°、(0.29±1.30)°、(0.40±0.86)°。误差调整后再次CBCT,结果显示摆位误差明显缩小(P<0.05)。结论食管癌放射治疗摆位误差在Y、Z方向上较为明显,个别患者还有较大的旋转误差,通过CBCT测量食管癌患者治疗前的摆位误差,并行6个自由度的在线调整误差,可明显减小平面误差和旋转误差,提高放疗准确性。

IGRT技术在放射治疗摆位中的应用

目的研究图像引导放射治疗在实施过程中的摆位误差。方法随机选取肿瘤放疗中心的70例患者,其中,头颈部肿瘤23例,胸部肿瘤27例,腹部肿瘤20例,分别采用热塑头模和体模固定,全部行CT模拟定位,患者在放疗期间第1周连续3次,以后每周1次,大分割放疗者每次均做锥束计算机体层摄影术(CBCT)扫描。将采集的CBCT图像与计划系统所生成的CT图像进行比较,并分析摆位误差。结果胸腹部摆位误差最大,头颈部摆位误差最小。结论 IGRT能够做到真正意义上的精确治疗,为精确放疗提供技术保证。

文献计量学视角下国内IGRT研究脉络及主题趋势可视化研究

筛选2005—2020年CNKI数据库收录的图像引导放射治疗(image-guided radiation therapy,IGRT)领域相关文献,应用文献计量学方法,运用CiteSpace软件从学科及基金分布、文献年度分布特征、期刊分布、作者合作网络、关键词共现和主题演进等层面进行了统计和可视化分析,指出了该领域研究的热点、趋势及难点,为深入了解和研究该领域的研究者提供了研究基础及思路。

基于IGRT技术的宫颈癌调强治疗摆位误差重复性研究

目的:利用IGRT技术采集的宫颈癌调强放射治疗前三次的摆位误差,研究宫颈癌的摆位重复性。方法:入组17例进行调强放射治疗的宫颈癌患者。治疗的前三次进行锥形束CT扫描,配准获得患者的摆位误差。分析摆位误差的变化和对三天之内的数据进行两两配对t检验,以获得宫颈癌摆位的重复性规律。结果:数值绝对值矫正后,平移的误差中沿着患者头脚方向的误差大于另外两个方向的误差。任意两组的对比均无统计学意义。结论:宫颈癌摆位中应特别注意沿身体头脚方向的平移误差。治疗中的摆位重复性无规律。再次摆位并没有减少摆位差。应进行多次的CBCT扫描及体位矫正。

IGRT技术在放射治疗摆位中的应用效果探究

目的:研究分析IGR.T技术在放射治疗摆位中的应用效果。方法:随机选取本科室2011年9月至2013年9月收治的肿瘤患者56例,分析患者的肿瘤部位得到:腹部肿瘤22例、胸部肿瘤18例、头颈部肿瘤16例,对全部的患者分别使用热塑头模以及体模固定,全部的患者使用螺旋CT进行准确定位。患者在接受放疗的期间第一个星期连续使用三次,之后为一个星期一次,大分割放疗患者每次均做锥束计算机体层摄影术扫描。分析比较计划系统所生成的CT图像跟采集的锥束计算机体层摄影术图像,详细的分析两者之间的摆位误差。结果:分析各个部位的摆位误差为:头颈部摆位误差最小,胸部以及腹部摆位误差最大。结论:IGRT技术在放射治疗摆位中就有非常显著的应用效果,可以做到精确治疗,保证精确放疗的买现。

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.

中晚期食道癌患者行IGRT放疗同步化疗治疗的疗效观察

目的:探析中晚期食道癌患者行IGRT放疗同步化疗治疗的疗效。方法:选取本院2011年9月至2013年19月收治的中晚期食道癌患者60例,根据治疗方法的不同分成对照组和观察组,各25例,其中对照组行IGRT放疗,观察组行IGRT放疗同步化疗。观察两组的疗效和不良反应。结果:观察组、对照组的总有效率分别为84%、68%,差异显著,具有统计学意义(P<0.05),两组不良反应均表现为放射性食道炎、恶心、呕吐、骨髓抑制等,各并发症发生率具有统计学意义。结论:IGRT放疗同步化疗治疗中晚期食道癌的疗效优于单纯IGRT放疗,患者可耐受不良反应。

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.

Strategies to tackle the challenges of external beam radiotherapy for liver tumors

Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies.

Incorporating GSA-SPECT into CT-based dose-volume histograms for advanced hepatocellular carcinoma radiotherapy

In single photon emission computed tomography-based three-dimensional radiotherapy(SPECT-B-3DCRT), im-ages of Tc-99 m galactosyl human serum albumin(GSA), which bind to receptors on functional liver cells, are merged with the computed tomography simulation im-ages. Functional liver is defined as the area of normal liver where GSA accumulation exceeds that of hepato-cellular carcinoma(HCC). In cirrhotic patients with a gigantic, proton-beam-untreatable HCC of ≥ 14 cm in diameter, the use of SPECT-B-3DCRT in combination with transcatheter arterial chemoembolization achieved a 2-year local tumor control rate of 78.6% and a 2-year survival rate of 33.3%. SPECT-B-3DCRT was applied to HCC to preserve as much functional liver as possible. Sixty-four patients with HCC, including 30 with Child B liver cirrhosis, received SPECT-B-3DCRT and none ex-perienced fatal radiation-induced liver disease(RILD). The Child-Pugh score deteriorated by 1 or 2 in > 20% of functional liver volume that was irradiated with ≥ 20 Gy. The deterioration in the Child-Pugh score decreased when the radiation plan was designed to irradiate ≤ 20% of the functional liver volume in patients givendoses of ≥ 20 Gy(FLV20Gy). Therefore, FLV20 Gy ≤ 20% may represent a safety index to prevent RILD during 3DCRT for HCC. To supplement FLV20 Gy as a qualitative index, we propose a quantitative indicator, F 20 Gy, which was calculated as F 20 Gy = 100% ×(the GSA count in the area irradiated with ≥ 20 Gy)/(the GSA count in the whole liver).

Modified simultaneous integrated boost radiotherapy for an unresectable huge refractory pelvic tumor diagnosed as a rectal adenocarcinoma

A clinical trial of radiotherapy with modified simultaneous integrated boost(SIB)technique against huge tumors was conducted.A 58-year-old male patient who had a huge pelvic tumor diagnosed as a rectal adenocarcinoma due to familial adenomatous polyposis was enrolled in this trial.The total dose of 77 Gy(equivalent dose in 2Gy/fraction)and 64.5 Gy was delivered to the center of the tumor and the surrounding area respectively,andapproximately 20%dose escalation was achieved with the modified SIB technique.The tumor with an initial maximum size of 15 cm disappeared 120 d after the start of the radiotherapy.Performance status of the patient improved from 4 to 0.Radiotherapy with modified SIB may be effective for patients with a huge tumor in terms of tumor shrinkage/disappearance,improvement of QOL,and prolongation of survival.

Stereotactic Radiotherapy Planning Using Modified Dynamic Conformal Arcs under Considering the Possibility for Amended Visual Organ Displacement Resulting from Early Tumor Shrinkage during Treatment for Perioptic Involvement of Myeloma

Treatment planning of radiotherapy for skull base involvement of multiple myeloma presenting with visual impairment should be optimized to alleviate symptoms immediately and sufficiently while minimizing toxicities. Two such patients were treated with fractionated stereotactic radiotherapy by using Dynamic Conformal Arcs (DCA) under image guidance based on bony anatomy alignment. DCA planning was optimized after considering the possibility for amendment of visual organ displacement resulting from early tumor shrinkage during treatment through 1) the use of a target volume with modified geometry as a surrogate for leaf adaptation in order to improve target coverage, and 2) manual adjustment of a subset of leaf positions to reduce the dose gradient immediately inside the target boundary facing the visual organs and to eliminate an undesirable dose hotspot. In both cases, anticipated geometric changes in the target volume associated with improvement of visual organ displacement toward the target centroid were observed before the completion of treatment. Favorable visual functional outcomes as well as local tumor control were achieved during 14 months and 4 months follow-up periods. Notably, inexorable visual loss in one patient was fully reversed within one month after radiotherapy. We described the modification techniques for DCA planning in detail.

Hi'CT:a pixel sensor-based device for ion tomography

Carbon ions,commonly referred to as particle therapy,have become increasingly popular in the last decade.Accurately predicting the range of ions in tissues is important for the precise delivery of doses in heavy-ion radiotherapy.Range uncertainty is currently the largest contributor to dose uncertainty in normal tissues,leading to the use of safety margins in treatment planning.One potential method is the direct relative stopping measurement(RSP)with ions.Heavy-ion CT(Hi′CT),a compact segmented full digital tomography detector using monolithic active pixel sensors,was designed and evaluated using a 430 MeV/u high-energy carbon ion pencil beam in Geant4.The precise position of the individual carbon ion track can be recorded and reconstructed using a 30μm×30μm small pixel pitch size.Two types of customized image reconstruction algorithms were developed,and their performances were evaluated using three different modules of CAT-PHAN 600-series phantoms.The RSP measurement accuracy of the tracking algorithm for different types of materials in the CTP404 module was less than 1%.In terms of spatial resolution,the tracking algorithm could achieve a 20%modulation transfer function normalization value of CTP528 imaging results at 5 lp/cm,which is significantly better than that of the fast imaging algorithm(3 lp/cm).The density resolution obtained using the tracking algorithm of the customized CTP515 was approximately 10.5%.In conclusion,a compact digital Hi'CT system was designed,and its nominal performance was evaluated in a simulation.The RSP resolution and image quality provide potential feasibility for scanning most parts of an adult body or pediatric patient,particularly for head and neck tumor treatment.

Static superconducting gantry‑based proton CT combined with X‑ray CT as prior image for FLASH proton therapy

Proton FLASH therapy with an ultra-high dose rate is in urgent need of more accurate treatment plan system(TPS)to promote the development of proton computed tomography(CT)without intrinsic error compared with the transformation from X-ray CT.This paper presents an imaging mode of proton CT based on static superconducting gantry different from the conventional rotational gantry.The beam energy for proton CT is fixed at 350 MeV,which is boosted by a compact proton linac from 230 MeV,and then delivered by the gantry to scan the patient’s body for proton imaging.This study demonstrates that the static superconducting gantry-based proton CT is effective in clinical applications.In particular,the imaging mode,which combines the relative stopping power(RSP)map from X-ray CT as prior knowledge,can produce much a higher accuracy RSP map for TPSs and positioning and achieve ultra-fast image for real-time image-guided radiotherapy.This paper presents the conceptual design of a boosting linac,static superconducting gantry and proton CT imaging equipment.The feasibility of energy enhancement is verified by simulation,and results from Geant4 simulations and reconstruction algorithms are presented,including the simulation verification of the advantage of the imaging mode.

胸部肿瘤使用手臂支撑架和不同配准方式的误差分析

目的为了提高摆位精度、提升患者摆位舒适性、加快摆位时间、减少摆位误差,比较手臂支撑托架与普通摆位在放疗中引起的摆位误差,分析手臂支撑托架的固定效果和使用的必要性;分析不同配准方式对摆位误差的影响。方法回顾性分析于2021年8月—2022年12月在眉山市中医医院接受放射治疗的40例胸部肿瘤患者作为分析样本。将这些患者随机分为两组,即A组和B组,各20例患者。A组为支撑架摆位,B组为普通摆位。A组:(1)头颈胸腹一体式固定框架;(2)固定头枕;(3)胸腹部长条热塑膜;(4)体表标记线;(5)手臂支撑托架。B组:(1)头颈胸腹一体式固定框架;(2)固定头枕;(3)胸腹部长条热塑膜;(4)体表标记线;(5)双手报肘置于额头辅助摆位。两组患者开始治疗第一周实行5次CBCT扫描,往后每周扫描一次记录其摆位误差数据;采用的配准方式为:(1)骨配准;(2)灰度配准;(3)靶区配准,A组和B组都采用以上三种方式进行配准并对Z(升降)Y(头脚)X(左右)等各项数据进行分析。结果两组相比手臂支撑托架组在骨、软组织、靶区配准方式中Z(升降)Y(头脚)X(左右)方向的统计学意义分别是骨Z(P>0.05),Y(P<0.05),X(P<0.05);软组织Z(P>0.05),Y(P<0.05),X(P<0.05);靶区Z(P>0.05),Y(P<0.05),X(P<0.05);AB两组分别使用同组不同配准方式对比在Z、Y、X方向的误差进行对比,B组仅在骨与靶区Y方向上(P>0.05),其余均P<0.05。结论因此在治疗胸部肿瘤时手臂支撑托架摆位误差小于普通摆位,在配准方式方面应首选为软组织配准。

螺旋断层放疗系统原理及其应用

目的:研究螺旋断层放疗系统的结构及治疗工作原理,初步探讨该设备在临床中的应用价值。方法:对国内第一台螺旋断层放疗设备系统展开研究,初步探讨螺旋断层与传统放疗技术相比在临床应用中的技术优势。结果:螺旋断层放疗系统是目前一种具有全新治疗技术的设备,其在CT的基础上融合直线加速器技术而得到了独一无二的新型组合,同时具备2种机器的功能特性。该系统已被证明了既能实现优异的调强放射治疗,又能做出卓越的图像引导放射治疗,甚至剂量引导下的放射治疗技术,开创了调强放射治疗(IMRT)计划、治疗实施和验证为一体。结论:图像引导下放射治疗(IGRT)和调强放射治疗技术,开辟了肿瘤放射治疗的新领域,它们在更好地控制肿瘤的情况下改善了患者的生存质量。Tomotherapy作为从一开始就被设计用来进行IGRT和IMRT治疗的设备,一直站在了技术发展的最前沿,而且将IGRT和IMRT技术发展得更为简单而高效。

In Room CT与电子射野影像系统在头颈部肿瘤图像引导放射治疗中配准的对比研究

目的应用In Room CT与电子射野影像系统(EPID)技术测量分析头颈部肿瘤图像引导放射治疗(IGRT)的摆位误差,并评价In Room CT在放疗中摆位修正的应用价值。方法选取施行IGRT的头颈部肿瘤患者20例,每周1次于放疗前行EPID摄片后,行In Room CT扫描,将EPID图像与DRR、In Room CT图像与计划CT图像配准得出摆位误差值。以In Room CT的误差值进行修正后放疗,放疗后再行EPID片的拍摄并与DRR配准。计算三组数据的均值、标准差,进行统计学处理。结果放疗前EPID组与In Room CT组在X,Y轴方向配准结果较为相近(P>0.05),Z轴方向(P<0.05);通过修正前后EPID配准比较,应用In Room CT修正,缩小了放疗摆位误差,Y、Z轴方向具有统计学意义(P<0.05)。结论 In Room CT与EPID图像都能很好地验证放疗靶区位置。In Room CT图像可以分析三维方向的影像误差,降低了EPID图像因影像重叠对摆位误差所产生在影响。