P01.10.B FACTORS IMPACTING THE QUALITY OF PATIENT-DERIVED CELLS (PDCS) FOR DRUG SCREENING IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND Use of patient derived cells (PDCs) is a new and approaching method of functional personalized medicine, exploring treatment response prediction on a patient specific level. In this regard, the multi-center, randomized, phase 2 ATTRACT trial in Austria aims to investigate the clinical potential of PDC-based drug screening in patients with newly-diagnosed, MGMT promoter unmethylated glioblastoma. While the quality of PDCs is a fundamental prerequisite for reliable and scalable drug testing, the factors impacting PDC viability as well as the comprehensive analysis of the biological resemblance to the original tumor remain poorly understood. MATERIAL AND METHODS We sought to identify factors influencing PDC quality for drug screening approaches. Patients with suspicion of glioblastoma are included in the Austrian Glioblastoma Biobank (GlioBank). Material was sampled during neurosurgical resection and transported to the CBmed laboratory overnight. Only samples with a minimum weight of 1g were processed further. The fresh tissue was mechanically and enzymatically dissociated and transferred to culture plates and cultivated in an optimized medium for 7-14 days (primary culture) and frozen for further analysis. The minimum amount of PDCs required for a drug screen with 28 drugs was defined as 4.5 x 10^5 cells. RESULTS 99 samples were obtained between May 2024 and March 2025. Of these, 81 samples were diagnosed as glioblastoma and thus were processed further. The median tumor weight used for PDC processing was 2.14 g (range 1-22g). 60/81 (74%) samples fulfilled the criteria of a full drug screen PDC culture, while in 16/81 (20%) only a compromised panel was possible. In 5/81 (6%) samples no successful PDC culture could be established. After approximately 14 days of culture in tumor cell enriching conditions, a median of 65.64 % of the cells were lost compared with the initiation of the primary culture. The weight of the initial tumor used for the generation of the PDCs significantly correlated with the cell number of the PDC culture (p<0.05), but not with the percentage of lost cells (p>0.05). The clinical factors age and gender of the patient, time between resection and placement in medium, transport time from surgery to the laboratory, histology or MGMT status did not impact the likelihood of obtaining enough cells for a full drug panel and also did not correlate with the percentage of lost cells from PDC start to end (p>0.05). Further analysis on methylation and mutational signatures and known genetic biomarkers (eg. TERT promoter alterations) are ongoing and will be reported. CONCLUSION We could establish a nation-wide program for PDC sampling enabling PDC-based drug screening within a prospective, randomized clinical trial. Clinical factors do not impact the PDC quality, while tissue weight is significantly associated with the cell number of the PDC culture.