Radical advances in image-guided radiotherapy techniques have been made over the past decade and are already being used in clinical settings. Imaging techniques that can guide and ensure the accuracy of the field of fire in real time have also been intensively researched and developed. More recently, these image data have been used again for the evaluation and correction of planned daily treatment doses. The most important advantage of IGRT is the avoidance of under- or over-dose surprises during treatment, and therefore it has been integrated into the planning and implementation of many clinical radiotherapy treatments. Fundamentals of image-guided radiation therapy (IGRT) Image-guided radiation therapy has made fundamental advances and is being used in clinical care. However, there are still many questions about how to effectively utilize IGRT techniques that need to be addressed. Significant advances have been made in imaging technology to accurately guide and confirm the accuracy of the beam in radiation therapy. More recently, these image data have been used to evaluate and correct daily radiation therapy doses. Image-guided technology has been rapidly integrated into the various software/hardware used in radiation therapy, providing many opportunities for daily use, but also leading to problems in optimizing integration with the daily workflow of radiation therapy. A clinical evaluation of the results of current IGRT techniques can provide guidance for subsequent basic technology research and clinical application exploration, and will actually influence the development of next-generation IGRT techniques. The current limitations and challenges of IGRT technology have been reviewed in other chapters of this book, and this chapter will focus on IGRT technology and its application in the clinic from the clinician’s perspective. The Need for Image-Guided Radiation Therapy From three-dimensional conformal radiotherapy (3D-CRT) to intensity-modulated radiation therapy (IMRT), improving the treatment benefit ratio has always been the goal of continuous improvement in radiotherapy technology. The more concentrated the radiation dose deposition, the more it helps to increase the dose to the tumor area and/or reduce the exposure of normal tissue. Advances in technology have significantly reduced the dose to adjacent important normal tissues and improved the quality of life for patients with head and neck and certain other tumors. The goal of IGRT is to reduce the residual geometric uncertainties in the actual target alignment and treatment delivery, with the aim of reducing the error between the actual delivered dose and the planned dose to a minimum. The goal of IGRT is to reduce the actual target alignment and treatment delivery uncertainties, i.e., residual geometric uncertainties, in order to minimize or negligible (or clinically insignificant) errors between the actual delivered dose and the planned dose, allowing the therapeutic benefits of IMRT and 3D-CRT to be realized. Imaging at the time of treatment reveals the extent and degree of tumor displacement, thus defining the central role of IGRT in radiation therapy. IMRT and 3D-CRT are more sensitive to these movements and alterations than 2D radiation therapy, with the potential clinical risk that the actual dose to the target area is lower than planned and that adjacent Normal tissue receives too high a dose. Without image guidance, the actual treatment benefit of IMRT and 3D-CRT techniques may be lower than that of conventional radiation therapy. Effective application of IGRT can avoid over- or under-dosing at the time of treatment that is inconsistent with the plan, which is the most important advantage of IGRT. In many clinical radiation treatments, IGRT has become an essential component in the application of advanced radiotherapy planning and implementation techniques. IGRT technology offers the opportunity to develop new radiotherapy practices in three ways: (a) as mentioned above, if a high degree of conformality of the radiotherapy dose to the tumor target area can be achieved, it is possible to increase the amount of tumor tissue irradiated while reducing the amount of normal tissue exposed, thereby improving local control of the tumor and reducing toxic side effects; (b) it is possible to reduce the number of treatment separations and to implement high-dose, low-separation therapy more safely (b) it can reduce the number of treatment compartments and allow safer implementation of high-dose, low-separation therapy. Stereotactic body radiotherapy (SBRT) is the most common high-dose hypofractionation treatment modality, which must be performed with close imaging guidance, otherwise small errors may significantly affect the clinical outcome. While the application of SBRT is still limited, the principles of hypofractionated therapy and dose escalation are widely applicable. In fact, due to the development of IGRT and other related technologies, the dose and fractionation pattern of radiation therapy for all or most tumors will likely change to some extent; (c) low fractionation regimens can reduce treatment costs, improve treatment efficacy, and increase the number of patients treated. Patients living far from treatment centers may not be able to receive traditional longer course radiation therapy regimens, and as the number of treatments decreases, radiation therapy for these patients will become feasible. In summary, these are strong arguments in favor of the use of IGRT in combination with other advanced radiotherapy planning and delivery techniques. Radiotherapy Practice: Reducing Fluctuations in Exposure Dose The potential advantage of IGRT is the reduction of the difference between the actual delivered dose and the planned prescribed dose, which is particularly important for cohorts of patients receiving radiotherapy with the same treatment regimen (same dose and same technique). In order to reduce the variability in the actual dose delivered between patients, three approaches are needed: (a) further clarification of the dose required for tumor control; (b) better understanding of the dose-volume relationships associated with the occurrence of toxic side effects; and (c) clarification of the utility of radiotherapy modifiers (e.g., radiosensitizers) in treatment. In clinical trials, improved consistency in the implementation of radiotherapy regimens within control and experimental groups may reduce the heterogeneity of clinical responses within study groups, thereby helping to identify differences in outcomes between study groups. Reduced variability in radiation dose delivery also contributed to improved outcomes, similar to the effect of treatment plan variability on outcomes. In a large randomized clinical trial of head and neck tumors, all treatment plans were reviewed by a panel of experts. The greater the plan variation, the worse the tumor control. These results reflect the importance of treatment plan quality control (QC) and quality assurance (QA). However, if dose variation in clinical trials is due to inconsistencies in treatment delivery, then the use of IGRT will facilitate the implementation of QC and QA for the treatment planning process. Thus, in today’s radiation therapy, there are quality control criteria for each step of the treatment planning and delivery process, as well as criteria for quality control implementation and review. A potentially more significant clinical value of IGRT is the increased physician focus on the actual dose to tumor and normal tissue, thus contributing to a better understanding of the relationship between dose and normal tissue side effects and tumor control probabilities (TCP). However, with the full integration of IGRT technology into clinical trials and the maturation of related results, the understanding of these relationships may be different from that of the past. With a better understanding of the normal tissue dose/volume toxicity response risk relationship, it will help identify the organs and volumes that need to be protected to better utilize the therapeutic benefits of IMRT. Currently, one of the issues facing clinicians is the need to decide on tissue protection and avoidance based on a limited or incomplete understanding of the tolerated volume of normal tissue when a portion of the volume is irradiated. Radiotherapy Practice: Application of Image-Guided Radiation Therapy Information IGRT is a dynamic process. While adhering to the basic principles of oncologic radiation therapy, treatment monitoring and IGRT-based radiation therapy decisions require extensive training and skill training. In order to treat prudently, a clear understanding of the treatment target area is required, often with the help of advanced imaging techniques. Imaging is involved in all major aspects of IGRT, including radiotherapy plan design, delivery, and monitoring of tumor response to treatment. Based on imaging data, patients can be evaluated online (before the start of each treatment), in real time (during treatment) and offline (between treatments. (Multiple images acquired before and after are usually analyzed after several split irradiations). With each assessment, more information about the patient can be obtained and, if necessary, clinical treatment can be intervened. This intervention can be as simple as repositioning the patient before treatment on the day of evaluation; or it can be the discovery of a regressed or enlarged tumor, or the appearance of a new metastasis that requires reconsideration or complete adjustment of the entire treatment plan and treatment goals. In the era of IGRT, what is seen on imaging during treatment can influence interventional decisions in three ways: (a) PTV boundaries; (b) radiotherapy plan design, including repositioning plans, dose distribution adjustments, and prescribed doses; and (c) overall treatment goals. The specific implementation may vary depending on the treatment facility and the patient population it treats. summarizes the role of IGRT techniques in the radiation treatment process. The circles on the left represent the ongoing medical evaluation and treatment of the patient. First, the patient is seen and the goals of treatment are defined: tumor control, risk of recurrence reduction or palliative decompensation therapy. Then a treatment plan is designed and treatment is initiated. During the course of treatment, patients are monitored by clinical assessment and diagnostic imaging. IGRT is central to this process. First IGRT images will be used to assess the accuracy of the treatment plan, and imaging information of tissue changes (tumor or normal tissue) may lead to adjustments or redesign of the treatment plan. Imaging assessment can be performed offline, online or in real time. In summary, the results of the imaging evaluation may require treatment modifications, including changes in irradiation technique, adjustments to the plan, or even changes in the overall goal of treatment. If IGRT can be applied effectively, it can play a crucial role in radiation therapy and even in the overall treatment of the tumor. Although the understanding and application of IGRT has occurred primarily in the past decade, the concept of “image guidance” is not new; X-ray fluoroscopy and plain film imaging have been around for a long time and have been introduced into the radiotherapy suite for decades to assist in the treatment of patients. Figure 2 shows a cobalt therapy machine with kV-level field imaging capability installed in Toronto in 1958 and its schematic. Although kV-level imaging within the treatment room was available at that time, this function was not well utilized, which was related to the simplicity of radiotherapy technology at that time, the low planned conformality and treatment dose, and the small impact of geometric uncertainty on the treatment effect. In addition, the process of image acquisition and analysis was much less advanced and faster than today, and could not achieve the efficiency and capability required for clinical work. Nowadays, many mature IGRT technologies are within reach and more advanced treatment devices incorporating image-guided capabilities are in development. Perhaps it is beyond our ability to determine how best to apply the technology now available to best benefit patients. IGRT technology has made amazing advances over the past decade, and much is known about the positional uncertainty effects that occur across patients; the extent and type of change in tumor or normal tissue during radiation therapy is just beginning to be understood. Observational analysis of continuous 3D volumetric imaging data of patients can help to identify possible geometric deformations.