CTNI-28. IN VITRO GLIOMA STEMLIKE CELL-BASED SCREENING TO PREDICT DRUG SENSITIVITY IN RECURRENTGLIOBLASTOMA: A CLINICAL SERIES AND SYSTEMATIC LITERATURE REVIEW

Abstract INTRODUCTION There is no standard care for recurrent glioblastoma (GBM) after surgery and radiochemotherapy. Lomustine is commonly used in clinical trials, while regorafenib, a multikinase inhibitor, has shown a survival benefit in the randomized multicentric REGOMA trial, becoming the standard treatment in several countries, including Italy. However, due to nonnegligible toxicity, early identification of likely responders is crucial for personalized treatment. Various studies have explored putative molecular predictors of response with conflicting results. Glioma stem-like cells (GSCs), the most treatment-resistant subpopulation, are believed to drive GBM recurrence post-chemoradiotherapy. Thus, GSCs might provide valuable insights into the drug sensitivity of recurrent GBM. MATERIALS AND METHODS Between 2020 and 2022, nine patients enrolled in a prospective study to obtain GSC cultures from tumor tissue obtained at first surgery were treated with regorafenib upon tumor recurrence. Four patients underwent reoperation before starting regorafenib. GSC cultures were exposed to increasing regorafenib doses in vitro to determine sensitivity (IC50). RESULTS The median progression-free survival (PFS) was 3 months, consistent with REGOMA data. Only one patient achieved 6-month PFS (11.1%). GSCs from this patient were the only ones with an IC50 below the plasma range of regorafenib during treatment (IC50 4.6 μM, range 5.2-8.1 μM). Additionally, this patient had not undergone reoperation before starting regorafenib. Systematic literature review showed few but promising studies in which therapy personalization was based on in vitro drug screening. CONCLUSIONS Although preliminary, these findings suggest a potential paradigm shift in personalized treatment for recurrent GBM, utilizing a GSC-based approach rather than molecular profiling. Further evaluation of GSCs from recurrent tumor tissue is necessary to determine their utility.