Search Results (367)

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Radiation-induced keratoconjunctivitis sicca (KCS) is a significant late complication in dogs receiving radiation therapy for intranasal tumors, particularly with hypofractionated intensity-modulated radiation therapy (IMRT). This retrospective case-control study was performed to identify anatomical and dosimetric risk factors for KCS in 15 canine patients treated with IMRT delivered in 4–6 weekly fractions of 8 Gy. Orbital structures were retrospectively contoured, and dose–volume metrics (D50) were calculated. Receiver operating characteristic (ROC) curve analysis and odds ratios were used to evaluate the associations between radiation dose and KCS development. Six dogs (33%) developed KCS within three months post-treatment. Statistically significant dose differences were observed between affected and unaffected eyes for the eyeball, cornea, and retina. ROC analyses identified dose thresholds predictive of KCS: 13.8 Gy (eyeball), 14.9 Gy (cornea), and 17.0 Gy (retina), with the retina showing the highest odds ratio (28.33). To ensure clinical relevance, KCS was diagnosed based on decreased tear production combined with corneal damage to ensure clinical relevance. This study proposes dose thresholds for ocular structures that may guide treatment planning and reduce the risk of KCS in canine patients undergoing IMRT. Further prospective studies are warranted to validate these thresholds and explore mitigation strategies for high-risk cases. Full article

Targeted radionuclide therapy (TRT) utilizes radiopharmaceuticals to deliver radiation directly to cancer cells while sparing healthy tissues. Beyond the absorbed dose of ablative radiation, TRT induces non-targeted effects (NTEs) that significantly enhance its therapeutic efficacy. These effects include radiation-induced bystander effects (RIBEs), abscopal effects (AEs), radiation-induced genomic instability (RIGI), and adaptive responses, which collectively influence the behavior of cancer cells and the tumor microenvironment (TME). TRT also modulates immune responses, promoting immune-mediated cell death and enhancing the efficacy of combination therapies, such as the use of immune checkpoint inhibitors. The molecular mechanisms underlying TRT involve DNA damage, oxidative stress, and apoptosis, with repair pathways like homologous recombination (HR) and non-homologous end joining (NHEJ) playing critical roles. However, challenges such as tumor heterogeneity, hypoxia, and radioresistance limit the effectiveness of this approach. Advances in theranostics, which integrate diagnostic imaging with TRT, have enabled personalized treatment approaches, while artificial intelligence and improved dosimetry offer potential for treatment optimization. Despite the significant survival benefits of TRT in prostate cancer and neuroendocrine tumors, 30–40% of patients remain unresponsive, which highlights the need for further research into molecular pathways, long-term effects, and combined therapies. This review outlines the dual mechanisms of TRT, direct toxicity and NTEs, and discusses strategies to enhance its efficacy and expand its use in oncology. Full article

Background/Objectives: Prostate cancer is the most frequent cancer in men, for which Radiotherapy (RT) is used as a radical or post-surgical treatment. Actinic proctitis is one of the most disabling side effects of RT. Intestinal microbiome studies have highlighted the importance of short-chain fatty acids, in particular butyric acid, for their beneficial effects over intestinal epithelial cells. The aim of this prospective study is to evaluate if treatment with micro-encapsulated sodium butyrate (MESB) can reduce the incidence of actinic proctitis during RT in prostate cancer patients. Methods: In total, 122 consecutive patients with prostate cancer treated in Radiotherapy Unit, Centro di Riferimento Oncologico, IRCCS Aviano, were enrolled. Patients received MESB (3 tablets/day) from one week before until four weeks after RT. They completed a diary, tracking daily bowel movements, rectal bleeding, abdominal pain, and perceived health status before, at the end, and one month after RT. Results: Although an improvement in symptoms was observed, when comparing interpatient data before RT vs. one month after the end of RT, statistically significant differences emerged only regarding abdominal pain (94.2% vs. 81.6% vs. 81.6%) (McNemar’s test p < 0.002). Conclusions: MESB appears effective in reducing radiation-induced bowel toxicity during RT, minimizing stool changes, incontinence, and abdominal pain. Although patients’ health perception declined at RT completion, it improved after one month, suggesting MESB may support clinical recovery post-treatment. Full article

Prostate cancer is one of the most prevalent malignancies in men, posing a significant public health challenge due to its high incidence and long-term treatment-related toxicities. Long-lived patients often experience prolonged side effects that can severely diminish their quality of life. Despite advancements in radiotherapy techniques like IMRT and VMAT, some patients still experience acute and late side effects. Current treatment protocols do not account for individual variability in normal-tissue radiosensitivity, highlighting the need for predictive tools and a personalised treatment approach. Genetic factors and molecular regulators like microRNAs (miRNAs) contribute to these variations by influencing DNA repair, inflammation, and apoptosis. This review explores potential biomarkers of radiotoxicity, focusing on immune-related factors such as IL-6 and TGF-β1, SNPs influencing radiosensitivity, miRNAs involved in radiation responses, and functional assays including the radiation-induced lymphocyte apoptosis (RILA) test. These approaches offer promising tools for identifying radiosensitive patients and enabling risk-adapted radiotherapy. Full article

High-Z nanoparticles (NPs) have the potential to revolutionize cancer radiotherapy by radiosensitising tumours. This is particularly important for radioresistant cancers such as glioblastoma. A newer NP candidate in this area is thulium oxide nanoparticles (TmNPs). However, prior to clinical assessment, ideal NP characteristics, including biocompatibility, biosafety, and preferential uptake in cancer, should be assessed. This in vitro study compares the effects of TmNP treatment, without radiation, on 9L gliosarcoma (9LGS), a well-established glioblastoma cell model, with exposure to Madin Darby Canine Kidney (MDCK) cells, a widely used non-cancerous cell model. The findings demonstrated selective uptake of TmNPs in 9LGS over MDCK following treatment. A biological assessment of toxicity confirmed minimal long-term effects on MDCK, whilst TmNPs were observed to induce some notable cell death in 9LGS. Excessive TmNP uptake in 9LGS over time was observed to induce cell vacuolisation, which resulted in cell death via necrosis. It was concluded that this was the explanation for the underlying mechanisms of TmNP toxicity in cancer cells. This study was therefore able to demonstrate not only that TmNPs are a biocompatible, cancer-selective candidate for radiosensitiser usage, but further provided a theory to explain its mechanisms of cancer cell toxicity. Full article

Since water contamination has become a serious concern, more effective environmental remediation methods are required. Chitosan (CHT)-based adsorbents have demonstrated high efficacy in removing pollutants due to their unique chemical and structural properties. However, their utilization remains limited by low environmental stability and the absence of effective adsorption sites. The functional moieties of CHT can be altered to improve its performance via graft modification and crosslinking. Compared to conventional hydrogel synthesis techniques, ionizing radiation-induced fabrication, using gamma or electron-beam irradiation, offers a promising platform for innovation across diverse fields. The prime focus of this review is on ionizing radiation developed CHT-based hydrogels to remove toxic heavy metals, dyes, organic contaminants, radionuclides, and humic substances. The fabrication strategy, adsorption mechanism, and factors affecting the adsorption capacity of CHT-based hydrogels are presented. This review aims to underscore the transformative potential of ionizing radiation-induced CHT hydrogels in environmental remediation by examining current research trends and identifying future prospects. Full article

Background: Breast cancer (BC) is the most common cancer in women worldwide. Much progress has been made to improve treatment options for patients suffering from the disease, including a novel therapy—Poly (ADP-ribose) polymerase inhibitor (PARPi) that specifically targets tumors with deficiencies in the Homologous Recombination (HR) DNA repair pathway. To benefit better from conventional therapy, many patients seek alternative supplementation, with 20–30% of cancer patients using herbal medication on top of their regular treatment. An example of such easily available over-the-counter supplements is curcumin, a natural compound derived from turmeric (Curcuma longa). Various studies reported the potential HR deficiency (HRD) inducing effect of curcumin in cancer cells. Methods: Eight BrC and three normal cell lines and a BrC PDX model were used to evaluate the effect of curcumin on RAD51 ionizing radiation-induced focus (IRIF) formation. Three breast BrC cell lines underwent further analysis using the BRCA2 Western blot technique. To assess cell survival after treatment with curcumin and/or PARPi, a clonogenic survival assay was performed on both normal and cancerous cell lines. Results: Curcumin treatment led to a reduction in RAD51 IRIF formation capacity across all tested models. A decrease in BRCA2 levels was observed in the tested cell lines. Our findings demonstrate that HRD can be induced in both cancerous and normal cells, suggesting that curcumin treatment may increase the risk of toxicity when combined with PARPi therapy. Conclusions: The use of curcumin in combination with certain anti-cancer treatments should not be implemented without extensive monitoring for deleterious side effects. Full article

Radiotherapy is commonly used for treating various types of cancer. In addition, adipose tissue is not routinely spared during typical radiation treatment. Although radiation is known to induce metabolic effects in patients, the effects of radiation therapy on adipose tissue have not been elucidated. Currently, few studies have investigated the impact of radiation exposure on adipose tissue, and these have primarily involved whole-body irradiation. This study aimed to understand the acutely persistent damage caused by clinically relevant radiation doses in adipocytes. Specifically, in vitro and in vivo, irradiated adipocytes increased reactive oxygen species (ROS) and lipid peroxidation levels and elevated lipolytic activity compared to unirradiated adipocytes. RNA sequencing also revealed the upregulation of senescence and inflammation pathways. We observed an increase in macrophage and T-cell accumulation at both 1 and 6 months after radiation exposure using in vivo models. Many of the changes observed in irradiated adipose tissue, including oxidative stress, metabolic dysfunction, inflammation, and senescence, are consistent with those observed in adipose tissue from obese patients, in which obesity is a known driver of many cancers. As adipose tissue damage is maintained chronically, protecting adipose tissue from the harmful effects of radiation exposure may improve radiation-induced toxicity and reduce cancer recurrence and progression. Full article

Cellulose is a sustainable biopolymer, being renewable and abundant, non-toxic, biodegradable, and easily functionalizable. However, the development of hydrogels for tissue engineering applications presents significant challenges that require interdisciplinary expertise, given the intricate and dynamic nature of the human body. This paper delves into current research focused on creating advanced cellulose-based hydrogels with tailored mechanical, biological, chemical, and surface properties. These hydrogels show promise in healing, regenerating, and even replacing human tissues and organs. The synthesis of these hydrogels employs a range of innovative techniques, including supramolecular chemistry, click chemistry, enzyme-induced crosslinking, ultrasound, photo radiation, high-energy ionizing radiation, 3D printing, and other emerging methods. In the realm of tissue engineering, various types of hydrogels are explored, such as stimuli-responsive, hybrid, injectable, bio-printed, electrospun, self-assembling, self-healing, drug-releasing, biodegradable, and interpenetrating network hydrogels. Moreover, these materials can be further enhanced by incorporating cell growth factors, biological molecules, or by loading them with cells or drugs. Looking ahead, future research aims to engineer and tailor hydrogels to meet specific needs. This includes exploring safer and more sustainable materials and synthesis techniques, identifying less invasive application methods, and translating these studies into practical applications. Full article

Background: The re-irradiation of centrally located lung tumors poses substantial risks due to prior dose exposure and proximity to critical structures. Accurate target delineation is crucial to minimize toxicity and ensure tumor coverage. Four-dimensional positron emission tomography/computed tomography (4D-PET/CT) integrates respiratory motion and metabolic data, offering improved delineation over static imaging. Its clinical utility in re-irradiation remains under-reported. Methods: A 67-year-old male presented with the central recurrence of squamous cell carcinoma in the right upper lobe, embedded in radiation-induced fibrosis, following prior chemoradiotherapy. Delineation using static PET underestimated tumor motion. A 4D-PET/CT-guided Stereotactic Body Radiation Therapy (SBRT) plan was developed with a prescription of 60 Gy in eight fractions. A comparative plan using static PET was generated to assess the dosimetric differences. Results: The internal target volume (ITV) from 4D-PET/CT was nearly double the size of the GTV from static PET, with a 5.1 mm discrepancy in the craniocaudal axis. The 4D-PET-based plan achieved 95.0% PTV coverage, while the static PET-based plan covered only 61.7%, illustrating the risk of underdosage without motion-resolved imaging. The patient completed the treatment without acute or late toxicity and showed a sustained metabolic response at one year (SUVmax from 13.4 to 5.8). Conclusions: This case demonstrates the clinical value of 4D-PET/CT in the SBRT re-irradiation of centrally located lung tumors, particularly in fibrotic regions where anatomical imaging is insufficient. It enabled accurate delineation, improved dosimetric coverage, and safe, effective retreatment. These findings support its integration into planning for complex thoracic re-irradiation. 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

Radiation therapy offers well-established benefits in enhancing loco-regional control, distant disease control, and breast-cancer-specific survival. However, it is not without its challenges, particularly in breast cancer patients, where advances in systemic therapies and other treatment modalities have significantly improved survival outcomes. As radiation oncologists, our responsibility is to deliver the most effective treatments while minimizing toxicity for each patient. This scoping review aims to retrieve and assess the literature on factors associated with increased radiation-induced late breast toxicity. Specifically, we seek to identify both non-modifiable variables and those that can be influenced by the choices made by radiation oncologists. This review highlights which clinical decisions could directly impact late breast toxicity following adjuvant radiation therapy after breast-conserving surgery. Full article

Proton beam therapy for head and neck cancers traditionally employs a fixed relative biological effectiveness (RBE) of 1.1, which may underestimate actual biological effects in critical structures. This study evaluates how Linear Energy Transfer (LET) optimization could potentially prevent radiation-induced brachial plexopathy (RIBP). (1) Case presentation: A 65-year-old male with stage IVA p16-positive oropharyngeal squamous cell carcinoma received pencil-beam-scanning intensity-modulated proton therapy with concurrent cisplatin. Due to a right level 4 neck node, the high-risk target volume overlapped with the brachial plexus, resulting in a D0.1cc of 70.3 Gy (RBE = 1.1). Four years post-treatment, the patient developed progressive right upper extremity paresthesia, weakness, and dysesthesia. Electromyography revealed myokymia consistent with brachial plexopathy, while MRI showed hyperintensity of the right brachial plexus corresponding to the radiation field. Conservative treatment with pentoxifylline, gabapentin, and physical therapy improved his symptoms. (2) Methods: The original treatment plan was retrospectively analyzed using Monte Carlo dose algorithms and LET-dependent RBE models from McMahon and McNamara. An LET-optimized plan was created to limit LET_d to 2.0 keV/µm in the brachial plexus. (3) Results: The relative biological equivalent (RBE) dose to 0.1cc of the brachial plexus was 77.8 Gy (CGE RBE), exceeding tolerance. The LET-optimized plan reduced the brachial plexus D0.1cc to 59.4 Gy (RBE = 1.1) and 63.2 Gy (CGE RBE), an 18.8% decrease, while maintaining target coverage. LET_d, within the brachial plexus enhancement, decreased from 5.3 to 2.6 keV/μm. (4) Conclusion: This case highlights the potential clinical importance of LET optimization in proton therapy planning, particularly when organs-at-risk overlap with target volumes. By reducing LET_d from 5.3 to 2.6 keV/μm and biological equivalent dose by 18.8%, LET optimization could potentially prevent late toxicities, like RIBP, while maintaining target coverage. Full article

Cancer pain is a common issue for patients, especially in the advanced stages of cancer, and significantly affects the quality of life (QoL), treatment tolerance, and overall treatment outcomes. Pain may be caused by primary tumors, metastases, or as a consequence of the inflammatory reaction of tissues surrounding the tumor following radiotherapy (RT). Effective pain management is crucial, especially with RT being a key method for alleviating cancer pain, particularly in cases of bone and soft tissue metastases. RT provides relief for 60–80% of patients by reducing tumor size and mitigating associated pain. Radiotherapy itself can also induce pain, especially radiation-induced neuropathic pain, which may require further treatment. Despite these potential side effects, RT remains an essential tool in managing cancer pain, though careful management of its toxicities is necessary to improve patient QoL and survival. Full article