Objectives and Specific Aims The goal of cancer treatment is cure without morbidity. Radiation can be an effective locoregional cancer treatment. While any tumor can be killed with enough radiation, any normal tissue can also be injured with sufficient dose to a given volume. The challenge is to deliver the appropriate dose to only those tissues containing tumor. Protons, with no exit dose beyond the target, irradiate less normal tissue than comparable photon (X-ray) fields. This can improve the therapeutic ratio of cure probability to complication risk. While many patients have been treated with protons with impressive clinical results in a number of disease sites, we believe that research can enable and enhance the use of protons in other disease sites. The objective of this multi-institutional program project is to apply advanced proton radiation planning and delivery techniques to improve outcome for patients with non-small cell lung cancer, liver tumors, pediatric medulloblastoma and rhabdomyosarcoma, spine/skull base sarcomas, and paranasal sinus malignancies. We hypothesize that through better use and understanding of the proton range in tissue, and study and management of motion and anatomic changes in the tumor and normal tissues, we can deliver higher precision proton therapy to further improve target coverage and/or reduce dose to nearby critical structures. To test this hypothesis, we propose four integrated projects: (1) Proton Dose Escalation and Proton vs. Photon Randomized Trials for the Treatment of Nonsmall Cell Lung Cancer, (2)lmproving the Therapeutic Ration of Proton Radiation Therapy in Challenging Clinical Sites, (3) Reducing Range Uncertainties in Proton Radiation Therapy, (4) Achieving What-You-See-ls-What-You-Get in Proton Radiation Therapy. The proton physical interactions sufficient to allow smallerspecific aims are to (1) develop an understanding of safety margins as well as more robust and conformal dose distributions, allowing protons to more nearly meet their full potential, and to verify that these advantages can be reliably achieved;(2) use these advantages in randomized clinical trials of protons vs. photons in lung cancer;and (3) to use these advantages in the proton therapy of a number of tumor sites for which protons are judged to have an increasingly important role and which have proven problematic for clinicians in the past.

Public Health Relevance

This research aims to improve cancer treatment for patients undergoing radiation therapy by improving our ability to direct the radiation at the tumor and spare adjacent normal tissue by using protons

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA021239-32
Application #
8142782
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (M1))
Program Officer
Vikram, Bhadrasain
Project Start
1997-04-01
Project End
2014-07-31
Budget Start
2011-09-21
Budget End
2012-07-31
Support Year
32
Fiscal Year
2011
Total Cost
$316,215
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Taylor, Paige A; Kry, Stephen F; Followill, David S (2017) Pencil Beam Algorithms Are Unsuitable for Proton Dose Calculations in Lung. Int J Radiat Oncol Biol Phys 99:750-756
Chang, Joe Y; Zhang, Wencheng; Komaki, Ritsuko et al. (2017) Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer. Radiother Oncol 122:274-280
Ning, Matthew S; Tang, Linglong; Gomez, Daniel R et al. (2017) Incidence and Predictors of Pericardial Effusion After Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 99:70-79
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Phukan, Rishabh; Herzog, Tyler; Boland, Patrick J et al. (2016) How Does the Level of Sacral Resection for Primary Malignant Bone Tumors Affect Physical and Mental Health, Pain, Mobility, Incontinence, and Sexual Function? Clin Orthop Relat Res 474:687-96
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
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
Eaton, Bree R; Esiashvili, Natia; Kim, Sungjin et al. (2016) Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma. Neuro Oncol 18:881-7
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

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