Details of out-field regional recurrence after involved-field irradiation with concurrent chemotherapy for locally advanced esophageal squamous cell carcinoma

OncoTargets and Therapy Dovepress open access to scientific and medical research Original Research OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 37.59.46.207 on 13-Jul-2018 For personal use only. Open Access Full Text Article Details of out-field regional recurrence after involved-field irradiation with concurrent chemotherapy for locally advanced esophageal squamous cell carcinoma This article was published in the following Dove Press journal: OncoTargets and Therapy 23 May 2016 Number of times this article has been viewed Xiaoli Zhang 1,2 Jinming Yu 1,2 Minghuan Li 2 Hui Zhu 2 Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 2 Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, People’s Republic of China 1 Correspondence: Jinming Yu Department of Radiation Oncology, Shandong Cancer Hospital and Institute, No 440 Jiyan Road, Jinan, Shandong 250117, People’s Republic of China Tel +86 531 8798 4729 Fax +86 531 8798 4079 Email Introduction Esophageal cancer, as a highly invasive and metastatic tumor, ranks among the top five leading causes of morbidity and mortality in the People’s Republic of China.1 Due to its biological and histological specificity, lymph node (LN) metastases are common, appearing early in the disease and often in “skip” patterns.2–4 A large majority of esophageal cancers are diagnosed at locally advanced stage with extensive nodal 3049 submit your manuscript | www.dovepress.com OncoTargets and Therapy 2016:9 3049–3057 Dovepress © 2016 Zhang et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/OTT.S100946 Powered by TCPDF (www.tcpdf.org) Background: The purpose of this study was to describe the patterns of out-field regional recurrence after involved-field irradiation (IFI) in definitive concurrent chemoradiotherapy (CCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) and identify the possible risk factors. Patients and methods: Eighty patients with LA-ESCC who received CCRT with IFI between January 2003 and January 2009 at the Shandong Cancer Hospital were recruited and analyzed. Imaging scans demonstrating first sites of failure were compared with original computed tomography-based radiation treatment plans, and failure patterns were defined as in-field, outfield regional (failures in initially uninvolved regional nodes), and distant failures. Results: After a median follow-up time of 52.6 months, 24 patients had evidence of out-field regional failure, 43 patients had evidence of in-field failure, and 33 patients had the evidence of distant failure. Multivariate analysis revealed that out-field regional failure was associated with clinical tumor status (T4 vs T1–3, odds ratio [OR] =6.547, P=0.002), tumor length (8 cm vs 8 cm, OR =4.130, P=0.036), response to CCRT (complete response vs no complete response, OR =2.646, P=0.035), and in-field failure (no in-field failure vs in-field failure, OR =1.32, P=0.016). Survival analyses indicated that, compared to in-field failure or distant failure alone group, out-field regional failure alone group tended to have longer overall (P=0.006) and progression-free survival (P=0.164). Conclusion: Our data suggested that the predominant failure pattern after IFI was not out-field regional failure, which also did not influence survival significantly, and that out-field regional failure did not shorten the time to disease recurrence, which also did not influence survival significantly. In addition, out-field regional failure was likely to appear later than in-field and distant failures. The relatively advanced local disease followed by poor local control and distant metastases contributed more to the poor outcome of LA-ESCC. Further prospective studies are needed to verify the findings of this study. Keywords: failure patterns, prognosis, risk factors Dovepress OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 37.59.46.207 on 13-Jul-2018 For personal use only. Zhang et al spread. Based on the results of Radiation Therapy Oncology Group 8501, concurrent chemoradiotherapy (CCRT) has been broadly applied as a standard management for patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).5 However, the radiation fields to be used in the treatment of LA-ESCC are controversial. Recent reports as well as our previous research have reported that using three-dimensional conformal radiotherapy (3D-CRT) without intentional elective node irradiation (ENI) led to a rate of isolated out-field failure of only 2%–13%.6–10 Hence, some researchers thought that the paucity of elective nodal failures (ie, recurrence in a nodal region without preexisting gross disease) may be in part due to the large competing risk of local recurrence, thereby obviating any regional control benefit from ENI. In the definitive chemotherapy setting, however, improved local control may uncover a benefit for aggressive prophylactic nodal irradiation. Thus, the omission of ENI did not sacrifice the overall survival (OS); to some extent that suggested the feasibility of in-field irradiation (IFI; nodal target volume included only the malignant nodes) using definitive 3D-CRT for locally advanced cases. However, the trend toward treating LA-ESCC with involved-field irradiation (IFI) has generated concern for the increased risk of nodal failure in untreated nodal area, as clinically uninvolved LNs may harbor microscopic disease.6–10 The purpose of this study was to retrospectively describe the patterns of out-field recurrence of IFI in CCRT for LA-ESCC and then identify the clinical factors that may be associated with failure in out-field volume. Patients and methods Patients Use of IFI with concurrent chemotherapy for esophageal cancer has been routine in the Department of Radiation Oncology (Shandong Cancer Hospital affiliated to Shandong University) since 2003. We retrospectively reviewed the clinical records of patients with LA-ESCC, who had been histologically confirmed by biopsy or brush sample between January 2003 and December 2009. All the included patients had no malignant tumor history and had received definitive IFI with concurrent chemotherapy consisting of cisplatin and fluorouracil. Patients underwent a series of standardized evaluations, incl (...truncated)