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Patient-Derived Organoids from Locally Advanced Gastric Adenocarcinomas Can Predict Resistance to Neoadjuvant Chemotherapy

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Patients (pts) with locally advanced gastric adenocarcinoma (LAGA) often receive neoadjuvant chemotherapy. A minority of patients do not respond to chemotherapy and thus may benefit from upfront surgery. Patient-derived organoids (PDOs) are an in vitro model that may mimic the chemotherapy response of the original tumors.

Methods

PDOs were generated from endoscopic biopsies of LAGAs prior to the initiation of chemotherapy and treated with the two chemotherapy regimens: FLOT and FOLFOX. Cell proliferation was assayed after 3–6 days. Following chemotherapy, pts underwent surgical resection, and percent pathological necrosis was determined.

Results

Successful PDOs were obtained from 13 of 24 (54%) LAGAs. Failure to generate PDOs were due to contamination (n = 3, 13%), early senescence (n = 3, 13%), and late senescence (n = 5, 21%). By H&E staining, there were significant similarities in tumor morphology and high concordance in immunohistochemical expression of 6 markers between tumors and derived PDOs. Four of 13 pts with successful PDOs did not undergo chemotherapy and surgery. For the remaining 9 pts, percent necrosis in resected tumors was ≤ 50% in 2 pts. The corresponding PDOs from these 2 pts were clearly chemoresistant outliers. The Pearson correlation coefficient between chemosensitivity of PDOs to FOLFOX (n = 2) or FLOT (n = 7) and percent tumor necrosis in resected tumors was 0.87 (p = 0.003).

Conclusions

PDOs from pts with LAGAs in many respects mimic the original tumors from which they are derived and may be used to predict resistance to neoadjuvant chemotherapy.

Synopsis

Patient-derived organoids (PDOs) can serve as personalized in vitro models of patient tumors. In this study, PDOs from locally advanced gastric cancers were able to reliably predict resistance to neoadjuvant chemotherapy.

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Author notes

  1. Changhwan Yoon and Ju Lu contributed equally.

Authors and Affiliations

  1. Department of Surgery, Columbia University Irving Medical Center, Milstein Hospital Building 7-002, 177 Fort Washington Avenue, New York, NY, 10032, USA

    Changhwan Yoon, Bang-Jin Kim, Sandra W. Ryeom & Sam S. Yoon

  2. Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China

    Ju Lu

  3. Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul, South Korea

    Soo-Jeong Cho

  4. Department of Biological Science, Hyupsung University, Hwaseong-Si, South Korea

    Jong Hyun Kim

  5. Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA

    Ryan H. Moy

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  1. Changhwan Yoon
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  2. Ju Lu
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Correspondence to Sam S. Yoon.

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This article was presented in the Plenary Session of the Society for Surgical Oncology Annual Meeting (Dallas, Texas) on March 20, 2022.

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Yoon, C., Lu, J., Kim, BJ. et al. Patient-Derived Organoids from Locally Advanced Gastric Adenocarcinomas Can Predict Resistance to Neoadjuvant Chemotherapy. J Gastrointest Surg 27, 666–676 (2023). https://doi.org/10.1007/s11605-022-05568-7

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  • DOI: https://doi.org/10.1007/s11605-022-05568-7

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