TMOD-11. IMAGING BASED INVASION METRIC PREDICTIVE OF RESPONSE TO ABT414 IN ORTHOTOPIC EGFRviii AMPLIFIED PATIENT DERIVED XENOGRAFTS
| Autor: | Andrea Hawkins-Daarud, Susan Christine Massey, Bianca M Marin, Jann N. Sarkaria, Pamela R. Jackson, Lauren Kasle, Ann C. Mladek, Kristin R. Swanson, Lisa E. Paulson |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Neuro-Oncology. 20:vi270-vi271 |
| ISSN: | 1523-5866 1522-8517 |
| Popis: | BACKGROUND: Failed trials involving targeted therapies face a daunting task of understanding whether the root cause was inadequate targeting, resistance, or insufficient delivery to the tumor. Previous work with a bio-mathematical model has shown the prognostic value of an imaging based invasion metric, D/ρ (mm(2)/yr), which is linearly correlated with the extent of tumor burden beyond the imaging abnormality. As this extent likely impacts the definition of sufficient drug delivery, we investigated whether this metric is able to predict response to ABT-414, an antibody drug conjugate targeting EGFR. METHODS: Preclinical experiments: After initial screening in vitro and in flank, the efficacy of ABT-414 was evaluated for three patient derived cell lines (PDXs), GBM6, GBM12, and GBM39, implanted orthotopically. All three showed strong response to ABT-414 in the previous experiments. In the orthotopic setting, GBM39 was very sensitive to therapy (> 155 days benefit), GBM12 was moderately sensitive (15–30 days benefit), and GBM6 was resistant to therapy (no benefit). Invasion Index: D/ρ was calculated for each cell line based on the original patients’ pre-treatment T1-weighted with Gd contrast and FLAIR MRIs. We then analyzed whether D/ρ was correlated with the observed response to ABT-414. RESULTS: GBM6 had the highest D/ρ = 4.7 (greatest proportion of tumor cells invaded beyond the imaging abnormality), GBM12 was in the middle with D/ρ = 1.7, and GBM39 had the lowest D/ρ = 0.9. This perfectly (inversely) correlates with the response patterns. GBM6 showed no response, GBM12 had a moderate response, and GBM39 showed the greatest response to ABT-414. CONCLUSION: Our results suggest that the imaging based tumor invasion metric, D/ρ, is inversely correlated with tumor response to ABT-414. This supports our hypothesis that drugs with low BBB permeability will be more beneficial for tumors with little tumor burden beyond the imaging abnormality. |
| Databáze: | OpenAIRE |
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