ES16.01 Proton Therapy

Abstract

Proton therapy is an attractive option for the treatment of lung cancer patients due to the physical properties of proton beams. Proton therapy allows a focused delivery of radiation at the Bragg peak, with very steep decline of the radiation dose beyond the target volume. These properties offer the possibility to 1) reduce toxicity by reducing the integral dose and the dose to adjacent normal tissues and 2) escalate the dose to the target in some patients. In this talk, I will summarise briefly the physics/radiobiology of protons and the need for adaptation. I will also discuss the rationale for the use of protons in patients with lung cancer, including reduction in integral dose, cardiac toxicity and reduction in haematological toxicity. The clinical trial evidence supporting the use of protons will be presented in early stage and locally advanced non-small cell lung cancer as well as in small-cell lung cancer. Finally I will discuss future research directions, including preclinical and drug-proton combination research, ongoing clinical trials, the model based-approach and the need for biomarkers. Liao Z, Lee JJ, Komaki R, eat l. 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. 2018;36(18):1813-1822 Chang JY, Jabbour SK, De Ruysscher D, et al; International Particle Therapy Co-operative Group Thoracic Subcommittee.Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2016;95(1):505-16. Vyfhuis MAL, Onyeuku N, Diwanji T, Mossahebi S, Amin NP, Badiyan SN, Mohindra P, Simone CB 2nd. Advances in proton therapy in lung cancer. Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618783878 C, Pawelke J, Seidlitz A, Peitzsch C, et al; “Radiobiology of Proton Therapy”: Results of an international expert workshop.Lühr A, von Neubeck Radiother Oncol. 2018; 128(1):56-67 Jin, J.Y., et al., Higher Radiation Dose to Immune System is Correlated With Poorer Survival in Patients With Stage III Non-small Cell Lung Cancer: A Secondary Study of a Phase 3 Cooperative Group Trial (NRG Oncology RTOG 0617). International Journal of Radiation Oncology Biology Physics, 2017. 99(2): p. S151-S152. Joseph, N., et al., Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy. Radiotherapy and Oncology, 2019. 135: p. 115-119. Durante, M., D.J. Brenner, and S.C. Formenti, Does Heavy Ion Therapy Work Through the Immune System? Int J Radiat Oncol Biol Phys, 2016. 96(5): p. 934-936. Lee, H.J., Jr., J. Zeng, and R. Rengan, Proton beam therapy and immunotherapy: an emerging partnership for immune activation in non-small cell lung cancer. Translational lung cancer research, 2018. 7(2): p. 180-188. Dess, R.T., et al., Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol, 2017. 35(13): p. 1395-1402. McWilliam, A., et al., Radiation dose to heart base linked with poorer survival in lung cancer patients. Eur J Cancer, 2017. 85: p. 106-113. Schulz-Ertner, D. and H. Tsujii, Particle radiation therapy using proton and heavier ion beams. J Clin Oncol, 2007. 25(8): p. 953-64. Gameiro, S.R., et al., Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell-Mediated Killing. Int J Radiat Oncol Biol Phys, 2016. 95(1): p. 120-30.