LAUSR

Efforts to increase tumor control and minimize toxic effects to normal tissue have been long-sought goals in the treatment of patients with locally advanced solid tumors who receive multimodal therapeutic approaches. For patients with non– small-cell lung cancer with clinically unresectable stage II to III disease, one standard of care for patients with a reasonable performance status is consideration of concomitant chemoradiotherapy, often with a platinum doublet and standard fractionation external-beam radiotherapy using conventional x-rays (photon energy). To minimize radiation-induced toxic effects to vital organs-at-risk in the thorax, such as the spinal cord, esophagus, lung parenchyma, bronchus, heart, and substructures, conformal radiotherapy approaches have been developed over the past 2 decades. Particle therapy can lessen the delivered integral dose, and the relatively steeper dose gradient compared with conventional x-rays can lead to superior conformality and potentially fewer toxic effects to normal tissue.1 However, well-designed, prospective clinical trials have lagged as the number of proton centers has increased. This is unfortunate and has delayed the generation of crucial evidencebased recommendations for use of this component of the anticancer toolbox. The MD Anderson multidisciplinary thoracic oncology program has completed an important phase 2 open-label, single-group assignment study for this patient cohort testing a definitive combined modality (carboplatin-paclitaxel and 74-Gy passively scattered proton thoracic radiotherapy).2 The primary goal was to increase overall survival (OS) by 8 months, based on RTOG-9410 as a historical control.3 The median OS and 5-year OS is reported at 26.5 months and 29.3%, respectively. Screening 121 patients led to a 69% yield of patients (N = 84) enrolled and a 53% yield of total patients (n = 64) accrued and eligible for analysis. This speaks to the real dedication that is needed to execute a prospective study of particle therapy in similar disease settings. While late pulmonary toxic effects were reported in nearly onequarter (23%) of patients, the rest of the toxicity profile was acceptable. The current NRG/RTOG protocol 1308 will seek to clarify any survival benefit when comparing photon and proton thoracic radiotherapy atop a platinum-doublet chemotherapy backbone in a randomized clinical trial (NCT01993810). If the results are encouraging, next-generation particle therapy trials for locally advanced non–small-cell lung cancer may seek to incorporate adaptive planning and delivery along with more advanced image guidance and proton beam modulation. At the end of the day, patients, clinicians, payers, vendors, and policy makers will anticipate the design, execution, and reporting of ongoing and future well-designed clinical trials testing particle therapy.