4D Robust Optimization in Intensity-Modulated Proton Therapy

描述（由申请人提供）：申请人的近期职业目标是过渡到一个高水平的独立研究人员，并在一个紧张和支持性的研究环境中建立一个小型实验室。从长远来看，申请人希望发展扎实的学术生涯，专注于医学放射物理领域的转化研究，影响最先进的放射治疗方式的各个方面。该候选人于2007年获得普林斯顿大学博士学位，后在洛斯阿拉莫斯国家实验室担任博士后研究员，在计算物理，数学和算法以及软件开发方面拥有丰富的经验，特别是大规模并行高性能计算（HPC）的代码开发。该候选人还具有扎实的分析和数学技能，可以解决复杂的物理问题，并具有跨学科背景。2010年7月加入德克萨斯大学MD安德森癌症中心放射物理系，任助理教授（研究方向）。MD安德森癌症中心是一家以研究为导向的综合性癌症医院，是美国领先的癌症中心。放射物理系提供必要的临床、研究和教育资源，以支持与癌症治疗有关的物理和剂量学研究。该科休斯顿质子治疗中心（PTC-H）于2006年5月开始对患者进行治疗。PTC-H是世界上为数不多的有能力使用扫描质子束进行强度和能量调制治疗的质子治疗中心之一，这是拟议研究的主要焦点。在奖励期间，候选人将专注于开发和验证新的先进放射治疗方法。在K25补助金的支持下，申请人计划1)在放射治疗的临床和研究方面获得深入的知识和实践经验；2)获得深入的解剖学知识；3)深入了解医学影像学知识；4)具有一定的生物统计学知识；5)具备一定的放射生物学知识。为了实现这些目标，申请人将与一组经验丰富的导师和合作研究人员合作，共同开展癌症放射治疗的项目，在莱斯大学和德克萨斯大学休斯顿健康科学中心学习学术课程，接受放射治疗的临床培训，并参加研讨会和会议。调强质子治疗（IMPT）的四维（4D）稳健优化已被选为K25培训计划的研究主题，以帮助申请人获得成为独立研究者所需的经验。使用IMPT治疗肺癌提出了许多挑战，需要通过研究来解决，以最大限度地提高这种有前途的模式的治疗效益。候选人在研究过程中所学到的知识将广泛应用于该领域的许多研究领域。原则上，IMPT

DESCRIPTION (provided by applicant): The applicant's immediate career goal is to make the transition to a high-caliber independent researcher and to establish a small laboratory in an intense and supportive research environment. In the long term, the applicant hopes to develop a solid academic career focusing on translational research in the area of medical radiation physics that impacts various aspects of the state-of-the-art radiotherapy modalities. The candidate, who obtained his PhD from Princeton University in 2007 and later worked at the Los Alamos National Laboratory as a postdoctoral researcher, has extensive prior experience in computational physics, mathematics and algorithms, and software development, especially code development in massive parallel high-performance computing (HPC). The candidate also has solid analytical and mathematical skills to solve complicated physics problems, along with an interdisciplinary background. In July 2010, the candidate joined the faculty of the Department of Radiation Physics of The University of Texas MD Anderson Cancer Center as an assistant professor (research track). MD Anderson is a research-driven, comprehensive cancer hospital and is the leading cancer center in the United States. The Department of Radiation Physics provides the clinical, research, and educational resources necessary to support physics and dosimetry research related to cancer therapy. The department's Proton Therapy Center-Houston (PTC-H) began patient treatments in May 2006. PTC-H is one of few proton treatment centers in the world to have the capability to deliver intensity- and energy-modulated treatments with scanned proton beams, which is the major focus of the proposed research. During the award period, the candidate will focus on the development and validation of novel advanced radiation therapy methodologies. With the support of this K25 grant, the applicant plans to 1) obtain in-depth knowledge and hands-on experience in the clinical and research aspects of radiation therapy; 2) obtain in- depth knowledge of anatomy; 3) obtain in-depth knowledge of medical imaging; 4) obtain moderate knowledge of biostatistics; and 5) obtain moderate knowledge of radiobiology. To achieve these objectives, the applicant will work with a group of experienced mentors and collaborating researchers on joint projects focusing on the radiotherapy of cancers, take academic courses at Rice University and The University of Texas-Health Science Center at Houston, undergo clinical training in radiation therapy, and attend seminars and conferences. Four-dimensional (4D) robust optimization of intensity-modulated proton therapy (IMPT) has been chosen as the research topic for this K25 training program to help the applicant gain the experience necessary to become an independent investigator. The use of IMPT to treat lung cancers presents numerous challenges that need to be addressed through research to maximize the therapeutic benefits of this promising modality. What the candidate learns during this research will be widely applicable to many areas of research in this field. In principle, IMPT has the greatest potential to provide highly conformal tumor target coverage, while sparing adjacent healthy organs. However, characteristics of protons (e.g., the abrupt drop-off of dose beyond the range and scattering) make IMPT highly vulnerable to uncertainties. Sources of uncertainty include tumor shrinkage, weight loss, variation in patient setup, respiratory motion, uncertainties in CT numbers and stopping power ratios, and approximations in proton dose calculation algorithms. The current practice for managing uncertainties in IMPT is similar to that for intensity-modulated radiation therapy (IMRT), i.e., assigning a safety margin around the clinical target volume to produce a planning target volume. The resulting dose distributions are, in general, not robust in the face of uncertainties, i.e., what is delivered to the patient may be significantly different from what is seen on the computer-designed treatment plan and may lead to unforeseen clinical consequences. Therefore, investigations leading to the development of suitable 4D robust optimization methods to improve the optimality and robustness of IMPT plans to uncertainties, including regular and irregular motion, are vital. Our hypothesis is that 4D robust optimization can render IMPT plans less sensitive to uncertainties and achieve better sparing of normal tissues (both by at least a factor of two) than conventional plans optimized on the basis of margins. We propose to test our hypothesis in the following specific aims: (1) to quantify anatomy motion and its uncertainty; (2) to develop and implement 4D IMPT optimization; (3) to enhance the IMPT plan robustness; and (4) to validate IMPT 4D robust optimization. Compared to previous 4D robust optimization approaches in IMRT, the research proposed by the applicant has several innovative aspects, including a "customized", as-small-as-necessary margin optimized spontaneously to handle uncertainties and regular motion, the use of perturbation theory, widely used in quantum mechanics to solve the Schr¿dinger equation, to handle irregular motion, and memory-distributed parallelization to solve the challenging high-computer-memory requirement problem. We expect that our pioneering 4D robust optimization research in IMPT will fill gaps in our knowledge about appropriate ways to minimize the influence of uncertainties in IMPT and lead to significant benefits for cancer patients, especially those with thoracic and abdominal cancers. This project doesn't involve activities outside of the United States or partnerships with international collaborators.