Recurrence pattern of squamous cell carcinoma in the midthoracic esophagus: implications for the clinical target volume design of postoperative radiotherapy

OncoTargets and Therapy Dovepress open access to scientific and medical research Original Research OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 54.37.117.73 on 12-Jul-2018 For personal use only. Open Access Full Text Article Recurrence pattern of squamous cell carcinoma in the midthoracic esophagus: implications for the clinical target volume design of postoperative radiotherapy This article was published in the following Dove Press journal: OncoTargets and Therapy 3 October 2016 Number of times this article has been viewed Xiaoli Wang 1,2,* Yijun Luo 1,2,* Minghuan Li 2 Hongjiang Yan 2 Mingping Sun 2 Tingyong Fan 2 School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, People’s Republic of China 1 *These authors contributed equally to this work Background: Postoperative radiotherapy has shown positive efficacy in lowering the recurrence rate and improving the survival rate for patients with esophageal squamous cell carcinoma (ESCC). However, controversies still exist about the postoperative prophylactic radiation target volume. This study was designed to analyze the patterns of recurrence and to provide a reference for determination of the postoperative radiotherapy target volume for patients with midthoracic ESCC. Patients and methods: A total of 338 patients with recurrent or metastatic midthoracic ESCC after radical surgery were retrospectively examined. The patterns of recurrence including locoregional and distant metastasis were analyzed for these patients. Results: The rates of lymph node (LN) metastasis were 28.4% supraclavicular, 77.2% upper mediastinal, 32.0% middle mediastinal, 50.0% lower mediastinal, and 19.5% abdominal LNs. In subgroup analyses, the rate of abdominal LN metastasis was significantly higher in patients with histological node-positive than that in patients with histological node-negative (P=0.033). Further analysis in patients with histological node-positive demonstrated that patients with three or more positive nodes are more prone to abdominal LN metastasis, compared with patients with one or two positive nodes (χ2=4.367, P=0.037). The length of tumor and histological differentiation were also the high-risk factors for abdominal LN metastasis. Conclusion: For midthoracic ESCC with histological node-negative, or one or two positive nodes, the supraclavicular and stations 2, 4, 5, and 7 LNs should be delineated as clinical target volume of postoperative prophylactic irradiation, and upper abdominal LNs should be excluded. While for midthoracic ESCC with three or more positive nodes, upper abdominal LNs should also be included. The length of tumor and histological differentiation should be considered comprehensively to design the clinical target volume for radiotherapy. Keywords: esophagus cancer, radiotherapy, recurrence and metastasis, clinical target volume Introduction Correspondence: Tingyong Fan Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jiyan Road 440, Jinan 250117, Shandong Province, People’s Republic of China Tel/fax +86 531 6762 6921 Email 6021 submit your manuscript | www.dovepress.com OncoTargets and Therapy 2016:9 6021–6027 Dovepress © 2016 Wang 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.S116348 Powered by TCPDF (www.tcpdf.org) Esophageal carcinomas (ECs) are one of the most malignant gastrointestinal cancers worldwide; they are the sixth most common cause of cancer-related mortality.1,2 In the People’s Republic of China, the predominant pathological type of EC is esophageal squamous cell carcinoma (ESCC), which is characterized by rapid development and fatal prognosis in most cases, and many tumors locate in the middle third thoracic. Surgery is an extremely important initial treatment for patients with ESCC. For patients with locally advanced ESCC, the standard treatment is neoadjuvant chemotherapy or Dovepress OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 54.37.117.73 on 12-Jul-2018 For personal use only. Wang et al chemoradiotherapy followed by esophagectomy with lymphadenectomy. However, most patients in the People’s Republic of China generally prefer surgery to neoadjuvant therapy as their initial therapeutic strategy, and surgery alone has shown rather disappointed survival rates, of which the 5-year survival rate is only 20%–50%.3–5 The recurrence rate of ESCC is as high as 40%–50% after radical resection, and locoregional recurrence is the main reason for treatment failure, not excepting patients with histological node-negative (pN0 stage).4,6,7 The current National Comprehensive Cancer Network (NCCN) guidelines still recommend surveillance for ESCC patients who have undergone curative resection. Therefore, it is extremely essential to evaluate the efficacy of adjuvant radiotherapy. According to multiple retrospective analyses, the addition of postoperative radiotherapy (PORT) has been associated with survival benefit in patients with positive lymph node (LN) metastasis (N+) or stage III.8–11 However, up until now, the appropriate LN clinical target volume (CTVn) for postoperative prophylactic irradiation therapy still remains disputed, especially for midthoracic ESCC. Recent and previous studies are consistent in revealing that the anastomosis, supraclavicular, and mediastinal lymph drainage areas should be delineated as the postoperative prophylactic irradiation target volume, while little effort has been made to study the patterns of recurrence of midthoracic ESCC according to the pathological LN status. To our knowledge, to date, only Zhang et al12 indicated that upper abdominal LNs should also be included as the postoperative prophylactic irradiation target volume for midthoracic ESCC patients with pathological node-positive. Based on the study by Zhang et al,12 we further analyzed the patterns of recurrence and metastasis of the midthoracic ESCC according to the pathological LN status after radical surgery, which was detected with follow-up computed tomography (CT), to identify the risk factors responsible for recurrence and to provide a reference for determination of the PORT target volume. Patients and methods Patients After obt (...truncated)