The overall goal of this project is to improve the proton therapy dose distributions that can confidently be delivered. The improvements are expected to be threefold: (1) the use with confidence of tighter margins around the target volume, thus reducing normal tissue complications, (2) reduced uncertainty in treatment planning and delivery through techniques such as image-guided interventions and robust optimization, and (3) confidence that the dose distribution which is delivered agrees, within explicit bounds, with what was planned. While proton therapy has been practiced for several decades with success, there remain a number of uncertainties and limitations that can compromise the benefit of protons, either by requiring undesirably large margins around the clinical target volume (with concomitant over irradiation of normal tissues) or by preventing the use of protons or limiting their optimal application in some important sites (e.g., lung). The hypothesis of this project is that improved accuracy in treatment planning and delivery methods and the application of intensity-modulated proton therapy (IMPT) and optimization techniques will lead to reductions in margins and in the difference between planned and delivered dose distributions;also that these reductions will be by a factor of at least 2 compared with the current values. To test this hypothesis, we will (1) quantify the impact of current uncertainties and the gains made possible with strategies to reduce uncertainties, (2) evaluate the potential of IMPT and optimization techniques for reducing margins and mitigating the impact of uncertainties, and (3) quantify the confidence limits on the planned dose distributions and verify that the differences between planned and delivered dose distributions are within confidence limits. The significance of the proposed research is that it should lead to reductions in margins, greater sparing of normal tissues, and greater potential for dose intensification. Additionally, it should lead to greater confidence that the planned and delivered proton therapy dose distributions are very nearly the same. The significance is further heightened by the need to minimize the possibility of suboptimal application of this very powerful modality whose use is rapidly proliferating around the world.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (M1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Yock, Torunn I; Yeap, Beow Y; Ebb, David H et al. (2016) Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study. Lancet Oncol 17:287-98
Hong, Theodore S; Wo, Jennifer Y; Yeap, Beow Y et al. (2016) Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. J Clin Oncol 34:460-8
Eaton, Bree R; Esiashvili, Natia; Kim, Sungjin et al. (2016) Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival. Int J Radiat Oncol Biol Phys 94:133-8
Giantsoudi, Drosoula; Sethi, Roshan V; Yeap, Beow Y et al. (2016) Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury. Int J Radiat Oncol Biol Phys 95:287-96
Park, Yang-Kyun; Sharp, Gregory C (2016) Gain Correction for an X-ray Imaging System With a Movable Flat Panel Detector and Intrinsic Localization Crosshair. Technol Cancer Res Treat 15:387-95
Bentefour, El H; Tang, Shikui; Cascio, Ethan W et al. (2015) Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements. Med Phys 42:1936-47
Doolan, P J; Testa, M; Sharp, G et al. (2015) Patient-specific stopping power calibration for proton therapy planning based on single-detector proton radiography. Phys Med Biol 60:1901-17
Min, Chul Hee; Zhu, Xuping; Grogg, Kira et al. (2015) A Recommendation on How to Analyze In-Room PET for In Vivo Proton Range Verification Using a Distal PET Surface Method. Technol Cancer Res Treat 14:320-5
Grogg, Kira; Alpert, Nathaniel M; Zhu, Xuping et al. (2015) Mapping (15)O production rate for proton therapy verification. Int J Radiat Oncol Biol Phys 92:453-9
Chen, Huixiao; Winey, Brian A; Daartz, Juliane et al. (2015) Efficiency gains for spinal radiosurgery using multicriteria optimization intensity modulated radiation therapy guided volumetric modulated arc therapy planning. Pract Radiat Oncol 5:49-55

Showing the most recent 10 out of 248 publications