Platelet-to-Lymphocyte Ratio Multiplied by the Cytokeratin-19 Fragment Level as a Predictor of Pathological Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma

Yuji Shishido; Tomoyuki Matsunaga; Shohei Sawata; Masahiro Makinoya; Wataru Miyauchi; Kozo Miyatani; Chihiro Uejima; Masaki Morimoto; Yuki Murakami; Takehiko Hanaki; Kyoichi Kihara; Manabu Yamamoto; Naruo Tokuyasu; Shuichi Takano; Teruhisa Sakamoto; Hiroaki Saito; Toshimichi Hasegawa; Yoshiyuki Fujiwara

doi:10.33160/yam.2021.08.003

Platelet-to-Lymphocyte Ratio Multiplied by the Cytokeratin-19 Fragment Level as a Predictor of Pathological Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma

Yonago Acta Med. 2021 Aug 24;64(3):249-259. doi: 10.33160/yam.2021.08.003. eCollection 2021 Aug.

Authors

Yuji Shishido¹, Tomoyuki Matsunaga¹, Shohei Sawata¹, Masahiro Makinoya¹, Wataru Miyauchi¹, Kozo Miyatani¹, Chihiro Uejima¹, Masaki Morimoto¹, Yuki Murakami¹, Takehiko Hanaki¹, Kyoichi Kihara¹, Manabu Yamamoto¹, Naruo Tokuyasu¹, Shuichi Takano¹, Teruhisa Sakamoto¹, Hiroaki Saito², Toshimichi Hasegawa¹, Yoshiyuki Fujiwara¹

Affiliations

¹ Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan.
² Department of Surgery, Japanese Red Cross Tottori Hospital, Tottori 680-8517, Japan.

Abstract

Background: The standard treatment for resectable advanced esophageal squamous cell carcinoma in Japan is surgery followed by neoadjuvant chemotherapy, and it is important to predict the effect of neoadjuvant chemotherapy before treatment. Therefore, this study aims to extract conventional blood examination data, such as tumor markers and/or inflammatory/nutritional index levels, that can predict the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy.

Methods: We retrospectively analyzed the medical records of 66 patients with thoracic esophageal squamous cell carcinoma who received neoadjuvant chemotherapy, followed by curative esophagectomy at Tottori University Hospital between June 2009 and December 2019.

Results: We demonstrated that the product of the platelet-to-lymphocyte ratio (PLR) multiplied by the cytokeratin-19 fragment (CYFRA) level, which was termed "PLR-CYFRA," is the most accurate indicator that predicts the pathological response to neoadjuvant chemotherapy, with the highest area under the curve [0.795 (95% confidence interval: 0.665-0.925), P < 0.001] in receiver operating characteristic analyses. Therefore, we divided patients into the PLR-CYFRA^Low (< 237.6, n = 21) and PLR-CYFRA^High (≥ 237.6, n = 45) groups and found that the percentage of PLR-CYFRA^Low was significantly higher in patients with a better pathological response (P < 0.001). Furthermore, patients with good pathological response had significantly better prognoses in terms of disease-specific survival (P = 0.014), recurrence-free survival (P = 0.014), and overall survival (P = 0.032). In the multivariate analysis, PLR-CYFRA was an independent predictor of the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy (P = 0.002).

Conclusion: Pretreatment PLR-CYFRA might be a useful and simple tool that predicts the pathological effect of neoadjuvant chemotherapy in esophageal squamous cell carcinoma.

Keywords: cytokeratin; esophageal cancer; lymphocyte; neoadjuvant chemotherapy; platelet.