Patient‐derived tumor organoids predict responses to irinotecan‐based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Issue 3 (5th October 2022)

• Record Type: Journal Article
• Authors: Lv, Tao; Shen, Lijun; Xu, Xiaoya; Yao, Ye; Mu, Peiyuan; Zhang, Hui; Wan, Juefeng; Wang, Yan; Guan, Ruoyu; Li, Xiaomeng; Fu, Guoxiang; Zhang, Long; Wang, Yaqi; Xia, Fan; Hu, Chen; Clevers, Hans; Zhang, Zhen; Hua, Guoqiang
• Is Part Of: International journal of cancer. Volume 152:Issue 3(2023)
• Page Start: 524
• Page End: 535
• Publication Date: 2022-10-05
• Subjects: complete response -- Irinotecan -- locally advanced rectal cancer -- organoid -- survival; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.34302
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: Adding irinotecan to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) increases the pathologic complete response (pCR) rate but brings more toxicities. Robust biomarkers to predict response to irinotecan‐based nCRT are extremely necessary for selecting the right patients. Our previous study suggests that patient‐derived tumor organoids (PDTOs) sensitivity to chemoradiotherapy matches patient responses. In this study, we investigated whether PDTOs sensitivity to irinotecan can predict complete response (CR) and survival. Eligible patients receiving irinotecan‐based nCRT between April 5, 2017 and December 11, 2020 were enrolled in the training cohort (n = 91) for response prediction and survival analysis. Patients receiving nCRT between February 21, 2021 and September 17, 2021 were included in the validation cohort (n = 27). Predictive performances of irinotecan organoid size ratio (OSR) for CR or pCR were evaluated. The irinotecan‐sensitive groups had higher response rates compared with the insensitive groups (training cohort: 71.8% vs 24.4%, P < .0001; validation cohort, 81.8% vs 18.8%, P = .002). Moreover, the irinotecan‐sensitive group had higher rates of 3‐year disease‐free survival (DFS: 71.6% vs 55.5%, P = .034) and distant metastasis‐free survival (DMFS, 77.9% vs 57.2%, P = .015) than the irinotecan‐insensitive group. 5‐FU and irradiation sensitivities failed to predict 3‐year DFS (5‐FU: 65.4% vs 61.9%, P = .643; irradiation: 84.8% vs 57.8%; P = .072). Performances of irinotecan OSR to predict CR or pCR were good in the training cohort (CR: AUC = 0.828; 95% CI = 0.723‐0.932; pCR: AUC = 0.864; 95% CI = 0.759‐0.961). The validation showed robust predictive ability (CR: AUC = 0.796, 95% CI = 0.5974‐0.9952; pCR: AUC = 0.917, 95% CI = 0.7921‐1.0000). Irinotecan sensitivity in PDTOs was a predictive and prognostic factor in LARC. Abstract : What's new? Irinotecan‐based neoadjuvant chemoradiotherapy (nCRT) yields increased response rates in locally advanced rectal cancer (LARC) but carries a high toxicity risk. To identify patients most likely to benefit from irinotecan‐based nCRT or nonoperative management, robust predictive models are crucial. This study assessed the predictive potential of patient‐derived tumor organoids (PDTOs) from LARC patients who underwent irinotecan‐based nCRT. Sensitivity of PDTOs to irinotecan predicted both response and survival in LARC. Irinotecan organoid size ratio predicted complete response and pathologic complete response. The findings highlight the potential of PDTOs in helping to identify LARC patients who might benefit from irinotecan or nonoperative management.