Proton Therapy in Non-small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) accounts for 85% of new lung cancer cases and has 5-year survival rates ranging from 92% in early-stage disease to as low as 13% in locally advanced cases. Radiation therapy is a key component in the treatment repertoire for NSCLC, where it is currently used alone or in combinations with chemotherapy and surgery. Despite the broad use of modern photon radiation techniques, as many as 25% of patients experience isolated locoregional recurrences, and toxicity has been proven to be a limiting factor in many cases. Proton beam therapy (PBT) has emerged as a potential solution to improve upon clinical outcomes in both early-stage and locally advanced disease. The proton beam allows for a sharp dose build-up and drop-off, which is particularly important in lung cancer where nearby structures include the heart, spinal cord, esophagus, and uninvolved lung. There are now numerous studies showing dosimetric advantages of PBT in early and locally advanced NSCLC, particularly in the heart and lung doses. Randomized data comparing clinical outcomes between proton and photon radiation are limited to a small number of studies. Despite early results suggesting improvements or at least comparable outcomes with PBT, the most recent randomized comparisons have failed to show significant differences in toxicity and local control between photon and proton therapy. As newer PBT techniques (e.g., intensity-modulated proton therapy) are increasingly utilized, more dramatic improvements in tumor control and toxicity may be demonstrated. It is also important to recognize that there may be certain subpopulations in which the benefits of proton therapy are greater, such as central early-stage tumors, previously irradiated tumors, and locally advanced tumors, while others may best be treated with traditional photon techniques. As immunotherapy becomes more prevalent in the treatment of NSCLC, improving local control and limiting the toxicity contributed by radiation will be increasingly important. The unique dosimetric advantages of PBT may allow for tumor dose escalation while maintaining normal tissue doses to improve local control, or treating the tumor to the standard dose while decreasing normal tissue doses to improve toxicity. Finally, given the high costs of proton therapy, where low insurance approval rates have limited trial enrollment, it will be important to determine the overall cost-benefit ratio.