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Prognostic impact of desmoplastic reaction in esophageal squamous cell carcinoma patients with neoadjuvant therapy

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Abstract

Aim

This study aimed to examine the prognostic value of desmoplastic reaction (DR) in esophageal squamous cell carcinoma (ESCC), particularly in patients who received neoadjuvant therapy, such as chemotherapy (NAC) or chemoradiotherapy (NACRT).

Method

In total, 153 patients with pStage II/III ESCC were included in this study. Ninety-one patients received neoadjuvant therapy (NAC, 70; NACRT, 21). Patients were classified according to three DR categories based on the presence of keloid-like collagen and/or myxoid stroma.

Results

In total, 50, 50, and 53 patients were classified as having mature, intermediate, and immature DR, respectively. The weighted kappa coefficient was 0.623 in the patients with preoperative treatments and 0.782, in those without. The 5-year disease-specific survival (DSS) rates in patients with intermediate/immature DR was significantly worse than those with mature DR (40.7% vs. 73.3%, p < 0.001). Similarly, the 5-year DSS rate in patients with intermediate/immature DR was significantly worse than those with mature DR in a study of patients who received neoadjuvant therapy (46.7% vs. 71.2%, p = 0.009). Multivariate analysis revealed that DR (hazard ratio [HR]: 3.15, 95% confidence interval [CI] 1.58–6.27, p = 0.001), along with N factors, was an independent risk factor for DSS. Moreover, multivariate analysis of patients who received neoadjuvant therapy revealed only DR (HR: 2.47, 95% CI 1.02–5.96, p = 0.045) as independent risk factors for DSS.

Conclusion

The DR classification was a valuable prognostic factor not only in the ESCC patients without neoadjuvant therapy but also in those with neoadjuvant therapy.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan

    Keita Kouzu, Yoshiki Kajiwara, Hironori Tsujimoto, Satsuki Mochizuki, Koichi Okamoto, Eiji Shinto, Yoji Kishi & Hideki Ueno

  2. Department of Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan

    Susumu Matsukuma

Authors
  1. Keita Kouzu
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  2. Yoshiki Kajiwara
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  4. Satsuki Mochizuki
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Contributions

Conceptualization, KK, YK and HU; writing—original draft preparation, KK and YK; writing—review and editing, HT, SM, KO, ES, YK, and SM; project administration, KK, YK and HU. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Yoshiki Kajiwara.

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Ethical Statement

All procedures followed were in accordance with the Helsinki Declaration of 1964 and later versions. The study protocol was approved by the Institutional Review Board of the National Defense Medical College (3125). Written informed consent was obtained from all participants in the study.

Conflicts of interest

The authors declare no conflicts of interest.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 30 KB)

Supplementary Fig. 1 A flowchart showing selection process of patients included in this study (PPTX 44 KB)

10388_2023_996_MOESM3_ESM.pptx

Supplementary Fig. 2 Disease-specific survival in esophageal squamous cell carcinoma patients differentiated using 3-tiers desmoplastic reaction classification. There is a significant difference in prognosis between mature and intermediate, and between mature and immature. In contrast, there is no significant difference in prognosis between intermediate and immature (PPTX 69 KB)

10388_2023_996_MOESM4_ESM.pptx

Supplementary Fig. 3 The cumulative recurrence rate after surgery. In patients with intermediate/immature, the cumulative recurrence rate was significantly higher than in those with mature DR (p = 0.023) (PPTX 71 KB)

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Kouzu, K., Kajiwara, Y., Tsujimoto, H. et al. Prognostic impact of desmoplastic reaction in esophageal squamous cell carcinoma patients with neoadjuvant therapy. Esophagus 20, 474–483 (2023). https://doi.org/10.1007/s10388-023-00996-z

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