Future technological developments in proton therapy - A predicted technological breakthrough.

In the current spectrum of cancer treatments, despite high costs, a lack of robust evidence based on clinical outcomes or technical and radiobiological uncertainties, particle therapy and in particular proton therapy (PT) is rapidly growing. Despite proton therapy being more than fifty years old (first proposed by Wilson in 1946) and more than 220,000 patients having been treated with in 2020, many technological challenges remain and numerous new technical developments that must be integrated into existing systems. This article presents an overview of on-going technical developments and innovations that we felt were most important today, as well as those that have the potential to significantly shape the future of proton therapy. Indeed, efforts have been done continuously to improve the efficiency of a PT system, in terms of cost, technology and delivery technics, and a number of different developments pursued in the accelerator field will first be presented. Significant developments are also underway in terms of transport and spatial resolution achievable with pencil beam scanning, or conformation of the dose to the target: we will therefore discuss beam focusing and collimation issues which are important parameters for the development of these techniques, as well as proton arc therapy. State of the art and alternative approaches to adaptive PT and the future of adaptive PT will finally be reviewed. Through these overviews, we will finally see how advances in these different areas will allow the potential for robust dose shaping in proton therapy to be maximised, probably foreshadowing a future era of maturity for the PT technique.

[Hybrid radiotherapy machines: Evolution or revolution?] / Machines de radiothérapie hybrides : évolution ou révolution ?

The arrival of new hybrid radiotherapy machines with MRI or PET is announced as a milestone in radiotherapy management. Based on recent literature, we will describe the contribution of each of these modalities and the technological challenges that have already been or are still to be addressed.

Technological evolution of radiation treatment: Implications for clinical applications.

The contemporary approach to the management of a cancer patient requires an "ab initio" involvement of different medical domains in order to correctly design an individual patient's pathway toward cure. With new therapeutic tools in every medical field developing faster than ever before the patient care outcomes can be achieved if all surgical, drug, and radiation options are considered in the design of the appropriate therapeutic strategy for a given patient. Radiation therapy (RT) is a clinical discipline in which experts from different fields continuously interact in order to manage the multistep process of the radiation treatment. RT is found to be an appropriate intervention for diverse indications in about 50% of cancer patients during the course of their disease. Technologies are essential in dealing with the complexity of RT treatments and for driving the increasingly sophisticated RT approaches becoming available for the treatment of Cancer. High conformal techniques, namely intensity modulated or volumetric modulated arc techniques, ablative techniques (Stereotactic Radiotherapy and Stereotactic Radiosurgery), particle therapy (proton or carbon ion therapy) allow for success in treating irregularly shaped or critically located targets and for the sharpness of the dose fall-off outside the target. The advanced on-board imaging, including real-time position management systems, makes possible image-guided radiation treatment that results in substantial margin reduction and, in select cases, implementation of an adaptive approach. The therapeutic gains of modern RT are also due in part to the enhanced anticancer activity obtained by coadministering RT with chemotherapy, targeted molecules, and currently immune checkpoints inhibitors. These main clinically relevant steps forward in Radiation Oncology represent a change of gear in the field that may have a profound impact on the management of cancer patients.

PET/CT in radiation oncology.

The progressive integration of positron emission tomography/computed tomography (PET/CT) imaging in radiation therapy has its rationale in the biological intertumoral and intratumoral heterogeneity of malignant lesions that require the individual adjustment of radiation dose to obtain an effective local tumor control in cancer patients. PET/CT provides information on the biological features of tumor lesions such as metabolism, hypoxia, and proliferation that can identify radioresistant regions and be exploited to optimize treatment plans. Here, we provide an overview of the basic principles of PET-based target volume selection and definition using 18F-fluorodeoxyglucose (18F-FDG) and then we focus on the emerging strategies of dose painting and adaptive radiotherapy using different tracers. Previous studies provided consistent evidence that integration of 18F-FDG PET/CT in radiotherapy planning improves delineation of target volumes and reduces the uncertainties and variabilities of anatomical delineation of tumor sites. PET-based dose painting and adaptive radiotherapy are feasible strategies although their clinical implementation is highly demanding and requires strong technical, computational, and logistic efforts. Further prospective clinical trials evaluating local tumor control, survival, and toxicity of these emerging strategies will promote the full integration of PET/CT in radiation oncology.

MR-guidance in clinical reality: current treatment challenges and future perspectives.

Magnetic Resonance-guided radiotherapy (MRgRT) marks the beginning of a new era. MR is a versatile and suitable imaging modality for radiotherapy, as it enables direct visualization of the tumor and the surrounding organs at risk. Moreover, MRgRT provides real-time imaging to characterize and eventually track anatomical motion. Nevertheless, the successful translation of new technologies into clinical practice remains challenging. To date, the initial availability of next-generation hybrid MR-linac (MRL) systems is still limited and therefore, the focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites.MRgRT can be considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach, especially due to the ability to use daily online adaptation strategies. Furthermore, MRL systems overcome the limitations of conventional image-guided radiotherapy, especially in soft tissue, where target and organs at risk need accurate definition. Nevertheless, some concerns remain regarding the additional time needed to re-optimize dose distributions online, the reliability of the gating and tracking procedures and the interpretation of functional MR imaging markers and their potential changes during the course of treatment. Due to its continuous technological improvement and rapid clinical large-scale application in several anatomical settings, further studies may confirm the potential disruptive role of MRgRT in the evolving oncological environment.

Current status of intensity-modulated radiation therapy for prostate cancer: History, clinical results and future directions.

External beam radiotherapy has changed dramatically over several decades with the improvement of computer hardware and software, and machinery developments. Intensity-modulated radiation therapy is the most sophisticated technique for all cancer treatment with radiation therapy, and is widely disseminated and available for daily use in many countries. Several retrospective and prospective studies have shown that intensity-modulated radiation therapy reduces the radiation dose in the organs at risk with diminished rates of acute and late toxicity, even with higher doses (>74 Gy). An important technique for the clinical use of intensity-modulated radiation therapy is image-guided radiation therapy. The clinical benefit for prostate image-guided radiation therapy has been assessed by comparing the outcomes of patients with either the image-guided radiation therapy or non-image-guided radiation therapy technique. These studies have shown that image-guided radiation therapy significantly decreases acute and late rectal and bladder toxicities. Randomized trials and meta-analysis have shown that higher doses result in better biochemical control. More recently, hypofractionated radiation therapy comparing hypofractionated radiation therapy versus conventional fractionated radiation therapy have shown that hypofractionated radiation therapy produces biochemical control and toxicity rated similar to those produced by conventional fractionated radiation therapy. The clinical use of ultrahypofractionated radiation therapy and simultaneous integrated boost technique is necessary to evaluate its further safety and benefits. Intensity-modulated radiation therapy is also widely accepted in the field of salvage therapy and for the patients with distant oligometastases. The purpose of the present review is to summarize the history of intensity-modulated radiation therapy, new techniques for intensity-modulated radiation therapy, hypofractionation and future directions for prostate cancer.

Keeping Up with the Hybrid Magnetic Resonance Linear Accelerators: How Do Radiation Therapists Stay Current in the Era of Hybrid Technologies?

The benefits of integrating magnetic resonance imaging (MRI) into radiotherapy planning have long been extolled, first appearing in the literature as early as 1986. Most often described as a tool to be used when registered to a planning computed tomography to improve target and organ at risk delineation, the use of MRI for on-board image guidance and as a sole imaging modality throughout the entire radiotherapy pathway is quickly becoming a reality for appropriately selected patient populations in academic centres throughout the world. With the commercialization of these integrated magnetic resonance - radiotherapy delivery systems, an MRI-only workflow will prove beneficial, with MRI being used for treatment planning, localization, and on-treatment plan adaptation. Despite these technological advancements, recent surveys indicate uptake of MRI in radiotherapy as a routine practice has proven challenging. Reasons cited for this slow uptake were primarily related to health economics and/or accessibility. Furthermore, these surveys, like much of the academic literature, shy away from focusing on safe, sustainable staffing models enabled by comprehensive and appropriate education and training. In stark contrast to conebeam computed tomography guided therapy, magnetic resonance - radiotherapy systems are currently being operated by teams of physicians, radiographers, and physicists because of the diverse and complex tasks required to deliver treatment. The pace of innovation in RT remains high and unfortunately the window of opportunity to implement appropriate education continues to narrow. It is vital that we establish a framework to future-proof our profession. In the era of magnetic resonance-guided radiotherapy, we have yet to address the question of how to devise a consensus on the requisite knowledge, skills, and competence for radiation therapists and therapy radiographers using and/or operating MRI that provides guidance, without becoming prohibitively costly or time consuming.

Advances in Auto-Segmentation.

Manual image segmentation is a time-consuming task routinely performed in radiotherapy to identify each patient's targets and anatomical structures. The efficacy and safety of the radiotherapy plan requires accurate segmentations as these regions of interest are generally used to optimize and assess the quality of the plan. However, reports have shown that this process can be subject to significant inter- and intraobserver variability. Furthermore, the quality of the radiotherapy treatment, and subsequent analyses (ie, radiomics, dosimetric), can be subject to the accuracy of these manual segmentations. Automatic segmentation (or auto-segmentation) of targets and normal tissues is, therefore, preferable as it would address these challenges. Previously, auto-segmentation techniques have been clustered into 3 generations of algorithms, with multiatlas based and hybrid techniques (third generation) being considered the state-of-the-art. More recently, however, the field of medical image segmentation has seen accelerated growth driven by advances in computer vision, particularly through the application of deep learning algorithms, suggesting we have entered the fourth generation of auto-segmentation algorithm development. In this paper, the authors review traditional (nondeep learning) algorithms particularly relevant for applications in radiotherapy. Concepts from deep learning are introduced focusing on convolutional neural networks and fully-convolutional networks which are generally used for segmentation tasks. Furthermore, the authors provide a summary of deep learning auto-segmentation radiotherapy applications reported in the literature. Lastly, considerations for clinical deployment (commissioning and QA) of auto-segmentation software are provided.

How rapid advances in imaging are defining the future of precision radiation oncology.

Imaging has an essential role in the planning and delivery of radiotherapy. Recent advances in imaging have led to the development of advanced radiotherapy techniques-including image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy and proton beam therapy. The optimal use of imaging might enable higher doses of radiation to be delivered to the tumour, while sparing normal surrounding tissues. In this article, we review how the integration of existing and novel forms of computed tomography, magnetic resonance imaging and positron emission tomography have transformed tumour delineation in the radiotherapy planning process, and how these advances have the potential to allow a more individualised approach to the cancer therapy. Recent data suggest that imaging biomarkers that assess underlying tumour heterogeneity can identify areas within a tumour that are at higher risk of radio-resistance, and therefore potentially allow for biologically focussed dose escalation. The rapidly evolving concept of adaptive radiotherapy, including artificial intelligence, requires imaging during treatment to be used to modify radiotherapy on a daily basis. These advances have the potential to improve clinical outcomes and reduce radiation-related long-term toxicities. We outline how recent technological advances in both imaging and radiotherapy delivery can be combined to shape the future of precision radiation oncology.

Adaptive radiotherapy for head and neck cancer: Are we ready to put it into routine clinical practice?

Patients with head and neck cancer who are treated with radiotherapy often have significant weight loss or tumor regression during treatment. Adaptive radiotherapy refers to acquiring new imaging during treatment and changing the parameters of the radiation plan based on the new imaging findings. There is accumulating evidence that adaptive radiotherapy can reduce toxicity and improve tumor control, though it is not yet known which patients benefit most. For patients with profound tumor regression, there is also uncertainty about how much to shrink the region receiving high radiation dose. Another form of adaptive radiotherapy uses advanced imaging such as positron emission tomography to visualize changes in tumor biology during treatment. Tumor regions that are thought to be more radioresistant can then be treated to a higher radiation dose, and vice-versa. Studies employing this strategy to boost radiation dose have shown a high rate of late toxicity, specifically the development of persistent mucosal ulcers. Therefore, this sort of adaptive radiotherapy is currently confined to the research setting.

Frontiers of cancer imaging and guided therapy using ultrasound, light, and microwaves.

This review describes emerging techniques within the last 5 years that employ ultrasound for detecting and staging malignancy, tracking metastasis, and guiding treatment. Ultrasound elastography quantifies soft tissue elastic properties that change as a tumor grows and proliferates. Hybrid imaging modalities that combine ultrasound with light or microwave energy provide novel contrast for mapping blood oxygen saturation, transport of particles through lymphatic vessels and nodes, and real-time feedback for guiding needle biopsies. Combining these methods with smart nanoparticles and contrast agents further promotes new paradigms for cancer imaging and therapy.

How Advances in Imaging Will Affect Precision Radiation Oncology.

Radiation oncology is 1 of the most structured disciplines in medicine. It is of a highly technical nature with reliance on robotic systems to deliver intervention, engagement of diverse expertise, and early adoption of digital approaches to optimize and execute the application of this highly effective cancer treatment. As a localized intervention, the dependence on sensitive, specific, and accurate imaging to define the extent of disease, its heterogeneity, and adjacency to normal tissues directly affects the therapeutic ratio. Image-based in vivo temporal monitoring of the response to treatment enables adaptation and further affects the therapeutic ratio. Thus, more precise intervention will enable fractionation schedules that better interoperate with advances such as immunotherapy. In the data set-rich era that promises precision and personalized medicine, the radiation oncology field will integrate these new data into highly protocoled pathways of care that begin with multimodality prediction and enable patient-specific adaptation of therapy based on quantitative measures of the individual's dose-volume temporal trajectory and midtherapy predictions of response. In addition to advancements in computed tomography imaging, emerging technologies, such as ultra-high-field magnetic resonance and molecular imaging will bring new information to the design of treatments. Next-generation image guided radiation therapy systems will inject high specificity and sensitivity data and stimulate adaptive replanning. In addition, a myriad of pre- and peritherapeutic markers derived from advances in molecular pathology (eg, tumor genomics), automated and comprehensive imaging analytics (eg, radiomics, tumor microenvironment), and many other emerging biomarkers (eg, circulating tumor cell assays) will need to be integrated to maximize the benefit of radiation therapy for an individual patient. We present a perspective on the promise and challenges of fully exploiting imaging data in the pursuit of personalized radiation therapy, drawing from the presentations and broader discussions at the 2016 American Society of Therapeutic Radiation Oncology-National Cancer Institute workshop on Precision Medicine in Radiation Oncology (Bethesda, MD).

Emerging technologies in stereotactic body radiotherapy.

Stereotactic body radiation therapy (SBRT) stems from the initial developments of intra-cranial stereotactic radiosurgery (SRS). Despite similarity in their names and clinical goals of delivering a sufficiently high tumoricidal dose, maximal sparing of the surrounding normal tissues and a short treatment course, SBRT technologies have transformed from the early days of body frame-based treatments with X-ray verification to primarily image-guided procedures with cone-beam CT or stereoscopic X-ray systems and non-rigid body immo-bilization. As a result of the incorporation of image-guidance systems and multi-leaf col-limators into mainstream linac systems, and treatment planning systems that have also evolved to allow for routine dose calculations to permit intensity modulated radiotherapy and volumetric modulated arc therapy (VMAT), SBRT has disseminated rapidly in the community to manage many disease sites that include oligometastases, spine lesions, lung, prostate, liver, renal cell, pelvic tumors, and head and neck tumors etc. In this article, we review the physical principles and paradigms that led to the widespread adoption of SBRT practice as well as technical caveats specific to individual SBRT technologies. From the perspective of treatment delivery, we categorically described (I) C-arm linac-based SBRT technologies; (II) robotically manipulated X-band CyberKnife® technology; and (III) emerging specialized systems for SBRT that include integrated MRI-linear accelerators and the imaged-guided Gamma Knife Perfexion Icon system with expanded multi-isocenter treatments of skull-based tumors, head-and-neck and cervical-spine lesions.

"Radio-oncomics" : The potential of radiomics in radiation oncology.

INTRODUCTION: Radiomics, a recently introduced concept, describes quantitative computerized algorithm-based feature extraction from imaging data including computer tomography (CT), magnetic resonance imaging (MRT), or positron-emission tomography (PET) images. For radiation oncology it offers the potential to significantly influence clinical decision-making and thus therapy planning and follow-up workflow. METHODS: After image acquisition, image preprocessing, and defining regions of interest by structure segmentation, algorithms are applied to calculate shape, intensity, texture, and multiscale filter features. By combining multiple features and correlating them with clinical outcome, prognostic models can be created. RESULTS: Retrospective studies have proposed radiomics classifiers predicting, e. g., overall survival, radiation treatment response, distant metastases, or radiation-related toxicity. Besides, radiomics features can be correlated with genomic information ("radiogenomics") and could be used for tumor characterization. DISCUSSION: Distinct patterns based on data-based as well as genomics-based features will influence radiation oncology in the future. Individualized treatments in terms of dose level adaption and target volume definition, as well as other outcome-related parameters will depend on radiomics and radiogenomics. By integration of various datasets, the prognostic power can be increased making radiomics a valuable part of future precision medicine approaches. CONCLUSION: This perspective demonstrates the evidence for the radiomics concept in radiation oncology. The necessity of further studies to integrate radiomics classifiers into clinical decision-making and the radiation therapy workflow is emphasized.

Major clinical research advances in gynecologic cancer in 2016: 10-year special edition.

In 2016, 13 topics were selected as major research advances in gynecologic oncology. For ovarian cancer, study results supporting previous ones regarding surgical preventive strategies were reported. There were several targeted agents that showed comparable responses in phase III trials, including niraparib, cediranib, and nintedanib. On the contrary to our expectations, dose-dense weekly chemotherapy regimen failed to prove superior survival outcomes compared with conventional triweekly regimen. Single-agent non-platinum treatment to prolong platinum-free-interval in patients with recurrent, partially platinum-sensitive ovarian cancer did not improve and even worsened overall survival (OS). For cervical cancer, we reviewed robust evidences of larger-scaled population-based study and cost-effectiveness of nonavalent vaccine for expanding human papillomavirus (HPV) vaccine coverage. Standard of care treatment of locally advanced cervical cancer (LACC) was briefly reviewed. For uterine corpus cancer, new findings about appropriate surgical wait time from diagnosis to surgery were reported. Advantages of minimally invasive surgery over conventional laparotomy were reconfirmed. There were 5 new gene regions that increase the risk of developing endometrial cancer. Regarding radiation therapy, Post-Operative Radiation Therapy in Endometrial Cancer (PORTEC)-3 quality of life (QOL) data were released and higher local control rate of image-guided adaptive brachytherapy was reported in LACC. In addition, 4 general oncology topics followed: chemotherapy at the end-of-life, immunotherapy with reengineering T-cells, actualization of precision medicine, and artificial intelligence (AI) to make personalized cancer therapy real. For breast cancer, adaptively randomized trials, extending aromatase inhibitor therapy, and ribociclib and palbociclib were introduced.

The future of image-guided radiotherapy will be MR guided.

Advances in image-guided radiotherapy (RT) have allowed for dose escalation and more precise radiation treatment delivery. Each decade brings new imaging technologies to help improve RT patient setup. Currently, the most frequently used method of three-dimensional pre-treatment image verification is performed with cone beam CT. However, more recent developments have provided RT with the ability to have on-board MRI coupled to the teleradiotherapy unit. This latest tool for treating cancer is known as MR-guided RT. Several varieties of these units have been designed and installed in centres across the globe. Their prevalence, history, advantages and disadvantages are discussed in this review article. In preparation for the next generation of image-guided RT, this review also covers where MR-guided RT might be heading in the near future.