Particle therapy in non-small cell lung cancer

The finite range of proton beams in tissues offers unique dosimetric advantages that theoretically allow the dose to the target to be escalated while minimizing exposure of surrounding tissues and thereby minimizing radiation-induced toxicity. These theoretical advantages have led to widespread adoption of proton therapy around the world for a wide variety of tumors at different anatomic sites. Many treatment-planning comparisons have shown that proton therapy has substantial dosimetric advantages over conventional photon (X-ray) radiation therapy. However, given the typically significant difference in cost between proton therapy versus conventional photon therapy, strong evidence of proton therapy's clinical benefits in terms of toxicity and survival is warranted. Some findings from retrospective studies, single-arm prospective studies, and a very few randomized clinical trials comparing these modalities are beginning to emerge. In this review, we examine the available data on proton therapy for (non-small cell lung cancer NSCLC). We begin by discussing the unique challenges involved in treating moving targets with significant tissue heterogeneity and the technologic efforts underway to overcome these challenges. We then discuss the rationale for minimizing normal tissue toxicity, particularly pulmonary, cardiac, and hematologic toxicity, within the context of previously unsuccessful attempts at dose escalation for lung cancer. Finally, we explore strategies for accelerating the development of trials aimed at measuring meaningful clinical endpoints and for maximizing the value of proton therapy by personalizing its use for individual patients.