In situ brain tumor detection using a Raman spectroscopy system-results of a multicenter study.

Safe and effective brain tumor surgery aims to remove tumor tissue, not non-tumoral brain. This is a challenge since tumor cells are often not visually distinguishable from peritumoral brain during surgery. To address this, we conducted a multicenter study testing whether the Sentry System could distinguish the three most common types of brain tumors from brain tissue in a label-free manner. The Sentry System is a new real time, in situ brain tumor detection device that merges Raman spectroscopy with machine learning tissue classifiers. Nine hundred and seventy-six in situ spectroscopy measurements and colocalized tissue specimens were acquired from 67 patients undergoing surgery for glioblastoma, brain metastases, or meningioma to assess tumor classification. The device achieved diagnostic accuracies of 91% for glioblastoma, 97% for brain metastases, and 96% for meningiomas. These data show that the Sentry System discriminated tumor containing tissue from non-tumoral brain in real time and prior to resection.

Inhibiting Histone Deacetylase as a Means to Reverse Resistance to Angiogenesis Inhibitors: Phase I Study of Abexinostat Plus Pazopanib in Advanced Solid Tumor Malignancies.

Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC). Results Fifty-one patients with RCC (N = 22) were enrolled, including 30 (59%) with one or more lines of prior VEGF-targeting therapy. Five dose-limiting toxicities, including fatigue (n = 2), thrombocytopenia (n = 2), and elevated AST/ALT (n = 1), were observed with schedule A; one dose-limiting toxicity was observed (elevated AST/ALT) was observed with schedule B. Grade ≥ 3 related adverse events included fatigue (16%), thrombocytopenia (16%), and neutropenia (10%). The recommended phase II dose was established as abexinostat 45 mg/m2 twice a day administered per schedule B plus pazopanib 800 mg/d. Objective response rate was 21% overall and 27% in the RCC subset. Median duration of response was 9.1 months (1.2 to > 49 months). Eight patients (16%) had durable control of disease for > 12 months. Durable tumor regressions were observed in seven (70%) of 10 patients with pazopanib-refractory disease, including one patients with RCC with ongoing response > 3.5 years. Peripheral blood histone acetylation and HDAC2 gene expression were associated with durable response to treatment. Conclusion Abexinostat is well tolerated in combination with pazopanib, allowing prolonged exposure and promising durable responses in pazopanib- and other VEGF inhibitor-refractory tumors, which supports epigenetically mediated reversal of treatment resistance.