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Cancer Medicine Aug 2023Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established.
PURPOSE
Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established.
MATERIALS AND METHODS
We retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022.
RESULTS
Overall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p < 0.001), higher incidence of liver metastases (89% vs. 9%, p<0.001), a lower incidence of lymph nodes metastases (16% vs. 46%, p = 0.043) and a lower incidence of BRAF mutation (0% vs. 55%, p<0.001) compared with patients with conjunctival melanoma (CM). The overall response rate of the first-line treatment was 18%. Three of the four patients with BRAF-mutated CM responded to dabrafenib and trametinib treatment. The median progression-free survival (PFS) and overall survival (OS) of first-line treatment were 5.1 and 11.9 months, respectively. Among patients with liver metastases, liver-directed treatment was correlated with better patient PFS (p < 0.001) and OS (p < 0.001) after adjusting for number of metastatic sites and primary sites.
CONCLUSION
CM and UM have different characteristics. Patient with CM had a high incidence of BRAF mutation, and the treatment of BRAF and MEK inhibitors conferred clinical benefit. Liver directed therapies had a potential benefit in disease control in patients with liver metastases.
Topics: Humans; Skin Neoplasms; Proto-Oncogene Proteins B-raf; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Orbital Neoplasms; China; Melanoma; Prognosis; Mutation
PubMed: 37409486
DOI: 10.1002/cam4.6273 -
Cancers Dec 2023Orbital and ocular adnexa lymphomas are rare neoplasms confined to the orbital region. The prognosis is generally favorable, with a high proportion of localized disease,... (Review)
Review
Orbital and ocular adnexa lymphomas are rare neoplasms confined to the orbital region. The prognosis is generally favorable, with a high proportion of localized disease, indolent clinical course, prolonged disease-free intervals, and low lymphoma-related mortality rate. We report our experience on eleven patients with confirmed histological diagnosis of lymphoma stage IE-IIE, treated between 2010 and 2021 with radiotherapy alone or in association with chemotherapy or immunotherapy. Eight patients were treated with primary radiotherapy only, while three received previous systemic treatments. Six patients were treated with Proton beam therapy (PBT), and five with external beam radiotherapy (EBRT). The five-year local control rate was 98%; only one patient developed an out-of-field recurrence. We also conducted a comprehensive literature review using electronic databases (PubMed, EMBASE, and Cochrane Library). Articles were selected based on their pertinence to treatment of the ocular and adnexal lymphoma focusing on radiotherapy techniques (electron beam radiotherapy, photon beam radiotherapy, or proton beam radiotherapy), treatment total dose, fractionation schedule, early and late radio-induced toxicities, and patient's clinical outcome. Radiotherapy is an effective treatment option for orbital lymphoma, especially as standard treatment in the early stage of orbital lymphoma, with excellent local control rate and low rates of toxicity.
PubMed: 38136328
DOI: 10.3390/cancers15245782 -
Laryngo- Rhino- Otologie May 2024Diagnosis and therapy of orbital diseases is an interdisciplinary challenge, in which i.e. otorhinolaryngologists, ophthalmologists, radiologists, radiation therapists,... (Review)
Review
Diagnosis and therapy of orbital diseases is an interdisciplinary challenge, in which i.e. otorhinolaryngologists, ophthalmologists, radiologists, radiation therapists, maxillo-facial surgeons, endocrinologists, and pediatricians are involved. This review article describes frequent diseases which both, otolaryngologists and ophthalmologists are concerned with in interdisciplinary settings. In particular the inflammatory diseases of the orbit including orbital complications, autoimmunological diseases of the orbit including Grave´s orbitopathy, and primary and secondary tumors of the orbit are discussed. Beside describing the clinical characteristics and diagnostic steps the article focusses on the interdisciplinary therapy. The review is completed by the presentation of most important surgical approaches to the orbit, their indications and possible complications. The authors tried to highlight the relevant facts despite the shortness of the text.
Topics: Humans; Orbital Diseases; Interdisciplinary Communication; Patient Care Team; Intersectoral Collaboration; Orbital Neoplasms
PubMed: 38697143
DOI: 10.1055/a-2216-8879 -
Advances in Ophthalmology Practice and... 2024The periocular skin is neoplasms-prone to various benign and malignant. Periocular malignancies are more aggressive and challenging to cure and repair than those in... (Review)
Review
BACKGROUND
The periocular skin is neoplasms-prone to various benign and malignant. Periocular malignancies are more aggressive and challenging to cure and repair than those in other skin areas. In recent decades, immunotherapy has significantly advanced oncology, allowing the autoimmune system to target and destroy malignant cells. Skin malignancies, especially periocular tumors, are particularly sensitive to immunotherapy. This technique has dramatically impacted the successful treatment of challenging tumors.
MAIN TEXT
Extraocular cancers, including eyelid (basal cell carcinoma, squamous cell carcinoma, melanoma, merkel cell carcinoma), conjunctival tumors (conjunctival melanoma, ocular surface squamous neoplasia) and other rare tumors, are unique and challenging clinical situations. Several genetic alterations associated with the pathogenesis of these diseases have been identified, and molecular mechanism are essential for the development of the immunotherapy agents, such as Hedgehog pathway inhibitors (vismodegib and sonidegib) for basal cell carcinoma, BRAF/MEK inhibitors (vemurafenib, dabrafenib, and encorafenib) for melanoma, and immune checkpoint inhibitors (Avelumab, pembrolizumab) for Merkel cell carcinoma.
CONCLUSIONS
The optimal treatment for periocular skin cancer depends on the type and size of the tumor and whether it involves orbital and adnexal structures. Adjuvant and neoadjuvant therapy with chemotherapy-targeted therapies and immune checkpoint inhibitors should be considered based on tumor type, tumor molecular profile, expected response rate, and candidacy for systemic treatment.
PubMed: 38590555
DOI: 10.1016/j.aopr.2024.02.003 -
Journal of Experimental & Clinical... Nov 2023Metabolic reprogramming of amino acids has been increasingly recognized to initiate and fuel tumorigenesis and survival. Therefore, there is emerging interest in the... (Review)
Review
Metabolic reprogramming of amino acids has been increasingly recognized to initiate and fuel tumorigenesis and survival. Therefore, there is emerging interest in the application of amino acid metabolic strategies in antitumor therapy. Tremendous efforts have been made to develop amino acid metabolic node interventions such as amino acid antagonists and targeting amino acid transporters, key enzymes of amino acid metabolism, and common downstream pathways of amino acid metabolism. In addition to playing an essential role in sustaining tumor growth, new technologies and studies has revealed amino acid metabolic reprograming to have wide implications in the regulation of antitumor immune responses. Specifically, extensive crosstalk between amino acid metabolism and T cell immunity has been reported. Tumor cells can inhibit T cell immunity by depleting amino acids in the microenvironment through nutrient competition, and toxic metabolites of amino acids can also inhibit T cell function. In addition, amino acids can interfere with T cells by regulating glucose and lipid metabolism. This crucial crosstalk inspires the exploitation of novel strategies of immunotherapy enhancement and combination, owing to the unprecedented benefits of immunotherapy and the limited population it can benefit. Herein, we review recent findings related to the crosstalk between amino acid metabolism and T cell immunity. We also describe possible approaches to intervene in amino acid metabolic pathways by targeting various signaling nodes. Novel efforts to combine with and unleash potential immunotherapy are also discussed. Hopefully, some strategies that take the lead in the pipeline may soon be used for the common good.
Topics: Humans; T-Lymphocytes; Tumor Microenvironment; Neoplasms; Energy Metabolism; Immunotherapy; Amino Acids
PubMed: 37924140
DOI: 10.1186/s13046-023-02845-4 -
Arquivos Brasileiros de Oftalmologia 2024Vascular anomalies comprise a wide spectrum of clinical manifestations related to disturbances in the blood or lymph vessels. They correspond to mainly tumors... (Review)
Review
Vascular anomalies comprise a wide spectrum of clinical manifestations related to disturbances in the blood or lymph vessels. They correspond to mainly tumors (especially hemangiomas), characterized by high mitotic activity and proliferation of the vascular endothelium, and malformations, endowed with normal mitotic activity and no hypercellularity or changes in the rate of cell turnover. However, the classifications of these lesions go beyond this dichotomy and consist various systems adapted for and by different clinical subgroups. Thus, the classifications have not reached a consensus and have historically caused confusion regarding the nomenclatures and definitions. Cavernous venous malformations of the orbit, previously called cavernous hemangiomas, are the most common benign vascular orbital lesions in adults. Herein, we have compiled and discussed the various evidences, including clinical, radiological, morphological, and molecular evidence that indicate the non-neoplastic nature of these lesions.
Topics: Humans; Hemangioma, Cavernous; Orbital Neoplasms; Orbit; Vascular Malformations
PubMed: 38655941
DOI: 10.5935/0004-2749.2023-0338 -
American Journal of Ophthalmology Case... Mar 2024To present a rare case of dedifferentiated liposarcoma of the orbit.
PURPOSE
To present a rare case of dedifferentiated liposarcoma of the orbit.
OBSERVATIONS
A 61-year-old male complained of left-sided proptosis, diplopia, and limited ocular motility for two years. Biopsy results at that time were suggestive of an atypical lipomatous neoplasm. Ten years later, he presented with increase in size of the mass and worsening of his symptoms. Imaging showed a multi-lobulated mass in the left orbit involving the intraconal, medial, and anterior orbit. Decompression and orbitotomy with biopsy were performed to debulk the mass. Pathology showed a low-grade well-differentiated liposarcoma and the patient was monitored thereafter annually. Eight years later, he complained of persistent proptosis and mass effect from the tumor resulting in ptosis and diplopia and underwent orbital exenteration. Histopathological analysis of the exenterated orbit revealed a focal area of dedifferentiated liposarcoma.
CONCLUSIONS AND IMPORTANCE
Dedifferentiation of an orbital mass can occur as a late complication years after the diagnosis of well-differentiated liposarcoma. Compared to the previously published cases of orbital liposarcoma, this presentation shows a prolonged timeline prior to dedifferentiation (18 years after initial diagnosis). Symptoms of growth or invasive features could indicate dedifferentiation and should warrant a biopsy.
PubMed: 38261879
DOI: 10.1016/j.ajoc.2023.101980 -
Investigative Ophthalmology & Visual... Dec 2023Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple short- and...
PURPOSE
Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple short- and long-term treatment toxicities. Reliable and informative models to assist clinicians are needed. Thus we developed and comprehensively characterized a novel preclinical platform of primary cell cultures and xenograft models of metastatic retinoblastoma to provide insights into the molecular biology underlying metastases and to perform drug screening for the identification of hit candidates with the highest potential for clinical translation.
METHODS
Orbital tumor, bone marrow, cerebrospinal fluid, and lymph node tumor infiltration specimens were obtained from seven patients with metastatic retinoblastoma at diagnosis, disease progression, or relapse. Tumor specimens were engrafted in immunodeficient animals, and primary cell lines were established. Genomic, immunohistochemical/immunocytochemical, and pharmacological analysis were performed.
RESULTS
We successfully established five primary cell lines: two derived from leptomeningeal, two from orbital, and one from lymph node tumor dissemination. After the intravitreal or intraventricular inoculation of these cells, we established cell-derived xenograft models. Both primary cell lines and xenografts accurately retained the histological and genomic features of the tumors from which they were derived and faithfully recapitulated the dissemination patterns and pharmacological sensitivity observed in the matched patients.
CONCLUSIONS
Ours is an innovative and thoroughly characterized preclinical platform of metastatic retinoblastoma developed for the understanding of tumor biology of this highly aggressive tumor and has the potential to identify drug candidates to treat patients who currently lack effective treatment options.
Topics: Animals; Humans; Retinoblastoma; Neoplasm Recurrence, Local; Cell Line; Disease Models, Animal; Retinal Neoplasms
PubMed: 38117242
DOI: 10.1167/iovs.64.15.27 -
Nature Communications Mar 2024CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually...
CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells. Proteomics analysis uncovers fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 results in dissociation of FUS from RNA polymerase II, leading to hyperphosphorylation of serine 2 in RNA polymerase II, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.
Topics: Humans; Female; Breast Neoplasms; Cell Line, Tumor; RNA Polymerase II; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor Proteins; Cyclin-Dependent Kinase 6; Protein Kinase Inhibitors; Drug Resistance, Neoplasm; Protein-Arginine N-Methyltransferases
PubMed: 38480701
DOI: 10.1038/s41467-024-46495-2