Gy Single Dose Research Articles

Protective effect of melatonin against radiobiological damage in the brain of rats exposed to low and high dose rate radiotherapy

This study aimed to investigate the radioprotective effect of melatonin (MLT) on brain damage in rats exposed to low and high dose rate radiotherapy. The dose rates of 10 MV photon beams used in the study were 600 MU/min and 2400 MU/min for low dose rate radiotherapy (LDR_RT) and high dose rate radiotherapy (HDR_RT), respectively. A total of 46 female Wistar albino rats aged between 8 and 12 weeks were divided in 6 groups. These groups were control, MLT, LDR_RT, HDR_RT, LDR_RT plus MLT and HDR_RT plus MLT, respectively. Rats in the radiation group received 16 Gy single dose whole body radiotherapy. Rats in the LDR_RT plus MLT and HDR_RT plus MLT groups received 10 mg/kg melatonin by intraperitoneal injection 15 min before radiotherapy. The rats were sacrificed 48 h after radiotherapy. Biochemical and histopathological methods analyzed radiation damage in rats. There was a statistically significant difference between the LDR_RT and HDR_RT radiation groups and the control group in terms of biochemical and histopathological parameters (p < 0.05). In the groups that received only LDR_RT and HDR_RT, the moderate neuro-degeneration scores were 1 and 4, respectively, while the moderate neuro-degeneration scores were 0 and 2 when MLT was applied to these groups. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzymes were decreased due to radiotherapy, whereas these enzymes were improved in MLT-treated groups. In conclusion, melatonin was found to be effective as a radioprotective agent in the prevention of brain damage caused by exposure to 10 MV photon radiation at dose rates of 600 MU/min and 2400 MU/min.

Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats

BackgroundMelissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation.MethodsHyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-β1) were determined.ResultsMO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes’ activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-β1/Smad pathway.ConclusionAccordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.

Single Dose vs. Fractionated High-Dose Rate Brachytherapy in Localized Prostate Cancer: Long Term Results

To evaluate long-term freedom from biochemical relapse (FFbR) and overall survival (OS) after single-dose high-dose-rate brachytherapy (HDR-BT) compared with 2 or 3 fraction schedules. HDR-BT, delivering 1 × 19 Gy or 1 × 20 Gy (A = 49), 2 × 13 Gy (B = 138) or 3 × 10.5 Gy (C = 106), was given to patients with intermediate or high-risk prostate cancer as their sole treatment. Patients were staged with pelvic MRI and isotope bone scan. Transperineal transrectal ultrasound guided implantation was followed by MRI based CTV definition based on GEC ESTRO guidelines. Biochemical relapse was assessed using the Phœnix definition (PSA nadir plus 2 µg/L). Patients were evaluated prospectively from 6 months after implant and bi-annually thereafter. Estimates of freedom from biochemical relapse, and overall survival (OS) were calculated using the Kaplan-Meier (K-M) method and the log-rank test to test for significance. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard model. For multivariate modelling a stepwise reduction method was used. Median follow-up was 123, 116 and 120 months (p = 0.4), (A, B, C, respectively). Neo-adjuvant and adjuvant androgen deprivation treatment was given to 80% of all patients, median duration was 9 months for A and 6 months for B and C. K-M estimates of FFbR, at 8 and 10 years, were 67% and 64% (Group A), 78% and 72% (Group B), and 80% and 76% (Group C). Differences in FFbR between dose groups was not significant (p = 0.2). Similarly, no significant difference was seen in OS. Eight and 10-year estimates were 81% and 75% (A), 85% and 74% (B), and 90% and 83% (C); p = 0.5. Hazard Ratios for risk of biochemical recurrence were significant for ADT administration (yes/no) and overall risk category, in multivariate analyses. Only the latter was significant in univariate analysis for risk of death, Gleason risk (low, intermediate, high), MRI tumor stage risk and overall risk category were significant in univariate analyses. Only tumor stage and Gleason risk were significant in multivariate analyses. Concerns around the efficacy of 19-20 Gy single dose HDR BT as monotherapy, based on early data, may have been unfounded. Long-term outcome data up to 10 years show no significant difference in PSA control and overall survival compared to 2 and 3 fractions of HDR-BT.

Lipid Polyunsaturated Fatty Acid Chains in Mouse Kidneys Were Increased within 5 min of a Single High Dose Whole Body Irradiation.

To understand the ultra-early reaction of normal organ lipids during irradiation, we investigated the response of lipids, including polyunsaturated fatty acid (PUFA) chains, which are particularly susceptible to damage by ROS, in mice's kidneys, lungs, brains, and livers within 5 min of single high-dose irradiation. In this study, we set up three groups of C56BL/6 male mice and conducted whole-body irradiation with 0 Gy, 10 Gy, and 20 Gy single doses. Kidney, lung, brain, and liver tissues were collected within 5 min of irradiation. PUFA-targeted and whole lipidomic analyses were conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that PUFA chains of kidney phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG) significantly increased within 5 min of 10 Gy and 20 Gy irradiation. The main components of increased PUFA chains in PC and PE were C18:2, C20:4, and C22:6, and in TG the main component was C18:2. The kidney lipidomes also showed significant changes from the perspective of lipid species, mainly dominated by an increase in PC, PE, TG, and signal lipids, while lipidomes of the lung, brain, and liver were slightly changed. Our results revealed that acute PUFA chains increase and other lipidomic changes in the kidney upon whole-body irradiation within 5 min of irradiation. The significantly increased lipids also showed a consistent preference for possessing PUFA chains. The lipidomic changes varied from organ to organ, which indicates that the response upon irradiation within a short time is tissue-specific.

Moderately Hypofractionated Radio(chemo)therapy With Simultaneous Integrated Boost for Recurrent, Previously Irradiated, High-grade Glioma.

The therapy of recurrent, previously irradiated, high-grade gliomas is still a major interdisciplinary challenge, and the overall prognosis remains poor. Reirradiation has been established as a major component of the management of relapse, in addition to further debulking surgery and systemic options. Herein, we present a moderately hypofractionated reirradiation concept with simultaneous integrated boost for such recurrent, previously irradiated tumors. From October 2019 to January 2021, 12 patients with recurrent malignant gliomas were re-irradiated. All patients had previously undergone surgery and irradiation with mostly normal fractions at the time of primary therapy. Radiotherapy of relapse was performed in all patients with 33 Gy, with 2.2 Gy single dose with a simultaneously integrated boost of 40.05 Gy with a single dose of 2.67 Gy in 15 fractions. Nine out of the 12 patients underwent debulking surgery before reirradiation, and seven patients received concurrent chemotherapy with temozolomide. The mean follow-up was 15.5 months. The median overall survival after recurrence was 9.3 months. The survival rate after 1 year was 33%. Toxicity during radiotherapy was low. In two patients, small areas of radionecrosis were observed at follow-up magnetic resonance imaging in the target volume; these patients were clinically asymptomatic. Moderate hypofractionation shortens the duration of radiotherapy and thereby improves accessibility for patients with limited mobility and prognosis, and achieves a respectable overall survival rate. Furthermore, the extent of late toxicity is also acceptable in these preirradiated patients.

Effects of X-ray irradiation on the redox status of mouse colorectal tissues

The effects of X-ray irradiation on the redox status of colorectal tissues were investigated using magnetic resonance redox imaging.The pyrrolidine-ring nitroxyl contrast agent, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP), was used as a suitable redox-sensitive contrast agent for colorectal tissues. The lower abdomen of an 8-week-old female C3H/HeSlc mouse was X-ray irradiated with a single 10-Gy dose under anesthesia. X-rays were collimated through a 19-mm slit made by a pair of 5-cm-thick lead blocks. MRI experiments using CmP as the contrast agent were conducted on mice irradiated by X-rays at different times, i.e., 2‒8 h, 1, 2, 4, 8, 12, and 16 day(s) after irradiation. Dynamic datasets of multi-slice T1-weighted images were obtained by repeating scans every 20 s for 22 min. The time course of the CmP-induced T1-weighted signal in colorectal tissues was analyzed. The relationship between mitochondrial damage and redox responses was also investigated.The k1 decay rate of CmP, which mainly reflects the biological reduction of nitroxyl radicals in tissue, was significantly suppressed on day 2, increased on day 8, and then recovered to the control level. The decrease in the k1 value on day 2 indicated the inhibition of biological activity in injured tissue. Further animal studies are required to verify the relationship between the redox response of the colorectum tissue and the mitochondrial damages. This magnetic resonance redox imaging technique has the potential to visualize radio-biological responses in the tissues of living animals.

Protective Potentials of Alpha-Lipoic Acid against Ionizing Radiation-Induced Brain Damage in Rats.

This study was aimed at determining the effects of alpha-lipoic acid on ionizing irradiation-induced oxidative damage and apoptosis in the brain of rats. The animals were exposed to whole-brain X-radiation with a 15 Gy single dose in the absence or presence of alpha-lipoic acid (200 mg/kg body weight) pretreatment for one week. The rats were divided into four groups (5 rats in each group): vehicle control, alpha-lipoic acid alone (ALA), radiation alone (RAD), and radiation plus alpha-lipoic acid (RAD+ALA). In the next stage, malondialdehyde (MDA), nitric oxide, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the brain tissue of the rats were measured. Furthermore, the Western blot analysis technique was performed to assess the NOX2, NOX4, and caspase-3 protein expression levels. Twenty-four hours after the irradiation, MDA and nitric oxide levels in the irradiated rats were significantly higher than those in the control group (p < 0.001); however, the pretreatment with alpha-lipoic acid resulted in a significant reduction in these stress oxidative markers (p < 0.05). Moreover, a significant decrease in CAT, SOD, and GPx levels was observed in the radiation group alone compared to the control group (p < 0.01); in contrast, the activities of these antioxidant enzymes significantly increased in the radiation plus alpha-lipoic acid group in comparison to the radiation group alone (p < 0.05). The results of Western blot analysis revealed that NOX2, NOX4, and caspase-3 protein expressions significantly elevated in the irradiated rats compared to the control group (p < 0.001). The pretreatment with alpha-lipoic acid could significantly decrease the expression levels of NOX2, NOX4, and caspase-3 in comparison with the radiation group alone (p < 0.05). According to the obtained findings, it can be mentioned that the alpha-lipoic acid pretreatment could mitigate the ionizing irradiation-induced oxidative damage and apoptosis in the brain of the rats.

Radiosensitization with Gadolinium Chelate-Coated Gold Nanoparticles Prevents Aggressiveness and Invasiveness in Glioblastoma.

This study aimed to evaluate the radiosensitizing potential of Au@DTDTPA(Gd) nanoparticles when combined with conventional external X-ray irradiation (RT) to treat GBM. Complementary biological models based on U87 spheroids including conventional 3D invasion assay, organotypic brain slice cultures, chronic cranial window model were implemented to investigate the impact of RT treatments (10 Gy single dose; 5×2 Gy or 2×5 Gy) combined with Au@DTDTPA(Gd) nanoparticles on tumor progression. The main tumor mass and its infiltrative area were analyzed. This work focused on the invading cancer cells after irradiation and their viability, aggressiveness, and recurrence potential were assessed using mitotic catastrophe quantification, MMP secretion analysis and neurosphere assays, respectively. In vitro clonogenic assays showed that Au@DTDTPA(Gd) nanoparticles exerted a radiosensitizing effect on U87 cells, and in vivo experiments suggested a benefit of the combined treatment "RT 2×5 Gy + Au@DTDTPA(Gd)" compared to RT alone. Invasion assays revealed that invasion distance tended to increase after irradiation alone, while the combined treatments were able to significantly reduce tumor invasion. Monitoring of U87-GFP tumor progression using organotypic cultures or intracerebral grafts confirmed the anti-invasive effect of Au@DTDTPA(Gd) on irradiated spheroids. Most importantly, the combination of Au@DTDTPA(Gd) with irradiation drastically reduced the number, the viability and the aggressiveness of tumor cells able to escape from U87 spheroids. Notably, the combined treatments significantly reduced the proportion of escaped cells with stem-like features that could cause recurrence. Combining Au@DTDTPA(Gd) nanoparticles and X-ray radiotherapy appears as an attractive therapeutic strategy to decrease number, viability and aggressiveness of tumor cells that escape and can invade the surrounding brain parenchyma. Hence, Au@DTDTPA(Gd)-enhanced radiotherapy opens up interesting perspectives for glioblastoma treatment.

Phenotypic Characteristics of Dormant Human Non-Small Cell Lung Cancer Cells Surviving Multifraction X-Ray Irradiation.

Phenotypic characteristics of human non-small cell lung cancer cells, A549 (p53 wild-type) and H1299 (p53-deficient) as well as their descendants surviving after multifraction X-ray irradiation at a cumulative dose of 60 Gy (sublines A549HR and H1299HR, respectively) were studied before and after additional 2 Gy single dose irradiation. In 24 h after the additional irradiation, we observed a significant increase in the proportion of cells with signs of entosis (by 5 times, p<0.05) and SA-β-gal+ cells (by 1.6 times, p<0.01) in the general population of A549HR cells. In contrast, a significant increase in the proportion of only SA-β-gal+ multinucleated giant cancer cells was revealed in the parental A549 cells. Additional single dose irradiation resulted in a significant (by 1.8 times, p<0.05) increase in the proportion of multinucleated giant cancer cells in H1299HR cells in comparison with their parental H1299 cells. These changes did not correlate with changes in the proportion of entotic cells, because their high basal content in the absence of functional p53 did not change in response to additional single dose irradiation. At the same time, both p53-deficient non-small cell lung cancer cell lines showed a significant (2.9-fold for H1299 and 5.5-fold for H1299HR cells, p<0.001) increase in the proportion of SA-β-gal+ cells in the general population, but not in the multinucleated giant cancer cells population.

BSCI-17 TOPIRAMATE DECREASES RADIATION-INDUCED CYTOTOXIC EDEMA IN HER2+ BRAIN METASTASES VIA AQUAPORIN 4 INHIBITION

Abstract Brain metastasis (BM) occurs in 30-40 % of breast cancer patients with Her2+ tumors, and radiation is part of the standard treatment for BM. About 10% of BM patients treated with radiation develop brain edema. We have shown that combination of Ado-trastuzumab Emtansine (T-DM1)-the main targeted therapy for metastatic Her2+ Breast Cancer- and radiation increases the risk of developing radionecrosis by 13.5-fold (Stump et al., 2019). We also showed that T-DM1 enhances radiation-induced astrocytic toxicity and cytotoxic edema through upregulation of aquaporin-4 water-transporter (AQP4). Here, we determined whether blockage of AQP4 would prevent astrocytic swelling –cytotoxic edema- in vitro and in vivo models of Her2+ BM. Results: Electron microscopy of brain cortex from mice treated with 35 Gy (single dose), showed acute astrocytic end-feet swelling and a significant increase in AQP4 expression compared with non-irradiated mice. Consistent with prior findings in murine astrocytes, primary human astrocytes (huAST) also upregulated AQP4 levels 24 h post-radiation (8 Gy), and T-DM1 treatment exacerbated this effect. AQP4 upregulation was concomitant with 4.8 fold increase in the astrocytic area (indicative of cytotoxic edema). The FDA-approved anti-epileptic and migraine prevention drug, Topiramate (TPM), which works as an AQP4 inhibitor, blocked radiation-induced astrocytic swelling in huAST in vitro. Thus, we tested whether pre-treatment with TPM could prevent radiation-induced edema in a mouse model of HER2+BMs. Mice were injected intracardially JmT1BR3 brain metastatic cells and ten days later randomized based on the total head flux to (1) Radiation + vehicle, (2) Radiation + TPM (2 days prior to irradiation), (3) Non-Radiation + vehicle, and (4) Non-radiation + TPM. TPM decreased brain-water content (a marker of brain edema) in irradiated mice as compared with vehicle-treated mice, without alteration of metastatic burden 21 days post-injection. These results suggest TPM could be repurposed as a preventive agent of radiation-induced brain edema.

Treatment of skin cancer arising within a burn scar (case report)

Background. In 1–2 % of cases, burn scars can cause more aggressive skin cancer that has a worse prognosis than conventional skin cancer. Most burn scar carcinomas are the squamous cell type (88 %) with the frequency of metastasis of 27 %. Due to the rarity of this malignancy and absence of guidance, treatment of scar carcinoma continues to be controversial. Surgical excision remains a standard mode of treatment for squamous cell carcinoma of the skin. Surgery is associated with problems to define a required limit to achieve clear margins; and subsequent grafting of the postoperative defect is limited due to the rigidity of the surrounding tissue and microcirculatory defects.Case description. We present a case report of squamous cell carcinoma of the skin originating from burn scars. The patient received a radical course of conformal external beam therapy with a total dose of of 68 Gy in 2 Gy single doses (34 fractions) resulting in an increase in the ulcer due to the destruction of the infiltrative component of the tumor. Radical electrosurgical excision of the tumor with a free TRAM-flap reconstruction in the MS-0 version (using the full width of the rectus abdominis muscle) was performed. Microvascular anastomoses were made between the deep lower epigastric and thoracodorsal vessels on the right. There were no postoperative complications. No evidence of recurrence and tumor progression was found with a follow-up for 7 months.Conclusion. A personified approach to the treatment of burn scar carcinoma demonstrated good treatment outcomes. Surgical reconstruction of the postoperative defect in these patients may require the use of composite flaps and, in specific cases, microsurgical techniques.

Relative biological effectiveness of single and split helium ion doses in the rat spinal cord increases strongly with linear energy transfer

Background and purposeDetermination of the relative biological effectiveness (RBE) of helium ions as a function of linear energy transfer (LET) for single and split doses using the rat cervical spinal cord as model system for late-responding normal tissue. Material and methodsThe rat cervical spinal cord was irradiated at four different positions within a 6 cm spread-out Bragg-peak (SOBP) (LET 2.9, 9.4, 14.4 and 20.7 keV/µm) using increasing levels of single or split doses of helium ions. Dose-response curves were determined and based on TD50-values (dose at 50% effect probability using paresis II as endpoint), RBE-values were derived for the endpoint of radiation-induced myelopathy. ResultsWith increasing LET, RBE-values increased from 1.13 ± 0.04 to 1.42 ± 0.05 (single dose) and 1.12 ± 0.03 to 1.50 ± 0.04 (split doses) as TD50-values decreased from 21.7 ± 0.3 Gy to 17.3 ± 0.3 Gy (single dose) and 30.6 ± 0.3 Gy to 22.9 ± 0.3 Gy (split doses), respectively. RBE-models (LEM I and IV, mMKM) deviated differently for single and split doses but described the RBE variation in the high-LET region sufficiently accurate. ConclusionThis study established the LET-dependence of the RBE for late effects in the central nervous system after single and split doses of helium ions. The results extend the existing database for protons and carbon ions and allow systematic testing of RBE-models. While the RBE-values of helium were generally lower than for carbon ions, the increase at the distal edge of the Bragg-peak was larger than for protons, making detailed RBE-modeling necessary.

Comparison of ultra-high versus conventional dose rate radiotherapy in a patient with cutaneous lymphoma

A patient with a cutaneous lymphoma was treated on the same day for 2 distinct tumors using a 15 Gy single electron dose given in a dose rate of 0.08 Gy/second versus 166 Gy/second. Comparing the two treatments, there was no difference for acute reactions, late effects at 2 years and tumor control.

Evaluation of the radio-protective role of PEG-Fe3O4 NPs on γ-irradiated male Wistar rats

This study explores the conceivable ameliorative outcome of iron oxide nanoparticles (1.5 mg/kg intraperitoneal (IP) injection) on γ-irradiated male Wistar rats. Iron oxide nanoparticles (Fe3O4 NPs) were prepared via the co-precipitation method using polyethylene glycol (PEG) as an emulsifier to yield PEG-Fe3O4 NPs. XRD, TEM, and FTIR clarified that PEG-Fe3O4 NPs were formed with a spherical shape (5–15 nm) and cubic crystal configuration. Whole-body γ-irradiation of rats at 5.5 Gy (single sublethal dose) instigated significant biochemical disorders in the blood picture, protein fractions, lipid profile, liver enzymes, and kidney function after three weeks post-irradiation. Histo-pathological images displayed diverse distortion in the liver and renal architecture after three weeks post-γ-irradiation. These distortions varied from swelling, vacuolization to necrosis and complete degeneration of the epithelial cells. Histopathological image of liver sections of the group injected by PEG-Fe3O4 NPs pre-γ-irradiation (group 4) showed Kupffer cells activation. Likewise, photomicrograph of the same group signposts the inhibition in the kidney morphological alterations induced by γ-irradiation. So In vivo administration of PEG-Fe3O4 NPs pre-γ-irradiation diminishes the impact of γ-irradiation to a great extent on biochemical and histological disorders. On the other hand, administration of the PEG-Fe3O4 NPs post-irradiation couldn't overcome the damaging effect of γ-irradiation. Therefore, PEG-Fe3O4 NPs can be a useful radio-protective agent when administered before γ-irradiation. This study introduces a thorough report on the radio-protective role of PEG-Fe3O4 NPs on γ-irradiated rats exploiting the biosafety of PEG-Fe3O4 NPs.

RADT-21. DUAL FET PET-GUIDED SIB IN RADIOTHERAPY OF NEWLY DIAGNOSED GLIOBLASTOMA - A PILOT STUDY

Abstract BACKGROUND PET using FET is a valuable tool to determine the actual glioblastoma infiltration.The FET-PET examination can be performed using the dual-time point acquisition of FET . Infiltration defined in dual FET PET corresponds to the location and shape of the recurrence. The aim of this study was to evaluate safety and efficacy of simultaneous integrated boost based on dual FET PET combined with temozolomide TMZ for the postoperative treatment of GBM. METHODS AND MATERIALS In a prospective pilot study, 17 patients were enrolled. All patient presented an active tumor in postoperative PET imaging. The radiotherapy was performed as an FET-PET-based integrated-boost IMRT. The prescribed dose was 78 and 60 Gy (single dose 2.6 and 2.0 Gy, respectively). The progression-free survival (PFS) and overall survival (OS), toxicities and radiation necrosis rate were evaluated. RESULTS The median follow up was 37 months.Two patients were found to have uncontrolled seizures during radiation treatment and were not able to received treatment per protocol. Patients treated per protocol presented new or increased neurological deficits in 7/15 cases in a month after irradiation. In 4 patients radiation necrosis was confirmed in pathological report after re-surgery. Three patients were still alive after 26,28 and 38 months of follow up without progression and any signs of treatment related late toxicity. The 2-year survival rate was 43% in all patients treated per protocol. Median overall survival (OS) and disease-free survival (DFS) were 20 and 12 months, respectively. In a subgroup of MGMT methylated and unmethylated the median survival was 25 and 12 months. CONCLUSIONS Our dose escalation concept with a total dose of 78 Gy, based on FET-PET, have lead to promising survival results even within MGMT unmethylated subgroup. However rate of early toxicity and radiation necrosis is high.

Identification of a Novel cGas/STING/Type I Interferon Specific Murine Cardiac Immune Landscape Following Radiation Therapy

<h3>Purpose/Objective(s)</h3> Cardiotoxicity from radiation treatment to the chest is a late toxicity that has been shown to increase with radiation dose. While clinical parameters and advances in radiation techniques have resulted in lower doses to the heart, the pathophysiologic mechanisms of radiation cardiotoxicity remains a debated topic. We have previously demonstrated that, in murine models, radiation activates a delayed, fibroblast-specific type I interferon response that is dependent on the cytosolic nucleic acid sensor, cGas and its downstream signaling protein STING. Indeed, STING knockout mice exhibit a survival advantage in comparison to wild type mice following a radiation challenge to the heart (20Gy x 1). In this study, we sought to evaluate the consequences of the type I interferon activation on cardiac tissue-specific white blood cell population and identify novel radiation-dependent changes of cardiac immune infiltrates. <h3>Materials/Methods</h3> All animal experiments were performed in accordance with IACUC guidelines. C57BL/6 wild type mice and C57BL/6 Tmem173^gt (catalytically inactive STING) were treated with either sham or 12 Gy single dose to the heart using opposing tangents. At 1 month, hearts were harvested and CD45+ positive cells were immunoprecipitated and sent for 3' single cell RNA (scRNA) sequencing using 10X genomics. ScRNA data was analyzed using Seurat 3.0 <h3>Results</h3> Our results show that radiation induces the upregulation of a subset of cardiac macrophages, interferon inducible cardiac (IFNIC) macrophages. This effect is that is abrogated in mice lacking a functional STING. Furthermore, we observed a general activation of innate immunity as evidenced by increases in the dendritic cell population as well as upregulation of non-classical class I MHC molecules in non-IFNIC macrophages. More surprisingly, we find that there is a marked increase in tissue specific B cell population following radiation, an effect that is completely abolished in mice lacking a functional STING. <h3>Conclusion</h3> We describe for the first time the immune landscape of heart tissue following radiation. We find a previously undescribed infiltration of IFNIC macrophages and a robust activation of an innate immunity. Furthermore, we find a strong effector humoral adaptive response, likely downstream. These findings open the possibility to further understand the role of immune infiltrates in mediation of normal tissue toxicity following radiation.

PO-1169 30 Gy single dose stereotactic radiation therapy in a series of patients with lung oligometastasis

PO-1169 30 Gy single dose stereotactic radiation therapy in a series of patients with lung oligometastasis

Time-sequential change in immune-related gene expression after irradiation in glioblastoma: next-generation sequencing analysis

ABSTRACT The time-sequential change in immune-related gene expression of the glioblastoma cell line after irradiation was evaluated to speculate the effect of combined immunotherapy with radiotherapy. The U373 MG glioblastoma cell line was irradiated with 6 Gy single dose. Next-generation sequencing (NGS) transcriptome data was generated before irradiation (control), and at 6, 24, and 48 h post-irradiation. Immune-related pathways were analyzed at each time period. The same analyses were also performed for A549 lung cancer and U87 MG glioblastoma cell lines. Western blotting confirmed the programmed death-ligand 1 (PD-L1) expression levels over time. In the U373 MG cell line, neutrophil-mediated immunity, type I interferon signaling, antigen cross-presentation to T cell, and interferon-γ signals began to increase significantly at 24 h and were upregulated until 48 h after irradiation. The results were similar to those of the A549 and U87 MG cell lines. Without T cell infiltration, PD-L1 did not increase even with upregulated interferon-γ signaling in cancer cells. In conclusions, in the glioblastoma cell line, immune-related signals were significantly upregulated at 24 and 48 h after irradiation. Therefore, the time interval between daily radiotherapy might not be enough to expect full immune responses by combined immune checkpoint inhibitors and newly infiltrating immune cells after irradiation.

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

Purpose: Previous reports investigating single fraction high dose rate (HDR) brachytherapy as monotherapy for localized prostate cancer have reported favorable toxicity profiles but higher than expected local failure rates. This analysis reports outcomes of a series of patients treated with single fraction HDR brachytherapy to an escalated whole gland dose of 21 Gy.