Prognostic Factors for Locoregional Recurrence in Patients with Thoracic Esophageal Squamous Cell Carcinoma Treated with Radical Two-Field Lymph Node Dissection: Results from Long-Term Follow-Up.
OBJECTIVE
To aim of this study was to determine the clinical and biological prognostic factors for locoregional recurrence (LRR) in patients with thoracic esophageal squamous cell carcinoma (ESCC) undergoing radical two-field lymph node dissection (2FLD).


METHODS
A total of 462 patients diagnosed with thoracic ESCC underwent radical esophagectomy between March 2001 and May 2010 at Sun Yat-Sen University Cancer Center. Clinical characteristics, CD44 expression, and tumor-infiltrating lymphocyte (TIL) levels were evaluated in 198 patients who underwent R0 dissection with long-term follow-up. Partial Cox regression analysis with leave-one-out cross-validation was performed to validate the selected risk factors.


RESULTS
With a median follow-up of 54 months, the 5-year local failure-free survival (LFFS) rate of 198 patients was 62.5%. Multivariate analysis revealed that T stage (p = 0.043), pathological positive tumor above the carina (p = 0.000), CD44 expression level (p = 0.045) and TIL level (p = 0.007) were prognostic factors for LFFS, while the Cox model with risk scores had an area under the curve value of 83.6% for the prediction of 5-year LFFS. The best cut-off value (sum score = 11.19) was used to determine the high- and low-risk groups, with patients at high risk having a significantly shorter 5-year LFFS than patients at low risk (p = 0.000). The LRR pattern revealed significantly high incidences of recurrent disease at the supraclavicular and cervical sites, mediastinum (above the carina), and anastomosis.


CONCLUSIONS
Our predictive model was able to distinguish between patients at high risk for LRR and patients at low risk for LRR. LRR primarily involved the upper thorax and this area must be considered in future study designs for radical trimodality treatment.
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
ShiLiang
S
Liu
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Simone
S
Anfossi
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
Bo
B
Qiu
Department of Thoracic Surgery, Fujian Provincial Tumor Hospital, Fuzhou, People's Republic of China.
YuZhen
Y
Zheng
Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
MuYan
M
Cai
Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
Jia
J
Fu
Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
Hong
H
Yang
Department of Clinical Statistics, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
Qing
Q
Liu
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
ZhaoLin
Z
Chen
Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
JianHua
J
Fu
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China.
MengZhong
M
Liu
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jared K
JK
Burks
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Steven H
SH
Lin
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
James
J
Reuben
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. liuhuisysucc@163.com.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, People's Republic of China. liuhuisysucc@163.com.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China. liuhuisysucc@163.com.|Guangdong Esophageal Cancer Research Institute, Guangzhou, Guangdong, People's Republic of China. liuhuisysucc@163.com.
Hui
H
Liu
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D016629:Esophagectomy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008197:Lymph Node Excision / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008482:Mediastinum; D008875:Middle Aged; D009333:Neck; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors
C497483:CD44 protein, human; D018960:Hyaluronan Receptors