Particle Therapy in Non-Small Cell Lung Cancer

Zhongxing Liao; Charles B. Simone II


Transl Lung Cancer Res. 2018;7(2) 

In This Article

Summary and Future Directions

Particle therapy has tremendous potential for treating thoracic cancer because of its superior dose distribution. However, the challenges in translating the dosimetric advantages of proton therapy to clinical benefits for patients with thoracic tumors are only beginning to be appreciated, and the development of technology to deliver proton therapy lags at least 20 years behind the development of the photon delivery technology. First, the greater vulnerability of protons to inherent heterogeneities in the beam path, to tumor and organ motion, to anatomic changes during the treatment, and to other factors poses significant challenges for proton treatment planning and for accurate and precise dose delivery. To fully realize the potential of particle therapy for thoracic cancer, extensive improvements are needed in all aspects of the treatment process, from simulation, planning algorithms, and volumetric image guidance through to real-time tracking and treatment adaptation. Highly conformal dose distribution is both basic and essential for demonstrating a clinical advantage for proton therapy in terms of preventing radiation pneumonitis, because expanding margins to counteract uncertainties would negate the dosimetric advantages of protons. Second, the commonly used normal tissue complication probability models based on photon therapy are not appropriate for proton therapy, and thus particle therapy-specific predictive models are needed that incorporate not only proton dose-distribution characteristics but also variations in RBE. Third, the need continues for designing and conducting "smart" proton therapy trials to establish clinical evidence and patient selection criteria to make proton therapy a truly personalized form of treatment. Future comparative trials could focus on endpoints that are common across all disease sites, such as cardiac toxicity, low-dose bath, and lymphopenia, instead of comparing one modality with another for a particular type of disease. Finally, new approaches to enhancing the dosimetric and biological advantages of proton therapy to improve clinical outcomes will require active and creative investigation, particularly image-guided hypofractionated IMPT and combinations of hypofractionated proton therapy with immunotherapy.