P01CA261669

Integrating Patient-Specific Clinical and Biological Factors Towards Individualizing Utilization of Proton and Photon Radiation Therapy - Overall Summary

This is a joint application for a Program Project Grant by Massachusetts General Hospital and MD Anderson Cancer Center. The progress we made in our most recent program projects (a P01 and a U19) has been critical to the clinical, physical, and biological aspects of proton therapy and its significance as an important cancer treatment modality.

The main achievements of the recently completed U19 (end date 8/31/20) were:

1. The development and activation of definitive esophagus, liver, and glioma randomized proton vs. photon therapy trials in cooperation with NRG, NCI, and NCTN.
2. Understanding and modeling the differences in response of normal tissues to highly disparate proton and photon dose distribution patterns.
3. Understanding the complexities of the biological effects of protons relative to photons.
4. The development of advanced intensity-modulated proton therapy incorporating physical uncertainties and the variable biological effectiveness of protons.

Our research also revealed major gaps in the knowledge of the biological effects of protons, significant limitations of the current population-based models of normal tissue and tumor response to protons vs. photons, and uncertainty in the appropriateness of proton therapy in the face of heterogeneities in patient characteristics and treatment techniques in unselected groups of patients.

On the bright side, our research also discovered the strong potential of proton therapy to reduce suppression of the immune system, which is commonly associated with photon therapy and has been shown to lead to adverse outcomes.

The overall goals of the proposed P01 are:

A. Understanding relative clinical, biological, and immunosuppressive effects of proton therapy vs. photon therapy.
B. Enhancing outcomes based on the physical, biological, and immunological properties of protons and photons.
C. Applying individualized (as opposed to population-based) approaches for the selection of the optimum radiation modality for each patient and to enhance the potential for outcomes with the use of radiation dose distributions tailored to the individual patient's baseline and tumor characteristics.

The achievement of these goals will be carried out in three projects:

Project 1: Understanding normal tissue toxicity to identify patients most likely to benefit from proton vs. photon therapy.
Project 2: Radiation-induced lymphopenia (RIL): Understanding, predictive modeling, and developing photon and proton-based mitigation strategies.
Project 3: Investigating enhanced sensitivity of tumors to proton beam therapy: Mechanisms and biomarkers.

The projects are highly integrated in that decisions regarding treatment modality selection, treatment technique, and optimization to maximally enhance the therapeutic ratio cannot be accomplished by any one project alone. Such decisions must consider and balance normal tissue complications, tumor response based on genotypic factors, and radiation-induced immunosuppression.

The three projects will be supported by an Administrative Core and three Resource Cores:

Core 1: Data management and computational support.
Core 2: Translational biospecimens and imaging biomarkers.
Core 3: Biostatistics.

The General Hospital Corporation

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]

Boston, Massachusetts 021142621 United States

Single Zip Code

National Cancer Institute Program Project Applications (P01 Clinical Trial Optional) (PAR-20-077)

Amendment Since initial award the total obligations have increased 375% from $2,940,354 to $13,977,566.