Side Effects Of Radiotherapy Research Articles

Incorporating economic methods into Cochrane systematic reviews: case studies in brain tumour research

BackgroundCochrane systematic reviews have established methods for identifying and critically appraising empirical evidence in health. In addition to evidence regarding the clinical effectiveness of interventions, the resource implications of such interventions can have a huge impact on a decision maker’s ability to adopt and implement them. In this paper, we present examples of the three approaches to include economic evidence in Cochrane reviews.MethodsThe Cochrane Handbook presents three different methods of integrating economic evidence into reviews: the Brief Economic Commentary (BEC), the Integrated Full Systematic Review of Economic Evaluations (IFSREE) and using an Economic Decision Model. Using the examples from three different systematic reviews in the field of brain cancer, we utilised each method to address three different research questions. A BEC was utilised in a review that evaluates the long-term side effects of radiotherapy (with or without chemotherapy). An IFSREE was utilised in a review comparing different treatment strategies for newly diagnosed glioblastoma in the elderly. Finally, an economic model was included in a review assessing diagnostic test accuracy for tests of codeletion of chromosomal arms in people with glioma.ResultsThe BEC mirrored the results of the main review and found a paucity of quality evidence with regard to the side effects of radiotherapy in those with glioma. The IFSREE identified a single economic evaluation regarding glioblastoma in the elderly, but this study had a number of methodological issues. The economic model identified a number of potentially cost-effective strategies for tests for codeletion of chromosomal arms 1p and 19q in people with glioma.ConclusionsThere are strengths and limitations of each approach for integrating economic evidence in Cochrane systematic reviews. The type of research question, resources available and study timeline should be considered when choosing which approach to use when integrating economic evidence.

First integrative oncology clinic in the Veteran Affairs (VA) Pittsburgh healthcare system.

e24041 Background: Integrative oncology (IO) is PROACTIVE and combines complementary with conventional care. The VA's comprehensive collection of integrative services is already in place. However, providers are often unaware of these, therefore veteran cancer patients don’t benefit from them. Prostate cancer is the most common cancer within the VA (31.8%), Aside from radiation/chemotherapy side effects (dry mouth, stomatitis, fatigue, neuropathy, gastrointestinal ) prostate cancer patients also have hormonal issues (hot flashes, low bone density, sexual dysfunction). Conventional treatments focus on symptoms (REACTIVE). Complementary and IO approaches are evidence-based toward specific treatment-related side effects. By educating and offering integrative approaches, we empower veterans to take charge of their health and well-being. Shifting our focus from treating only the disease to treating the entire patient, will improve health outcomes. Methods: Recruit 40 prostate cancer patients with fatigue, radiation-induced diarrhea, neuropathy, nausea, vomiting, anorexia, constipation, sexual dysfunction, and emotional issues(depression, anxiety, poor sleep, lack of energy). Identify/train providers to focus on concerning areas. Develop VA Personal Health Plans (PHP) to identify patients mission, aspiration, and purpose (MAP). Offer acupuncture, yoga, Reiki, TaiChi, meditation, biofeedback for headaches - Video Support group. Assessment tools. In late 2022, we reached our goal of 40 prostate cancer patients and opened clinic enrollment to patients of all cancer types. Results: The pilot IO clinic began in 2020, with 40 patients. In 2022, we expanded services to patients with other cancer types. Integrative options improved surgical outcomes, minimize chemotherapy /radiation side effects, boost morale, and optimize clinical outcomes. There is a high-interest level among oncology staff and patients. Resources are abundant but need organization and refinement to effectively present IO to our patients. Conclusions: There is huge potential for integrative oncology to improve the clinical, laboratory, and quality-of-life outcomes of cancer patients. We were able to construct a program within the Veteran Affairs, using existing integrative resources with high patient engagement. Currently, we plan to expand services to other VA sites nationwide.

Repurposing of Various Current Medicines as Radioprotective Agents.

The side effects of ionising radiation include skin changes, dry mouth, hair loss, low blood count, and the mutagenic effect on normal cells when utilized in radiotherapy for cancer treatment. These radiations can cause damage to the cell membrane, lipids, proteins, and DNA and generate free radicals. Evidence reports stated that radiotherapy accounts for 17-19% of secondary malignancies, labelling this treatment option a double-edged sword. Radioprotective molecules are used for mitigating radiotherapy's side effects. These agents show free radical scavenging, antioxidant, collagen synthesis inhibition, protease inhibition, immune stimulation, increased cytokine production, electron transfer, and toxicity reduction properties. The most frequently used amifostine has an array of cancer applications, showing multitarget action as nephroprotective to cisplatin and reducing the chances of xerostomia. Many other agents, such as metformin, edaravone, mercaptopropionylglycine, in specific diseases, such as diabetes, cerebral infarction, cystinuria, have shown radioprotective action. This article will discuss potentially repurposed radioprotectors that can be used in the clinical setting, along with a brief discussion on specific synthetic agents like amifostine and PrC-210. Rigorous literature search using various electronic databases, such as PubMed, ScienceDirect, Scopus, EMBASE, Bentham Science, Cochrane Library, etc., was made. Peer-review research and review papers were selected, studied, reviewed, and analysed. Safety and risk-free treatment can be guaranteed with the repurposed agents. Agents like metformin, captopril, nifedipine, simvastatin, and various others have shown potent radioprotective action in various studies. This review compiled repurposed synthetic radioprotective agents.

Synthesis of an "all-in-one" nanotherapeutic platform for triple-amplification chemodynamic therapy of osteosarcoma

High recurrence rates after surgery and unacceptable side effects of chemotherapy and radiotherapy are challenges in the treatment of osteosarcoma (OS). Therefore, the development of nanoplatforms with combined tumor inhibition efficiency and fewer side effects is a promising strategy for the treatment of OS. In this paper, a biocompatible therapeutic nanoplatform (Fe-Zr@PDA@GOx) was constructed with a simple and efficient strategy for the treatment of OS. First, as an excellent Fenton reaction reagent, iron ions in the nanoplatform can generate highly toxic hydroxyl radicals (•OH) with hydrogen peroxide (H2O2) in the tumor microenvironment and induce tumor cell death. Then, the modification of polydopamine endows the nanoplatform with photothermal responsiveness, with a photothermal conversion efficiency of 28.0%. Importantly, the conversed heat by polydopamine both promotes the release of glucose oxidase (GOx) and increases the rate of the Fenton reaction. Furthermore, GOx-mediated starvation treatment (SDT) can also provide suitable reaction conditions and sufficient H2O2 to realize the amplification of chemodynamic therapy (CDT). Finally, the doping of Zr ions can interact with Fe to form dual active centers in the Fenton reaction and further accelerate the generation of •OH. Both in vitro and in vivo experiments reveal the synergistic photothermal/CDT/SDT anti-tumor effect. Therefore, this work provides an effective strategy for the treatment of OS.

Uncovering the Q-marker and potential mechanisms of Qishan Formula for lung cancer based on multi-technology

Qishan Formula (QSF) is mainly used to treat lung cancer and its side effects of radiotherapy and chemotherapy. Although the clinical efficacy of QSF has been recognized, its mechanism of action and active ingredients are still unclear. This study aims to explore the potential Q-Marker of QSF and reveal its anti-lung cancer mechanism. Firstly, the fingerprints of 10 batches of QSF were established, and the potential Q-markers were screened by chemometrics, then network pharmacology and molecular docking methods were used to explore its anti-lung cancer mechanism. Finally, the potential Q-markers were quantitatively by UPLC-QDA. The results showed that 48 common peaks were identified by the established fingerprint, and calycosin, ginsenoside Rg1, atractylenolide III, atractylenolide I and ginsenoside Rb1 were screened as potential Q-Markers of QSF by chemometrics. Network pharmacology and molecular docking found that the potential Q-Markers may regulate various signaling pathways through targets such as FOS, IL6, EGFR, ESR1, MAPK1, and MAPK3, and play a therapeutic role in lung cancer. Besides, the established UPLC-QDA can also perform quality control for Q-Markers of QSF. This study can provide academic ideas and lay a foundation for the comprehensive quality control and mechanism research of QSF and other compound preparation.

Autophagy gene Atg7 regulates the development of radiation-induced skin injury and fibrosis of skin.

Radiation-induced skin injury, which may progress to fibrosis, is a severe side effect of radiotherapy in patients with cancer. However, currently, there is a lack of preventive or curative treatments for this injury. Meanwhile, the mechanisms underlying this injury remain poorly understood. Here, we elucidated whether autophagy is essential for the development of radiation-induced skin injury and the potential molecular pathways and mechanisms involved. We used the myofibroblast-specific Atg7 knockout (namely, conditional Atg7 knockout) mice irradiated with a single electron beam irradiation dose of 30Gy. Vaseline-based 0.2% rapamycin ointment was topically applied once daily from the day of irradiation for 30days. On day 30 post irradiation, skin tissues were harvested for further analysis. In vitro, human foreskin fibroblast cells were treated with rapamycin (100nM) for 24h and pretreated with 3-MA (5mM) for 12h. Macroscopic skin manifestations, histological changes, and fibrosis markers at the mRNA and protein expression levels were measured. Post irradiation, the myofibroblast-specific autophagy-deficient (Atg7Flox/Flox Cre+ ) mice had increased fibrosis marker (COL1A1, CTGF, TGF-β1, and α-SMA) levels in the irradiated area and had more severe macroscopic skin manifestations than the control group (Atg7Flox/Flox Cre- ) mice. Treatment with an autophagy agonist rapamycin attenuated macroscopic skin injury scores and skin fibrosis marker levels with decreased epidermal thickness and dermal collagen deposition in Atg7Flox/Flox Cre+ mice compared with the vehicle control. Moreover, in vitro experiment results were consistent with the in vivo results. Together with studies at the molecular level, we found that these changes involved the Akt/mTOR pathway. In addition, this phenomenon might also relate to Nrf2-autophagy signaling pathway under oxidative stress conditions. In conclusion, Atg7 and autophagy-related mechanisms confer radioprotection, and reactivation of the autophagy process can be a novel therapeutic strategy to reduce and prevent the occurrence of radiodermatitis, particularly skin fibrosis, in patients with cancer.

Bone marrow mesenchymal stem cell transplantation alleviates radiation-induced myocardial fibrosis through inhibition of the TGF-β1/Smad2/3 signaling pathway in rabbit model

Backgroundand purpose: Radiotherapy (RT) is an effective treatment for most malignant chest tumors. However, radiation-induced myocardial fibrosis (RIMF) is a serious side effect of RT. Currently, due to the mechanism of RIMF has not been fully elucidated, there is a lack of effective therapeutic approach. In this study, we aimed to investigate the role and possible mechanisms of bone marrow mesenchymal stem cells (BMSCs) in the therapy of RIMF. Materials and methodsTwenty-four New Zealand white rabbits were allotted into four groups (n = 6). Rabbits in the Control group received neither irradiation nor treatment. A single dose of 20 Gy heart X-irradiation was applied to the RT group, RT + PBS group and RT + BMSCs group. Rabbits in the RT + PBS group and RT + BMSCs group were injected with 200 μL PBS or 2 × 106 cells via pericardium puncture 24 h following irradiation, respectively. Echocardiography was used to test the cardiac function; Then the heart samples were collected, and processed for histopathological, Western blot and immunohistochemistry investigations. ResultsIt was observed that BMSCs have therapeutic effect on RIMF. Compared with the Control group, inflammatory mediators, oxidative stress and apoptosis were significantly increased, meanwhile, cardiac function was remarkably decreased in the RT group and RT + PBS group. However, in the BMSCs group, BMSCs significantly improved cardiac function, decreased inflammatory mediators, oxidative stress and apoptosis. Furthermore, BMSCs remarkably reduced the expression level of TGF-β1 and the phosphorylated-Smad2/3. ConclusionsIn conclusion, our research indicates BMSCs have the potential to alleviate RIMF through TGF-β1/Smad2/3 and would be a new therapeutic approach for patients with myocardial fibrosis.

Consideration of lung dose changes when establishing lung cancer treatment plans according to tumor changes

PurposeThe purpose of this study was to determine if treatment dose to the lungs can be considered in the initial treatment planning according to change in tumor size during treatment. MethodsLung dose was evaluated in 26 patients who underwent re-planning CT (reCT) due to changes in tumor size during lung cancer treatment with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT). Relevant parameters were V5, V10, V20, V30, V40, and mean lung dose. ResultsDose parameters to most lungs followed a normal distribution, but there were no statistically significant results for changes in lung dose after reCT. Patients with only lungs surrounding the tumor tended to have a 7.6% decrease in mean bilateral lung dose (MBLD) as tumor volume decreased. In contrast, patients with ribs and vertebrae within the target region showed a 5.9% increase in MBLD. Mean dose to the bilateral lungs before and after reCT increased (positively correlated) with high-density material in the planned target volume (PTV). ConclusionsThis study found a correlation of radiological dose to the lungs to presence of high-density material in the PTV. In such patients, reducing lung dose in the initial treatment plan is expected to reduce radiation side effects.

Verification of 3D-CRT dose distribution in ArcCheck phantom using Monte Carlo code

3D-CRT is an advanced radiotherapy technique that minimizes radiation therapy side effects. It delivers high-energy radiation beams from multiple angles, precisely targeting the tumor and minimizing exposure to healthy tissue. Therefore, this study aims to investigate dose distribution of 3D-CRT in ArcCheck Phantom using Monte Carlo (MC) code. Prior to application, simulations were performed on a virtual homogeneous phantom made of PMMA material using the MC-based EGSnrc program at various beam angles, including 0°, 45°, 90°, 135°, 180°, and 270°, to determine the dose distribution that the target would receive. The results showed that a proper dose distribution on the phantom in the surface area. Furthermore, accumulating the dose distribution from all angles yields a maximum dose at the isocenter, which is consistent with the 3D-CRT technique. Moreover, a comparison of the MC simulation and experimental data showed a similar qualitative dose distributions indicating that the EGSnrc simulation is a valid tool for validating the radiation dose distribution process in the ArcCheck phantom .

Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer

Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival. Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation. Statistical models were used to test associations between clinical characteristics and outcomes, including upper GI bleeding, radiation treatment breaks, and weight loss during therapy. Between 1999 and 2012, 211 patients were treated with radiation for pancreatic cancer. All patients received concurrent chemotherapy with either gemcitabine (174) or 5-fluorouracil (27), and 67 received intensity modulated radiation therapy (IMRT). Overall, 18 patients experienced an upper GI bleed related to treatment, with 70% of bleeds occurring in the stomach or duodenum, and among those patients, 11 (61%) patients had a pancreatic head tumor and 17 (94%) patients had a metallic biliary stent. IMRT was associated with decreased risk of postradiation nausea (odds ratio, 0.27 [0.11, 0.67], P=.006) compared with 3-dimensional conformal radiation. Regarding long-term toxicities, patients with a metallic biliary stent at the time of radiation therapy were at a significantly higher risk of developing upper GI bleeding (unadjusted hazard ratio [HR], 15.41 [2.02, 117.42], P=.008), even after controlling for radiation treatment modality and prescribed radiation dose (adjusted HR, 17.38 [2.26, 133.58], P=.006). Furthermore, biliary stent placement was associated with a higher risk of death (HR, 1.99 [1.41, 2.83], P < .001) after adjusting for demographic, treatment-related, and patient-related variables. Metallic biliary stents may be associated with an increased risk of upper GI bleeding and mortality. Furthermore, IMRT was associated with less nausea and short-term toxicity compared with 3-dimensional conformal therapy.

Recognition and Management of the Long-term Effects of Cranial Radiation.

Cranial radiation is ubiquitous in the treatment of primary malignant and benign brain tumors as well as brain metastases. Improvement in radiotherapy targeting and delivery has led to prolongation of survival outcomes. As long-term survivorship improves, we also focus on prevention of permanent side effects of radiation and mitigating the impact when they do occur. Such chronic treatment-related morbidity is a major concern with significant negative impact on patient's and caregiver's respective quality of life. The actual mechanisms responsible for radiation-induced brain injury remain incompletely understood. Multiple interventions have been introduced to potentially prevent, minimize, or reverse the cognitive deterioration. Hippocampal-sparing intensity modulated radiotherapy and memantine represent effective interventions to avoid damage to regions of adult neurogenesis. Radiation necrosis frequently develops in the high radiation dose region encompassing the tumor and surrounding normal tissue. The radiographic findings in addition to the clinical course of the patients' symptoms are taken into consideration to differentiate between tissue necrosis and tumor recurrence. Radiation-induced neuroendocrine dysfunction becomes more pronounced when the hypothalamo-pituitary (HP) axis is included in the radiation treatment field. Baseline and post-treatment evaluation of hormonal profile is warranted. Radiation-induced injury of the cataract and optic system can develop when these structures receive an amount of radiation that exceeds their tolerance. Special attention should always be paid to avoid irradiation of these sensitive structures, if possible, or minimize their dose to the lowest limit.

SP-0025 Biomarkers of radiation-induced side effects in head & neck radiotherapy

SP-0025 Biomarkers of radiation-induced side effects in head & neck radiotherapy

TLR4-A Pertinent Player in Radiation-Induced Heart Disease?

The heart is one of the organs that is sensitive to developing delayed adverse effects of ionizing radiation (IR) exposure. Radiation-induced heart disease (RIHD) occurs in cancer patients and cancer survivors, as a side effect of radiation therapy of the chest, with manifestation several years post-radiotherapy. Moreover, the continued threat of nuclear bombs or terrorist attacks puts deployed military service members at risk of exposure to total or partial body irradiation. Individuals who survive acute injury from IR will experience delayed adverse effects that include fibrosis and chronic dysfunction of organ systems such as the heart within months to years after radiation exposure. Toll-like receptor 4 (TLR4) is an innate immune receptor that is implicated in several cardiovascular diseases. Studies in preclinical models have established the role of TLR4 as a driver of inflammation and associated cardiac fibrosis and dysfunction using transgenic models. This review explores the relevance of the TLR4 signaling pathway in radiation-induced inflammation and oxidative stress in acute as well as late effects on the heart tissue and the potential for the development of TLR4 inhibitors as a therapeutic target to treat or alleviate RIHD.

Differences in radiation-induced heart dysfunction in male versus female rats

Purpose Radiation therapy remains part of the standard of care for breast, lung, and esophageal cancers. While radiotherapy improves local control and survival, radiation-induced heart dysfunction is a common side effect of thoracic radiotherapy. Cardiovascular dysfunction can also result from non-therapeutic total body radiation exposures. Numerous studies have evaluated the relationship between radiation dose to the heart and cardiotoxicity, but relatively little is known about whether there are differences based on biological sex in radiation-induced heart dysfunction (RIHD). Materials and Methods We evaluated whether male and female inbred Dahl SS rats display differences in RIHD following delivery of 24 Gy in a single fraction to the whole heart using a 1.5 cm beam size (collimater). We also compared the 2.0 cm vs. 1.5 cm collimator in males. Pleural and pericardial effusions and normalized heart weights were measured, and echocardiograms were performed. Results Female SS rats displayed more severe RIHD relative to age-matched SS male rats. Normalized heart weight was significantly increased in females, but not in males. A total of 94% (15/16) of males and 55% (6/11) of females survived 5 months after completion of radiotherapy (p < .01). Among surviving rats, 100% of females and 14% of males developed moderate-to-severe pericardial effusions at 5 months. Females demonstrated increased pleural effusions, with the mean normalized pleural fluid volume for females and males being 56.6 mL/kg ± 12.1 and 10.96 mL/kg ± 6.4 in males (p = .001), respectively. Echocardiogram findings showed evidence of heart failure, which was more pronounced in females. Because age-matched female rats have smaller lungs, a higher percentage of the total lung was treated with radiation in females than males using the same beam size. After using a larger 2 cm beam in males which results in higher lung exposure, there was not a significant difference between males and females in terms of the development of moderate-to-severe pericardial effusions or pleural effusions. Treatment of males with a 2 cm beam resulted in comparable increases in LV mass and reductions in stroke volume to female rats treated with a 1.5 cm beam. Conclusion Together, these results illustrate that there are differences in radiation-induced cardiotoxicity between male and female SS rats and add to the data that lung radiation doses, in addition to other factors, may play an important role in cardiac dysfunction following heart radiation exposure. These factors may be important to factor into future mitigation studies of radiation-induced cardiotoxicity.

Risk assessment, surveillance, and nonpharmaceutical prevention of acute radiation dermatitis: results of amulticentric survey among the German-speaking radiation oncology community.

Radiation dermatitis (RD) represents one of the most frequent side effects in radiotherapy (RT). Despite technical progress, mild and moderate RD still affects major subsets of patients and identification and management of patients with ahigh risk of severe RD is essential. We sought to characterize surveillance and nonpharmaceutical preventive management of RD in German-speaking hospitals and private centers. We conducted asurvey on RD among German-speaking radiation oncologists inquiring for their evaluation of risk factors, assessment methods, and nonpharmaceutical preventive management of RD. Atotal of 244health professionals from public and private institutions in Germany, Austria, and Switzerland participated in the survey. RT-dependent factors were deemed most relevant for RD onset followed by lifestyle factors, emphasizing the impact of treatment conceptualization and patient education. While abroad majority of 92.8% assess RD at least once during RT, 59.0% of participants report RD at least partially arbitrarily and 17.4% stated to classify RD severity solely arbitrarily. 83.7% of all participants were unaware of patient-reported outcomes (PROs). Consensus exists on some lifestyle recommendations like avoidance of sun exposure (98.7%), hot baths (95.1%), and mechanical irritation (91.8%) under RT, while deodorant use (63.4% not at all, 22.1% with restrictions) or application of skin lotion (15.1% disapproval) remain controversial and are not recommended by guidelines or evidence-based practices. Identification of patients at an increased risk of RD and subsequent implementation of adequate preventive measures remain relevant and challenging aspects of clinical routines. Consensus exists on several risk factors and nonpharmaceutical prevention recommendations, while RT-dependent risk factors, e.g., the fractionation scheme, or hygienic measures like deodorant use remain controversial. Surveillance is widely lacking methodology and objectivity. Intensifying outreach in the radiation oncology community is needed to improve practice patterns.

Topical Phenytoin Versus Placebo in the Management of Acute Radiation-Induced Dermatitis in Patients with Breast Cancer: A Double-Blind Randomized Controlled Trial

Background: Acute radiodermatitis (ARD) is a common side effect of breast cancer radiotherapy. It includes erythema, burning sensation, swelling, epilation, desquamation, ulceration, or necrosis. So far, there has been no consensus about the best practice in preventing /treating ARD. Objectives: This is the first study to assess the efficacy of topical phenytoin in the prevention and treatment of ARD. Methods: This prospective randomized double-blind trial was a placebo-controlled study. A total of 70 patients with breast cancer were included. They were referred for breast radiotherapy after breast conservative surgery. Patients were randomly assigned to either the topical phenytoin or placebo group. Both ointments were applied twice and daily on affected areas of the chest. Acute radiodermatitis was evaluated every week, for 5 weeks, during radiotherapy. A blinded-to-treatment physician used the “(radiation therapy oncology group) RTOG dermatitis scoring” to do so. Results: During the first 3 weeks, ARD was neither severe (RTOG &lt; 2) nor statistically different between the two treatment groups (P &gt; 0.05). However, after the 3rd week, the ARD score was lower in phenytoin group than in the placebo group (P &lt; 0.05). Conclusions: Phenytoin topical ointment could postpone the occurrence and/or decrease the severity of ARD in patients with breast cancer.

High-Dose Ionizing Radiation Accelerates Atherosclerotic Plaque Progression by Regulating P38/NCOA4-Mediated Ferritinophagy/Ferroptosis of Endothelial Cells

Radiation therapy (RT) significantly increased the incidence of coronary artery diseases, especially atherosclerosis. Endothelial dysfunction has been the major side effect of RT among tumor patients who received RT. However, the involvement between endothelial dysfunction and radiation-induced atherosclerosis (RIA) remains unclear. Here, we constructed a murine model of RIA, aiming to uncover its underlying mechanisms and identify novel strategies for RIA prevention and treatment. Eight-week-old ApoE-/- mice that were fed a Western diet were subjected to partial carotid ligation (PCL). Four weeks later, ionizing radiation (IR) of 10 Gy was performed to verify the detrimental role of IR on atherogenesis. Ultrasound imaging, RT quantitative polymerase chain reaction, histopathology and immunofluorescence, and biochemical analysis were performed 4 weeks after IR. To study the involvement of endothelial ferroptosis induced by IR in RIA, mice after IR were administrated with ferroptosis agonist (cisplatin) or antagonist (ferrostatin-1) intraperitoneally. Western blotting, autophagic flux measurement, reactive oxygen species level detection, and coimmunoprecipitation assay were carried out in vitro. Furthermore, to determine the effect of ferritinophagy inhibition on RIA, in vivo knockdown of NCOA4 was carried out by pluronic gel. We verified that accelerated plaque progression was concomitant with endothelial cell (EC) ferroptosis after IR induction, as suggested by a higher level of lipid peroxidation and changes in ferroptosis-associated genes in the PCL+IR group than in the PCL group within vasculature. In vitro experiments further validated the devastating effects of IR on oxidative stress and ferritinophagy in ECs. Mechanistic experiments revealed that IR induced EC ferritinophagy and subsequent ferroptosis in a P38/NCOA4-dependent manner. Both in vitro and in vivo experiments confirmed the therapeutic effect of NCOA4 knockdown in alleviating IR-induced ferritinophagy/ferroptosis of EC and RIA. Our findings provide novel insights into the regulatory mechanisms of RIA and first prove that IR accelerates atherosclerotic plaque progression by regulating ferritinophagy/ferroptosis of ECs in a P38/NCOA4-dependent manner.

A Subset of Breg Cells, B10, Contributes to the Development of Radiation-Induced Pulmonary Fibrosis

Radiation-induced pulmonary fibrosis (RIPF) is a serious side effect of radiotherapy, but the underlying mechanisms are unknown. B10 cells, as negative B regulatory cells, play important roles in regulating inflammation and autoimmunity. However, the role of B10 cells in RIPF progression is unclear. The aim of this study was to determine the role of B10 cells in aggravating RIPF and the underlying mechanism. The role of B10 cells in RIPF was studied by constructing mouse models of RIPF and depleting B10 cells with an anti-CD22 antibody. The mechanism of B10 cells in RIPF was further explored through cocultivation of B10 cells and MLE-12 or NIH3T3 cells and administration of an IL-10 antibody to block IL-10. B10 cell numbers increased significantly during the early stage in the RIPF mouse models compared with the controls. In addition, depleting B10 cells with the anti-CD22 antibody attenuated the development of lung fibrosis in mice. Subsequently, we confirmed that B10 cells induced EMT and the transformation of myofibroblasts via activation of STAT3 signaling in vitro. After blockade of IL-10, it was verified that IL-10 secreted by B10 cells mediates the EMT of myofibroblasts, thereby promoting RIPF. Our study uncovers a novel role for IL-10-secreting B10 cells that could be a new target of research for relieving RIPF.

A qualitative analysis of female patient perspectives on physician communication regarding sexual dysfunction associated with pelvic radiotherapy.

Sexual dysfunction is a known side effect of pelvic radiotherapy, resulting from a complex intersection of physiologic and psychosocial factors. Maintaining sexual function is relevant to long-term quality of life and is an important aspect of survivorship. Many female patients report being insufficiently informed before treatment about the potential sexual side effects of radiation therapy. To elucidate how radiation oncologists communicate sexual function side effects with their female patients and how discussing sexual side effects of cancer treatment can positively affect patient-physician rapport. Semistructured interviews in English and Spanish were conducted with 20 female participants who received pelvic radiation as part of their cancer treatment. Patients responded to advertisements or were referred by physicians. All interviews were conducted virtually between June and October 2021. Thematic analysis was conducted with NVivo. Patients also completed an online demographics survey in REDCap. We found 4 primary themes addressing patient perspectives on patient-physician communication of sexual dysfunction and how it affected the cancer care experience. Theme 1: This may be expected, but I didn't expect it! The participants who were not properly informed about sexual side effects felt blindsided and embarrassed about their symptoms. Theme 2: I do not feel like a woman anymore . . . The psychological impact included lower self-esteem and no longer feeling sexy nor like a woman. Theme 3: Fine, I'll deal with this myself! Patients turned to the internet rather than their doctors for answers once they began experiencing symptoms, and they found information, normalization, and community online. Theme 4: Ask me about my sex life and find out if sex is a priority for me. Participants emphasized that their radiation oncologist should take a sexual history early to monitor sexual dysfunction and to identify individual patient priorities surrounding sex posttreatment. This evidence provides a guide to patient-physician communication that may help to mitigate the impacts of radiotherapy on female sexual function as well as the negative impact that the absence of communication about sexual dysfunction may have on patient-physician trust. While this project did have a small sample size, there is considerable diversity in race, education level, and age, with interviews conducted in Spanish and English. Overall these findings provide physicians with important information about the unmet information needs of patients and their preferences for how to help them feel more prepared and less distressed when sexual dysfunction occurs.

Image masking using convolutional networks improves performance classification of radiation pneumonitis for non-small cell lung cancer.

Radiation pneumonitis (RP) is a serious side effect of radiotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC). Image cropping reduces training noise and may improve classification accuracy. This study proposes a prediction model for RP grade ≥ 2 using a convolutional neural network (CNN) model with image cropping.The 3D computed tomography (CT) images cropped in the whole-body, normal lung (nLung), and nLung regions overlapping the region over 20Gy (nLung∩20Gy) used in treatment planning were used as the input data. The output classifies patients as RP grade < 2 or RP grade ≥ 2. The sensitivity, specificity, accuracy, and area under the curve (AUC) were evaluated using the receiver operating characteristic curve (ROC).The accuracy, specificity, sensitivity, and AUC were 53.9%, 80.0%, 25.5%, and 0.58, respectively, for the whole-body method, and 60.0%, 81.7%, 36.4%, and 0.64, respectively, for the nLung method. For the nLung∩20Gy method, the accuracy, specificity, sensitivity, and AUC improved to 75.7%, 80.0%, 70.9%, and 0.84, respectively.The CNN model, in which the input image is segmented in the normal lung considering the dose distribution, can help predict an RP grade ≥ 2 for NSCLC patients after definitive radiotherapy.