Prognosis and Benefit Factors of Definitive Concurrent Chemoradiotherapy for Patients with Oligometastatic Esophageal Squamous Cell Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> To clarify the efficacy of definitive concurrent chemoradiotherapy (dCRT) for patients with synchronous oligometastatic esophageal squamous cell carcinoma (SOEC), and to construct the decision tree models for predicting the risk of progression and death. <h3>Materials/Methods</h3> A total of 532 patients with SOEC from two centers between January 2012 and December 2018 were enrolled in this study, including 292 patients who received chemotherapy alone (CT alone) and 240 patients who underwent dCRT, and each patient had ≤5 metastatic lesions and metastatic organs ≤3. Propensity score matching (PSM) was performed to control potential confounding factors. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were locoregional control and treatment-related toxicities. Cox regression was used to screen important explanatory variables. The decision trees that optimally partitioned patients with different PFS and OS rates were then built by recursive partitioning analysis (RPA). <h3>Results</h3> The median age of the entire cohort was 63 years (range, 32–82). With a median follow-up time of 37 months (IQR: 21.6-55.8), ORR was 42.1% for the CT alone group and 57.9% for the dCRT group (<i>P</i>=0.000). Median PFS of the CT alone group and dCRT group was 7.6 and 9.7 months, respectively (<i>P</i>=0.000), and median OS was 15.2 and 18.5 months, respectively (<i>P</i>=0.000). PSM analysis verified the same trend (all <i>P</i><0.05). Cox multivariate analysis indicated that treatment modality was an independent prognostic factor associated with PFS (<i>P</i>=0.000) and OS (<i>P</i>=0.008). The minimum complexity parameters (CP) corresponding to a standard deviation range of the minimum cross-validation error were 0.014 and 0.011 for PFS and OS, respectively. The final decision trees after pruning divided patients with SOEC into low, intermediate and high-risk groups by RPA, and the corresponding cumulative risk function curves were drawn by fitting the survival function of patients with different risk levels (all <i>P</i><0.01). Time-dependent receiver operating characteristic (ROC) curves and maximum area under the curves (AUC) of decision trees for progression and death risk were 0.807(95% CI: 0.719-0.894) and 0.911(95% CI: 0.850-0.973), respectively. Calibration curve also demonstrated that the decision trees have favorable hierarchical value. Other major treatment-related toxicities of grade III or higher included radiation pneumonitis (6.7%) and radiation esophagitis (7.1%) for the dCRT group. No treatment-related deaths were observed throughout the study period. <h3>Conclusion</h3> Compared with CT alone, dCRT as a first-line treatment for patients with SOEC has superior survival and amenable toxicity. With the continuous consolidation chemotherapy, OS also achieved significant improvement. The predictive information of our decision tree should be integrated into future clinical trials to provide effective and accurate decision-making for the management of patients with OEC.