Search Results (239)

Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article

Background/Objectives: Radiotherapy (RT) is a mainstay of clinical cancer therapy that causes broad immune responses. The complement system is a pivotal effector mechanism in the innate immune response, but the impact of RT is less well understood. This study investigates the interaction between RT and the complement system as a possible approach to improve immune responses in cancer treatment. Methods: Human solid cancer (lung, prostate, liver, breast cancer), lymphoma, and leukemia cells were irradiated using X-rays and treated with polyclonal antibodies or anti-CD20 monoclonal antibodies, respectively. Chromium release assay was applied to measure cell lysis after radiation with or without complement-activating antibody treatment. The expression of membrane-bound complement regulatory proteins (mCRPs; CD46, CD55, CD59), which confer resistance against complement activation, CD20 expression, apoptosis, and radiation-induced DNA double-strand breaks (γH2AX), was measured by flow cytometry. The radiosensitivity of tumor cells was assessed by colony-forming assay. Results: We demonstrate that RT profoundly impacts complement function by upregulating the expression of membrane-bound complement regulatory proteins (mCRPs) on tumor cells in a dose- and time-dependent manner. Impaired complement-mediated tumor cell lysis could thus potentially contribute to radiotherapeutic resistance. We also observed RT-induced upregulation of CD20 expression on lymphoma and leukemic cells. Notably, complement activation prior to RT proved more effective in inducing RT-dependent early apoptosis compared to post-irradiation treatment. While complement modulation does not significantly alter RT-induced DNA-damage repair mechanisms or intrinsic radiosensitivity in cancer cells, our results suggest that combining RT with complement-based anti-cancer therapy may enhance complement-dependent cytotoxicity (CDC) and apoptosis in tumor cells. Conclusions: This study sheds light on the complex interplay between RT and the complement system, offering insights into potential novel combinatorial therapeutic strategies and a potential sequential structure for certain tumor types. Full article

Stereotactic Body Radiotherapy (SBRT) has emerged as a pivotal treatment modality for early-stage non-small cell lung cancer (NSCLC), offering highly precise, high-dose radiation delivery. However, several clinical challenges remain, particularly in the treatment of central or ultracentral tumors, which are located near critical structures such as the heart, bronchi, and great vessels. The introduction of MRI-guided SBRT has significantly improved targeting precision, allowing for better assessment of tumor motion and adjacent organ structures. Additionally, SBRT has demonstrated efficacy in multifocal NSCLC, providing an effective option for patients with multiple primary tumors. Recent advances also highlight the role of SBRT in locally advanced NSCLC, where it is increasingly used as a complementary approach to concurrent chemotherapy or in cases where surgery is not feasible. Moreover, the combination of SBRT with immunotherapy has shown promising potential, enhancing tumor control and immunological responses. Furthermore, SBRTs application in SCLC is gaining momentum as a palliative and potentially curative option for selected patients. This narrative review explores these evolving clinical scenarios, the technical innovations supporting SBRT, and the integration of immunotherapy, providing an in-depth look at the new frontiers of SBRT in lung cancer treatment. Despite the challenges, the ongoing development of personalized approaches and technological advancements continues to push the boundaries of SBRTs clinical utility in lung cancer. Full article

Brain metastases (BMs) are the most common intracranial tumors in adults. Their heterogeneity, potential multifocality, and complex biomolecular behavior pose significant diagnostic and therapeutic challenges. Artificial intelligence (AI) has the potential to revolutionize BM diagnosis by facilitating early lesion detection, precise imaging segmentation, and non-invasive molecular characterization. Machine learning (ML) and deep learning (DL) models have shown promising results in differentiating BMs from other intracranial tumors with similar imaging characteristics—such as gliomas and primary central nervous system lymphomas (PCNSLs)—and predicting tumor features (e.g., genetic mutations) that can guide individualized and targeted therapies. Intraoperatively, AI-driven systems can enable optimal tumor resection by integrating functional brain maps into preoperative imaging, thus facilitating the identification and safeguarding of eloquent brain regions through augmented reality (AR)-assisted neuronavigation. Even postoperatively, AI can be instrumental for radiotherapy planning personalization through the optimization of dose distribution, maximizing disease control while minimizing adjacent healthy tissue damage. Applications in systemic chemo- and immunotherapy include predictive insights into treatment responses; AI can analyze genomic and radiomic features to facilitate the selection of the most suitable, patient-specific treatment regimen, especially for those whose disease demonstrates specific genetic profiles such as epidermal growth factor receptor mutations (e.g., EGFR, HER2). Moreover, AI-based prognostic models can significantly ameliorate survival and recurrence risk prediction, further contributing to follow-up strategy personalization. Despite these advancements and the promising landscape, multiple challenges—including data availability and variability, decision-making interpretability, and ethical, legal, and regulatory concerns—limit the broader implementation of AI into the everyday clinical management of BMs. Future endeavors should thus prioritize the development of generalized AI models, the combination of large and diverse datasets, and the integration of clinical and molecular data into imaging, in an effort to maximally enhance the clinical application of AI in BM care and optimize patient outcomes. Full article

The phototherapeutic applications of porphyrin-based nanoscale metal–organic frameworks (nMOFs) are limited by the poor penetration of conventional excitation light sources into biological tissues. Radiodynamic therapy (RDT), which directly excites photosensitizers using X-rays, can overcome the issue of tissue penetration. However, RDT faces the problems of low energy conversion efficiency, requiring a relatively high radiation dose, and the potential to cause damage to normal tissues. Researchers have found that by using some metals with high atomic numbers (high Z) as X-ray scintillators and coordinating them with porphyrin photosensitizers to form MOF materials, the excellent antitumor effect of radiotherapy (RT) and RDT can be achieved under low-dose X-ray irradiation, which can not only effectively avoid the penetration limitations of light excitation methods but also eliminate the defect issues associated with directly using X-rays to excite photosensitizers. This review summarizes the relevant research work in recent years, in which researchers have used metal ions with high Z, such as Hf⁴⁺, Th⁴⁺, Ta⁵⁺, and Bi³⁺, in coordination with carboxyl porphyrins to form MOF materials for combined RT and RDT toward various cancer cells. This review compares the therapeutic effects and advantages of using different high-Z metals and introduces the application of the heavy atom effect. Furthermore, it explores the introduction of a chemodynamic therapy (CDT) mechanism through iron coordination at the porphyrin center, along with optimization strategies such as oxygen delivery using hemoglobin to enhance the efficacy of these MOFs as radiosensitizers. This review also summarizes the potential of these materials in preclinical applications and highlights the current challenges they face. It is expected that the summary and prospects outlined in this review can further promote preclinical biomedical research into and the development of porphyrin-based nMOFs. Full article

Pre-metastatic niche (PMN) formation is a critical step in metastatic progression. However, the biological effects of subtherapeutic doses of ionizing radiation (SDIRs) following radiotherapy on this process remain unclear. Using a 4T1 breast cancer mouse model, we investigated the effects of SDIRs (3 × 0.3 Gy) on lung PMN development and metastasis upon SDIR exposure on days 8–10 post-tumor injection, followed by mastectomy and analyzed on day 24. SDIRs significantly increased the total metastatic volume (TMV) in lungs, suggesting an accelerated PMN formation. Mechanistically, the SDIR acted as an early catalyst for niche priming, upregulating Bv8 expression, enhancing neutrophil recruitment, and increasing MMP9, S100A8, and Il6 production in the PMN by day 11. Moreover, SDIR drives metastasis through distinct mechanisms. Proteomic analysis revealed SDIR-driven metabolic reprogramming, with a shift away from fatty acid metabolism toward glycolysis and lipid accumulation within the PMN. This shift contributes to extracellular matrix (ECM) remodeling, immune modulation, and the upregulation of adhesion-related pathways, shaping a microenvironment that accelerates metastatic outgrowth. By reprogramming the pre-metastatic lung, the SDIR highlights the need to integrate organ-specific radiation exposure into metastasis models. Metabolic and immune-stromal pathways emerge as potential therapeutic targets, underscoring the importance of refining radiotherapy strategies to mitigate unintended pro-metastatic effects. Full article

Background: The use of nanoradiosensitizers is a promising strategy for the precision enhancement of tumor tissue damage during radiotherapy. Methods: Here, we propose a novel biocompatible theranostic agent based on gadolinium fluoride doped with cerium and terbium (Gd_0.7Ce_0.2Tb_0.1F₃ NPs), which showed pronounced radiocatalytic activity when exposed to photon or proton beam irradiation, as well as remarkable MRI contrast ability. A scheme for the production of biocompatible colloidally stable Gd_0.7Ce_0.2Tb_0.1F₃ NPs was developed. Comprehensive physicochemical characterization of these NPs was carried out, including TEM, SEM, XRD, DLS, and EDX analyses, as well as UV–vis spectroscopy and MRI relaxation assays. Results: Cytotoxicity analysis of Gd_0.7Ce_0.2Tb_0.1F₃ NPs in vitro and in vivo revealed a high level of biocompatibility. It was shown that Gd_0.7Ce_0.2Tb_0.1F₃ NPs effectively accumulate in MCF-7 tumor cells. A study of their radiosensitizing activity demonstrated that the combined effect of Gd_0.7Ce_0.2Tb_0.1F₃ NPs and X-ray irradiation leads to a dose-dependent decrease in mitochondrial membrane potential, a sharp increase in the level of intracellular ROS, and the subsequent development of radiation-induced apoptosis. Conclusions: This outstanding radiosensitizing effect is explained by the radiocatalytic generation of reactive oxygen species by the nanoparticles, which goes beyond direct physical dose enhancement. It emphasizes the importance of evaluating the molecular mechanisms underlying the sensitizing effectiveness of potential nanoradiosensitizers before choosing conditions for their testing in in vivo models. Full article

Stereotactic body radiotherapy (SBRT) delivers ablative radiation doses with sub-millimeter precision. Radiogenomic studies, meanwhile, provide insights into how tumor-intrinsic genetic factors influence responses to such high-dose treatments. This review explores the radiobiological mechanisms underpinning SBRT efficacy, emphasizing the roles of DNA damage response (DDR) pathways, tumor suppressor gene alterations, and inflammatory signaling in shaping tumor radiosensitivity or resistance. SBRT induces complex DNA double-strand breaks (DSBs) that robustly activate DDR signaling cascades, particularly via the ATM and ATR kinases. Tumors with proficient DNA repair capabilities often resist SBRT, whereas deficiencies in key repair genes can render them more susceptible to radiation-induced cytotoxicity. Mutations in tumor suppressor genes may impair p53-dependent apoptosis and disrupt cell cycle checkpoints, allowing malignant cells to evade radiation-induced cell death. Furthermore, SBRT provokes the release of pro-inflammatory cytokines and activates innate immune pathways, potentially leading to immunogenic cell death and reshaping the tumor microenvironment. Radiogenomic profiling has identified genomic alterations and molecular signatures associated with differential responses to SBRT and immune activation. These insights open avenues for precision radiotherapy approaches, including the use of genomic biomarkers for patient selection, the integration of SBRT with DDR inhibitors or immunotherapies, and the customization of treatment plans based on individual tumor genotypes and immune landscapes. Ultimately, these strategies aim to enhance SBRT efficacy and improve clinical outcomes through biologically tailored treatment. This review provides a comprehensive summary of current knowledge on the genetic determinants of response to stereotactic radiotherapy and discusses their implications for personalized cancer treatment. 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

Introduction: Interventional radiotherapy (brachytherapy, IRT, BT) has evolved with technological advancements, improving dose precision while minimizing exposure to healthy tissues. The integration of 3D-printing technology in IRT has enabled the development of patient-specific devices, optimizing treatment personalization and dosimetric accuracy. Methods: A systematic literature search was conducted in PubMed, Scopus, and Google Scholar to identify studies published between 2020 and 2024 on 3D-printing applications in IRT. The selection process resulted in 74 peer-reviewed articles categorized by radioactive source, brachytherapy technique, endpoint of the 3D-printed product, and study type. Results: The analysis highlights the growing implementation of 3D-printed devices in brachytherapy, particularly in gynecological, prostate, and skin cancers. Most studies focus on technique, including intracavitary, interstitial, and contact applications, with custom applicators and templates emerging as predominant endpoints. The majority of studies involved in vivo clinical applications, followed by in silico computational modeling and in vitro experiments. Conclusions: The upward trend in scientific publications underscores the growing attention on 3D printing for enhancing personalized brachytherapy. The increasing use of 3D-printed templates and applicators highlights their role in optimizing dose delivery and expanding personalized treatment strategies. The current research trend is shifting toward real-world data and in vivo studies to assess clinical applications, ensuring these innovations translate effectively into routine practice. The integration of 3D printing represents a major advancement in radiation oncology, with the potential to enhance treatment efficacy and patient outcomes. Future research should focus on standardizing manufacturing processes and expanding clinical validation to facilitate broader adoption. 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

Radiotherapy (RT) has undergone transformative advancements since its inception over a century ago. This review highlights the most promising and impactful innovations shaping the current and future landscape of RT. Key technological advances include adaptive radiotherapy (ART), which tailors treatment to daily anatomical changes using integrated imaging and artificial intelligence (AI), and advanced image guidance systems, such as MR-LINACs, PET-LINACs, and surface-guided radiotherapy (SGRT), which enhance targeting precision and minimize collateral damage. AI and data science further support RT through automation, improved segmentation, dose prediction, and treatment planning. Emerging biological and targeted therapies, including boron neutron capture therapy (BNCT), radioimmunotherapy, and theranostics, represent the convergence of molecular targeting and radiotherapy, offering personalized treatment strategies. Particle therapies, notably proton and heavy ion RT, exploit the Bragg peak for precise tumor targeting while reducing normal tissue exposure. FLASH RT, delivering ultra-high dose rates, demonstrates promise in sparing normal tissue while maintaining tumor control, though clinical validation is ongoing. Spatially fractionated RT (SFRT), stereotactic techniques and brachytherapy are evolving to treat challenging tumor types with enhanced conformality and efficacy. Innovations such as 3D printing, Auger therapy, and hyperthermia are also contributing to individualized and site-specific solutions. Across these modalities, the integration of imaging, AI, and novel physics and biology-driven approaches is redefining the possibilities of cancer treatment. This review underscores the multidisciplinary and translational nature of modern RT, where physics, engineering, biology, and informatics intersect to improve patient outcomes. While many approaches are in various stages of clinical adoption and investigation, their collective impact promises to redefine the therapeutic boundaries of radiation oncology in the coming decade. Full article

Synchrotron radiation light sources have been successfully utilized in material science, biomedicine, and other fields due to their high intensity, excellent monochromaticity, coherence, and collimation. In recent years, synchrotron radiation has significantly expedited the advancement of medical applications, particularly through innovations in imaging and radiotherapy. For instance, synchrotron X-ray imaging has enabled high-contrast and spatial–temporal resolution images for early-stage diagnosis of breast cancer and cardiovascular diseases, offering superior diagnostic accuracy compared to conventional methods. Additionally, novel synchrotron radiation-based radiotherapy techniques, such as microbeam therapy and stereotactic radiotherapy, have shown great potential for clinical application by enabling precise tumor targeting while minimizing damage to surrounding healthy tissues. These advancements are projected to redefine imaging diagnostics and therapeutic strategies, particularly for resistant cancers, by offering enhanced precision, reduced radiation doses, and improved therapeutic outcomes. This review provides an overview of synchrotron radiation beamline characteristics, recent breakthroughs in imaging and radiotherapy, and their emerging applications in treating heart, breast, lung, bone, and brain conditions. Full article

This study investigates the generation of synthetic CT (sCT) images from zero echo time (ZTE) MRI to support MR-only radiotherapy, which can reduce image registration errors and lower treatment planning costs. Since MRI lacks the electron density data required for accurate dose calculations, generating reliable sCTs is essential. ZTE MRI, offering high bone contrast, was used with two deep learning models: attention deep residual U-Net (ADR-Unet) and derived conditional generative adversarial network (cGAN). Data from 17 head and neck cancer patients were used to train and evaluate the models. ADR-Unet was enhanced with deep residual blocks and attention mechanisms to improve learning and reconstruction quality. Both models were implemented in-house and compared to standard U-Net and Unet++ architectures using image quality metrics, visual inspection, and dosimetric analysis. Volumetric modulated arc therapy (VMAT) planning was performed on both planning CT and generated sCTs. ADR-Unet achieved a mean absolute error of 55.49 HU and a Dice score of 0.86 for bone structures. All the models demonstrated Gamma pass rates above 99.4% and dose deviations within 2–3%, confirming clinical acceptability. These results highlight ADR-Unet and cGAN as promising solutions for accurate sCT generation, enabling effective MR-only radiotherapy. Full article

Objective: Radiotherapy is a primary method for cancer treatment, wherein radiation doses are divided into multiple sessions or fractions to effectively target tumors and minimize damage to surrounding tissues. Methods: In this study, we leverage reinforcement learning (RL) to enhance treatment planning with the aim of improving the adaptability and robustness of RL agents given the inherent inaccuracies in tumor growth models. A 2D simulation model of tumor growth is employed, where tabular RL techniques are used to determine the optimal treatment strategies. We emphasize the significance of tissue damage predictions and incorporate the Lyman NTCP model to assess treatment outcomes, analyzing complications across three simulated body sites: the rectum, head and neck and lung. Results: For all the tumor sites, the RL approach significantly reduces healthy tissue damage by 10.7%, 49.1% and 37.5%, respectively, for rectal, head and neck and lung cancers compared with the baseline treatment. Conclusions: The RL-based approach in radiotherapy not only achieves tumor eradication but also significantly reduces healthy tissue damage compared with traditional treatment methods. This study demonstrates the potential of reinforcement learning to optimize treatment planning in radiotherapy, offering a promising path towards more personalized and effective cancer treatments. Full article