Evolving Role of Stereotactic Body Radiation Therapy in the Management of Spine Metastases: Defining Dose and Dose Constraints.

When treating solid tumor spine metastases, stereotactic high-dose-per-fraction radiation, given in a single fraction or in a hypofractionated approach, has proved to be a highly effective and safe therapeutic option for any tumor histology, in the setting of de novo therapy, as salvage treatment of local progression after previous radiation, and in the postoperative setting. There are variations in practice based on the clinical presentation, goals of therapy, as well as institutional preferences. As a biologically potent therapy, a thoughtful and careful attention to detail with patient selection, treatment planning, and delivery is crucial for treatment success.

Nelfinavir induces radiation sensitization in pituitary adenoma cells.

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution, and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir's effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 days, 17 days with nelfinavir treatment, 27 days with radiation 6 Gy, and 41 days with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on Western blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies.