High-dose Irradiation Research Articles

Demographic Disparities Related to Fertility Preservation Counseling in Patients Undergoing Bone Marrow Transplantation

Infertility is a well-documented adverse effect associated with certain chemotherapeutic agents and radiation therapy.1 High-dose chemotherapy and/or total body irradiation (TBI) are utilized in preparation for bone marrow transplant (BMT), with the intent of achieving complete myeloablation prior to transplant.2 BMT is commonly used as a curative treatment modality for both malignant and benign hematologic conditions. Given this necessary exposure to high-dose chemotherapy and TBI, both male and female patients undergoing BMT are therefore at extremely high risk of impaired fertility later in life. Discussions concerning fertility preservation are often psychologically challenging for patients preparing to undergo BMT. To address these concerns, many institutions have developed fertility preservation counseling programs that aim to provide patients and caregivers with the necessary information to make informed decisions regarding fertility preservation. As is the case with many resources in healthcare, certain populations have more access to these resources than others. The goal of this study was to gain insight into if demographic features such as age, race, socioeconomic status, and underlying diagnosis/indication for BMT impacted the likelihood that a patient received fertility preservation counseling prior to transplant. It was hypothesized that there would be statistically significant differences in the rates of fertility preservation counseling when patients are compared by age, gender, race, socioeconomic status, and underlying diagnosis. A pre-existing database of BMT patients treated at the University of Rochester Medical Center was used to generate a study population of 244 patients between the ages of 0-39 years old who underwent BMT between 2012-2020. Demographic features including age, gender, race, insurance type, zip code, and indication for transplant were extracted from the database. A retrospective chart review was then conducted to identify if patients had a visit with a reproductive endocrinology and infertility (REI) specialist or if any documented fertility preservation counseling occurred prior to transplant. Odds ratios were then calculated for each of the aforementioned independent demographic variables. The overall prevalence of documented fertility preservation counseling was low. Approximately 20% of patients had a documented REI visit, while 47% had any form of documented fertility preservation counseling. There were differences in the prevalence of fertility preservation counseling related to patient age at transplant and median county income. Adult patients (age >18) were more likely than pediatric patients (age <18) to have a documented visit with an REI specialist (OR 2.99, 95% CI 1.37-6.51, p=0.0059) and more likely to have any documented fertility preservation counseling (OR 3.49, 95% CI 1.97-6.16, p<0.0001). Patients living in counties where the median income was >$60,000/year were more likely than patients living in counties with a median income of <$60,000/year to have a visit with an REI specialist (OR 4.25, 95% CI 1.89-9.54, p=0.0005) or any documented fertility preservation counseling (OR 2.72, 95% CI 1.59-4.64, p=0.0002). There were no statistically significant disparities in the prevalence of fertility preservation counseling based on patient gender, race, insurance type, or indication for transplant. These findings demonstrates that there are statistically significant differences in the prevalence of documented fertility preservation counseling based on demographic features, specifically on the basis of age and socioeconomic status. It is unclear if these findings represent the true prevalence of fertility preservation counseling, as some counseling is likely not adequately documented in the electronic medical record. Future studies are needed to design and implement improved fertility preservation counseling mechanisms, and to ensure adequate documentation of this counseling. Footnotes: 1. Rodriguez-Wallberg KA. Principles of cancer treatment: impact on reproduction. Adv Exp Med Biol. 2012;732:1-8. doi:10.1007/978-94-007-2492-1_1 2. Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124(3):344-353. doi:10.1182/blood-2014-02-514778

Gamma Knife Radiosurgery as a Salvage Treatment for Nasopharyngeal Carcinoma with Skull Base and Intracranial Invasion (T4b).

It is usually difficult to achieve good outcomes with salvage treatment for recurrent nasopharyngeal carcinoma (NPC) because of its deep-seated location, surrounding critical structures, and patient history of high-dose irradiation. Gamma Knife radiosurgery (GKS) is a treatment option for malignancies with skull base and intracranial invasion. We conducted a retrospective, observational, single-center study including 15 patients with recurrent NPC (stage T4b) involving the skull base and intracranial invasion, who underwent GKS as a salvage treatment. Patients were enrolled over 12 years. Per a previous study, the TNM classification T4b was subclassified into T4b1 and T4b2, defined as the involvement of the skull base or cavernous sinus with an intracranial extension of <5 mm and >5 mm, respectively. The effect of prognostic factors, including age, sex, survival period, magnetic resonance imaging (MRI) presentation, presence of other distant metastases, tumor volume, marginal dose, maximal dose, and Karnofsky Performance Status (KPS), on outcomes was analyzed. The patients with T4b1 NPC (p = 0.041), small tumor volume (p = 0.012), higher KPS (p < 0.001), and no other metastasis (p = 0.007) had better outcomes after GKS treatment, suggesting that it is a viable treatment modality for NPC. We also suggest that detailed brain imaging studies may enable the early detection of intracranial invasion.

Evaluation of Riboflavin as an enhancer for X-ray and EBeam irradiation treatment of Tulane virus

Ionizing technologies rely on high doses of irradiation to achieve 5-log reduction of foodborne viruses. We hypothesized that riboflavin (vitamin B2), a singlet oxygen enhancer could synergize the virucidal effects of electron beam (eBeam) and X-ray doses by using Tulane virus as a model virus. Concentrations of up to 1% w/v riboflavin were evaluated against 1 kGy X-ray treatments. Also 0.1% riboflavin was evaluated against eBeam treatments up to 10 kGy. The results showed that riboflavin did not enhance the sensitivity of Tulane virus to either eBeam or X-ray treatments.

Study on antibacterial mechanism of electron beam radiation on Aspergillus flavus

Contamination with Aspergillus flavus, which produces carcinogenic metabolites, during the post-harvest storage of agricultural products seriously endangers human health and safety. In this study, the efficacy of short-term electron beam irradiation processing with high sterilization efficiency, no contamination and no additives was evaluated for the prevention and control of A. flavus. The effects of irradiation on Aspergillus growth were determined based on analyses of physical and chemical indexes, morphology, mycelial growth, spore germination rates, mycelial dry weights, and toxin-producing ability. The effects of irradiation on the cell membrane and cell wall of A. flavus were investigated based on assays of the chitin content, chitinase activity, protein concentration, and malondialdehyde content. Damage to the antioxidant system was determined by the hydrogen peroxide content, catalase activity, superoxide dismutase activity, superoxide anion radical scavenging activity and rates of 1,1-diphenyl-2-trinitrophenylhydrazine inhibition. The inhibitory effect of irradiation on peanut invasion by A. flavus was verified. After irradiation, the thallus morphology was destroyed, mycelial growth was inhibited, and the spore germination rate, mycelial dry weight, and toxin-producing ability of A. flavus were reduced. Chitinase activity and the malondialdehyde content increased, while the chitin and total protein contents decreased. Catalase activity, superoxide dismutase activity, superoxide anion radical scavenging activity, and the rate of 1,1-diphenyl-2-trinitrophenylhydrazine inhibition decreased, while the hydrogen peroxide content increased after irradiation. These findings suggested that electron beam irradiation can effectively inhibit the normal growth and toxin production of A. flavus. Irradiation increased cell membrane permeability and decreased the integrity of the cell wall. The antioxidant system was damaged to some extent. Compared with that in unirradiated A. flavus, high-dose electron beam irradiation effectively inhibited growth. As a means of postharvest control, electron beam irradiation may have wide applications in the agricultural industry.

Effects of Gamma Irradiation on Physicochemical and Sensory Properties of Cooked Beef Sausages

Gamma irradiation could be considered a promising technology to extend food products' shelf life. Emulsion products with 40 and 65% meat contents were irradiated at 2, 4, 6, and 8 kGy doses. Residual nitrite, total volatile basic nitrogen (TVB-N), and thiobarbituric acid (TBA) values were measured during 0, 7, 14, 21, and 28 d of storage at 4 ̊C. The color was analyzed at weeks 0 and 4 during storage. Irradiation at 8 kGy significantly (p &lt; 0.05) reduced nitrite residues in both groups. The TVB-N value in the irradiated samples was significantly lower than in the non-irradiated samples. Also, the high irradiation doses at 6 and 8 kGy significantly (p &lt; 0.05) reduced the red index (a-value) and increased the TBA values of both products. High malondialdehyde contents were induced by high irradiation doses. Sensory evaluation results showed that the 8-kGy-treated products had the lowest color, taste, and odor scores, whereas 2 and 4-kGy doses could be suitable to maintain sensorial characteristics. Overall findings suggested the use of lower gamma irradiation doses to decrease residual nitrite and extend the shelf life of meat products.

Alleviation of Severe Skin Insults Following High-Dose Irradiation with Isolated Human Fetal Placental Stromal Cells.

Skin exposure to high-dose irradiation, as commonly practiced in radiotherapy, affects the different skin layers, causing dry and wet desquamation, hyperkeratosis fibrosis, hard to heal wounds and alopecia and damaged hair follicles. Fetal tissue mesenchymal stromal cells (f-hPSC) were isolated from excised human fetal placental tissue, based on their direct migration from the tissue samples to the tissue dish. The current study follows earlier reports on for the mitigation of acute radiation syndrome following whole body high-dose exposure with remotely injected f-hPSC. Both the head only and a back skin flap of mice were irradiated with 16 &18 Gy, respectively, by 6MeV clinical linear accelerator electron beam. In both locations, the irradiated skin areas developed early and late radiation induced skin damages, including cutaneous fibrosis, lesions, scaring and severe hair follicle loss and reduced hair pigmentation. Injection of 2 × 106 f-hPSC, 3 and 8 weeks following 16 Gy head irradiation, and 1 and 4 weeks following the 18 Gy back skin only irradiation, resulted in significantly faster healing of radiation induced damages, with reduction of wet desquamation as measured by surface moisture level and minor recovery of the skin viscoelasticity. Detailed histological morphometry showed a clear alleviation of radiation induced hyperkeratosis in f-hPSC treated mice, with significant regain of hair follicles density. Following 16 Gy head irradiation, the hair follicles density in the scalp skin was reduced significantly by almost a half relative to the controls. A nearly full recovery of hair density was found in the f-hPSC treated mice. In the 18 Gy irradiated back skin, the hair follicles density dropped in a late stage by ~70% relative to naïve controls. In irradiated f-hPSC treated mice, it was reduced by only ~30% and was significantly higher than the non-treated group. Our results suggest that local injections of xenogeneic f-hPSC could serve as a simple, safe and highly effective non-autologous pro-regenerative treatment for high-dose radiation induced skin insults. We expect that such treatment could also be applied for other irradiated organs.

Characterization of pixelated silicon detectors for daily quality assurance measurements in proton therapy

The advanced imaging and delivery techniques in proton therapy allow conformal high-dose irradiation of the target volume with high accuracy using pencil beam scanning or beam shaping apertures. These irradiation methods increasingly include small radiation fields with large dose gradients, which require detector systems with high spatial resolution for quality assurance. In addition the measurement of all success parameters for daily quality assurance with only one proton field and one simple detector system would save a lot of time in clinical usage. Based on their good spatial resolution and high rate compatibility, pixelated silicon detectors could meet the new requirements. To assess their applicability in proton therapy, ATLAS pixelated silicon detectors are used to measure the lateral beam profile with high spatial resolution. Furthermore, a dose dependent detector calibration is presented to allow the measurement of the requested output constancy. A strategy to verify the proton energy during the daily quality assurance is under study. Promising results from proof-of-principle measurements at the West German Proton Therapy Centre in Essen, Germany, have been obtained.

Anlotinib Enhances the Antitumor Activity of High-Dose Irradiation Combined with Anti-PD-L1 by Potentiating the Tumor Immune Microenvironment in Murine Lung Cancer

<h3>Purpose/Objective(s)</h3> Radioimmunotherapy has become one of the most promising strategies for cancer treatment. Preclinical and clinical studies have demonstrated that antiangiogenic therapy can improve the efficacy of immunotherapy and sensitize radiotherapy through a variety of mechanisms. However, it is undefined whether angiogenesis inhibitors can enhance the effect of radioimmunotherapy. In this study, we aim to explore the role of anlotinib (AL3818) on the combination of radiotherapy and immune checkpoint inhibitors in Lewis lung carcinoma mouse. <h3>Materials/Methods</h3> C57BL/6 mouse subcutaneous tumor model was used to evaluate the ability of different treatment regimens in tumor growth control. Immune response and immunophenotyping including the quantification and activation were determined by flow cytometry, multiplex immunofluorescence and multiplex immunoassay. <h3>Results</h3> Triple therapy (radiotherapy combined with anti-PD-L1 and anlotinib) increased tumor-infiltrating lymphocytes and reversed the immunosuppressive effect of radiation on the tumor microenvironment in mouse model. Compared with radioimmunotherapy, the addition of anlotinib also boosted the infiltration of CD8⁺ T cells and M1 cells, and caused a decrease in the number of MDSCs and M2 cells in mice. The levels of IFN-gamma, IL-18 were the highest in the triple therapy group, while the levels of IL-23, IL-13, IL-1 beta, IL-2, IL-6, IL-10 and Arg-1 were significantly reduced. NF-κB, MAPK and AKT pathways were down regulated in triple therapy compared with radioimmunotherapy. Thus, the tumor immune microenvironment was significantly improved. As a consequence, triple therapy displayed greater benefit in antitumor efficacy. <h3>Conclusion</h3> Our findings indicate that anlotinib might be a potential synergistic treatment for radioimmunotherapy to achieve better antitumor efficacy in NSCLC patients by potentiating the tumor immune microenvironment.

Correlations on the Structure and Properties of Collagen Hydrogels Produced by E-Beam Crosslinking.

In this study, a collagen hydrogel using collagen exclusively produced in Romania, was obtained by electron beam (e-beam) crosslinking. The purpose of our study is to obtain new experimental data on the crosslinking of collagen and to predict as faithfully as possible, its behavior at high irradiation doses and energies. To pursue this, the correlations between macromolecular structure and properties of collagen hydrogels were determined by rheological analysis, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Differential Scanning Calorimetry (DSC), respectively. The gel fraction, swelling degree, and network parameters of the collagen hydrogels were also investigated at different irradiation doses. Through experimental exploration, we concluded that irradiation with e-beam up to 25 kGy induces crosslinking processes in collagen structure without producing advanced degradation processes. E-beam technology is a great method to develop new materials for medical applications without adding other chemical reagents harmful to human health. The future aim is to develop new wound dressings for rapid healing based on collagen, through irradiation technologies.

Genetic diversity in gladiolus by using gamma rays

This investigation was carried out to determine the effects of gamma radiation on germination characteristics of gladiolus corms. This experiment was conducted through a factorial design in randomized complete block with three replications. Two factors included cultivars of gladiolus (Red Advance, White Prosperity, Amsterdam, and Rose Supreme) and doses of gamma radiation (0, 15, 25, 35, 45, 55, 65, and 75 Gy). The results showed that corm weight, corm size, and number of daughter corms decreased with increasing radiation doses, however, low dose (15 Gy) stimulated them. High doses of gamma irradiation (75 Gy) showed the lethal effects on various vegetative traits. The low yield at high doses can be due to the reduced vegetative growth as a result of gamma treatments. The results of this study suggest a dose of 40-65 Gy as the optimal dose to improve the vegetative traits of gladiolus.Keywords: Gladiolus, Genetic diversity, Corm, Mutation

Impact of intragranular misorientation on void swelling and inter-granular cavities after ion irradiation in standard and additive manufacturing 316L austenitic steels

Additive manufacturing (AM) is a promising technology for the design of materials with complex geometries with reduced cost and material waste. In order to be used in the nuclear industry, the capability of AM materials, in term of radiation resistance must be compared with materials elaborated in conventional ways. In this work, the radiation resistance of 316L austenitic stainless steels (ASSs) elaborated by AM is compared to a solution-annealed 316L ASS after irradiation with 5 MeV Fe5+ for 3 dpa at 550 °C (873 K). After irradiation, cavities are mainly located near grain boundaries for all studied alloys. Intra-granular cavities are only found in the AM material after heat treatment and are likely to be remaining porosity already present before irradiation. No cavities in intra-granular position are found in the conventional 316L ASS or in the AM material after hot isostatic pressing (HIP) at 1100 °C. It suggests that the void swelling ASSs starts by the formation of cavities at grain boundaries followed by a formation of cavities in intra-granular position, conventionally studied. Loops in the AM material with a hot treatment at 700 °C are heterogeneously distributed due to a bimodal distribution of grains in terms of intra-granular misorientation. The intra-granular misorientation drastically reduces the loop density after irradiation. Frank and perfect loops are found to be only interstitial-type loops. The larger cavities’ size and the more advanced dislocations network in the AM HIP sample suggests a slightly reduced radiation swelling resistance for the AM material but further investigations at higher irradiation dose have to be done.

Application of Advanced Non-Linear Spectral Decomposition and Regression Methods for Spectroscopic Analysis of Targeted and Non-Targeted Irradiation Effects in an In-Vitro Model.

Irradiation of the tumour site during treatment for cancer with external-beam ionising radiation results in a complex and dynamic series of effects in both the tumour itself and the normal tissue which surrounds it. The development of a spectral model of the effect of each exposure and interaction mode between these tissues would enable label free assessment of the effect of radiotherapeutic treatment in practice. In this study Fourier transform Infrared microspectroscopic imaging was employed to analyse an in-vitro model of radiotherapeutic treatment for prostate cancer, in which a normal cell line (PNT1A) was exposed to low-dose X-ray radiation from the scattered treatment beam, and also to irradiated cell culture medium (ICCM) from a cancer cell line exposed to a treatment relevant dose (2 Gy). Various exposure modes were studied and reference was made to previously acquired data on cellular survival and DNA double strand break damage. Spectral analysis with manifold methods, linear spectral fitting, non-linear classification and non-linear regression approaches were found to accurately segregate spectra on irradiation type and provide a comprehensive set of spectral markers which differentiate on irradiation mode and cell fate. The study demonstrates that high dose irradiation, low-dose scatter irradiation and radiation-induced bystander exposure (RIBE) signalling each produce differential effects on the cell which are observable through spectroscopic analysis.

The mapping of mRNA alterations elucidates the etiology of radiation-induced pulmonary fibrosis.

The etiology of radiation-induced pulmonary fibrosis is not clearly understood yet, and effective interventions are still lacking. This study aimed to identify genes responsive to irradiation and compare the genome expression between the normal lung tissues and irradiated ones, using a radiation-induced pulmonary fibrosis mouse model. We also aimed to map the mRNA alterations as a predictive model and a potential mode of intervention for radiation-induced pulmonary fibrosis. Thirty C57BL/6 mice were exposed to a single dose of 16Gy or 20Gy thoracic irradiation, to establish a mouse model of radiation-induced pulmonary fibrosis. Lung tissues were harvested at 3 and 6months after irradiation, for histological identification. Global gene expression in lung tissues was assessed by RNA sequencing. Differentially expressed genes were identified and subjected to functional and pathway enrichment analysis. Immune cell infiltration was evaluated using the CIBERSORT software. Three months after irradiation, 317 mRNAs were upregulated and 254 mRNAs were downregulated significantly in the low-dose irradiation (16Gy) group. In total, 203 mRNAs were upregulated and 149 were downregulated significantly in the high-dose irradiation (20Gy) group. Six months after radiation, 651 mRNAs were upregulated and 131 were downregulated significantly in the low-dose irradiation group. A total of 106 mRNAs were upregulated and 4 downregulated significantly in the high-dose irradiation group. Several functions and pathways, including angiogenesis, epithelial cell proliferation, extracellular matrix, complement and coagulation cascades, cellular senescence, myeloid leukocyte activation, regulation of lymphocyte activation, mononuclear cell proliferation, immunoglobulin binding, and the TNF, NOD-like receptor, and HIF-1 signaling pathways were significantly enriched in the irradiation groups, based on the differentially expressed genes. Irradiation-responsive genes were identified. The differentially expressed genes were mainly associated with cellular metabolism, epithelial cell proliferation, cell injury, and immune cell activation and regulation.

Optimizing the Small Animal Radiation Research Platform (SARRP) for High-Dose Rate Focal Irradiation Studies

<h3>Purpose/Objective(s)</h3> The objective of the study is to enable high-dose rate focal irradiation in small animal models through modification of a commercial small animal radiation research platform (SARRP), which is widely used by investigators for preclinical research in radiation oncology. Small animal pre-clinical research is a fundamental part of clinical translation of novel treatment techniques. Currently, the SARRP system only enables dose rate of 3.5 Gy/min at the nominal isocenter. However, preclinical studies to investigate SBRT ablative models, such as those for the lung, liver, and more recently the heart, require much higher dose rates (ideally at least 10-20 Gy/min) and the current SARRP system setup requires long anesthesia time to deliver the required radiation dose to the animals. In addition, emerging applications such as lattice SBRT for larger tumors (which requires the delivery of a large grid of focal irradiation spots in a short time), is currently impossible with the current SARRP system. Here, we present our work to optimize the SARRP system using a modified beam collimation system to allow high-dose rate focal irradiation studies <i>in vivo</i>, while enabling a highly flexible set of collimator sizes and shapes to be used. <h3>Materials/Methods</h3> A commercial SARRP system with nominal source-to-axis distance (SAD) of 35 cm was studied in this work. In order to be able to perform experiments at a higher dose rate, a dedicated beam collimation apparatus was designed to provide a short source-to-surface distance (SSD) of 14 cm. Measurements were performed using an ionization chamber and radiochromic film dosimeter to measure the dose rate using the original beam collimation assembly at the isocenter (35 cm SSD), and using our dedicated beam collimation assembly at 14 cm SSD. Measurements were at the surface and at 2 cm depth in phantom with and without the x-ray filter in place. <h3>Results</h3> The SARRP system with standard collimation assembly provides a dose rate of 3.5 Gy/min at 2 cm depth in phantom at 35 cm SAD. The dose rate measured using our apparatus increased by a factor of 4.9, reaching 17 Gy/min, at 14 cm SSD and 2 cm depth in phantom. Removing the x-ray filter would additionally increase the dose rate by another factor of 6 at the surface and 1.7 at 2 cm depth in phantom. <h3>Conclusion</h3> The SARRP system with our modified collimation system would allow <i>in vivo</i> experiments with dose rates of 17-29 Gy/min at 14 cm SSD.

Oral Mucosal Sparing in High-Dose Total Body Irradiation (TBI) prior to Stem Cell Transplantation (SCT) for Acute Leukemia

<h3>Purpose/Objective(s)</h3> High-dose TBI prior to SCT for acute leukemia has been previously associated with superior leukemic control at the expense of non-relapse mortality (NRM). High-grade oral mucositis (OM) may contribute to NRM. We hypothesized that oral mucosal sparing (OMS) TBI delivered with intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) might reduce NRM due to acute OM (occurring within 30 days). <h3>Materials/Methods</h3> Patients treated with high dose, IMRT/VMAT-based TBI prior to SCT for acute lymphocytic leukemia (ALL) or myeloid leukemia (AML) at our institution between 09/2020 and 02/2022 were retrospectively identified. TBI was prescribed to 13.2 or 12 Gy, given in 8 twice daily fractions at least 6 hours apart. The planning target volume (PTV) was defined as the entire body minus organs at risk including the heart, lungs, kidneys, and breasts. After the first 15 patients, we adopted the OMS technique in which the mucosal surfaces of the oral cavity and oropharynx were excluded from the PTV and limited to mean dose < 7 Gy. Fisher's exact tests were used to compare proportions between groups and T-tests were used to compare means between groups. Toxicity was graded according to CTCAEv5. <h3>Results</h3> 25 patients met inclusion criteria. Median patient age was 28 years (range 18-65). 18 patients (72%) had B-ALL, 6 (24%) had T-ALL, and 1 (4%) had AML. Conditioning chemotherapy was cyclophosphamide (n=5, 20%), etoposide (n=9, 36%), or fludarabine (n=11, 44%). Graft vs host disease (GVHD) prophylaxis was mycophenolate mofetil, cyclophosphamide, and tacrolimus (n=12, 48%) or tacrolimus and methotrexate (n=13, 52%). The mean oral mucosal dose was 6.6 Gy vs 13.9 Gy for sparing vs non-sparing, respectively (p < 0.0001). Highest grade OM was 0 (n=7, 28%), 1 (n=1, 4%), 2 (n=3, 12%), 3 (n=11, 44%), or 5 (n=3, 12%). Median time to grade ≥3 OM was 8.5 days (range 0-15) after SCT. Four patients had NRM, including one case of fatal GVHD, and three due to severe OM leading to aspiration pneumonia and fatal respiratory failure (days +4, +5, +8). All three NRM due to OM occurred in patients treated before OMS was instituted (3 of 15 patients, 20%). While no cases of NRM due to OM occurred in patients treated with OMS, the difference was not statistically significant (p = 0.2). Likewise, there was no difference in risk of any OM (90% vs 60%, p=0.2) or grade ≥3 OM (60% vs 53%, p = 0.8) for sparing vs non-sparing, respectively. There was a non-significant trend towards decreased NRM from OM in patients receiving fludarabine (0 of 11) vs etoposide (1 of 9, 11%) or cyclophosphamide (2 of 5, 40%) (p = 0.08), though 91% of patients who received fludarabine also received mucosal sparing. There was no difference in NRM due to OM by GVHD prophylactic regimen (p = 0.5). <h3>Conclusion</h3> The etiology of acute OM following TBI for acute leukemia is multifactorial. Though limited by sample size, these results suggest exclusion of the oral mucosa from TBI with IMRT/VMAT effectively reduces dose to the oral mucosa and may decrease risk of NRM from OM.

Palliative High-Dose Radiotherapy for Ulcerative Breast Lesions

<h3>Purpose/Objective(s)</h3> Breast cancer with skin invasion may cause decreased quality of life due to bleeding, self-destruction, and pain. However, there is no consensus on the optimal dose for palliative irradiation. In this study, we investigated the efficacy and safety of relatively high-dose treatment to sustain tumor control and symptom relief in patients with long-term survival expectations. <h3>Materials/Methods</h3> Between June 2013 to April 2021, a total of 32 patients who received relatively high-dose palliative irradiation for breast cancer with skin invasion at our institution were selected. Radiotherapy was performed at a total dose of 45-70 Gy with 2-3 Gy per fraction. (45 Gy/15 Fr:1, 50 Gy/20 Fr:3, 54 Gy/18Fr:1, 60 Gy/24 Fr:4, 60 Gy/20 Fr:19, 60 Gy/30 Fr:2, 70 Gy/35 Fr:2) We retrospectively analyzed the efficacy of local control, symptomatic relief, and adverse events. <h3>Results</h3> Median follow-up was 9.0months (range:2.6-69.6months). The median age was 65years (range: 36-89years), 27 cases (84%) had distant metastasis at the time of radiotherapy. After radiotherapy, 29 cases (91%) had symptomatic relief of bleeding, discharge, or pain. Of the 30 cases in which CT was taken, 28 cases (93%) showed tumor reduction, of which 6 cases showed subsequent re-growth. The median duration of local control was 4.9months (range: 1.23-68.87months), and the 6-month local control rate was 86.9%, 12-month local control rate was 68.3%, and 24-month local control rate was 60.7%. Acute adverse events included dermatitis in G3/G2/G1 = 13/14/5 cases (40/44/16%), and late adverse events included pneumonitis in G2/G1 = 1/15 cases (3/47%). No other late adverse events above G3 were observed. <h3>Conclusion</h3> The local control and symptom relief of relatively high-dose therapy are favorable. The frequency of late adverse events, such as pneumonitis, is within an acceptable range. Further investigation on prescription dose and safety is required.

Ga68]-DOTATATE/MRI-Guided Fractionated Stereotactic Radiosurgery for Residual/Recurrent Atypical Meningiomas – Local Control and Salvage Requirements in a Single Institution Series

<h3>Purpose/Objective(s)</h3> The NCI-sponsored phase III NRG protocol BN-003 randomizing completely resected atypical meningiomas to observation or fractionated radiotherapy to the resection bed requires clinical equipoise to ethically randomize patients between the two arms. A radiographically complete resection, required for protocol eligibility, may be Simpson Grade 1, 2, or 3, which differ in excision completeness and thus in risk of recurrence. Meningiomas express high levels of somatostatin receptor 2A, which avidly binds [68Ga]-DOTATATE, a PET tracer that permits differentiation of postoperative scar tissue from residual/recurrent meningioma. We hypothesized that using [68Ga]-DOTATATE PET/MRI would permit the radiosurgical treatment of patients with atypical (WHO Grade 2) meningiomas not completely removed at surgery, thereby sparing normal brain high-dose irradiation and shortening treatment from six weeks to one. We prospectively accrued patients with residual/recurrent atypical meningiomas at our institution and subsequently investigated their local control (LC) and salvage requirements after treatment with fractionated stereotactic radiosurgery (fSRS) that incorporated [68Ga]-DOTATATE PET/MRI in the planning process. <h3>Materials/Methods</h3> We approached patients with pathologically confirmed atypical meningioma for an Institutional Review Board approved prospective trial of [68Ga]-DOTATATE PET/MRI imaging. fSRS (35 Gy in 5 fractions) was offered to patients with positive findings. 20 tumors in 19 patients were treated. Patients were scheduled for follow-up MRI and [Ga68]-DOTATATE PET scanning per protocol on an at least semi-annual basis. Not all patients have yet presented for follow-up imaging. LC duration was calculated from the first day of fSRS until the most recent MRI. No patients were lost to follow-up. <h3>Results</h3> 20 fSRS sessions were delivered, LC was achieved at fSRS sites in all patients. Median follow-up is 15.9 months (range: 0-35.7, SD 11.1). One patient progressed remote from the original site of disease and was managed with [Lu177]-DOTATATE and salvage SRS to a new nodular focus. Two patients had surgical bed recurrences, one of which was managed with salvage re-resection (now WHO Grade III), followed by fractionated radiotherapy; the other is pending salvage fSRS. Overall, 16/19 patients (84%) have experienced progression-free survival to date after [Ga68]-DOTATATE PET/MRI guided fSRS of residual/recurrent atypical meningioma. No unusual toxicities were reported by patients in follow-up, and no patients required treatment for radiation injury. <h3>Conclusion</h3> [Ga68]-DOTATATE PET/MRI can assist with radiation management of residual/recurrent atypical meningiomas through improving the ability to discern what volumes of tissue require aggressive focal treatment, and what volumes are at low risk and can be spared treatment. Further follow-up will help clarify the value of this approach.

Antibody based conditioning for allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for many patients with hematological malignancies and nonmalignant hematopoietic disorders. To achieve stable engraftment of donor hematopoietic stem cells (HSCs), recipient HSC deletion is needed to create space for incoming donor HSCs and donor HSCs must escape immune rejection by the recipient. Conventional allo-HSCT requires high dose of irradiation and/or chemotherapy to produce sufficient host stem cell and immune system ablation to permit donor HSC engraftment. However, these procedures also result in nonspecific tissue injury that can cause short- and long-term adverse effects as well as incite and amplify graft-versus-host-disease (GVHD). The delivery of targeted radiotherapy to hematopoietic tissues with the use of a radioimmunoconjugate (ROIC) as a part of transplant preparative regimen has shown clinical benefits. ROIC clinical data provide evidence for decreased relapse without increased transplant-related mortality by delivering higher targeted radiation to sites of malignancy than when given in a nontargeted fashion. An alternative approach to allo-HSCT has been developed and tested in preclinical mouse models in which nonmyeloablative preconditioning with low dose of the alkylating agent (busulfan) or lower systemic dose of irradiation combined with co-stimulatory pathway blockade (CTLA4-Ig, anti-CD40L monoclonal antibody) and/or immunosuppressive drugs have been used. Under these conditions, mixed chimerism and transplantation tolerance to fully MHC mismatched donor marrow was observed. Recently, several novel proof-of-concept antibody-mediated preconditioning methods have been developed that can selectively target hematopoietic stem and immune cells with minimal overall toxicity. Antibody-drug-conjugate (ADC) combined with reduced intensity conditioning or high dose ADC as single dose monotherapy have shown promise for allo-HSCT in preclinical models. The purpose of the current review is to discuss the literature exploring antibody-based conditioning that includes native antibody, radiolabeled antibody conjugates, and ADC for allo-HSCT.

Critical role of the deep electron trap in explaining the inconsistency of sensitivity-corrected natural and regenerative growth curves of quartz OSL at high irradiation doses

Natural quartz minerals that contain impurities, complex defect structures, and multiple trap levels within their crystals have been widely used for optically stimulated luminescence (OSL) dosimetry. Accurate application of the single-aliquot regenerative-dose (SAR) protocol requires an equivalence between the sensitivity-corrected natural and regenerative growth curves. In this work, the sensitivity-corrected natural and regenerative growth curves of quartz OSL are modelled using a comprehensive kinetic model based on the band theory of solids. We demonstrate that the trapping behaviour of the deep electron trap exerts a critical influence on the inconsistency of the sensitivity-corrected natural and regenerative growth curves at high irradiation doses. A delay in saturation of the deep electron trap at high irradiation doses leads to a substantial increase in electron competition in the recombination centres during the irradiation of the test dose and a decrease in electron competition in the centres during the subsequent stimulation of the test dose OSL. As a consequence, the test dose OSL responses as functions of irradiation doses are inconsistent (incompatible) between natural and regenerative aliquots, and the sensitivity-corrected regenerative growth curve tends to be higher than the natural one in the high-dose region. There may be substantial deep electron traps within the crystal of natural quartz that cause their delayed saturation at high irradiation doses.

Impact of Electron Beam Irradiation on the Developmental Stages of Callosobruchus maculatus (Coleoptera: Bruchidae) and Bactrocera zonata (Diptera: Tephritidae)

Abstract An eco-friendly electron beam irradiation (EBI) technology was used to assess the effect of EBI on the different development stages of Callosobruchus maculatus (F.) and Bactrocera zonata (Saunders). No adults emerged after 3-d-old eggs of C. maculatus were irradiated with 304.8 Gy of EBI, and no adults emerged from the F1 generation of larvae and pupae irradiated with 103.6 Gy. The adult stage of C. maculatus was the most tolerant of EBI, with a high dose (414.3 Gy) irradiation of the adult stage resulting in complete prevention of the F1 generation adult emergence. Large-scale tests confirmed that 414.3 Gy was an effective dose for the phytosanitary and security treatment for C. maculatus. An EBI dose of 414.3 Gy prevented B. zonata egg hatching. EBI doses of 304.8, 414.3, and 653.5 Gy prevented the development of first, second, and third larval instars to pupation, respectively. Using the criterion of adult emergence from the F1 generation, targeting the third larval stage, considered the most tolerant stage to EBI, a dose of 304.8 Gy was effective for quarantine and security treatment of B. zonata.