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Abstract
Background: Neoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used, and their comparative efficacy and safety remain unclear.

Methods: Patients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in this study. Of note, 3 different nCRT regimens were retrospectively compared: conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial (CROSS). The overall survival (OS), pathologic complete response (pCR), toxicity, and treatment compliance rates were analyzed.

Results: Among the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. The OS rates at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (P = .653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and nonhematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, and 5.5% and 0.8% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P = .002 and P = .030). Weight loss of > 5% was observed in 44.0%, 51.4%, and 32.5% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). In the multivariate analysis, clinical T stage (P = .004), N stage (P = .012), FP chemotherapy regimen (P = .013), surgical resection (P < .001), hematologic toxicity (P = .001), and weight loss (P = .004) were significantly associated with poor OS.

Conclusion: The choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting that it may be the optimal treatment option among the groups.

Affiliations

Hyunki Park 1, Kyungmi Yang 1, Jae Myoung Noh 1, Young Mog Shim 2, Hong Kwan Kim 2, Yong Soo Choi 2, Jong Ho Cho 2, Jong-Mu Sun 3, Hyun Ae Jung 3, Sehhoon Park 3, Hana Park 4, Dongryul Oh 5
1Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
2Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
3Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
4Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea.
5Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: dongryul.oh@samsung.com.