Image guided radiotherapy for prostate cancer

The purpose of external beam radiotherapy is to sterilize malignant tumours and at the same time to avoid complications by radiation injury to the surrounding healthy tissues. Modern radiation techniques in recent years have allowed to safely escalate the dose by approximately 10% for the treatment of prostate cancer, resulting in a disease control that is nowadays comparable to surgery or permanent seed implant brachytherapy. Two recent technical developments have dramatically increased the precision of radiation dose delivery: conformal radiotherapy and image guided radiotherapy (IGRT). Conformal radiotherapy aims to shape the dose distribution to the shape of the target. At least equally important as conformality is the accurate spatial delivery of the conformal dose distribution to the target. Conventional patient positioning by skin drawings and lasers is an imprecise way to target the prostate within the pelvis. The need for adequate patient/target setup led in recent years to the development of a variety of solutions. They bear in common that setup is no longer guided by skin marks but by some imaging modality. An ideal IGRT system would allow for daily prostate imaging without possible introduction of errors due to image-acquisition itself, do so within a reasonable time frame, without the necessity for implanted radio-opaque markers and preferentially without exposing the patient to radiation. A solution that combines all these features is inexistent so far.     

Adaptive radiotherapy for bladder cancer reduces integral dose despite daily volumetric imaging

We studied the integral radiation dose in 27 patients who had adaptive radiotherapy for bladder cancer using kilo voltage cone beam CT imaging. Compared to conventional radiotherapy the reduction in margin and choice of best plan of three for the day resulted in a lower total dose in most patients despite daily volumetric imaging.     

La radiothérapie guidée par l’image (IGRT)

Image guided radiation therapy (IGRT) is a major technical innovation of radiotherapy. It allows locating the tumor under the linear accelerator just before the irradiation, by direct visualization (3D mode soft tissue) or indirect visualization (2D mode and radio-opaque markers). The technical implementation of IGRT is done by very different complex devices. The most common modality, because available in any new accelerator, is the cone beam CT. The main experiment of IGRT focuses on prostate cancer. Preliminary studies suggest the use of IGRT combined with IMRT should increase local control and decrease toxicity, especially rectal toxicity. In head and neck tumors, due to major deformation, a rigid registration is insufficient and replanning is necessary (adaptive radiotherapy). The onboard imaging delivers a specific dose, needed to be measured and taken into account, in order not to increase the risk of toxicity. Studies comparing different modalities of IGRT according to clinical and economic endpoints are ongoing; to better define the therapeutic indications.     

Adaptive Radiotherapy in the Management of Cervical Cancer: Review of Strategies and Clinical Implementation

The complex and varied motion of the cervix–uterus target during external beam radiotherapy (EBRT) underscores the clinical benefits afforded by adaptive radiotherapy (ART) techniques. These gains have already been realised in the implementation of image-guided adaptive brachytherapy, where adapting to anatomy at each fraction has seen improvements in clinical outcomes and a reduction in treatment toxicity. With regards to EBRT, multiple adaptive strategies have been implemented, including a personalised internal target volume, offline replanning and a plan of the day approach. With technological advances, there is now the ability for real-time online ART using both magnetic resonance imaging and computed tomography-guided imaging. However, multiple challenges remain in the widespread dissemination of ART. This review investigates the ART strategies and their clinical implementation in EBRT delivery for cervical cancer.     

A Systematic Review of Organ Motion and Image-guided Strategies in External Beam Radiotherapy for Cervical Cancer

Advanced radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT), may significantly benefit cervical cancer patients, in terms of reducing late toxicity and potentiating dose escalation. Given the steep dose gradients around the planning target volume (PTV) with IMRT planning, internal movement of organs during treatment may cause geographical miss of the target and unnecessary organs at risk (OAR) inclusion into high dose regions. It is therefore important to consider the extent and patterns of organ motion and to investigate potential image-guided radiotherapy (IGRT) solutions before implementing IMRT for cervical cancer. A systematic literature search was carried out using Medline, Embase, Cochrane Library, Web of Science, Cinahl and Pubmed. Database-appropriate search strategies were developed based upon terms for uterine neoplasms, IGRT, organ motion and target volume. In total, 448 studies were identified and screened to find 39 relevant studies, 12 of which were abstracts. These studies show that within the target volume for cervical cancer radiotherapy, uterine motion is greater than cervical. Uterine motion is predominantly influenced by bladder filling, cervical motion by rectal filling. Organ motion patterns are patient specific, with some having very little (5 mm) and others having much larger shifts (40 mm) of the target volume. Population-based clinical target volume (CTV)–PTV margins would be large (up to 4 cm around the uterus), resulting in unnecessary OAR inclusion within the PTV, reducing the benefits of IMRT. Potential solutions include anisotropic margins with increased margins in the anteroposterior and superoinferior directions, or greater PTV margins around the uterine fundus than the cervix. As pelvic organ motion seems to be patient specific, individualised PTV margins and adaptive IGRT strategies have also been recommended to ensure target volume coverage while increasing OAR sparing. Although these strategies are promising, they need significant validation before they can be adopted into clinical practice.     

图像引导对宫颈癌放疗中直肠、膀胱照射剂量的影响

目的 分析宫颈癌根治性外照射图像引导与否对直肠和膀胱受照剂量的影响,探讨IGRT技术合理应用的模式。方法 选取2012—2016年于陆军总院行HT的宫颈癌患者20例。每次治疗前均进行MVCT扫描,应用MVCT图像在HT的自适应模块上进行剂量重建,得到当次的受量,并模拟出该次无图像引导下的受量;将各单次剂量分布和对应的融合CT图像传输至形变软件MIM6.0中进行剂量叠加,得到总照射剂量。对比图像引导与否对直肠及膀胱受量和体积的影响。结果 无图像引导的Plan-2的直肠和膀胱受量均高于图像引导下的Plan-1,其中直肠Dmax、V50及膀胱V50均不同(P=0.040、0.000、0.047);分次间初次治疗的Dmax和V50及治疗第13~21次的直肠V50与Plan-1比差异有统计学意义(P=0.047、0.037,P=0.009、0.017、0.028),首次及21~23次放疗的膀胱Vmax、V50与Plan-1比接近有统计学意义(P=0.061、0.053,P=0.072、0.058)。结论 图像引导可以降低直肠和膀胱的受照剂量及体积,尤其是直肠从图像引导获益更大;建议外照射半量左右(13次左右),肿瘤退缩明显时段,重新定位修改治疗计划;对于难以实现全程图像引导的情况下,进行选择性的图像引导,也可以达到有效地降低直肠和膀胱损伤发生的效果。     

CT-guided intensity-modulated radiotherapy for bladder cancer: isocentre shifts, margins and their impact on target dose.

BACKGROUND AND PURPOSE: Image-guided radiotherapy (IGRT) has great potential to improve the treatment of tumour sites that exhibit large geometrical uncertainties such as the bladder. This study quantifies the size and direction of the daily 3D isocentre shift resulting from the use of IGRT and its impact on reducing the margins required. The changes to target dose coverage, delivered dose and dose homogeneity appearing when used in conjunction with intensity-modulated radiotherapy (IMRT) are also assessed. MATERIALS AND METHODS: The study is performed using a series of 19 bladder cancer patients that underwent weekly repeat conventional CT scanning during their 6-7 weeks treatment course. The isotropic margin required to cover various percentages of the volumes of the repeat scans CTVs is found by growing the planning scan PTV by incrementing the margin in steps of 1mm until full coverage is obtained. The optimum daily isocentre shift is determined by moving the repeat scan CTV in 3D so that its volume that lies outside the planning CTV is minimised. Reduction in the isotropic margin after applying the optimum isocentre shift is found by repeating the above procedure. Individual optimum sizes of the six margins required in the sup/inf/ant/post/right/left directions are determined using a recently published empirical margin determination method. Finally, five-field IMRT plans are set up (that minimise the dose deviation throughout the target) using different planning CTV margin alternatives, the optimal isocentre shifts are applied and the target dose distributions are assessed after recalculation without changing any of the beam parameters. RESULTS: Without use of IGRT (i.e., without shifting to the optimal isocentre), an isotropic margin of 30mm is required to cover fully all the CTV volumes on the repeat scans for all patients. The direction of the optimum isocentre shift required is random with an average directional shift less than 1mm and is unlikely to exceed an absolute value of 15mm (average of 7mm). Applying the optimum isocentre shift reduces the isotropic margin to 16mm for full volume coverage. Determining the optimum margin individually in each of six orthogonal directions reduces the target volume by approximately 30% but requires complex daily planning. Applying the optimum isocentre shift to IMRT plans shows little change to the overall mean target dose of 100% (an average increase of 1%), but produces a spread in the daily mean dose ranging from 96% to 106%. The 3D dose variation over the target is within the 95-107% acceptable range in 72% of cases for a 12mm uniform margin, which increases to 91% if any deviation from the daily prescribed dose is removed. The minimum and maximum doses within the target can show significant changes. CONCLUSION: The use of IGRT in the treatment of bladder cancer leads to a marked reduction in the margins required. When used in conjunction with IMRT, the pre-treatment plan is shown to be acceptable for daily treatment (after shifting the isocentre) in terms of the resulting dose distribution provided the correct daily mean dose is delivered. That can be achieved by rescaling the daily monitor units for each treatment beam.     

Radiothérapie guidée par l’image et adaptative

Image-guided radiotherapy (IGRT) aims to take into account anatomical variations occurring during irradiation by visualization of anatomical structures. It may consist of a rigid registration of the tumour by moving the patient, in case of prostatic irradiation for example. IGRT associated with intensity-modulated radiotherapy (IMRT) is strongly recommended when high-dose is delivered in the prostate, where it seems to reduce rectal and bladder toxicity. In case of significant anatomical deformations, as in head and neck tumours (tumour shrinking and decrease in volume of the salivary glands), replanning appears to be necessary, corresponding to the adaptive radiotherapy. This should ideally be “monitored” and possibly triggered based on a calculation of cumulative dose, session after session, compared to the initial planning dose, corresponding to the concept of dose-guided adaptive radiotherapy. The creation of “planning libraries” based on predictable organ positions (as in cervical cancer) is another way of adaptive radiotherapy. All of these strategies still appear very complex and expensive and therefore require stringent validation before being routinely applied.     

Radiothérapie guidée par l’image des cancers prostatiques : concepts et implications

Intensity modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) are technological developments, which when applied in a model of prostate cancer, led to a significant reduction in the toxicity and digestive and urinary sequelae of 3D conformational radiotherapy. The major clinical benefits of these techniques with regard to reduced digestive and urinary toxicity are unequivocal since very few sequelae have been reported at 10 years (2% of grade 2 and 1% of grade 3 digestive toxicity; 11% of grade 2 and 5% of grade 3 urinary toxicity). Even when these two techniques are combined, IG–IMRT significantly diminishes late genitourinary toxicity. In the absence of adaptive radiotherapy, there are many IGRT protocols and repositioning techniques, and every step in the IGRT process must be carried out with extreme rigor: installing the patient and contention system, repositioning technique with or without fiduciary markers, type of repositioning imaging, definition of margins inherent in each technique (prostate, seminal vesicles and/or pelvic lymph nodes), frequency of repositioning during treatment, dietary constraints with or without rectal lavage. For these reasons, every centre that performs IGRT must carefully and rigorously assess the uncertainties of repositioning linked to the IGRT technique. In this review, we analyzed data from the literature based on dosimetric studies and the proven clinical impact in order to answer the different questions asked by radiation oncologists at every step of the IGRT process for cancer of the prostate. Recommendations are made for the repositioning protocols according to the most widely used repositioning techniques: fiduciary markers or soft tissues, kV-CBCT or MV-CBCT, 3D ultrasonography.     

Image-guided radiotherapy for rectal cancer: a systematic review

Radiotherapy for rectal cancer is becoming more conformal. Both the rectum and the mesorectum are mobile structures and the use of image-guided radiotherapy techniques may improve treatment delivery. Studies up to 2008 have previously been reviewed; rectal motion was mostly studied in bladder and prostate cancer cases. Large variations were seen in both the rectal volume and rectal wall displacement during the treatment course. We reviewed the literature on primary rectal cancer. A systematic review was conducted using Medline and Embase databases using the keywords 'rectal, radiotherapy, IGRT, image guided, organ motion, internal margin, target shape/volume'. Nine studies looked at both inter- and intrafractional motion of the gross tumour volume, rectum, mesorectum and the clinical target volume using a variety of imaging modalities. There was significant movement in the upper mesorectum. There was a strong relationship between rectal filling and mesorectal motion. Differences according to gender and body mass index have been reported. One study showed adequate dose to the rectum despite rectal motion and deformation. Current margin recipes may not apply to deformable structures. Suggested margins for the clinical target volume to planning target volume expansion are between 1 and 3.5cm. There may be a role for re-imaging and re-planning during a treatment course. From the available data, electronic portal imaging devices should continue to be used to match for bony anatomy. Additional information on internal motion can be obtained by cone beam computer tomography or tomotherapy and if available its use should be considered. Individualised anisotropic margins may be required. Further work is required to assess the optimal imaging modality, whether to match to bone or soft tissue, and to assess if internal motion affects treatment outcome.     

A cone beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy

PURPOSE: There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. METHODS AND MATERIALS: The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CT(ref)) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. RESULTS: A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CT(ref), mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. CONCLUSIONS: Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance.     

Radiothérapie guidée par la tomographie conique (cone beam computed tomography) : mise en œuvre et applications cliniques

The kV cone beam CT (CBCT) consists of an X-ray tube and a flat panel detector placed perpendicularly to the treatment beam, allowing the acquisition of hundreds of projections in one rotation of the gantry about the patient. Available in all new linear accelerators, the CBCT provides volumetric imaging in treatment position proving the realization of image- and dose-guided radiotherapy (IGRT and DGRT). The clinical indications correspond to mobile tumours irradiating with high precision required techniques, such as stereotactic, hypofractionated or high dose radiotherapy. The clinical experience is still very limited and concerns mainly prostate, head and neck and lung tumours. The registration and treatment protocols are briefly described. Quality control and training are major issues. CBCT based IGRT is a new technique which needs to be optimized. However, it should provide significant clinical benefit in combination with intensity modulated radiotherapy and new imaging modalities for target delineation.     

Image-Guided Radiotherapy for Pelvic Cancers: A Review of Current Evidence and Clinical Utilisation

The meticulous selection and utilisation of image-guided radiotherapy (IGRT) are essential for optimal radiotherapy treatment delivery when using highly conformal treatment techniques in pelvic radiotherapy. Pelvic IGRT has several general IGRT issues to consider (such as choice of match strategy, prioritisation between multiple treatment targets and margin estimates) as well as issues specific to pelvic radiotherapy, in particular large inter-fraction organ variation. A range of interventions, including adaptive treatment strategies, have been developed to address these challenges. This review covers general considerations for the clinical implementation of pelvic IGRT in routine practice and provides an overview of current knowledge regarding pelvic inter-fraction organ motion. Published IGRT evidence for each of the major tumour sites (gynaecological, prostate, bladder, rectal and anal cancer) is summarised, as are state-of-the-art adaptive approaches. General recommendations for the implementation of an institutional pelvic IGRT strategy include.•Ensuring consistency between treatment intent and the IGRT approach utilised.•Ensuring minimum national and international IGRT guidance is followed while considering the benefit of daily volumetric IGRT.•Ensuring the appropriate allied health professionals (namely therapy radiographers/radiation therapists) lead on undertaking IGRT.•Ensuring the IGRT workflow procedure is clear and includes an escalation process for difficult set-ups.•Ensuring a robust IGRT service is in place before implementing advanced adaptive approaches.     

图像引导的放射治疗技术

胸腹部肿瘤因呼吸等生理运动处于不断运动的状态,影响成像、治疗计划和治疗过程的精确度。图像引导放疗(IGRT)技术有望解决运动肿瘤的精确治疗问题,它主要分为3个研究方向。其中,呼吸门控放疗开展较早,已经进入临床应用;集成放疗成像系统把定位和治疗设备合二为一,实现常规模拟定位、锥形束CT和实时成像等功能;射束同步放疗技术以四维CT成像技术为基础,控制动态多叶光栅使射束随着肿瘤的运动而不断运动,是最理想的放疗实现模式。     

Gating and tracking, 4D in thoracic tumours

The limited ability to control for a tumour's location compromises the accuracy with which radiation can be delivered to tumour-bearing tissue. The resultant requirement for larger treatment volumes to accommodate target uncertainty restricts the radiation dose because more surrounding normal tissue is exposed. With image-guided radiation therapy (IGRT), these volumes can be optimized and tumouricidal doses may be delivered, achieving maximum tumour control with minimal complications. Moreover, with the ability of high precision dose delivery and real-time knowledge of the target volume location, IGRT has initiated the exploration of new indications in radiotherapy such as hypofractionated radiotherapy (or stereotactic body radiotherapy), deliberate inhomogeneous dose distributions coping with tumour heterogeneity (dose painting by numbers and biologically conformal radiation therapy), and adaptive radiotherapy. In short: “individualized radiotherapy”. Tumour motion management, especially for thoracic tumours, is a particular problem in this context both for the delineation of tumours and organs at risk as well as during the actual treatment delivery. The latter will be covered in this paper with some examples based on the experience of the UZ Brussel. With the introduction of the NOVALIS system (BrainLAB, Feldkirchen, Germany) in 2000 and consecutive prototypes of the ExacTrac IGRT system, gradually a hypofractionation treatment protocol was introduced for the treatment of lung tumours and liver metastases evolving from motion-encompassing techniques towards respiratory-gated radiation therapy with audio-visual feedback and most recently dynamic tracking using the VERO system (BrainLAB, Feldkirchen, Germany). This evolution will be used to illustrate the recent developments in this particular field of research.     

放射物理学及分子放射生物学在临床放疗实践中的应用和未来发展

最近几年,放射物理学和分子放射生物学的进步促进了放射肿瘤学的显著发展.目前,我们从常规的二维放疗到三维适形放疗,已进入了调强放疗(intensity-modulated radiotherapy,IMRT)和影像引导放疗(image-guided radiotherapy,IGRT)的时代.IMRT/IGRT可对肿瘤组织进行适形治疗,对正常组织适形地避免照射,从而改善肿瘤控制并减少治疗相关的放射损伤.目前无框架立体定向放射手术(stereotactic radiosurgery,SRS)和立体定向体部放疗(stereotactic body radiotherapy,SBRT)已进入临床应用,这为放射肿瘤临床提供了更多的治疗选择.随着影像引导技术的进步,近距离放疗得到了发展,尤其是应用于早期前列腺癌,获得了非常满意的长期疗效.带电粒子治疗,包括质子疗法是新开发的充满前景的领域.放疗与传统化疗、激素疗法、新的靶向治疗和基因疗法联合使用为克服放疗抗拒、改善放疗指数提供了更好的局部-区域和全身癌症控制效果.最近进行的一项关于头颈部癌的随机临床试验表明,与单纯放疗相比,放疗联合靶向治疗可以提高患者生存率,而在功能或分子影像学方面取得的进步为提高人们对肿瘤靶区的认识提供了新的机会(例如乏氧区),并可进行对应放射剂量的调强治疗.在放疗中整合PET/CT可在治疗计划测定中有助于进行靶区勾画和对放疗反应的评估.放射抗拒相关的肿瘤干细胞、基因表达图谱分析以及毫微秒技术也是新进展的领域,随着个体化用药的发展,正在作进一步研究.     

Les promesses de la radiothérapie. Focus sur les tumeurs pulmonaires

Radiotherapy is a key cancer treatment, which greatly modified its practice in recent years thanks to medical imaging and technical improvements. The systematic use of computed tomography (CT) for treatment planning, the imaging fusion/co-registration between CT/magnetic resonance imaging (MRI) or CT/positron emission tomography (PET) improve target identification/selection and delineation. New irradiation techniques such as image-guided radiotherapy (IGRT), stereotactic radiotherapy or hadron therapy offer a more diverse therapeutic armamentarium to patients together with lower toxicity. Radiotherapy, as well as medical oncology, tends to offer a personalized treatment to patients thanks to the IGRT, which takes into account the inter- or intra-fraction anatomic variations. IGRT leads to adaptive radiotherapy (ART) with a new planification in the treatment course in order to decrease toxicity and improve tumor control. The use of systemic therapies with radiations needs to be studied in order to improve efficiency without increasing toxicities from these multimodal approaches. Finally, radiotherapy advances were impacted by radiotherapy accidents like Epinal. They led to an increased quality control with the intensification of identity control, the emergence of in vivo dosimetry or the experience feedback committee in radiotherapy. We will illustrate through the example of lung cancer.