Search Results (2,631)

Background: Lattice Radiation Therapy (LRT), a spatially fractionated stereotactic radiotherapy (SBRT) technique, has shown promising results in the palliative treatment of large tumors. The focus of our first analysis of 56 lesions ≥7 cm was on the extent of shrinkage following palliative LRT (mean 50%) and assessment of its effect duration (: mean 6 months). Herewith we present an updated analysis of our single-center LRT cohort, with a focus on LRT outcome across diagnoses and applied LRT regimens. Methods: We assessed the clinical outcome following LRT in 66 patients treated for 81 lesions between 01.2022 and 05.2025. LRT protocols included simultaneous integrated boost (sib-) LRT in 49 lesions (5 × 4–5 Gy to the entire mass with sib of 9–13 Gy to lattice vertices). Alternatively mainly in pre-irradiated and/or very large lesions—a single-fraction stereotactic LRT (SBRT-LRT) of 1 × 20 Gy to vertices only was delivered to 26 lesions. In six cases with modest response to single fraction SBRT-LRT, the sib-LRT schedule was added 4–8 weeks later. Results: The median age was 68 years (18–93). Main tumor locations were abdomino-pelvic (n = 34) and thoracic (n = 17). Histopathological diagnoses included carcinoma (n = 34), sarcoma (n = 31), and melanoma (n = 16). 31% of all lesions have been previously irradiated. 73% of cases underwent concurrent or peri-LRT systemic therapy. The mean/median overall survival (OS) time of the cohort was 7.6/4.6 months (0.4–40.2), 11.9/5.8 months in 16/66 alive, and 6.4/4.3 months in deceased patients, respectively. 82% of symptomatic patients reported immediate subjective improvement (PROM), with a lifelong response duration in most cases. Progressive disease (PD: >10% increase in initial volume) was found in 9%, stable disease (SD +/−10% of initial volume) in 19% of scanned lesions, and shrinkage (>10% reduction in initial volume) in 75%, with a mean/median tumor volume reduction of 51/60%. The extent of shrinkage was found to be 11–30%/31–60%/61–100% in 38/24/38% of lesions. Response rates (PD, SD, shrinkage) following the two applied LRT regimens, as well as those related to sarcoma and carcinoma diagnoses, were found to be comparable. Treatment tolerance was excellent (G0-1). Conclusions: Palliative LRT provides rapid subjective relief in ~80% of symptomatic patients. Radiologic shrinkage was stated in 75% of FU-scanned lesions, with a lifelong effect duration in most patients. LRT was found effective across histologies, with a similar extent of shrinkage in carcinoma and sarcoma following 1F SBRT- and 5F sib-LRT regimens, respectively. Full article

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has emerged as a promising multifunctional agent in dermatology and cosmetic science. The review provides an updated synthesis of CBD’s topical therapeutic potential, challenges, and evolving regulatory frameworks. CBD exhibits diverse biological effects, including anti-inflammatory, antioxidant, antibacterial, analgesic, lipostatic, antiproliferative, moisturising, and anti-ageing properties through interactions with the skin’s endocannabinoid system (ECS), modulating CB1, CB2, TRPV channels, and PPARs. Preclinical and clinical evidence support its efficacy in managing acne, psoriasis (including scalp psoriasis), atopic and seborrheic dermatitis, and allergic contact dermatitis. CBD also relieves pruritus through neuroimmune modulation and promotes wound healing in conditions such as pyoderma gangrenosum and epidermolysis bullosa. In hair disorders such as androgenetic alopecia, it aids follicular regeneration. CBD shows promise in managing skin cancers (melanoma, squamous cell carcinoma, Kaposi sarcoma) and pigmentation disorders such as melasma and vitiligo. It enhances skin rejuvenation by reducing oxidative stress and boosting collagen and hydration. However, there are challenges regarding CBD’s physicochemical stability, skin penetration, and regulatory standardisation. As consumer demand for natural, multifunctional skincare grows, further research is essential to validate its long-term safety, efficacy, and optimal formulation strategies. Full article

Objective: This study introduces an explainable, radiomics-based machine learning framework for the automated classification of sarcoma tumors using MRI. The approach aims to empower clinicians, reducing dependence on subjective image interpretation. Methods: A total of 186 MRI scans from 86 patients diagnosed with bone and soft tissue sarcoma were manually segmented to isolate tumor regions and corresponding healthy tissue. From these segmentations, 851 handcrafted radiomic features were extracted, including wavelet-transformed descriptors. A Random Forest classifier was trained to distinguish between tumor and healthy tissue, with hyperparameter tuning performed through nested cross-validation. To ensure transparency and interpretability, model behavior was explored through Feature Importance analysis and Local Interpretable Model-agnostic Explanations (LIME). Results: The model achieved an F1-score of 0.742, with an accuracy of 0.724 on the test set. LIME analysis revealed that texture and wavelet-based features were the most influential in driving the model’s predictions. Conclusions: By enabling accurate and interpretable classification of sarcomas in MRI, the proposed method provides a non-invasive approach to tumor classification, supporting an earlier, more personalized and precision-driven diagnosis. This study highlights the potential of explainable AI to assist in more secure clinical decision-making. Full article

Background and Clinical Significance: Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms with low metastatic potential but a high recurrence rate. Approximately 60–80% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors (ALKis) a key therapeutic option. However, resistance to ALKis remains a significant clinical challenge, necessitating alternative treatment strategies. Case Presentation: We report the case of a 23-year-old woman diagnosed with a metastatic TPM3::ALK fusion-positive IMT, initially managed with crizotinib and ceritinib. Disease progression prompted a switch to alectinib, followed by lorlatinib in combination with immune checkpoint inhibitors (nivolumab + ipilimumab). The patient tolerated this regimen well, with manageable side effects, and has remained progression-free for over three years, demonstrating the potential efficacy of ALK-ICI combination therapy. Conclusions: This case highlights the rapid development of resistance to first- and second-generation ALKis and the emerging role of immune checkpoint inhibitors (ICIs) in IMT treatment. PD-L1 expression in ALK-positive IMTs suggests an immune escape mechanism, supporting combination ALK-ICI therapy as a viable approach. The successful long-term disease control achieved in this case underscores the importance of molecular profiling in guiding personalized treatment strategies for IMT. This report contributes to the growing body of evidence supporting precision medicine and immunotherapy in rare sarcomas. Full article

Introduction and Aim: Renal transplant recipients face significant long-term graft and patient loss due to post-transplant malignancies. This study aimed to characterize post-transplant malignancies, determine mortality risk factors, and evaluate patient outcomes. Materials and Methods: This retrospective study included 2052 kidney transplant recipients who underwent transplantation between 1976 and 2019 at our institution, other national centers, or international facilities, and who had at least six months of follow-up. Regardless of the transplant center, all patients were followed exclusively at our nephrology department for post-transplant care. A comprehensive review of patient files was conducted, encompassing demographic data, malignancy type and treatment, mortality rates, tissue compatibility assessments, viral serology results, immunosuppression protocols, acute rejection history, and pre-transplant malignancies. The relationships between these variables and mortality were examined. Results: A total of 167 malignant events were observed in 163 patients out of 2052 renal transplant patients (7.9%). The female patients comprised 34.4% (n = 56) of the participants. Ages at transplantation and malignancy diagnosis had medians of 40.0 (13–72) and 50.0 (23–78) years, respectively. The leading malignancy was skin cancer at 30.0%, with Kaposi sarcoma at 11.3% and post-transplant lymphoproliferative disease at 10.6% following. Of the patients followed up, 58.9% (93 patients) had mortality. In univariate analysis, older age at transplant, older age at malignancy diagnosis, and male sex were associated with mortality; however, no independent predictors were identified in the multivariate model (all p > 0.05), likely due to sample size limitations and inter-variable collinearity. Mortality showed statistically significant associations (p < 0.05) with increased age at transplantation, increased age at malignancy diagnosis, and male gender. Conclusions: Post-transplant malignancies significantly compromise both graft longevity and patient survival. Particularly aggressive skin cancers demand heightened clinical vigilance. Early detection through regular dermatological screening, patient education, and timely biopsies must become integral to long-term transplant care protocols. Full article

Chondrosarcomas (CSs) are generally slow-growing tumors of cartilage-producing cells, and the second most common primary bone malignancy following osteosarcoma. CSs are typically resistant to conventional chemo- and radiotherapy, and aggressive surgical resection with wide margins remains the only effective treatment option. Immunotherapies and targeted therapies in CSs have failed in clinical trials, and no prognostic biomarkers exist within the clinic. Although CSs have undergone histologic and genetic analysis, the molecular mechanisms that drive their pathogenesis and resistance are still largely unknown. A deeper understanding of the molecular biology and dysregulated pathways in CSs is essential for more efficient precision therapies. Several integrated large-scale genetic and epigenetic studies have recently been reported in CS, with several distinguished pathways holding therapeutic promise. In this review, we summarize the advances in the molecular biology of CSs, focusing on both genomic and epigenomic mechanisms as well as potential biomarkers and targets. These studies highlight several valuable clinical opportunities for earlier detection, prognostic accuracy, and therapeutic targeting that may improve patient outcomes in CSs. Full article

Background: Pelvic resections represent some of the most challenging procedures in orthopedic oncology, often necessitating the sacrifice of large bone segments and, subsequently, the loss of nearby soft tissues. Our study aims to evaluate the impact of surgical resections of pelvic bone tumors on the performance of the pelvic floor and digestive, urinary, and genital systems. Methods: We evaluated all malignant or locally aggressive pelvic bone tumors treated with bone resection in our institution between January 2017 and January 2024. The reconstructive approaches were recorded. Pre- and post-operative MRI and CT scans were used to evaluate the grade of pelvic prolapse. The prolapse of the pelvic floor was assessed with the M-line, the H-line, and the anorectal angle. Hydronephrosis was also evaluated. Urinary and fecal incontinence were evaluated with the Pelvic Floor Impact Questionnaire (PFIQ7). Results: Thirty cases were included in our study. Nine cases were treated with custom-made prostheses, five had ice-cone prostheses, two massive allografts, and one composite allograft-prosthesis. The others had no bone reconstruction. Meshes were used to reconstruct the pelvic floor in 9 cases. Patients with discontinuity of the pelvic ring had a significantly higher grade of pelvic prolapse (M-line) and worse PFIQ7 scores. Conclusions: The resection of pelvic bone tumors represents one of the main challenges in orthopedic oncology. While planning surgical demolition and performing the subsequent reconstruction, surgeons should also consider the impact of the surgical treatment on the pelvic floor and surrounding organs. Intra-operative reconstructions and post-operative rehabilitation are advisable. Full article

Sarcomas are tumors of mesenchymal origin that are generally resistant to systemic therapies and prone to local recurrence despite current multimodal treatment approaches. Focused ultrasound (FUS) is a noninvasive therapeutic technology that may enhance standard treatment strategies for primary solid malignancies. FUS exerts its effects through diverse mechanisms, including high-intensity focused ultrasound (HIFU) thermal ablation, histotripsy, sonodynamic therapy, immunomodulation, and hyperthermia-enhanced drug delivery. In this narrative review, we summarize the mechanisms of focused ultrasound that have been investigated for the treatment of sarcomas and highlight the results of preclinical, veterinary, and clinical studies related to this area. Full article

High-grade sarcomas often lack typical morphological features and exhibit no clear differentiation, often leading to a diagnosis of undifferentiated sarcoma (US). Pleomorphic leiomyosarcoma (PLMS) is a high-grade sarcoma consisting of a typical leiomyosarcoma (LMS) component alongside dedifferentiated high-grade areas. A few decades ago, PLMS was regarded as a subtype of high-grade sarcoma previously referred to as malignant fibrous histiocytoma; it is now classified as a variant of LMS. The mechanisms underlying myogenic differentiation and their relevance to the pathological diagnosis of high-grade sarcomas remain poorly understood. To investigate the gene expression networks associated with myogenic differentiation, we employed Cap Analysis of Gene Expression (CAGE) to distinguish PLMS from other high-grade sarcoma subtypes. We analyzed 27 frozen high-grade sarcoma samples, comprising 10 PLMSs, 11 high-grade myxofibrosarcomas, 3 dedifferentiated liposarcomas, 2 USs, and 1 high-grade sarcoma not otherwise specified, using CAGE profiling. Hierarchical clustering based on differentially expressed genes identified by CAGE separated 7 of the 10 PLMSs from other high-grade sarcomas, while the remaining 3 PLMSs clustered with a single US case. CAGE analysis also revealed that the myostatin (MSTN) promoter (false discovery rate [FDR] < 0.05) was more strongly activated in the high-grade sarcoma group lacking morphological and immunohistochemical smooth muscle differentiation than in the PLMS group, whereas the alpha smooth muscle actin (ACTA2) promoter (FDR < 0.05) was more prominently activated in the PLMS group. Immunohistochemical analysis showed reduced or absent myostatin expression in PLMSs, in contrast to diffuse myostatin expression in other high-grade sarcomas. Smooth muscle actin, encoded by ACTA2, was expressed in all 10 PLMS cases but only in 11 of 17 other high-grade sarcomas. Furthermore, both conventional immunohistochemistry and double immunostaining revealed that myostatin and myogenic markers exhibited largely mutually exclusive expression patterns within these tumors. A validation study was performed using 59 soft tissue sarcoma cases, including 27 PLMSs and 16 LMSs. Loss or reduction in myostatin expression was confirmed in both LMS and PLMS, and the ratio of myostatin loss was comparable (62.5% in LMS vs. 63% in PLMS). Collectively, these findings suggest that myostatin contributes to smooth muscle differentiation in high-grade sarcomas and has potential utility as a diagnostic marker. Full article

Background and Objective: Colorectal cancer (CRC) most commonly metastasizes to the liver and lungs; however, synchronous metastases to pelvic structures such as the vagina and urethra are extremely rare, posing a significant diagnostic and therapeutic challenge. This report describes an unusual case of sigmoid colon adenocarcinoma with synchronous metastases to the vagina and urethra, highlighting its diagnostic evaluation and the value of a multidisciplinary approach. Methods: A 59-year-old woman with a history of deep vein thrombosis treated with apixaban presented with chronic constipation and pelvic bleeding. A gynecological evaluation revealed a vaginal lesion. A colonoscopy, biopsy, pelvic magnetic resonance imaging, and molecular profiling were performed. Treatment included chemotherapy (capecitabine and oxaliplatin), panitumumab, and pelvic radiotherapy. Results: The biopsy confirmed a moderately differentiated invasive adenocarcinoma in the sigmoid colon with synchronous metastases to the vagina and urethra. Molecular profiling identified a rat sarcoma virus oncogene and BRAF (B-Raf proto-oncogene), allowing for the use of targeted therapy. The patient achieved a complete response according to RECIST 1.1 criteria and significant symptomatic improvement, including pain reduction, although dosages were adjusted for thrombocytopenia. She is currently continuing palliative treatment with good tolerance and durable symptomatic improvement. Conclusions: This case underscores the need to consider unusual metastatic sites in patients with colorectal cancer presenting with gynecological symptoms. Early diagnosis, based on imaging and histology, alongside molecular characterization, is crucial for effective personalized therapy. Multidisciplinary coordination is key to optimizing clinical outcomes in these rare metastatic presentations. Full article

Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article

Background: Angiosarcomas (ASs) represent a heterogeneous and highly aggressive subset of tumors that respond poorly to systemic treatments and are associated with short progression-free survival (PFS) and overall survival (OS). The aim of this study was to develop and validate an immune-related prognostic model—termed the AS score—using data from two independent sarcoma cohorts. Methods: A prognostic model was developed using a previously characterized cohort of 25 angiosarcoma samples. Candidate genes were identified via the Maxstat algorithm (Maxstat v0.7-25 for R), combined with log-rank testing. The AS score was then computed by weighing normalized gene expression levels according to Cox regression coefficients. For external validation, transcriptomic data from TCGA Sarcoma cohort (n = 253) were analyzed. The Immunoscore—which reflects the tumor immune microenvironment—was inferred using the ESTIMATE package (v1.0.13) in R. All statistical analyses were performed in RStudio (v 4.0.3). Results: Four genes—IGF1R, MAP2K1, SERPINE1, and TCF12—were ultimately selected to construct the prognostic model. The resulting AS score enabled the classification of angiosarcoma cases into two prognostically distinct groups (p = 0.00012). Cases with high AS score values, which included both cutaneous and non-cutaneous forms, exhibited significantly poorer outcomes, whereas cases with low AS scores were predominantly cutaneous. A significant association was observed between the AS score and the Immunoscore (p = 0.025), with higher Immunoscore values found in high-AS score tumors. Validation using TCGA sarcoma cohort confirmed the prognostic value of both the AS score (p = 0.0066) and the Immunoscore (p = 0.0029), with a strong correlation between their continuous values (p = 2.9 × 10⁻⁸). Further survival analysis, integrating categorized scores into four groups, demonstrated robust prognostic significance (p = 0.00021). Notably, in tumors with a low Immunoscore, AS score stratification was not prognostic. In contrast, among cases with a high Immunoscore, the AS score effectively distinguished outcomes (p < 0.0001), identifying a subgroup with poor prognosis but potential sensitivity to immunotherapy. Conclusions: This combined classification using the AS score and Immunoscore has prognostic relevance in sarcoma, suggesting that angiosarcomas with an immunologically active microenvironment (high Immunoscore) and poor prognosis (high AS score) may be prime candidates for immunotherapy and this approach warrants prospective validation. Full article

Porcine lymphotropic herpesviruses -1, -2, and -3 (PLHV-1, PLHV-2, and PLHV-3) are gammaherpesviruses that are widespread in pigs. These viruses are closely related to the human pathogens Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), both of which are known to cause severe diseases in humans. To date, however, no definitive association has been established between PLHVs and any disease in pigs. With the growing interest in xenotransplantation as a means to address the shortage of human organs for transplantation, the safety of using pig-derived cells, tissues, and organs is under intense investigation. In preclinical trials involving pig-to-nonhuman primate xenotransplantation, another porcine herpesvirus—porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV)—was shown to be transmissible and significantly reduced the survival time of the xenotransplants. In the present study, we examined donor pigs and their respective baboon recipients, all of which were part of preclinical pig heart xenotransplantation studies, for the presence of PLHV. PLHV-1, PLHV-2, and PLHV-3 were detected in nearly all donor pigs; however, no evidence of PLHV transmission to the baboon recipients was observed. Full article

Background: Soft tissue sarcomas (STSs) are a rare and heterogeneous group of mesenchymal tumors with limited response to current therapies, particularly in advanced stages. STS tumors were traditionally considered “cold” tumors, characterized by limited immune infiltration and low immunogenicity. However, emerging evidence is challenging this perception, highlighting a potentially critical role for the immune system in STS biology. Objective: Building on our previous findings suggesting impaired natural killer (NK) cell activity in STS patients, we aimed to perform an in-depth characterization of peripheral NK cells in STS. Methods: Peripheral blood samples from STS patients and sex- and age-matched healthy donors were analyzed to assess NK cell degranulation, IFNγ production, and receptor repertoire. Results: Functional assays revealed a notable reduction in both degranulation and IFNγ production in NK cells from STS patients. STS patients also exhibited dysregulated expression of activating and inhibitory NK cell receptors. Principal component analysis (PCA) identified CD27 and NKp44 as critical markers for distinguishing STS patients from healthy donors. Increased CD27 expression represents a shift towards a more regulatory NK cell phenotype, and we found that CD27 expression was negatively correlated with NK cell degranulation and IFNγ production. ROC curve analysis demonstrated strong potential to distinguish between the groups for both CD27 (AUC = 0.85) and NKp44 (AUC = 0.94). Conclusion: In conclusion, STS patients exhibited impaired NK cell function, altered receptor repertoire, and a shift towards a less cytotoxic and more regulatory phenotype. Full article

Background and Clinical Significance: Myxoid liposarcoma (MLS) is a malignant soft tissue tumor that often presents as a painless, slow-growing mass and is known for its atypical extrapulmonary metastatic pattern. Although sciatic nerve involvement is rare, when present, it usually causes neurologic symptoms. In this case, a large MLS silently expanded and completely encased the sciatic nerve without causing deficits, highlighting the importance of early imaging, multidisciplinary planning, and individualized surgical strategy in managing complex soft tissue sarcomas. Case Presentation: This case report describes a 67-year-old male with a 30 cm encapsulated myxoid liposarcoma of the posterior left thigh. The tumor had grown insidiously over one year and completely encased the sciatic nerve without causing pain, paresthesia, or motor impairment. Selective embolization was performed preoperatively to minimize blood loss. A posteromedial surgical approach allowed for en bloc resection with negative margins and preservation of sciatic nerve integrity. Histopathology confirmed a myxoid liposarcoma composed primarily of spindle-shaped tumor cells. The patient experienced no postoperative complications or neurologic deficits. At the two-year follow-up, he remains disease-free with full functional recovery. Conclusions: This case illustrates the potential for large, asymptomatic myxoid liposarcomas to encase critical neurovascular structures without infiltration. Preoperative embolization as part of a multidisciplinary plan was key to achieving safe resection and excellent functional outcomes. Full article