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Compton-based prompt gamma (PG) imaging is being investigated by several groups as a potential solution for in vivo range monitoring in proton therapy. The performance of this technique depends on the detector system as well as the ability of the reconstruction method to obtain good spatial resolution to establish a quantitative correlation between the PG emission and the proton beam range in the patient. To evaluate the feasibility of PG imaging for range monitoring, we quantitatively evaluated the emission distributions reconstructed by a Maximum Likelihood Expectation Maximization (MLEM) and a Stochastic Origin Ensemble (SOE) algorithm. To this end, we exploit experimental and Monte Carlo (MC) simulation data acquired with the Polaris-J Compton Camera (CC) prototype. The differences between the proton beam range (R

The purpose of this study was to determine the types, proportions, and energies of secondary particle interactions in a Compton camera (CC) during the delivery of clinical proton beams. The delivery of clinical proton pencil beams ranging from 70 to 200 MeV incident on a water phantom was simulated using Geant4 software (version 10.4). The simulation included a CC similar to the configuration of a Polaris J3 CC designed to image prompt gammas (PGs) emitted during proton beam irradiation for the purpose of in vivo range verification. The interaction positions and energies of secondary particles in each CC detector module were scored. For a 150-MeV proton beam, a total of 156,688(575) secondary particles per 10(8) protons, primarily composed of gamma rays (46.31%), neutrons (41.37%), and electrons (8.88%), were found to reach the camera modules, and 79.37% of these particles interacted with the modules. Strategies for using CCs for proton range verification should include methods of reducing the large neutron backgrounds and low-energy non-PG radiation. The proportions of interaction types by module from this study may provide information useful for background suppression.

Simple Summary Chordoma 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. Abstract 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.

The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral‐opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields. Dose volume histograms (DVH) were generated for the prostate, rectum, bladder, and right and left femoral heads. The normal tissue complication probability (NTCP) for ≥grade 2 rectal toxicity was calculated using the Lyman–Kutcher–Burman model and compared between patients with and without the rectal spacer. A significantly lower mean rectal DVH was achieved in patients with rectal spacer compared to those without. For LAT plans, the mean rectal V70 with and without rectal spacer was 4.19 and 13.5%, respectively. For LAO/RAO plans, the mean rectal V70 with and without rectal spacer was 5.07 and 13.5%, respectively. No significant differences were found in any rectal dosimetric parameters between the LAT and the LAO/RAO plans generated with the rectal spacers. We found that ≥ 9 mm space resulted in a significant decrease in NTCP modeled for ≥grade 2 rectal toxicity. Rectal spacers can significantly decrease modeled rectal dose and predicted ≥grade 2 rectal toxicity in prostate cancer patients treated in silico with PBS. A minimum of 9 mm separation between the prostate and anterior rectal wall yields the largest benefit.

The authors investigated how the characteristics of the detectors used in a three-stage Compton camera (CC) affect the CC's ability to accurately measure the emission distribution and energy spectrum of prompt gammas (PG) emitted by nuclear de-excitations during proton therapy. The detector characteristics they studied included the material (high-purity germanium [HPGe] and cadmium zinc telluride [CZT]), Doppler broadening (DB), and resolution (lateral, depth, and energy).The authors simulated three-stage HPGe and CZT CCs of various configurations, detecting gammas from point sources with energies ranging from 0.511 to 7.12 MeV. They also simulated a proton pencil beam irradiating a tissue target to study how the detector characteristics affect the PG data measured by CCs in a clinical proton therapy setting. They used three figures of merit: the distance of closest approach (DCA) and the point of closest approach (PCA) between the measured and actual position of the PG emission origin, and the calculated energy resolution.For CCs with HPGe detectors, DB caused the DCA to be greater than 3 mm for 14% of the 6.13 MeV gammas and 20% of the 0.511 MeV gammas. For CCs with CZT detectors, DB caused the DCA to be greater than 3 mm for 18% of the 6.13 MeV gammas and 25% of the 0.511 MeV gammas. The full width at half maximum (FWHM) of the PCA in the ẑ direction for HPGe and CZT detectors ranged from 1.3 to 0.4 mm for gammas with incident energy ranging from 0.511 to 7.12 MeV. For CCs composed of HPGe detectors, the resolution of incident gamma energy calculated by the CC ranged from 6% to 1% for gammas with true incident energies from 0.511 to 7.12 MeV. For CCs composed of CZT detectors, the resolution of gamma energy calculated by the CC ranged from 10% to 1% for gammas with true incident energies from 0.511 to 7.12 MeV. For HPGe and CZT CCs in which all detector effect were included, the DCA was less than 3 mm for 75% and 68% of the detected gammas, respectively, and restricting gammas to those having energy greater than 2.0 MeV increased these percentages to 83% and 77% for HPGe and CZT, respectively. Distributions of the true gamma origins and the PCA after detector characteristics had been included showed good agreement on beam range and some loss of resolution for the lateral profile of the PG emission. Characteristic energy lines were evident in the calculated gamma energy spectrum.The authors found the following: (1) DB is the dominant source of spatial and energy resolution loss in the CCs at all energy levels; (2) the largest difference in the spatial resolution of HPGe and CZT CCs is that the spatial resolution distributions of CZT have broader tails. The differences in the FWHM of these distributions are small; (3) the energy resolution of both HPGe and CZT three-stage CCs is adequate for PG spectroscopy; and (4) restricting the gammas to those having energy greater than 2.0 MeV can improve the achievable image resolution.