Innovations in image-guided radiotherapy

The limited ability to control for the location of a tumour 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 radiotherapy (IGRT) these volumes can be optimized and tumoricidal doses can be delivered, achieving maximal 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 for radiotherapy, some of which were previously considered infeasible.     

Image-guided radiotherapy: has it influenced patient outcomes?

Cancer control and toxicity outcomes are the mainstay of evidence-based medicine in radiation oncology. However, radiotherapy is an intricate therapy involving numerous processes that need to be executed appropriately in order for the therapy to be delivered successfully. The use of image-guided radiation therapy (IGRT), referring to imaging occurring in the radiation therapy room with per-patient adjustments, can increase the agreement between the planned and the actual dose delivered. However, the absence of direct evidence regarding the clinical benefit of IGRT has been a criticism. Here, we dissect the role of IGRT in the radiotherapy (RT) process and emphasize its role in improving the quality of the intervention. The literature is reviewed to collect evidence that supports that higher-quality dose delivery enabled by IGRT results in higher clinical control rates, reduced toxicity, and new treatment options for patients that previously were without viable options.     

A (short) history of image-guided radiotherapy.

Progress in radiotherapy is guided by the need to realize improved dose distributions, i.e. the ability to reduce the treatment volume toward the target volume and still ensuring coverage of that target volume in all dimensions. Poor ability to control the tumour's location limits the accuracy with which radiation can be delivered to tumour-bearing tissue. Image-guided radiation therapy (IGRT) aims at in-room imaging guiding the radiation delivery based on instant knowledge of the target location and changes in tumour volume during treatment. Advancements are usually not to be attributed to a single event, but rather a combination of many small improvements that together enable a superior result. Image-guidance is an important link in the treatment chain and as such a major factor in this synergetic process. A historic review shows that many of the so-called new developments are not so new at all, but did not make it into mainstream radiotherapy practice at that time. Recent developments in improved IT infrastructures, novel irradiation techniques, and better knowledge of functional and morphologic information may have created the need and optimal environment to revive the interest in IGRT.     

头颈部肿瘤自适应放疗的研究进展

调强放射治疗(intensity-modulated radiation therapy,IMRT)是头颈部恶性肿瘤的重要治疗方法之一。但在IMRT过程中,摆位误差、解剖结构的移位及变形、肿瘤退缩或进展及形状改变等,可导致靶区和危及器官的照射剂量和体积出现“偏差”,影响IMRT的精确性。图像引导的放射治疗(image-guidedradiotherapy,IGRT)可部分纠正摆位误差,从而提高放疗精度,但不能解决非刚性误差以及解剖结构变化带来的剂量差异。自适应放射治疗(adaptive radiation therapy,ART)是在IMRT和IGRT基础上出现的新型放疗技术,能修正IMRT和IGRT靶区和危及器官的偏差。通过患者图像、剂量等反馈信息对原治疗计划重新优化和调整,这是一种基于反馈控制理论的治疗策略。其目的是使放射治疗更加精确化、个体化。     

Apport de la radiothérapie guidée par l’image et repositionnement du patient dans le cancer anorectal

Intensity-modulated radiation therapy is recommended in anal squamous cell carcinoma treatment and is increasingly used in rectal cancer. It adapts the dose to target volumes, with a high doses gradient. Intensity-modulated radiation therapy allows to reduce toxicity to critical normal structures and to consider dose-escalation studies or systemic treatment intensification. Image-guided radiation therapy is a warrant of quality for intensity-modulated radiation therapy, especially for successful delivery of the dose as planned. There is no recommended international or national anorectal cancer image-guided radiation therapy protocol currently available. Dose-escalation trials or expert opinions about intensity-modulated/image-guided radiation therapy good practice guidelines recommend daily volumetric imaging throughout the treatment or during the five first fractions and weekly thereafter as a minimum. Image-guided radiation therapy allows to reduce margins related to patient setup errors. Internal margin, related to the internal organ motion, needs to be adapted according to short- or long-course radiotherapy, gender, rectal location; it can be higher than current recommended planning target volume margins, particularly in the upper and anterior part of mesorectum, which has the most significant movement. Image-guided radiation therapy based on volumetric imaging allows to take target volume shrinkage into account and to develop adaptive strategies, in particular for mesorectum shrinkage during rectal cancer treatment. Lastly, the emergence of new image-guided radiation therapy technologies including MRI (which plays a major role in pelvic tumours assessment and diagnosis) opens up interesting perspectives for adaptive radiotherapy, taking into account both organs’ movements and tumour shrinkage.     

« Dose-painting » : mythe ou réalité ?

“Dose-painting” radiotherapy allows for a heterogeneous delivery of radiation within the tumour volume by targeting radioresistant areas defined by functional imaging. Within gross tumour volume, it is possible to define one or more target volumes based on biology (biological target volume [BTV]) and to apply a strategy of intensity modulated radiation therapy (IMRT) that will deliver a higher dose to these regions. In this review of the literature, we will highlight the biological elements responsible for radioresistance, and how to image them, then we will detail the radiotherapy techniques necessary for this approach, before presenting clinical results in various situations (head and neck tumours, prostate, brain tumours, etc.). Despite many difficulties that make dose-painting IMRT unusable in routine nowadays, biology-guided radiation therapy represents one of the major pathways of development of radiotherapy in the coming years.     

Image-guided radiotherapy]

Recent advances in radiation oncology are based on improvement in dose distribution thanks to IMRT and improvement in target definition through new diagnostic imaging such as spectroscopic or functional MRI or PET. However, anatomic variations may occur during treatment decreasing the benefit of such optimization. Image-guided radiotherapy reduces geometric uncertainties occurring during treatment and therefore should reduce dose delivered to healthy tissues and enable dose escalation to enhance tumour control. However, IGRT experience is still limited, while a wide panel of IGRT modalities is available. A strong quality control is required for safety and proper evaluation of the clinical benefit of IGRT combined or not with IMRT.     

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。     

Radiothérapie conformationnelle avec modulation d’intensité (RCMI) guidée par l’image : impact de l’augmentation du volume irradié à faible dose ?

Image-guided radiotherapy (IGRT) combined or not with intensity-modulated radiation therapy (IMRT) are new and very useful techniques. However, these new techniques are responsible of irradiation at low dose in large volumes. The control of alignment, realignment of the patient and target positioning in external beam radiotherapy are increasingly performed by radiological imaging devices. The management of this medical imaging depends on the practice of each radiotherapy centre. The physical doses due to the IGRT are however quantifiable and traceable. In one hand, these doses appear justified for a better targeting and could be considered negligible in the context of radiotherapy. On the other hand, the potential impact of these low doses should deserve the consideration of professionals. It appears important therefore to report and consider not only doses in target volumes and in “standard” organs at risk, but also the volume of all tissue receiving low doses of radiation. The recent development of IMRT launches the same issue concerning the effects of low doses of radiation. Indeed, IMRT increases the volume of healthy tissue exposed to radiation. At low dose (< 100 mGy), many parameters have to be considered for health risk estimations: the induction of genes and activation of proteins, bystander effect, radio-adaptation, the specific low-dose radio-hypersensitivity and individual radiation sensitivity. With the exception of the latter, the contribution of these parameters is generally protective in terms of carcinogenesis. An analysis of secondary cancers arising out of field appears to confirm such notion. The risk of secondary tumours is not well known in these conditions of treatment associating IMRT and IGRT. It is therefore recommended that the dose due to imaging during therapeutic irradiation be reported.     

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.     

Technical Radiotherapy Advances – The Role of Magnetic Resonance Imaging-Guided Radiation in the Delivery of Hypofractionation

Safe delivery of hypofractionated radiotherapy requires high levels of accuracy due to the high doses of radiation delivered per fraction. Magnetic resonance guided radiotherapy (MRgRT) represents a new treatment paradigm which allows improved visualisation of targets and organs at risk, alongside the capability to adapt the treatment plan in real time prior to treatment delivery. There are challenges to delivering hypofractionated radiotherapy with conventional image-guided radiotherapy (IGRT) techniques and MRgRT may help to improve accuracy in radiation delivery in a number of clinical and anatomical scenarios.Specifically, there is an emerging role of MRgRT in delivering stereotactic body radiotherapy (SBRT) for locally advanced pancreatic cancer (LAPC) due to the superior soft tissue contrast provided by Magnetic Resonance Imaging combined with the ability to accommodate variation in anatomical appearances during treatment delivery. Reported data on the use of MRgRT in LAPC and it's role in enabling dose escalation are discussed in this article.There are further potential benefits to the use of MRgRT, for example the use of functional imaging during treatment delivery and generation of synthetic computed tomography, which have previously been impractical or unachievable. The overall aim of this article is to demonstrate the utility of MRgRT in facilitating safe delivery of hypofractionated radiotherapy and to highlight ways in which it may help to overcome challenges posed by current IGRT techniques.     

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.     

IGRT in rectal cancer

To date, no great interest has been shown in the clinical implementation of recent Image-guided radiation therapy (IGRT) modalities in rectal cancer since only a few studies have been published on this issue. This may be explained by the fact that with current treatment modalities locoregional recurrences are already very low (around 10%). However, there is still room for improvement in treatment of high risk patients (cT3 CRM+, cT4, N+). In these patients better results may be obtained improving radiation technique from 2D to 3D, which showed to be more reliable in terms of target coverage. Also, when higher doses are delivered, Intensity Modulated Radiation Therapy (IMRT) may be used to spare small bowel. But before employing 3D irradiation or IMRT, a proper definition of our clinical target volume (CTV) and planning target volume (PTV) is needed. The CTV should encompass the tumour site, the mesorectum and the lateral nodes, recognized as the most likely sites of local recurrence, with different incidence according to tumour stage. Recent studies discussed the correct delineation of these target volumes in respect of tumour site and stage. From the preliminary results of a study conducted in Rome University 2D planning seemed insufficient to cover the different target volumes especially in T4 patients compared to 3D planning. Also an appropriate PTV margin is necessary in order to manage set-up errors and organ motion. Particularly in these patients, the knowledge of mesorectal movement is required to avoid target missing. Large mesorectal displacements were observed in a study carried out in Leuven University in collaboration with Rome University. A systematic review of the literature together with the data from these first experiences led to the awareness that IGRT could help us to follow the target volume and organs at risk during the treatment, allowing adjustments to improve accuracy in dose delivery, especially when dose escalation studies are planned in the treatment of rectal cancer.     

The role of radiotherapy in the treatment of desmoid tumours

From 1974 to 1983 in the Netherlands Cancer Institute, 21 patients with desmoid tumours were treated with radiation therapy. Nineteen patients were irradiated postoperatively (11 patients had micro- or macroscopic residual disease, 8 patients treated for recurrent disease had narrow surgical margins), 2 patients with inoperable tumours were treated with radiation alone. The entire involved muscle received a dose of 40 Gy, while a boost of 20 Gy was delivered to the tumour bed. Local control was achieved in 19 out of 21 patients, with an actuarial 5 year disease-free survival of 90%. No relation could be found between the amount of tumour present and local control. With careful set-up of treatment fields and long-term physical therapy, complications like fibrosis, ankylosis and oedema could be minimised. These excellent results with radiotherapy for minimal residual tumour, or even for macroscopic tumour, makes mutilating surgery unnecessary.     

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.     

The use of fiducial markers in image‐guided radiotherapy for gastric cancer

The use of fiducial markers (FM) in image‐guided radiotherapy (IGRT) to increase treatment precision is emerging for upper gastrointestinal malignancies. To our knowledge there is no data beyond technical reports for the use of FMs in IGRT for gastric cancers in the current literature. We report a case of an 89‐year old gentleman with localised gastric cancer who was deemed unfit for surgery and chemotherapy. He had FMs inserted endoscopically around the tumour via ultrasound guidance and received radiotherapy with a high‐dose palliative intent via a two‐phase technique to 54 Gy in 30 fractions with IGRT. The use of FMs allowed confidence in tumour delineation and together with IGRT enabled precise and safe delivery of a higher dose. The patient tolerated the treatment without significant toxicity and had no evidence of residual or recurrent tumour 12 months following radiotherapy. The use of FMs with IGRT in upper gastrointestinal malignancies warrants further collaborative studies.     

Image-guided Adaptive Radiotherapy for Bladder Cancer

Technological advancement has facilitated patient-specific radiotherapy in bladder cancer. This has been made possible by developments in image-guided radiotherapy (IGRT). Particularly transformative has been the integration of volumetric imaging into the workflow. The ability to visualise the bladder target using cone beam computed tomography and magnetic resonance imaging initially assisted with determining the magnitude of inter- and intra-fraction target change. It has led to greater confidence in ascertaining true anatomy at each fraction. The increased certainty of dose delivered to the bladder has permitted the safe reduction of planning target volume margins. IGRT has therefore improved target coverage with a reduction in integral dose to the surrounding tissue. Use of IGRT to feed back into plan and dose delivery optimisation according to the anatomy of the day has enabled adaptive radiotherapy bladder solutions. Here we undertake a review of the stepwise developments underpinning IGRT and adaptive radiotherapy strategies for external beam bladder cancer radiotherapy. We present the evidence in accordance with the framework for systematic clinical evaluation of technical innovations in radiation oncology (R-IDEAL).     

Technological advances in radiotherapy for the treatment of localised prostate cancer

There is good evidence that radiation dose escalation in localised prostate cancer is associated with increased cell kill. The traditional two-dimensional (2D) technique of treatment planning and delivery is limited by normal tissue toxicity, such that the dose that can be safely delivered to the prostate by external beam radiotherapy is 65-70 Gy. Several technological advances over the last 20 years have enhanced the precision of external beam radiotherapy (EBRT), and have resulted in improved outcomes. The three-dimensional conformal radiotherapy (3D-CRT) approach reduces the dose-limiting late side-effect of proctitis and has allowed for dose escalation to the whole prostate to 78 Gy. More recently, intensity modulated radiotherapy (IMRT), an advanced form of conformal therapy, has resulted in reduced rectal toxicity when using doses greater than 80 Gy. In addition, IMRT can potentially escalate the dose to specific parts of the prostate where there are resistant subpopulations of tumour clonogens, or can be used to extend the high-dose region to pelvic lymph nodes. The addition of androgen deprivation to conventional radiotherapy has an impact on survival and local control. Initial hormone therapy causes cytoreduction of the prostate cancer allowing for a reduction in radiotherapy volume as well as an additive effect on cell kill. Long-term adjuvant androgen deprivation has been shown to improve overall survival in more advanced tumours. Prostate brachytherapy is now a recognised treatment for those with low-risk disease. It achieves similar long-term outcome to other treatment modalities. Brachytherapy can be used as monotherapy for localised disease, or as boost treatment following conventional EBRT for locally advanced disease. New techniques are available to improve the precision of both target definition and treatment verification. This so-called image-guided radiotherapy will help to enhance the accuracy of dose delivery by correcting both for inter-fraction positional variation and for intra-fraction movement of the prostate in real-time and will allow for tighter tumour margins and avoidance of normal tissues, thereby enhancing the safety of treatment.     

Broadening the scope of image-guided radiotherapy (IGRT)

The recent wave of enthusiasm for image guidance in radiation therapy is largely due to the advent of on-line imaging devices. The current narrow definition of image-guided radiotherapy (IGRT), in fact, essentially connotes the use of near real-time imaging during treatment delivery to reduce uncertainties in target position and should therefore be termed IGRT-D. However, a broader (and more appropriate) context of image-guidance should include: (1) detection and diagnosis, (2) delineation of target and organs at risk, (3) determining biological attributes, (4) dose distribution design, (5) dose delivery assurance and (6) deciphering treatment response through imaging i.e. the 6 D's of IGRT. Strategies to advance these areas will be discussed.