Comparative Outcomes and Toxicity in Patients With Esophageal Cancer After Trimodality Therapy With Step-and-Shoot...

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).

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.

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.

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.