An online rectal cancer tumoroid biorepository: A resource to facilitate multimodal data integration.
Authors: Alvarez Janet , Zambare Wini , Wu Chao , Bleu Paulina , Bercz Aron , Satravada Baby , Kundra Ritika , De Bruijn Ino , Schultz Nikolaus , Shia Jinru , Cercek Andrea , Nash Garrett Michael , Widmar Maria , Wei Iris H. , Pappou Emmanouil , Paty Philip , Garcia-Aguilar Julio , Romesser Paul Bernard , Weiser Martin R. , Smith Jesse Joshua 
Published: January 2024

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Background: Advancing genetic and computational technologies have increased the complexity and quantity of data available in the field of rectal cancer research. As such, there is a need for a centralized source of data to aid and organize current research efforts. To this end, our team has created a unique online biorepository of rectal cancer tumoroids which may serve as a resource for a community of researchers. Methods: The rectal cancer tumoroid biorepository was created in cBioPortal in 2015. Organoids were derived from patient tumor samples (tumoroids). These samples represented multiple treatment timepoints and included primary, recurrent, and metastatic tumors. These tumoroids were further analyzed by various assays such as MSK-IMPACT and IC50 (to fluorouracil, FOLFOX, and FOLFIRI) to obtain patient-specific genomic and chemosensitivity data. A tumoroid profile was then created in cBioPortal for each sample. Clinical information was collected by chart review and annotated into the tumoroid profiles using the unique features of cBioPortal. These included interactive filters and graphical depictions of patient demographics, clinical and pathologic staging, treatment course, clinical response, overall survival, and disease-free survival. Results were organized in an intuitive visual display for convenient analysis. Novel features such as chemosensitivity plots and an interactive patient timeline were incorporated as well. Results: In total, 401 rectal cancer tumoroids have been derived from 177 unique patients. Approximately 32% of the tumoroids were from patients 50 years or younger, and 63% of patients have a treatment naïve sample in our repository. Ten percent of tumoroids were derived from T1-T2 tumors, 56% from T3 tumors, and 17% from T4 tumors. Additionally, 14% of tumoroids were derived from primary tumor recurrences while 6% were derived from metastases. Of the 78% of tumoroids with completely annotated clinical data, 8% were MSI-H, 11% were clinical complete responders, and 5.5% were pathologic complete responders. Lastly, complete IC50 data with clinical correlates has been established for 20% of tumoroids. These data show that tumoroids with a high sensitivity to chemotherapy (FOLFOX) correlated with a 3.3-fold increase in clinical complete response rates in the corresponding patients (p=0.0263). Conclusions: Integrating histopathological, clinicogenomic, and tumoroid response data, this expanding online resource provides a platform to identify valid biomarkers for patient treatment response. This publicly available biorepository built within cBioPortal is intuitive and flexible to accommodate and organize a wide range of data and has the potential to serve as an important resource in rectal cancer research.