Abstract 3418: Pre-treatment patient-derived esophageal squamous cell carcinoma organoids as a predictive platform for docetaxel, cisplatin and fluorouracil neoadjuvant chemotherapy

Abstract Background: Patient-derived organoids (PDOs) are a promising platform for functional precision oncology. In esophageal squamous cell carcinoma (ESCC), docetaxel/cisplatin/fluorouracil (DCF) is a standard neoadjuvant regimen, yet some patients show poor pathological response, underscoring the need for treatment-naïve biopsy-derived PDO models to predict individual benefit. Methods: Treatment-naïve endoscopic biopsies from ESCC patients were used to generate three-dimensional PDOs in Matrigel-based, growth factor-supplemented culture. We analyzed 48 consecutive cases collected after technical standardization. Successful establishment was defined as organoid formation after the first cell seeding, and long-term maintenance as ≥5 passages. Long-term PDOs from patients who received DCF followed by esophagectomy were subjected to 72-hour dose-response assays; IC50 values were compared with pathological response and clinical course. Results: PDOs were successfully established in 45/48 cases, and long-term maintenance was achieved in 10/48. Three long-term PDO cases received preoperative DCF alone and underwent esophagectomy (Cases A-C). Case A (pT2N2M0, Ryan grade 1, Ly0, V0) showed low IC50 values for all three drugs, indicating broad in vitro sensitivity concordant with good pathological response without lymphovascular invasion. Case B (pT3N0M0, Ryan grade 2, Ly0, V0, positive margin) exhibited markedly elevated IC50 values for all drugs, consistent with global drug resistance and suboptimal local control. Case C (pT3N1M0, Ryan grade 2, Ly1b, V1b) showed selective resistance to docetaxel but low IC50 values for cisplatin and 5-fluorouracil, paralleling an intermediate pathological response with persistent lymphovascular invasion. PDO drug sensitivity patterns qualitatively paralleled the degree of pathological response, with triple-sensitive PDOs associated with more favorable regression. Conclusions: Although the current long-term maintenance rate of ESCC PDOs remains modest, PDOs derived from pre-treatment biopsies showed concordance between in vitro DCF sensitivity and clinical response, supporting their potential as a platform to predict neoadjuvant efficacy. Further case accrual and refinement of culture conditions may enable individualized perioperative treatment strategies guided by PDO-derived drug sensitivity. Citation Format: Hajime Kashima, Kazuhiro Noma, Akito Shimizu, Yasushige Takeda, Yohei Mizusawa, Tasuku Matsumoto, Hijiri Matsumoto, Tomoyoshi Kunitomo, Masashi Hashimoto, Naoaki Maeda, Satoru Kikuchi, Shunsuke Tanabe, Hotaka Kawai, Toshiaki Ohara, Hiroshi Tazawa, Hiroshi Nakagawa, Toshiyoshi Fujiwara. Pre-treatment patient-derived esophageal squamous cell carcinoma organoids as a predictive platform for docetaxel, cisplatin and fluorouracil neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3418.