Purpose: Intensity‐Modulated Radiation Therapy (IMRT), including its variations (including IMRT, Volumetric Arc Therapy (VMAT), and Tomotherapy), is a widely used and critically important technology for cancer treatment. It is a knowledge‐intensive technology due not only to its own technical complexity, but also to the inherently conflicting nature of maximizing tumor control while minimizing normal organ damage. As IMRT experience and especially the carefully designed clinical plan data are accumulated during the past two decades, a new set of methods commonly termed knowledge‐based planning (KBP) have been developed that aim to improve the quality and efficiency of IMRT planning by learning from the database of past clinical plans. Some of this development has led to commercial products recently that allowed the investigation of KBP in numerous clinical applications. In this literature review, we will attempt to present a summary of published methods of knowledge‐based approaches in IMRT and recent clinical validation results.Methods: In March 2018, a literature search was conducted in the NIH Medline database using the PubMed interface to identify publications that describe methods and validations related to KBP in IMRT including variations such as VMAT and Tomotherapy. The search criteria were designed to have a broad scope to capture relevant results with high sensitivity. The authors filtered down the search results according to a predefined selection criteria by reviewing the titles and abstracts first and then by reviewing the full text. A few papers were added to the list based on the references of the reviewed papers. The final set of papers was reviewed and summarized here.Results: The initial search yielded a total of 740 articles. A careful review of the titles, abstracts, and eventually the full text and then adding relevant articles from reviewing the references resulted in a final list of 73 articles published between 2011 and early 2018. These articles described methods for developing knowledge models for predicting such parameters as dosimetric and dose‐volume points, voxel‐level doses, and objective function weights that improve or automate IMRT planning for various cancer sites, addressing different clinical and quality assurance needs, and using a variety of machine learning approaches. A number of articles reported carefully designed clinical studies that assessed the performance of KBP models in realistic clinical applications. Overwhelming majority of the studies demonstrated the benefits of KBP in achieving comparable and often improved quality of IMRT planning while reducing planning time and plan quality variation.Conclusions: The number of KBP‐related studies has been steadily increasing since 2011 indicating a growing interest in applying this approach to clinical applications. Validation studies have generally shown KBP to produce plans with quality comparable to expert planners while reducing the time and efforts to generate plans. However, current studies are mostly retrospective and leverage relatively small datasets. Larger datasets collected through multi‐institutional collaboration will enable the development of more advanced models to further improve the performance of KBP in complex clinical cases. Prospective studies will be an important next step toward widespread adoption of this exciting technology.

For intermediate and high risk prostate cancer, both the prostate gland and seminal vesicles are included in the clinical target volume. Internal motion patterns of these two organs vary, presenting a challenge for adaptive treatment. Adaptive techniques such as isocenter repositioning and soft tissue alignment are effective when tumor volumes only exhibit translational shift, while direct re-optimization of the intensity-modulated radiation therapy (IMRT) plan maybe more desirable when extreme deformation or differential positioning changes of the organs occur. Currently, direct re-optimization of the IMRT plan using beamlet (or fluence map) has not been reported. In this study, we report a novel on-line re-optimization technique that can accomplish plan adjustment on-line. Deformable image registration is used to provide position variation information on each voxel along the three dimensions. The original planned dose distribution is used as the 'goal' dose distribution for adaptation and to ensure planning quality. Fluence maps are re-optimized via linear programming, and a plan solution can be achieved within 2 min. The feasibility of this technique is demonstrated with a clinical case with large deformation. Such on-line ART process can be highly valuable with hypo-fractionated prostate IMRT treatment.

This study evaluated the dosimetric impact of various treatment techniques as well as collimator leaf width (2.5 vs 5 mm) for three groups of tumors – spine tumors, brain tumors abutting the brainstem, and liver tumors. These lesions often present challenges in maximizing dose to target volumes without exceeding critical organ tolerance. Specifically, this study evaluated the dosimetric benefits of various techniques and collimator leaf sizes as a function of lesion size and shape. Fifteen cases (5 for each site) were studied retrospectively. All lesions either abutted or were an integral part of critical structures (brainstem, liver or spinal cord). For brain and liver lesions, treatment plans using a 3D-conformal static technique (3D), dynamic conformal arcs (DARC) or intensity modulation (IMRT) were designed with a conventional linear accelerator with standard 5 mm leaf width multi-leaf collimator, and a linear accelerator dedicated for radiosurgery and hypofractionated therapy with a 2.5 mm leaf width collimator. For the concave spine lesions, intensity modulation was required to provide adequate conformality; hence, only IMRT plans were evaluated using either the standard or small leaf-width collimators. A total of 70 treatment plans were generated and each plan was individually optimized according to the technique employed. The Generalized Estimating Equation (GEE) was used to separate the impact of treatment technique from the MLC system on plan outcome, and t-tests were performed to evaluate statistical differences in target coverage and organ sparing between plans. The lesions ranged in size from 2.6 to 12.5 cc, 17.5 to 153 cc, and 20.9 to 87.7 cc for the brain, liver, and spine groups, respectively. As a group, brain lesions were smaller than spine and liver lesions. While brain and liver lesions were primarily ellipsoidal, spine lesions were more complex in shape, as they were all concave. Therefore, the brain and the liver groups were compared for volume effect, and the liver and spine groups were compared for shape. For the brain and liver groups, both the radiosurgery MLC and the IMRT technique contributed to the dose sparing of organs-at-risk(OARs), as dose in the high-dose regions of these OARs was reduced up to 15%, compared to the non-IMRT techniques employing a 5 mm leaf-width collimator. Also, the dose reduction contributed by the fine leaf-width MLC decreased, as dose savings at all levels diminished from 4 – 11% for the brain group to 1 – 5% for the liver group, as the target structures decreased in volume. The fine leaf-width collimator significantly improved spinal cord sparing, with dose reductions of 14 – 19% in high to middle dose regions, compared to the 5 mm leaf width collimator. The fine leaf-width MLC in combination with the IMRT technique can yield dosimetric benefits in radiosurgery and hypofractionated radiotherapy. Treatment of small lesions in cases involving complex target/OAR geometry will especially benefit from use of a fine leaf-width MLC and the use of IMRT.

In current standard radiation therapy process, patient anatomy is represented by the snapshot of computed tomographic images at the simulation for treatment planning. However, patient anatomy during the treatment course is not static, and the changes can be in the order of centimeters. The goal of the adaptive radiation therapy (ART) is to measure and account these variations in the treatment process, so that the optimal planned dose distribution is the same as the final delivered dose distribution. The field of the ART is rapidly evolving. The implementation of the ART principle is built on technical components in 3 main areas: image guidance, dose verification, and plan adaptation. The purpose of this review was to present different ART methods currently developed and used by different investigators.