Abstract 3090: Patient derived cancer organoids predict clinical response for patients with locally advanced rectal cancer
Authors: Udgata Shirsa , Sunil Aishwarya , Schmitz Rebecca L. , Pantha Barsha , Gillette Amani , Kratz Jeremy , Grogan Patrick , DeStefanis Rebecca , Johnson Katherine , Kraus Sean , Carchman Evie , Lawson Elise , Sanger Christina , Heise Charles , Bassetti Michael , Kimple Randall , Lemmon Kayla , Larson Morgan , Pasch Cheri , Skala Melissa , Deming Dustin 
Published: June 2022

Abstract
Background: Locally advanced rectal cancer (LARC) is a common disease in the US, with a growing incidence in younger patients. These patients undergo multimodality treatments including chemotherapy, radiation, and surgery. For some patients this is likely over-treatment, while other patients require further treatment escalation. To date there is no clinical tool to know the potential benefit of these individual therapies. Patient-derived cancer organoids (PDCOs) are beginning to be evaluated for use as a means to predict individual patient response to clinical therapies. Here we use PDCOs from patients with LARC to compare the PDCO response to the individual clinical response.
Methods: Fresh LARC tissues from patients undergoing an endoscopy and tattooing procedure were obtained following consent on an IRB-approved protocol. PDCOs were cultured in using Matrigel and our previously published CRC organoids media. Following culture maturation, PDCOs were treated with control media, 5uM 5FU, 10uM Oxaliplatin, Combination (FOLFOX), XRT (2Gy) or 5FU and XRT. Brightfield imaging was performed at baseline and following 96 hours of treatment. Glass’s delta is used as a measure of the organoid treatment effect. A Glass’s delta of 1.25 was used as a threshold of treatment response based on prior studies. Clinical imaging was evaluated using standard RECIST v1.1 criteria of the objective response.
Results: Endoscopic LARC biopsy samples were obtained from 22 patients. 11 of the 22 samples were able to be grown as PDCOs. To date 9 cultures have been treated with FOLFOX and 9 have been treated with 5FU and XRT. For those treated with FOLFOX, 3/9 had a Glass’s delta greater than 1.25 and all of these patients has a clinical partial response (PR). None of those patients’ whose PDCOs did not achieve a Glass’s delta of at least 1.25 had a PR to FOLFOX clinically. No PDCO’s treated with 5FU and XRT achieved a Glass’s delta of &gt;1.25. 3/9 PDCOs had a Glass’s delta &gt;1.0. All of these patients had a PR. Of the 7 patients whose PDCOs did not achieve a Glass’s delta of 1 in response to 5FU and XRT, none had a clinical PR (Glass’s delta range 0.6-0.93).
Conclusion: PDCOs hold great promise as a tool to predict clinical outcomes for patients with LARC. Further evaluations need to establish improved methods of PDCO generation from biopsy samples and confirm the optimum response thresholds for prediction of treatment response.
Citation Format: Shirsa Udgata, Aishwarya Sunil, Rebecca L. Schmitz, Barsha Pantha, Amani Gillette, Jeremy Kratz, Patrick Grogan, Rebecca DeStefanis, Katherine Johnson, Sean Kraus, Evie Carchman, Elise Lawson, Christina Sanger, Charles Heise, Michael Bassetti, Randall Kimple, Kayla Lemmon, Morgan Larson, Cheri Pasch, Melissa Skala, Dustin Deming. Patient derived cancer organoids predict clinical response for patients with locally advanced rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3090.