The goal of cancer treatment is cure without morbidity. Radiation can be an effective locoregional cancer treatment. The challenge is to deliver the appropriate dose to only the tumor without exposing normal tissues to excessive dose. Protons, with no exit dose beyond the target, irradiate less normal tissue than comparable photon fields. This can improve the therapeutic ratio of cure vs. complication. While many patients have been treated with protons with impressive clinical results in a number of disease sites, and while protons have in fact become widely accepted in some clinical scenarios, further research can greatly enhance the clinical effectiveness and applicability of protons, particularly through intensity-modulated proton therapy (IMPT). IMPT is a powerful tool with unique opportunities to improve both outcomes the understanding of physical and biophysical aspect of protons through its markedly different dose patterns. The primary objective of this multi-institutional program project is to study and refine IMPT to improve outcome in randomized phase II trials for cancers of the lung, liver, oropharynx, nasopharynx and brain;and in non-randomized phase l/ll trials for pediatric CNS tumors needing craniospinal irradiation, retroperitoneal sarcoma, breast, atypical and malignant meningioma, and glioblastoma. This project supports the mission of the NCI to improve the treatment and continuing care of cancer patients. The hypothesis is that through better understanding of the proton interactions with tissues, and study and management of motion and anatomic changes, higher accuracy in proton therapy (PT) can be achieved to further improve target coverage, reduce the dose bath and elaborate and manage biophysical determinants of treatment response. Four integrated projects are proposed: (1) Assessment of the Effectiveness of IMPT vs. IMRT through Randomized Clinical Trials;(2) Exploratory Phase l/ll Clinical Studies to Improve the Therapeutic Ratio of PT;(3) Assessing and Understanding the Impact of Physical and Biological Factors on Outcomes of PT;and (4) Improving Outcomes by Optimally Exploiting Physical and Biological Characteristics of Protons.

Public Health Relevance

This research aims to improve radiation treatment for cancer patients by improving our ability to direct the radiation at the tumor to spare adjacent normal tissue by using protons (charged particles) with intensity-modulated proton therapy. This can potentially improve cancer cure rates, reduce side effects, or both, depending on the clinical scenario. With an increasing number of proton centers in the United States and abroad, the research in this program project is increasingly important for public health.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19CA021239-35
Application #
8670311
Study Section
Special Emphasis Panel (ZCA1-RPRB-C (J1))
Program Officer
Vikram, Bhadrasain
Project Start
1997-04-01
Project End
2019-08-31
Budget Start
2014-09-25
Budget End
2015-08-31
Support Year
35
Fiscal Year
2014
Total Cost
$2,343,081
Indirect Cost
$487,909
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Niedzielski, Joshua S; Yang, Jinzhong; Liao, Zhongxing et al. (2016) (18)F-Fluorodeoxyglucose Positron Emission Tomography Can Quantify and Predict Esophageal Injury During Radiation Therapy. Int J Radiat Oncol Biol Phys 96:670-8
Gunn, G Brandon; Blanchard, Pierre; Garden, Adam S et al. (2016) Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma. Int J Radiat Oncol Biol Phys 95:360-7
Hall, David C; Makarova, Anastasia; Paganetti, Harald et al. (2016) Validation of nuclear models in Geant4 using the dose distribution of a 177 MeV proton pencil beam. Phys Med Biol 61:N1-N10
Unkelbach, Jan; Botas, Pablo; Giantsoudi, Drosoula et al. (2016) Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer. Int J Radiat Oncol Biol Phys 96:1097-1106
Niedzielski, Joshua S; Yang, Jinzhong; Stingo, Francesco et al. (2016) Objectively Quantifying Radiation Esophagitis With Novel Computed Tomography-Based Metrics. Int J Radiat Oncol Biol Phys 94:385-93
Wang, Xin Shelley; Shi, Qiuling; Williams, Loretta A et al. (2016) Prospective Study of Patient-Reported Symptom Burden in Patients With Non-Small-Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy. J Pain Symptom Manage 51:832-8
Underwood, Tracy; Paganetti, Harald (2016) Variable Proton Relative Biological Effectiveness: How Do We Move Forward? Int J Radiat Oncol Biol Phys 95:56-8
Unkelbach, Jan; Bussière, Marc R; Chapman, Paul H et al. (2016) Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations. Int J Radiat Oncol Biol Phys 95:1067-74
Taylor, Paige A; Kry, Stephen F; Alvarez, Paola et al. (2016) Results From the Imaging and Radiation Oncology Core Houston's Anthropomorphic Phantoms Used for Proton Therapy Clinical Trial Credentialing. Int J Radiat Oncol Biol Phys 95:242-8
Peeler, Christopher R; Mirkovic, Dragan; Titt, Uwe et al. (2016) Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma. Radiother Oncol :

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