Original Article
Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma Dong Lin1,2*, Longfei Ma1,2*, Ting Ye1,2, Yunjian Pan1,2, Longlong Shao1,2, Zuodong Song1,2, Shujun Jiang1,2, Haiquan Chen1,2, Jiaqing Xiang1,2 1
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; 2Department of Oncology, Shanghai
Medical College, Fudan University, Shanghai 200032, China Contributions: (I) Conception and design: H Chen, J Xiang; (II) Administrative support: D Lin, L Ma; (III) Provision of study materials or patients: D Lin, L Ma, T Ye, Y Pan, L Shao, Z Song, S Jiang; (IV) Collection and assembly of data: D Lin, L Ma; (V) Data analysis and interpretation: D Lin, L Ma, T Ye, Y Pan, L Shao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. *These authors contributed equally to this work. Correspondence to: Haiquan Chen. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong’an Rd, Shanghai 200032, China. Email: [email protected]; Jiaqing Xiang. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong’an Rd, Shanghai 200032, China. Email: [email protected].
Background: For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). Methods: We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. Results: A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. Conclusions: Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation. Keywords: Esophageal squamous cell carcinoma (ESCC); neoadjuvant therapy; survival Submitted Sep 24, 2016. Accepted for publication Jan 01, 2017. doi: 10.21037/jtd.2017.02.19 View this article at: http://dx.doi.org/10.21037/jtd.2017.02.19
Introduction
did not result in consistent conclusions (2-7). The strategy
For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach (1). However, randomized trials
remains investigational, especially for patients with
© Journal of Thoracic Disease. All rights reserved.
esophageal squamous cell carcinoma (ESCC), which is the predominant type in China (8). We retrospectively reviewed
jtd.amegroups.com
J Thorac Dis 2017;9(2):318-326
Journal of Thoracic Disease, Vol 9, No 2 February 2017
all of the patients underwent surgery following neoadjuvant therapy for locally advanced ESCC during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC), and evaluated the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). The study has been approved by the Ethics Committee of FUSCC. Methods Patients We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced ESCC during January 1st, 2013 and December 31st, 2015 in FUSCC. Patients were restaged according to the 6th TNM Stage System (9). Locally advanced ESCC was defined as cT3–4 or cN1. Recent years in our center, patients with M1a including supraclavicular node involvement and/or celiac node involvement usually received neoadjuvant therapy followed by surgery. With respect to pretherapeutic workup, all patients underwent a complete history, physical examination and biochemistry tests. This consisted of an upper gastrointestinal endoscopy, a chest enhanced computed tomography (CT) and ultrasonography (US). For patients with some particular symptoms or signs, further examination including positron emission tomography computed tomography (PET-CT) was applied. Physical condition was evaluated by pulmonary function test, electrocardiogram, cardiac sonography, and so on. Patients without complete pretherapeutic workup in FUSCC were excluded from the study.
319
determine whether surgery would be performed. Surgery was regularly scheduled at about 4 weeks after the completion. In this study, patients received two-field lymphadenectomy (2FLND) or three-field lymphadenectomy (3FLND), including Ivor-Lewis and McKeown procedures. Cervical node dissection was conducted by a collar incision. The procedures were as previously reported (10,11). R0 resection was defined as microscopically confirmed no tumor cell residual. R1 and R2 resection were defined as microscopically confirmed tumor cell residual and macroscopically confirmed tumor cell residual, respectively. In this study, patients were restaged according to the 6th TNM stage system. Pathological complete response (pCR) was confirmed when histological analysis of the specimen revealed the absence of tumor cell in both primary lesion and involved nodes (ypT0N0M0). The postoperative ypTNM stage was compared with the pretherapeutic cTNM stage to determine down-staging. Any death within 90 days after the operation or within any time before the hospital discharge was defined as postoperative death. Follow-up Patients were usually followed up at our outpatient clinic every 3 months for the first 2 years after the operation, and every 6 months for 3–5 years. Oncological investigations such as CT and US were done during the time. For patients with particular symptoms and signs, additional examinations would be conducted. A combination of clinical service records, phone calls, and letters was used to determine each patient status as of May 2016. A total of 50 patients were included in the study according to the criteria.
Treatment and evaluation
Statistical analysis
In China, there was no neoadjuvant therapy based upon high-level evidence for locally advanced esophageal cancer. The chemotherapy regimen was usually based on platinum coordination combined with 5-fluorourail (5-FU). The combination with paclitaxel (PTX) or docetaxel (DOC) was also frequently applied. The radiotherapy dose was usually 41.4–50.4 Gy delivered in each fraction of 1.8 or 2 Gy. Intensity modulated radiotherapy (IMRT) were planned by a CT simulator. If both chemotherapy and radiotherapy were administrated, then they were conducted concurrently. After completion of neoadjuvant therapy, patients received a series of workup as above to evaluate the responses and to
Statistical analysis was performed by Statistical Package for the Social Sciences software (IBM SPSS version 22, Chicago, IL, USA). The survival curve was calculated by the Kaplan-Meier method. In this study, the OS was defined as the interval between the date of neoadjuvant therapy and the date of death or the date of the last follow-up. DFS was defined as the interval between the date of neoadjuvant therapy and the date of relapse or date of last follow-up. The log-rank test was used for univariate analyses and Cox proportional hazards model was used for multivariate analyses. Statistical analysis was considered to be significant when the probability value (P value) was less than 0.05 (P
Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma Dong Lin1,2*, Longfei Ma1,2*, Ting Ye1,2, Yunjian Pan1,2, Longlong Shao1,2, Zuodong Song1,2, Shujun Jiang1,2, Haiquan Chen1,2, Jiaqing Xiang1,2 1
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; 2Department of Oncology, Shanghai
Medical College, Fudan University, Shanghai 200032, China Contributions: (I) Conception and design: H Chen, J Xiang; (II) Administrative support: D Lin, L Ma; (III) Provision of study materials or patients: D Lin, L Ma, T Ye, Y Pan, L Shao, Z Song, S Jiang; (IV) Collection and assembly of data: D Lin, L Ma; (V) Data analysis and interpretation: D Lin, L Ma, T Ye, Y Pan, L Shao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. *These authors contributed equally to this work. Correspondence to: Haiquan Chen. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong’an Rd, Shanghai 200032, China. Email: [email protected]; Jiaqing Xiang. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong’an Rd, Shanghai 200032, China. Email: [email protected].
Background: For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). Methods: We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. Results: A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. Conclusions: Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation. Keywords: Esophageal squamous cell carcinoma (ESCC); neoadjuvant therapy; survival Submitted Sep 24, 2016. Accepted for publication Jan 01, 2017. doi: 10.21037/jtd.2017.02.19 View this article at: http://dx.doi.org/10.21037/jtd.2017.02.19
Introduction
did not result in consistent conclusions (2-7). The strategy
For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach (1). However, randomized trials
remains investigational, especially for patients with
© Journal of Thoracic Disease. All rights reserved.
esophageal squamous cell carcinoma (ESCC), which is the predominant type in China (8). We retrospectively reviewed
jtd.amegroups.com
J Thorac Dis 2017;9(2):318-326
Journal of Thoracic Disease, Vol 9, No 2 February 2017
all of the patients underwent surgery following neoadjuvant therapy for locally advanced ESCC during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC), and evaluated the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). The study has been approved by the Ethics Committee of FUSCC. Methods Patients We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced ESCC during January 1st, 2013 and December 31st, 2015 in FUSCC. Patients were restaged according to the 6th TNM Stage System (9). Locally advanced ESCC was defined as cT3–4 or cN1. Recent years in our center, patients with M1a including supraclavicular node involvement and/or celiac node involvement usually received neoadjuvant therapy followed by surgery. With respect to pretherapeutic workup, all patients underwent a complete history, physical examination and biochemistry tests. This consisted of an upper gastrointestinal endoscopy, a chest enhanced computed tomography (CT) and ultrasonography (US). For patients with some particular symptoms or signs, further examination including positron emission tomography computed tomography (PET-CT) was applied. Physical condition was evaluated by pulmonary function test, electrocardiogram, cardiac sonography, and so on. Patients without complete pretherapeutic workup in FUSCC were excluded from the study.
319
determine whether surgery would be performed. Surgery was regularly scheduled at about 4 weeks after the completion. In this study, patients received two-field lymphadenectomy (2FLND) or three-field lymphadenectomy (3FLND), including Ivor-Lewis and McKeown procedures. Cervical node dissection was conducted by a collar incision. The procedures were as previously reported (10,11). R0 resection was defined as microscopically confirmed no tumor cell residual. R1 and R2 resection were defined as microscopically confirmed tumor cell residual and macroscopically confirmed tumor cell residual, respectively. In this study, patients were restaged according to the 6th TNM stage system. Pathological complete response (pCR) was confirmed when histological analysis of the specimen revealed the absence of tumor cell in both primary lesion and involved nodes (ypT0N0M0). The postoperative ypTNM stage was compared with the pretherapeutic cTNM stage to determine down-staging. Any death within 90 days after the operation or within any time before the hospital discharge was defined as postoperative death. Follow-up Patients were usually followed up at our outpatient clinic every 3 months for the first 2 years after the operation, and every 6 months for 3–5 years. Oncological investigations such as CT and US were done during the time. For patients with particular symptoms and signs, additional examinations would be conducted. A combination of clinical service records, phone calls, and letters was used to determine each patient status as of May 2016. A total of 50 patients were included in the study according to the criteria.
Treatment and evaluation
Statistical analysis
In China, there was no neoadjuvant therapy based upon high-level evidence for locally advanced esophageal cancer. The chemotherapy regimen was usually based on platinum coordination combined with 5-fluorourail (5-FU). The combination with paclitaxel (PTX) or docetaxel (DOC) was also frequently applied. The radiotherapy dose was usually 41.4–50.4 Gy delivered in each fraction of 1.8 or 2 Gy. Intensity modulated radiotherapy (IMRT) were planned by a CT simulator. If both chemotherapy and radiotherapy were administrated, then they were conducted concurrently. After completion of neoadjuvant therapy, patients received a series of workup as above to evaluate the responses and to
Statistical analysis was performed by Statistical Package for the Social Sciences software (IBM SPSS version 22, Chicago, IL, USA). The survival curve was calculated by the Kaplan-Meier method. In this study, the OS was defined as the interval between the date of neoadjuvant therapy and the date of death or the date of the last follow-up. DFS was defined as the interval between the date of neoadjuvant therapy and the date of relapse or date of last follow-up. The log-rank test was used for univariate analyses and Cox proportional hazards model was used for multivariate analyses. Statistical analysis was considered to be significant when the probability value (P value) was less than 0.05 (P
