Abstract
BackgroundTo assess the comparative efficacy and safety of elective nodal irradiation (ENI) and involved-field irradiation (IFI) in patients with esophageal cancer (EC) receiving neoadjuvant chemoradiotherapy plus surgery (nCRTS).Material and methodsPubMed, Embase, Cochrane Library, Web of Science and major meetings were searched for randomized controlled trials (RCTs) that compared at least two of the following treatment regimens: nCRTS, neoadjuvant chemotherapy plus surgery (nCTS), and surgery (S) alone. Overall survival (OS) was the primary outcomes of interest, reported as hazard ratio (HR) and 95% confidence intervals (CIs). A Bayesian network meta-analysis was performed to compare all regimens simultaneously.ResultsTwenty-nine RCTs with a total of 5212 patients were included in the meta-analysis. Both nCRTS adopting ENI (nCRTS-ENI) (HR = 0.63, 95% CI: 0.48–0.83) and nCRTS adopting IFI (nCRTS-IFI) (HR = 0.75, 95% CI: 0.66–0.86) significantly improved OS compared to S alone. No significant differences in OS, locoregional recurrence, distant metastases, R0 resection and postoperative mortality were observed between nCRTS-ENI and nCRTS-IFI. In subgroup analyses, nCRTS-IFI showed a significant OS advantage over nCTS (HR = 0.78, 95% CI: 0.63–0.96) and S alone (HR = 0.50, 95% CI: 0.38–0.68) for esophagus squamous cell carcinoma (ESCC), but nCRTS-ENI did not; nCRTS-ENI using three-dimensional radiotherapy (3D-RT) resulted in an improved OS compared to that with 2D-RT (HR = 0.58, 95% CI: 0.34–0.99). Based on treatment ranking in term of OS, nCRTS-IFI (0.90) and nCRTS-ENI (0.96) was ranked the most effective treatment for ESCC and esophagus adenocarcinoma (EAC), respectively.ConclusionEither adopting ENI or IFI, nCRTS is likely to be the optimal treatment for resectable EC, and nCRTS-IFI and nCRTS-ENI seem to be more effective for patients with ESCC and EAC, respectively. Future head to head comparison trials are needed to confirm these findings.
Highlights
Esophagus cancer (EC) is the eighth most common cancer worldwide and the sixth most common cause of cancerrelated deaths [1, 2]
Both neoadjuvant chemoradiotherapy plus surgery (nCRTS) adopting elective nodal irradiation (ENI) (HR = 0.63, 95% confidence intervals (CIs): 0.48–0.83) and nCRTS adopting involved-field irradiation (IFI) (HR = 0.75, 95% CI: 0.66–0.86) significantly improved Overall survival (OS) compared to surgery alone (S alone)
NCRTS-IFI showed a significant OS advantage over neoadjuvant chemotherapy plus surgery (nCTS) (HR = 0.78, 95% CI: 0.63–0.96) and S alone (HR = 0.50, 95% CI: 0.38–0.68) for esophagus squamous cell carcinoma (ESCC), but nCRTS-ENI did not; nCRTS-ENI using three-dimensional radiotherapy (3D-NR Not reported (RT)) resulted in an improved OS compared to that with 2D-RT (HR = 0.58, 95% CI: 0.34–0.99)
Summary
Esophagus cancer (EC) is the eighth most common cancer worldwide and the sixth most common cause of cancerrelated deaths [1, 2]. It should be noted that radiation fields used for patients receiving nCRTS are inconsistent in trials, which might affect the outcomes. Efficacy of ENI and IFI has been compared in patients with locally advanced EC undergoing radical CRT in some retrospective studies [23,24,25,26], but with different results. No trials have compared the two radiation fields directly in patients undergoing nCRTS, and there are still questions around which is more superior, and what is the suitable patient population for adopting ENI or IFI. To assess the comparative efficacy and safety of elective nodal irradiation (ENI) and involved-field irradiation (IFI) in patients with esophageal cancer (EC) receiving neoadjuvant chemoradiotherapy plus surgery (nCRTS)
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