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Defining population response of patient-derived colorectal cancer organoids against prospective clinical outcomes

Authors :
Elise H. Lawson
Noelle K. LoConte
Katherine A. Johnson
Nicole Lassen
Sam J. Lubner
Melissa C. Skala
Dustin A. Deming
Aishwarya Sunil
Cheri A. Pasch
Daniel Mulkerin
Charles P. Heise
Eugene F. Foley
Daniel E. Abbott
Kristina A. Matkowskyj
Nataliya Volodymyrivna Uboha
Shujah Rehman
Kayla K. Lemmon
Amani A. Gillette
Jeremy D. Kratz
Evie Carchman
Source :
Journal of Clinical Oncology. 38:177-177
Publication Year :
2020
Publisher :
American Society of Clinical Oncology (ASCO), 2020.

Abstract

177 Background: No current clinical tool can predict the efficacy of cancer therapeutics for patients with colorectal cancer (CRC). We recently demonstrated the feasibility of using patient-derived cancer organoids (PDCOs) to examine therapeutic response and tumor heterogeneity for individual patients with CRC via optical metabolic imaging (OMI). Here we expand these analyses in a cohort of patients with clinical outcomes. Methods: CRC tissue was collected from patients on IRB-approved protocols. PDCOs were matured and treated with chemotherapy regimens concurrent with patient treatment. Previously established effect size response thresholds were used for diameter ( > 1.5) and OMI ( > 0.5) following 48 hours of treatment. OMI measures the intrinsic autofluorescence of NAD(P)H and FAD using 2-photon microscopy without specific reagents or dyes. Clinical outcomes were prospectively collected by manual chart review. Results: 12 CRC PDCOs were established from patients with CRC. PDCOs were collected from initial diagnosis and advanced setting of both primary and metastatic sites by core needle biopsy and surgical resection. Differential growth rates were observed across lines. PDCOs with RAS/RAF alterations had more uniform growth, while PDCOs without these alterations demonstrated more heterogeneous growth and metabolism. Clinical correlation of PDCOs response with recurrence of disease in the adjuvant setting will be presented. Cases with prior 5-FU-based chemotherapy at the time of PDCO collection had intermediate sensitivity. For PDCOs collected pre-treatment, PDCO response predicted clinical response for 5 of 6 cases using predefined sensitivity thresholds. In the case that overall PDCO response did not predict clinical response, a heterogenous response was observed with distinct sensitive and resistant populations. Across PDCOs, greater post-treatment heterogeneity was observed in resistant lines compared to those with treatment sensitivity. Conclusions: Tumor heterogeneity in treatment response can be assessed using PDCOs growth and metabolism. The utility of PDCOs to predict clinical outcomes for patients with CRC deserves further prospective validation.

Details

ISSN :
15277755 and 0732183X
Volume :
38
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi...........ae5f43bc78ca400e835eb47b797ed121
Full Text :
https://doi.org/10.1200/jco.2020.38.4_suppl.177