R01CA255661

Real-Time MRI-Guided Adaptive Radiotherapy of Unresectable Pancreatic Cancer - Project Summary

Pancreatic cancer has the highest mortality rate of all cancers, with a 5-year survival rate of only 9%. Surgery still represents the only curative treatment option, though less than 20% of patients are candidates for resection. Approximately 30-40% of patients present with locally advanced unresectable tumors with no significant chance of long-term survival through standard treatments.

The use of ablative radiation doses (biologically equivalent doses of 100GY) produces results that are comparable to surgical resection in patients with inferior prognostic features. However, organ motion, due to respiratory motion, must be managed to minimize toxicity in the gastrointestinal tract.

In this project, we will develop novel real-time volumetric MRI technology that can guide radiotherapy to enable the use of ablative doses with minimal risk. Our technique, called MR Signature Matching (MRSIGMA), pre-learns 3D motion states and assigns unique motion signatures during an offline learning phase and performs fast signature acquisition and matching during an online matching phase. We have demonstrated real-time tracking of liver tumors with an imaging latency (acquisition plus reconstruction) of about 250 ms using MRSIGMA.

We will collaborate with Elekta to implement MRSIGMA on the Unity MR-LINAC system and to link the output of MRSIGMA with the multileaf collimator (MLC) system to enable the radiation beam to track the 3D position and shape of the moving tumor in real-time.

Specific aims are as follows:

1. Develop deep learning reconstruction of undersampled dynamic MRI data for rapid motion database generation during offline learning and adaptation during online matching.

A. Develop a convolutional neural network for rapid reconstruction of motion-resolved data (<10 seconds).
B. Detect anatomical changes, such as motion baseline drifts, and adapt the motion database accordingly.
C. Perform initial validation on a dynamic MRI phantom and ten volunteers.

2. Validate the potential of MRSIGMA for real-time volumetric tumor motion imaging on fifty patients with locally advanced unresectable pancreatic cancer.

A. Accuracy hypothesis: Real-time MRSIGMA is noninferior to a non-real-time XDGRASP reference.
B. Reproducibility hypothesis: Two MRSIGMA scans present equivalent real-time imaging performance.

3. Develop and validate on dynamic phantoms the proposed MRSIGMA-guided MLC tracking in collaboration with Elekta.

A. Develop software to control the MLC with the output of MRSIGMA.
B. Evaluate tracking latency, geometric error, reproducibility, and dosimetric accuracy.

Sloan-Kettering Institute For Cancer Research

TO DEVELOP THE MEANS TO CURE AS MANY CANCER PATIENTS AS POSSIBLE AND TO CONTROL THE DISEASE IN THOSE PATIENTS WHO ARE NOT CURED. CANCER TREATMENT RESEARCH INCLUDES THE DEVELOPMENT AND EVALUATION OF IMPROVED METHODS OF CANCER TREATMENT THROUGH THE SUPPORT AND PERFORMANCE OF BOTH FUNDAMENTAL AND APPLIED LABORATORY AND CLINICAL RESEARCH. RESEARCH IS SUPPORTED IN THE DISCOVERY, DEVELOPMENT, AND CLINICAL TESTING OF ALL MODES OF THERAPY INCLUDING: SURGERY, RADIOTHERAPY, CHEMOTHERAPY, AND BIOLOGICAL THERAPY INCLUDING MOLECULARLY TARGETED THERAPIES, BOTH INDIVIDUALLY AND IN COMBINATION. IN ADDITION, RESEARCH IS CARRIED OUT IN AREAS OF NUTRITIONAL SUPPORT, STEM CELL AND BONE MARROW TRANSPLANTATION, IMAGE GUIDED THERAPIES AND STUDIES TO REDUCE TOXICITY OF CYTOTOXIC THERAPIES, AND OTHER METHODS OF SUPPORTIVE CARE THAT MAY SUPPLEMENT AND ENHANCE PRIMARY TREATMENT. 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.

93.395 - Cancer Treatment Research

National Cancer Institute (NCI) [HHS - NIH]

New York, New York 100656007 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 419% from $640,178 to $3,323,920.