Proton beam irradiation induces invisible modifications under the surface of painted parchment

Ion beam analysis plays an important role in cultural heritage (CH) studies as it offers a combination of simultaneous and complementary analytical techniques (PIXE/PIGE/RBS) and spatially resolved mapping functions. Despite being considered non-destructive, the potential risk of beam-induced modifications during analysis is increasingly discussed. This work focuses on the impact of proton beams on parchment, present in our CH in form of unique historical manuscripts. Parchment is one of the organic, protein-based CH materials believed to be the most susceptible to radiation-induced changes. Various modification patterns, observed on parchment cross-sections by optical and electron microscopy are reported: discoloration (yellowing), formation of cavities and denaturation of collagen fibers. Considerable modifications were detected up to 100 µm deep into the sample for beam fluences of 4 µC/cm2 and higher. The presence of ultramarine paint on the parchment surface appears to increase the harmful effects of proton radiation. Based on our results, a maximum radiation dose of 0.5 µC/cm2 can be considered as ‘safe boundary’ for 2.3 MeV PIXE analysis of parchment under the applied conditions.

Online learning in proton radiation therapy: the future in the post-Covid-19 pandemic era?

Objective: The Covid-19 pandemic placed unprecedented strain on medical education and led to a vast increase in online learning. Subsequently, the XXXX International Proton School moved from face-to-face to online. Delegate feedback and current literature were studied to determine benefits, challenges, and potential solutions, for online proton therapy education. Methods: The course was converted to a six-week online course with twice weekly two-hour sessions. Feedback was studied pre, during, and post course regarding demographics, learning objectives, proton therapy knowledge, ease of engagement, technical difficulties, and course format. Statistical analyses were performed for proton therapy knowledge pre and post course. Results: An increase in delegate attendance was seen with increased international and multidisciplinary diversity. Learner objectives included treatment planning, clinical applications, physics, and centre development. Average learner reported scores of confidence in proton therapy knowledge improved significantly from 3, some knowledge, to 4, adequate knowledge after the course (p<0.0001). There were minimal reported difficulties using the online platform, good reported learner engagement, and shorter twice weekly sessions were reported conducive for learning. Recordings for asynchronous learning addressed time zone difficulties. Conclusions: The obligatory switch to online platforms has catalysed a paradigm shift towards online learning with delegates reporting educational benefit. We propose solutions to challenges of international online education, and a pedagogical model for online proton therapy education. Advances in knowledge: Online education is an effective method to teach proton therapy to international audiences. The future of proton education includes a hybrid of online and practical face-to-face learning depending on the level of cognitive skill required.

Investigation on the performance dependence of proton radiated SiGe HBTs with emitter area and temperature

The DC and AC performances of proton radiated Silicon-Germanium (SiGe) Heterojunction Bipolar Transistors (HBTs) with different emitter areas at liquid nitrogen temperature (77 K), room temperature and heating hotplate (393 K) were presented in this work. Performance dependence on the emitter area and temperature was investigated. Results showed that SiGe HBTs with a large emitter area had more damage by proton radiation. Furthermore, the SiGe HBTs showed better tolerance to proton radiation at extreme temperatures than at room temperature. To reveal the underlying mechanism, the radiated SiGe HBTs were modeled based on the device structure and parameters. The electron density, Shockley–Read–Hall (SRH) recombination and carrier mobility were extracted from the device model and demonstrated to have major impacts on the performance dependence of the radiated SiGe HBTs. The results provide useful guidance for the application of SiGe HBTs at extreme environments.

Dosimetric Evaluation of Photons Versus Protons in Postmastectomy Planning for Ultrahypofractionated Breast Radiotherapy

Background: Ultrahypofractionation can shorten the irradiation period. This study is the first dosimetric investigation comparing ultrahypofractionation using volumetric arc radiation therapy (VMAT) and intensity-modulated proton radiation therapy (IMPT) techniques in postmastectomy treatment planning. Materials and methods: Twenty postmastectomy patients (10-left and 10-right sided) were replanned with both VMAT and IMPT techniques. There were 4 scenarios: left chest wall, left chest wall including regional nodes, right chest wall, and right chest wall including regional nodes. The prescribed dose was 26 Gy (RBE) in 5 fractions. For VMAT, a 1-cm bolus was added for 2 in 5 fractions. For IMPT, robust optimization was performed on the CTV structure with a 3-mm setup uncertainty and a 3.5% range uncertainty. This study aimed to compare the dosimetric parameters of the PTV, ipsilateral lung, contralateral lung, heart, skin, esophageal, and thyroid doses. Results: The PTV-D95 was kept above 24.7 Gy in both VMAT and IMPT plans. The ipsilateral lung mean dose of the IMPT plans was comparable to that of the VMAT plans. In three of four scenarios, the V5 of the ipsilateral lung in IMPT plans was lower than in VMAT plans. The Dmean and V5 of heart dose were reduced by a factor of 4 in the IMPT plans of the left side. For the right side, the Dmean of the heart was less than 1 Gy for IMPT, while the VMAT delivered approximately 3 Gy. The IMPT plans showed a significantly higher skin dose owing to the lack of a skin-sparing effect in the proton beam. The IMPT plans provided lower esophageal and thyroid mean dose. Conclusion: Despite the higher skin dose with the proton plan, IMPT significantly reduced the dose to adjacent organs at risk, which might translate into the reduction of late toxicities when compared with the photon plan. Key words: proton therapy, ultrahypofractionation, postmastectomy, breast irradiation

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

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.

Combined Effects of Proton Radiation and Simulated Microgravity on the Cell Viability and ALP Activity of Murine Osteoblast Cells

Proton radiation (PR) and microgravity (μG) are two key factors that impact living things in space. This study aimed to explore the combined effects of PR and simulated μG (SμG) on bone function. Mouse embryo osteoblast precursor cells (MC3T3-E1) were irradiated with proton beams and immediately treated with SμG for 2 days using a three-dimensional clinostat. All samples were subjected to cell viability, alkaline phosphatase (ALP) activity and transcriptome assays. The results showed that cell viability decreased with increasing doses of PR. The peak ALP activity after PR or SμG alone was lower than that obtained with the non-treatment control. No difference in cell viability or ALP activity was found between 1 Gy PR combined with SμG (PR-SμG) and PR alone. However, 4 Gy PR-SμG resulted in decreased cell viability and ALP activity compared with those obtained with PR alone. Furthermore, Gene Ontology analysis revealed the same trend. These results revealed that PR-SμG may lead to reductions in the proliferation and differentiation capacities of cells in a dose-dependent manner. Our data provide new insights into bone-related hazards caused by multiple factors, such as PR and μG, in the space environment.

Dosimetric Results for Adjuvant Proton Radiation Therapy of HPV-Associated Oropharynx Cancer

Purpose One significant advantage of proton therapy is its ability to improve normal tissue sparing and toxicity mitigation, which is relevant in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Here, we report our institutional experience and dosimetric results with adjuvant proton radiation therapy (PRT) versus intensity-modulated radiotherapy (IMRT) for Human Papilloma Virus (HPV)-associated OPSCC. Materials and Methods This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved equivalent IMRT plan to serve as a reference. Endpoints included dosimetric outcomes to the organs at risk (OARs), local regional control (LRC), progression-free survival (PFS), and overall survival (OS). Descriptive statistics, a 2-tailed paired t test for dosimetric comparisons, and the Kaplan-Meier method for disease outcomes were used. Results Fifty-three patients were identified. Doses delivered to OARs compared favorably for PRT versus IMRT, particularly for the pharyngeal constrictors, esophagus, larynx, oral cavity, and submandibular and parotid glands. The achieved normal tissue sparing did not negatively impact disease outcomes, with 2-year LRC, PFS, and OS of 97.0%, 90.3%, and 97.5%, respectively. Conclusion Our study suggests that meaningful normal tissue sparing in the postoperative setting is achievable with PRT, without impacting disease outcomes.

DNA Dosimetry with Gold Nanoparticle Irradiated by Proton Beams: A Monte Carlo Study on Dose Enhancement

Heavy atom nanoparticles, such as gold nanoparticles, are proven effective radiosensitizers in radiotherapy to enhance the dose delivery for cancer treatment. This study investigated the effectiveness of cancer cell killing, involving gold nanoparticle in proton radiation, by changing the nanoparticle size, proton beam energy, and distance between the nanoparticle and DNA. Monte Carlo (MC) simulation (Geant4-DNA code) was used to determine the dose enhancement in terms of dose enhancement ratio (DER), when a gold nanoparticle is present with the DNA. With varying nanoparticle size (radius = 15–50 nm), distance between the gold nanoparticle and DNA (30–130 nm), as well as proton beam energy (0.5–25 MeV) based on the simulation model, our results showed that the DER value increases with a decrease of distance between the gold nanoparticle and DNA and a decrease of proton beam energy. The maximum DER (1.83) is achieved with a 25 nm-radius gold nanoparticle, irradiated by a 0.5 MeV proton beam and 30 nm away from the DNA.