Utilization of neoadjuvant intensity-modulated radiation therapy and proton beam therapy for esophageal cancer in the United States

Background: Randomized esophageal cancer (EC) trials have utilized two- or three-dimensional conformal radiotherapy (3DCRT). Advanced radiotherapy (RT) techniques [(ARTs): intensity-modulated radiotherapy (IMRT) and proton beam therapy (PBT)] may have benefits, but are relatively unproven. This is the first study to date evaluating utilization of ARTs versus 3DCRT in the trimodality setting in the United States.

Methods: The National Cancer Data Base (NCDB) was queried (2004-2013) for newly-diagnosed cT1b-T4bN0/N+M0 EC receiving neoadjuvant CRT followed by esophagectomy. The primary objective was to assess temporal trends, with multivariable logistic regression analysis assessing factors predictive of receiving ARTs. Secondarily, Kaplan-Meier analysis evaluated overall survival (OS), Cox proportional hazards modeling determined variables associated with OS, and postoperative complications were compared between cohorts.

Results: Altogether, 3,138 patients met criteria; 1,398 (45%) received 3DCRT, and 1,740 (55%) received ARTs (99% IMRT, 1% PBT). Temporally, utilization of ARTs is steadily rising in the United States, from 20% in 2004 to 69% in 2013, corresponding with a progressive decrease in utilization of 3DCRT. ARTs were more often delivered with advancing age, squamous cell histology, N2+ disease, and at academic centers (P<0.05 for all). Centers in the Southwest were more likely to use ARTs, and those in the Midwest least likely (P<0.05 for both). As expected, there were no OS differences (P=0.8477); there were also no differences in postoperative events (P>0.05 for all). Treatment at an academic center independently correlated with improved OS (P<0.001).

Conclusions: Utilization of ARTs (IMRT in the vast majority) is steadily rising in the United States; 3DCRT is now used in a minority of patients. This has implications for payers and insurance coverage. ART use is impacted by not only age and disease factors, but also regional and facility differences. Treatment at an academic facility independently correlated with higher survival, which has implications for patient counseling.