Comparative Outcomes and Toxicity in Patients With Esophageal Cancer After Trimodality Therapy With Step-and-Shoot Intensity-Modulated Radiation Therapy Versus Volumetric Modulated Arc Therapy: The MD Anderson Experience

Aims: To evaluate outcomes and toxicity after intensity-modulated radiation therapy given as step-and-shoot (SS) or volumetric modulated arc therapy (VMAT) for patients with locally advanced esophageal cancer treated with trimodality therapy (i.e. neoadjuvant concurrent chemoradiation therapy followed by surgery).

Materials and methods: Patients consecutively treated with trimodality therapy including IMRT in 2001-2022 (n = 449) were retrospectively reviewed, and 106 pairs of propensity-matched SS and VMAT patients were identified. Survival, recurrence, surgery-related prognostic factors, and chemoradiation-related toxicities were evaluated between groups.

Results: Baseline characteristics were balanced between both groups except for body mass index, history of other cancer, clinical disease stage, and use of induction chemotherapy. Median follow-up time was 40 months. Relative to SS, VMAT led to higher 3-year overall survival (OS; P = 0.028, hazard ratio [HR] 0.645, 95% confidence interval [CI] 0.436-0.954) but not progression-free, locoregional recurrence-free, or distant metastasis-free survival. No predictor of excellent OS by SS versus VMAT was identified in multivariable analyses. However, VMAT was associated with reduced odds of postoperative cardiac complications (P < 0.001, odds ratio [OR] 0.296, 95% CI 0.148-0.591), pulmonary complications (P = 0.048, OR 0.539, 95% CI 0.292-0.994), pathologic partial response or worse (≥10% viable cells; P = 0.003, OR 0.418, 95% CI 0.235-0.743), and positive/close margins (P = 0.023, OR 0.346, 95% CI 0.138-0.867) relative to SS. VMAT was also associated with reduced rates of chemoradiation therapy-related weight loss (33.0% versus 79.2%, P < 0.001), fatigue (40.6% versus 68.9%, P < 0.001), nausea (31.1% versus 58.5%, P < 0.001) and cardiac toxicity (0% versus 6.6%, P = 0.007) than SS.

Conclusion: Based on this single institution, retrospective study with a 40-month median follow-up, VMAT utilization in trimodality treatment for locally advanced esophageal cancer appears to be associated with improved OS and rates of concurrent chemoradiation therapy-related toxicity and reduced initial 12-month postoperative complications relative to SS IMRT. Multi-institutional prospective trials addressing the limitations of this study and with longer follow-ups are warranted to validate these findings.