Search Results (731)

Alanine dosimetry based on Electron Paramagnetic Resonance (EPR) spectroscopy has been a reliable reference and transfer dosimetry method in high-dose applications, valued for its high precision, accuracy and long-term stability. Additional characteristics, such as dose-rate independence up to 10¹⁰ Gy/s under electron beam (e-beam) irradiation, electron energy independence and tissue equivalence, position alanine EPR as a promising candidate to address dosimetric challenges arising in e-beam Flash Radiotherapy (RT), where radiation energy is delivered at Ultra-High Dose-Rates (UHDR) ≥ 40 Gy/s. At such dose-rates, reliable real-time monitoring dosimeters such as ionization chambers in conventional RT, suffer from ion recombination, compromising accuracy in dose determination. Several studies are currently focused on developing real-time beam monitoring systems dedicated specifically for e-beam Flash RT. This creates a need for standardized reference dosimetry methods to validate beam parameters determined by these systems under investigation. This review provides an overview of the potential and limitations of the alanine EPR dosimetry method for control, validation and verification of e-beam Flash RT beam parameters at doses less than 10 Gy, where the method has shown low sensitivity and increased uncertainty. It further discusses strategies to optimize alanine EPR measurements to enhance sensitivity and accuracy at these dose levels. Improved measurement procedures will ensure reliable and accurate e-beam Flash RT accelerator commissioning, performance checks, patient safety and treatment efficacy across all therapeutic dose ranges. Full article

Objective: Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. Although immunotherapy has transformed MCC management, published data remain limited. This comprehensive review evaluates current evidence on immune checkpoint inhibitors (ICIs) in MCC, in relation to other treatment modalities such as surgery and radiotherapy. Methods: Peer-reviewed articles published between January 2000 and August 2025 were searched manually in four databases: Scopus, ScienceDirect, PubMed and MEDLINE, using the keywords “Merkel cell carcinoma” AND “immunotherapy” AND “immune checkpoint inhibitors”. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was employed. Results: ICIs can be given in different settings: (A) Neoadjuvant: The CheckMate 358 trial reported a 54.5% response rate among 33 radiologically evaluable patients treated with nivolumab, each showing over 30% tumor reduction. (B) Adjuvant: (1) The ADMEC-O phase II trial demonstrated improved disease-free survival with adjuvant nivolumab. (2) The ADAM phase III trial evaluates adjuvant avelumab in node-positive patients post-surgery/radiation, with common side effects including nausea, fatigue, and itching. (3) STAMP, a phase III trial, investigates pembrolizumab in stage I–III MCC. Both ADAM and STAMP have completed accrual and results are pending. (C) Primary therapy: KEYNOTE-017 and JAVELIN trials reported a 60% overall response rate and ~40% 3-year progression-free survival with first-line pembrolizumab or avelumab. Both agents also show promise as salvage therapies. Conclusions: ICIs demonstrate encouraging outcomes in MCC across various treatment stages. Continued research is essential to optimize treatment timing and integrate multimodal therapies. Full article

Introduction and Objectives: Local recurrence (LR) in patients treated with surgery for renal cell carcinoma (RCC) remains a significant clinical challenge that requires thorough investigation. Our study aimed to identify the relative risk factors and explore the optimal clinical management of LR. Materials and Methods: We conducted a non-randomized, observational, retrospective multicentric registry involving multiple Italian urological centers. We included patients treated with surgery (either nephron-sparing or radical nephrectomy) who later developed LR, defined as recurrence in the ipsilateral kidney or renal fossa. Patients with hereditary syndromes or metastatic disease at the time of LR diagnosis were excluded. Results: We reported 135 cases of LR with the following characteristics: most primary lesions were monofocal (85.7%), with a median size of 42 mm (23–53), the median R.E.N.A.L. score was 7 (6–8), and the median Padua score was 7 (6–9). Patients were treated with robot-assisted techniques in 59% of cases, laparoscopic surgery in 32.4%, and open surgery in 8.6%. Nephron-sparing surgery was performed in 75.2% of cases. Ischemia occurred in 61% of the cases, with a median ischemia time of 21 min (15.5–24). Intraoperative complications occurred in 3.8% of cases, while postoperative complications were reported in 13.8%, all of which were grade ≤3 according to the Clavien–Dindo classification. The primary tumors were pT1a in 43.5% of cases, pT1b in 26.3%, pT2 in 14.7% and pT3 in 15.5%. Histologically, 84% of cases were clear cell, 11.3% papillary type 1 or 2, and 3.7% chromophobe. Sarcomatoid/rhabdoid variants were present in 10.5% of cases. The median rate of LR was 1.3% (range 0.2–3.6), while the median time to LR was 18 months (12–39). LR occurred in the ipsilateral kidney in 70.5% of cases and in the ipsilateral renal fossa in 29.5%. The median rate of PSM in LR cases at initial surgery was 2.4% (range 0–4.3), while the median rate of negative surgical margin (NSM) in LR cases at initial surgery was 0.1 (0–0.3). Following LR diagnosis, most patients (49.2%) underwent surgery, 29.1% received cryoablation or radiotherapy, 17.1% received systemic treatment alone, and 4.6% followed a watchful waiting/active surveillance approach. At a median follow-up of 62 months, the highest oncological control in terms of 5-year cancer-specific survival and overall survival rates was achieved in surgically treated patients. The PSM, the histological variant, and their combination were found to be independent variables correlated with the occurrence of LR, with relative risks of 3.62, 2.71, and 8.12, respectively. Conclusions: LR after nephron-sparing or radical nephrectomy represents a significant clinical dilemma. Known risk factors are not always sufficient to predict recurrence, emphasizing the necessity of consistent radiological follow-up per guideline recommendations. Early detection of recurrence and a multidisciplinary approach involving expert centers are crucial for optimizing patient outcomes. Full article

Background/Objectives: Male breast cancer (MBC) is a rare malignancy representing less than 1% of all breast cancer cases, with rising incidence worldwide. Current treatment strategies largely rely on extrapolation from female breast cancer, despite clear biological and clinical distinctions. This review aims to summarize current knowledge on non-metastatic MBC, with a particular focus on genetic predisposition, tumor biology, and recent therapeutic advances. Methods: A systematic literature search was conducted using PubMed and PMC databases to identify clinical trials, observational studies and systematic reviews related to MBC published up to 1st June, 2025. Studies were selected for their relevance to genetic and molecular features, as well as treatment outcomes in non-metastatic disease. Results: Fifty-one studies were included in the review. Findings confirm the predominance of hormone receptor–positive tumors in MBC and underscore the central role of BRCA2 mutations. Germline mutations in BRCA2 and BRCA1 were reported in approximately 1 and 2% of male cases, respectively. Additional germline alterations were identified in PALB2, CHEK2, and other DNA repair genes. Comparative analyses of surgical approaches showed no significant difference in survival between breast-conserving surgery and mastectomy. Postmastectomy radiotherapy improved overall survival compared to surgery alone. Adjuvant tamoxifen therapy was independently associated with significant survival benefits, although adherence remains a challenge. Conclusions: MBC is a biologically distinct and molecularly heterogeneous disease. Breast-conserving surgery appears safe and effective in selected patients. Adjuvant radiotherapy and tamoxifen confer clear survival advantages. The lack of male-specific clinical trials remains a major limitation in optimizing evidence-based care for MBC. Full article

Cancer is a major challenge to global health, and its incidence rate and mortality are expected to continue to rise in the coming decades. Traditional treatment methods such as surgery, radiotherapy, and chemotherapy have limitations, which has prompted people to explore new treatment strategies. As a promising therapeutic approach, oncolytic viruses can selectively target and lyse tumor cells while avoiding damage to normal tissues. This article systematically reviews the mechanisms by which oncolytic viruses induce various forms of cell death, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. We explored the direct killing effect of oncolytic viruses and their ability to activate local and systemic antitumor immunity, with a focus on the latest developments in the clinical application of oncolytic viruses, such as the development of novel recombinant viruses. In addition, we also analyzed strategies to enhance the efficacy of oncolytic viruses through gene modification, combination therapy, and targeted delivery systems. A deeper understanding of the multiple mechanisms of action of oncolytic viruses can help us develop more effective and personalized cancer treatment plans. Future research should focus on optimizing oncolytic viruses to overcome tumor drug resistance and improve patient prognosis, making them an important pillar of cancer treatment. Full article

Radiotherapy employs high-energy X-rays to precisely target tumor tissues while minimizing damage to the surrounding healthy structures. Although its clinical efficacy is well established, the immunomodulatory effects of ionizing radiation remain complex and context-dependent. This study investigated the biological effects of radiotherapeutic doses on immune cells by evaluating lymphocyte viability, phenotypic profiles, and cytokine expression levels. Peripheral blood mononuclear cells (PBMCs) were isolated from six healthy donors and irradiated with 0, 2, or 6 Gy using a 6 MV linear accelerator (LINAC). Dose validation with an ionization chamber demonstrated strong agreement between estimated and measured values (intraclass correlation coefficient = 1, 95% CI). Immune subsets, including T cells (CD3+), helper T cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+CD4+Foxp3+), and natural killer (CD3-CD56+) cells, along with intracellular cytokines interleukin-12 (IL-12) and interferon-gamma (IFN-γ), were analyzed via flow cytometry at multiple time points. The results showed a significant, dose-dependent decline in overall lymphocyte viability (p < 0.01) compared to control. Cytotoxic T cells were the most radiosensitive, followed by helper and regulatory T cells, while NK cells were the most radioresistant. IL-12 expression initially increased post-irradiation, while IFN-γ levels remained variable. These findings demonstrate that radiation induces distinct alterations in immune phenotypes and cytokine profiles, which may shape the immune response. Immune profiling following irradiation may therefore provide valuable insights for optimizing combination strategies that integrate radiotherapy and immunotherapy in cancer treatment. Full article

Iron oxide nanoparticles (IONPs) have emerged as key materials in magnetic hyperthermia (MH), a minimally invasive cancer therapy capable of selectively inducing apoptosis, ferroptosis, and other cell death pathways while sparing surrounding healthy tissue. This review synthesizes advances in the design, functionalization, and biomedical application of magnetic nanoparticles (MNPs) for MH, highlighting strategies to optimize heating efficiency, biocompatibility, and tumor targeting. Key developments include tailoring particle size, shape, and composition; doping with metallic ions; engineering multicore nanostructures; and employing diverse surface coatings to improve colloidal stability, immune evasion, and multifunctionality. We discuss preclinical and clinical evidence for MH, its integration with chemotherapy, radiotherapy, and immunotherapy, and emerging theranostic applications enabling simultaneous imaging and therapy. Special attention is given to the role of MNPs in immunogenic cell death induction and metastasis prevention, as well as novel concepts for circulating tumor cell capture. Despite promising results in vitro and in vivo, clinical translation remains limited by insufficient tumor accumulation after systemic delivery, safety concerns, and a lack of standardized treatment protocols. Future progress will require interdisciplinary innovations in nanomaterial engineering, active targeting technologies, and real-time treatment monitoring to fully integrate MH into multimodal cancer therapy and improve patient outcomes. Full article

Radiation-induced intestinal injury (RIII), a severe complication of abdominopelvic radiotherapy, causes intestinal ischemia, ulcers, and necrosis, severely impacting patients’ quality of life. Currently, effective treatments are limited, and a specific cure remains elusive. Our previous research showed that lactoferrin (LF) can promote intestinal stem cell (ISC) proliferation and tissue repair; however, its oral administration is limited by rapid degradation in the gastric environment. In this study, we developed LF-loaded liposomal nanoparticles (Lip-LF) using a simple ethanol injection method. The optimal formulation (cholesterol/egg yolk lecithin ratio 2:8, LF concentration 12.5 mg/mL) achieved a drug-loading capacity of 6.8% and a narrow size distribution (0.2 < PDI < 0.4). In vitro experiments demonstrated that Lip-LF protected LF from pepsin degradation in simulated gastric fluid (SGF), retaining over 80% integrity after 120 min, while releasing in simulated intestinal fluid (SIF). In vivo imaging revealed prolonged gastrointestinal retention of Lip-LF compared to free LF. In a murine model of RIII (12 Gy whole-body irradiation), Lip-LF significantly restored villus counts, increased crypt height, and promoted goblet-cell regeneration. Immunohistochemical and qPCR analyses revealed enhanced ISCs proliferation and upregulation of repair-associated genes, including Pcna and Olfm4. These findings demonstrate that Lip-LF protects LF from gastric degradation and enhances its targeted delivery to the intestine, improving its therapeutic efficacy in repairing RIII. Lip-LF thus offers a promising strategy for managing RIII. Full article

Background and Clinical Significance: Adenoid cystic carcinoma (ACC) is a rare neoplasm of salivary glands, accounting for approximately 2–4% of all ACCs of head and neck malignancies. Adenoid cystic carcinoma (ACC) of the larynx is exceedingly rare, accounting for only 0.07–0.25% of all laryngeal tumors. Within the larynx, ACC may arise in various locations; however, the subglottic region is most commonly affected, representing approximately 64% of cases. ACC typically manifests as a slow-growing tumor with a pronounced tendency for perineural invasion and local recurrence. Current treatment strategies primarily involve surgical resection followed by adjuvant radiotherapy. Chemotherapy demonstrates limited efficacy and is generally reserved for advanced, recurrent, or metastatic disease. Given the rarity of this malignancy and the limited number of cases reported in the literature, we aim to contribute to the existing body of knowledge by presenting a clinical case of laryngeal ACC. Case Presentation: A 77-year-old male with a significant smoking history (more than 20 cigarettes per day for over 40 years) presented to our department in October 2023 with persistent dysphonia lasting several months. Endoscopic evaluation of the upper aerodigestive tract revealed an extensive neoplastic lesion involving the larynx. Contrast-enhanced computed tomography (CT) confirmed the presence and extent of the lesion. The patient subsequently underwent surgical resection and was referred for adjuvant postoperative radiotherapy. Unfortunately, the patient died of a myocardial infarction a few days before radiotherapy could be initiated. Conclusions: Due to the rarity of laryngeal adenoid cystic carcinoma, further studies are necessary to define optimal management strategies. Sharing clinical experiences and outcomes is essential, as there is currently no universally accepted treatment consensus for this uncommon malignancy. At the same time, our aim is to highlight the importance of histological subtype and perineural invasion which have to be considered as important prognostic factors when dealing with ACC. Full article

Background/Objectives: This study investigates the dosimetric impact of a 3D-printed applicator integrating multilayer catheter geometry and high-density shielding, designed for contact interventional radiotherapy (IRT) in non-melanoma skin cancer (NMSC) treatment. The aim is to assess its potential to enhance target coverage and reduce doses in organs at risk (OARs). Methods: A virtual prototype of a multilayer applicator was designed using 3D modeling software and realized through fused deposition modeling. Dosimetric simulations were performed using both TG-43 and TG-186 formalisms on CT scans of a water-equivalent phantom. A five-catheter array was reconstructed, and lead-cadmium-based alloy shielding of varying thicknesses (3–15 mm) was contoured. CTVs of 5 mm and 8 mm thickness were analyzed along with a neighboring OAR. Dosimetric endpoints included V95%, V100%, V150% (CTV), D_2cc (OAR), and therapeutic window (TW). Results: Compared to TG-43, the TG-186 algorithm yielded lower OAR doses while maintaining comparable CTV coverage. Progressive increase in shielding thickness led to improved V95% and V100% values and a notable reduction in OAR dose, with an optimal trade-off observed between 6 and 9 mm of shielding. The TW remained above 7 mm across all configurations, supporting its use in lesions thicker than conventional guidelines recommend. Conclusions: The integration of multilayer catheter geometry with high-density shielding in a customizable 3D-printed applicator enables enhanced dose modulation and OAR sparing in superficial IRT. This approach represents a step toward personalized brachytherapy, aligning with the broader movement in radiation oncology toward patient-specific solutions, adaptive planning, and precision medicine. Future directions should include prototyping and mechanical testing of the applicator, experimental dosimetric validation in phantoms, and pilot clinical feasibility studies to translate these promising in silico results into clinical practice. Full article

Background/Objectives: Sarcopenia, defined as the progressive loss of muscle mass and function, is increasingly recognized in pediatric cancer patients as a significant clinical and prognostic factor. Sarcopenia in children arises from malignancy-related inflammation, malnutrition, and treatment toxicity, negatively affecting treatment response, recovery, and quality of life. Methods: We searched MEDLINE and Scopus for English-written articles published over the last five years using synonyms for the terms “sarcopenia” and “pediatric cancer”. Screening and data extraction were performed in a duplicate-blinded method. We qualitatively synthesized eligible articles. Results: Recent studies identify pre-treatment sarcopenia as a marker of poor prognosis, especially in hepatoblastoma and neuroblastoma. Total psoas muscle area (tax) and skeletal muscle index (SMI) are emerging diagnostic tools, though standardized methods remain lacking. Sarcopenia’s etiology is multifactorial, involving impaired mitochondrial metabolism, chemotherapy-induced appetite loss, and systemic inflammation. Sarcopenic obesity is common, particularly among leukemia survivors, often masked by normal BMI. Survivors also face reduced bone density, impaired immunity, and persistent muscle loss, linked to prior therapies such as radiotherapy and hematopoietic stem cell transplantation. Increase in muscle mass post-treatment correlates with better survival outcomes. Conclusions: Early detection of sarcopenia can support timely interventions such as nutritional support and physical activity. Yet, significant diagnostic heterogeneity across existing studies hampers definitive conclusions regarding its true prevalence and the optimal assessment method. Standardized diagnostic criteria are urgently needed to enable more reliable prevalence estimates and evidence-based clinical strategies. Full article

Background: Breast reconstruction following mastectomy has become an essential procedure in breast cancer treatment due to its positive impact on patients’ quality of life. Among the various reconstruction techniques, the use of expanders followed by implants has gained popularity. In this context, acellular dermal matrices (ADM) have been introduced as an adjunct to improve implant coverage, lower pole support, and aesthetic outcomes. However, their use has also been associated with higher costs and a potential increase in postoperative complications, which remains a matter of debate. We aimed to determine the relationship between acellular dermal matrix and postoperative outcomes and complications. Methods: An observational retrospective study was conducted with patients who underwent immediately breast mastectomy followed by tissue expander reconstruction from January 2022 to June 2024. Patients were divided into two groups depending on reconstructive plane. Results: The final cohort contained 87 patients. Smoking, radiotherapy and dermal matrix were associated with a higher complication rates. After risk-adjustment, dermal matrix use led to a higher rates of surgical site infection (OR 7.62, p = 0.029) in the prepectoral plane, and higher rates of overall complications (OR 3.34, p = 0.05) and surgical wound dehiscence (OR 6.04, p = 0.048) in the retropectoral plane. Conclusions: These findings highlight the importance of individualized surgical planning, particularly concerning the use of acellular dermal matrix, which were associated with increased risks of surgical site infection, dehiscence, and global complications. Further research is required to establish standardized guidelines for the optimal selection surgical technique. Full article

This review covers issues related to the characteristics, diagnosis, and treatment of colorectal cancer (CRC). It discusses traditional methods of treating colorectal cancer, including surgery, chemotherapy, and radiotherapy, as well as modern approaches, including targeted therapies, immunotherapy, and innovative gene therapy strategies. Particular attention is paid to the identification of molecular subtypes of CRC, which has revolutionized treatment in advanced stages of the disease and contributed to improved patient survival. The role of biomarkers, including liquid biopsy, in diagnosis, therapy monitoring, and treatment response assessment is emphasized. The potential of artificial intelligence in planning and optimizing surgical procedures is also discussed, opening up new possibilities in personalized therapy. This article provides up-to-date knowledge on the molecular mechanisms of CRC, diagnostic prospects, and directions for the development of precision therapies, serving as a valuable source of information for both clinicians involved in the treatment of CRC and patients wishing to deepen their knowledge of the disease and modern therapeutic options. Full article

Background: We evaluated the long-term treatment outcomes of patients with clinically localized and locally advanced prostate cancer (PC) who underwent high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT). The primary objective was to identify the optimal timing for discontinuing prostate-specific antigen (PSA) monitoring after HDR-BT. Methods: This analysis included 338 patients with PC who received HDR-BT combined with EBRT between 2006 and 2022 and had a minimum follow-up of 5 years. The patients were stratified based on their PSA levels, and factors associated with recurrence were identified. Results: The median observation period was 8.9 years (range, 5.0–19.0 years). The 10-year recurrence-free survival rate was 92.0%, with 26 recurrences. PSA levels at 5 and 7 years were significantly correlated with oncological outcomes after HDR-BT. Multivariate analysis revealed that a PSA level of >0.2 ng/mL at 5 years was an independent poor prognostic factor for recurrence (hazard ratio, 117.57; 95% confidence interval, 6.22–2223.37; p = 0.001). No patient with a PSA level of ≤0.2 ng/mL at 7 years developed recurrences. Conclusions: Based on our long-term data, we propose that PSA monitoring may be safely discontinued in patients with a PSA level of ≤0.2 ng/mL 7 years after HDR-BT because the risk of recurrence beyond this point is exceedingly low. Full article

Primary aggressive oral lymphomas (PAOL) are a rare subset of extranodal non-Hodgkin lymphomas arising in the oral cavity without evidence of other systemic involvement at diagnosis. PAOL accounts for only about 2–3% of all lymphomas. They most commonly belong to aggressive B-cell subtypes such as Diffuse large B-cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL), with occasional cases of Burkitt lymphoma and T-cell/NK-cell lymphomas. Clinically, these malignancies often present with non-specific symptoms (e.g., swelling, pain, ulceration, tooth mobility) that mimic benign dental conditions, leading to diagnostic delays. An integrated diagnostic approach—combining thorough oral examination, imaging (CT, MRI, PET), and definitive biopsy with immunohistochemistry and genetic studies—is critical for accurate diagnosis and staging. Treatment typically involves systemic chemotherapy, often combined with rituximab for CD20+ tumors and adjunctive radiotherapy for localized disease. Ongoing research into the genomic and microenvironmental landscape of PAOL is paving the way for novel targeted therapies to improve outcomes. In HIV+ or transplant patients, PAOL are often driven by viral co-infections (EBV, HHV-8) and may require tailored therapy, including optimization of immune status. The dentist’s role encompasses not only diagnosis but also active participation in cancer therapy through preventive and supportive dental care, and persists thereafter by monitoring for recurrence and treating chronic treatment sequelae. This review provides a comprehensive overview of PAOL‘s epidemiology, clinical-pathologic and molecular features, current and emerging treatments, and the essential collaborative role of dentists and hematologists in patient care. Full article