Predictive value of nodal maximum standardized uptake value of pretreatment [18F]fluorodeoxyglucose positron emission tomography imaging in patients with esophageal cancer

Diseases of the Esophagus (2017) 30, 1–10 DOI: 10.1093/dote/dox021 Original Article Predictive value of nodal maximum standardized uptake value of pretreatment [18F]fluorodeoxyglucose positron emission tomography imaging in patients with esophageal cancer W.-K. Yap,1 Y.-C. Chang,2,3 C.-K. Tseng,1 C.-H. Hsieh,4,5 Y.-K. Chao,6 P.-J. Su,7 M.-M. Hou,7 C.-K. Yang,7 P.-C. Pai,1 C.-R. Lin,1,8 C.-E. Hsieh,1 Y.-Y. Wu,1 T.-M. Hung1 2 Department of Radiation Oncology, Department of Nuclear Medicine and Molecular Imaging Center, 4 Department of Medical Imaging and Radiological Sciences, Circulating Tumor Cell Lab, Division of Medical 5 Oncology, Department of Internal Medicine, Department of Chemical and Materials Engineering, Chang Gung 6 7 University, Taoyuan, Taiwan, Division of Thoracic Surgery, Department of Surgery, Division of Medical Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou Medical Center and Chang Gung Uni8 versity, and School of Nursing, College of Medicine 3 SUMMARY. We retrospectively reviewed 102 patients with esophageal cancer (97.1% squamous cell carcinoma, 96.1% stage III) received FDG-PET staging and were treated by chemoradiotherapy with or without resection to assess whether the pretreatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) maximum standardized uptake value (SUVmax) of the primary tumor and metastatic lymph nodes can predict the prognosis of patients with esophageal cancer. Receiver operating characteristic analysis was performed to find the cutoff values for primary tumor SUVmax and nodal SUVmax. The influence of clinical factors including primary tumor SUVmax and nodal SUVmax on local progression-free survival, nodal progression-free survival (NPFS), distant metastasesfree survival (DMFS), and overall survival (OS) were evaluated using univariate and multivariate analyses. A total of 40 patients received esophagectomy after neoadjuvant chemoradiotherapy (trimodality), while 62 patients received definitive chemoradiotherapy (dCRT). The median follow-up was 26.4 months. The SUVmax of primary tumor had no significant predictive value on all outcomes, while the SUVmax of metastatic lymph nodes had predictive value on several outcomes. High nodal SUVmax (≥7) predicted for worse outcomes than low nodal SUVmax (<7) in the patients who received dCRT (two-year DMFS, 17% vs. 92%, P < 0.001; NPFS, 14% vs. 81%, P = 0.001; OS, 21% vs. 50%, P = 0.003), but not in those received trimodality. On multivariate analysis of patients receiving dCRT, nodal SUVmax was the strongest independent predictor on DMFS (hazard ratio [HR] 13.93, P < 0.001), NPFS (HR 3.99, P = 0.026), PFS (HR 2.90, P = 0.003), and OS (HR 3.80, P = 0.001). High pretreatment nodal SUVmax predicts worse treatment outcomes for the patients treated with dCRT. KEY WORDS: Chemoradiotherapy, ESCC, FDG PET, nodal SUVmax, treatment outcomes. Address correspondence to: Dr Tsung-Min Hung, MD, Department of Radiation Oncology, Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan. E-mail: Specific author contributions: Study concepts: Tsung-Min Hung, Wing-Keen Yap. Study design: Tsung-Min Hung, Wing-Keen Yap. Data acquisition: Wing-Keen Yap, Chen-Kan Tseng, Yu-Chuan Chang, Yao-Yu Wu. Quality control of data and algorithms: Tsung-Min Hung, Wing-Keen Yap. Data analysis and interpretation: Tsung-Min Hung, Wing-Keen Yap. Statistical analysis: Tsung-Min Hung, Wing-Keen Yap, Ching-Rong Lin. Manuscript preparation: Wing-Keen Yap, Yu-Chuan Chang. Manuscript editing: Tsung-Min Hung, Chen-Kan Tseng, Chia-Hsun Hsieh, Yin-Kai Chao, Po-Jung Su, Ming-Mo Hou, Chan-Keng Yang, Ping-Ching Pai, Cheng-En Hsieh. Manuscript review: Tsung-Min Hung, Wing-Keen Yap, Yu-Chuan Chang, Chen-Kan Tseng, Chia-Hsun Hsieh,Yin-Kai Chao, Po-Jung Su, Ming-Mo Hou, Chan-Keng Yang, Ping-Ching Pai, Yao-Yu Wu, Ching-Rong Lin, Cheng-En Hsieh. All the authors have made a significant contribution to this manuscript, have seen and approved the final manuscript, and have agreed to its submission to Diseases of the Esophagus. Financial support: None. Conflicts of interest: The authors have no conflicts of interest to declare. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board of our hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For retrospective study formal consent is not required. Submission declaration and verification: This work is not currently under consideration for publication elsewhere and has not previously been published. These data has been presented at the ASTRO’s 58th Annual Meeting (2016; Boston, MA, USA). All authors have contributed significantly and have read and approved the manuscript.  C The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: 1 1 2 Diseases of the Esophagus INTRODUCTION MATERIAL AND METHODS The institutional review board of our hospital approved this study. We retrospectively reviewed the electronic medical records of 102 patients with histologically confirmed stage IIA to IIIC (according to American Joint Committee on Cancer seventh edition) esophageal cancer receiving chemoradiotherapy (at least 4000 cGy of radiation dose) with or without resection in our hospital between August 2009 and June 2015. The pretreatment staging examinations include chest and abdominal CT, endoscopic ultrasound, and FDG-PET. PET Pretreatment FDG-PET scans were performed for the staging purpose. The subjects were asked to fast at least 4 hours before the examination. Patients were injected intravenously with 200–444 MBq of [18F]FDG, depending on body weight, and images were acquired 50–90 min after the intravenous administration of the tracer. Whole-body PET/CT emission Treatment The regimens of chemotherapy consist of cisplatin and 5-fluorouracil, or paclitaxel and carboplatin. For the patients who received cisplatin and 5-fluorouracil, the radiation dose of neoadjuvant chemoradiotherapy was 4000–4500 cGy in 20–25 fractions. For those who received paclitaxel and carboplatin, the neoadjuvant radiation dose was 4140 cGy in 23 fractions following chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) protocol.14 After completion of neoadjuvant chemoradiotherapy, all patients underwent a surgical evaluation by chest and abdominal CT, and endoscopic ultrasound. Radical esophagectomy was performed if the patient was feasible for surgery (resectable disease, and medically fit, and no interval distant metastasis after neoadjuvant chemoradiotherapy) and the patient consents to the surgery. For patients with a middle or lower third of the esophagus tumor, a limited right thoracotomy or a thoracoscopic incision followed by reconstruction with an intratho (...truncated)