Special stereotactic radiotherapy techniques: procedures and equipment for treatment simulation and dose delivery

Stereotactic radiotherapy (SRT ) is a multi-step procedure with each step requiring extreme accuracy. Physician-dependent accuracy includes appropriate disease staging, multi-disciplinary discussion with shared decision-making, choice of morphological and functional imaging methods to identify and delineate the tumor target and organs at risk, an image-guided patient set-up, active or passive management of intra-fraction movement, clinical and instrumental follow-up. Medical physicist-dependent accuracy includes use of advanced software for treatment planning and more advanced Quality Assurance procedures than required for conventional radiotherapy. Consequently, all the professionals require appropriate training in skills for high-quality SRT.Thanks to the technological advances, SRT has moved from a “frame-based” technique, i.e. the use of stereotactic coordinates which are identified by means of rigid localization frames, to the modern “frame-less” SRT which localizes the target volume directly, or by means of anatomical surrogates or fiducial markers that have previously been placed within or near the target. This review describes all the SRT steps in depth, from target simulation and delineation procedures to treatment delivery and image-guided radiation therapy. Target movement assessment and management are also described.     

Cardiac toxicity of lung cancer radiotherapy

Radical radiotherapy of lung cancer with dose escalation has been associated with increased tumor control. However, these attempts to continually improve local control through dose escalation, have met mixed results culminating in the findings of the RTOG trial 0617, where the heart dose was associated with a worse overall survival, indicating a significant contribution to radiation-induced cardiac morbidity. It is, therefore, very likely that poorly understood cardiac toxicity may have offset any potential improvement in overall survival derived from dose escalation and may be an obstacle that limits disease control and survival of patients. The manifestations of cardiac toxicity are relatively common after high dose radiotherapy of advanced lung cancers and are independently associated with both heart dose and baseline cardiac risk. Toxicity following the treatment may occur earlier than previously thought and, therefore, heart doses should be minimized. In patients with lung cancer, who not only receive substantial heart dose, but are also older with more comorbidities, all cardiac events have the potential to be clinically significant and life-threatening.Sophisticated radiation treatment planning techniques, charged particle therapy, and modern imaging methods in radiotherapy planning, may lead to reduction of the heart dose, which could potentially improve the clinical outcomes in patients with lung cancer. Efforts should be made to minimize heart radiation exposure whenever possible even at doses lower than those generally recommended. Heart doses should be limited as much as possible.A heart dosimetry as a whole is important for patient outcomes, rather than emphasizing just one parameter.     

MRI-guided lung SBRT: Present and future developments

Stereotactic body radiotherapy (SBRT) is rapidly becoming an alternative to surgery for the treatment of early-stage non-small cell lung cancer patients. Lung SBRT is administered in a hypo-fractionated, conformal manner, delivering high doses to the target. To avoid normal-tissue toxicity, it is crucial to limit the exposure of nearby healthy organs-at-risk (OAR).Current image-guided radiotherapy strategies for lung SBRT are mostly based on X-ray imaging modalities. Although still in its infancy, magnetic resonance imaging (MRI) guidance for lung SBRT is not exposure-limited and MRI promises to improve crucial soft-tissue contrast. Looking beyond anatomical imaging, functional MRI is expected to inform treatment decisions and adaptations in the future.This review summarises and discusses how MRI could be advantageous to the different links of the radiotherapy treatment chain for lung SBRT: diagnosis and staging, tumour and OAR delineation, treatment planning, and inter- or intrafractional motion management. Special emphasis is placed on a new generation of hybrid MRI treatment devices and their potential for real-time adaptive radiotherapy.     

Artificial intelligence in radiotherapy

Artificial intelligence (AI) has already been implemented widely in the medical field in the recent years. This paper first reviews the background of AI and radiotherapy. Then it explores the basic concepts of different AI algorithms and machine learning methods, such as neural networks, that are available to us today and how they are being implemented in radiotherapy and diagnostic processes, such as medical imaging, treatment planning, patient simulation, quality assurance and radiation dose delivery. It also explores the ongoing research on AI methods that are to be implemented in radiotherapy in the future. The review shows very promising progress and future for AI to be widely used in various areas of radiotherapy. However, basing on various concerns such as availability and security of using big data, and further work on polishing and testing AI algorithms, it is found that we may not ready to use AI primarily in radiotherapy at the moment.     

Techniques for adaptive prostate radiotherapy

Variations in the position and shape of the prostate make accurate setup and treatment challenging. Adaptive radiation therapy (ART) techniques seek to alter the treatment plan, at one or more points throughout the treatment course, in response to changes in patient anatomy observed between planning and pre-treatment images. This article reviews existing and developing ART techniques for prostate cancer along with an overview of supporting in-room imaging technologies. Challenges to the clinical implementation of adaptive radiotherapy are also discussed.     

Challenges of radiotherapy: Report on the 4D treatment planning workshop 2013

This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop.     

Dosimetric evaluation of irregular surface compensator and intensity-modulated radiotherapy in breast radiotherapy

BackgroundThis dosimetric study aims to evaluate the dosimetric advantage of the irregular surface compensator (ISC) compared with the intensity-modulated radiotherapy (IMRT).Materials and methodsTen patients with whole breast irradiation were planned with the ISC and IMRT techniques. Six different beam directions were selected for IMRT and ISC plans. The treatment plans were evaluated with respect to planning target coverage, dose homogeneity index (DHI) and organs at risk (OARs) sparing. Monitor units (MUs) and the delivery time were analysed for treatment efficiency.ResultsThe ISC technique provides a better coverage of the PTV and statistically significantly better homogeneity of the dose distribution. For the ipsilateral lung and heart, ISC and IMRT techniques deliver almost the same dose in all plans. However, MU counts and delivery time were significantly lower with the IMRT technique (p < 0.05).ConclusionFor breast radiotherapy, when the ISC method was compared to the IMRT method, ISC provided better dose distribution for the target.     

Recommendations of the Spanish Societies of Radiation Oncology (SEOR), Nuclear Medicine & Molecular Imaging (SEMNiM), and Medical Physics (SEFM) on 18F-FDG PET-CT for radiotherapy treatment planning

Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) is a valuable tool for diagnosing and staging malignant lesions. The fusion of PET and computed tomography (CT) yields images that contain both metabolic and morphological information, which, taken together, have improved the diagnostic precision of PET in oncology. The main imaging modality for planning radiotherapy treatment is CT. However, PET-CT is an emerging modality for use in planning treatments because it allows for more accurate treatment volume definition. The use of PET-CT for treatment planning is highly complex, and protocols and standards for its use are still being developed. It seems probable that PET-CT will eventually replace current CT-based planning methods, but this will require a full understanding of the relevant technical aspects of PET-CT planning. The aim of the present document is to review these technical aspects and to provide recommendations for clinical use of this imaging modality in the radiotherapy planning process.     

Tridimensional dose evaluation of the respiratory motion influence on breast radiotherapy treatments using conformal radiotherapy,forward IMRT,and inverse IMRT planning techniques

PurposeTo evaluate the respiratory motion influence on the tridimensional (3D) dose delivery to breast-shaped phantoms using conformal radiotherapy (3D-RT), Field-in Field (FiF), and IMRT planning techniques.MethodsThis study used breast-shaped phantoms filled with MAGIC-f gel dosimeter to simulate the breast, and an oscillation platform to simulate the respiratory motion. The platform allowed motion in the anterior-posterior direction with oscillation amplitudes of 0.34 cm, 0.88 cm, and 1.22 cm. CT images of the static phantom were used for the 3D-RT, FiF, and IMRT treatment planning. Five phantoms were prepared and irradiated for each planning technique evaluated. Phantom 1 was irradiated static, phantoms 2–4 were irradiated moving with the three different motion amplitudes, and phantom 5 was used as a reference. The 3D dose distributions were obtained by relaxometry of magnetic resonance imaging, and the respiratory motion influence in the doses distribution was accessed by gamma evaluations (3%/3mm/15% threshold) comparing the measurements of the phantoms irradiated under movement with the static ones.ResultsThe mean gamma approvals for three oscillatory amplitudes were 96.44%, 93.23%, and 91.65%; 98.42%, 95.66%, and 94.31%; and 94.49%, 93.51%, and 86.62% respectively for 3D-RT, FiF and IMRT treatments. A gamma results profile per slice along the phantom showed that for FiF and IMRT irradiations, most of the failures occurred in the central region of the phantom.ConclusionsBy increasing the respiratory motion movement, the dose distribution variations for the three planning techniques were more pronounced, being the FiF technique variations the smallest one.     

An international survey of imaging practices in radiotherapy

Improvements in delivery of radiation dose to target tissues in radiotherapy have increased the need for better image quality and led to a higher frequency of imaging patients. Imaging for treatment planning extends to function and motion assessment and devices are incorporated into medical linear accelerators (linacs) so that regions of tissue can be imaged at time of treatment delivery to ensure dose distributions are delivered as accurately as possible. A survey of imaging in 97 radiotherapy centres in nine countries on six continents has been undertaken with an on-line questionnaire administered through the International Commission on Radiological Protection mentorship programme to provide a snapshot of imaging practices. Responses show that all centres use CT for planning treatments and many utilise additional information from magnetic resonance imaging and positron emission tomography scans. Most centres have kV cone beam CT attached to at least some linacs and use this for the majority of treatment fractions. The imaging options available declined with the human development index (HDI) of the country, and the frequency of imaging during treatment depended more on country than treatment site with countries having lower HDIs imaging less frequently. The country with the lowest HDI had few kV imaging facilities and relied on MV planar imaging intermittently during treatment. Imaging protocols supplied by vendors are used in most centres and under half adapt exposure conditions to individual patients. Recording of patient doses, a knowledge of which is important in optimisation of imaging protocols, was limited primarily to European countries.     

Assessing the need for adaptive radiotherapy in head and neck cancer patients using an automatic planning tool

BackgroundUnbiased analysis of the impact of adaptive radiotherapy (ART) is necessary to evaluate dosimetric benefit and optimize clinics’ workflows. The aim of the study was to assess the need for adaptive radiotherapy (ART) in head and neck (H&N) cancer patients using an automatic planning tool in a retrospective planning study.Materials and methodsThirty H&N patients treated with adaptive radiotherapy were analysed. Patients had a CT scan for treatment planning and a verification CT during treatment according to the clinic’s protocol. Considering these images, three plans were retrospectively generated using the iCycle tool to simulate the scenarios with and without adaptation: 1) the optimized plan based on the planning CT; 2) the optimized plan based on the verification CT (ART-plan); 3) the plan obtained by considering treatment plan 1 re-calculated in the verification CT (non-ART plan). The dosimetric endpoints for both target volumes and OAR were compared between scenarios 2 and 3 and the SPIDERplan used to evaluate plan quality.ResultsThe most significant impact of ART was found for the PTVs, which demonstrated decreased D98% in the non-ART plan. A general increase in the dose was observed for the OAR but only the spinal cord showed a statistical significance. The SPIDERplan analysis indicated an overall loss of plan quality in the absence of ART.ConclusionThese results confirm the advantages of ART in H&N patients, especially for the coverage of target volumes. The usage of an automatic planning tool reduces planner-induced bias in the results, guaranteeing that the observed changes derive from the application of ART.     

Imaging opportunities for treatment planning in intraoperative electron beam radiotherapy (IOERT): Developments in the context of RADIANCE system

AimThe purpose of this report is to store the information of the pre-planning and compare this data with the actual data of the procedure.BackgroundCurrently, intraoperative electron beam radiotherapy clinical practice lacks a treatment planning system.Materials and methodsThe RADIANCE concept approaches treatment planning by providing the user with a navigation platform based on a three-dimensional imaging system in which the radiation oncologist can target the tumor and risk areas in different sections (axial, coronal, sagittal), while a volume rendering engine displays a 3D image that is automatically updated as we make any changes of the space. Finally, the user may select the parameters of the applicator, energy and dose of treatment to optimize the procedure. Six cases are clinically described and illustrated.ResultsRADIANCE is a useful tool in planning IOERT. Tumor segmentation and risk areas with minimal guide in the selection of parameters for the applicator. Complex locations are challenging, where the experience and skill of the radiation oncologist is necessary to optimize the process. New developments include imaging innovated uses. Intraoperative imaging will approach reality and allow real time, dosimetry estimations, stereotactic recognition of patient and tumor bed position, will guide automatization of radiation beam recognition and pre-robotic arrangements with linear accelerator movements.ConclusionsRADIANCE offers a new imaging expansion for IOERT, in the context of a multidisciplinary approach to optimize and define the treatment parameters to approximate the actual treatment radiotherapy procedure.     

Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p < 0.05. Of the 45 female and 110 male patients, the median age was 64. Seventy-three percent had cT3 disease and there was a mean tumour distance from the anal verge of 7 cm. Time to surgical resection following radiotherapy ranged from 4 to 162 days with a median of 50 days, with a complete pathological response seen in 21% of patients. Patients exhibiting a favourable pathological response had smaller median pre- and postradiotherapy tumour size and had a greater change in tumour size following treatment (p < 0.01). Patients who received the majority of their radiotherapy fractions after 12:00 pm were more likely to show a complete or moderate pathological response (p = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (p < 0.004), although no relationship was seen between response and tumour distance from the anal verge. Females were less likely to exhibit several of the above responses. Neoadjuvant radiotherapy for locally advanced rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.     

VMAT-like plans for magnetic resonance guided radiotherapy: Addressing unmet needs

PurposeVMAT delivery technique is currently not applicable to Magnetic Resonance-guided radiotherapy (MRgRT) hybrid systems. Aim of this study is to evaluate an innovative VMAT-like (VML) delivery technique.Material and methodsFirst, planning and dosimetric evaluation of the MRgRT VML treatment have been performed on 10 different disease sites and the results have been compared with the corresponding IMRT plans. Then, in the second phase, 10 of the most dosimetrically challenging locally advanced pancreas treatment plans have been retrospectively re-planned using the VML approach to explore the potentiality of this new delivery technique. Finally, VML robustness was evaluated and compared with the IMRT plans, considering a lateral positioning error of ± 5 mm.ResultsIn phase one, all VML plans were within constraint for all OARs. When PTV coverage is considered, in the 50% of the cases VML PTV coverage is equal or higher than in IMRT plan. In the remaining 50%, the highest target under coverage difference in comparison with IMRT plan is −1.71%. The mean and maximum treatment time differences (VML-IMRT) is 0.2 min and 3.1 min respectively. In phase two, the treatment time variation (VML-IMRT), shows a mean, maximum and minimum variations of 1.3, 4.6 and −0.6 min respectively. All VML plans have a better target coverage if compared with IMRT plans, keeping in any case the OARs constraints within tolerance. VML doesn’t increase plan robustness.ConclusionVMAT-like treatment approach appeared to be an efficient planning solution and it was decided to clinically implement it in daily practice, especially in the frame of hypo fractionated treatments.     

Abdominal imaging dose in radiology and radiotherapy – Phantom point dose measurements,effective dose and secondary cancer risk

PurposeTo compare abdominal imaging dose from 3D imaging in radiology (standard/low-dose/dual-energy CT) and radiotherapy (planning CT, kV cone-beam CT (CBCT)).MethodsDose was measured by thermoluminescent dosimeters (TLD’s) placed at 86 positions in an anthropomorphic phantom. Point, organ and effective dose were assessed, and secondary cancer risk from imaging was estimated.ResultsOverall dose and mean organ dose comparisons yield significantly lower dose for the optimized radiology protocols (dual-source and care kV), with an average dose of 0.34±0.01 mGy and 0.54±0.01 mGy (average ± standard deviation), respectively. Standard abdominal CT and planning CT involve considerably higher dose (13.58 ± 0.18 mGy and 18.78±0.27 mGy, respectively). The CBCT dose show a dose fall-off near the field edges. On average, dose is reduced as compared with the planning or standard CT (3.79 ± 0.21 mGy for 220° rotation and 7.76 ± 0.37 mGy for 360°), unless the high-quality setting is chosen (20.30 ± 0.96 mGy). The mean organ doses show a similar behavior, which translates to the estimated secondary cancer risk. The modelled risk is in the range between 0.4 cases per million patient years (PY) for the radiological scans dual-energy and care kV, and 300 cases per million PY for the high-quality CBCT setting.ConclusionsModern radiotherapy imaging techniques (while much lower in dose than radiotherapy), involve considerably more dose to the patient than modern radiology techniques. Given the frequency of radiotherapy imaging, a further reduction in radiotherapy imaging dose appears to be both desirable and technically feasible.     

功能与分子影像在头颈部肿瘤放射治疗计划和疗效评价中的应用

目前临床普遍采用功能与分子影像检测手段能来评价头颈部肿瘤的放射治疗计划和疗效,可指导个体化治疗从而提高疗效。文章概述了功能与分子影像技术CT,MRI,PET-CT,超声检测技术在头颈部肿瘤放射治疗计划制定和疗效评价中的应用进展。结果显示,不同分子影像检测方法如在检查时机的选择、诊断和鉴别诊断的价值、观察放射治疗后肿瘤的残存和复发、预测放射治疗效果、指导后续治疗等方面均可起到重要作用。采用图像融合技术进行联合应用,如PET-CT和MRI-CT等,可提高检测的准确率。临床医生需在常规影像学手段的基础上,根据头颈部肿瘤患者病情和治疗方法的不同选用正确的功能和分子影像检测手段,更好地指导制定放射治疗计划及综合评价放射治疗后的疗效。     

Quantification in oncologic FDG-PET: A scientific overview

F18-Fluorodeoxyglose Positron Emission Tomography (FDG-PET) has gained wide acceptance in cancer patient management for initial diagnosis, staging, prognosis and patient monitoring. FDG-PET is also of interest for radiotherapy treatment planning. FDG-PET imaging has the potential to yield a quantitative assessment of glucose metabolism in tumours, which might be extremely helpful for differential diagnosis, patient monitoring and delineation of the biologically active tumour volume. The most accurate approach to assess the glucose metabolic rate (GMR) is by combining dynamic PET imaging and kinetic analysis. However, this requires a lengthy acquisition and an estimate of the arterial input function, which make the approach unpractical for clinical use. Several alternative strategies have thus been proposed to assess the GMR in tumours more easily. The presentation will review these different approaches, from the simplest one (using the Standardized uptake values [SUV] as done almost in all clinical centres) to more advanced approaches (for instance requiring at least one blood sample drawing).     

Predicting response to endovascular therapies: Dissecting the roles of local lesion complexity,systemic comorbidity,and clinical uncertainty

Through decades of use and refinement, endovascular stents have become part and parcel of the management of obstructive atherosclerotic lesions. Upon stent placement, a variety of biophysical reactions ensue, governed not only by the mechanical and material properties of the device, but also the impact these properties have on the local vascular biology. Anatomic changes and vascular deformations give rise to solid mechanical and fluid forces that are the proximate, functional drivers of the induced reparative response. Powerful computational tools and advanced imaging techniques allow us to define these forces with high precision and increasingly, at a patient-specific level. We have also gained fundamental insights into how these forces influence subcellular and cellular processes, and, through application of a variety of model systems, how they subsequently drive an integrated tissue response. Clinical studies extend understanding to actual patients and pathophysiologic scenarios. These tools and insights take on added weight given the real risks that accompany the many substantial benefits of stenting. Complex lesions remain difficult to manage and continue to be associated with worse outcomes. While many patients respond well to treatment, others suffer treatment failures and recurrent events – sometimes catastrophic. Overcoming such variability requires that we move towards individualized treatment plans. Doing so necessitates that we develop not just a qualitative understanding of involved phenomena, but a quantitative ability to predict integrated outcomes. Given the multi-scale nature of the vascular response to stenting, it is critical that models, be they computational, bench-top, animal, or clinical, can be verified, validated, and made interrelated. This review provides an overview of the biophysics governing endovascular stenting, their integration in real-world endovascular settings, and how simulation and statistical approaches are helping to bridge the gap between qualitative model understanding and quantitative clinical prediction.     

肝转移癌放射治疗进展

过去的几十年,在肝转移癌的治疗方面,放疗已经越来越多的应用于临床。对于局部肝转移癌,临床上往往采取加大剂量已提高局部控制率,以期提高患者生产期。但是,对于有症状的广泛性肝转移患者则给以全肝低剂量照射。放疗已成为不适合手术或化疗等方式的肝转移癌患者的有效治疗手段。放疗靶区勾画及放疗技术进步更好的保护了高剂量靶区周围的正常肝脏组织,使得提高靶区放疗剂量的手段很好的应用于临床。关于肝转移癌的适形与立体定向放疗治疗的提高局控率及生存期的临床研究不断出现。本文就局部肝转移的根治放疗与全肝的姑息放疗临床数据做相关综述,认为放疗在肝转移癌的治疗中是安全,有效的。但是,肝转移癌的临床随机试验研究仍较匮乏。