Search Results (67)

Background/Objectives: Radiotherapy of the chest wall after mastectomy frequently leads to fibrosis, reduced tissue elasticity, erythema, pain and chronic skin-related symptoms that complicate reconstructive strategies. Autologous fat grafting has been proposed as a regenerative option for radiation induced soft tissue damage, but clinical data focused on patient-reported symptoms remain limited. The objective of this study was to describe symptomatic and clinical changes after autologous fat grafting in irradiated postmastectomy chest wall tissue. Methods: This pilot observational study included five female patients with a history of mastectomy followed by adjuvant chest wall radiotherapy. All patients underwent a single session of standard autologous fat grafting without adipose derived stem cell enrichment. Patient-reported symptoms, including pruritus, local discomfort, burning sensation and erythema, were recorded preoperatively and at six months using a standardized 0 to 5 scale. Scar pliability was assessed by two experienced physicians using the same scale. Only descriptive statistical analysis was performed. Results: All patients demonstrated lower postoperative symptom scores at six months. Mean reductions were observed for erythema (71.4 percent), burning sensation (61.1 percent) and pruritus (57.1 percent). Local discomfort decreased by 33.3 percent. Mean scar pliability scores increased from 2.2 to 3.2. No postoperative complications, such as infection, fat necrosis or oil cyst formation, were recorded. All patients completed the six month follow up. Conclusions: In this small pilot observational study, autologous fat grafting was well tolerated and associated with descriptive improvement of patient-reported symptoms and scar pliability in irradiated postmastectomy chest wall tissue. These findings suggest a potential symptomatic benefit of fat grafting, while larger studies with objective imaging and histological correlation are required to confirm efficacy and durability. Full article

Background: Radiotherapy is a cornerstone of treatment for cervical and endometrial cancers but is associated with vascular and perivascular changes that can increase surgical complexity and perioperative morbidity. While these effects are well documented in head, neck, and mediastinal irradiation, the pelvic vasculature remains underexplored. Methods: We retrospectively analyzed 119 patients who underwent pelvic oncologic surgery after RT (57.1% cervical cancer, 42.9% endometrial cancer). Intraoperative vascular findings were recorded and correlated with tumor type, perioperative complications, and vascular injury. Logistic regression was used to identify predictors of perioperative morbidity. Results: Perivascular fibrosis (21.8%) and inflammatory thrombosis (10.1%) were the most frequent intraoperative vascular changes, with no significant differences between tumor types. Most patients required no vascular procedure; when needed, simple venorrhaphy was sufficient, and no complex vascular reconstructions were performed. Perioperative complications occurred more frequently in cervical cancer patients (RR = 2.66; p = 0.02), with hemorrhage and urinary tract injury being the most common. Cervical tumor site and perivascular fibrosis were borderline predictors of complications. Conclusions: Neoadjuvant RT induces measurable intraoperative vascular changes without significantly increasing major vascular injury, particularly in experienced surgical settings. Cervical cancer patients represent a higher-risk subgroup, underscoring the need for meticulous surgical planning and multidisciplinary perioperative management. Perivascular fibrosis may serve as a marker for operative risk stratification, and long-term vascular surveillance is warranted due to the potential for delayed macrovascular events. Full article

Mediastinal radiotherapy plays a central role in the treatment of several malignancies, particularly Hodgkin lymphoma and breast cancer. However, exposure to thoracic radiation is associated with long-term cardiovascular complications, among which valvular heart disease (VHD) is increasingly recognized. Radiation-induced VHD typically presents after a latency period of 10–20 years and is characterized by progressive valve fibrosis, thickening, and calcification, most commonly affecting the left-sided valves. Management of radiation-induced VHD generally follows standard guidelines but remains challenging due to extensive calcification and coexisting radiation-related cardiac or pulmonary injury. A history of thoracic radiotherapy is associated with increased perioperative risk and may negatively impact surgical outcomes, which often alters the risk–benefit balance and favors less invasive therapeutic approaches. Advances in the transcatheter approach have expanded treatment options for this high-risk population; however, data on long-term outcomes remain limited. Evolving dose-reduction techniques, such as deep-inspiration breath-hold, intensity-modulated radiotherapy, and proton therapy, together with predictive dosimetric models, aim to minimize future cardiac toxicity. Given the delayed onset and progressive nature of radiation-associated VHD, structured long-term surveillance is essential to enable early detection and timely intervention in cancer survivors at risk. Full article

Background: Radiation-induced pulmonary fibrosis (RPF) remains a major burden of successful lung cancer radiotherapy. Clinically validated drugs targeting RPF remains scarce. Methods: We employed a transcriptome-based drug repurposing approach using REMEDY, a computational platform built on the Library of Integrated Network-Based Cellular Signatures (LINCS). Differentially expressed genes (DEGs) derived from radiation-induced lung injury (RILI) models were used as a query to identify compounds capable of reversing pro-fibrotic expression profile. Among top-ranked candidates, homoharringtonine (HHT), an FDA-approved protein synthesis inhibitor, was selected for experimental validation. Anti-fibrotic effects of HHT were assessed using an optimized in vitro fibrotic model based on activation of MRC-5 human lung fibroblasts. Complementary in silico molecular docking analyses were also conducted to explore the mechanistic basis of HHT’s actions. This represents the first transcriptome-guided, LINCS-based drug repurposing study applied specifically to radiation-induced pulmonary fibrosis, utilizing RPF-derived molecular signatures rather than general fibrosis-related datasets. Results: HHT significantly attenuated key fibrotic phenotypes, including fibroblast proliferation, myofibroblast differentiation, and extracellular matrix (ECM) production. Notably, HHT suppressed expression of cyclin D1 and α-smooth muscle actin (α-SMA), and reduced collagen deposition. Mechanistic investigations revealed that HHT modulates two pro-fibrotic pathways: RhoA/ROCK and Wnt/β-catenin signaling. Molecular docking further suggested that HHT may directly interact with fibrosis-related receptors such as integrins and Frizzled, providing structural insight into its anti-fibrotic potential. These findings underscore the novelty of reassigning HHT to a radiation-specific fibrotic context using a signature-reversal strategy uniquely tailored to RPF biology. Conclusions: Our findings identify HHT as a promising treatment of RPF, offering a dual mechanism of action—interruption of protein synthesis and targeted inhibition of fibrotic signaling pathways. This study highlights the value of computational drug repurposing platforms for accelerating therapeutic discovery. Further preclinical investigations are warranted to evaluate HHT’s in vivo efficacy and clinical applicability in RPF. Full article

Background/Objectives: Radiotherapy (RT) induces oxidative stress and structural damage in solid tissues, including the liver. This study aimed to investigate the histological and immunohistochemical effects of dexmedetomidine (DEX) and amifostine on their potential protective and regenerative properties against liver injury induced by radiation therapy. Methods: This study consisted of five randomized groups: control, RT, RT-D100, RT-D200, and RT-A (Amifostine). A total of 100 µg/kg DEX, 200 µg/kg DEX, and 200 µg/kg amifostine were administered before radiotherapy as per the experimental design. After RT, liver specimens were analyzed for histological alterations, including periportal and perisinusoidal fibrosis, vacuolization, and pyknotic nuclei. Furthermore, immunohistochemistry investigations were conducted to evaluate apoptosis, mitosis, oxidative stress, and neural regeneration in non-neuronal liver tissue following radiotherapy and subsequent treatment. Results: The control group’s liver tissue exhibited standard histological architecture, whereas the RT group displayed severe cellular degeneration, periportal and perisinusoidal fibrosis, cytoplasmic vacuolization, and an increase in pyknotic nuclei. The apoptotic index was markedly reduced in the RT-D100 and RT-D200 groups relative to the RT group. Furthermore, caspase-3 immunoactivity was negligible in the control group, while a significant increase was observed in the RT group. The administration of amifostine significantly increased GAP-43 levels. Conclusions: DEX mitigates RT-induced hepatic injury chiefly through antioxidant and anti-apoptotic pathways, whereas amifostine promotes hepatic regeneration by modulating GAP-43. Full article

Radiation-induced lung inflammation (RILI) is a major complication of thoracic radiotherapy, characterized by excessive inflammation and subsequent fibrosis that compromise pulmonary function and treatment outcomes. This study explores the pharmacological properties of a newly synthesized Lipoxin A4 analogue (CYNC-2) to mitigate RILI by modulating the AMP-activated protein kinase (AMPK)/NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome pathway. A murine RILI model was established in mice by delivering a single high-dose (ablative) X-ray irradiation to the left lung. Mice in the treatment group received CYNC-2 via tail-vein injection three times per week for 2 weeks. The effects of CYNC-2 on RILI were evaluated histological, immunohistochemical analysis of lung tissues, cytokine profiling, lung function testing using a FlexiVent system, and micro-computed tomography (micro-CT) imaging of lung damage. In parallel, two human lung cell lines—L132 (normal bronchial epithelial cells) and A549 (lung carcinoma cells)—were irradiated with 6 Gy X-rays and treated with CYNC-2 to assess cell viability and changes in AMPK/NLRP3 pathway markers via qPCR and immunofluorescence. Lung tissue sample from patients who underwent thoracic radiotherapy were also examined to validate key findings. CYNC-2 activated AMPK and inhibited mTOR signaling, which suppressed NLRP3 inflammasome activation and led to reduced secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TGF-β1). In vitro, CYNC-2 mitigated radiation-induced inflammatory responses and preserved cellular viability. Overall, CYNC-2 effectively dampened acute pulmonary in the RILI model. These findings suggest that targeting the AMPK/NLRP3 inflammasome pathway via a stable LXA4 analogue such as CYNC-2 is a promising therapeutic strategy to improve clinical outcomes for patients receiving thoracic radiation therapy. Full article

Objective: This study aimed to investigate the potential splenic tissue damage induced by radiotherapy (RT) and the potential protective effect of different doses of dexmedetomidine on this damage at the histopathological, immunohistochemical, and biochemical levels. Materials and Methods: In our study, Sprague Dawley rats were randomly divided into four groups: Control, Radiotherapy (RT; 8 Gy), RT + Dexmedetomidine 100 µg/kg (RT-D100), and RT + Dexmedetomidine 200 µg/kg (RT-D200). A single dose of 8 Gy radiotherapy was administered to each RT group. Spleen tissues were examined histologically with hematoxylin-eosin and immunohistochemically with anti-Caspase-3, anti-TGF-β1, and anti-TGF-β3 using light microscopy. TBARS and total thiol levels were also analyzed to assess oxidative stress and antioxidant capacity. Results: Histopathological results showed a significant decrease in white pulp diameter, decreased cellular density, and increased congestion in the red pulp in the RT group. Significant fibrosis, sinusoidal dilatation, vacuolization, and amyloid deposition were detected in the white pulp in the RT group. Regarding anti-caspase-3 immunoreactivity, strong positivity increased in the red pulp in the RT group, while a significant increase was observed in the white pulp in both the RT-D100 and RT groups. While the proportion of TGF-β1 immunopositive cells did not change significantly in the RT group, they increased significantly in both dexmedetomidine groups (especially RT-D200). TGF-β3 expression increased significantly only in the RT-D100 group. In biochemical analyses, TBARS levels increased significantly in the RT-D100 group. Total thiol levels decreased in the RT group and increased in the dexmedetomidine-treated groups. Conclusions: While RT caused histopathological damage and increased oxidative stress in spleen tissue, dexmedetomidine reduced this damage in a dose-dependent manner. The different immunohistochemical profiles of TGF-β1 and TGF-β3 suggest that these cytokines may have different functions in the spleen. 100 µg/kg dexmedetomidine stimulates a regenerative response through TGF-β3, while 200 µg/kg dexmedetomidine may provide immune regulation and antioxidative defense through TGF-β1. Full article

Purpose: This systematic review aims to analyze the literature on the application of AI in predicting patient outcomes and treatment-related toxicity in those undergoing SBRT or SRS across heterogeneous tumor sites. Materials and methods: Our review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, EMBASE and Scopus were systematically searched for English-language human studies evaluating AI for outcome and toxicity prediction in patients undergoing SBRT or SRS for solid tumors. Search terms included (“Stereotactic Body Radiotherapy” OR “SBRT” OR “Stereotactic Radiosurgery” OR “SRS” OR “Stereotactic Ablative Radiotherapy” OR “SABR”) AND (“Artificial Intelligence” OR “AI” OR “Machine Learning” OR “Deep Learning” OR “Radiomics”) AND (“Response Prediction” OR “Response to Treatment” OR “Outcome Prediction”) AND (“Toxicity” OR “Side Effects” OR “Treatment Toxicities” OR “Adverse Events”). Results: The search yielded 29 eligible retrospective studies, published between 2020 and 2025. Eight studies addressed early-stage primary lung cancer, highlighting the potential of AI-based models in predicting radiation-induced pneumonitis, fibrosis and local control. Five studies investigated AI models for predicting hepatobiliary toxicity following SBRT for liver tumors. Sixteen studies involved SRS-treated patients with brain metastases or benign intracranial neoplasms (e.g., arteriovenous malformations, vestibular schwannomas, meningiomas), exploring AI algorithms for predicting treatment response and radiation-induced changes. In the results, AI might have been exploited to both reaffirm already known clinical predictors and to identify novel imaging, dosimetric or biological biomarkers. Examples include predicting radiation pneumonitis in lung cancer, residual liver function in hepatic tumors and local recurrence in brain metastases, thus supporting tailored treatment decisions. Conclusions: Combining AI with SBRT could greatly enhance personalized cancer care by predicting patient-specific outcomes and toxicity. AI models analyze complex datasets, including imaging and clinical data, to identify patterns that traditional methods may miss, thus enabling more accurate risk stratification and reducing variability in treatment planning. With further research and clinical validation, this integration could make radiotherapy safer, more effective and contribute to advancement in precision oncology. Full article

Ionizing radiation (IR) poses a dual challenge in medicine; while essential for cancer therapy, it inflicts collateral damage to normal tissues, particularly the gastrointestinal (GI) tract. High-dose IR triggers acute radiation syndrome (ARS), characterized by crypt stem cell depletion, mucosal barrier disruption, inflammation, and potential progression to fibrosis and secondary malignancy. Emerging evidence identifies the epithelial kinase doublecortin-like kinase 1 (DCLK1)—highly expressed in GI tuft cells and cancer stem-like cells—as a master regulator of post-IR responses. DCLK1 integrates DNA repair (via p53/ATM), and survival signaling (via NF-κB, TGF-β, and MAPK) to promote epithelial regeneration, yet these same mechanisms contribute to therapy resistance and oncogenesis. DCLK1 further modulates the immune microenvironment by skewing macrophages toward an immunosuppressive M2 phenotype, enhancing tissue remodeling, angiogenesis, and immune evasion. Preclinical studies demonstrate that DCLK1 inhibition sensitizes tumors to radiotherapy while preserving mucosal repair. Therapeutic strategies targeting DCLK1, alongside radioprotective agents, immunomodulators, and senolytics, may enhance regeneration, limit fibrosis, and eradicate therapy-resistant cancer stem cells. This review highlights DCLK1’s dual role in regeneration and tumorigenesis and evaluates its potential as a therapeutic target and biomarker in IR-induced GI damage. Full article

During radiotherapy, X-rays can deliver significant doses of ionising radiation to both cancerous and healthy tissue, often leading to undesirable side effects that compromise patient outcomes. While the cellular effects of such therapeutic X-ray exposures are well studied, the impact on extracellular matrix (ECM) proteins remains poorly understood. This study characterises the response of ECM proteins, including the major tissue components collagen I and fibronectin (FN), to X-ray doses similar to those used in clinical practice (50 Gy, as employed in breast radiotherapy, and 100 Gy), using a combination of gel electrophoresis, biochemical assays, and mass spectrometry-based peptide location fingerprinting (PLF) analysis. In purified protein solutions, 50 Gy X-ray exposure led to the fragmentation of constituent collagen I α chains. Irradiation of purified plasma FN (pFN) induced localised changes in peptide yields (detected by liquid chromatography and tandem mass spectrometry (LC-MS/MS) and PLF) and enhanced its binding to collagen I. In complex environments, such as newly synthesised fibroblast-derived ECM and mature ex vivo breast tissue, X-ray exposure induced peptide yield changes in not only collagen I and FN but also key basement membrane proteins, including collagen IV, laminin, and perlecan. Intracellular proteins associated with gene expression (RPS3, MeCP2), the cytoskeleton (moesin, plectin), and the endoplasmic reticulum (calnexin) were also found to be impacted. These X-ray-induced structural changes may impair the ECM integrity and alter cell–ECM interactions, with potential implications for tissue stiffening, fibrosis, and impaired wound healing in irradiated tissues. Full article

Radiation-induced cardiac toxicity is a recognized complication in patients undergoing thoracic radiotherapy. A crucial manifestation of this toxicity is the damage caused to coronary arteries, which can result in accelerated atherosclerosis that may remain undetected for many years. As cancer survival rates continue to improve, the incidence of radiation-induced coronary artery disease (RICAD) is increasing, making it one of the leading causes of morbidity and mortality among patients treated with radiotherapy for mediastinal cancers. The pathophysiology of RICAD involves a complex interplay of cellular mechanisms, including endothelial dysfunction, inflammation, and fibrosis. These processes are related to several molecular insults such as DNA damage, telomere erosion, and mitochondrial dysfunction. However, to fully understand the initiation and progression of the disease, further research is critical to uncover additional contributing factors. Different strategies for preventing cardiovascular complications in cancer patients are gaining significant attention. Recent advancements in radiotherapy, particularly the new FLASH radiotherapy technique, show promise in reducing the incidence of these complications. This review focuses on the effects of radiotherapy on coronary artery disease, exploring the underlying cellular and molecular mechanisms, as well as potential strategies to prevent RICAD. Full article

Objective: Radiotherapy administered to control thoracic cancers results in a partial irradiation of the heart at mean doses up to 19 Gy, which increases the risk of developing a spectrum of cardiovascular diseases known as radiation-induced heart disease (RIHD). As inflammation is a major driver of the development of RIHD, we investigated the potential of the anti-inflammatory agent cannabidiol (CBD) to attenuate irradiation-induced cardiovascular damage in vivo. Methods: Female C57BL/6 mice were given daily injections of CBD (i.p., 20 mg/kg body weight) for 4 weeks beginning either 2 weeks prior to 16 Gy irradiation of the heart or at the time of irradiation. Mice were sacrificed 30 min and 2, 4, and 10 weeks after irradiation to investigate the expression of inflammatory markers and stress proteins in primary cardiac endothelial cells (ECs). DNA double-strand breaks, immune cell infiltration, and signs of fibrosis were studied in explanted heart tissue. Results: We showed that the irradiation-induced upregulation of the inflammatory markers ICAM-1 and MCAM was only attenuated when treatment with CBD was started 2 weeks prior to irradiation but not when the CBD treatment was started concomitant with irradiation of the heart. The protective effect of CBD was associated with a decrease in irradiation-induced DNA damage and an increased expression of protective heat shock proteins (Hsp), such as Hsp32/Heme-oxygenase-1 (HO-1) and Hsp70, in the heart tissue. While the upregulation of the inflammatory markers ICAM-1 and MCAM, expression was prevented up to 10 weeks after irradiation by CBD pre-treatment, and the expression of VCAM-1, which started to increase 10 weeks after irradiation, was further upregulated in CBD pre-treated mice. Despite this finding, 10 weeks after heart irradiation, immune cell infiltration and fibrosis markers of the heart were significantly reduced in CBD pre-treated mice. Conclusion: CBD treatment before irradiation mediates beneficial effects on murine hearts of mice, resulting in a reduction of radiation-induced complications, such as vascular inflammation, immune cell infiltration, and fibrosis. Full article

Head and neck cancer encompasses a diverse group of malignant neoplasms originating in regions such as the oral cavity, oropharynx, hypopharynx, larynx, sinonasal cavities, and salivary glands. HNC represents a significant public health challenge, and recent reports indicate an increment in the incidence of HNC in young adults. In 2020, approximately 377,700 new HNC cases and 177,800 HNC-related deaths were reported globally. Major risk factors include tobacco smoking, alcohol consumption, and human papillomavirus (HPV) infections. HNC impacts vital functions such as breathing, swallowing, and speech. Treatments for this type of cancer within this complex anatomy include surgery, radiotherapy, and chemotherapy combinations. Radiotherapy is often an essential component of both curative and palliative HNC treatment, balancing tumor control with the preservation of function and appearance. However, its use can damage adjacent normal tissues, causing acute or chronic toxicity. One complication of HNC irradiation is VF fibrosis, which leads to severe voice impairments, significantly affecting patients’ quality of life. Fibrosis involves excessive and aberrant deposition of extracellular matrix, driven by factors such as TGF-β1 and inflammatory cytokines, which ultimately impair the flexibility and function of VF. Current radiation-induced fibrosis treatments primarily focus on symptom management and include systemic therapies like corticosteroids, anti-inflammatory drugs, and antioxidants. However, these treatments have limited efficacy. Experimental approaches targeting molecular pathways involved in fibrosis are being explored. Given the limitations of these treatments, advancing research is crucial to develop more effective therapeutic strategies that can significantly improve the quality of life for HNC patients, especially those vulnerable to VF fibrosis. Full article

Purpose: This study aimed to clarify the protective effect of astilbin (AST) on radiation-induced pulmonary fibrosis (RIPF) and explore its underlying molecular mechanism, focusing on non-coding RNAs. Methods: Mouse lung epithelial cells (MLE-12 and TC-1) and C57BL/6J mice were used to establish in vitro radiation injury models and in vivo RIPF models, respectively. Cell viability, apoptosis, the epithelial-to-mesenchymal transition (EMT), and fibrosis-related markers were assessed using cell-counting kit-8 assays, Western blotting, immunohistochemistry, and histological staining. High-throughput sequencing identified differentially expressed circRNAs. The mechanistic studies included RNA-FISH, a dual-luciferase reporter assay, an RNA immunoprecipitation (RIP) assay, and loss-of-function experiments. Results: AST significantly alleviated radiation-induced apoptosis and EMT in vitro, as well as RIPF in vivo. AST treatment reduced collagen deposition, fibrosis-related protein expression, and EMT marker changes. High-throughput sequencing revealed that AST upregulated circPRKCE, a non-coding RNA that functions through a ceRNA mechanism by binding to miR-15b-5p, thereby promoting Smad7 expression and suppressing the TGF-β/Smad7 pathway. Knockdown of circPRKCE abolished AST’s protective effects, confirming its pivotal role in mediating AST’s anti-fibrotic activity. Conclusions: This study demonstrates that Astilbin alleviates radiation-induced pulmonary fibrosis via circPRKCE targeting the TGF-β/Smad7 pathway to inhibit EMT, suggesting AST as a potential therapeutic agent for managing this severe complication of radiotherapy. Full article

Background: Intensity modulated radiotherapy with helical tomotherapy (IMRT-HT) is used in the breast cancer (BC) treatment for years now to obtain homogeneous dose distribution in the treated volumes and reduce the doses to organs at risk. The purpose of this study was to evaluate our experience in terms of local control, overall survival, progression free survival and adverse events in BC patients treated with IMRT-HT with long term follow-up. Methods: This study is a retrospective data analysis of patients irradiated with IMRT-HT. Overall survival (OS) and progression free survival (PFS) curves were plotted with Kaplan-Meier method. We also analyzed the OS and PFS data by molecular subgroups of the population. Long-term toxicities including skin, cardiac and pulmonary complications were also evaluated. Multivariant logistic regression analysis was performed to determine the independent predictors of the side effects. Results: Between 2009 and 2015, a total of 194 breasts in 179 women with nonmetastatic breast cancer were treated. Most of the tumors were grade III and N+. With a median follow-up of 10 years, we observed 9 local recurrences, 2 loco-regional recurrences, and 29 patients experienced metastatic disease. Only 18 patients are dear, of them 7 cases with breast cancer death. At 10 years, the Local recurrence free survival was 95.3% [95%CI: 92.1–98.5], the loco-regional relapse free survival was 94.5% [91.1–98.1]. The metastases free survival was 82.9% [76.9–89.3]. The progression free survival was 79.9 [73.6–86.7]. The cancer specific survival was 94.3%, and the overall survival 88% [82.8–93.5]. At long term, there were no cardiac, lung, thyroid, digestive radio induced toxicities. A small number of patients experienced grade I or II fibrosis. Conclusions: IMRT-HT could be safely used for adjuvant breast cancer irradiation in patients with complex anatomy. IMRT-HT provides favourable long-term prognosis, while late toxicity is acceptable. Full article