Comprehensive dissection of rectal cancer organoids in responses to chemoradiation

The responses of cancer organoids to treatments in vitro can predict the clinical outcomes of corresponding patients. Here, we further uncover that the responses of cancer organoids to combined treatments predict the clinical outcomes of locally advanced rectal cancer (LARC) patients more faithfully than monotherapy with 92.50% and 93.75% accuracy in the discovery and validation cohorts, respectively, which is partly due to the synergistic (3.91%, 5/128) and antagonistic (4.69%, 6/128) treatment interactions in combined chemoradiation. In addition, our detailed analysis reveals that the time point for collecting survival data of organoids is critical to the efficacy of organoids' responses to treatments for predicting the clinical outcomes of LARC patients. Besides, our current data favor the addition of irinotecan for neoadjuvant treatment of LARC patients. The comprehensive dissection of rectal cancer organoids in responses to chemoradiation here may have significant implications for the broad application of organoids in cancer precision treatments.