Utility of Pancreatic Tumor Scrapings for Organoid Development and Precision Medicine Strategies

Patient-derived organoids (PDOs) hold promise for predicting individualized drug responses, but their establishment is often constrained by the limited availability of tumor material and prior neoadjuvant treatment. Standard PDO generation relies on dissected tissue slices from the cut surface of the tumor which may include both the invasive front, where it is postulated that more aggressive cancer cells reside, and potentially fewer viable neoplastic cells in the tumor center. This study investigates whether scraping the PDAC cut surface is a feasible method for PDO establishment compared to standard tissue samples, in order to take advantage of the potential harvesting of viable neoplastic cells from the invasive front. Tumor scrapings from 26 patients and matched tissue slices from 20 patients were collected. PDOs were successfully established from 10 tumor scrapings and 8 matched tissue slices, including 3 neoadjuvant-treated cases. Organoid histologic architecture was comparable to the surgical tumor specimens, with paired scraping and tissue slice PDOs showing genomic and transcriptomic concordance. Pharmacotyping demonstrated that scraping PDOs reliably captured patient-specific chemosensitivity, highlighting the potential for a viable alternative method to standard tissue slice PDOs. As proliferative and treatment-resistant neoplastic cells often originate from the tumor edge, increasing representation of the periphery and across the tumor may offer a more comprehensive model of invasive tumor biology, improving the clinical and research utility of PDOs.]]>