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      Elective nodal irradiation versus involved-field irradiation in patients with esophageal cancer receiving neoadjuvant chemoradiotherapy: a network meta-analysis

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          Abstract

          Background

          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).

          Material and methods

          PubMed, 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.

          Results

          Twenty-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.

          Conclusion

          Either 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.

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          Inference from Iterative Simulation Using Multiple Sequences

          Andrew Gelman, Donald B Rubin (1992)
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            Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial.

            Marc Ychou, Valérie Boige, Jean-Pierre Pignon … (2011)
            After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma. Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS. Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio [HR] for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups. In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.
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              Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial.

              (2002)
              The outlook for patients with oesophageal cancer undergoing surgical resection with curative intent is poor. We aimed to assess the effects of preoperative chemotherapy on survival, dysphagia, and performance status in this group of patients. 802 previously untreated patients with resectable oesophageal cancer of any cell type were randomly allocated either two 4-day cycles, 3 weeks apart, of cisplatin 80 mg/m(2) by infusion over 4 h plus fluorouracil 1000 mg/m(2) daily by continuous infusion for 4 days followed by surgical resection (CS group, n=400), or resection alone (S group, 402). Clinicians could choose to give preoperative radiotherapy to all their patients irrespective of randomisation. Primary outcome measure was survival time. Analysis was by intention to treat. No patients dropped out of the study. Resection was microscopically complete in 233 (60%) of 390 assessable CS patients and 215 (54%) of 397 S patients (p<0.0001). Postoperative complications were reported in 146 (41%) CS and 161 (42%) S patients. Overall survival was better in the CS group (hazard ratio 0.79; 95% CI 0.67-0.93; p=0.004). Median survival was 512 days (16.8 months) in the CS group compared with 405 days (13.3 months) in the S group (difference 107 days; 95% CI 30-196), and 2-year survival rates were 43% and 34% (difference 9%; 3-14). Two cycles of preoperative cisplatin and fluorouracil improve survival without additional serious adverse events in the treatment of patients with resectable oesophageal cancer.
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                Author and article information

                Contributors
                Tingting Liu: tingting504@163.com
                Silu Ding: dsllnsy@163.com
                Jun Dang:
                ORCID: http://orcid.org/0000-0002-1408-4749
                dangjunsy@163.com
                Hui Wang: cindydyt@163.com
                Jun Chen: cjsyxkyy@163.com
                Guang Li: gl1963516@yahoo.com
                Journal
                Journal ID (nlm-ta): Radiat Oncol
                Journal ID (iso-abbrev): Radiat Oncol
                Title: Radiation Oncology (London, England)
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1748-717X
                Publication date (Electronic): 16 October 2019
                Publication date PMC-release: 16 October 2019
                Publication date Collection: 2019
                Volume: 14
                Electronic Location Identifier: 176
                Affiliations
                [1 ]GRID grid.412636.4, Department of Radiation Oncology, , The First Hospital of China Medical University, ; Shenyang, China
                [2 ]Department of Radiation Oncology, Anshan Cancer Hospital, Anshan, China
                [3 ]Department of Radiation Oncology, General Hospital of Benxi Iron & Steel Industry Group of Liaoning Health Industry Group, Shenyang, China
                [4 ]Department of Radiation Oncology, Shenyang Chest Hospital, Shenyang, China
                Author information
                http://orcid.org/0000-0002-1408-4749
                Article
                Publisher ID: 1388
                DOI: 10.1186/s13014-019-1388-8
                PMC ID: 6794743
                PubMed ID: 31619265
                SO-VID: f70290fa-4e5b-43ba-b43d-a34b35d4205f
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 9 May 2019
                Date accepted : 30 September 2019
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: esophagus cancer,neoadjuvant chemoradiotherapy,elective nodal irradiation,involved-field irradiation,network meta-analysis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: esophagus cancer, neoadjuvant chemoradiotherapy, elective nodal irradiation, involved-field irradiation, network meta-analysis

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