Abstract
Simple SummaryChordoma is a rare, slow-growing cancer of the spinal cord. Photon radiation therapy and surgery are the standard of care for chordoma. Proton radiation therapy has become an increasingly common treatment in comparison to photon radiation therapy due to the ability to reduce off-target radiation dose. However, there is still an increased risk of toxicity to the surrounding critical structures that lead to poor treatment outcomes. Moreover, the biologic effectiveness of protons to sterilize chordoma cells remains uncertain and likely varies according to the proton energy spectrum throughout the proton field. We aim to investigate the tumoricidal properties of proton radiation therapy at the middle and end of the proton radiation field and elucidate variations in the relative biological effectiveness for chordoma cells. Our study helps quantify the therapeutic value of treating chordoma near the end of the proton field, where linear energy transfer is relatively high.Background: 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.
Highlights
Radiation is a common treatment modality for cancer [1], and photon-based radiation therapy is conventionally used, due to the limited mode of delivery via multipleX-ray beams, there is an increased risk of toxicity to surrounding normal tissue [2]
The proton gantry was rotated to deliver the beam from beneath the plates, and tissue-equivalent plastic slabs were placed beneath the plates (Figure 2A,B) to position the cell-culture plates at a radiologic depth corresponding to the middle of the Spread-Out Bragg Peak (SOBP)
16 Gy for U-CH2 and 8 Gy for Mug-chor1 did not show any statistically significant killing because the dose was so high that the survival fraction at Middle of the Spread-Out Bragg Peak (M-SOBP) was < 1%
Summary
Radiation is a common treatment modality for cancer [1], and photon-based radiation therapy is conventionally used, due to the limited mode of delivery via multipleX-ray beams, there is an increased risk of toxicity to surrounding normal tissue [2]. Chora common treatment for cancer [1],which and photon-based domaRadiation is a rareisslow-growing cancermodality of the spinal cord occurs moreradiation commonly on therapy is conventionally used, due to the limited mode of delivery via multiple the sacral, followed by cranial and thoracic-lumber regions [3]. Chorposition of the chordoma tumor and the limitation of photon radiation, proton beam radoma is a rare slow-growing cancer of the spinal cord which occurs more commonly on diation therapy (PBRT). (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor 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). We conclude that there seems to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
