Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer

Tao Lv; Lijun Shen; Xiaoya Xu; Ye Yao; Peiyuan Mu; Hui Zhang; Juefeng Wan; Yan Wang; Ruoyu Guan; Xiaomeng Li; Guoxiang Fu; Long Zhang; Yaqi Wang; Fan Xia; Chen Hu; Hans Clevers; Zhen Zhang; Guoqiang Hua

doi:10.1002/ijc.34302

Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer

Tao Lv, Lijun Shen, Xiaoya Xu, Ye Yao, Peiyuan Mu, Hui Zhang, Juefeng Wan, Yan Wang, Ruoyu Guan, Xiaomeng Li, Guoxiang Fu, Long Zhang, Yaqi Wang, Fan Xia, Chen Hu, Hans Clevers, Zhen Zhang, Guoqiang Hua

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

9 Citations (Scopus)

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.

Original language	English
Journal	International Journal of Cancer
DOIs	https://doi.org/10.1002/ijc.34302
Publication status	E-pub ahead of print - 26 Sept 2022

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10.1002/ijc.34302

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Lv, T., Shen, L., Xu, X., Yao, Y., Mu, P., Zhang, H., Wan, J., Wang, Y., Guan, R., Li, X., Fu, G., Zhang, L., Wang, Y., Xia, F., Hu, C., Clevers, H., Zhang, Z., & Hua, G. (2022). Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. International Journal of Cancer. https://doi.org/10.1002/ijc.34302

@article{85ade0fd31924a3d873f4dffe059ef41,

title = "Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer",

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.",

author = "Tao Lv and Lijun Shen and Xiaoya Xu and Ye Yao and Peiyuan Mu and Hui Zhang and Juefeng Wan and Yan Wang and Ruoyu Guan and Xiaomeng Li and Guoxiang Fu and Long Zhang and Yaqi Wang and Fan Xia and Chen Hu and Hans Clevers and Zhen Zhang and Guoqiang Hua",

note = "{\textcopyright} 2022 UICC.",

year = "2022",

month = sep,

day = "26",

doi = "10.1002/ijc.34302",

language = "English",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "Wiley-Liss Inc.",

}

Lv, T, Shen, L, Xu, X, Yao, Y, Mu, P, Zhang, H, Wan, J, Wang, Y, Guan, R, Li, X, Fu, G, Zhang, L, Wang, Y, Xia, F, Hu, C, Clevers, H, Zhang, Z & Hua, G 2022, 'Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer', International Journal of Cancer. https://doi.org/10.1002/ijc.34302

TY - JOUR

T1 - Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer

AU - Lv, Tao

AU - Shen, Lijun

AU - Xu, Xiaoya

AU - Yao, Ye

AU - Mu, Peiyuan

AU - Zhang, Hui

AU - Wan, Juefeng

AU - Wang, Yan

AU - Guan, Ruoyu

AU - Li, Xiaomeng

AU - Fu, Guoxiang

AU - Zhang, Long

AU - Wang, Yaqi

AU - Xia, Fan

AU - Hu, Chen

AU - Clevers, Hans

AU - Zhang, Zhen

AU - Hua, Guoqiang

PY - 2022/9/26

Y1 - 2022/9/26

N2 - 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.

AB - 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.

U2 - 10.1002/ijc.34302

DO - 10.1002/ijc.34302

M3 - Article

C2 - 36161653

SN - 0020-7136

JO - International Journal of Cancer

JF - International Journal of Cancer

ER -

Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer

Abstract

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