R01CA262017

Personalized Motion Management for Truly 4D Lung Radiotherapy

It is well-recognized that unanticipated respiration-induced motion can result in significant errors in planned vs delivered dose in thoracic radiotherapy (RT), resulting in local regional failure and/or increased radiation-induced toxicity. In this proposal, we build upon our previous motion management research and aim to overcome the limitations of current motion management strategies, which tend to underrepresent both the extent and the spatiotemporal complexity of respiratory motion.

Our overall premise is that, as our field adopts increasingly more potent forms of RT, real-time single-point monitoring needs to be replaced by real-time volumetric monitoring to capture complex motion. Recently available integrated magnetic resonance imaging (MRI)+linac systems aim to address the limitations of current conventional solutions. However, the high cost and complexity of these systems, as well as engineering and technological challenges, have proven to be substantial barriers to their widespread clinical adoption (less than 1% of the total US install base for linacs).

To address this unmet clinical need, we form an academic-industrial partnership to investigate and develop a novel in-room real-time motion management solution for lung RT that combines 4DMRI and 4DCT (4D=3D+time).

In Aim 1, we develop and investigate rapid 4DMRI techniques. In Aim 2, we merge the volumetric motion information derived from 4DMRI and 4DCT to create a patient-specific, multi-cycle motion model that incorporates the geometric fidelity and electron density information from CT with the soft-tissue contrast and dose-free, long-term monitoring from MRI. This model is parameterized by the spatial positions of MRI-compatible electromagnetic (EM) sensors placed on the thoracoabdominal surface of the patient. By knowing the position of these sensors at any given time point, we can estimate the corresponding position of each voxel within the irradiated volume. At each treatment fraction, the model is rebuilt using in-room KV fluoroscopy prior to delivery to account for inter-fraction (day-to-day) changes in external-internal correspondence and updated using KV fluoroscopy during dose delivery to account for intra-fraction changes.

In Aim 3, we develop two identical preclinical prototype systems (EndoScoutRT) and form end-user teams tasked with formulating clinical workflows, quality assurance guidelines, and strategies for clinical translation. In Aim 4, we perform end-user evaluation of the prototype systems by conducting a prospective non-interventional clinical study in 44 lung cancer patients at two institutions. We compare the performance of our model-based motion management to current standard-of-care and MRI+linac based real-time motion management.

Our team has extensive expertise in clinical study design, image-guided RT, rapid MRI, and real-time motion management. We anticipate that the successful clinical translation of this approach (beyond the current scope) will enable safer administration of highly potent and clinically effective forms of thoracic RT.

University Of Maryland, Baltimore

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Baltimore, Maryland 21201 United States

Single Zip Code

Academic-Industrial Partnerships for Translation of Technologies for Diagnosis and Treatment (R01 - Clinical Trial Optional) (PAR-18-530)

Amendment Since initial award the total obligations have increased 365% from $658,497 to $3,062,893.