Search Results (21)

Background/Objectives: We aimed to evaluate the demographic characteristics, clinical findings, and survival outcomes of patients diagnosed with orbital metastasis, considering primary tumor type, age, and gender variables. Methods: In this observational study, demographic data, tumor localization, histopathological diagnoses, and survival times of 83 patients followed for secondary orbital metastasis at Çukurova University Ophthalmology Department between 2003 and 2023 were retrospectively reviewed. Subgroup analyses were performed according to age (<18 and ≥19), gender, and primary tumor groups. Results: The study included 83 patients (51 (61.4%) females and 32 (38.6%) males). The mean age at diagnosis was found to be 40.8 ± 24.6 years. A total of 24.1% of the cases were in the pediatric age group (mean age 5.9 years), and the most common tumor metastasizing to the orbit in this group was neuroblastoma (80%). In adult patients, the two most frequent tumors metastasizing to the orbit were breast cancer (33.3%) and lung cancer (14.3%). The most common clinical findings were proptosis (32.5%) and blurred vision (26.2%). Orbital metastases were observed more frequently in females than in males (61.4% vs. 38.6%). This ratio was similar in the pediatric age group (65.0% vs. 35.0%). The mean survival time after metastasis was calculated as 316.7 ± 68.6 days. Female patients had a significantly longer survival time after metastasis compared to males (mean 400.4 vs. 165.4 days; p = 0.037). The median survival after metastasis was 86 days for patients with breast cancer and 204 days for patients with neuroblastoma. Conclusions: The most common source of orbital metastases in females is breast cancer, while neuroblastoma is prominent in pediatric patients. Despite all available treatment options, the prognosis after orbital metastasis is poor; this highlights the importance of early diagnosis and a multidisciplinary approach. Full article

We present a rare case of delayed retrobulbar and adrenal metastases from renal cell carcinoma (RCC), diagnosed 5.5 years after radical nephrectomy. The patient exhibited symptomatic orbital involvement, with imaging revealing a hypervascular retrobulbar mass and an incidental right adrenal lesion, indicative of an oligometastatic state. Owing to the patient’s refusal of surgical resection, stereotactic ablative radiotherapy (SABR) was delivered to the retrobulbar lesion at a total dose of 40 Gy in five fractions, concurrently with immune checkpoint inhibitor therapy. Treatment planning prioritized sparing adjacent critical structures, including the optic chiasm and brainstem. Follow-up over 4 years demonstrated sustained radiologic stability and volume reduction in both metastatic lesions without evidence of progression. This case underscores the potential efficacy of SABR in achieving durable local control of RCC metastases, particularly in anatomically constrained regions where surgery is unfeasible. Moreover, it highlights the value of a multidisciplinary, multimodal treatment approach incorporating advanced radiotherapy techniques and systemic immunotherapy. Lastly, it reinforces the importance of prolonged surveillance in RCC survivors due to the potential for late metastatic recurrence at uncommon sites. Full article

Purpose: The objective of this study was to evaluate the implementation of a Multidisciplinary Tumor Board (MDTB) strategy in the treatment of patients with uveal melanoma. Methods: A retrospective analysis was conducted on the implementation of MDTB meetings over a 24-month period. During this time, 72 intraocular tumors were discussed, including 59 confirmed cases of uveal melanoma. The MDTB involved a core group of specialists (e.g., ophthalmologists, oncologists, and radiologists), with other experts included when clinically appropriate. To assess patient satisfaction with the MDTB approach, a structured questionnaire was administered, including items on clarity of communication, perceived quality of care, and overall satisfaction, which were ranked on a 5-point scale. Results: A total of 319 patients with ocular, periocular, or orbital tumors were discussed during the study period, of which, 72 had intraocular tumors. A total of 13 (18%) were diagnosed to have choroidal metastases, whereas 59 (82%) had uveal melanomas. The average time between patient care and MDTB discussion was 15.9 days (IQR: 7.5–16.5). The mean time between the case discussion and the implementation of recommendations (diagnostic, therapeutic, or referral decisions) was 14.8 days (IQR: 6.0–23.75). Overall, 4 (7%) patients were classified as Stage I, 16 (27%) as Stage IIa, 18 (31%) as Stage IIb, 7 (12%) as Stage IIIa, 2 (3%) as Stage IIIb, and 12 (20%) as Stage IV. Regarding the satisfaction questionnaire, all patients (100%) agreed to have the clinical case discussed at the TB even though this could result in a delay in diagnostic/therapeutic implementation. However, only 60% of patients perceived they had been directly involved in the decision-making process. Conclusions: In selected cases of uveal melanoma and other types of cancer, MDTBs should be recognized as a gold standard in cancer care, allowing for comprehensive decision-making that draws on a wide range of highly specialized expertise. Full article

Background: This study aims to analyze the clinical, radiological, and histopathological features, as well as the long-term follow-up, of patients with breast carcinoma orbital metastases. Methods: The study was a multicentric retrospective observational case series. The medical records of 32 female patients affected by breast carcinoma orbital metastases referred to three tertiary referral centers from January 2016 to December 2023 were reviewed. The demographic characteristics of the population, clinical ophthalmological presentation, histological features, orbital metastasis latency, disease-related survival (DRS), and mortality rate were analyzed. Results: The median age of the patients was 62.50 years (interquartile range (IQR): 74.50–57.50). The prevalent histotype of the orbital metastases of breast cancer was lobular carcinoma (75.00% of cases). The median orbital metastasis latency time was 39.50 months (IQR: 134.00–10.25). The median disease-related survival (DRS) during the observational period was 35 months, and the 24-month survival rate was 70.73%. The overall mortality rate in our population was 50%. Conclusions: The most frequent histotype of breast cancer orbital metastasis is lobular carcinoma. The primary tumor precedes the onset of orbital metastasis in most cases and usually presents as a mass occupying space and infiltrating the orbit. Orbital metastases are a sign of an advanced stage of the disease, which has a high mortality rate and a low DRS. Full article

Murine xenograft models are valuable and increasingly used preclinical tools in cancer research to understand disease pathogenesis and guide treatment options. The aim of this narrative review is to summarize the studies that employed mouse xenograft models, using cell lines, patient-derived tumors, or organoids, in endometrial cancer (EC) research, detailing their methodology and main findings. We identified 27 articles reporting on heterotopic EC xenografts, including subcutaneous, subrenal capsule, intraperitoneal, and retro-orbital models, and 18 articles using orthotopic xenografts. Subcutaneous xenografts generated using either cell lines or patient tumors have been widely used; however, their low engraftment rates and the inability to recapitulate main clinical features such as metastases limit their translational value. Subrenal capsule models showed improved engraftment rates compared to subcutaneous models, but tumors exhibited slower and constrained tumor growth. Orthotopic models are technically more challenging to generate and monitor, but tumor growth occurs in a relevant microenvironment and EC ortho-xenografts exhibit high engraftment rates and metastases to clinically relevant sites. Cell line-based xenograft (CDX) models are attractive tools because they are convenient, easy to use, and amenable to genetic modifications, making them suitable for proof-of-concept approaches and large-scale studies. EC xenografts developed from patient tumors (PDTXs) are more labor/cost-intensive for their establishment but can capture the genetic and molecular heterogeneity within and across histologic subtypes and can inform personalized patient treatment. EC organoid-based xenograft (PDOX) models combine the advantages of both CDXs and PDTXs since they are more time- and cost-effective, faithfully maintain tumor characteristics and therapeutic responses, and can be genetically modified. Despite substantial progress in EC management, there are still several unmet needs. Efficient targeted treatments are currently indicated only for a small subgroup of patients, while women with recurrent or advanced-stage EC have very few therapeutic options and their prognosis remains unfavorable. Novel (targeted) drugs, combinational regimens and tools to predict the real drug response in patients are urgently needed. Xenograft models are expected to inform about disease mechanisms and to help identify novel therapeutic options and suitable target patients. Full article

The orbital manifestation of a solitary fibrous tumor (SFT) is exceptionally rare and poses specific challenges in diagnosis and treatment. Its rather exceptional behavior among all SFTs comprises a high tendency towards local recurrence, but it rarely culminates in metastatic disease. This raises the question of prognostic factors in orbital SFTs (oSFTs). Telomerase reverse transcriptase (TERT)-promoter mutations have previously been linked to an unfavorable prognosis in SFTs of other locations. We analyzed the prevalence of TERT promoter mutations of SFTs in the orbital compartment. We performed a retrospective, descriptive clinico-histopathological analysis of nine cases of oSFTs between the years of 2017 and 2021. A TERT promoter mutation was present in one case, which was classified with intermediate metastatic risk. Local recurrence or progress occurred in six cases after primary resection; no distant metastases were reported. Multimodal imaging repeatedly showed particular morphologic patterns, including tubular vascular structures and ADC reduction. The prevalence of the TERT promoter mutation in oSFT was 11%, which is similar to the prevalence of extra-meningeal SFTs of the head and neck and lower than that in other extra-meningeal compartments. In the present study, the TERT promoter mutation in oSFT manifested in a case with an unfavorable prognosis, comprising aggressive local tumor growth, local recurrence, and eye loss. Full article

Background: The ocular involvement of neuroendocrine neoplasms (NENs) is uncommon and mainly represented by metastases from gastrointestinal and lung neuroendocrine tumors. Primary orbital NENs are even less common and their diagnostic and therapeutic management is a challenge. Methods: A systematic review of the literature was conducted from 1966 to September 2023 on PubMed to identify articles on orbital NENs and to summarize their clinical–pathological features, diagnosis and therapeutic management. Furthermore, we presented a case of a locally advanced retro-orbital primary neuroendocrine tumor that was referred to the certified Center of Excellence of Sant’Andrea Hospital, La Sapienza University of Rome, Italy. Results: The final analysis included 63 records on orbital NENs and 11 records focused on primary orbital NENs. The localization was mostly unilateral and in the right orbit; proptosis or exophthalmos represented the initial symptoms. The diagnostic work-up and therapeutic management was discussed and a diagnostic algorithm for the suspicion of primary orbital NENs was proposed. Conclusions: A multidisciplinary approach is required for the management of primary orbital NENs, emphasizing the importance of early referral to dedicated centers for prompt differential diagnosis, tailored treatment, and an improved quality of life and survival. Full article

Introduction: The purpose of this study was to assess the overall survival (OS) and disease-free survival (DFS) of patients who underwent orbital exenteration for periorbital, conjunctival, and primary intraorbital carcinomas. Additionally, we assessed the outcomes of anterior retrograde temporalis muscle flap restoration. Methods: For all patients who had orbital exenteration in the previous five years, a non-comparative retrospective assessment of their medical records, histology, and radiographic imaging was carried out. We investigated the relationships between the various qualitative factors using Cramer’s V Kaplan–Meier (KM) analysis. For each of the patient’s categorical factors that were of relevance, estimates of the survival distribution were displayed, and log-rank tests were used to determine whether the survival distributions were equal. Results: This study looks at 19 participants. The sample is made up of 13 men (68%) and 6 women (32%). The degree of relationship (Cramer’s V index) between lymph node metastases (N) and the existence of distant metastases (M) is high, at 64%, and is statistically significant because the p-value is 0.0034 < 0.005. Lymph node metastases had a statistically significant impact on overall survival (p = 0.04 < 0.05). Thirteen of the nineteen patients tested had no palsy (68%). There was no one presenting a CSF leak. Conclusion: Our findings show how crucial it is to identify any lymph node involvement that orbital neoplasms may have. In patients who have received many treatments, sentinel lymph node biopsy (SLNB) may be used to determine the stage and spread of the cancer. To determine whether additional tumor characteristics may be explored, more expertise in the SLNB field for patients with orbital cancer who have received many treatments may be helpful. To prevent additional scarring and to be comparable to previous techniques for facial nerve lesions, the anterior retrograde approach and the transorbital procedure for temporal muscle flap in-setting are both effective methods. Full article

We report a case of orbital metastasis of infiltrative breast carcinoma in a 65-year-old man. The patient was diagnosed with stage four breast cancer one year before, for which a mastectomy was performed. He refused postoperative radiotherapy and chemotherapy at that time. He had a history of lung, liver, and mediastinal metastases. At admission, he presented with blurred vision, diplopia, ocular pain, and mild swelling of the upper lid of the left eye (LE). Computed tomography (CT) of the brain and orbit revealed a front-ethmoidal tissue mass with left orbital and frontal intracranial extension. Ophthalmologic examination revealed exophthalmos on the LE with a downward and outward deviation of the eyeball, proptosis, and intraocular pressure (IOP) of 40 mmHg. The patient’s treatment started with topical maximal anti-glaucomatous drops and radiotherapy sessions. After three weeks of follow-up, there was a gradual improvement of local symptoms and signs and a normal IOP. Full article

The β⁻ emitter, rhenium-188 (¹⁸⁸Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares chemical similarities with its congener element technetium, whose nuclear isomer technetium-99m (^99mTc) is the current workhorse of diagnostic nuclear medicine. The differences between these two elements have a significant impact on the radiolabelling methods and should always receive critical attention. This review aims to highlight what needs to be considered to design a successful radiopharmaceutical incorporating ¹¹⁸Re. Some of the most effective strategies for preparing therapeutic radiopharmaceuticals with ¹⁸⁸Re are illustrated and rationalized using the concept of the inorganic functional group (core) and a simple ligand field theoretical model combined with a qualitative definition of frontiers orbitals. Of special interest are the Re(V) oxo and Re(V) nitrido functional groups. Suitable ligands for binding to these cores are discussed, successful clinical applications are summarized, and a prediction of viable future applications is presented. Rhenium-188 decays through the emission of a high energy beta particle (2.12 MeV max energy) and a half-life of 16.9 h. An ideal biological target would therefore be a high-capacity target site (transporters, potential gradients, tumour microenvironment) with less emphasis on saturable targets such as overexpressed receptors on smaller metastases. Full article

Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP–NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP–NENs who developed BMs. Methods: A retrospective single-centre analysis of consecutive patients with EP–NENs (August 2004–February 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis was estimated (Kaplan–Meier). Results: Of 730 patients, 17 (1.9%) had BMs, median age 61 years (range 15–77); 8 (53%) male, unknown primary NEN site: 40%. Patients with BMs had grade 3 (G3) EP–NENs 11 (73%), G2: 3 (20%), G1: 1 (7%). Eight (53%) had poorly differentiated NENs, 6 were well-differentiated and 1 was not recorded. Additionally, 2 (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. The relative risk of developing BMs was 7.48 in patients with G3 disease vs. G1 + G2 disease (p = 0.0001). Median time to the development of BMs after NEN diagnosis: 15.9 months (range 2.5–139.5). Five patients had a solitary BM, 12 had multiple BMs. Treatment of BMs were surgery (n = 3); radiotherapy (n = 5); 4: whole brain radiotherapy, 1: conformal radiotherapy (orbit). Nine (53%) had best supportive care. Median OS from NEN diagnosis was 23.6 months [95% CI 15.2–31.3]; median time to death from BMs diagnosis was 3.0 months [95% CI 0.0–8.3]. Conclusion: BMs in patients with EP–NENs are rare and of increased risk in G3 vs. G1 + G2 EP–NENs. Survival outcomes are poor, and a greater understanding is needed to improve therapeutic outcomes. Full article

Specific genomic alterations have been found in primary breast cancer involving driver mutations that result in tumorigenesis. Metastatic breast cancer, which is uncommon at the time of disease onset, variably impacts patients throughout the course of their disease. Both the molecular profiles and diverse genomic pathways vary in the development and progression of metastatic breast cancer. From the most common metastatic site (bone), to the rare sites such as orbital, gynecologic, or pancreatic metastases, different levels of gene expression indicate the potential involvement of numerous genes in the development and spread of breast cancer. Knowledge of these alterations can, not only help predict future disease, but also lead to advancement in breast cancer treatments. This review discusses the somatic landscape of breast primary and metastatic tumors. Full article

Orbital metastases are a rare but life-altering complication in cancer. Most commonly seen in breast cancer, metastases to the optic nerves or extraocular muscles can have a devastating impact on visual acuity and quality of life. Hormone receptor status plays a central role in metastatic breast cancer treatment, with endocrine therapy often representing first-line therapy in hormone-receptor-positive cancers. Staging and treatment response evaluation with positron emission tomography (PET) computed tomography (CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) is limited by high physiologic uptake in the intracranial and intraorbital compartments. Thus, traditional staging scans with 18F-FDG PET/CT may under-detect intraorbital and intracranial metastatic disease and inaccurately evaluate active metastatic disease burden. In comparison, 18F-fluoroestradiol (18F-FES) is a novel estrogen-receptor-specific PET radiotracer, which more accurately assesses the intracranial and intraorbital compartments in patients with estrogen-receptor-positive (ER+) cancers than 18F-FDG, due to lack of physiologic background activity in these regions. We present two cases of breast cancer patients with orbital metastases confirmed on MR imaging who underwent PET/CT imaging with 18F-FES and 18F-FDG. Multimodality imaging with 18F-FES PET/CT offers higher detection sensitivity of orbital metastases, compared with traditional 18F-FDG PET/CT imaging, and can improve the assessment of treatment response in patients with estrogen-receptor-positive (ER+) cancers. Full article

Background: Orbital metastases often lead to severe functional impairment. The role of resection, orbital exenteration, and complementary treatments is still debated. We systematically reviewed the literature on orbital metastases. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon PRISMA guidelines to identify studies on orbital metastases. Clinical characteristics, management strategies, and survival were analyzed. Results: We included 262 studies comprising 873 patients. Median age was 59 years. The most frequent primary tumors were breast (36.3%), melanoma (10.1%), and prostate (8.5%) cancers, with median time interval of 12 months (range, 0–420). The most common symptoms were proptosis (52.3%) and relative-afferent-pupillary-defect (38.7%). Most metastases showed a diffuse location within the orbit (19%), with preferential infiltration of orbital soft tissues (40.2%). In 47 cases (5.4%), tumors extended intracranially. Incisional biopsy (63.7%) was preferred over fine-needle aspiration (10.2%), with partial resection (16.6%) preferred over complete (9.5%). Orbital exenteration was pursued in 26 patients (3%). A total of 305 patients (39.4%) received chemotherapy, and 506 (58%) received orbital radiotherapy. Post-treatment symptom improvement was significantly superior after resection (p = 0.005) and orbital radiotherapy (p = 0.032). Mean follow-up was 14.3 months, and median overall survival was 6 months. Fifteen cases (1.7%) demonstrated recurrence with median local control of six months. Overall survival was statistically increased in patients with breast cancer (p < 0.001) and in patients undergoing resection (p = 0.024) but was not correlated with orbital location (p = 0.174), intracranial extension (p = 0.073), biopsy approach (p = 0.344), extent-of-resection (p = 0.429), or orbital exenteration (p = 0.153). Conclusions: Orbital metastases severely impair patient quality of life. Surgical resection safely provides symptom and survival benefit compared to biopsy, while orbital radiotherapy significantly improves symptoms compared to not receiving radiotherapy. Full article

Although its incidence has increased over the last decades, conjunctival melanoma (CM) remains a rare but challenging periocular malignancy. While there is currently no recognized standard of care, “no-touch” surgical excision followed by adjuvant treatments is usually recommended. Despite its small size, managing CM is challenging for clinicians. The first challenge is the high risk of tumour local recurrence that occurs in about one third of the patients. The management of locally advanced CM (≥T2) or multiple recurrences may require mutilating surgeries such as orbital exenteration (OE). The second challenge is the metastatic spread of CM that occurs in about one quarter of patients, regardless of whether complete surgical excision is performed or not. This highlights the infiltrative and highly aggressive behaviour of CM. Recently, attention has been directed towards the use of eye-sparing strategies to avoid OE. Initially, wide conservative surgeries followed by customized brachytherapy or radiotherapy have appeared as viable strategies. Nowadays, new biological insights into CM have revealed similarities with cutaneous melanoma. These new findings have allowed clinicians to reconsider the management of locally advanced CM with “medical” eye-sparing treatment as well as the management of metastatic spread. The aim of this review was to summarize the current and future perspectives of treatment for CM based on recent biological findings. Full article