Electron Radiotherapy Research Articles

Dosimetry Evaluation of Treatment Planning Systems in Patient-Specific 3D Printed Anthropomorphic Phantom for Breast Cancer after Mastectomy using a Single-Beam 3D-CRT Technique for Megavoltage Electron Radiation Therapy.

The patient-specific 3D printed anthropomorphic phantom is used for breast cancer after mastectomy developed by the laboratory of medical physics and biophysics, Department of Physics, Institut Teknologi Sepuluh Nopember, Indonesia. This phantom is applied to simulate and measure the radiation interactions occurring in the human body either using the treatment planning system (TPS) or direct measurement with external beam therapy (EBT) 3 film. This study aimed to provide dose measurements in the patient-specific 3D printed anthropomorphic phantom using a TPS and direct measurements using single-beam three-dimensional conformal radiation therapy (3DCRT) technique with electron energy of 6 MeV. In this experimental study, the patient-specific 3D printed anthropomorphic phantom was used for post-mastectomy radiation therapy. TPS on the phantom was conducted using a 3D-CRT technique with RayPlan 9A software. The single-beam radiation was delivered to the phantom with an angle perpendicular to the breast plane at 337.3° at 6 MeV with a total prescribed dose of 5000 cGy/25 fractions with 200 cGy per fraction. The doses at planning target volume (PTV) and right lung confirmed a non-significant difference both for TPS and direct measurement with P-values of 0.074 and 0.143, respectively. The dose at the spinal cord showed statistically significant differences with a P-value of 0.002. The result presented a similar skin dose value using either TPS or direct measurement. The patient-specific 3D printed anthropomorphic phantom for breast cancer after mastectomy on the right side has good potential as an alternative to the evaluation of dosimetry for radiation therapy.

On the potential biological impact of radiation-induced acoustic emissions during ultra-high dose rate electron radiotherapy: a preliminary study

Ionizing radiation pulses delivered at ultra-high dose rates in emerging FLASH radiotherapy can result in high-intensity low-frequency thermoacoustic emissions that may have a biological impact. This study aims at providing insights into the thermoacoustic emissions expected during FLASH radiotherapy and their likelihood of inducing acoustic cavitation. The characteristics of acoustic waves induced by the energy deposition of a pulsed electron beam similar to previous pre-clinical FLASH radiotherapy studies and their propagation in murine head-like phantoms are investigated in-silico. The results show that the generated pressures are sufficient to produce acoustic cavitation due to resonance in the irradiated object. It suggests that thermoacoustics may, in some irradiation scenarios, contribute to the widely misunderstood FLASH effect or cause adverse effects if not taken into account at the treatment planning stage.

Multidisciplinary Approach to the Diagnosis and Therapy of Mycosis Fungoides

Mycosis fungoides is the most common primary cutaneous T-cell lymphoma, characterized by skin-homing CD4+ T cells derivation, indolent course, and low-grade of malignancy. Mycosis fungoides's classic type typically onsets with cutaneous erythematous patches, plaque, and tumor. In WHO-EORTC classification, folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin are recognized as distinct variants of mycosis fungoides, because of their clinical and histological features, behavior, and /or prognosis. Mycosis fungoides often shows diagnostic difficulties, due to its absence of specific features and lesional polymorphism. A patient's treatment requires staging. In about 10% of cases, mycosis fungoides can progress to lymph nodes and internal organs. Prognosis is poor at advanced stage and management needs a multidisciplinary team approach. Advanced stage disease including tumors, erythroderma, and nodal, visceral, or blood involvement needs skin directed therapy associated with systemic drugs. Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.

Auto-commissioning of a Monte Carlo electron beam model with application to photon MLC shaped electron fields

Objective. Presently electron beam treatments are delivered using dedicated applicators. An alternative is the usage of the already installed photon multileaf collimator (pMLC) enabling efficient electron treatments. Currently, the commissioning of beam models is a manual and time-consuming process. In this work an auto-commissioning procedure for the Monte Carlo (MC) beam model part representing the beam above the pMLC is developed for TrueBeam systems with electron energies from 6 to 22 MeV. Approach. The analytical part of the electron beam model includes a main source representing the primary beam and a jaw source representing the head scatter contribution each consisting of an electron and a photon component, while MC radiation transport is performed for the pMLC. The auto-commissioning of this analytical part relies on information pre-determined from MC simulations, in-air dose profiles and absolute dose measurements in water for different field sizes and source to surface distances (SSDs). For validation calculated and measured dose distributions in water were compared for different field sizes, SSDs and beam energies for eight TrueBeam systems. Furthermore, a sternum case in an anthropomorphic phantom was considered and calculated and measured dose distributions were compared at different SSDs. Main results. Instead of the manual commissioning taking up to several days of calculation time and several hours of user time, the auto-commissioning is carried out in a few minutes. Measured and calculated dose distributions agree generally within 3% of maximum dose or 2 mm. The gamma passing rates for the sternum case ranged from 96% to 99% (3% (global)/2 mm criteria, 10% threshold). Significance. The auto-commissioning procedure was successfully implemented and applied to eight TrueBeam systems. The newly developed user-friendly auto-commissioning procedure allows an efficient commissioning of an MC electron beam model and eases the usage of advanced electron radiotherapy utilizing the pMLC for beam shaping.

GPU-accelerated Monte Carlo simulation of electron and photon interactions for radiotherapy applications

Objective. The Monte Carlo simulation software is a valuable tool in radiation therapy, in particular to achieve the needed accuracy in the dose evaluation for the treatment plans optimisation. The current challenge in this field is the time reduction to open the way to many clinical applications for which the computational time is an issue. In this manuscript we present an innovative GPU-accelerated Monte Carlo software for dose valuation in electron and photon based radiotherapy, developed as an update of the FRED (Fast paRticle thErapy Dose evaluator) software. Approach. The code transports particles through a 3D voxel grid, while scoring their energy deposition along their trajectory. The models of electromagnetic interactions in the energy region between 1 MeV—1 GeV available in literature have been implemented to efficiently run on GPUs, allowing to combine a fast tracking while keeping high accuracy in dose assessment. The FRED software has been bench-marked against state-of-art full MC (FLUKA, GEANT4) in the realm of two different radiotherapy applications: Intra-Operative Radio Therapy and Very High Electron Energy radiotherapy applications. Results. The single pencil beam dose-depth profiles in water as well as the dose map computed on non-homogeneous phantom agree with full-MCs at 2% level, observing a gain in processing time from 200 to 5000. Significance. Such performance allows for computing a plan with electron beams in few minutes with an accuracy of ∼%, demonstrating the FRED potential to be adopted for fast plan re-calculation in photon or electron radiotherapy applications.

Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival

Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P=.02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P=.02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

Flexible real-time skin dosimeter based on a thin-film copper indium gallium selenide solar cell for electron radiation therapy.

Various dosimeters have been proposed for skin dosimetry in electron radiotherapy. However, one main drawback of these skin dosimeters is their lack of flexibility, which could make accurate dose measurements challenging due to air gaps between a curved patient surface and dosimeter. Therefore, the purpose of this study is to suggest a novel flexible skin dosimeter based on a thin-film copper indium gallium selenide (CIGS) solar cell, and to evaluate its dosimetric characteristics. The CIGS solar cell dosimeter consisted of (a) a customized thin-film CIGS solar cell and (b) a data acquisition (DAQ) system. The CIGS solar cell with a thickness of 0.33mm was customized to a size of 10×10mm2 . This customized solar cell plays a role in converting therapeutic electron radiation into electrical signals. The DAQ system was composed of a voltage amplifier with a gain of 1000, a voltage input module, a DAQ chassis, and an in-house software. This system converted the electrical analog signals (from solar cell) to digital signals with a sampling rate of ≤50kHz and then quantified/visualized the digital signals in real time. We quantified the linearity/ sampling rate effect/dose rate dependence/energy dependence/field size output factor/reproducibility/curvature/bending recoverability/angular dependence of the CIGS solar cell dosimeter in therapeutic electron beams. To evaluate clinical feasibility, we measured the skin point doses by attaching the CIGS solar cell to an anthropomorphic phantom surface (for forehead, mouth, and thorax). The CIGS-measured doses were compared with calculated doses (by treatment planning system) and measured doses (by optically stimulated luminescent dosimeter). The normalized signals of the solar cell dosimeter increased linearly as the delivered dose increased. The gradient of the linearly fitted line was 1.00 with an R-square of 0.9999. The sampling rates (2, 10, and 50kHz) of the solar cell dosimeter showed good performance even at low doses(<50 cGy). The solar cell dosimeter exhibited dose rate independence within 1% and energy independence within 3% error margins. The signals of the solar cell dosimeter were similar(<1%) when penetrating the same side of the CIGS cell regardless of the rotation angle of the solar cell. The field size output factor measured by the solar cell dosimeter was comparable to that measured by the ion chamber. The solar cell signals were similar between the baseline (week 1) and the last time point (week 4). Our detector showed curvature independence within 1.8% (curvatures of<0.10mm- ) and bending recovery (curvature of 0.10mm-1 ). The differences between measured doses (CIGS solar cell dosimeter vs. optically stimulated luminescent dosimeter) were 7.1%, 9.6%, and 1.0% for forehead, mouth, and thorax, respectively. We present the construction of a flexible skin dosimeter based on a CIGS solar cell. Our findings demonstrate that the CIGS solar cell has a potential to be a novel flexible skin dosimeter for electron radiotherapy. Moreover, this dosimeter is manufactured with low cost and can be easily customized to various size/shape, which represents advantages over other dosimeters.

Estimating the skin dose near to the applicator and acute toxicity in breast cancer patients: An intraoperative electron radiotherapy technique.

Intraoperative electron radiation therapy (IOERT) is one of the most recently popular therapeutic methods for breast cancer. This study aimed to measure the skin dose near the applicator during IOERT of breast cancer patients, as well as, the incidence of acute toxicity after surgery. Thirty-six female patients participated in the current study with the prescribed dose of 21 and 12 Gy for IOERT as full and boost, respectively. The skin dose was investigated based on different applicator sizes, tumor bed thicknesses, and monitor units (MUs). The energy was chosen 8 MeV, and EBT3 film was used for the dosimetric process. In addition, the acute toxicity included healing time for the surgical wound, scaling of the skin, itching, necrosis, redness as well as seroma formation for 1 week and 1 month were recorded. The results were compared to those of 22 patients who underwent the surgery without IOERT. The highest skin dose for the patients was obtained 2.09 Gy, which is lower than the threshold dose (6 Gy). Furthermore, the findings showed that the average skin dose was higher in bigger applicator sizes and MU and lower tumor bed thicknesses. The average of wound healing for the patient underwent IOERT and without the use of IOERT (as the control group) was 19.32 and 11.67 days, respectively. One month after surgery, the volume of aspirated seroma was higher in the patients who performed IOERT compared to the control group (250 ml vs. 200 ml). It is notable that there were not observed any redness, itching, scaling, and necrosis in both investigated groups. Owing to the results, the skin dose during IOERT was lower than the recommended level. The dose of IOERT as a full was higher than boost which can be related to the lower number of the patients in full method; however, there was a well-tolerated without severe acute complication, especially seroma formation and wound healing time in both full and boost methods.

Radiosensitization effect of radiofrequency hyperthermia in the presence of PEGylated-gold nanoparticles on the MCF-7 breast cancer cells under 6 MeV electron irradiation.

The purpose of the study was to investigate the radiosensitization effect of radiofrequency (RF) hyperthermia in combination with PEGylated gold nanoparticles (PEG-GNPs) on MCF-7 breast cancer cells under electron beam radiotherapy (EBRT) based on the clonogenic assay. The cell death of MCF-7 breast cancer cells treated with 13.56 MHz capacitive RF hyperthermia (power: 150W) for 2, 5, 10, and 15 min combined with 6 MeV EBRT, with a dose of 2 Gy, was evaluated in the presence of 20 nm PEG-GNPs with a low nontoxic concentration (20 mg/l). All the treatment groups were incubated for 14 days. Thereafter, survival fractions and viability of the cells were calculated and analyzed against the control group. The presence of PEG-GNPs inside the MCF-7 cancer cells during electron irradiation decreased cell survival significantly (16.7%) compared to irradiated cells without GNPs. Applying hyperthermia before electron irradiation with a capacitive RF system decreased cell survival by about 53.7%, while hyperthermia without irradiation did not show any significant effect on cell survival. Combining the hyperthermia with the presence of PEG-GNPs in the cells decreased the cell survival by about 67% at the electron irradiation, showing their additive radiosensitization effect. Low nontoxic concentration of 20 nm PEG-GNPs increases the radiosensitization effect of combining 6 MeV EBRT and RF hyperthermia on MCF-7 cancer cells. Combining hyperthermia with PEG-GNPs in electron radiotherapy could be an appropriate method for enhancing radiotherapy effectiveness on cancerous cells which can be studied on different cells and electron energies in future research.

Dosimetric characteristics of the LIAC intraoperative radiotherapy beams: Assessment of sensitivity to measurement errors at the commissioning phase

Commissioning of the LIAC intraoperative electron radiotherapy (IOERT) unit relies on the vendor's SWL-LIAC software. This software simulates the percentage depth-doses (PDDs), off-axis dose profiles and relative output factors (ROFs) for all beams based on a small set of input measurements. To date, the impact of various possible measurement errors during commissioning on LIAC dosimetric characteristics has not been studied in detail. We aimed to assess the sensitivity of the dosimetric characteristics of the ‘LIAC 12 MeV’ IOERT unit beams to various measurement errors in the commissioning phase by obtaining the magnitude of the influence of each error.The required SWL-LIAC inputs (PDDs of applicator diameters 3, 7, and 10 cm and open field) were measured with intentional applicator misalignments including 1° rotation or lateral (2 mm) or vertical (±2 mm) displacements. Also, inaccurate water surface definition for the detector was simulated by using PDDs that were shifted by ±2 mm. The errors were applied one at a time. To identify the most influential errors, the computed relative dosimetric characteristics resulting from such erroneous measurement conditions were compared to the corresponding ‘error-free’ ones. The depths of 90% and 50% doses (R90 and R50, respectively) were investigated further.All the resulting errors in R90, R50, flatness, symmetry and penumbra were within 3.9 mm, 2.8 mm, 4.3%, 4.6% and 3.5 mm, respectively. The overall averages of the absolute differences in these indices from the error-free fields were 0.8 mm, 0.8 mm, 0.6%, 0.4% and 0.5 mm, respectively. Errors in water surface definition for the detector had 4.4 to 22 times greater influence on PDDs than the other errors. The corresponding values for the profiles were 1.3–5.8 times. Among the errors in applicator alignment, PDDs and profiles were more affected by rotational and vertical ‘stand-in’ applicator misalignments, respectively. The R90 and R50 values were less affected by the errors in the small (3 and 4 cm diameter) and 45° bevelled applicators.To conclude, on average, the studied errors caused relatively small changes in beam characteristics although the maximum magnitudes of the observed errors were fairly substantial. Among the investigated errors, defining the water surface inaccurately has the largest impact on the dosimetric characteristics. Overall, sensitivity to the studied errors was found to be greatest with large-diameter flat applicators and/or lower electron energies. Although individual errors in applicator alignment have less effect on dosimetric characteristics compared to water surface error, given that these errors may occur simultaneously during dosimetry, special attention should be paid to placing the applicator correctly at the surface. Special set-up aids, such as our in-house tool for aligning applicators, are therefore indicated. The findings also further highlight the need for checking the water level periodically in long-term dosimetry procedures.

Systematic review of intraoperative radiation therapy for head and neck cancer.

Multidisciplinary treatments with surgery, radiation therapy, and chemotherapy are the cornerstones in the management of locally advanced head and neck malignancies. In most cases, radiation is delivered via external beam radiation therapy (EBRT). Intraoperative radiation therapy (IORT), on the other hand, is the delivery of precise doses of radiation to selected target volumes within the exposed surgical field while at the operating room. Most studies on its use on head and neck cancers are limited to single-institutional retrospective case series. We performed a systematic review to consolidate the existing literature on IORT for head and neck malignancies. Fifty-two studies representing a mixed population of 2,389 patients were included in this review. IORT via electrons (intraoperative electron radiation therapy), brachytherapy (intraoperative high dose-rate brachytherapy) or photons was administered in numerous settings, but most commonly as part of a reirradiation regimen following salvage surgery for recurrent tumours. Often, additional EBRT was also planned postoperatively. This review illustrates that IORT is a promising treatment modality in head and neck cancer. Multiple single-institutional studies spanning several decades have demonstrated benefit in terms of local control with reasonable toxicity. However, randomised trials comparing it with current standards of care are still needed.

Improved procedures for production and purification of 135La from enriched [135Ba]BaCO3 on a 16.5 MeV cyclotron

Lanthanum-135 (135La) is a favorable Auger electron emitter with a high Auger electron yield and low gamma emission, making it promising for Auger electron radiotherapy. However, successful application requires reliable and scalable 135La production. Up to now, metallic natural barium (natBa) is a commonly used target material, but this material is sensitive to moisture and oxidation. BaCO3 has also been tested, due to its higher chemical stability. However, BaCO3 has poor thermal conductivity, limiting the applicable current and making high yield production challenging. In this study, we pressed a mixture of enriched [135Ba]BaCO3 and fine aluminum (Al) powder to provide a stable target with improved thermal conductivity compared to pure BaCO3. After 4 h of irradiation with a 16.5 MeV proton beam at 20 μA current, 1.62 ± 0.18 GBq was produced from a 200 mg [135Ba]BaCO3:Al (1:2, w/w) target. This corresponded to a saturation yield of 11.91 ± 1.31 GBq (or 596 ± 66 MBq/μA). A purification procedure involving initial precipitation, followed by a single composite column containing a layer of TK200 resin and a second layer of branched DGA resin was developed, with 97.1 ± 3.6 % decay corrected 135La recovery. [135La]LaCl3 was obtained in an effective molar activity of 79.6 ± 25.3 MBq/nmol (DOTA titration), 104.0 ± 40.4 MBq/nmol (DTPA titration) and 186.5 ± 83.8 MBq/nmol (CHX-A″-DTPA titration), and a radionuclidic purity (RNP) of >99.9 % at end of purification, hereby demonstrating a purity suitable for radiopharmaceutical use.

Formula omitted]: New R&D platform with unique capabilities for electron FLASH and VHEE radiation therapy and radiation biology under preparation at PITZ

At the Photo Injector Test facility at DESY in Zeuthen (PITZ), an R&D platform for electron FLASH and very high energy electron radiation therapy and radiation biology is being prepared (FLASHlab@PITZ). The beam parameters available at PITZ are worldwide unique. They are based on experiences from 20 + years of developing high brightness beam sources and an ultra-intensive THz light source demonstrator for ps scale electron bunches with up to 5 nC bunch charge at MHz repetition rate in bunch trains of up to 1 ms length, currently 22 MeV (upgrade to 250 MeV planned). Individual bunches can provide peak dose rates up to 1014 Gy/s, and 10 Gy can be delivered within picoseconds. Upon demand, each bunch of the bunch train can be guided to a different transverse location, so that either a “painting” with micro beams (comparable to pencil beam scanning in proton therapy) or a cumulative increase of absorbed dose, using a wide beam distribution, can be realized at the tumor. Full tumor treatment can hence be completed within 1 ms, mitigating organ movement issues. With extremely flexible beam manipulation capabilities, FLASHlab@PITZ will cover the current parameter range of successfully demonstrated FLASH effects and extend the parameter range towards yet unexploited short treatment times and high dose rates. A summary of the plans for FLASHlab@PITZ and the status of its realization will be presented.

Intraoperative electron radiotherapy in early invasive ductal breast cancer: 6-year median follow-up results of a prospective monocentric registry

BackgroundIntraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial.MethodsAt Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical).ResultsThirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan–Meier estimate of local recurrence was 2.7%.ConclusionsThe rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.

Assessment of out-of-field radiation doses for high dose per pulse intraoperative electron beam radiotherapy using TLD-100

PurposeThis research aims to assess the out-of-field surface doses for different combinations of electron energy, applicator size, and distance from the applicator wall of high dose-per-pulse IntraOperative electron Radiation Therapy (IOeRT) using thermoluminescent dosimeters (TLDs). Materials and methodsThe out-of-field doses for various combinations of IOeRT electron beam energy/applicator size were measured using ionometric dosimetry. The calibrated LiF:Mg,Ti dosimeters (TLD-100) were used to make the measurements. TLD results were benchmarked using an Advanced Markus chamber and a polymethyl methacrylate slab phantom. TLDs were read out using a HARSHAW (type 4000) manual TLD reader. ResultsThe TLDs received out-of-field absorbed doses ranging from 0.033 to 0.545 mGy/MU depending on the applicator size, electron energy, and distance from the applicator's outer wall. The mean discrepancies between TLDs and Advanced Markus ion chamber measured data were about 1.82% in the PMMA slab phantom at a depth of maximum dose for each electron energy. ConclusionThe skin surface dose can be significant during IOeRT. The maximum out-of-field doses have occurred at high electron beam energy and closer distances around the applicator wall. TLD can measure the skin's dose level according to its good agreement with the reference Advanced Markus dosimeter. The TLD-100 can be used as a reliable dosimeter for intraoperative radiation dosimetry.

Practice-oriented solutions integrating intraoperative electron irradiation and personalized proton therapy for recurrent or unresectable cancers: Proof of concept and potential for dual FLASH effect.

Oligo-recurrent disease has a consolidated evidence of long-term surviving patients due to the use of intense local cancer therapy. The latter combines real-time surgical exploration/resection with high-energy electron beam single dose of irradiation. This results in a very precise radiation dose deposit, which is an essential element of contemporary multidisciplinary individualized oncology. Patient candidates to proton therapy were evaluated in Multidisciplinary Tumor Board to consider improved treatment options based on the institutional resources and expertise. Proton therapy was delivered by a synchrotron-based pencil beam scanning technology with energy levels from 70.2 to 228.7 MeV, whereas intraoperative electrons were generated in a miniaturized linear accelerator with dose rates ranging from 22 to 36 Gy/min (at Dmax) and energies from 6 to 12 MeV. In a period of 24 months, 327 patients were treated with proton therapy: 218 were adults, 97 had recurrent cancer, and 54 required re-irradiation. The specific radiation modalities selected in five cases included an integral strategy to optimize the local disease management by the combination of surgery, intraoperative electron boost, and external pencil beam proton therapy as components of the radiotherapy management. Recurrent cancer was present in four cases (cervix, sarcoma, melanoma, and rectum), and one patient had a primary unresectable locally advanced pancreatic adenocarcinoma. In re-irradiated patients (cervix and rectum), a tentative radical total dose was achieved by integrating beams of electrons (ranging from 10- to 20-Gy single dose) and protons (30 to 54-Gy Relative Biological Effectiveness (RBE), in 10-25 fractions). Individual case solution strategies combining intraoperative electron radiation therapy and proton therapy for patients with oligo-recurrent or unresectable localized cancer are feasible. The potential of this combination can be clinically explored with electron and proton FLASH beams.

Implementation of pencil beam redefinition algorithm (PBRA) for intraoperative electron radiation therapy (IOERT) treatment planning

PurposeSimilar to other radiation therapy techniques, intraoperative electron radiation therapy (IOERT) can benefit from an online treatment planning system (TPS). Among all the analytical electron dose calculation algorithms, pencil beam redefinition algorithm (PBRA) has shown an acceptable accuracy in inhomogeneities. The input dataset for PBRA includes electron planar fluence, mean direction and root mean square (RMS) spread about the mean direction which had been introduced based on the conventional linear accelerator geometry in former studies. Herein, three methods for implementing PBRA for IOERT system are presented. MethodsThe initialization parameters were identified using Monte Carlo (MC) simulation of a dedicated IOERT system equipped with a cylindrical 10 cm applicator, irradiating a water phantom. Phase space distribution of electrons was recorded on a plane below the applicator. The input dataset was extracted for 2 × 2 mm2 pixels and energy bin width of 1 MeV. ResultsPBRA was implemented with three initialization methods and compared to MC. The 3D gamma analysis of the algorithm with the Formula method, which was in best agreement with MC in a simple water phantom, showed passing rates of more than 99 % for all nominal energies and it was 97.1 % for 8 MeV in the presence of protecting disk and irregular surface. Implementing PBRA on CUDA C++ resulted in 5 s run time for 8 MeV nominal energy in a water phantom. ConclusionsThe agreement between PBRA dose calculation and MC is promising for the development of an intraoperative TPS for IOERT.

PO10: Case Presentation and Workflow for a 3D Printed Mold for HDR Brachytherapy of the Lower Lip

<h3>Introduction</h3> Interstitial head and neck brachytherapy is a versatile tool but requires intense patient and clinical resources as well as a high level of physician skill. For certain lesions, 3D printed brachytherapy molds may provide an "easier" alternative to interstitial brachytherapy. Recently, a patient presented with a progressive recurrent squamous cell carcinoma (SCC) in situ of the lower lip two years after prior Mohs surgery. As surgery for removal of the lesion would be disfiguring, radiotherapy was pursued. Electron radiotherapy would be difficult due to the curved surface. Thus, brachytherapy options were considered, however the use of interstitial brachytherapy would have been technically difficult as well as invasive. Commercial surface brachytherapy applicators would not fit the lesion and location, and therefore, a 3D printed brachytherapy applicator was utilized. <h3>Materials and Methods</h3> To create the 3D printed mold, two CT scans were required prior to mold design - one scan with radiopaque wires to define the target volume on the CT scan, and a second scan without wires, used to accurately define the patient surface for the 3D-printed mold. In this instance, the lower lip had to be rolled outward to expose the lesion and had to be immobilized in this position. Immobilization of the lower lip was achieved with adhesive attached to the lip and chest (Figure 1.a.). A standard bite block was inserted into the patient's mouth to keep the teeth in a reproducible position with the final intent that the 3D mold could be designed to attach to this bite block. CT scans were acquired at 1.25 mm thickness. A 3D mold was designed using our standard process in the Adaptiiv 3D bolus software. A pre-plan was created with the mold design in BrachyVision (Varian, Palo Alto, CA) to determine if the desired dosimetry to the target volume was achievable. Once a final mold design was approved, printing utilized an Axiom20 3D printer with Cheetah TPU. <h3>Results</h3> The final mold is shown in Figure 1.b and 1.c., illustrating that the mold was designed to fit over the pegs of the bite block. Several mold designs were considered, and ultimately an open bottomed mold was selected (Figure 1.d.) to allow for visualization of setup and also in case the lip swelled during treatment. A final CT of the patient with the mold in place was obtained to evaluate final mold fit and perform final CT planning (Figure 1.f.), as well as to acquire setup measurements (Figure 1.e.). Air gaps were minimal and only in two locations over the treatment volume which were all ≤1.5mm. The patient received 40 Gy in 10 fractions every other day. Near the end of treatment, topical lidocaine was applied to the patient's lip to help with applicator tolerance. Follow-up pictures are shown in Figure 1.g-i. Some moist desquamation was visible at the 1 week follow-up but resolved by six weeks posttreatment. At 10 months, the patient shows no signs of recurrence and no significant treatment-related toxicities. <h3>Conclusions</h3> A recurrent SCC in situ of the lower lip was successfully immobilized, planned, and treated with HDR brachytherapy using a custom 3D-printed mold. The benefits of the 3D mold allow for rigid immobilization of the lip for a reproducible and comfortable setup. Further research is needed into the optimal indications and applicator designs for 3D-printed applicators for head and neck brachytherapy.

Intraoperative electron radiation therapy after salvage surgery in gynecological cancers and retroperitoneal sarcomas: outcomes and adverse effects.

Salvage surgery is considered an option for isolated recurrences of retroperitoneal and pelvic tumors, in patients who have undergone previous radiotherapy. In order to increase local control intra operative electron radiation therapy (IOERT) can be used in these patients to administer additional radiation dose. We evaluated the outcomes and adverse effects in patients with retroperitoneal sarcoma and gynecologic tumors after salvage surgery and IOERT. Twenty patients were retrospectively analyzed. Twenty-three IOERT treatments were performed after surgery. Six (30%) were sarcoma and 14 (70%) were gynecological carcinoma. Administered dose depended on previous dose received with external beam radiotherapy (EBRT) and proximity to critical structures. The toxicities were scored using the Common Terminology Criteria for Adverse Events version 4.0. The median age of the patients was 51 years (range 34-70). After a median follow-up of 32 months (range 1-68), in the sarcoma group the local control rate was 66.6%; while in the gynecological group the local control rate was 64.3%. In relation to late toxicity, one patient had a Grade 2 vesicovaginal fistula, and one patient presented Grade 4 enterocolitis and enteric intestinal fistula. IOERT could have a role in the treatment of retroperitoneal sarcomas in primary tumors after EBRT, as it may suggest a benefit in local control or recurrences after surgical resection in those at high risk of microscopic residual disease. The addition of IOERT to salvage resection for isolated recurrence of gynecologic cancers suggest favorable local control in cases with concern for residual microscopic disease.

Study of the backscattering of electron beams with energies typical of radiotherapy

During radiotherapy, the dose of electrons backscattered into the tissue should be taken into account. According to the available data on the electron backscattering phenomenon, the backscatter rate varies depending on the specific radiotherapy delivery configuration. Using the Monte Carlo code MCNPX, the backscattering distribution and their saturation values for electron beams with energies between 4 MeV and 25 MeV (the energies used in electron therapy) of various materials such as polystyrene, aluminum, copper and lead were obtained. Data obtained with MCNPX show that the probability of electron backscattering is strongly dependent on the effective atomic number and the energy of the electron. For low energy electrons, the backscattering probability depends less on the energy and is mainly a function of the effective atomic number of the backscatter material. The saturation values of the backscattering are distributed as a linear function of the effective atomic number of the scattering material for all investigated energies. Therefore, it is recommended that equipment and accessories used with patients in electron radiotherapy LINAC be materials with low atomic numbers (Z), and that a layer of low Z material be used over a higher Z material for protection.