Adverse Effects Of Radiotherapy Research Articles

Safety of Reduction Mammaplasty and Mastopexy After Breast Conservation Therapy and Radiation Therapy: A Case Series.

Conservative surgery and radiotherapy (CS + RT) have become the standard of care for early-stage breast cancer as an alternative to mastectomy. With the increasing rate of obesity and incidence of macromastia, surgeons increasingly encounter patients with a history of breast radiation desiring breast reduction. However, elective breast surgery after irradiation remains to be controversial due to known adverse effects of radiation, especially on wound healing, and unknown effects of lumpectomy on traditional pedicle choices. Herein, we present our experiences and outcomes of reduction mammaplasties and mastopexies in patients with breast cancer previously treated with CS + RT. Between 2009 and 2020, 13 patients undergoing reduction mammaplasty or mastopexy, who have previously underwent CS + RT with or without axillary surgery, were included in this study. Surgical techniques and complications, including delayed wound healing, infection, fat necrosis, and nipple-areolar necrosis, were recorded and analyzed based on the irradiated versus nonirradiated sides. Of the 13 patients, delayed wound healing occurred in 7% on the irradiated side and 15% on the nonirradiated sides (P > 0.05). No significant correlation was observed between the number of complications and time of elective breast surgery from the last radiation therapy. Complications between irradiated and nonirradiated breasts did not significantly differ in both the reduction mammaplasty and mastopexy groups. Reduction mammaplasty and mastopexy in patients with a history of lumpectomy and breast irradiation can be safely performed and should be considered in those experiencing macromastia or asymmetry post-CS + RT.

Nanoparticle-based delivery systems as emerging therapy in retinoblastoma: recent advances, challenges and prospects.

Retinoblastoma is the most common intraocular malignancy in children. The treatment of this rare disease is still challenging in developing countries due to delayed diagnosis. The current therapies comprise mainly surgery, radiotherapy and chemotherapy. The adverse effects of radiation and chemotherapeutic drugs have been reported to contribute to the high mortality rate and affect patients' quality of life. The systemic side effects resulting from the distribution of chemotherapeutic drugs to non-cancerous cells are enormous and have been recognized as one of the reasons why most potent anticancer compounds fail in clinical trials. Nanoparticulate delivery systems have the potential to revolutionize cancer treatment by offering targeted delivery, enhanced penetration and retention effects, increased bioavailability, and an improved toxicity profile. Notwithstanding the plethora of evidence on the beneficial effects of nanoparticles in retinoblastoma, the clinical translation of this carrier is yet to be given the needed attention. This paper reviews the current and emerging treatment options for retinoblastoma, with emphasis on recent investigations on the use of various classes of nanoparticles in diagnosing and treating retinoblastoma. It also presents the use of ligand-conjugated and smart nanoparticles in the active targeting of anticancer and imaging agents to the tumour cells. In addition, this review discusses the prospects and challenges in translating this nanocarrier into clinical use for retinoblastoma therapy. This review may provide new insight for formulation scientists to explore in order to facilitate the development of more effective and safer medicines for children suffering from retinoblastoma.

Custom-made radiotherapy prosthesis for external and internal radiotherapy in a patient with lip cancer.

Definitive radiotherapy is an effective treatment for early-stage lip cancer. The goal of radiotherapy is to irradiate the cancer site effectively while protecting healthy surrounding tissue from the adverse effects of radiation. To this end, radiotherapy prostheses have been widely and effectively used. A maxillofacial prosthodontist working in collaboration with a radiation oncologist can create a custom-made radiotherapy prosthesis that minimizes adverse effects. This report demonstrates the successful use of spacers in external beam radiotherapy and brachytherapy in consideration of the patient's radiation therapy treatment plan and wearing conditions, ensuring adequate availability and preventing radiation-related complications.

Congo red protects bacteriophages against UV irradiation and allows for the simultaneous use of phages and UV for membrane sterilization

Congo red dye protects bacteriophages from the adverse effects of UV radiation, allowing for simultaneous membrane surface cleaning from biofoundries.

Quercetin inclusion complex gels ameliorate radiation-induced brain injury by regulating gut microbiota

Radiation-induced brain injury (RIBI) is a serious adverse effect of radiotherapy. RIBI has garnered considerable clinical attention owing to its powerful effects on brain function and cognition; however, no effective treatment is available. The microbiota–gut–brain axis theory is a novel concept of treating RIBI by regulating gut microbiota. Quercetin, a particularly common flavonoid compound, has a wide range of biological activities and can regulate gut microbiota; however, it has poor solubility and dispersibility. In the present study, oral gels of inclusion complex comprising quercetin and HP-β-CD were prepared, which increased quercetin dispersion and extended its release time in the intestinal tract. First, the relative abundance and diversity of gut microbiota in RIBI mice changed after oral administration of quercetin inclusion complex gels (QICG). Second, the spontaneous activity behavior and short-term memory ability as well as anxiety level were improved. Third, changes in physical symptoms were observed, including a decrease in TNF-α and IL-6 levels. H&E staining revealed that gut epithelial injury and intestinal inflammation as well as hippocampal inflammation were ameliorated. Antibiotics treatment (Abx) mice were developed to disrupt the mice's original gut microbiota composition. No significant improvement was observed in behavior or histopathology after oral administration of QICG in Abx mice of RIBI, indicating that the effect of QICG on improving RIBI was regulated by intestinal microbiota. Finally, the QICG preparation is efficient, exerting a protective effect on RIBI by regulating gut microbiota via the microbiota–gut–brain axis, which provides a novel idea for RIBI treatment.

Circulating levels of IL-6 and TGF-β1 in patients with prostate cancer undergoing radiotherapy: associations with acute radiotoxicity and fatigue symptoms

BackgroundThe goal of research was to investigate the possible relations between serum concentrations of IL-6 and TGF-β1, individual and clinical characteristics, and adverse effects of radiotherapy in patients with prostate cancer: acute and late genitourinary and gastrointestinal toxicity, and fatigue.MethodsThirty-nine patients with localized or locally advanced prostate cancer who were treated with radiotherapy were enrolled in this study. The acute radiotoxicity grades and fatigue levels were assessed during the radiotherapy and 1 month after the radiotherapy. Estimation of the late radiotoxicity was performed every three months in the first year, every four months in the second year, and then every six months. Serum levels of IL-6 and TGF-β1 were determined before radiotherapy and after the 25th radiotherapy fraction by ELISA.ResultsThe significant positive association between diabetes mellitus and changes in acute genitourinary toxicity grades during the radiotherapy was observed in prostate cancer patients. In addition, patients who were smokers had significantly higher maximum fatigue levels in comparison with patients who were non-smokers. The circulating IL-6 levels were significantly higher after the 25th radiotherapy fraction in comparison with levels determined before radiotherapy. The significant positive correlations between pretreatment TGF-β1 levels and maximum genitourinary toxicity grades and between TGF-β1 levels after the 25th fraction and genitourinary toxicity grades after the 25th fraction, were found. The pretreatment IL-6 concentrations and TGF-β1 concentrations after the 25th fraction were positively correlated with maximum genitourinary toxicity grades. The IL-6 levels after the 25th fraction were positively associated with genitourinary toxicity grades after this fraction. The pretreatment IL-6 concentrations were significantly positively correlated with maximum fatigue scores. The significant positive correlation between IL-6 concentrations and fatigue scores after the 25th fraction was determined. The positive correlations between IL-6 and TGF-β1 concentrations measured after the 25th fraction and maximum fatigue scores were observed.ConclusionsOur results suggest that serum levels of IL-6 and TGF-β1 might influence the severity of acute genitourinary radiotoxicity and fatigue in patients with prostate cancer. Combining clinical parameters and circulating cytokine levels might be useful for the prediction of adverse reactions to radiotherapy.

The effect of electromagnetic waves of mobile phones on DNA, RNA content and kidney function in rats before, during and after pregnancy and their offspring

Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation cause many concerns about their effects on human health. This study was designed to investigate the effect of exposure to a 900-MHz electromagnetic waves (EMW) produced by mobile phones on nucleic acids (DNA and RNA), protein content, kidney function (levels of urea and creatinine) and oxidative stress (malondialdehyde, MDA level) in rats before, during and after pregnancy periods and their offspring. A total of 32 Wistar albino female rats were divided into 4 equal groups (8 each): 1- unexposed (control group); 2- pre-pregnancy (2 h/d for 21 d) EMW-exposed group; 3- during pregnancy (2 h/d for 21 d) EMW-exposed group; 4- during and after pregnancy (2 h/d for each period) EMW-exposed group. Dams, new born and young rats (40-50 g) of all groups were sacrificed and kidney tissues were harvested for determination of parameters under investigation. A high significant decrease in DNA, RNA and protein levels were found of all periods in exposed groups compared to control. No difference in protein, DNA and RNA content in new born and young rats of pre-pregnancy EMW exposed rats, however these parameters were increased significantly in new born and young rats of both during and during and after pregnancy exposed groups compared to control. There was no difference in new born kidney function and oxidative stress of all exposed groups compared to control. However, these parameters were increased significantly in young rats of both during and during and after pregnancy exposed groups as well in all exposed groups compared to control. In conclusion, the EMW propagated from mobile phones have harmful effects on DNA, RNA and protein content as well kidney function and oxidative stress of exposed rats and their offspring. Therefore, people may use various antioxidants and avoid exposure to EMW for a long periods to prevent the potential adverse effects of exposure to EMW.

Comparing outcomes of single-port insufflation endoscopic breast-conserving surgery and conventional open approach for breast cancer

BackgroundIn the surgical treatment of breast cancer, the goal of surgeons is to continually create and improve minimally invasive surgical techniques to increase patients’ quality of life. Currently, routine breast-conserving surgery is often performed using two obvious incisions. Here, we compare the clinical efficacy and aesthetic outcomes of a novel technique using one incision, called ‘single-port insufflation endoscopic breast-conserving surgery’ (SIE-BCS), vs. conventional breast-conserving surgery (C-BCS) in patients with early-stage breast cancer.MethodsA total of 180 patients with stage I or stage II breast cancer participated in this study, of whom 63 underwent SIE-BCS and 117 underwent C-BCS. Logistic regression analysis was conducted to assess the risk of local recurrence and metastasis. Aesthetic outcomes were evaluated using the BREAST-Q scale.ResultsThe mean operation time was significantly longer for SIE-BCS (194.9 ± 71.5 min) than for C-BCS (140.3 ± 56.9 min), but the mean incision length was significantly shorter for SIE-BCS than for C-BCS (3.4 ± 1.2 cm vs. 8.6 ± 2.3 cm). While both surgeries yielded similar BREAST-Q ratings for satisfaction with breasts and sexual well-being, SIE-BCS was associated with significantly better ratings for physical well-being (chest area) and psychological well-being. Additionally, SIE-BCS was associated with decreased rates of adverse effects of radiation. The preliminary analysis showed that SIE-BCS did not increase the risk of local recurrence or metastasis.ConclusionThe novel single-port insufflation endoscopic assisted BCS technique is feasible, safe, and improves patients’ postoperative comfort and psychological well-being, as compared to the conventional technique.

Stereotactic radiosurgery for orbital cavernous hemangiomas.

The goal of this study was to assess the safety and efficacy of single-session Gamma Knife radiosurgery (GKRS) for orbital cavernous hemangiomas (OCHs). Patients who presented with an OCH between September 1999 and May 2022 and were treated with single-session GKRS were included in this single-center cohort study. There were 23 patients (7 males and 16 females) in this study. The median margin dose was 12 Gy (range 11-13 Gy). The median clinical and radiological follow-ups were 45 months (range 5-190 months) and 45 months (range 6-190 months), respectively. Nine (69.2%) of 13 patients with visual acuity impairment had improvement in best corrected visual acuity. Of the 8 patients with visual field defects, 5 patients (62.5%) had complete resolution. Tumor regression was observed in 22 patients (95.7%). The mean relative reduction in tumor volume was 82.6% ± 23.7%. The relative reductions in tumor volume were 33%, 49%, 72%, 84%, and 89% at 6, 12, 24, 36, and 48 months, respectively. Adverse effects of radiation were not observed. GKRS appears to be safe and efficacious for treating OCHs over long-term follow-up. The treatment is associated with a high rate of regression in OCHs and remarkable improvement in both visual acuity and visual field deficits.

Safety of the total neo-adjuvant therapy in rectal cancer treatment. Preliminary results of the randomized trial

AIM: assess tolerability and safety of total neoadjuvant therapy (TNT) with three consolidation courses of XELOX for patients with rectal carcinoma.PATIENTS AND METHODS: patients with histologically proven rectal carcinoma were randomly assigned in two groups: in the TNT group after the neoadjuvant CRT 50–54 Gy with capecitabine 3 consolidation courses of XELOX were done, in the CTR group — conventional neoadjuvant CRT 50–54 Gy with capecitabine. The RTOG scale was used to assessed radial reactions, and the NCI-CTC v5.0 scale was used to evaluate toxicity. For selected patients with a complete clinical response «watch and wait» approach was used. Postoperative complications were graded according with the Clavien-Dindo scale. The primary endpoint of study was the complete response rate (clinical and pathomorphological). Secondary endpoints of study: frequency and structure of intraoperative and postoperative complications, the rate of grade 3–4 toxicity of radiotherapy and chemotherapy, R0-resection rates. The study was registered on the ClinicalTrials.gov (NCT04747951).RESULTS: between October 2020 and March 2022, 145 patients were enrolled in the randomized study: 72 patients in the TNT group and 73 patients in the CRT group. The full course of neoadjuvant treatment was completed in 90% patients in the TNT group, comparing with 96% in the CRT group (p = 0.65). The total rate of severe adverse effects of radiation therapy was 59% in the TNT group, comparing with 67% in the CRT group (p = 0.48), with 3–4 grade by RTOG scale were observed only in two cases in the CRT group. During chemotherapy severe adverse effects were observed in 54% in the TNT group comparing with 19% in the CRT group (p < 0.001). Grade 3–4 toxicity was 3% in the TNT group comparing with 2% in the CRT group. The rate of intra- and postoperative complications did not differ between two groups.CONCLUSION: TNT is a safe alternative to conventional CRT.

Domain-adaptive denoising network for low-dose CT via noise estimation and transfer learning.

In recent years, low-dose computed tomography (LDCT) has played an important role in the diagnosis CT to reduce the potential adverse effects of X-ray radiation on patients, while maintaining the same diagnostic image quality. Deep learning (DL)-based methods have played an increasingly important role in the field of LDCT imaging. However, its performance is highly dependent on the consistency of feature distributions between training data and test data. Due to patient's breathing movements during data acquisition, the paired LDCT and normal dose CT images are difficult to obtain from realistic imaging scenarios. Moreover, LDCT images from simulation or clinical CT examination often have different feature distributions due to the pollution by different amounts and types of image noises. If a network model trained with a simulated dataset is used to directly test clinical patients' LDCT data, its denoising performance may be degraded. Based on this, we propose a novel domain-adaptive denoising network (DADN) via noise estimation and transfer learning to resolve the out-of-distribution problem in LDCT imaging. To overcome the previous adaptation issue, a novel network model consisting of a reconstruction network and a noise estimation network was designed. The noise estimation network based on a double branch structure is used for image noise extraction and adaptation. Meanwhile, the U-Net-based reconstruction network uses several spatially adaptive normalization modules to fuse multi-scale noise input. Moreover, to facilitate the adaptation of the proposed DADN network to new imaging scenarios, we set a two-stage network training plan. In the first stage, the public simulated dataset is used for training. In the second transfer training stage, we will continue to fine-tune the network model with a torso phantom dataset, while some parameters are frozen. The main reason using the two-stage training scheme is based on the fact that the feature distribution of image content from the public dataset is complex and diverse, whereas the feature distribution of noise pattern from the torso phantom dataset is closer to realistic imaging scenarios. In an evaluation study, the trained DADN model is applied to both the public and clinical patient LDCT datasets. Through the comparison of visual inspection and quantitative results, it is shown that the proposed DADN network model can perform well in terms of noise and artifact suppression, while effectively preserving image contrast and details. In this paper, we have proposed a new DL network to overcome the domain adaptation problem in LDCT image denoising. Moreover, the results demonstrate the feasibility and effectiveness of the application of our proposed DADN network model as a new DL-based LDCT image denoising method.

A long-term nutritional assessment of maxillary cancer patients undergoing prosthodontic rehabilitation after surgery: A longitudinal study.

To evaluate the nutritional status (NS) of patients planned for maxillectomy and prosthodontic rehabilitation using three nutritional assessment methods. This longitudinal study enrolled 18 planned maxillectomy patients following the inclusion and exclusion criteria. NS was evaluated at five stages: before surgery (S0), 2 weeks after surgery (S1), 3 months after insertion of intermediate obturator (S2), just before fabrication of definitive obturator (S3), and 3 months after insertion of definitive obturator (S4) using two nutritional assessment tools i.e. Patient Generated -Subjective Global Assessment (PG-SGA) &Nutritional risk index (NRI); and body composition indicators i.e. body mass index (BMI), fat free mass (FFM), total body water (TBW), skeletal muscle mass (SMM) and skeletal muscle mass index (SMMI).To determine the changes in patient's nutritional status among different time points Repeated Measure ANOVA with Bonferroni post hoc adjustments was used. Out of 18 patients, 12 were completed the study. NS of maxillectomy patients deteriorates significantly (p<.05) till stage S2. At S3, significant improvement occurred as compared to stage S2, but it remained significantly less than pre-surgical level. However, at stage S4, all parameters were statistically comparable to S0 (p>.05) except for PG-SGA (p<.001) and SMM (p=.044). NS of maxillectomy patients worsen post surgically due to surgical morbidity and adverse effects of radiotherapy (RT) but improves with post-surgical healing, resolution of sequel of RT and improved oral function due to well-adapted obturator prosthesis.

Evaluation of the skin protective effects of niosomal-entrapped annona squamosa against UVA irradiation.

Annona squamosa is a medicinal plant that has been used in folk medicine since antiquity. The goal of this study is to see how effective Annona squamosa leaf extract (A.S.L.E) or its niosomal-entrapped preparation is at protecting skin from UVA irradiation. The prepared niosomal-entrapped A.S.L.E has been characterized via spectrophotometry and transmission electron microscopy imaging. Furthermore, the entrapment efficiency and in vitro release of A.S.L.E were determined. In this study, ex vivo and freshly prepared samples from the dorsal region of the rats' skin were used as biological samples, which were divided into five groups: control UVA-unexposed, unprotected UVA-exposed, A.S.L.E-protected UVA-exposed, and niosomal-entrapped A.S.L.E UVA-exposed. UVA irradiation was performed by exposing the skin samples to a UVA-producing lamp for 4h. Samples from various groups were then examined using FTIR spectroscopy, histopathology, and protein electrophoresis methods. The results showed that A.S.L.E has a skin protective effect against UVA irradiation. The niosomal-entrapped A.S.L.E was more effective than the native plant leaf extract in protecting skin from the damaging effects of UVA. Therefore, the nanotechnologically formulated preparation, niosomal-entrapped A.S.L.E, can be used as an effective photoprotector (sunscreen) against the adverse effects of UVA radiation.

СТАБИЛИЗАЦИЯ ПОКАЗАТЕЛЕЙ СМЕШАННОЙ СЛЮНЫ ЧЕЛОВЕКА ПОД ВОЗДЕЙСТВИЕМ ЭЛЕКТРОМАГНИТНОГО ИЗЛУЧЕНИЯ ПЕРСОНАЛЬНОГО КОМПЬЮТЕРА

Subject is oral fluid and its changes under the influence of electromagnetic radiation from a personal computer.&#x0D; Purpose of research is to identify changes in the physicochemical parameters of the mixed saliva of users before and after working on the computer; to determine the protective properties of the mouthwash against the impact of computer electromagnetic radiation on the oral fluid. &#x0D; Methodology. The research work involved 20 men aged 20–24 years. The study consists of two blocks. The first block is aimed at identifying changes in the physicochemical parameters of mixed saliva under the influence of electromagnetic radiation from a personal computer. The second block is focused on determining the protective properties of the rinse aid of a well-known Russian brand from the effects of electromagnetic radiation from a personal computer on the oral fluid. The material of the study is oral fluid, which was used for potentiometric determination of pH, acid and alkaline buffer capacities, surface tension, total protein concentration, inorganic phosphorus, ammonium, potassium, sodium, magnesium, calcium, and α-amylase activity. The obtained data were processed in the Statistica 8.0 program. Basic statistics are applied, multiple comparison of fees using the Friedman criterion. Pairwise comparison of collections was carried out using the Wilcoxon test. The result is presented as the median (lower and upper quartiles). Differences were considered significant at p &lt; 0.05.&#x0D; Results. The action of the electromagnetic field of a personal computer caused a decrease in the level of most of the physicochemical parameters of mixed saliva. The use of a mouthwash from a well-known Russian commercial and industrial company helped to reduce the number of saliva components exposed to electromagnetic radiation from a personal computer.&#x0D; Conclusion. The electromagnetic radiation of a personal computer has an adverse effect on the physicochemical parameters of mixed saliva. The rinse aid makes it possible to stabilize the changes in the mixed saliva of a person, caused by the action of the electromagnetic field of a personal computer. This hygienic product can be considered as a way to protect the oral fluid of computer users from the adverse effects of electromagnetic radiation from a personal computer.

Breast cancer patient-reported outcomes on level 1 and level 2 oncoplastic procedures using BREAST-Q®.

In breast cancer management not only mortality and surgical morbidity measurements are important but also patient satisfaction indexes. The authors evaluated the satisfaction and health-related quality of life (HRQOL) using the breast-conserving therapy (BCT) and breast reduction (BR) modules of BREAST-Q®. This is a cross-sectional study that analyzed breast cancer patients consecutively submitted to breast surgery between January 2011 and April 2018 using two modules of BREAST-Q®. 968 patients were contacted and 232 answers were gathered: 171 patients submitted to oncoplastic level 1 surgery answered the BCT module and 61 submitted to oncoplastic level 2 surgery answered the BR module. Clinical data were retrieved from patients' medical records. Among the 232 questionnaires received, the median scores for psychosocial well-being, sexual well-being and (postoperative) satisfaction with breasts for BCT and BR modules were, respectively, 77.0 and 73.5 (p = 0.17); 62.0 and 53.0 (p = 0.14); 72.0 and 66.0 (p = 0.66). The median of adverse effects of radiation in the BCT module was 87.0. The median satisfaction with outcome in the BR module was 86.0. Both groups of patients revealed high scores of satisfaction with care. For the BCT patients, satisfaction with breasts strongly correlated with sexual well-being and was moderately correlated with psychosocial and physical well-being. For the BR patients, the satisfaction with outcome strongly correlated with satisfaction with medical team and moderately correlated with the remaining scales. Both oncoplastic surgery levels yielded similar satisfaction outcomes when assessed using BCT and BR modules of BREAST-Q®.

Health-Related Quality of Life After Breast Reconstruction: Comparing Outcomes Between Reconstruction Techniques Using the BREAST-Q

BackgroundReconstruction of the breast following mastectomy can improve patients’ health-related quality of life (HRQL). We aimed to assess HRQL in women after mastectomy and breast reconstruction and to identify differences in HRQL related to the reconstruction method used.MethodsA cross-sectional study was performed on patients who had undergone breast reconstruction in Helsinki University Hospital between 08/2017 and 7/2019. The postoperative HRQL was assessed using the BREAST-Q (2.0) Reconstruction Module. The results were compared between patients with different reconstruction methods using the Kruskal–Wallis test.ResultsA total of 146 patients were identified. Microvascular flaps (n = 77) were the most common method for primary breast reconstruction, followed by latissimus dorsi (LD) flaps (n = 45), fat grafting (n = 18) and implant reconstruction (n = 6). The satisfaction with breasts was high in all groups (median 61, IQR 49–71). The physical well-being of the chest was high regardless of the reconstructive method (median 100, IQR 80–100). However, women with fat grafting reported more adverse effects of radiation (median 17, IQR 14–17 vs. 18, IQR 17–18 for other groups, p = 0.02). Donor site morbidity was low, and patients reported high satisfaction with the back (median 66/100, IQR57-90) and abdomen (median 9/12, IQR 8–10), and physical well-being of the back (median 61/100, IQR 53–70) and abdomen (median 65/100, IQR 60–86).ConclusionsThe patient-reported HRQL after breast reconstruction is high. Most women report being satisfied with the reconstruction, irrespective of the reconstruction method used. The reconstruction method can thus be chosen individually in cooperation between the patient and the surgeon.

Radiotherapy Adverse Effects Management Training for Health Workers in Andalas University Hospital

ABSTRACT Cancer services in Indonesia have experienced a rapid increase with the addition of radiotherapy facilities in various hospitals. Increasing radiotherapy facilities will also increase the incidence of adverse radiation effects. Based on the initial survey, it was found that health workers from various professions, including doctors, nurses, and radiographers, did not understand radiotherapy and the side effects that could occur to patients. Training aims: To increase the knowledge of health workers and skills in managing adverse effects according to the competence of each profession. Pre-training survey was used to find the knowledge and skills discrepancy. Online training is provided with knowledge transfer, followed by monitoring practice in the field. It was found that the understanding and skills of health workers regarding the adverse effects of radiation increased, Based on the results of the pre-test, post-test, and practice evaluation of 37 training participants. It is hoped that from this training, the quality of cancer services will be better and can improve the quality of life of patients undergoing radiotherapy treatment Keywords: Radiotherapy, Adverse Effects, Health Workers

Melatonin Prevents UVB-Induced Skin Photoaging by Inhibiting Oxidative Damage and MMP Expression through JNK/AP-1 Signaling Pathway in Human Dermal Fibroblasts.

Exposure to ultraviolet (UV) irradiation causes damage to the skin and induces photoaging. UV irradiation stimulates production of reactive oxygen/nitrogen species, which results in activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) in fibroblasts. MAPKs are responsible for activation of activator protein-1 (AP-1), which subsequently upregulates expression of matrix metalloproteinases (MMPs). Melatonin is a potent free radical scavenger which is known to have photoprotective effects. The aim of this study is to investigate the underlying molecular mechanisms for the photoprotective effects of melatonin in UVB-irradiated primary human dermal fibroblasts (HDFs) in terms of EGFR activation, oxidative/nitrosative damage, JNK/AP-1 activation, MMP activities, and the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and type I procollagen (PIP-C). In this study, HDFs were pretreated with 1 μM of melatonin and then irradiated with 0.1 J/cm2 of UVB. Changes in the molecules were analyzed at different time points. Melatonin inhibited UVB-induced oxidative/nitrosative stress damage by reducing malondialdehyde, the ratio of oxidized/reduced glutathione, and nitrotyrosine. Melatonin downregulated UV-induced activation of EGFR and the JNK/AP-1 signaling pathway. UVB-induced activities of MMP-1 and MMP-3 were decreased and levels of TIMP-1 and PIP-C were increased by melatonin. These findings suggest that melatonin can protect against the adverse effects of UVB radiation by inhibiting MMP-1 and MMP-3 activity and increasing TIMP-1 and PIP-C levels, probably through the suppression of oxidative/nitrosative damage, EGFR, and JNK/AP-1 activation in HDFs.

CCN-CL: A content-noise complementary network with contrastive learning for low-dose computed tomography denoising

In recent years, low-dose computed tomography (LDCT) has played an increasingly important role in the diagnosis CT to reduce the potential adverse effects of x-ray radiation on patients while maintaining the same diagnostic image quality. Current deep learning-based denoising methods applied to LDCT imaging only use normal dose CT (NDCT) images as positive examples to guide the denoising process. Recent studies on contrastive learning have proved that the original images as negative examples can also be helpful for network learning. Therefore, this paper proposes a novel content-noise complementary network with contrastive learning for an LDCT denoising task. First, to better train our proposed network, a contrastive learning loss, taking the NDCT image as a positive example and the original LDCT image as a negative example to guide the network learning is added. Furthermore, we also design a network structure that combines content-noise complementary learning strategy, attention mechanism, and deformable convolution for better network performance. In an evaluation study, we compare the performance of our designed network with some of the state-of-the-art methods in the 2016 NIH-AAPM-Mayo Clinic Low Dose CT Grand Challenge dataset. The quantitative and qualitative evaluation results demonstrate the feasibility and effectiveness of applying our proposed CCN-CL network model as a new deep learning-based LDCT denoising method.

Abstract 2732: A mathematical model for optimization of combination therapy involving targeted radionuclide and CAR-T cell therapy

Abstract Background: Immunotherapy with chimeric antigen receptor - T (CAR-T) cells and targeted radionuclide therapy (TRT) are two highly promising therapies in cancer treatment. Often, these therapies show limited efficacy in complete eradication of cancer cells making the combination of these two therapies an attractive cancer treatment option. The complications involved in dosing and scheduling of these therapies make mathematical modeling an appropriate method for analyzing and predicting disease response to these therapies. Here we propose a mathematical model evaluating disease response to the combination of these two therapies and explore the optimization of their dosing and scheduling. Methods: An ordinary differential equation-based formalism is proposed for simulation of tumor response to CAR-T cell therapy as well as TRT. CAR-T cell dose and injected radioactivity was input to the model. Among others, key model parameters included tumor proliferation rate, tumor cell and CAR-T cell radiosensitivity, CAR-T cell killing rate, CAR-T cell decay rate indicating persistence. Preclinical experiments involving CS1- CAR-T cell therapy and 225Ac-DOTA-Daratumumab TRT in a multiple myeloma mice model were used to parameterize the model. Sensitivity study of the model parameters using overall survival (OS) and progression-free survival (PFS) as evaluation metrics, was performed to elucidate the parameters with highest impact. Results: OS and PFS were 97 and 55 days when CAR-T cell therapy was given prior to TRT as compared to OS of 43 days for untreated control mice. Sensitivity study of model parameters showed that tumor proliferation has the highest impact on survival metrics. For a ±50% change in tumor proliferation rate, OS changed by -41%/+111% and PFS changed by -62%/+147%. Similar changes in TRT injected activity and CAR-T cell dose changed OS by ± 15% and ±21% respectively. Accordingly, PFS changed by roughly ±32% and ±45% respectively. A variation of the interval between the therapies showed that faster growing tumors required a shorter interval between the two therapies. The sequence of therapies was also changed and TRT prior to CAR-T cell therapy demonstrated shorter PFS (43 days) due to the adverse effects of radiation on CAR-T cells. Conclusion: For a fixed dose of TRT and CAR-T cells, tumor proliferation rate was found to be the prime factor impacting therapy interval. The presented work shows the key parameters required for planning and optimizing preclinical experiments and clinical trials. Using disease, CAR-T cell and radionuclide-specific parameters as shown in this work as well as incorporating immune stimulating effects of radiation would make it an extremely potent tool for optimizing combination therapies. Citation Format: Vikram Adhikarla, Dennis Awuah, Alexander B. Brummer, Enrico Caserta, Amrita Krishnan, Flavia Pichiorri, Megan M. Minnix, John E. Shively, Jeffrey Y.C. Wong, Xiuli Wang, Russell C. Rockne. A mathematical model for optimization of combination therapy involving targeted radionuclide and CAR-T cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2732.