Objectives and Specific Aims Any tumor cell can be eradicated with a sufficiently high dose of radiation;conversely, any normal tissue can be injured with sufficient dose to a given volume. The challenge for clinicians is to deliver the appropriate dose to only those tissues containing tumor. Proton radiation fields, with no exit beyond the target, deliver less radiation to normal tissues than comparable photon (x-ray) fields. This improves the therapeutic ratio (of cure probability to complication risk) because irradiation of normal tissue does not benefit the patient. We have treated nearly 7,000 cancer patients with proton therapy at the Harvard Cyclotron and Francis H. Burr Proton Therapy Center (FHBPTC) since 1974. We have achieved significant gains in clinical outcomes for a number of disease sites including chondrosarcomas and chordomas of the skull base and cervical spine (95% and 50% local control, respectively), paranasal sinus tumors (82% local control), ocular melanoma (97% local control), and prostate cancer (80% biochemically disease-free). At the FHBPTC, we have been able to expand the range of diseases treated to include pediatric malignancies at nearly any anatomic site including craniospinal axis treatment under anesthesia, nasopharyngeal carcinoma, lung and hepatocellular tumors under respiratory gating, and pelvic and retroperitoneal sarcomas. We believe that research in this field can further iimprove our utilization of the proton beam in the clinic to enhance treatment outcome. We hypothesize that, mainly through the use of advanced imaging technology, we can deliver higher precision proton therapy to further improve target coverage and/or reduced dose to nearby critical structures. We propose 3 integrated projects (1)Clinical Utilization of the Physical Advantages of Proton Therapy, (2)Optimizing the Use of Protons in the Clinic, and (3) Morbidity Reduction with Proton Radiation Therapy to test this hypothesis.
The specific aims of the projects are to develop dose guided proton therapy techniques including PET/CT imaging to measure the activation of positron emitters through the proton beam, to control range in the presence of organ motion, and to advance beam delivery strategies for intensity modulated proton therapy to further improve therapeutic ratio. In selected clinical sites where tumor closely invests normal tissue, morbidity reduction with targetted biologic agents will also be explored.
|Pulsifer, Margaret B; Duncanson, Haley; Grieco, Julie et al. (2018) Cognitive and Adaptive Outcomes After Proton Radiation for Pediatric Patients With Brain Tumors. Int J Radiat Oncol Biol Phys 102:391-398|
|Liao, Zhongxing; Lee, J Jack; Komaki, Ritsuko et al. (2018) Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 36:1813-1822|
|Jeter, Melenda D; Gomez, Daniel; Nguyen, Quynh-Nhu et al. (2018) Simultaneous Integrated Boost for Radiation Dose Escalation to the Gross Tumor Volume With Intensity Modulated (Photon) Radiation Therapy or Intensity Modulated Proton Therapy and Concurrent Chemotherapy for Stage II to III Non-Small Cell Lung Cancer: A P Int J Radiat Oncol Biol Phys 100:730-737|
|Frank, Steven J; Blanchard, Pierre; Lee, J Jack et al. (2018) Comparing Intensity-Modulated Proton Therapy With Intensity-Modulated Photon Therapy for Oropharyngeal Cancer: The Journey From Clinical Trial Concept to Activation. Semin Radiat Oncol 28:108-113|
|Lin, Yu-Fen; Chen, Benjamin P; Li, Wende et al. (2018) The Relative Biological Effect of Spread-Out Bragg Peak Protons in Sensitive and Resistant Tumor Cells. Int J Part Ther 4:33-39|
|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|
|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|
|Sanford, Nina N; Yeap, Beow Y; Larvie, Mykol et al. (2017) Prospective, Randomized Study of Radiation Dose Escalation With Combined Proton-Photon Therapy for Benign Meningiomas. Int J Radiat Oncol Biol Phys 99:787-796|
|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|
|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|
Showing the most recent 10 out of 260 publications