Apart from problems such as poor osseointegration, stress shielding, and wear debris-associated bone cell death, a major concern of metallic orthopedic implants is that they slowly corrode under in vivo environments. It is possible that continuous tissue exposure to metallic corrosion products limits orthopedic implant efficacy; this is especially true for patients receiving implants due to bone cancer. To date, there is no metallic orthopedic implant available in the market that specifically deals with the prevention and/or recurring cancer that may happen in these patients. The objective of this study was to deal with these problems in an integrated way by introducing a new biomaterial to the orthopedic community with anticancer chemistry: selenium (Se). In this study, six types of Se compacts were tested for bone cell (osteoblast) adhesion under in vitro conditions. Two types of cylindrical compacts were made with conventional Se metal particles in the micron (6.539 +/- 1.364-microm diameter) and submicron (0.963 +/- 0.139-microm diameter) range. These two types of compacts were chemically etched with different concentrations of NaOH to create two additional types of Se particles in each category: conventional size particles with nanosurface roughness and nanometer particles (0.204- to 0.264-microm diameter). Results showed for the first time, enhanced osteoblast adhesion on particulate surfaces of the compacts made from conventional Se compared with reference nonparticulate wrought titanium sheets. More importantly, this study provided the first evidence that osteoblast density was further increased on the surfaces of the Se compacts with nanometer particles. These initial findings indicate that there may be a promising future for nanoparticulate Se as an anticancer biocompatible orthopedic material.
133 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with HTMB treated with P are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-1, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had HTMB, defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n=26) or other tests (n=2) approved by the Molecular Tumor Board. Pts with MSI-H tumors were ineligible. Dosing of P was 2 mg/kg (n=8) or 200 mg (n=20) IV over 30 mins, every 3 wks. Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16+ wks according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight pts enrolled from June 2017 to November 2018; 1 pt was ineligible and excluded. HTMB ranged from 9 to 54 Muts/Mb. Table (N=27) summarizes demographics and outcomes. Tumor MS status was reported stable for 25 pts, ambiguous for 1 pt, and not available for 1 pt. One PR (MS stable and 10 Muts/Mb) and 7 SD16+ were observed for DC and OR rates of 28% (90% CI, 16% to 45%) and 4% (95% CI, 0% to 19%), respectively. 2 pts each had grade 3 AEs at least possibly related to P including abdominal infection, anorexia, colitis, diarrhea, fatigue, nausea, and vomiting; 1 also had SAE of acute kidney injury. Conclusions: Monotherapy with P showed anti-tumor activity in heavily pre-treated CRC pts with HTMB . Additional study is warranted to confirm the efficacy of P in this population. Clinical trial information: NCT02693535. [Table: see text]
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