Chordoma is a
cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat
chordoma is resection followed by
radiation therapy. Since,
chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result,
chordoma has a high chance of recurrence and developing resistance to
radiation therapy. In addition, treatment of
chordoma by conventional
radiation therapy can also damage normal tissues surrounding
chordoma. Thus, current therapeutic options to treat
chordoma are insufficient and novel
therapies are desperately needed to treat locally advanced and metastatic
chordoma. (2) Methods: In the present investigation, human
chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with
Proton Beam Radiation using the clinical superconducting
cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP).
Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of
proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a
proton radiation in the middle of the SOBP. We observed differences in the survival of both Human
chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing.
Proton field at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as
DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3-1.7) at the E-SOBP compared with the M-SOBP.