Search Results (35)

Purpose: To develop an accelerator neutron source suitable for boron neutron capture therapy—a new promising method for treating malignant tumors—and to develop dosimetry tools and methods. Methods: Research into the transport and acceleration of a beam of charged particles, development and manufacture of an accelerator neutron source, study of the radiation generated, and development and implementation of dosimetry tools and methods. Results: A facility called VITA has been created, which includes a tandem electrostatic accelerator of an original design for producing a 2.3 MeV 10 mA proton beam, a lithium target for generating neutrons in the ⁷Li(p,n)⁷Be reaction, and a beam shaping assembly for forming a therapeutic neutron beam. The facility at the institute is used for scientific research, the facility in Xiamen (China) is used for clinical trials, and the facility in Moscow (Russia) will soon be used for clinical trials. Also, new tools and methods for measuring the boron dose, γ-ray dose, and sum of the fast neutron dose and the nitrogen dose have been proposed and implemented. The conducted studies demonstrated the high efficiency of the VITA^® facility, the first possibility of implementing prompt γ-ray spectroscopy for boron imaging, and the first possibility of implementing lithium neutron capture therapy, which has advantages over BNCT, and also presented the results of the development of new tools and methods for measuring the boron dose, γ-ray dose, and the sum of the fast neutron dose and the nitrogen dose. Conclusions: The authors strongly recommend using prompt γ-ray spectroscopy in treatment and developing lithium neutron capture therapy, including in combination with BNCT, and note the high efficiency, reliability and compactness of the VITA^® facility. Full article

Proton therapy offers superior dose localization, yet the biological effects of low-energy protons relevant to superficial tissues remain underexplored. We report the design and validation of a proton irradiation setup developed at the Tandem Accelerator of NCSR “Demokritos” for controlled radiobiological experiments. Monte Carlo simulations using Geant4 and Monte Carlo Damage Simulation (MCDS—Monte Carlo Damage Simulation) were used to determine proton energy spectra, linear energy transfer (LET), and predicted DNA damage yields. A single layer (15–20 μm in thickness) of human keratinocytes (HaCaT) was irradiated at doses from 0.65 to 3.65 Gy, and γ-H2AX foci were quantified as markers of tracks including one or more DNA double-strand breaks. The system achieved a uniform dose rate of 0.37 Gy/min, as calculated with Geant4, with a mean proton energy of 4.1 MeV (LET ≈ 8 keV/μm). A strong correlation (R² = 0.93) was observed between proton dose and γH2AX foci per nucleus (~10 foci/Gy), reflecting damage-inducing proton tracks rather than individual DNA double-strand breaks. At higher doses, an increased fraction of cells exhibited pan-nuclear γH2AX staining, characterized by a diffuse γH2AX signal throughout the nucleus and commonly associated with extensive or clustered DNA damage and global chromatin phosphorylation. These responses are consistent with the well-established dense ionization patterns produced by low-energy protons, as indicated by the LET spectrum and supported by MCDS-predicted clustered damage yields. While the γH2AX assay does not directly resolve simple versus complex DNA lesions, the agreement between Monte Carlo modeling and the observed cellular stress responses indicates that the irradiation platform reliably reproduces the expected biological signatures of low-energy proton exposure. Consequently, the developed system provides a robust experimental tool for systematic investigations of cellular radiosensitivity and radiotoxicity, with potential applications in skin dosimetry and radioprotection. Full article

The global cancer burden continues to increase worldwide. Among the various treatment options, radiotherapy (RT), which employs high-energy ionizing radiation to destroy cancer cells, is one of the primary modalities for cancer. However, increasing the absorbed dose to the target volume also increases the risk of damage to surrounding healthy tissues. This radiation-induced toxicity to normal tissues limits the desirable dosage that can be delivered to the tumor, thereby constraining the effectiveness of radiation therapy in achieving tumor control. FLASH radiotherapy (FLASH-RT) has emerged as a promising technique due to its biological advantages. FLASH-RT involves the delivery of radiation at an ultra-high dose rate (≥40 Gy/s). Unlike conventional RT, FLASH-RT achieves comparable tumor control rates while significantly reducing damage to surrounding normal tissues, a phenomenon known as the FLASH effect. Although the mechanism behind the FLASH effect is not fully understood, this approach shows considerable promise for future cancer treatment. The development of specialized treatment planning systems (TPS) becomes imperative to facilitate the clinical implementation of FLASH-RT from experimental studies. These systems must account for the unique characteristics of FLASH-RT, including ultra-high dose rate delivery and its distinctive radiobiological effects. Critical reassessment and optimization of treatment planning protocols are essential to fully leverage the therapeutic potential of the FLASH effect. This review examines key considerations for the TPS development of electron and proton FLASH-RT, including electron and proton FLASH techniques, biological models, crucial beam parameters, and dosimetry, providing essential insights for optimizing TPS and advancing the clinical implementation of this promising therapeutic modality. Full article

Very-high-energy electron (VHEE) beams, ranging from 50 to 300 or 400 MeV, are the subject of intense research investigation, with considerable interest concerning applications in radiation therapy due to their accurate energy deposition into large and deep-seated tissues, sharp beam edges, high sparing properties, and minimal radiation effects on normal tissues. The very-high-energy electron beam, which ranges from 50 to 400 MeV, and Ultra-High-Energy Electron beams up to 1–2 GeV, are considered extremely effective for human tumor therapy while avoiding the spatial requirements and cost of proton and heavy ion facilities. Many research laboratories have developed advanced testing infrastructures with VHEE beams in Europe, the USA, Japan, and other countries. These facilities aim to accelerate the transition to clinical application, following extensive simulations for beam transport that support preclinical trials and imminent clinical deployment. However, the clinical implementation of VHEE for FLASH radiation therapy requires advances in several areas, including the development of compact, stable, and efficient accelerators; the definition of sophisticated treatment plans; and the establishment of clinically validated protocols. In addition, the perspective of VHEE for accessing ultra-high dose rate (UHDR) dosimetry presents a promising procedure for the practical integration of FLASH radiotherapy for deep tumors, enhancing normal tissue sparing while maintaining the inherent dosimetry advantages. However, it has been proven that a strong effort is necessary to improve the main operational accelerator conditions, ensuring a stable beam over time and across space, as well as compact infrastructure to support the clinical implementation of VHEE for FLASH cancer treatment. VHEE-accessing ultra-high dose rate (UHDR) perspective dosimetry is integrated with FLASH radiotherapy and well-prepared cancer treatment tools that provide an advantage in modern oncology regimes. This study explores technological progress and the evolution of electron accelerator beam energy technology, as simulated by the ASTRA code, for developing VHEE and UHEE beams aimed at medical applications. FLUKA code simulations of electron beam provide dose distribution plots and the range for various energies inside the phantom of PMMA. Full article

Background: Ferrabis(dicarbollide) ([o-FESAN]⁻) in combination with proton–boron fusion therapy (PBFT) or boron neutron capture therapy (BNCT) are promising alternative radiation modalities for the treatment of breast cancer. The aim of this study was to explore the underlying effects of [o-FESAN]⁻ radio enhancement on breast cancer cells in vitro and in vivo, and to perform comparative dosimetry calculations. Methods: The cellular effects on SKBR-3 and MDA-MB-231 breast cancer cells and MDA-MB-231 xenograft-bearing nude mice induced by carrier-free [o-FESAN]⁻ after BNCT or PBFT were evaluated following recommended protocols. Monte Carlo (MC) dosimetry calculations were performed at the cellular scale for both radiation modalities. Results: Selective retention of [o-FESAN]⁻ within the cytoplasm and nucleus of SKBR-3 and MDA-MB-231 breast cancer cells is demonstrated. Moreover, in vivo studies with MDA-MB-231 xenograft-bearing nude mice show appreciable accumulation of [o-FESAN]⁻ in the tumor. Both radiation modalities induce loss of cellular viability and survival. Comparative dosimetry studies between proton and neutron irradiation agree with the viability data, showing a good correlation between absorbed dose vs. cellular effects. In the case of PBFT, cell structural changes are likely due to necrosis caused by the production of reactive oxygen species (ROS). To explain the radio enhancement effects in more detail, other mechanisms should be taken into consideration. Conclusions: Our results validate the effectiveness of both PBFT and BNCT therapeutic modalities, warranting further studies on carrier-free [o-FESAN]⁻ as a candidate drug for potential clinical translation of radio enhancers in binary radiation therapies. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) for skull base reirradiation is particularly challenging, as patients have already received substantial radiation doses to the region, and nearby normal organs may have approached their tolerance limit from prior treatments. In this study, we reviewed the characteristics and capabilities of four advanced external beam radiation delivery systems and four modern treatment planning systems and evaluated the treatment plan quality of each technique using skull base reirradiation patient cases. Methods: SBRT plans were generated for sixteen skull base reirradiation patients using four modalities: the GK plan for the Elekta Leksell Gamma Knife Perfexion/ICON, the CyberKnife (CK) plan for the Accuray CyberKnife, the intensity-modulated proton therapy (IMPT) plan for the Hitachi ProBeat-FR proton therapy machine, and the volumetric-modulated arc therapy (VMAT) plan for the Varian TrueBeam STx. These plans were evaluated and compared using two novel gradient indices in addition to traditional dosimetry metrics for targets and organs at risk (OARs). The steepest border gradient quantified the percent prescription dose fall-off per millimeter at the boundary between the target and adjacent critical structures. This gradient index highlighted the system’s ability to spare nearby critical OARs. The volume gradient assessed the extent of dose spread outside the target toward the patient’s body. Results: All plans achieved comparable target coverage and conformity, while IMPT and VMAT demonstrated significantly better uniformity. The GK plans exhibited the highest border gradient, up to 20.9%/mm, followed by small-spot-size IMPT plans and CK plans. Additionally, IMPT plans showed the benefit of reduced dose spread in low-dose regions and the lowest maximum and mean doses to the brainstem and carotid artery. Conclusions: The advanced external beam radiotherapy modalities evaluated in this study are well-suited for SBRT in skull base reirradiation, which demands precise targeting of tumors with highly conformal doses and steep dose gradients to protect nearby normal structures. Full article

Intrahepatic cholangiocarcinoma is an aggressive malignancy with rising incidence and poor outcomes. This review examines recent advancements in locoregional therapies for unresectable intrahepatic cholangiocarcinoma, focusing on external beam radiotherapy, transarterial radioembolization (TARE), hepatic artery infusion pump (HAIP) chemotherapy, and liver transplantation. Stereotactic body radiation therapy and proton beam therapy have shown promise in achieving local control and improving survival. TARE, with personalized dosimetry, has demonstrated encouraging results in select patient populations. HAIP chemotherapy, primarily studied using floxuridine, has yielded impressive survival outcomes in phase II trials. Liver transplantation, once contraindicated, is now being reconsidered for carefully selected patients with localized disease. While these locoregional approaches show potential, randomized controlled trials comparing them to standard systemic therapy are lacking. Patient selection remains crucial, with factors such as liver function, tumor burden, and molecular profile influencing treatment decisions. Ongoing research aims to optimize treatment sequencing, explore combination strategies with systemic therapies, and refine phenotype identification and patient selection criteria. As the landscape of intrahepatic cholangiocarcinoma management evolves, a multidisciplinary approach is essential to tailor treatment strategies and improve outcomes for patients with this challenging disease. Full article

Background/Objectives: Spatial fractionation of proton fields as sub-millimeter beamlets to treat cancer has shown better sparing of healthy tissue whilst maintaining the same tumor control. It is critical to ensure primary standard dosimetry is accurate and ready to support the modality’s clinical implementation. Methods: This work provided a proof-of-concept, using the National Physical Laboratory’s Primary Standard Proton Calorimeter (PSPC) to measure average absorbed dose-to-water in a pMBRT field. A 100 MeV mono-energetic field and a 2 cm wide SOBP were produced with a spot-scanned proton beam incident on a collimator comprising 15 slits of 400 µm width, each 5 cm long and separated by a center-to-center distance of 4 mm. Results: The results showed the uncertainty on the absorbed dose-to-water in the mono-energetic beam was dominated by contributions of 1.4% and 1.1% ($k$ = 1) for the NPL PSPC and PTW Roos chambers, respectively, originating from the achievable positioning accuracy of the devices. In comparison, the uncertainty due to positioning in the SOBP for both the NPL PSPC and PTW Roos chambers were 0.4%. Conclusions: These results highlight that it may be more accurate and reliable to perform reference dosimetry measuring the Dose-Area Product or in an SOBP for spatially fractionated fields. Full article

Cancer is the second leading cause of death worldwide. Around half of all cancer patients undergo some type of radiation therapy throughout the course of their treatment. Photon radiation remains (RT) the most widely utilized modality of radiotherapy despite recent advancements in proton radiation therapy (PBT). PBT makes use of the particle’s biological property known as the Bragg peak to better spare healthy tissue from radiation damage, with data to support that this treatment modality is less toxic than photon RT. Hence, proton radiation dosimetry looks better compared to photon dosimetry; however, due to proton-specific uncertainties, unexpected acute, subacute, and long-term toxicities can be encountered. Reported neurotoxicity resulting from proton radiation treatments include radiation necrosis, moyamoya syndrome, neurosensory toxicities, brain edema, neuromuscular toxicities, and neurocognitive toxicities. Pulmonary toxicities include pneumonitis and fibrosis, pleural effusions, and bronchial toxicities. Pericarditis, pericardial effusions, and atrial fibrillations are among the cardiac toxicities related to proton therapy. Gastrointestinal and hematological toxicities are also found in the literature. Genitourinary toxicities include urinary and reproductive-related toxicities. Osteological, oral, endocrine, and skin toxicities have also been reported. The side effects will be comparable to the ones following photon RT, nonetheless at an expected lower incidence. The toxicities collected mainly from case reports and clinical trials are described based on the organs affected and functions altered. Full article

Background: Pelvic reirradiation of de novo rectal or anal cancer after prior prostate cancer RT poses a significant risk of urinary and rectal fistula. In this report we describe the use of a rectal spacer to improve dosimetry and reduce this risk. Methods: Patients undergoing anorectal radiotherapy (RT) after prior prostate RT who had a rectal spacer placed prior to RT were identified in a prospective database. Patient, disease, and treatment characteristics were collected for these patients. Survival data were calculated from the end of RT. Radiation was delivered with intensity-modulated radiation therapy (IMRT) or proton beam therapy (PBT) following rectal spacer placement. Results: Rectal spacer placement with hydrogel injected transperineally under transrectal ultrasound guidance was successful in all five patients. MR/CT simulation 1–2 weeks post-spacer placement and IMRT or PBT delivered to a dose of 36–50 Gy in 24–30 fractions once or twice daily were tolerated well by all patients. The V100% of the PTV ranged from 62–100% and mean rectal and bladder dose ranged from 39–46 Gy and 16–40 Gy, respectively. At the last follow-up, three patients were alive and without evidence of disease up to 48 months out from treatment. There were no acute or late grade 3 or higher toxicities observed, but acute grade 2 proctitis was observed in all patients. Conclusions: The use of a rectal spacer placement to improve dosimetry of IMRT and PBT after prior prostate RT is safe and feasible in appropriately selected anorectal cancer patients. Full article

Proton therapy is increasingly widespread and requires an accelerator to provide the high energy protons. Most often, the accelerators used for proton therapy are cyclotrons and the maximum initial beam energy (MIBE) is about 230 MeV or more to be able to achieve a range of approximately 30 cm in water. We ask whether such a high energy is necessary for adequate dosimetry for pathologies to be treated with proton beams. Eight patients of different clinical sites (brain, prostate, and head and neck cancers) were selected to conduct this study. We analyzed the tumor dose coverage and homogeneity, as well as healthy tissue protection for MIBE values of 120, 160, 180, 200 and 230 MeV. For each patient, a proton plan was developed using the particular MIBE and then using multifield optimization (MFO). In this way, 34 plans in total were generated to fulfill the unique clinical goals. This study found that MIBE of 120 MeV for brain tumors; 160 MeV for head and neck cancer; and remarkably, for prostate cancer, only 160 MeV for one patient case and 180 MeV for the remainder satisfied the clinical goals (words: 187 < approx. 200 words or less) Full article

Background and purpose: Proton therapy has been shown to provide dosimetric benefits in comparison with IMRT when treating prostate cancer with whole pelvis radiation; however, the optimal proton beam arrangement has yet to be established. The aim of this study was to evaluate three different intensity-modulated proton therapy (IMPT) beam arrangements when treating the prostate bed and pelvis in the postoperative setting. Materials and Methods: Twenty-three post-prostatectomy patients were planned using three different beam arrangements: two-field (IMPT₂B) (opposed laterals), three-field (IMPT₃B) (opposed laterals inferiorly matched to a posterior–anterior beam superiorly), and four-field (IMPT₄B) (opposed laterals inferiorly matched to two posterior oblique beams superiorly) arrangements. The prescription was 50 Gy radiobiological equivalent (GyE) to the pelvis and 70 GyE to the prostate bed. Comparisons were made using paired two-sided Wilcoxon signed-rank tests. Results: CTV coverages were met for all IMPT plans, with 99% of CTVs receiving ≥ 100% of prescription doses. All organ at risk (OAR) objectives were met with IMPT₃B and IMPT₄B plans, while several rectum objectives were exceeded by IMPT₂B plans. IMPT₄B provided the lowest doses to OARs for the majority of analyzed outcomes, with significantly lower doses than IMPT₂B +/− IMPT₃B for bladder V30–V50 and mean dose; bowel V15–V45 and mean dose; sigmoid maximum dose; rectum V40–V72.1, maximum dose, and mean dose; femoral head V37–40 and maximum dose; bone V40 and mean dose; penile bulb mean dose; and skin maximum dose. Conclusion: This study is the first to compare proton beam arrangements when treating the prostate bed and pelvis. four-field plans provided better sparing of the bladder, bowel, and rectum than 2- and three-field plans. The data presented herein may help inform the future delivery of whole pelvis IMPT for prostate cancer. Full article

Optical fibres are gaining popularity for relative dosimetry in proton therapy due to their spatial resolution and ability for near real-time acquisition. For FLASH proton therapy, these fibres need to handle higher dose rates and larger doses than for conventional proton dose rates. We developed a multi-point fibre sensor embedded in a 3D-printed phantom which can measure the profile of a FLASH proton beam. Seven PMMA fibres of 1 mm diameter were embedded in a custom 3D-printed plastic phantom of the same density as the fibres. The phantom was placed in a proton beam with FLASH dose rates at the TRIUMF Proton Therapy Research Centre (PTRC). The sensor was exposed to different proton energies, 13.5 MeV, 19 MeV and 40.4 MeV, achieved by adding PMMA bolus in front of the phantom and three different beam currents, varying the dose rates from 7.5 to 101 Gy/s. The array was able to record beam profiles in both transverse and axial directions in relative agreement with measurements from EBT-XD radiochromic films (transverse) and Monte Carlo simulations (axial). A decrease in light output over time was observed, which might be caused by radiation damage in the matrix of the fibre and characterised by an exponential decay function. Full article

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V_40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for D_max. For the CTV, the FLASH plans resulted in a higher D_max than the clinical plans (116.9% vs. 103.3%). For the rectum, the V_40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT. Full article

Purpose: Given that the current standard of proton therapy (PT) for prostate cancer is through bilateral beams, this modality is typically avoided when it comes to treatment of patients with hip prosthesis. The purpose of this study was to evaluate whether novel PT methods, i.e., anterior proton beams and proton arc therapy (PArc), could be feasible options to treat this patient subpopulation. We evaluate PT methods in the context of dosimetry and robustness and compare with standard of practice volumetric modulated arc therapy (VMAT) to explore any potential benefits. Methods: Two PT and one VMAT treatment plans were retrospectively created for 10 patients who participated in a clinical trial with a weekly repeat CT (rCT) imaging component. All plans were robustly optimized and featured: (1) combination anterior oblique and lateral proton beams (AoL), (2) PArc, and (3) VMAT. All patients had hydrogel spacers in place, which enabled safe application of anterior proton beams. The planned dose was 70 Gy (RBE) to the entire prostate gland and 50 Gy (RBE) to the proximal seminal vesicles in 28 fractions. Along with plan dose–volume metrics, robustness to setup and interfractional variations were evaluated using the weekly rCT images. The linear energy transfer (LET)-weighted dose was evaluated for PArc plans to ensure urethra sparing given the typical high-LET region at the end of range. Results: Both PT methods were dosimetrically feasible and provided reduction of some key OAR metrics compared to VMAT except for penile bulb, while providing equally good target coverage. Significant differences in median rectum V35 (22–25%), penile bulb Dmean (5 Gy), rectum V61 (2%), right femoral head Dmean (5 Gy), and bladder V39 (4%) were found between PT and VMAT. All plans were equally robust to variations. LET-weighted dose in urethra was equivalent to the physical dose for PArc plans and hence no added urethral toxicity was expected. Conclusions: PT for treatment of prostate cancer patients with hip prosthesis is feasible and equivalent or potentially superior to VMAT in quality in some cases. The choice of radiotherapy regimen can be personalized based on patient characteristics to achieve the best treatment outcome. Full article