Translational studies in flash particle radiotherapy

Active Project Grant Awarded Last action

Award ID
P01CA257904
Recipient
Awarding agency
Obligated
$39,811,987

Award facts

Assistance listing
93.395 Cancer Treatment Research
Completion date 95% complete
Place of performance
Philadelphia, PA 19104, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Radiation therapy (RT) is used in the curative setting for many cancers including sarcomas and lung and pancreatic cancer. Despite significant improvements over the past few decades, there is still much room for improvement as patients still develop RT-induced injuries or second malignant neoplasms. Flash radiotherapy, which delivers a large dose of radiation at an ultra-high dose rate could potentially reduce toxicity. Our overall hypothesis is that proton/carbon particle flash RT is superior to standard particle RT in protecting normal tissues while the two modalities will be equipotent in controlling malignant growth. Project 1, which focuses on pancreatic cancer, will define the dosimetric and biophysical parameters that will maximally spare normal intestine tissues using flash proton therapy (f-PRT) without compromising antitumor effects. IT will delineate mechanistic aspects of differential response of normal intestinal tissues, by focusing on the relative sparing of the stem/progenitor cell population. Project 1 will also employ P53+/- transgenic mouse models to dissect the genetic determinants of differential GI toxicity of standard proton therapy (s-PRT) VS f-PRT. Project 2 will explore the ability of f-PRT to ameliorate adverse events (inflammation, fibrosis, lymphedema, changes to bone structure, radiation-induced cancers) that pose barriers to the treatment of sarcomas with RT. We will also carry out a phase 1/2 trial that will treat canine patients with osteosarcomas definitively with f-PRT. Project 3 will compare the efficacy of flash-RT given with carbon ION radiotherapy (c- RT) VS. Standard dose rate and compare IT to electron f-RT. Studies will focus on the mitigation of normal tissue injury in nsclc with an emphasis on the impact of normal tissue and intratumoral hypoxia to response following c-RT. Lastly, project 4 will develop and validate the use of pencil beam scanning (PBS) technology for particle f-RT. IT will analyze spatiotemporal variations and sobp (spread out bragg peak) VS. Shoot through PBS and develop dose delivery algorithms for modeling biological effects for PBS-based flash proton therapy. These tools will be incorporated in the experimental plans of project 1-3. These projects are supported by 4 cores including an administrative core (core a), physics-dosimetry core (core b), which will offer infrastructure services to harmonize dosimetry between various sites and a comparative pathology core (core c) for tissue preparation for histopathological evaluation. Statistical services will be provided by core d. Collectively, this highly integrated effort led by recognized leaders in radiation and tumor biology, aims to define the biological, dosimetric and biophysical parameters and molecular mechanisms under which flash RT is most effective in tumors and tissues we deem the most likely to be first tested in clinical trials. IT is our belief that only by acquiring this knowledge will this exciting and novel modality be ushered into the clinic in a safe and effective manner to improve therapeutic outcome and quality of life of cancer patients.

Transactions

Action Obligated Date
Amendment $239,984
Amendment $2,159,855
Amendment $2,159,855
Amendment $0
Amendment $0
Amendment $2,177,692
Amendment $2,177,692
Amendment $9,201
Amendment $9,201
Amendment $9,201
Amendment $120,910
Amendment $120,910
Amendment $120,910
Amendment $120,910
Amendment $82,806
Amendment $82,806
Amendment $82,806
Amendment $82,806
Amendment $82,806
Amendment $2,176,388
Amendment $2,176,388
Amendment $2,176,388
Amendment $2,176,388
Amendment $2,176,388
Amendment $2,176,388
Amendment $2,391,268
Amendment $2,391,268
Amendment $2,391,268
Amendment $2,391,268
Amendment $2,391,268
Amendment $0
Amendment $0
Amendment $0
Amendment $2,478,484
Original award $2,478,484
Show all 35

Subawards

Subrecipient Amount Awarded
University Health Network "Statement of Work Dr. Kirsch, University Health Network 1. Analyze small intestine from mice exposed to FLASH and standard dose rate radiation to define the… $86,421
Universitätsklinikum Heidelberg As a subcontractor and Co-Leader of this project we, Drs. Amir Abdollahi and Amato Giaccia, will manage communication among the HIT/UKHD and Oxford University… $173,457
University Of Oxford "Subcontract statement of work-Oxford We will measure the drop in oxygen levels during FLASH irradiation in the irradiated cell media in real-time using an… $92,199
Universitätsklinikum Heidelberg As a subcontractor and Co-Leader of this project we, Drs. Amir Abdollahi and Amato Giaccia, will manage communication among the HIT/UKHD and Oxford University… $182,130
University Health Network Statement of Work Dr. Kirsch, University Health Network 1. Analyze small intestine from mice exposed to FLASH and standard dose rate radiation to define the… $73,751
University Of Oxford Subcontract statement of work-Oxford We will measure the drop in oxygen levels during FLASH irradiation in the irradiated cell media in real-time using an… $4,601
University Of Oxford $92,022

Quick answers

Who received award P01CA257904?

P01CA257904 was awarded to The Trustees Of The University Of Pennsylvania by National Cancer Institute (National Institutes of Health) on February 15, 2022.

How much is award P01CA257904 worth?

$39,811,987 has been obligated on P01CA257904.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login