Osteosarcoma is the most common primary bone tumour in dogs, with approximately 75% of cases occurring in the appendicular skeleton. Standard-of-care therapy consists of limb amputation followed by carboplatin chemotherapy. A minority of dogs have limb-sparing treatments including stereotactic body radiation therapy (SBRT) or surgery. SBRT has a high incidence of pathologic fracture (41%-80% of cases) following treatment, which often results in amputation or euthanasia. Prophylactic bone stabilisation following SBRT has not been recommended due to high complication rates. The IlluminOss system (IS) is an intramedullary implant consisting of a light-curable polymer within an inflatable balloon catheter, which is approved in humans for traumatic fractures and prevention of fractures secondary to bone metastases. We performed a study to assess the safety and feasibility of using the IS following SBRT in six dogs with suspected appendicular osteosarcoma. The IS was placed the day after completion of SBRT. Five of six dogs received adjuvant carboplatin chemotherapy. The IS was well tolerated with no implant-associated infections or immediate post-operative complications occurring. Pathologic fractures occurred in four dogs with a median fracture-free interval of 107 days. Three dogs ultimately underwent amputation due to pathologic fractures. No other post-operative complications occurred. The median survival time was 156 days. These findings suggest that the IS may be a palliative option for dogs following SBRT, but further research to optimise use in the dog and evaluation of the use of the IS with ancillary fixation is necessary.

Background and Objectives: Sarcomas are rare malignancies of mesenchymal origin comprising less than 1% of all adult solid tumors, exhibiting marked histological heterogeneity and variable clinical behavior. Data from Eastern European tertiary oncology centers remain scarce. This study characterized the clinicopathological features, treatment modalities, and survival outcomes of patients with sarcomas of the extremities and trunk treated at the "Prof. Dr. Alexandru Trestioreanu" Institute of Oncology from Bucharest over a ten-year period. Materials and Methods: We conducted a retrospective analysis of 164 patients diagnosed with sarcomas of the extremities and trunk between 2010 and 2020 at "Prof. Dr. Alexandru Trestioreanu" Institute of Oncology. Variables included age, sex, tumor localization, histological subtype, immunohistochemical profile, treatment modalities, recurrence, metastatic spread, and overall survival (OS). Kaplan-Meier curves estimated survival; log-rank tests were applied for subgroup comparisons. Results: The cohort comprised 82 males and 82 females (50.0% each), with a mean age of 48.8 ± 18.3 years. The lower limb was the most frequent site (n = 96, 58.5%), particularly the thigh/femur (34.1%). The most common subtypes were undifferentiated pleomorphic sarcoma (14.6%), osteosarcoma (12.2%), and fibrosarcoma (11.0%). Surgery was performed in 75.6%, chemotherapy in 80.5%, and radiotherapy in 59.8%. Local recurrence occurred in 35.4% and distant metastases in 41.5%. The median OS was 96.0 months (vital status known for 160/164 patients; 90 deceased, 70 alive; OS duration available in 126 patients). Metastatic disease was associated with shorter observed survival in descriptive Kaplan-Meier analysis (log-rank p < 0.001); this comparison is exploratory given the time-dependent nature of the variable. Survival ranged from 11.5 months (leiomyosarcoma) to 162.5 months (dermatofibrosarcoma protuberans) by histotype. Conclusions: This study provides clinically relevant epidemiological and survival data from Romania. The findings illustrate real-world heterogeneity of sarcoma presentations and outcomes at an Eastern European tertiary center and highlight the need for improved diagnostic standardization, prospective data collection, and integration within specialized sarcoma networks.

We report an unusual case of brain radionecrosis following fractionated stereotactic radiotherapy (FSRT) delivered to a calvarial metastasis in a patient with metastatic luminal A breast cancer. A 40-year-old woman developed three subcentimetric brain lesions during follow-up, initially interpreted as new metastases and treated with FSRT. Subsequent radiological progression and advanced imaging suggested radionecrosis, which was confirmed histologically after surgical resection. Retrospective dosimetric analysis revealed that all lesions arose within the high-dose isodose region of the previously irradiated skull metastasis, despite compliance with established brain dose constraints. This case highlights a previously unreported risk of brain radionecrosis after stereotactic irradiation of skull bone metastases and underscores the need for caution in treatment planning and imaging interpretation.

Background: Breast cancer with isolated bone metastases at initial diagnosis represents a clinically distinct metastatic phenotype, often associated with more indolent biology and relatively favorable outcomes compared with visceral metastatic disease. The survival impact of resecting the intact primary breast tumor in de novo metastatic breast cancer remains controversial. In this study, we evaluated the association between primary breast surgery and overall survival (OS), defined as the time from diagnosis to death attributable to breast cancer, in patients presenting with isolated bone metastatic breast cancer. Methods: We performed a retrospective population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Because the SEER variable for bone metastasis at diagnosis is available from 2010 onward and HER2-defined subtype information is available in the modern SEER era, the effective study period was defined as 2010-2021 rather than the full 2000-2021 SEER release period. Patients with breast cancer and isolated bone metastases at presentation, without evidence of lung, liver, brain, or other distant metastatic sites at diagnosis, were included. Demographic and clinicopathological variables, including age, sex, race, biologic subtype, histology, chemotherapy, radiotherapy, and primary breast surgery, were analyzed. Overall survival (OS), defined as the time from diagnosis to death attributable to breast cancer, was estimated using Kaplan-Meier methods and compared using the log-rank test. Independent prognostic factors were evaluated using multivariable Cox proportional hazards modeling. Results: A total of 6500 eligible patients were identified. Surgery of the primary breast tumor was performed in 1513 (23.3%) patients, and 62.8% received chemotherapy. Five-year overall survival (OS) was significantly higher among patients who underwent surgery than among those who did not undergo surgery (59.5% vs. 38.6%; p < 0.001). In multivariable analysis, primary breast surgery remained independently associated with improved OS (hazard ratio [HR] 0.54, 95% CI 0.48-0.62; p < 0.001). Age, histology, chemotherapy, radiotherapy, and biologic subtype were also associated with prognosis. Sex was not significant in the unadjusted analysis (p = 0.188), and the multivariable sex finding was interpreted cautiously because only 96 men were included. Conclusions: In this population-based cohort of patients with de novo breast cancer and isolated bone metastases, primary breast surgery was associated with improved survival among selected patients. However, this association should not be interpreted as causal, given the inherent limitations of observational registry data, including treatment selection, potential immortal-time bias, unmeasured metastatic burden, performance status, systemic therapy type and response, and local symptom burden, which are not fully captured in SEER. These findings support careful multidisciplinary consideration of local therapy in selected patients, while emphasizing the need for confirmation in prospectively designed studies.

The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide belonging to the calcitonin family, discovered as a product of alternative splicing of the calcitonin gene. CGRP has emerged as a pleiotropic signaling molecule with widespread distribution in the central and peripheral nervous systems, particularly within primary sensory neurons. This narrative review synthesizes current knowledge on the CGRP system, integrating recent advances in its molecular structure, gene organization, and post-translational processing with high-resolution structural insights into its heterodimeric receptor complex (CLR-RAMP1) obtained through cryo-electron microscopy. We also include long-term safety data on anti-CGRP monoclonal antibodies, emerging cardiovascular risk signals, and novel therapeutic applications in vestibular migraine and pediatric populations. The intracellular signaling cascades activated by CGRP, including the canonical cAMP-PKA pathway, MAP kinase activation, and context-dependent calcium signaling, are discussed in relation to its diverse physiological functions. These encompass vasodilation, nociception modulation, neurogenic inflammation, gastrointestinal motility, bone metabolism, tissue regeneration, and energy homeostasis. The central role of CGRP in migraine pathophysiology is examined to understand the development of targeted therapies. The current pharmacological landscape is reviewed, including the evolution of small-molecule CGRP receptor antagonists (gepants) through three generations and the four approved monoclonal antibodies targeting CGRP or its receptor, with comparative analysis of their efficacy, safety profiles, and clinical positioning. Beyond migraine, emerging and predominantly preclinical roles of the CGRP system are discussed in chronic pain, osteoarthritis, cardiovascular diseases, sepsis, cancer (particularly bone metastases and tumor microenvironment immunomodulation), and neurodegenerative disorders such as Alzheimer's disease. In these areas, the available evidence remains heterogeneous and, in most cases, is not yet sufficient to support clinical translation. Finally, future directions are discussed, including the development of stable CGRP analogs, allosteric modulators, and the potential expansion of therapeutic applications into oncology, intensive care medicine, and neuroprotection.

High-risk neuroblastoma (HR-NB) remains a therapeutic challenge in low- and middle-income countries. We retrospectively analyzed the clinical characteristics, treatment response, transplant outcomes, event-free survival, and overall survival of pediatric patients with HR-NB treated with intensive multimodality therapy, including autologous stem cell transplant (ASCT) at a resource-limited tertiary cancer center between January 2013 and January 2024. Children aged 18 years or younger received rapid-COJEC induction chemotherapy, followed by surgical resection when feasible, ASCT with busulfan-melphalan conditioning, radiotherapy, and differentiation therapy with 13-cis-retinoic acid. Eighteen patients were included, with a male-to-female ratio of 2:1 and a median age of 4 years. The adrenal gland was the most common primary site in 55.55% of patients. Bone marrow and bone metastases were present in 72.2% and 44.4% of patients, respectively. Complete response after induction was achieved in 44.4% of patients. Median neutrophil engraftment occurred at 13 days. At a median follow-up of 17 months, 55.5% of patients were alive in remission. Relapse occurred in 50%, with most succumbing to the disease. There was no treatment-related mortality. Two-year event-free and overall survival were 55.3% and 65.6%, respectively. Outcomes were comparable to other resource-limited settings, and the lack of complete response after induction did not adversely affect event-free survival.

Invasive ductal carcinoma of the breast is known to typically metastasise to the lungs, liver, bone and brain, with subcutaneous soft tissue involvement being rare, with only eight cases reported internationally. We report the case of a woman with a history of left-sided invasive ductal carcinoma treated with a mastectomy and adjuvant therapy, who presented 7 years later with a 2.8 cm subcutaneous lesion over the contralateral shoulder. Histopathological examination and immunohistochemistry confirmed metastatic invasive ductal carcinoma, displaying a morphological and receptor profile congruent with her primary tumour. This case highlights the potential for late and atypical metastatic presentations of breast cancer and underlines the importance of maintaining diagnostic vigilance in long-term survivors.

This study aimed to analyze the clinical characteristics of metachronous breast cancer bone metastasis (BCBM) and construct a graded prognostic assessment (GPA) model. A retrospective analysis was conducted on the clinical data of newly diagnosed breast cancer patients with bone metastasis (BM). Data collected included initial involvement of bone substructures and metastatic burden other than BM. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA) were used to evaluate the efficacy of the Cox regression model, and a GPA model for overall survival (bmOS) after BM was constructed. The DeLong test was used to compare the area under the curve (AUC) of the training and validation sets to validate the model efficacy. A total of 2103 BMs were detected in 308 patients with metachronous BCBM. The most common sites were the thoracic spine (24.8%), lumbar spine (16.7%), ribs (11.9%), and iliac bone (10.2%); 80.1% of the lesions were osteolytic. Independent prognostic risk factors for bmOS included in the GPA model included initial stage, molecular subtype, time to BM (TTBM), BM numbers, and extraosseous visceral metastases (EVM). The model showed no statistically significant difference in AUC between the training and validation sets (DeLong test, P > 0.05). Patients were divided into three risk strata based on GPA scores (0-8.5), with significant differences in median survival: 60.3, 40.0, and 32.6 months in the training set (P < 0.001), and 64.0, 41.6, and 25.3 months in the validation set (P < 0.001). Initial treatment failure was predominantly due to bone progression (39.3%) and visceral progression (28.2%). In conclusion, the prognosis of patients with metachronous BCBM exhibits significant heterogeneity. The GPA model developed in this study can serve as a practical prognostic assessment tool and provide a reference for individualized treatment planning.