Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

Abstract

Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

Keywords: lung cancer; post-operative radiation therapy (PORT); proton beam therapy (PBT); radiotherapy; re-irradiation.

Figure 1

Percent depth dose curve of proton beam vs. photon beam demonstrating that protons do not deposit dose beyond the prescribed depth, whereas photon do.

Figure 2

Hypothetical benefit of dose escalation with proton beam therapy over photon radiotherapy, as demonstrated as detrimental in Radiation Therapy Oncology Group (RTOG) 0617.

Figure 3

Example Showing the Sensitivity of Proton Beam Therapy to Anatomic Changes. Patient being treated with pencil beam scanning for a cT3N0 NSCLC developed an effusion after two weeks of radiotherapy (panel A: dose colorwash at initial simulation; panel B: dose colorwash at verification scan 2 weeks into radiotherapy). Planning tumor volume outlined in light blue. Dose colorwash shown cutoff at 90% in both panels. In panel B, compared to panel A (dose distribution at initial CT simulation), the target volume is significantly undercovered.