Search

Purpose: In this study, a C-series linear accelerator was configured to enable rapid and reliable conversion between the production of conventional electron beams and an ultrahigh-dose-rate (UHDR) electron beamline to the treatment room isocenter for FLASH radiation therapy. Efforts to tune the beam resulted in a consistent, stable UHDR beamline., Methods and Materials: The linear accelerator was configured to allow for efficient switching between conventional and modified electron output modes within 2 minutes. Additions to the air system allow for retraction of the x-ray target from the beamline when the 10 MV photon mode is selected. With the carousel set to an empty port, this grants access to the higher current pristine electron beam normally used to produce clinical photon fields. Monitoring signals related to the automatic frequency control system allows for tuning of the waveguide while the machine is in a hold state so a stable beam is produced from the initial pulse. A pulse counting system implemented on an field-programmable gate array-based controller platform controls the delivery to a desired number of pulses. Beam profiles were measured with Gafchromic film. Pulse-by-pulse dosimetry was measured using a custom electrometer designed around the EDGE diode., Results: This method reliably produces a stable UHDR electron beam. Open-field measurements of the 16-cm full-width, half-maximum gaussian beam saw average dose rates of 432 Gy/s at treatment isocenter. Pulse overshoots were limited and ramp up was eliminated. Over the last year, there have been no recorded incidents that resulted in machine downtime due to the UHDR conversions., Conclusions: Stable 10 MeV UHDR beams were generated to produce an average dose rate of 432 Gy/s at the treatment room isocenter. With a reliable pulse-counting beam control system, consistent doses can be delivered for FLASH experiments with the ability to accommodate a wide range of field sizes, source-to-surface distances, and other experimental apparatus that may be relevant for future clinical translation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Very High Energy Electron (VHEE) beams are a promising alternative to conventional radiotherapy due to their highly penetrating nature and their applicability as a modality for FLASH (ultra-high dose-rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose-rates. This paper presents an in depth exploration of the focusing achievable at the current CLEAR (CERN Linear Electron Accelerator for Research) facility, for beam energies >200 MeV. A shorter, more optimal quadrupole setup was also investigated using the TOPAS code in Monte Carlo simulations, with dimensions and beam parameters more appropriate to a clinical situation. This work provides insight into how a focused VHEE radiotherapy beam delivery system might be achieved., (© 2024. The Author(s).)

Purpose: Clinical translation of FLASH-radiotherapy (RT) to deep-seated tumours is still a technological challenge. One proposed solution consists of using ultra-high dose rate transmission proton (TP) beams of about 200-250 MeV to irradiate the tumour with the flat entrance of the proton depth-dose profile. This work evaluates the dosimetric performance of very high-energy electron (VHEE)-based RT (50-250 MeV) as a potential alternative to TP-based RT for the clinical transfer of the FLASH effect., Methods: Basic physics characteristics of VHEE and TP beams were compared utilizing Monte Carlo simulations in water. A VHEE-enabled research treatment planning system was used to evaluate the plan quality achievable with VHEE beams of different energies, compared to 250 MeV TP beams for a glioblastoma, an oesophagus, and a prostate cancer case., Results: Like TP, VHEE above 100 MeV can treat targets with roughly flat (within ± 20 %) depth-dose distributions. The achievable dosimetric target conformity and adjacent organs-at-risk (OAR) sparing is consequently driven for both modalities by their lateral beam penumbrae. Electron beams of 400[500] MeV match the penumbra of 200[250] MeV TP beams and penumbra is increased for lower electron energies. For the investigated patient cases, VHEE plans with energies of 150 MeV and above achieved a dosimetric plan quality comparable to that of 250 MeV TP plans. For the glioblastoma and the oesophagus case, although having a decreased conformity, even 100 MeV VHEE plans provided a similar target coverage and OAR sparing compared to TP., Conclusions: VHEE-based FLASH-RT using sufficiently high beam energies may provide a lighter-particle alternative to TP-based FLASH-RT with comparable dosimetric plan quality., Competing Interests: Declaration of competing interest Andreas Bratel, Eric Landström and Erik Engwall are employees of RaySearch Laboratories AB. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this study, some confusing points about electron film dosimetry using white polystyrene suggested by international protocols were verified using a clinical linear accelerator (LINAC). According to international protocol recommendations, ionometric measurements and film dosimetry were performed on an SP34 slab phantom at various electron energies. Scaling factor analysis using ionometric measurements yielded a depth scaling factor of 0.923 and a fluence scaling factor of 1.019 at an electron beam energy of <10 MeV (i.e., R50 < 4.0 g/cm2). It was confirmed that the water-equivalent characteristics were similar because they have values similar to white polystyrene (i.e., depth scaling factor of 0.922 and fluence scaling factor of 1.019) presented in international protocols. Furthermore, percentage depth dose (PDD) curve analysis using film dosimetry showed that when the density thickness of the SP34 slab phantom was assumed to be water-equivalent, it was found to be most similar to the PDD curve measured using an ionization chamber in water as a reference medium. Therefore, we proved that the international protocol recommendation that no correction for measured depth dose is required means that no scaling factor correction for the plastic phantom is necessary. This study confirmed two confusing points that could occur while determining beam characteristics using electron film dosimetry, and it is expected to be used as basic data for future research on clinical LINACs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Electrons with kinetic energy up to a few hundred MeV, also called very high energy electrons (VHEE), are currently considered a promising technique for the future of radiation therapy (RT) and in particular ultra-high dose rate (UHDR) therapy. However, the feasibility of a clinical application is still being debated and VHEE therapy remains an active area of research for which the optimal conformal technique is also yet to be determined., Purpose: In this work, we will apply two existing formalisms based on analytical Gaussian multiple-Coulomb scattering theory and Monte Carlo (MC) simulations to study and compare the electron and bremsstrahlung photon dose distributions arising from two beam delivery systems (passive scattering with or without a collimator or active scanning)., Methods: We therefore tested the application of analytical and MC models to VHEE beams and assessed their performance and parameterization in the energy range of 6-200 MeV. The optimized electron beam fluence, the bremsstrahlung, an estimation of central-axis and off-axis x-ray dose at the practical range and neutron contributions to the total dose, along with an extended parameterization for the photon dose model were developed, together with a comparison between double scattering (DS) and pencil beam scanning (PBS) techniques. MC simulations were performed with the TOPAS/Geant4 toolkit to verify the dose distributions predicted by the analytical calculations., Results: The results for the clinical energy range (between 6 and 20 MeV) as well as for higher energies (VHEE range between 20 and 200 MeV) and for two treatment field sizes (5 × 5 and 10 × 10 cm 2 ) are reported, showing a reasonable agreement with MC simulations with mean differences below 2.1%. The relative contributions of photons generated in the medium or by the scattering system along the central-axis (up to 50% of the total dose) are also illustrated, along with their relative variations with electron energy., Conclusions: The fast analytical models parametrized in this study allow an estimation of the amount of photons produced behind the practical range by a DS system with an accuracy lower than 3%, providing important information for the eventual design of a VHEE system. The results of this work could support future research on VHEE radiotherapy., (© 2023 American Association of Physicists in Medicine.)

Objective . A calibration service based on a primary standard calorimeter for the direct determination of absorbed dose for proton beams does not exist. A new Code of Practice (CoP) for reference dosimetry of proton beams is being developed by a working party of the UK Institute of Physics and Engineering in Medicine (IPEM), which will recommend that ionisation chambers are calibrated directly in their clinical beams against the proposed Primary Standard Proton Calorimeter (PSPC) developed at the National Physical Laboratory (NPL). The aim of this work is to report on the use of the NPL PSPC to directly calibrate ionisation chambers in a low-energy passively scattered proton beam following recommendations of the upcoming IPEM CoP. Approach . A comparison between the dose derived using the proposed IPEM CoP and the IAEA TRS-398 protocol was performed, andkQvalues were determined experimentally for three types of chambers. In total, 9 plane-parallel and 3 cylindrical chambers were calibrated using the two protocols for two separate visits. Main results . The ratio of absorbed dose to water obtained with the PSPC and with ionisation chambers applying TRS-398 varied between 0.98 and 1.00, depending on the chamber type. The new procedure based on the PSPC provides a significant improvement in uncertainty where absorbed dose to water measured with a user chamber is reported with an uncertainty of 0.9% (1σ), whereas the TRS-398 protocol reports an uncertainty of 2.0% and 2.3% (1σ) for cylindrical and plane-parallel chambers, respectively. ThekQvalues found agree within uncertainties with those from TRS-398 and Monte Carlo calculations. Significance . The establishment of a primary standard calorimeter for the determination of absorbed dose in proton beams combined with the introduction of the associated calibration service following the IPEM recommendations will reduce the uncertainty and improve consistency in the dose delivered to patients., (© 2022 Institute of Physics and Engineering in Medicine.)

Introduction: This study presents an empirical method to model the high-energy photon beam percent depth dose (PDD) curve by using the home-generated buildup function and tail function (buildup-tail function) in radiation therapy. The modeling parameters n and μ of buildup-tail function can be used to characterize the Collimator Scatter Factor (Sc) either in a square field or in the different individual upper jaw and lower jaw setting separately for individual monitor unit check., Methods and Materials: The PDD curves for four high-energy photon beams were modeled by the buildup and tail function in this study. The buildup function was a quadratic function in the form of [Formula: see text] with the main parameter of d (depth in water) and n, while the tail function was in the form of e-μd and was composed by an exponential function with the main parameter of d and μ. The PDD was the product of buildup and tail function, PDD = [Formula: see text]. The PDD of four-photon energies was characterized by the buildup-tail function by adjusting the parameters n and μ. The Sc of 6 MV and 10 MV can then be expressed simply by the modeling parameters n and μ., Results: The main parameters n increases in buildup-tail function when photon energy increased. The physical meaning of the parameter n expresses the beam hardening of photon energy in PDD. The fitting results of parameters n in the buildup function are 0.17, 0.208, 0.495, 1.2 of four-photon energies, 4 MV, 6 MV, 10 MV, 18 MV, respectively. The parameter μ can be treated as attenuation coefficient in tail function and decreases when photon energy increased. The fitting results of parameters μ in the tail function are 0.065, 0.0515, 0.0458, 0.0422 of four-photon energies, 4 MV, 6 MV, 10 MV, 18 MV, respectively. The values of n and μ obtained from the fitted buildup-tail function were applied into an analytical formula of Sc = nE(S)0.63μE to get the collimator to scatter factor Sc for 6 and 10 MV photon beam, while nE, μE, S denotes n, μ at photon energy E of field size S, respectively. The calculated Sc were compared with the measured data and showed agreement at different field sizes to within ±1.5%., Conclusions: We proposed a model incorporating a two-parameter formula which can improve the fitting accuracy to be better than 1.5% maximum error for describing the PDD in different photon energies used in clinical setting. This model can be used to parameterize the Sc factors for some clinical requirements. The modeling parameters n and μ can be used to predict the Sc in either square field or individual jaws opening asymmetrically for treatment monitor unit double-check in dose calculation. The technique developed in this study can also be used for systematic or random errors in the QA program, thus improves the clinical dose computation accuracy for patient treatment., Competing Interests: The authors have declared that no competing interests exist.

Photo neutrons are generated from high-energy medical X-ray linacs via photo-nuclear reactions with the materials of target and collimator as well as therapeutic X-rays. Such photo neutrons sometimes make unwanted influences and are not negligible for the aspects of radiation protection and radiation control. In this article, fundamental principle of such photo-neutron generation is briefly explained. The side effects induced by the photo neutrons are summarized. In addition, some techniques of the detection and measurement of photo neutrons are introduced.

Background: Studies have revealed that salvage surgery after definitive chemoradiotherapy (CRT) for unresectable advanced non-small cell lung cancer improves survival with acceptable surgical adverse events. Few reports exist regarding pneumonectomy or the bronchoplastic procedure in this setting., Methods: Between 2008 and 2018, 27 patients (21 men; median age, 61 years) underwent salvage surgery after definitive CRT for non-small cell lung cancer. We investigated postoperative short- and long-term outcomes of salvage surgery and aimed to elucidate the feasibility of pneumonectomy or the bronchoplastic procedure., Results: The median radiation dose was 60 Gy. The median period from the last day for irradiation to the operative day was 8.5 months. Pneumonectomy was performed in 9 patients, including 2 carinal resections; lobectomy was performed in 18 patients, including 5 bronchoplasties. Bronchial wrapping was performed in 9 cases (33%), R0 resection was achieved in 24 (89%), and postoperative complications were detected in 16 (59%). Although bronchopleural fistulas were found in only 2 patients who underwent pneumonectomy, arrhythmia was observed more frequently in patients who underwent the bronchoplastic procedure (P = .05). Regarding major complications, no relationship with any factors were found. The 90-day mortality was 0%. The 5-year overall and recurrence-free survival were 63% and 27%, respectively. R0 resection was a good prognostic factor for recurrence-free survival (P = .001)., Conclusions: Perioperative short- and long-term outcomes of salvage surgery after definitive CRT for non-small cell lung cancer were acceptable. Complete resection offered a better recurrence-free survival. The bronchoplastic procedure or pneumonectomy should be considered as an option even after administration of high-dose CRT., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: In this study, procedures were developed to achieve efficient reversible conversion of a clinical linear accelerator (LINAC) and deliver ultrahigh-dose-rate (UHDR) electron or conventional beams to the treatment room isocenter for FLASH radiation therapy., Methods and Materials: The LINAC was converted to deliver UHDR beam within 20 minutes by retracting the x-ray target from the beam's path, positioning the carousel on an empty port, and selecting 10 MV photon beam energy in the treatment console. Dose rate surface and depth dose profiles were measured in solid water phantom at different field sizes with Gafchromic film and an optically stimulated luminescent dosimeter (OSLD). A pulse controller counted the pulses via scattered radiation signal and gated the delivery for a preset pulse count. A fast photomultiplier tube-based Cherenkov detector measured the per pulse beam output at a 2-ns sampling rate. After conversion back to clinical mode, conventional beam output, flatness, symmetry, field size, and energy were measured for all clinically commissioned energies., Results: The surface average dose rates at the isocenter for 1-cm diameter and 1.5-in diameter circular fields and for a jaws-wide-open field were 238 ± 5 Gy/s, 262 ± 5 Gy/s, and 290 ± 5 Gy/s, respectively. The radial symmetry of the beams was within 2.4%, 0.5%, and 0.2%, respectively. The doses from simultaneous irradiation of film and OSLD were within 1%. The photomultiplier tube showed the LINAC required ramp up time in the first 4 to 6 pulses before the output stabilized, after which its stability was within 3%., Conclusions: At the isocenter of the treatment room, 10 MeV UHDR beams were achieved. The beam output was reproducible but requires further investigation of the ramp up time, equivalent to ∼1 Gy, requiring dose monitoring. The UHDR beam can irradiate both small and large subjects to investigate potential FLASH radiobiological effects in minimally modified clinical settings, and the dose rate can be further increased by reducing the source-to-surface distance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Intensity-modulated radiotherapy (IMRT) for cervical cancer yields favorable results in terms of oncological outcomes, acute toxicity, and late toxicity. Limited data are available on clinical results with volumetric modulated arc therapy (VMAT). This study's purpose is to compare outcome and toxicity with VMAT to conventional 3D conformal radiotherapy (3DCRT), giving special consideration to the influence of patient- and treatment-related parameters on side effects., Materials and Methods: Patients with cervical cancer stage I-IVA underwent radiotherapy alone or chemoradiotherapy using 3DCRT (n = 75) or VMAT (n = 30). Survival endpoints were overall survival, progression-free survival, and locoregional control. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Late Effects of Normal Tissues criteria were used for toxicity assessment. Toxicity and patient- and treatment-related parameters were included in a multivariable model., Results: There were no differences in survival rates between treatment groups. VMAT significantly reduced late small bowel toxicity (OR = 0.10, p = 0.03). Additionally, VMAT was associated with an increased risk of acute urinary toxicity (OR = 2.94, p = 0.01). A low body mass index (BMI; OR = 2.46, p = 0.03) and overall acute toxicity ≥grade 2 (OR = 4.17, p < 0.01) were associated with increased overall late toxicity., Conclusion: We demonstrated significant reduction of late small bowel toxicity with VMAT treatment, an improvement in long-term morbidity is conceivable. VMAT-treated patients experienced acute urinary toxicity more frequently. Further analysis of patient- and treatment-related parameters indicates that the close monitoring of patients with low BMI and of patients who experienced relevant acute toxicity during follow-up care could improve late toxicity profiles.

Purpose: New therapeutic options in radiotherapy (RT) are often explored in preclinical in-vivo studies using small animals. We report here on the feasibility of modern megavoltage (MV) linear accelerator (LINAC)-based RT for small animals using easy-to-use consumer 3D printing technology for dosimetric optimization and quality assurance (QA)., Methods: In this study we aimed to deliver 5×2Gy to the half-brain of a rat using a 4MV direct hemi-field X-ray beam. To avoid the beam's build-up in the target and optimize dosimetry, a 1cm thick, customized, 3D-printed bolus was used. A 1:1 scale copy of the rat was 3D printed based on the CT dataset as an end-to-end QA tool. The plan robustness to HU changes was verified. Thermoluminescent dosimeters (TLDs), for both MV irradiations and for kV imaging doses, and a gafchromic film were placed within the phantom for dose delivery verifications. The phantom was designed using a standard treatment planning software, and was irradiated at the LINAC with the target aligned using kV on-board imaging., Results: The plan was robust (dose difference<1% for HU modification from 0 to 250). Film dosimetry showed a good concordance between planned and measured dose, with the steep dose gradient at the edge of the hemi-field properly aligned to spare the contralateral half-brain. In the treated region, the mean TLDs percentage dose differences (±2 SD) were 1.3% (±3.8%) and 0.9% (±1.7%) beneath the bolus. The mean (±2 SD) out-of-field dose measurements was 0.05Gy (±0.02Gy) for an expected dose of 0.04Gy. Imaging doses (2mGy) still spared the contralateral-brain., Conclusions: Use of consumer 3D-printers enables dosimetry optimization and QA assessment for small animals MV RT in preclinical studies using standard LINACS., (Copyright © 2020. Published by Elsevier GmbH.)

Background: Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients., Methods: This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale., Discussion: The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance., Trial Registration: The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. "Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)"., Study Status: Ongoing study. Start of recruitment was December 2019.

Ionization chamber dosimetry is predominantly used for determination of the absorbed dose to water in 60 Co and high-energy radiotherapy photon beams. The most widespread ionization chambers employed for absolute or reference dose determinations in reference conditions are the Farmer-type cylindrical ionization chambers. The Farmer-type ionization chambers have a variety of constructions and materials and their responses vary in the radiation beam. Clinical accelerators, in addition to conventional photon beams with flattening-filter, can also deliver flattening-filter-free (FFF) photon beams. The responses of five different Farmer-type cylindrical ionization chambers were experimentally examined with reference to absorbed dose determination in reference conditions when using the International Atomic Energy Agency (IAEA) - American Association of Physicists in Medicine (AAPM) Technical Reports Series no. 483 (TRS-483) and the IAEA TRS-398 dosimetry protocol in the present investigation. The irradiations were performed using 60 Co and megavoltage photon beams with 6 MV, 15 MV, 6 MV FFF and 10 MV FFF nominal photon energies. The chamber calibrations were performed at different Secondary Standard Dosimetry Laboratories and are traceable to primary standards at different Primary Standard Dosimetry Laboratories. The chambers were also cross-calibrated at our laboratory using 60 Co γ-beam. The variation found in the data regarding the reference dose determination using the various Farmer-type chambers in the photon beams employed was about 1% at maximum. Thus, the selection of the ionization chamber in reference dose determinations may affect the outcomes. The differences in the absorbed dose values were similar in the conventional as well as in the FFF photon beams. For the FFF photon beams the absorbed dose computations were performed using the IAEA-AAPM TRS-483 dosimetry protocol. Two of the ionization chambers used had identical construction but different central electrodes, i.e. graphite versus aluminium. The results obtained using these two chambers show that, in the photon beams examined, the employed correction for the central electrode (p cel ) regarding these two chambers is associated with an inaccuracy which is larger than the calculated uncertainty for this correction. The outcomes found in the present experimental investigation using the various ionization chambers also indicate possible inaccuracy in the employed beam quality correction factors (k Q ) and imply the need for a revision of these factors.

Purpose: Treating deep-seated bulky tumors with traditional single-field Cerrobend GRID-blocks has many limitations such as suboptimal target coverage and excessive skin toxicity. Heavy traditional GRID-blocks are a concern for patient safety at various gantry-angles and dosimetric detail is not always available without a GRID template in user's treatment planning system. Herein, we propose a simple, yet clinically useful multileaf collimator (MLC)-based three-dimensional (3D)-crossfire technique to provide sufficient target coverage, reduce skin dose, and potentially escalate tumor dose to deep-seated bulky tumors., Materials/methods: Thirteen patients (multiple sites) who underwent conventional single-field cerrobend GRID-block therapy (maximum, 15 Gy in 1 fraction) were re-planned using an MLC-based 3D-crossfire method. Gross tumor volume (GTV) was used to generate a lattice pattern of 10 mm diameter and 20 mm center-to-center mimicking conventional GRID-block using an in-house MATLAB program. For the same prescription, MLC-based 3D-crossfire grid plans were generated using 6-gantry positions (clockwise) at 60° spacing (210°, 270°, 330°, 30°, 90°, 150°, therefore, each gantry angle associated with a complement angle at 180° apart) with differentially-weighted 6 or 18 MV beams in Eclipse. For each gantry, standard Millenium120 (Varian) 5 mm MLC leaves were fit to the grid-pattern with 90° collimator rotation, so that the tunneling dose distribution was achieved. Acuros-based dose was calculated for heterogeneity corrections. Dosimetric parameters evaluated include: mean GTV dose, GTV dose heterogeneities (peak-to-valley dose ratio, PVDR), skin dose and dose to other adjacent critical structures. Additionally, planning time and delivery efficiency was recorded. With 3D-MLC, dose escalation up to 23 Gy was simulated for all patient's plans., Results: All 3D-MLC crossfire GRID plans exhibited excellent target coverage with mean GTV dose of 13.4 ± 0.5 Gy (range: 12.43-14.24 Gy) and mean PVDR of 2.0 ± 0.3 (range: 1.7-2.4). Maximal and dose to 5 cc of skin were 9.7 ± 2.7 Gy (range: 5.4-14.0 Gy) and 6.3 ± 1.8 Gy (range: 4.1-11.1 Gy), on average respectively. Three-dimensional-MLC treatment planning time was about an hour or less. Compared to traditional GRID-block, average beam on time was 20% less, while providing similar overall treatment time. With 3D-MLC plans, tumor dose can be escalated up to 23 Gy while respecting skin dose tolerances., Conclusion: The simple MLC-based 3D-crossfire GRID-therapy technique resulted in enhanced target coverage for de-bulking deep-seated bulky tumors, reduced skin toxicity and spare adjacent critical structures. This simple MLC-based approach can be easily adopted by any radiotherapy center. It provides detailed dosimetry and a safe and effective treatment by eliminating the heavy physical GRID-block and could potentially provide same day treatment. Prospective clinical trial with higher tumor-dose to bulky deep-seated tumors is anticipated., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide. It is also the second most common cause of cancer‑associated mortality; it accounted for about 9.2% of all cancer deaths in 2018, most of which were due to resistance to therapy. The main treatment for CRC is surgery, generally associated with chemotherapy, radiation therapy and combination therapy. However, while chemo‑radiotherapy kills differentiated cancer cells, mesenchymal stem‑like cells are resistant to this treatment, and this can give rise to therapy‑resistant tumors. Our previous study isolated T88 primary colon cancer cells from a patient with sporadic colon cancer. These cells exhibited mesenchymal and epithelial features, high levels of epithelial‑to‑mesenchymal transition transcription factors, and stemness markers. In addition, it was revealed that lithium chloride (LiCl), a specific glycogen synthase kinase (GSK)‑3β inhibitor, induced both the mesenchymal‑to‑epithelial transition and differentiation, and also reduced cell migration, stemness features and cell plasticity in these primary colon cancer cells. The aim of the present study was to investigate the effect of LiCl treatment on the viability of primary colon cancer cells exposed to 7 Gy delivered by high‑energy photon beams, which corresponds to 6 megavolts of energy. To achieve this aim, the viability of irradiated T88 cells was compared with that of irradiated T88 cells pre‑treated with LiCl. As expected, it was observed that LiCl sensitized primary colon cancer cells to high‑energy photon irradiation treatment. Notably, the decrease in cell viability was greater with combined therapy than with irradiation alone. To explore the molecular basis of this response, the effect of LiCl on the expression of Bax, p53 and Survivin, which are proteins involved in the apoptotic mechanism and in death escape, was analyzed. The present study revealed that LiCl upregulated the expression of pro‑apoptotic proteins and downregulated the expression of proteins involved in survival. These effects were enhanced by high‑energy photon irradiation, suggesting that LiCl could be used to sensitize colon cancer cells to radiation therapy.

Background: Extraskeletal osteosarcoma is an extremely rare disease, comprising less than 0.1% of all cancers diagnosed in the United States, of which less than 5% occur in the upper extremities. The management of two cases of pediatric upper extremity extraskeletal osteosarcoma is discussed., Case Description: Two children initially noticed painless left upper extremity masses at the ages of 16 and 13, respectively. Following a period of several months, both lesions became symptomatic, necessitating operative intervention, which revealed giant cell-rich extraskeletal osteosarcoma; PET staging following gross total resection revealed no residual or metastatic disease in either patient. After extensive discussion with the patients and family, adjuvant chemotherapy was initiated for one patient, and adjuvant radiation therapy was initiated in both patients., Conclusions: Despite the rarity of these tumors, the importance of radiation therapy has been established by current and ongoing studies such as the Children's Oncology Group study ARST0332. Radiation therapy remains an important component of the multimodality therapy comprising optimal treatment of this disease, despite the relative paucity of long-term outcome data derived from level I evidence., (© 2019 Wiley Periodicals, Inc.)

In intraoperative electron radiation therapy (IOERT) the energy of the electron beam is selected under the conventional assumption of water-equivalent tissues at the applicator end. However, the treatment field can deviate from the theoretic flat irradiation surface, thus altering dose profiles. This patient-based study explored the feasibility of acquiring intraoperative computed tomography (CT) studies for calculating three-dimensional dose distributions with two factors not included in the conventional assumption, namely the air gap from the applicator end to the irradiation surface and tissue heterogeneity. In addition, dose distributions under the conventional assumption and from preoperative CT studies (both also updated with intraoperative data) were calculated to explore whether there are other alternatives to intraoperative CT studies that can provide similar dose distributions. The IOERT protocol was modified to incorporate the acquisition of intraoperative CT studies before radiation delivery in six patients. Three studies were not valid to calculate dose distributions due to the presence of metal artefacts. For the remaining three cases, the average gamma pass rates between the doses calculated from intraoperative CT studies and those obtained assuming water-equivalent tissues or from preoperative CT studies were 73.4% and 74.0% respectively. The agreement increased when the air gap was included in the conventional assumption (98.1%) or in the preoperative CT images (98.4%). Therefore, this factor was the one mostly influencing the dose distributions of this study. Our experience has shown that intraoperative CT studies are not recommended when the procedure includes the use of shielding discs or surgical retractors unless metal artefacts are removed. IOERT dose distributions calculated under the conventional assumption or from preoperative CT studies may be inaccurate unless the air gap (which depends on the surface irregularities of the irradiated volume and on the applicator pose) is included in the calculations., Competing Interests: The authors have declared that no competing interests exist.

Background: Multimodality treatment for head and neck cancer leads to substantial functional and esthetic impairment mainly manifested as radiation-induced skin fibrosis (RIF) in combination with volumetric defects and reduction in neck mobility. This study assessed the impact of lipotransfer as part of secondary surgical procedure(s) in patients treated for head and neck malignancies., Methods: Retrospective analysis was performed between 2005 and 2016. All patients with a history of head and neck malignancy, multimodal treatment including at least surgery or radiotherapy, and at least 2-year disease-free survival were included. Thirty-eight patients (22 men, 16 women) matched the inclusion criteria., Results: Thirty seven (97%) reported esthetic and functional improvements in their RIF and volumetric defect at follow-up of 32 months. Major improvement in esthetic and functional outcome was reported by 24 (63%) patients and surgeons and minor by 13 patients and surgeons (34%) without causing any complications. Lipotransfer was also found to significantly improve patient's psychological health postoperatively as showed by significant improvements in Derriford Appearance Scale (DAS24), Short Form Health Survey (SF-36), and University of Washington Quality of Life Questionnaire (UW-QOL V4) scores (P < .001)., Conclusions: Lipotransfer is effective for volume restoration and treating scar and RIF from head and neck defects., (© 2019 Wiley Periodicals, Inc.)

Pluridirectional high-energy agile scanning electronic radiotherapy (PHASER) is next-generation medical linac technology for ultra-rapid highly conformal image-guided radiation, fast enough to "freeze" physiological motion, affording improved accuracy, precision, and potentially superior FLASH radiobiological therapeutic index. Designed for compactness, economy, and clinical efficiency, it is also intended to address barriers to global access to curative radiotherapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to investigate how common temporomandibular disorder (TMD) symptoms are among head and neck cancer (HNC) patients before and after oncological treatment., Methods: Eighty-nine patients with HNC receiving radiotherapy were enrolled in the study. Patients were examined before radiotherapy and at 6 and 12 months after radiotherapy to evaluate the function and tenderness of the temporomandibular jaw and the muscles of mastication as well as the patient-reported symptoms., Results: At 6 months after radiotherapy, there was a large increase in the number of patients reporting problems with opening their mouth, fatigue, stiffness, and pain of the jaw. Sixty-eight percent of the patients had symptoms of TMD before oncological treatment and 94% and 81% had symptoms at the 6- and 12-month follow-up, respectively., Conclusion: The signs and symptoms of TMD escalate after radiotherapy, with symptoms peaking at 6 months after radiotherapy. Most commonly, patients suffer from restricted mouth opening, stiffness, fatigue, and pain of the jaw., (© 2019 Wiley Periodicals, Inc.)

Introduction: To assess the impact of primary and secondary therapies for high- and intermediate-risk prostate cancer on health-related quality of life (HRQoL)., Materials and Methods: A prospective study was initiated in 2007 at Center for Prostate Disease Research Multicenter National Database sites. Longitudinal patterns in HRQoL from baseline (pre-treatment) to 5 years post-diagnosis were examined for patients with high- and intermediate-risk prostate cancer, treated by radical prostatectomy (RP) or external beam radiation therapy (EBRT). Change in HRQoL was modeled using linear regression models fit with generalized estimating equations. The probability of maintaining HRQoL was compared between patients receiving RP only versus RP with secondary treatment., Results: Of 445 men with high- and intermediate-risk prostate cancer, 228 underwent RP and 143 had EBRT± androgen deprivation therapy (ADT). Fifty received secondary therapy (EBRT and/or ADT or chemotherapy) after RP. RP patients showed a greater decline over time in sexual function and bother and urinary function compared to EBRT±ADT patients. Patients who had secondary therapy after RP were less likely to maintain their HRQoL compared to those who had RP alone. These differences were most pronounced for sexual and hormonal function., Conclusions: Prostate cancer patients experience significant declines in HRQoL after primary therapy. Additional secondary therapy after RP, in the form of EBRT and/or ADT, appears to be responsible for further deterioration in HRQoL outcomes.

Conventional radiotherapy is mainly applied by linear accelerators. Although linear accelerators provide dual (electron/photon) radiation beam modalities, both of them are intrinsically produced by a megavoltage electron current. Modern radiotherapy treatment techniques are based on suitable devices inserted or attached to conventional linear accelerators. Thus, precise control of delivered beam becomes a main key issue. This work presents an integral description of electron beam deflection control as required for novel radiotherapy technique based on convergent photon beam production. Theoretical and Monte Carlo approaches were initially used for designing and optimizing device´s components. Then, dedicated instrumentation was developed for experimental verification of electron beam deflection due to the designed magnets. Both Monte Carlo simulations and experimental results support the reliability of electrodynamics models used to predict megavoltage electron beam control., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The out-of-field dose in radiation therapy is a growing concern in regards to the late side-effects and secondary cancer induction. In high-energy x-ray therapy, the secondary neutrons generated through photonuclear reactions in the accelerator are part of this secondary dose. The neutron dose is currently not estimated by the treatment planning system while it appears to be preponderant for distances greater than 50 cm from the isocenter. Monte Carlo simulation has become the gold standard for accurately calculating the neutron dose under specific treatment conditions but the method is also known for having a slow statistical convergence, which makes it difficult to be used on a clinical basis. The neutron track length estimator, a neutron variance reduction technique inspired by the track length estimator method has thus been developped for the first time in the Monte Carlo code GATE to allow a fast computation of the neutron dose in radiotherapy. The details of its implementation, as well as the comparison of its performances against the analog MC method, are presented here. A gain of time from 15 to 400 can be obtained by our method, with a mean difference in the dose calculation of about 1% in comparison with the analog MC method.

AAPM Report 142 recommends and the State of Ohio requires that the imaging dose be quantified in radiotherapy applications. Using the TG51 dose calibration protocol for MV Imaging dose measurement requires knowledge of the k Q parameter for the beam quality and the ionization chamber type under investigation. The %dd(10) x of the Varian TrueBeam 2.5 MV imaging beam falls outside the range of the available data for the calculation of the k Q value. Due to the similarities of the 2.5 MV imaging beam and the 60 Co beam, we and others made the assumption that k Q = 1.0 in TG51 calculations. In this study, we used the TG21 and TG51 calibration protocols in conjunction to validate that k Q = 1.0 for the 2.5 MV imaging beam using a PTW 30013 farmer chamber. Standard measurements for TG51 absolute dosimetry QA were performed at 100 cm SSD, 10 cm depth, 10 × 10 field size, delivering 100 Monitor Units to a waterproof Farmer Chamber (PTW TN30013) for both 2.5 and 6 MV. Both the TG21 and TG51 formalisms were used to calculate the dose to water per MU at d max (D w /MU) for the 6 MV beam. The calculated outputs were 1.0005 and 1.0004 cGy/MU respectively. The TG21 formalism was then used to calculate (D w /MU) for the 2.5 MV imaging beam. This value was then used in the TG51 formalism to find k Q for the 2.5 MV imaging beam. A k Q value of 1.00 ± 0.01 was calculated for 2.5 MV using this method., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Prostate-specific antigen nadir (nPSA) after radiotherapy for localized prostate cancer has been investigated as a predictor. However, nPSA usually requires several years, limiting its clinical utility. We investigated the significance of nPSA within 12 months (nPSA12) after low-dose-rate prostate brachytherapy (LDR-PB) or external beam radiotherapy (EBRT) on treatment outcomes. Between 2006 and 2014, 663 patients with prostate cancer were treated with LDR-PB or EBRT at two institutions. Four hundred and seventy-four men received LDR-PB and 189 men received EBRT, without androgen deprivation therapy. The Kaplan-Meier method was used for biochemical failure (BF)-free survival (BFFS) and distant metastasis (DM)-free survival (DMFS) analyses, and multivariable Cox regression analysis was performed. The median follow-up was 61.3 months. The median nPSA12 in the LDR-PB and EBRT cohorts was 0.7 and 1.0 ng/mL, respectively. The 7-year BFFS and DMFS rates in LDR-PB patients with nPSA12 ≤ 0.7 ng/mL were 99.1% and 99.5%, respectively; when nPSA12 was >0.7 ng/mL, they were 90.2% and 94.8%, respectively. In EBRT patients with nPSA12 ≤ 1.0 ng/mL, BFFS and DMFS rates were 85.4% and 98.5%, respectively; when nPSA12 was >1.0 ng/mL, they were 67.1% and 87.2%, respectively. nPSA12 was an independent predictor of BF and DM in both cohorts (LDR-PB, P = 0.004 and 0.020, respectively; EBRT, P = 0.005 and 0.041, respectively). The nPSA12 after LDR-PB or EBRT is significantly associated with treatment outcomes of prostate cancer. Higher nPSA12 may identify patients at high risk of relapse who might benefit from salvage treatment., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

For the ionometric determination of the absorbed dose to water, D w , in high-energy electron beams from a clinical accelerator, beam quality dependent correction factors, k Q , are required. By using a water calorimeter, these factors can be determined experimentally and potentially with lower standard uncertainties than those of the calculated k Q factors, which are tabulated in various dosimetry protocols. However, one of the challenges of water calorimetry in electron beams is the small measurement depths in water, together with the steep dose gradients present especially at lower energies. In this investigation, water calorimetry was implemented in electron beams to determine k Q factors for different types of cylindrical and plane-parallel ionization chambers (NE2561, NE2571, FC65-G, TM34001) in 10 cm  ×  10 cm electron beams from 6 MeV to 20 MeV (corresponding beam quality index R 50 ranging from 1.9 cm to 7.5 cm). The measurements were carried out using the linear accelerator facility of the Physikalisch-Technische Bundesanstalt. Relative standard uncertainties for the k Q factors between 0.50% for the 20 MeV beam and 0.75% for the 6 MeV beam were achieved. For electron energies above 8 MeV, general agreement was found between the relative electron energy dependencies of the k Q factors measured and those derived from the AAPM TG-51 protocol and recent Monte Carlo-based studies, as well as those from other experimental investigations. However, towards lower energies, discrepancies of up to 2.0% occurred for the k Q factors of the TM34001 and the NE2571 chamber.

After a brief history of the major evolutions of positron emission tomography since its introduction in 1972, this article reviews the recent improvements and novel trends in positron emission tomography with a special focus on the time of flight that is currently the major research topic. Novel emerging acquisition modalities, such as dual tracer acquisition, inline hadron therapy dose imaging and yttrium-90 imaging are reviewed.

This study deals with the role of texture analysis as a predictive factor of radiation-induced insufficiency fractures in patients undergoing pelvic radiation., Introduction: This study aims to assess the texture analysis (TA) of computed tomography (CT) simulation scans as a predictive factor of insufficiency fractures (IFs) in patients with pelvic malignancies undergoing radiation therapy (RT)., Methods: We performed an analysis of patients undergoing pelvic RT from January 2010 to December 2014, 24 of whom had developed pelvic bone IFs. We analyzed CT-simulation images using ImageJ macro software and selected two regions of interest (ROIs), which are L5 body and the femoral head. TA parameters included mean (m), standard deviation (SD), skewness (sk), kurtosis (k), entropy (e), and uniformity (u). The IFs patients were compared (1:2 ratio) with controlled patients who had not developed IFs and matched for sex, age, menopausal status, type of tumor, use of chemotherapy, and RT dose. A reliability test of intra- and inter-reader ROI TA reproducibility with the intra-class correlation coefficient (ICC) was performed. Univariate and multivariate analyses (logistic regression) were applied for TA parameters observed both in the IFs and the controlled groups., Results: Inter- and intra-reader ROI TA was highly reproducible (ICC > 0.90). Significant TA parameters on paired t test included L5 m (p = 0.001), SD (p = 0.002), k (p = 0.006), e (p = 0.004), and u (p = 0.015) and femoral head m (p < 0.001) and SD (p = 0.001), whereas on logistic regression analysis, L5 e (p = 0.003) and u (p = 0.010) and femoral head m (p = 0.027), SD (p = 0.015), and sex (p = 0.044)., Conclusions: In our experience, bone CT TA could be correlated to the risk of radiation-induced IFs. Studies on a large patient series and methodological refinements are warranted.

Purpose: Melanoma is mainly treated by surgery and rarely with radiation because of the high radioresistance of this tumor. Nevertheless, radiotherapy is the preferred treatment modality for unresectable lesions and avoiding cosmetic disfigurement caused by surgical excision. This study investigated the therapeutic advantage of gold nanoparticles (AuNPs) for kilovoltage X-ray treatment of melanoma., Materials and Methods: Commercial AuNPs were evaluated for cytotoxicity and cellular internalization. The sensitivity of human skin melanoma cells to 150 and 450 kVp X-ray exposure was assessed in terms of clonogenicity with or without spherical AuNP treatment., Results: AuNP treatment elicited dose enhancement effect on melanoma cells exposed to kilovoltage X-rays. Treatment with 320 μM 50 nm AuNPs before exposure to 150 kVp X-rays at 2 Gy resulted in clonogenic cell death equivalent to that caused by 4.3 Gy X-rays without AuNP treatment., Conclusion: AuNPs of 50 nm in size can regulate melanoma cells in kilovoltage X-ray treatment by functioning as dose-enhancement agent and thus improving radioresponse of the cells. Melanomas of stages T1-T3 gain therapeutic benefits from 150 kVp X-ray treatment.

Objectives/hypothesis: The purpose of this study was to report the outcomes of a retrospective consecutive cohort study of patients with T1N0M0 glottic carcinoma treated with 4-MV or 6-MV radiotherapy., Study Design: Retrospective case-control study., Methods: This was a retrospective review of all patients with T1N0M0 glottic carcinoma treated with radiotherapy between January 2000 and December 2012 in the Department of Radiation Oncology at National Cancer Center Singapore. A total of 124 patients were included. Clinical endpoints of interest were: local control (LC), overall survival (OS), and disease-specific survival (DSS). Other prognostic factors for LC were also analyzed: age, gender, smoking status, T substage, dose fraction, field size, anterior commissure involvement, total dose, and overall treatment time., Results: Six-megavolt photon radiotherapy was used in 73 patients and 4-MV photon radiotherapy in 51 patients. Median follow-up was 4.9 years. The 5-year LC and OS were as follows: 4 MV, 91.6% and 83.4%; 6 MV, 88.8% and 82.8%; and the 5-year LC, OS, and DSS for all patients were 90.4%, 83.3%, and 98.3%. There was no significant difference in LR and OS between 4-MV and 6-MV radiotherapy (P = .92, P = .16, respectively). In the univariate analysis of LC, none of the prognostic factors was statistically significant. Twenty patients (23%) developed second primary cancers, the majority in the lungs., Conclusions: Six-megavolt photon radiotherapy yields comparable results to 4-MV photons. Bolus and computed tomographic simulation are useful to ensure adequate dose coverage of target volume. Follow-up postradiotherapy should incorporate chest imaging, smoking cessation advice, and thyroid function test., Level of Evidence: 4 Laryngoscope, 127:1061-1067, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Gold nanoparticles modified by thio-glucose are believed to increase the toxicity of radiotherapy in human malignant cells. We report the effect of thio-glucose bound gold nanoparticles (Glu-G nanoparticles), 16 nm in size, on two human lung (QU-DB) and breast (MCF7) cancer cell lines combined with kilo and megavoltage X-rays., Materials and Methods: The shape and surface characteristics, the size distribution and light absorption spectrum of the prepared nanoparticles were measured by transmission electron microscopy, dynamic light scattering, and ultraviolet-visible spectrophotometry, respectively. The cell uptake was assayed using the atomic absorption spectrometry. Mitochondrial activity, colony formation, and comet assays were applied to assess and compare the enhanced radiotoxicity of 100 KV and 6 MV X-rays, when combined with Glu-G nanoparticles., Results: Glu-G nanoparticles had no significant toxicity for MCF7 and QU-DB cells up to 100 micromolar concentration. Compared to radiation alone, the intracellular uptake of Glu-G nanoparticles resulted in increased inhibition of cell proliferation by 64.1% and 38.7% for MCF7 cells, and 64.4% and 32.4% for QU-DB cells by 100 kVp and 6 MV X-rays, respectively. Comet assay confirmed an increase of DNA damage as a result of combination of 6 MV photons with Glu-G nanoparticles., Conclusion: Glu-G nanoparticles have remarkable potential for enhancing radiotoxicity of both low and high energy photons in MCF7 and QU-DB cells.

Purpose: Gold nanoparticles (GNP) act as a radiosensitizer in radiation therapy. However, recent studies have shown contradictory evidence in terms of radiosensitization in the presence of GNP combined with X-ray megavoltage energy (MV) on different cell types. In this study, the effect of GNP on radiosensitization enhancement of HT-29 human colorectal cancer cells at MV X-ray energy was evaluated., Materials and Methods: The cytotoxicity and radiosensitization of GNP were evaluated in HT-29 human colorectal cancer cells by MTS-assay and multiple MTS-assay, respectively. Cellular uptake was assayed using graphite furnace atomic absorption spectrometry (GFAAS). Apoptosis and cell cycle progression were determined by an Annexin V-FITC/propidium iodide (PI) kit and PI/RNase solution with flow cytometry, respectively., Results: Results showed that the cell viability of the HT-29 cells was not influenced by exposure to different concentrations of GNP (10-100 μM). GNP alone did not affect the cell cycle progression and apoptosis. In contrast, GNP, in combination with radiation (9 MV), induced more apoptosis. The interaction of GNP with MV energy resulted in a significant radiosensitization enhancement compared with irradiation alone., Conclusion: It was concluded that GNP may work as bio-inert material on HT-29 cancer cells and their enhancement of radiosensitization may be due to increase in the absorbed irradiation dose.

Purpose: Gold nanoparticles (GNP) have significant potential as radiosensitizer agents due to their distinctive properties. Several studies have shown that the surface modification of nanoparticles with methyl polyethylene glycol (mPEG) can increase their biocompatibility. However, the present study investigated the radiosensitization effects of mPEG-coated GNP (mPEG-GNP) in B16F10 murine melanoma cells under irradiation of 6 MeV Electron beam., Materials and Methods: The synthesized GNP were characterized by UV-Visible spectroscopy, dynamic light scattering, transmission electron microscopy, and zeta potential. Enhancement of radiosensitization was evaluated by the clonogenic assay at different radiation doses of megavoltage electron beams., Results: It was observed that mPEG-GNP with a hydrodynamic size of approximately 50 nm are almost spherical and cellular uptake occurred at all concentrations. Both proliferation efficiency and survival fraction decreased with increasing mPEG-GNP concentration. Furthermore, significant GNP sensitization occurred with a maximum dose enhancement factor of 1.22 at a concentration of 30 μM., Conclusions: Pegylated-GNP are taken up by B16F10 cancer cells and cause radiosensitization in the presence of 6 MeV electrons. The radiosensitization effects of GNP may probably be due to biological processes. Therefore, the underlying biological mechanisms beyond the physical dose enhancement need to be further clarified.

Total-skin electron beam therapy (TSEBT) is one of most effective treatments that has been used for cutaneous T-cell lymphoma. Low-dose TSEBT regimens (10-12 Gy) appear to be an effective alternative to conventional-dose TSEBT (30-36 Gy), yielding short-term remission of cutaneous manifestations with minimal toxicity. TSEBT can be administered to patients any time after a diagnosis of mycosis fungoides (MF). Patients requiring rapid relief from cutaneous lesions or symptoms may particularly benefit from TSEBT as an initial therapy. Radiotherapy (RT) dose, boost radiation delivery, maintenance treatment, and radiation tolerability may enhance remission rates and improve relapse-free survival following TSEBT. In addition, salvage local RT or TSEBT may be safely applied with high effectiveness. In this review, we focus on the use of TSEBT in patients with several forms of primary cutaneous T-cell lymphoma, and highlight the potential of low-dose TSEBT as part of a promising therapeutic approach., (© 2017 S. Karger GmbH, Freiburg.)

Aim: The aim of this study was to assess the therapeutic effect of intraoperative radiotherapy, describe the method and examine the results of our experience., Background: Breast conserving therapy has recently become a standard treatment modality in patients with early invasive cancer. Radiotherapy, along with surgery, is an integral part of such treatment. The important thing of radiotherapy is to deliver a high dose to the tumour bed. One of the methods is the intraoperative radiotherapy., Materials and Methods: The analysis comprised 41 breast cancer patients treated with breast conserving surgery. Patient's range age was 35-80 years. Cancer type distribution inlcuded: 95% ductal carcinoma, 5% other carcinoma. Applicator size: 4 cm. (12%), 5 cm. (64%), 6 cm. (17%), 7 cm. (7%). Electron energies: 6 MeV (22%), 8 MeV (56%), 10 MeV (22%). Intraoperative radiation therapy was delivered in the operating theatre during surgery. After that, all patients were treated with whole breast irradiation., Results: 41 patients treated with IORT procedures completed. In general there were no severe postoperative complications and we did not detect tumor recurrence in any patient even if the time elapsed from the treatment is still short., Conclusions: Due to its exceptional physical and radiobiological properties, intraoperative radiation therapy can be a good alternative to other methods of boosting dose to the postoperative site in management., Key Words: Breast cancer, IORT, intraoperative radiotherapy, Surgery.

High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40-55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction., Competing Interests: D.L.P. has filed for a patent that is relevant to this work. All other authors do not report competing financial or non-financial interest relevant to this work.

Background and Purpose: Aside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase of the relative biological effectiveness (RBE) of antiprotons near the end of range. We have performed the first-ever direct measurement of the RBE of antiprotons both at rest and in flight., Materials and Methods: Experimental data were generated on the RBE of an antiproton beam entering a tissue-like target consisting of V79 cells embedded in gelatin with an energy providing a range of approximately 10cm., Results: The RBE in the entrance channel (the "plateau") is only slightly above the value for a comparable proton beam, and remains low until the proximal edge of the spread-out Bragg peak (SOBP). A steep increase of RBE is seen starting from the onset of the SOBP., Conclusions: This paper reports the final results of the experiment AD-4/ACE at CERN on the first-ever direct measurement of RBE of antiprotons and constitutes the first step toward developing treatment plans., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood., Methods and Materials: Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control and on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis., Results: MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT., Conclusions: These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Out-of-field doses from radiotherapy can cause harmful side effects or eventually lead to secondary cancers. Scattered doses outside the applicator field, neutron source strength values, and neutron dose equivalents have not been broadly investigated for high-energy electron beams. To better understand the extent of these exposures, we measured out-of-field dose characteristics of electron applicators for high-energy electron beams on two Varian 21iXs, a Varian TrueBeam, and an Elekta Versa HD operating at various energy levels. Out-of-field dose profiles and percent depth-dose curves were measured in a Wellhofer water phantom using a Farmer ion chamber. Neutron dose was assessed using a combination of moderator buckets and gold activation foils placed on the treatment couch at various locations in the patient plane on both the Varian 21iX and Elekta Versa HD linear accelerators. Our findings showed that out-of-field electron doses were highest for the highest electron energies. These doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. The Elekta linear accelerator had higher electron out-of-field doses than the Varian units examined, and the Elekta dose profiles exhibited a second dose peak about 20 to 30 cm from central-axis, which was found to be higher than typical out-of-field doses from photon beams. Electron doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. With respect to neutron dosimetry, Q values and neutron dose equivalents increased with electron beam energy. Neutron contamination from electron beams was found to be much lower than that from photon beams. Even though the neutron dose equivalent for electron beams represented a small portion of neutron doses observed under photon beams, neutron doses from electron beams may need to be considered for special cases.

In a radiotherapy facility, safety in areas next to the treatment room can be of concern when irradiating downward due to oblique x-ray transmission through the floor and/or walls, especially in areas immediately adjacent or underground. Even when there is no basement underneath, a usual conservative solution is to build a thick concrete slab as the base for the treatment room. Of course, this implies deeper soil excavation and higher associated costs. As a convenient alternative, the limiting walls can be buried a certain depth below floor level to shield oblique, downward irradiation. Besides, for space considerations, laminated barriers are usually employed, and some additional shielding to the floor may be required (L-shaped barriers). In this work, the author introduces an analytical method for calculating the required wall penetration below floor level or, alternatively, the additional floor shielding for L-shaped barriers, taking into account in either case the attenuation properties of the earth underneath the vault. Interestingly, the required penetration depth for a given wall barrier (primary or secondary), relative to a reference thickness, is only a function of basic attenuation data. Likewise, for a laminated, lead-concrete barrier, the required dimensions depend on the relative amount of lead used for the wall and on the corresponding attenuation data. The shielding design criteria developed in this work to protect underground nearby sites is conservative in nature, yet it yields optimal shield dimensions for wall footing and for wall-floor shielding, avoiding the need to construct oversized concrete slab floors.

This study evaluated absorbed dose measurements in the build-up region of conventional (FF) versus flattening filter-free (FFF) photon beams. The absorbed dose in the build-up region of static 6 and 10MV FF and FFF beams was measured using radiochromic film and extrapolation chamber dosimetry for single beams with a variety of field sizes, shapes and positions relative to the central axis. Removing the flattening filter generally resulted in slightly higher relative build-up doses. No considerable impact on the depth of maximum dose was found., (Copyright © 2016. Published by Elsevier GmbH.)

Purpose Microbeam Radiotherapy (MRT) is a promising pre-clinical cancer therapy which represents a radical departure from the radiobiological principles of conventional radiotherapy (CRT). In order to translate MRT to human clinical trials, robust normal tissue toxicity data are required. This review summarizes the normal tissue effects reported by pre-clinical MRT animal studies and compares these data to clinical recommendations in CRT. Conclusion Few pre-clinical studies are specifically designed to evaluate the dose-response of normal tissue to MRT. However, it remains clear that a range of normal tissues can tolerate peak MRT doses at least an order of magnitude higher than CRT. Furthermore, the dose deposited in the valley regions, predominantly determined by microbeam spacing, has a greater influence on the normal tissue response to MRT compared to the peak regions. The development of a new normal tissue complication probability model for MRT, in conjunction with a treatment planning system, will be pivotal in the collection of robust normal tissue toxicity data and the translation of MRT to clinical use.

Objective: The present study compares in silico treatment plans using hybrid plan technique during hypofractionated radiation of mammary carcinoma with simultaneous integrated boost (SIB). The influence of 6 MV photon radiation in flattening filter free (FFF) mode against the clinical standard flattening filter (FF) mode is to be examined., Patients and Methods: RT planning took place with FF and FFF radiation plans for 10 left-sided breast cancer patients. Hybrid plans were realised with two tangential IMRT fields and one VMAT field. The dose prescription was in line with the guidelines in the ARO-2010-01 study. The dosimetric verification took place with a manufacturer-independent measurement system., Results: Required dose prescriptions for the planning target volumes (PTV) were achieved for both groups. The average dose values of the ipsi- and contralateral lung and the heart did not differ significantly. The overall average incidental dose to the left anterior descending artery (LAD) of 8.24 ± 3.9 Gy in the FFF group and 9.05 ± 3.7 Gy in the FF group (p < 0.05) were found. The dosimetric verifications corresponded to the clinical requirements. FFF-based RT plans reduced the average treatment time by 17 s/fraction., Conclusion: In comparison to the FF-based hybrid plan technique the FFF mode allows further reduction of the average LAD dose for comparable target volume coverage without adverse low-dose exposure of contralateral structures. The combination of hybrid plan technique and 6 MV photon radiation in the FFF mode is suitable for use with hypofractionated dose schemes. The increased dose rate allows a substantial reduction of treatment time and thus beneficial application of the deep inspiration breath hold technique.

Background: We compared different image-guidance (IG) strategies for prostate cancer with high-precision IG intensity-modulated radiation therapy (IMRT) using TomoTherapy® (Accuray Inc., Madison, WI, USA) and linear accelerator (LINAC)-IMRT and their impact on planning target volume (PTV) margin reduction. Follow-up data showed reduced bladder toxicity in TomoTherapy patients compared to LINAC-IMRT. The purpose of this study was to quantify whether the treatment delivery technique and decreased margins affect reductions in bladder toxicity., Patients and Methods: Setup corrections from 30 patients treated with helical TomoTherapy and 30 treated with a LINAC were analyzed. These data were used to simulate three IG protocols based on setup error correction and a limited number of imaging sessions. For all patients, gastrointestinal (GI) and genitourinary (GU) toxicity was documented and correlated with the treatment delivery technique., Results: For fiducial marker (FM)-based RT, a margin reduction of up to 3.1, 3.0, and 4.8 mm in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively, could be achieved with calculation of a setup correction from the first three fractions and IG every second day. Although the bladder volume was treated with mean doses of 35 Gy in the TomoTherapy group vs. 22 Gy in the LINAC group, we observed less GU toxicity after TomoTherapy., Conclusion: Intraprostate FMs allow for small safety margins, help decrease imaging frequency after setup correction, and minimize the dose to bladder and rectum, resulting in lower GU toxicity. In addition, IMRT delivered with TomoTherapy helps to avoid hotspots in the bladder neck, a critical anatomic structure associated with post-RT urinary toxicity.

Aim: To compare simultaneous integrated boost plans for intensity-modulated proton therapy (IMPT), helical tomotherapy (HT), and RapidArc therapy (RA) for patients with head and neck cancer., Patients and Methods: A total of 20 patients with squamous cell carcinoma of the head and neck received definitive chemoradiation with bilateral (n = 14) or unilateral (n = 6) neck irradiation and were planned using IMPT, HT, and RA with 54.4, 60.8, and 70.4 GyE/Gy in 32 fractions. Dose distributions, coverage, conformity, homogeneity to planning target volumes (PTV)s and sparing of organs at risk and normal tissue were compared., Results: All unilateral and bilateral plans showed excellent PTV coverage and acceptable dose conformity. For unilateral treatment, IMPT delivered substantially lower mean doses to contralateral salivary glands (< 0.001-1.1 Gy) than both rotational techniques did (parotid gland: 6-10 Gy; submandibular gland: 15-20 Gy). Regarding the sparing of classical organs at risk for bilateral treatment, IMPT and HT were similarly excellent and RA was satisfactory., Conclusion: For unilateral neck irradiation, IMPT may minimize the dry mouth risk in this subgroup but showed no advantage over HT for bilateral neck treatment regarding classical organ-at-risk sparing. All methods satisfied modern standards regarding toxicity and excellent target coverage for unilateral and bilateral treatment of head and neck cancer at the planning level.

Background and Purpose: To assess the quality of very-high energy electron (VHEE) scanning pencil beam radiation therapy in relation to state-of-the-art volumetric modulated arc therapy (VMAT) and to determine the extent of its application., Material and Methods: We planned five clinical cases with VHEE scanning pencil beams of 100 and 120MeV, equally distributed in a coplanar arrangement around the patient. The clinical cases included acoustic neuroma, and liver, lung, esophagus, and anal cancer cases. We performed Monte Carlo (MC) dose calculations and we optimized the dose in a research version of RayStation. VHEE plan performance was compared against clinically delivered VMAT., Results: With equal target coverage, mean doses to organs at risk (OARs) were on average 22% lower for the VHEE plans compared to the VMAT plans. Dose conformity was equal or superior compared to the VMAT plans and integral dose to the body was in average 14% (9-22%) lower for the VHEE plans., Conclusions: The dosimetric advantages of VHEE as demonstrated for a variety of clinical cases, combined with the theoretical ultra fast treatment delivery, afford VHEE scanning pencil beam radiotherapy a suitable and potentially superior alternative for cancer radiotherapy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures., Patients and Methods: From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of  4 Gy twice a week, or 12 fractions of  3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week., Results: The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted electron fields (p = 0.000); in 15 of 16 patients fractures were located in the abutment regions. The other significant predictive factors for rib fractures were a higher fraction dose (p = 0.040), large RT fields, and treatment before the year 2000., Discussion and Conclusion: ReRT + HT results in long-term LC. The majority of rib fractures were located in the photon/electron abutment area, emphasizing the disadvantage of field overlap. Large abutted photon/electron fields combined with 4 Gy fractions increase the number of rib fractures in this study group. However, as these factors were highly correlated no relative importance of the individual factors could be estimated. Increasing the number of HT sessions a week does not increase the risk of rib fractures.