kV Photon Research Articles

Intraoperative radiotherapy combined with spinal stabilization surgery—a novel treatment strategy for spinal metastases based on a first single-center experiences

IntroductionCurrent treatment of spinal metastases (SM) aims on preserving spinal stability, neurological status, and functional status as well as achieving local control. It consists of spinal surgery followed by radiotherapy and/or systemic treatment. Adjuvant therapy usually starts with a delay of a few weeks to prevent wound healing issues. Intraoperative radiotherapy (IORT) has previously been successfully applied during brain tumor, breast and colorectal carcinoma surgery but not in SM, including unstable one, to date. In our case series, we describe the feasibility, morbidity and mortality of a novel treatment protocol for SM combining stabilization surgery with IORT.MethodsSingle center case series on patients with SM. Single session stabilization by navigated open or percutaneous procedure using a carbon screw-rod system followed by concurrent 50 kV photon-IORT (ZEISS Intrabeam). The IORT probe is placed via a guide canula using navigation, positioning is controlled by IOCT or 3D-fluroscopy enabling RT isodose planning in the OR.Results15 (8 female) patients (71 ± 10y) received this treatment between 07/22 and 09/23. Median Spinal Neoplastic Instability Score was 8 [7–10] IQR. Most metastasis were located in the thoracic (n = 11, 73.3%) and the rest in the lumbar (n = 4, 26.7%) spine. 9 (60%) patients received open, 5 (33%) percutaneous stabilization and 1 (7%) decompression only. Mean length of surgery was 157 ± 45 min. Eleven patients had 8 and 3 had 4 screws placed. In 2 patients radiotherapy was not completed due to bending of the guide canula with consecutive abortion of IORT. All other patients received 8 Gy isodoses at mdn. 1.5 cm [1.1–1.9, IQR] depth during 2-6 min. The patients had Epidural Spinal Cord Compression score 1a-3. Seven patients (46.7%) experienced adverse events including 2 surgical site infection (one 65 days after surgery).Conclusion50 kV photon IORT for SM and consecutive unstable spine needing surgical intervention is safe and feasible and can be a promising technique in selected cases.

118 Intraoperative Radiotherapy Combined With Spinal Stabilization Surgery. A Novel Treatment Strategy for Spinal Metastases. First Experiences at a Single Center

INTRODUCTION: Contemporary treatment of spinal metastases (SM) aims on preserving spinal stability, neurological status, local control and functional status. It consists of spinal surgery followed by radio- and chemotherapy. Adjuvant therapy is performed after several weeks to prevent wound healing issues. Intraoperative radiotherapy (ioRT) is a solution to shorten treatment time, successfully applied in brain tumor, breast and colorectal surgery but not SM to date. METHODS: Results on morbidity and mortality of ioRT combined with stabilization surgery in SM in a first single center series are described. Stabilization is performed as CT-navigated open or percutaneous procedure using a carbon screw-rod system followed by 50kV photon-ioRT using the ZEISS Intrabeam during a single session in prone position. The ioRT probe is placed through a guide canula via navigation and positioning is controlled by ioCT to enable RT isodose planning in the OR. Patient characteristics, perioperative specifications and postoperative follow up along with adverse events (AE) are reported. RESULTS: 11 (7 female) patients (69 ± 9.4y) received treatment from 07/22-04/23. Median SINS was 8 [7-10] IQR, with metastasis located in thoracic (n = 9) and lumbar (n = 2) spine. 6 patients receive open, 4 percutaneous stabilization and 1 decompression only. Mean length of surgery was 153±52 min. with 2 Patients receiving 4 and 8 patients receiving 8 screws respectively. In 2 Patients radiotherapy was not completed due to bending of the guide canula with consecutive security abortion of ioRT. All other patients received 8Gy isodoses during 2-6 min. Patients treated had ESCC 1a-2. Mean follow up was 63 ± 49 days. 4 patients experienced AEs including 1 case of fatal surgical site infection. CONCLUSIONS: 50 kV photon ioRT for SM can be a promising technique for selected cases of SM.

Evaluating delivered radiation dose in intraoperative radiotherapy for breast cancer using TLD

The extra radiation that it delivers has been questioned by patients, physicians, and the public for early breast cancer patients of intraoperative radiotherapy (IORT). This investigation concerns a left breast Rando phantom with a lumpectomy cavity of 30 cm3 of left breast of Rando phantom made of polymethylmethacrylate (PMMA). Thermoluminescent dosimetry (TLD) was used to evaluate the extra radiation dose or air kerma (kair) rate under IORT from 20 Gy, 50 kV of an Xoft Axxent system. TLDs were first calibrated using 50 kV photons, and then inserted at phantom positions that were close to the positions of the represented organs and tissues. Equivalent doses (DT) delivered to the organ at risks (OAR) were evaluated according to ICRP 103. Entrance surface doses (ESD) or skin doses (Dskin) varied markedly among positions close to the lumpectomy cavity. The dose was 20 Gy at the surface of a balloon applicator and kair varied from 6.40 ± 0.92 Gy down to 1.20 ± 0.30 mGy along the left-right axis of the 17th slice of Rando. These experimental results are compared with those in the literature. The shielding effect of the tungsten-impregnated rubber was also evaluated. This study supports recommendations to patients, relatives, physicians and radiologists concerning IORT.

Design of a novel nanoparticle to use X-ray fluorescence of TiO2 to induce photodynamic effects in the presence of PpIX

BackgroundRadiotherapy and photodynamic therapy are the methods of cancer treatment. Although one limitation of photodynamic therapy (PDT) is the limited penetration depth of light through tissue, using X-rays does not have this restriction. Self-lighting nanoparticles can convert X-rays into UV/visible. This study focuses on a newly designed nanostructure containing mesoporous silica nanoparticles (MSN), titanium dioxide nanoparticles (TiO2, anatase grade), and protoporphyrin IX (PpIX) as a photosensitizer to overcome the limitations of photodynamic therapy. MethodsAfter the synthesis and characterization of Ti-MSN/PpIX@PVP nanostructure, two ROSes (OH* and 1O2) were measured when the nanostructures were irradiated with 100 kV and 6 MV photons. The toxicity of Ti-MSN/PpIX@PVP nanostructure in presence and absence of radiation was investigated on DFW and HT-29 cell lines. The in-vitro experiments were analyzed using the MTT assay and colony count assay. Finally, the effect of light exposure in the presence of Ti-MSN/PpIX@PVP nanostructure on the two cell lines was studied. The in-vitro studies were evaluated using the Synergism Index (Syn) and Dose Enhancement Factor (DEF). ResultsBased on the FESEM (field emission scanning electron Microscopy) images and DLS (dynamic light scattering) measurements, the size of Ti-MSN/PpIX nanostructure was determined as (35.2 nm) and (168.4 nm), respectively. Based on the spectrofluorimetry results, 100 kV photons produced more ROSes than 6 MV photons. The results of MTT assay and colony formation for X-PDT show Syn >1, except for 100 kV photons for HT-29 cell line. The nanostructure also reduced colony formation induced by X-PDT more effectively when irradiated by 100 kV photons on DFW cells. The results obtained from conventional PDT showed that the ED 50 of the HT-29 cell line was 6 times higher than that of the DFW cell line. ConclusionDesigning and synthesizing Ti-MSN/PpIX@PVP nanostructures offer a promising strategy for reducing the current challenges in PDT and for developing and advancing X-PDT as an innovative cancer treatment technique.

DNA Damage of Iron-Gold Nanoparticle Heterojunction Irradiated by kV Photon Beams: A Monte Carlo Study

This study aims to evaluate the dependence of DNA damage on the proportion of iron and gold in iron-gold nanoparticle heterojunctions using Monte Carlo simulations. The simulation setup included a spherical nanoparticle with varying percentages of iron and gold, irradiated by photon beams of different energies (50–150 keV). The Geant4-DNA Monte Carlo code was utilized for the accurate tracking of radiation transport. The results reveal that DNA damage increases with a higher percentage of gold volume in the heterojunction, primarily due to photoelectric enhancement. Furthermore, a lower photon beam energy of 50 keV induces greater DNA damage compared to energies of 100 keV and 150 keV. The findings suggest that for effective cancer cell eradication through DNA damage, the gold volume should be equal to or greater than 50% in the iron-gold nanoparticle heterojunction. In conclusion, the findings from this study will shed light on the potential of iron-gold nanoparticle heterojunctions in enhancing radiotherapy outcomes. The investigation of DNA damage resulting from the combination of contrast agents and radiosensitizers is crucial for advancing cancer research and treatment. The knowledge gained from this research will aid in the development of personalized and effective radiotherapy approaches, ultimately improving patient outcomes in cancer treatment.

Comparison of intraoperative radiotherapy as a boost vs. simultaneously integrated boosts after breast-conserving therapy for breast cancer.

Currently, there are no data from randomized trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost in women at high risk of local recurrence. The aim of this retrospective analysis was to compare the toxicity and oncological outcome of IORT or simultaneous integrated boost (SIB) with conventional external beam radiotherapy (WBI) after breast conserving surgery (BCS). Between 2009 and 2019, patients were treated with a single dose of 20 Gy IORT with 50 kV photons, followed by WBI 50 Gy in 25 or 40.05 in 15 fractions or WBI 50 Gy with SIB up to 58.80-61.60 Gy in 25-28 fractions. Toxicity was compared after propensity score matching. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. A 1:1 propensity-score matching resulted in an IORT + WBI and SIB + WBI cohort of 60 patients, respectively. The median follow-up for IORT + WBI was 43.5 vs. 32 months in the SIB + WBI cohort. Most women had a pT1c tumor: IORT group 33 (55%) vs. 31 (51.7%) SIB group (p = 0.972). The luminal-B immunophenotype was most frequently diagnosed in the IORT group 43 (71.6%) vs. 35 (58.3%) in the SIB group (p = 0.283). The most reported acute adverse event in both groups was radiodermatitis. In the IORT cohort, radiodermatitis was grade 1: 23 (38.3%), grade 2: 26 (43.3%), and grade 3: 6 (10%) vs. SIB cohort grade 1: 3 (5.1%), grade 2: 21 (35%), and grade 3: 7 (11.6%) without a meaningful difference (p = 0.309). Fatigue occurred more frequently in the IORT group (grade 1: 21.7% vs. 6.7%; p = 0.041). In addition, intramammary lymphedema grade 1 occurred significantly more often in the IORT group (11.7% vs. 1.7%; p = 0.026). Both groups showed comparable late toxicity. The 3- and 5-year local control (LC) rates were each 98% in the SIB group vs. 98% and 93% in the IORT group (LS: log rank p = 0.717). Tumor bed boost using IORT and SIB techniques after BCS shows excellent local control and comparable late toxicity, while IORT application exhibits a moderate increase in acute toxicity. These data should be validated by the expected publication of the prospective randomized TARGIT-B study.

Gold Nanoparticle (AuNP) as a Therapeutic Enhancer for Radio – And Immunotherapy Therapy Combination in Triple Negative Breast Cancer

<h3>Purpose/Objective(s)</h3> Triple negative breast cancer (TNBC) is the most aggressive breast cancer (BC) form, with a high metastases rate and a very low survival. The aggressiveness of TNBC coupled with a significant toxicity and suboptimal chemotherapy outcomes underscores the urgency for new TNBC treatments. In recent years, immunotherapy has emerged as a promising option. In particular, immune checkpoint blockers (ICB) targeting PD-L1/PD1 inhibitory T cell check point pathway showed clinical responses and have been explored for TNBC. Unfortunately, the response rates to standalone ICB therapy are low (15-20%), indicating the presence of inhibitory immune mechanisms. Radiation therapy (RT) has been widely used in BC therapies. In addition to antitumor (antiproliferative) effects, RT has been evidenced to stimulate immune tumor rejection through immunomodulation of the tumor microenvironment (TME) that has been shown to enhance the response to immunotherapy in mouse BC models. Antitumor RT effects, including TME immunomodulation, can be improved by using radiosensitizers, such as gold nanoparticles (AuNPs). We hypothesize that AuNP potentiates RT-induced immunomodulatory effects, leading to a more efficient response to ICB in TNBC. To test this hypothesis, we used AuNP as an enhancer of RT-induced immunological TME changes, to improve ICB therapy response in murine orthotopic syngeneic 4T1Luc TNBC model. <h3>Materials/Methods</h3> Female Balb/c mice bearing 4T1Luc tumors received intratumoral injections of 14 nm AuNPs. After 24h mice were irradiated with fractionated regimen of 3 × 6 Gy dose using 225 kV photons. After the 3rd RT dose, mice received 3 doses of anti-PD-L1 antibody that were 4 days apart. Therapeutic efficiency was determined by assessing the tumor growth and animal survival. Tumor tissue immunohistochemistry determined the expression of TME immunological markers and immune cell tumor infiltration. <h3>Results</h3> AuNPs improved response to anti PD-L1 treatment in mice receiving RT, shown by significant delay in tumor growth and increase in survival compared to the animals receiving RT+ AuNP (p<0.01) and to the animals receiving RT+ anti PD-L1 or RT alone (p<0.05). These results were accompanied with changes in the expression of TME immunological markers and T cell and macrophage infiltration. <h3>Conclusion</h3> In TNBC patients, induction of antitumor immune response may play a critical role in improving clinical outcomes. Here we show that AuNP enhanced the effect of a fractionated RT regimen that has significantly improved the response to anti PD-L1 treatment in 4T1Luc TNBC mouse model. This effect was measured by a delay in tumor growth and an increase in animal survival. These findings support the role of immunological mechanisms in TNBC and provide a platform for designing multimodal TNBC RT formulations with novel radiosensitizers or immunotherapy.

Quantifying Radiosensitization of PSMA-Targeted Gold Nanoparticles on Prostate Cancer Cells at Megavoltage Radiation Energies by Monte Carlo Simulation and Local Effect Model.

Active targeting gold nanoparticles (AuNPs) are a very promising avenue for cancer treatment with many publications on AuNP mediated radiosensitization at kilovoltage (kV) photon energies. However, uncertainty on the effectiveness of AuNPs under clinically relevant megavoltage (MV) radiation energies hinders the clinical translation of AuNP-assisted radiation therapy (RT) paradigm. The aim of this study was to investigate radiosensitization mediated by PSMA-targeted AuNPs irradiated by a 6 MV radiation beam at different depths to explore feasibility of AuNP-assisted prostate cancer RT under clinically relevant conditions. PSMA-targeted AuNPs (PSMA-AuNPs) were synthesized by conjugating PSMA antibodies onto PEGylated AuNPs through EDC/NHS chemistry. Confocal fluorescence microscopy was used to verify the active targeting of the developed PSMA-AuNPs. Transmission electron microscopy (TEM) was used to demonstrate the intracellular biodistribution of PSMA-AuNPs. LNCaP prostate cancer cells treated with PSMA-AuNPs were irradiated on a Varian 6 MV LINAC under varying depths (2.5 cm, 10 cm, 20 cm, 30 cm) of solid water. Clonogenic assays were carried out to determine the in vitro cell survival fractions. A Monte Carlo (MC) model developed on TOPAS platform was then employed to determine the nano-scale radial dose distribution around AuNPs, which was subsequently used to predict the radiation dose response of LNCaP cells treated with AuNPs. Two different cell models, with AuNPs located within the whole cell or only in the cytoplasm, were used to assess how the intracellular PSMA-AuNP biodistribution impacts the prostate cancer radiosensitization. Then, MC-based microdosimetry was combined with the local effect model (LEM) to calculate cell survival fraction, which was benchmarked against the in vitro clonogenic assays at different depths. In vitro clonogenic assay of LNCaP cells demonstrated the depth dependence of AuNP radiosensitization under clinical megavoltage beams, with sensitization enhancement ratio (SER) of 1.14 ± 0.03 and 1.55 ± 0.05 at 2.5 cm depth and 30 cm depth, respectively. The MC microdosimetry model showed the elevated percent of low-energy photons in the MV beams at greater depth, consequently resulting in increased dose enhancement ratio (DER) of AuNPs with depth. The AuNP-induced DER reached ~5.7 and ~8.1 at depths of 2.5 cm and 30 cm, respectively. Microdosimetry based LEM accurately predicted the cell survival under 6 MV beams at different depths, for the cell model with AuNPs placed only in the cell cytoplasm. TEM results demonstrated the distribution of PSMA-AuNPs in the cytoplasm, confirming the accuracy of MC microdosimetry based LEM with modelled AuNPs distributed within the cytoplasm. We conclude that AuNP radiosensitization can be achieved under megavoltage clinical radiotherapy energies with a dependence on tumor depth. Furthermore, the combination of Monte Carlo microdosimetry and LEM will be a valuable tool to assist with developing AuNP-aided radiotherapy paradigm and drive clinical translation.

Accelerated Partial Breast Irradiation with Intraoperative Radiotherapy Is Effective in Luminal Breast Cancer Patients Aged 60 Years and Older.

Adjuvant whole breast irradiation (AWBI) improves local control and survival in breast cancer patients after breast-conserving surgery. Between 2010 and 2017, 823 patients ≥ 60 years with ER-positive, Her-2 negative, clinically N0 breast cancer underwent breast-conserving surgery (BCS) at the West Pomeranian Oncology Center. Intraoperative radiotherapy (IORT) with kV photons was applied to 199 (24.2%) patients according to the IORT protocol, and AWBI only was applied to 624 (75.8%). IORT patients in cases with lymph node metastasis, lobular type presence, extensive in situ components, lymphatic vessel invasion, or resection margin < 2 mm, additionally underwent AWBI. Median follow-up was 74 months. There were two (1%) breast relapses in the IORT protocol group and one (0.2%) in the AWBI-only group. In each group, one axillary lymph node relapse was diagnosed (0.5% and 0.2%, respectively). There were two local relapses in the IORT-only group, and they were treated further with BCS and AWBI. Although locoregional relapse-free survival differed between the AWBI-only and IORT protocol groups (98.5% vs. 99.7%, p = 0.048), the local control, distant metastasis-free survival, and breast cancer-specific survival were similar. IORT is a reasonable option to avoid AWBI in ER-positive, Her-2 negative, cN0 women with breast cancer aged ≥ 60 years.

Estimating Proton Stopping Power Ratio of a Novel Iodinated Rectal Hydrogel Spacer Using Dual Energy Computed Tomography

A novel iodinated rectal hydrogel spacer (I-RS) has been developed to make the gel radiopaque on CT compared to the standard rectal hydrogel spacers (S-RS). As the iodine in I-RS strongly absorbs kV photons, the accuracy of currently employed CT calibration built into a single energy CT (SECT) becomes inaccurate to determine the proton stopping power ratio (PSR) of the injected gel. Direct measurements of PSR mediated by I-RS with proton beams has been reported; however, those measurements were conducted under ideal conditions without fully accounting for density heterogeneity mediated by air bubbles co-injected with the gel during placement. This study used dual-energy CT (DECT) to estimate I-RS PSR in patients undergoing CT simulation for prostate cancer (PCa) radiotherapy (RT).Sequential scans at 90 and 140 kVp were acquired for 7 intact PCa (I-RS n = 5, S-RS n = 2) on a Philips Brilliance scanner. PSR was reconstructed following the method proposed by Torikoshi and improved by Yang, and compared to similar measurements when I-RS was replaced with S-RS. A pre-calculated table correlating effective atomic number with all possible Hounsfield Unit (HU) combinations from two sequential scans was implemented to accelerate reconstruction. PSRs were compared between DECT and SECT, and between I-RS and S-RS.In gel, HU measurements were heterogeneous (range -372 - +358). The mean PSR on reconstruction when using DECT was 0.966 (0.940-0.980) for I-RS. Replacement of I-RS with S-RS HU density resulted in a mean PSR of 0.937 (0.926-0.941) by DECT. PSR for I-RS on SECT was 1.107, and 1.014 for S-RS. The estimated difference between PSR in I-RS and S-RS on DECT vs. SECT were 14% and 8%, respectively.These data demonstrate that the use of I-RS in proton RT treatment planning could overestimate proton range due to underestimating PSR when CT simulation is performed using standard SECT. Notably, PSR absolute value reported here is different compared to previously reported in vitro data under ideal conditions and may be related to differences in gel heterogeneity in vivo. Heterogeneity is highlighted by the wide range of gel HU measurements. Direct measurements of PSR will be obtained in a planned future experiment. These data suggest that PSR overestimation due to I-RS should be considered when planning PCa treatment using proton therapy for patients who get I-RS to reduce treatment toxicity.

Does FLASH deplete oxygen? Experimental evaluation for photons, protons, and carbon ions.

To investigate experimentally, if FLASH irradiation depletes oxygen within water for different radiation types such as photons, protons, and carbon ions. This study presents measurements of the oxygen consumption in sealed, 3D-printed water phantoms during irradiation with x-rays, protons, and carbon ions at varying dose rates up to 340Gy/s. The oxygen measurement was performed using an optical sensor allowing for noninvasive measurements. Oxygen consumption in water only depends on dose, dose rate, and linear energy transfer (LET) of the irradiation. The total amount of oxygen depleted per 10Gy was found to be 0.04% atm - 0.18% atm for 225kV photons, 0.04% atm - 0.25% atm for 224MeV protons, and 0.09% atm - 0.17% atm for carbon ions. Consumption depends on dose rate by an inverse power law and saturates for higher dose rates because of self-interactions of radicals. Higher dose rates yield lower oxygen consumption. No total depletion of oxygen was found for clinical doses. FLASH irradiation does consume oxygen, but not enough to deplete all the oxygen present. For higher dose rates, less oxygen was consumed than at standard radiotherapy dose rates. No total depletion was found for any of the analyzed radiation types for 10Gy dose delivery using FLASH.

Recommendations for simulating and measuring with biofabricated lung equivalent materials based on atomic composition analysis

Monte Carlo simulations of lung equivalent materials often involve the density being artificially lowered rather than a true lung tissue (or equivalent plastic) and air composition being simulated. This study used atomic composition analysis to test the suitability of this method. Atomic composition analysis was also used to test the suitability of 3D printing PLA or ABS with air to simulate lung tissue. It was found that there was minimal atomic composition difference when using an artificially lowered density, with a 0.8 % difference in Nitrogen the largest observed. Therefore, excluding infill pattern effects, lowering the density of the lung tissue (or plastic) in simulations should be sufficiently accurate to simulate an inhaled lung, without the need to explicitly include the air component. The average electron density of 3D printed PLA and air, and ABS and air were just 0.3 % and 1.3 % different to inhaled lung, confirming their adequacy for MV photon dosimetry. However large average atomic number differences (5.6 % and 20.4 % respectively) mean that they are unlikely to be suitable for kV photon dosimetry.

Monte Carlo studies in Gold Nanoparticles enhanced radiotherapy: The impact of modelled parameters in dose enhancement

Over the last decades, Gold Nanoparticles (AuNPs) have been presented as an innovative approach in radiotherapy (RT) enhancement. Several studies have proven that the irradiation of tumors containing AuNPs could lead to more effective tumor control than irradiation alone. Studies with low kV photons and AuNPs conclude in encouraging results regarding the level of radioenhancement. However, experimental and theoretical studies with MV photons report controversial findings concerning the correlation between dose enhancement effect and tumor cell killing. The great variation in the experimental protocols and simulations complicates the comparison of their outcomes and depicts the need for limiting the variety of investigated parameters. Our purpose is to point out a possible direction for building realistic Monte Carlo (MC) models that could end up with promising results in MV photons RT enhancement. We explored published in silico studies concerning AuNPs enhanced RT from 2010 to 2019. In this review, we discuss the different AuNPs and MV photon beams characteristics that have been reported and their effect in dose enhancement. AuNPs size, concentration, type of distribution along with photon beams energy and the presence of flattening filter in linear accelerators seem to be the major parameters that determine AuNPs radioenhancement in silico. Prior to AuNPs clinical translation in photon radiotherapy, in silico studies should emphasize on nanodosimetry and track structure codes than condensed history ones. Toxicity estimation and biological aspects should be implemented in MC simulations so as to achieve accurate and realistic modelling of AuNPs driven RT.

Results of intraoperative radiotherapy given as a boost after breast conserving-surgery.

Whole breast irradiation after breast-conserving surgery (BCS) with an external beam boost of 10-16 Gy is currently the standard treatment in breast cancer. Various modalities have been used for tumor bed boost irradiation. This study aimed to evaluate the local recurrence rate, overall survival rate (OSR), toxicity and cosmetic outcome of intraoperative radiotherapy (IORT) as a boost followed by whole breast irradiation in patients who received BCS. This is a retrospective study. Between December 2009 and March 2017, 81 patients who underwent BCS with IORT as a boost were enrolled in this study. For IORT, a single dose of 20 Gy was delivered using a 30-50 kV photon beam, intraoperatively. All patients received whole breast radiation therapy (WBRT) of 42.5-50 Gy over 4-5 weeks. The primary endpoint was a 3-year local recurrence rate. Secondary endpoints included the OSR, toxicity and cosmetic outcome at 6 months after radiation treatment. At a median follow-up of 43 months, ipsilateral local recurrence was observed in one of the 81 patients (1.2%) which occurred in the same quadrant of the breast index. The 3-year OSR was 89.8%. Treatment was well-tolerated with no grade 3-4 acute and late toxicity, and 87% of patients were recorded as excellent-good cosmesis. The use of BCS with IORT as a boost resulted in a low local recurrence rate and excellent cosmetic outcome in early breast cancer. Thus, IORT as a boost could be considered as an alternative to an external beam boost. Prospective studies are needed to confirm this data.

Radiation and Gold Nanoparticle Increase the Expression of Immunogenic Cell Death Markers in MDA MB 231 Breast Cancer Model

Tumor immunogenic cell death (ICD) plays a major role in stimulating host anti-cancer immune response that can determine the success of cancer radiotherapy (RT). Additionally, ICD can also be induced by radiation itself. The main feature of ICD is the release of immunogenic molecules by dying cells, termed damage associated molecular patterns (DAMPs) that act on innate and adaptive immune components to induce long-lasting antitumor immunity. Two breast cancer (BCa) DAMPs involved in phagocytosis and dendritic cell antigen presentation are Calreticulin (CLR) and HMGB1; loss of HMGB1 expression is linked to poor clinical prognosis. Therefore, these molecules are being studied for their therapeutic and prognostic potential. As RT, either alone or in combination, is often part of standard BCa therapies, the effect of RT and radiosensitizers, such as gold nanoparticles (AuNPs), on DAMPs expression must be considered when designing new protocols, especially if combining RT with an adjuvant mode such as immunotherapy. The goal of this study was to measure the effect of radiation on CLR and HMGB-1 expression in the presence and absence of a novel AuNP radiosensitizer in MDA MB 231 BCa in vitro and in vivo models. We hypothesized that AuNP modulates radiation induced ICD by altering CLR and HMGB1 expression. In vitro: MDA MB 231 cells were incubated for 3h with 14nm AuNPs and irradiated. After 48h and 72h the percentages of CLR and HMGB1 positive cells were determined by flow cytometry. In vivo: Female nude mice bearing MDA MB 231 tumors received intratumoral injections of 14 nm AuNPs. After 24h mice were irradiated with 15 Gy dose using 160 kV photons. Mice were euthanized, histological sections prepared, stained with anti CLR antibodies and analyzed by light microscopy. In vitro, radiation induced increase in the percentages of CLR and HMGB1 positive cells was potentiated by AuNP at 48h and 72h time points. In control cells, AuNP alone increased the percent of HMGB1 positive cells at both time points. The percent of CLR positive cells was increased at 72h only. In vivo, in animals receiving RT or AuNP only, CLR expression was increased relative to control animals and CLR was detected extracellularly after RT, and extra- and intracellularly after AuNP alone. However, after combined RT and AuNP, CLR expression was higher than after single treatments and was detected both, extra- and intracellularly. In BCa patients, induction of ICD may play a critical role in improving clinical outcomes. Here we show that AuNP enhanced the immunogenic effect of a single irradiation dose in BCa cells and mouse model. This effect was measured by an increase in the expression of CLR and HMGB1, DAMPs critical to the response of BCa. In addition, AuNP alone exhibited an immunogenic effect similar to RT alone. These findings support that BCa depends on ICD and provide a platform for designing multimodal BCa RT formulations with novel radiosensitizers or immunotherapy.

An Internet of Things app for monitor unit calculation in superficial and orthovoltage skin therapy

Purpose: We developed an app for Internet of Things (IoT) device such as smartphone or tablet to calculate the monitor unit in superficial and orthovoltage skin therapy. The app can run both on the Windows and Android operation system. Methods: The IoT app was created based on the formula to calculate the monitor unit in skin therapy using kV photon beams. The calculation was based on databases of dose variables such as relative exposure factor and backscatter factor. The calculation also considered the stand-off and stand-in correction according to the inverse-square and inverse-cube law. Verification of the app was carried out by comparing the monitor unit results with those from hand calculations. Results: The frontend window of the app provided a user-friendly interface to the user for inputting prescription dose, beam and treatment setup variables. The user could save the calculation record electronically, generate a printout or send it to other radiation staff using the IoT. Verification of the app showing that deviation between the monitor units calculated by the app and by hand is insignificant. Conclusion: The verified IoT app can effectively calculate the monitor unit in superficial and orthovoltage skin therapy. The app takes advantages of all innate features of IoT such as real time communication, Internet access, data transfer and sharing.

The effect of the horizontal metallic drive on reference dosimetry in the SNC 3D scanner water tank.

Accurate quantification of absorbed radiation dose is important for safe and effective delivery of radiation therapy. An important aspect to this is reference dosimetry, which is performed under reference conditions specified by international codes of practice. Such measurements are usually performed in a water phantom. In the Sun Nuclear Corporation (SNC) three‐dimensional (3D) scanner water tank system the detector holder is fixed to a horizontal metallic drive rail (MDR) which is in close proximity to the active volume of the detector. In this project, the dosimetric effects of the MDR on reference dosimetry were investigated for MV photons, MeV electrons, and kV photons by comparing reference dosimetry measurements in the SNC 3D scanner against similar measurements in a Standard Imaging (SI) one‐dimensional (1D) tank and against measurements in the SNC 3D scanner with an additional, custom‐made spacer placed beneath the chamber holder to increase the chamber ‐ MDR separation. A second experiment investigated the difference in chamber reading dependent on chamber to MDR separation by fixing the chamber in the tank independently of the MDR and successively moving the MDR vertically to alter the separation. The results showed that measurements in the SNC 3D scanner agree with both SI 1D tank and SNC 3D scanner with spacer to within ±0.3% for MV photons, ±0.1% for electrons and ±1.2% for kV photons within the calculated setup uncertainty. The second experiment showed that the contribution of backscatter from the MDR was significant if the distance between MDR and chamber was reduced below the chamber's designed position in the SNC 3D scanner. The exception was for kV photons where the contribution of backscatter from the MDR was measured to be 0.5% at the designed distance. Further investigation would be useful for kV photons, where the experiment showed relatively large measurement uncertainties.

The actual benefit of intraoperative radiation therapy using 50kV x-rays in early breast cancer: A retrospective study of 676 patients.

This French study reports the 5-year results of partial-breast irradiation using intraoperative radiation therapy (IORT) with 50kV x-rays, in select early breast cancer patients. We report a retrospective analysis of 676 consecutive early breast cancer patients treated between November 2011 and December 2015 by partial-breast irradiation using the INTRABEAM® system. Patients were highly selected based on the ASTRO and GEC-ESTRO criteria and underwent breast-conservative surgery and IORT, completed with additional whole-breast irradiation (WBI) when unexpected unfavorable prognostic factors were found at the final pathology report. Patients' outcomes relative to local and distant control, overall and breast cancer-specific survival, and toxicity are presented, as well as rates of additional WBI. Additional WBI was mandatory in one third of patients (31%), mainly due to lymph node involvement and extensive intraductal component. With a median follow-up time of 54months, the 5-year local recurrence rate was 1.7% [95%CI: 0.9-3.3]; the median time to local recurrence was 23months; ipsilateral breast recurrences mainly occurred in the same quadrant (7/11); in the restricted population, meeting all predefined criteria and treated with IORT alone (406 patients), the local recurrence rate was 1.5% [95%CI: 0.6-3.6]. Five-year distant tumor control was 98.6% [95%CI: 97.2-99.3], and the median time to distant recurrence was 22months. Five-year overall survival was 96.5% [95%CI: 94.2-97.8], and 5-year breast cancer-specific survival was 98.9% [95%CI: 97.6-99.7]. In patients treated with IORT alone, there was no grade 3 toxicity, only four grade 3 (mainly fibrosis) affected patients treated with IORT and WBI. Grade 1-2 toxicity rates were 14% and 34.4% in patients treated with IORT alone and IORT plus WBI, respectively. Partial-breast irradiation using IORT by a 50 kV photon device is safe and well-tolerated in select patients with early breast cancer and is a valuable option in patients reluctant for adjuvant WBI.

Small-field dosimetry with a high-resolution 3D scanning water phantom system for the small animal radiation research platform SARRP: a geometrical and quantitative study

Improvements in dosimetry in preclinical radiation research facilitate the application of results to the newest radiotherapy techniques, reducing gaps that hinder translation. Currently, guidelines for small-field kV photon dosimetry of small animal irradiators have not been published, and most of the publications are based on radiochromic film dosimetry. In this study, we evaluated the performance of four detectors, three ionization chambers (ICs): (PTW Advanced Markus, PTW Semiflex 31010, PTW PinPoint-3D 31016) and one solid-state detector (PTW 60017 unshielded Diode E) regarding their suitability for relative dosimetry of the small animal radiation research platform SARRP (220 kVp). The measurements were performed in a high-resolution 3D scanning phantom, centering the detectors in the field following the in-plane and cross-plane profiles method at two depths. Depth dose curves (PDDs) and profiles were measured in water for field sizes ranging from 40 × 40 mm2 to 5 × 5 mm2. Quantitative analysis was performed through global and local dose differences (DDs) between the PDDs and the Advanced Markus parallel plate IC data and through the gamma index (γ) criteria for profiles compared against data from EBT3 films provided by the manufacturer. Compared to the Advanced Markus IC, the PDD results suggest that PinPoint-3D is suitable for depth measurements at this beam quality, even near the surface, with agreements better than 1%. Semiflex 31010 was accurate to within 1.5% for measurements deeper than 5 mm. Diode E showed a dramatic DD and should not be recommended for the field sizes and kVp evaluated in this study. In agreement with γ analyses, PinPoint-3D and Diode E are good candidates for profile measurements of field sizes from 40 × 40 mm2 to 10 × 10 mm2. For 5 × 5 mm2 profiles, only Diode E showed good results, making it a recommended detector for profile measurements.

Dose to water versus dose to medium from cavity theory applied to small animal irradiation with kilovolt x-rays

Dose reporting is a matter of concern in the preclinical field as the different dose descriptors dose-to-water-in-medium and dose-to-medium-in-medium coexist. For kV photons differences between both quantities are expected to be amplified due to photon energy absorption coefficients differences for different media, and could represent a limiting factor for accurate translation of pre-clinical research into clinical trials. The main goal of this study was to analyse the relationship between and for kV irradiation of small animals, using different flavours of the intermediate cavity theory (ICT).Irradiations of mathematical phantoms and a mouse CT scan, both with different voxel sizes and materials, were investigated. A modified version of the Monte Carlo code DOSXYZnrc was used to derive and convert to using ICT. Local photon spectra were generated in different regions of the mouse.Depending on energy and cavity size, which we equate to the voxel size, ranged from 0.68 to 4.37 times . Higher kV energy combined with very small cavity sizes yielded decreased in comparison to ; this behaviour was reversed for larger cavities combined with lower kV energies. Hence, the impact of the cavity dimensions on estimated is significant on pre-clinical kV beams. and in the ex vivo male mouse were found to differ by −29% to 286%. Caution is advised when using the ICT due to a lack of consensus on weighting factor (d-parameter) deriving methods; for the same irradiation conditions, different d-values affected up to 20%. Pre-clinically, such divergence between dose descriptors could enable biological damage.The abiding debate over which quantity to favour is foreseen to linger while it is unclear which quantity correlates better with the biological effects of ionizing irradiation: preclinical radiotherapy might represent an ideal platform for measurement-based studies to settle this fundamental question. Finally, dose distribution comparisons require caution and should use the same reporting quantity.