Radiation Toxicity Research Articles

Proton radiotherapy for rectal cancer

AIM: to assess the effectiveness of proton radiotherapy as part of a combined approach to the treatment of rectal malignancies and to assess acute radiation toxicity, which directly affects patients’ quality of life.PATIENTS AND METHODS: between 2020 and 2023, a study included 74 patients with rectal cancer. The mean age of the patients was 65 ± 9.9 years, 44 (60%) males. Stage I occurred in 8 (10.8%) patients, stage II — in 14 (18.9%) patients, stage III — in 52 (70.3%) patients. At the first stage, all patients completed proton radiation therapy in the classical fractionation mode.RESULTS: of the adverse events, 49 (66%) patients had grade 1–2 radiation reactions in the form of proctitis and cystitis. There were no local radiation reactions of grade 3 or higher. Systemic complications of grade 3 were noted in 2 (2%) patients in the form of hematological toxicity — anemia (1%), afebrile neutropenia (2%). Of the 62 operated patients, 12 (19.3%) people showed complete therapeutic pathomorphosis. With a median follow-up of 23 months (13;35), 1 (1.35%) patient showed continued tumor growth 28 months after completed radiotherapy, 2 (2.7%) patients had local recurrence 3 and 18 months after treatment. Distant metastases to the lungs, liver, or bones were detected in 9 (12.2%) patients, median — 12 months (6;23). Mortality during the entire observation period was 9 (12.2%) patients. Sixty-two (83.8%) patients showed no signs of relapse or progression of the disease, of which 9 (14.5%) patients did not receive any treatment after chemoradiotherapy and are in the process of active follow-up.CONCLUSION: proton radiation therapy in patients with rectal cancer in two-year overall survival (90.5%) and progression-free survival (88.9%) are comparable with the literature data of recent studies, but are superior in overall survival pathological response (19.3%).

Systematic review of adherence to swallow and trismus exercises during radiation therapy for head and neck cancer.

Understanding the barriers and facilitators for prophylactic swallowing and trismus exercises for patients undergoing radiation to the head and neck may help exercise adherence. The analysis reviews all published reports of exercise adherence with a critical appraisal following PRISMA guidelines. A total of 137 potential papers were identified; 20 studies met the inclusion criteria. The most commonly reported facilitators for swallowing and trismus exercises were regular clinician contact and online resources to reinforce instructions, set goals, and manage radiation toxicities. Social support and perceived benefit from exercises were also reported to be of help. The most common barriers to exercise were radiation toxicities, anxiety, feeling overwhelmed with information, and not understanding the reason for the exercises. Understanding facilitators and barriers to adherence is critical when designing exercise interventions for patients undergoing radiation for head and neck cancer.

Proximity Effects of Electromagnetic Field Radiation from Cellular Wireless System on Living Things and Their Mitigation Techniques

Research on electromagnetic field radiation exposure from cellular wireless systems is expected to become more important, allowing researchers to provide solutions for the effects of this radiation on human living beings. During the research, experiment animals were unprotected to RF radiations for 8 hours every day for 30 days. The exposure duration involved the placement of test animals in Plexiglass boxes. An RF transmitter was placed on the cage's roof from within. The transmitter emitted EMF radiations that were noted in rats. An elevated plus maze and open field test was utilized to determine behavioral parameters. On the 8th, 15th and 30th day of exposure, behavioral tests were administered. According to our findings, EMF radiation toxicity is closely linked with the exposure to this form of radiation. An increase in the toxicity level was observed as exposure time passed. Furthermore, this research demonstrated that EMF radiation exposure resulted in neuronal injury. The RF transmitter was subjected to tests with shielding materials, including woven and non-woven fabrics, which serve as technical textiles for electromagnetic radiation protection.

Outcomes of pericardial complications among patients with solid and liquid cancer: Analysis of National Inpatient Sample database.

e23073 Background: Pericardial complications (PC) are common in malignancy as sequelae of metastasis, direct toxicity of radiation or chemotherapy, or pericardial infection/inflammation due to malignancy. The goal of this study was to assess the cardiovascular outcomes of pericardial complications among patients with solid and liquid cancer. Methods: The National Inpatient Sample from the years 2015 to 2018 was queried to assess cardiovascular outcomes in the setting of pericardial complications (acute pericarditis, chronic constrictive pericarditis, chronic adhesive pericarditis, hemopericardium, cardiac tamponade and other unspecified pericarditis) for patients that have any solid or liquid malignancy. Outcomes included in-hospital mortality, acute kidney injury (AKI), heart failure (HF), cardiogenic shock (CS), myocardial infarction (MI), sudden cardiac arrest (SCA), mechanical circulatory support (MCS), major adverse cardiovascular and cerebrovascular events (MACCE), and stroke. Outcomes were assessed using chi-square analysis using STATA. Results: A total of 1,183,619 cancer patients with PC (n = 20,410.00; 1.7%) and without PC (n = 1,163,209.60; 98.3%) were included. The mean age of patients with and without PC was 58 and 59 years, respectively. The average length of stay in the hospital was 14 and eight days in patients with and without PC, respectively. The most common complications were electrolyte disorders (51.2%, p = 0.000) and arrhythmias (40.4 %, p = 0.000) for patients with and without PC. Patients with PC had higher incidence of in-hospital mortality (11.7% vs 5.1%, p = 0.000), AKI (37.8% vs 22.1%, p = 0.000), HF (25.7% vs 15.5%, p = 0.000), CS (2.7% vs 0.4%, p = 0.000), MI (3.6% vs 2.0%, p = 0.000), SCA (3.2% vs 1.0%, p = 0.000), MCS (0.7% vs 0.1%, p = 0.000), and MACCE (17% vs 7.9%, p = 0.000) compared to cancer patients without PC. There was no difference in outcomes in terms of stroke (1.2% vs 1.2%, p = 0.879). The yearly trend was stable for length of stay among both groups while adjusted total hospital cost was progressively increasing from 2015 to 2018, with a greater net increase in those with PC. Yearly trends of complications were stable among both cohorts. Conclusions: Pericardial complications are prevalent in up to 1.7% of cancer patients, and they are associated with worse cardiovascular outcomes as compared to patients without pericardial complications. Patients with PC also have a higher incidence of in-hospital mortality.

Exploring the Potential of Metformin in Mitigating Radiation-induced Gastrointestinal and Hematopoietic System Injury in Rats After Whole-body X-ray Radiation: An Experimental Study.

The modern world faces a growing concern about the possibility of accidental radiation events. The Hematopoietic system is particularly vulnerable to radiationinduced apoptosis, which can lead to death. Metformin, a drug used to treat diabetes, has been shown to protect normal cells and tissues from the toxic effects of radiation. This study aimed to evaluate the effectiveness of metformin in mitigating radiation injury to the gastrointestinal and hematological systems of rats. The study involved 73 male rats. After total body irradiation with 7.5 Gy of X-rays, rats were treated with metformin. Seven days later, the rats were sacrificed and blood samples were taken for evaluation. The study found that metformin was not effective in mitigating radiation injury. The histopathological assessment showed no significant changes in goblet cell injury, villi shortening, inflammation, or mucous layer thickness. In terms of biochemical evaluation, metformin did not significantly affect oxidative stress markers, but irradiation increased the mean MDA level in the radiation group. The complete blood count revealed a significant decrease in WBC and platelet, counts in the radiation group compared to the control group, but no significant difference was found between the radiation and radiation + metformin groups. In conclusion, metformin may not be a good option for reducing radiation toxicity after accidental exposure. Despite treatment, there was no improvement in platelet, white blood cell, and lymphocyte counts, nor was there any decrease in oxidative stress. Further research is needed to explore other potential treatments for radiation injury.

Influence of intensity-modulated radiation therapy on long-term survival and late injury in patients with nasopharyngeal carcinoma after induction chemotherapy.

e24048 Background: To retrospectively analyze the effect of nasopharyngeal primary tumor (GTVnx) target delineation after induction chemotherapy on the long-term survival and late injury of patients after intensity-modulated radiotherapy, so as to provide a reference for the optimal treatment of nasopharyngeal carcinoma. Methods: Retrospective analysis was performed on 52 patients with nasopharyngeal carcinoma who underwent target delineation and radiotherapy after induction chemotherapy in our department from December 2011 to October 2013. All patients underwent long-term survival follow-up and analysis of late injury. The survival rate was calculated by Kaplan-Meier method and log-rank test, Univariate prognostic analysis was performed. Cox model was used to conduct multivariate prognostic analysis. The late radiation toxicity was Evaluation by RTOG/EORTC. Results: From December 2011 to October 2013,52 patients were enrolled in the study group. The follow-up period was up to December 2020. Among them, 23 patients died and the mortality rate was 44.23%, the recurrence rate was 0.38%. Serious adverse reactions occurred in 7 cases (13.2%). The 1,3,5,8 year survival rates were as follows: OS was 94.2%, 82.7%, 65.4%, 49.6%, LRFS was 96.2%, 82.7%, 63.5%, 46.2%, the survival rates of DMFS were 94.2%, 78.8%, 59.6% and 44.2%. Conclusions: The 5 and 8-years OS, LRFS and DMFS of NPC after induction chemotherapy patients treated with IMRT was relatively high, Distant metastasis was the main cause of treatment failure, The main late injuries include grade Ⅰ / Ⅱ hearing impairment, dysphagia dental, caries, xerostomia, the grade Ⅲ and Ⅳ late radiation injury was lower.

Response of Microbial Communities to Naturally Occurring Radioactive Material-Contaminated Sediments: A Microcosm-Based Study.

There is a growing need to understand the potential ecological impacts of contaminants in offshore oil and gas infrastructure, especially if that infrastructure is to be left in situ as a decommissioning option. Naturally occurring radioactive material (NORM) is one type of contaminant found in solid deposits on internal surfaces of infrastructure that poses potential ecological harm if released into the marine environment. Microbes are important components of marine sediment ecosystems because they provide ecosystem services, yet the impacts of NORM contamination to these communities are not well understood. The present study aimed to investigate the response of benthic microbial communities to NORM-contaminated scale, collected from an offshore oil and gas system, via controlled laboratory microcosm studies. Changes to microbial communities in natural sediment and sediments spiked with NORM at radium-226 activity concentrations ranging from 9.5 to 59.8 Bq/kg (in partial equilibria with progeny) over 7 and 28 days were investigated using high-throughput sequencing of environmental DNA extracted from experimental sediments. There were no significant differences in microbial community composition between control and scale-spiked sediments over 7 and 28 days. However, we observed a greater presence of Firmicutes in the scale-mixed treatment and Chloroflexi in the scale-surface treatments after 28 days. This could suggest selection for species with contaminant tolerance or potential resilience to radiation and metal toxicity. Further research is needed to explore microbial tolerance mechanisms and their potential as indicators of effects of radionuclide-contaminated sediments. The present study demonstrated that microcosm studies can provide valuable insights about the potential impacts of contamination from oil and gas infrastructure to sediment microbial communities. Environ Toxicol Chem 2024;43:1648-1661. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Oral administration of probiotic spore ghosts for efficient attenuation of radiation-induced intestinal injury

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients’ quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.

Synthesis and preclinical evaluation of 68Ga-labeled PSMA tracers with improved pharmacological properties

Prostate cancer (PCa) is one of the most common tumors in men, with the overexpression of prostate-specific membrane. In this study, we developed four new 68Ga-labeled PSMA-targeting tracers by introducing quinoline, phenylalanine and decanoic acid groups to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Four radiotracers were synthesized with radiochemical purity >95 %, and exhibited high stability in vivo and in vitro. The inhibition constants (Ki) of SDTWS01-04 to PSMA were in the nanomolar range (<10 nM). Micro PET/CT imaging and biodistribution analysis revealed that 68Ga-SDTWS01 enabled clear tumor visualization in PET images at 1.5 h post-injection, with excellent pharmacokinetic properties. Notably, the kidney uptake of 68Ga-SDTWS01 significantly reduced, with higher tumor-to-kidney ratio (0.36 ± 0.02), tumor-to-muscle ratio (24.31 ± 2.10), compared with 68Ga-PSMA-11 (T/K: 0.15 ± 0.01; T/M: 14.97 ± 1.40), suggesting that 68Ga-SDTWS01 is a promising radiotracer for the diagnosis of PCa. Moreover, SDTWS01 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for the treatment of PCa.

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity

BackgroundNon-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts.ResultPsyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles.ConclusionThese supplements may be useful in combination with radiotherapy in patients with pelvic malignancy.C3P3Z-i-BEWcsPG8U_9P4fVideo

Prospective comparison of acute severe toxicities between smokers and non-smokers during radiotherapy for head and neck cancers

Background and purposeThe association between smoking and acute radiation toxicities of head and neck cancer (HNC) is currently unproven. The aim of the study was to compare the occurrence of acute severe toxicity between active and non-active smokers treated for HNC by radiotherapy. Materials and methodsA prospective monocentric cohort study included patients treated by (chemo)radiotherapy for HNC from January 2021 to January 2023. Smoking status was recorded. Patients underwent a medical exam weekly during the radiotherapy to report acute toxicities according to the Common Terminology Criteria for Adverse Effects system version 5.0. Primary endpoint was the occurrence of at least one grade ≥ 3 acute toxicity among mucositis, dysphagia and dermatitis. ResultsAmong the 102 patients included, 27.4 % were active smokers, 58.8 % were former smokers and 13.7 % had never smoked. Regarding toxicity, 23.5 % (n = 24) patients experienced severe mucositis, 37.2 % (n = 38) severe dysphagia, 13.7 % (n = 14) severe dermatitis and 54.9 % (n = 56) experienced at least one of them. Occurrence of severe acute toxicity was not statistically associated with smoking during radiotherapy (64.3 % among active smokers versus 51.3 % among non-active smokers; p = 0.24). On multivariate analysis, concurrent chemotherapy (87.5 % vs 65.2 %; OR = 5.04 [1.64–15.52]; p = 0.004) and 2.12 Gy versus 2 Gy fractionation schedule (64.3 % vs 41.3 %; OR = 2.53 [1.09–5.90]; p = 0.03) were significantly associated with severe acute toxicity. ConclusionThis study did not find an association between smoking during radiotherapy for HNC and occurrence of severe acute toxicities.

Mini-Beam Spatially Fractionated Radiation Therapy for Whole-Brain Re-Irradiation—A Pilot Toxicity Study in a Healthy Mouse Model

For patients with recurrent brain metastases, there is an urgent need for a more effective and less toxic treatment approach. Accumulating evidence has shown that spatially fractionated radiation therapy (SFRT) is able to provide a significantly higher therapeutic ratio with lower toxicity compared to conventional radiation using a uniform dose. The purpose of this study was to explore the potential low toxicity benefit of mini-beam radiotherapy (MBRT), a form of SFRT, for whole-brain re-irradiation in a healthy mouse model. Animals first received an initial 25 Gy of uniform whole-brain irradiation. Five weeks later, they were randomized into three groups to receive three different re-irradiation treatments as follows: (1) uniform irradiation at 25 Gy; (2) MBRT at a 25 Gy volume-averaged dose (106.1/8.8 Gy for peak/valley dose, 25 Gy-MBRT); and (3) MBRT at a 43 Gy volume-averaged dose (182.5/15.1 Gy for peak/valley dose, 43 Gy-MBRT). Animal survival and changes in body weight were monitored for signs of toxicity. Brains were harvested at 5 weeks after re-irradiation for histologic evaluation and immunostaining. The study showed that 25 Gy-MBRT resulted in significantly less body weight loss than 25 Gy uniform irradiation in whole-brain re-irradiation. Mice in the 25 Gy-MBRT group had a higher level of CD11b-stained microglia but also maintained more Ki67-stained proliferative progenitor cells in the brain compared to mice in the uniform irradiation group. However, the high-dose 43 Gy-MBRT group showed severe radiation toxicity compared to the low-dose 25 Gy-MBRT and uniform irradiation groups, indicating dose-dependent toxicity. Our study demonstrates that MBRT at an appropriate dose level has the potential to provide less toxic whole-brain re-irradiation. Future studies investigating the use of MBRT for brain metastases are warranted.

Abstract PO1-22-03: Radiation Toxicity and Treatment Outcomes in Breast Cancer Patients with ATM Pathogenic and VUS Mutations: Implications for Personalized Therapy

Abstract Introduction: Previous studies have shown that ATM (ataxia-telangiectasia mutated) mutations may be associated with increased radiation sensitivity and altered treatment response. However, there is a limited understanding of the clinical implications and optimal management strategies for breast cancer patients with ATM mutations receiving radiotherapy (RT). The aim of our study is to assess the impact of ATM mutations on radiation response and treatment outcomes in breast cancer patients undergoing RT. Material and Methods: A total of 79 female patients diagnosed with breast cancer were included in the study, with 31 (39.3%) having pathogenic (P) and likely pathogenic (LP) variants (all of the variants were heterozygous) and 48 (60.8%) having VUS variants detected through whole ATM gene sequencing screening for patients in accordance with NCCN clinical practice guideline. Statistical analysis, including descriptive, graphical, and inferential methods, such as the Kolmogorov-Smirnov test, Mann-Whitney U Test, and Chi-square tests, was conducted using SPSS version 25.0 to evaluate the normal distribution of continuous variable scores and perform quantitative and qualitative comparisons between groups at a 95% confidence level (p &amp;lt; 0.05). Results: The median age of the patients was 44 years (range: 24-74), with 75% of them being 50 years old or younger .The rate of breast cancer in patients with VUS variants was significantly higher in those aged 50 and below compared to those with P/LP variants (83% vs. 61%, p=0.028). There was no statistically significant difference in clinical stage, tumour histological type, and molecular subtype classification based on ATM gene variant type (P/LP vs. VUS) among the patients (p&amp;gt;0.05), but the rate of high tumour grade was significantly higher in the VUS variant group (65% vs. 40%, p=0.034). The rate of patients who received RT was 87%, with 26 patients receiving radiation to the breast or chest wall and 43 patients receiving additional regional lymph node irradiation. There were no statistically significant differences in surgical and systemic treatment types and RT dose based on ATM gene variant type (P/LP vs. VUS) (p&amp;gt;0.05). Among the patients who received RT, 33 (48%) experienced early-stage skin reactions, and 15 (22%) experienced late-stage skin reactions according to Common Terminology Criteria for Adverse Events (CTCAE) v5. No Grade 3, 4 and 5 early and late toxicity were observed . The rate of early (83% vs. 23%; p&amp;lt; 0.001) and late (35% vs. 13%; p=0.029) skin reactions was significantly higher in the P/LP variant group compared to the VUS variant group. Grade I lymphedema was observed in 2 (2.5%) patients, 1 (3.2%) in the P/LP group and 1 (2.1%) in the VUS group (p&amp;gt;0.05). Among the 23 patients who underwent breast reconstruction, 1 (4%) had implant revision and 1 (4%) experienced implant loss, both of which were observed in the pathogenic variant group (p&amp;gt;0.05). Conclusion: Limited clinical data exists on RT toxicity in breast cancer patients with ATM gene mutations, and clear guidelines for decision-making are lacking. Our study revealed higher rates of acute and chronic skin reactions in the P/LP variant group, highlighting the need for further investigation into the impact of these variants on treatment outcomes and patient management. However, it is crucial to manage these reactions effectively and not allow them to hinder treatment. Additional research and interventions are warranted to better understand and address these reactions, aiming to enhance the overall treatment experience and outcomes for patients with ATM gene mutations. Citation Format: Evrim Tezcanli, Seda Eroz, Ugur Ozbek, Ahmet Yesilyurt, CIHAN URAS, Nuran Bese. Radiation Toxicity and Treatment Outcomes in Breast Cancer Patients with ATM Pathogenic and VUS Mutations: Implications for Personalized Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-03.

L. plantarum and L. casei synergistically mitigate Gastro-Intestinal Acute Radiation Syndrome (GI-ARS)

Introduction: Incidental or accidental acute exposure to ionizing radiation causes radiation toxicity, for which there are no known medical countermeasures (MCMs). Ionizing radiation alters host gut epithelium as well as the gut microbiome. We sought to investigate if radiation induced gut dysbiosis occurred as a result of depletion of gut-protective bacteria, and if probiotic supplementation of such bacteria could help mitigate GI-ARS post ionizing radiation exposure. Methods: Adult C57BL/6 mice were subjected to total body irradiation, and a defined concentration of probiotics (either individually or combined) were given 24 h after radiation exposure. Mice were sacrificed 24 hours post treatment (i.e., 48 h post irradiation). Vascular-to-luminal flux of FITC-inulin was measured to evaluate intestinal mucosal permeability and endotoxemia by measuring plasma lipopolysaccharide. Gut microbiota was analyzed by 16S rRNA sequencing. Intestinal epithelial junctions were analyzed by immunofluorescence confocal microscopy and mucosal inflammatory response by RT-PCR for cytokine expression. Systemic inflammation was evaluated by ELISA for plasma cytokines. Results and conclusion: Our data show that radiation altered the taxonomic composition of the microbiota compared to age-matched sham treated mice. Shannon index analysis showed a significant decrease in α-diversity in irradiated mice. Bray-Curtis analysis indicated significant differences in microbiota composition between Sham and IR groups. E. coli abundance was increased whereas Lactobacillus abundance was decreased, particularly L. plantarum and L. casei. Probiotic supplementation with individual Lactobacillus species each mitigated radiation induced intestinal barrier dysfunction, gut specific as well as systemic inflammatory cytokine expression and endotoxemia. Our preliminary data further indicates that L. plantarum affects Epidermal Growth Factor Receptor (EGFR)-mediated signaling whereas L. casei was EGFR-independent. Interestingly, combined supplementation in a 1:1 ratio further enhanced recovery compared to adding the individual effects. Individual supplementation of L. plantarum and L. casei to irradiated mice reduced intestinal (ileal) permeability by 2-fold and 3-fold respectively, whereas combined supplementation reduced ileal permeability almost 8-fold compared to irradiated but untreated mice. This data indicates that L. plantarum and L. casei mitigate GI-ARS by distinct cellular mechanisms. Furthermore, data show that a mixture of these probiotic species is more effective in radio-mitigation than individually. Further mechanistic analysis will be required to identify cross-talking targets between mechanisms of these probiotics and synergistic radio-mitigation. In conclusion, Lactobacillus species are potential MCMs for the treatment of GI-ARS. Funding acknowledgements: NIH/NIAID, UO1-AI170019, UO1-AI172991. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Treatment Related Acute Toxicities Between Treatment with 3D-CRT and IMRT in Localised Prostate Cancer.

To compare the acute toxicities of two radiation treatment techniques, intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (3D-CRT) in localised prostate adenocarcinoma. Descriptive study. Place and Duration of the Study:Department of Oncology, Dr. Ziauddin Hospital, Karachi, Pakistan, from July 2016 to June 2022. Patients with localised prostate adenocarcinoma who underwent treatment using two different advanced radiotherapy techniques i.e., IMRT and 3D-CRT were recruited during the study period. They were followed up for six months for acute gastrointestinal (GI) and genitourinary (GU) adverse events (acute toxicities) related to both treatment modalities according to Modified radiation therapy oncology group (RTOG) criteria. The acute toxicities were assessed at the 2nd, 4th, and 6th week during treatment and at the 3rd and 6th month after treatment. There were 78 patients, with 39 patients in each group. The mean age was 68 ± 10 years in the 3D-CRT and 68 ± 07 years in the IMRT group. Patients in the IMRT group exhibited markedly lower treatment-related acute GI and GU effects at the end of 4th and 6th weeks for anorectal pain (p = 0.04) and (p = 0.01) and burning micturition (p = 0.003) and (p = 0.01), respectively. Furthermore, at 3 months anorectal pain (p = 0.02), loose stools (p = 0.005), and burning micturition (p = 0.01) were present and at 6 months anorectal pain was (p = 0.01) still present. Radiation therapy modalities 3D-CRT and IMRT both showed acceptable toxicity profile in the management of localised prostate cancer, while IMRT group exhibited significantly lower treatment-related acute GI and GU effects. 3D-CRT (3-Dimensional Conformal Radiation Therapy), IMRT (Intensity-Modulated Radiation Therapy), Radiation toxicity.

3128: Self-applied photobiomodulation therapy for radiation toxicity in head and neck cancer patients

3128: Self-applied photobiomodulation therapy for radiation toxicity in head and neck cancer patients

Development and first-in-human study of PSMA-targeted PET tracers with improved pharmacokinetic properties.

A series of new 68Ga-labeled tracers based on [68Ga]Ga-PSMA-617 were developed to augment the tumor-to-kidney ratio and reduce the activity accumulation in bladder, ultimately minimize radiation toxicity to the urinary system. We introduced quinoline group, phenylalanine and decanoic acid into different tracers to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Their binding affinity onto LNCaP cells was determined through in vitro saturation assays and competition binding assays. In vivo metabolic study, PET imaging and biodistribution experiment were performed in LNCaP tumor-bearing B-NSG male mice. The most promising tracer was selected for first-in-human study. Four radiotracers were synthesized with radiochemical purity (RCP) > 95% and molar activity in a range of 20.0-25.5GBq/μmol. The binding affinities (Ki) of TWS01, TWS02 to PSMA were in the low nanomolar range (< 10nM), while TWS03 and TWS04 exhibited binding affinities with Ki > 20nM (59.42nM for TWS03 and 37.14nM for TWS04). All radiotracers exhibited high stability in vivo except [68Ga]Ga-TWS03. Micro PET/CT imaging and biodistribution analysis revealed that [68Ga]Ga-TWS02 enabled clear tumor visualization in PET images at 1.5h post-injection, with higher tumor-to-kidney ratio (T/K, 0.93) and tumor-to-muscle ratio (T/M, 107.62) compared with [68Ga]Ga-PSMA-617 (T/K: 0.39, T/M: 15.01) and [68Ga]Ga-PSMA-11 (T/K: 0.15, T/M: 24.00). In first-in-human study, [68Ga]Ga-TWS02 effectively detected PCa-associated lesions including primary and metastatic lesions, with lower accumulation in urinary system, suggesting that [68Ga]Ga-TWS02 might be applied in the detection of bladder invasion, with minimized radiation toxicity to the urinary system. Introduction of quinoline group, phenylalanine and decanoic acid into different tracers can modulate the binding affinity and pharmacokinetics of PSMA in vivo. [68Ga]Ga-TWS02 showed high binding affinity to PSMA, excellent pharmacokinetic properties and clear imaging of PCa-associated lesions, making it a promising radiotracer for the clinical diagnosis of PCa. Moreover, TWS02 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for PCa treatment without significant side effects. The clinical evaluation of this study was registered On October 30, 2021 at https://www.chictr.org.cn/ (No: ChiCTR2100052545).

Tomotherapy in synchronous and metachronous bilateral breast cancer: Clinical experience.

The objective of this research is to present our firsthand experience and provide up-to-date data for the further study of cases involving simultaneous breast irradiation using helical Tomotherapy, ©Accuray Inc. The radical treatment options for bilateral breast cancer are surgery, chemotherapy, and radiation therapy. Being that radiotherapy for bilateral breast cancer is challenging due to limitations in the geometry of modern radiotherapy equipment, helical Tomotherapy was chosen as an appropriate technique of irradiation. The retrospective review focused on the records of patients who underwent bilateral irradiation of the breast or chest wall and regional lymph nodes using helical Tomotherapy. Only four patients with bilateral breast cancer completed a radiation therapy course in our center from 2018 to 2023. Two patients underwent radical mastectomy with lymph node dissection on both sides before irradiation. For the other two patients, radical mastectomy was done after neoadjuvant chemotherapy. Acute radiation toxicity scoring was based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Only mild adverse effects, such as general weakness and slight skin irritation below Grade 3, were observed, with no instances of skin swelling, dryness, or pigmentation noted. Evaluation of late complications revealed tissue fibrosis in the area of the internal mammary nodes and respiratory failure with various severity. Complications and deterioration in the cardiovascular system were not observed during the follow-up period, which varied from 3 to 48months. Our results show the efficacy of using helical Tomotherapy considering positive outcomes, being that three out of four patients are in remission with low acute toxicity and late complications. There are a small number of articles describing bilateral breast cancer treatment with helical Tomotherapy. On this occasion, our data could contribute to the studies of tolerant doses for organs at risk and improve the parameters of treatment plans for bilateral breast cancer. Since the small sample of patients with bilateral breast cancer limits the study, a larger cohort of patients is essential to obtain statistically reliable results.

Comparison of novel PSMA-targeting [177Lu]Lu-P17-087 with its albumin binding derivative [177Lu]Lu-P17-088 in metastatic castration-resistant prostate cancer patients: a first-in-human study.

Prostate-specific membrane antigen (PSMA) is a promising target for diagnosis and radioligand therapy (RLT) of prostate cancer. Two novel PSMA-targeting radionuclide therapy agents, [177Lu]Lu-P17-087, and its albumin binder modified derivative, [177Lu]Lu-P17-088, were evaluated in metastatic castration-resistant prostate cancer (mCRPC) patients. The primary endpoint was dosimetry evaluation, the second endpoint was radiation toxicity assessment (CTCAE 5.0) and PSA response (PCWG3). Patients with PSMA-positive tumors were enrolled after [68Ga]Ga-PSMA-11 PET/CT scan. Five mCRPC patients received [177Lu]Lu-P17-087 and four other patients received [177Lu]Lu-P17-088 (1.2 GBq/patient). Multiple whole body planar scintigraphy was performed at 1.5, 4, 24, 48, 72, 120 and 168h after injection and one SPECT/CT imaging was performed at 24h post-injection for each patient. Dosimetry evaluation was compared in both patient groups. Patients showed no major clinical side-effects under this low dose treatment. As expected [177Lu]Lu-P17-088 with longer blood circulation (due to its albumin binding) exhibited higher effective doses than [177Lu]Lu-P17-087 (0.151 ± 0.036 vs. 0.056 ± 0.019 mGy/MBq, P = 0.001). Similarly, red marrow received 0.119 ± 0.068 and 0.048 ± 0.020 mGy/MBq, while kidney doses were 0.119 ± 0.068 and 0.046 ± 0.022 mGy/MBq, respectively. [177Lu]Lu-P17-087 demonstrated excellent tumor uptake and faster kinetics; while [177Lu]Lu-P17-088 displayed a slower washout and higher average dose (7.75 ± 4.18 vs. 4.72 ± 2.29 mGy/MBq, P = 0.018). After administration of [177Lu]Lu-P17-087 and [177Lu]Lu-P17-088, 3/5 and 3/4 patients showed reducing PSA values, respectively. [177Lu]Lu-P17-088 and [177Lu]Lu-P17-087 displayed different pharmacokinetics but excellent PSMA-targeting dose delivery in mCRPC patients. These two agents are promising RLT agents for personalized treatment of mCRPC. Further studies with increased dose and frequency of RLT are warranted to evaluate the potential therapeutic efficacy. 177Lu-P17-087/177Lu-P17-088 in Patients with Metastatic Castration-resistant Prostate Cancer (NCT05603559, Registered at 25 October, 2022). URL OF REGISTRY: https://classic. gov/ct2/show/NCT05603559 .

Effects of Bone Marrow Sparing and TGF-β3 Treatment in Total Body Irradiation of C57BL/6J Mice

Introduction: Mortality from acute radiation syndrome is frequently caused by hematopoietic or gastrointestinal radiotoxicity, the latter of which currently has no effective treatment. Transforming growth factor-beta 3 (TGF-β3) may decrease the severity of radiation-induced gastrointestinal damage in mice. In addition, treatment with TGF-β3 may alleviate radiation-induced fibrosis. Objectives: The current study aimed to investigate the effect of TGF-β3 treatment on acute and late radiotoxicity in whole body irradiated mice. Methods: C57BL/6J mice were total body irradiated with 8.5 Gy X-rays with or without shielding of one hind leg to alleviate hematopoietic radiotoxicity. The effects of intravenous TGF-β3 treatment were investigated. Body weight and pain expression were monitored. Intestine, lung, and liver tissues were preserved and analyzed. Alpha smooth muscle actin (α-SMA) expression in MRC-5 cells after 3.5 Gy X-irradiation combined with TGF-β3 treatment was analyzed using flow cytometry. Results: All total body irradiated animals died within ten days after irradiation. Ninety-three percent of femur-shielded mice survived until sampling or termination. No effect of TGF-β3 treatment was observed in either group. No increase in collagen content was detected in the lungs or liver from irradiated mice regardless of TGF-β3 treatment. In vitro, α-SMA expression increased synergistically after irradiation and TGF-β3 treatment. Conclusions: Shielding of the femur during total body irradiation decreased acute gastrointestinal radiation toxicity and increased survival. TGF-β3 treatment did not impact symptoms or survival. TGF-β3 treatment and irradiation increased α-SMA expression in MRC-5 cells synergistically.