Clinicopathological analysis of 719 pediatric and adolescents’ ocular tumors and tumor-like lesions:a retrospective study from 2000 to 2018 in China

AIM:To describe the clinicopathologic features and classification of pediatric and adolescent ocular tumors and tumor-like lesionsMETHODS:A total of 719 cases of pathologically confirmed ocular tumors and tumor-like lesions in a pediatric population from two academic institutions over an 18-year period were retrospectively analyzed.The main outcome measures were the clinical and pathological features of the cases.RESULTS:Benign tumors accounted for 92.1%of all cases while malignant tumors accounted for 7.9%.The most common ocular benign tumors were(epi-)dermoid cysts(19.8%),nevi(15.2%),corneal dermoid tumors(9.8%),and calcified epitheliomas(8.8%).The most common ocular malignant tumors were retinoblastoma(80.8%),and rhabdomyosarcoma(3.9%).Eyelid and ocular surface tumors comprised 73.3%of benign tumors while intraocular and orbital cavity comprised 94.2%of malignant tumors.For tumor site,the upper eyelid was up to 1.79 times more than lower eyelid(P<0.05).Age at surgery and sex also had an association with different lesions(P=0.006,P=0.035,respectively).CONCLUSION:Most ocular tumors and tumor-like lesions in children and adolescents are benign.Pediatric ocular tumors are distinct from those in adults in terms of histological origin.(Epi-)dermoid cysts are the most common benign tumors while retinoblastomas the most common malignant tumors.

TNF related apoptosis-inducing ligand and its receptors in ocular tumors

Most of the ocular tumors have poor prognosis, and they remain a difficult problem in the area of ophthalmology. With the rapid development of molecular biology and immunologic techniques and the deep research on ocular tumor related genes, it becomes possible to diagnose and treat malignant tumors from the molecular level. The tumor necrosis factor related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) super family, is a promising candidate, either alone or in combination with established cancer therapies, since it can initiate apoptosis through the activation of their death receptors. The ability of TRAIL to selectively induce apoptosis of transformed, virus-infected or tumor cells but not normal cells promotes the development of TRAIL-based cancer therapy. Here, we will review TRAIL and its receptors' structure, function, mechanism of action and application in ocular tumors therapy.

Guiding function of positron emission tomographycomputed tomography examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma

AIM:To explore the role of positron emission tomographycomputed tomography(PET-CT)examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma(OAML).METHODS:The general clinical data,postoperative PET-CT results,treatment regimens,and the prognosis of 21 histopathologically confirmed OAML patients between October 2017 and September 2021 were collected.Among the 21 patients,five patients underwent surgical treatment alone,13 patients underwent surgical treatment combined with radiotherapy,and three patients underwent surgical treatment combined with chemotherapy.RESULTS:The follow-up period ranged from 8 to 79mo,with four cases of recurrence and no deaths.Through PETCT examination,two patients exhibited both local ocular metabolic elevation and systemic metastasis,and one of these patients had cervical lymph node metastasis,while the other had submandibular and parotid gland metastasis.Nine patients showed only local ocular metabolic elevation,while 10 patients had no abnormal metabolic activity locally.CONCLUSION:PET-CT examination plays a crucial role in detecting residual lesions and recurrence following tumor resection,aiding in precise disease staging,and facilitating the development of personalized treatment plans,ultimately improving patient prognosis.

An Overview of the Control System for Dose Delivery at the UCSF Dedicated Ocular Proton Beam

Since 1978, the University of California San Francisco (UCSF) Ocular Tumor Program has been using particle therapy for treating ocular patients with malignant as well as benign eye disease. Helium ion beams were used initially and were produced by two synchrotron-based systems: first by the 184-inch synchro-cyclotron and later by the Bevalac, at the Lawrence Berkeley National Laboratory (LBNL). Since 1994, protons, produced by a cyclotron-based system at the Crocker Nuclear Laboratory (CNL) Eye Treatment Facility (ETF), have been used for this purpose. The CNL cyclotron produces a 67.5 MeV beam, allowing for a uniquely homogeneous beam for eye treatment, without degradation of the beam or manipulation of the beam line. This paper describes, in detail, the control system for beam delivery, as implemented for measuring and delivering the radiation to ocular tumors at CNL. The control system allows for optimal delivery and rapid termination of the irradiation after the desired dose is achieved. In addition, several safeguard systems are discussed, as these are essential for such a system in the event of failure of software, electronics, or other hardware. The QA analysis shows that the total range of the proton beam is 30.7 ± 1.0 mm in water at iso-center. The beam distal penumbra (80% - 20%) is 1.1 mm for a range-modulated beam at a collimator to iso-center distance of 50 mm. Daily QA checks confirm that the range and modulation is within 0.1 mm. The beam flatness and symmetry in a 25 mm diameter beam are ±1% - 2%. Variation in the daily dosimetry system, as compared to standard dosimetry, is within ±3.5%, with a mean variation of 0.72(±1.9)% and 0.85(±2.3)% for segmented transmission ionization chambers IC1 (upstream) and IC2 (downstream), respectively. From May 1994 to the end of 2015, UCSF has treated 1838 proton ocular patients at the Davis ETF. During this period, no treatments were missed due to any cyclotron or control system failures. The overall performance, maintenance, and quality assurance of the cyclotron and the ocular control system have been excellent.

Whole Body Positron Emission Tomography/Computed Tomography （PET/CT） in the Evaluation of Ophthalmic Tumors

The clinical value of whole body positron emission tomography/computed tomography （PET/CT） as an imaging tool in diagnosis of ophthalmic tumors was investigated. The retrospective observational case series were performed on the patients with suspected ophthalmic tumors who underwent whole body PET/CT. The golden standard of diagnosis was the final pathological diagnosis or the results of long-term follow-up for patients without surgery/ biopsy. PET/CT findings were compared with the golden standard. The sensitivity, specificity, accuracy an^t positive likelihood ratio of PET/CT in the detection of ophthalmic tumors were calculated. The clinical application of PET/CT in different types of ophthalmic tumors was evaluated. The results showed that 30 patients （18 males and 12 females） with a mean age of 43.0 years （range 4-63 years） were collected. The mean sizes of orbital tumors and intraocular tumors were 26.8 mmxl7.8 mm and 11.2 minx6.1 mm, respectively. The overall sensitivity, specificity, accuracy and positive likelihood ratio of whole body PET/CT in ophthalmic tumors were 76.5%, 71.4%, 75.0% and 2.67, and were 62.5%, 100% and 70.0% in intraocular tumors, and those were 100%, 60.0% and 84.6% in orbital tumors, respectively. PET/CT findings were applied to help make appropriate treatment options in 27 out of 30 patients （90.0%）, and 12 （40.0%） patients changed the treatment strategy. False negative results in 4 cases and false positive results in 2 cases were observed in this series. It was suggested that PET/CT was an effective imaging modality in detecting, diagnosing and developing therapeutic schedule for patients with ophthalmic tumors. It was more sensitive and accurate for detecting orbital tumors than for detecting intraocular tumors.

Targeted therapy for malignant ocular melanomas

In a comprehensive literature review,PubMed,Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of ocular tumors,mainly conjunctival and uveal melanoma(UM).Conjunctival malignant melanomas showed similarities in clinical and genetic aspects with cutaneous melanomas.Many therapies with checkpoint inhibitors already established for cutaneous melanomas may be a treatment option for conjunctival malignant melanomas with shared traits.Existing targeted therapies are for example checkpoint inhibitors like pembrolizumab or nivolumab.As a corollary,due to marked differences in clinics and genetics between UMs and conjunctival melanomas(CMs)or cutaneous melanomas,it has remained elusive whether the available possibilities of molecular targeted therapy will be an option for the therapy of metastasizing UMs.Possible novel ways of treating UM are being explored.Fotemustine or the inoculation of dendritic cells with tumorous RNA or sunitinib in combination with cisplatin and or tamoxifen may be used in future to treat UM.While CM are treatable using targeted therapies,UM have not been researched enough to find working targeted therapy options.Further research has to be done in order to find acceptable treatment options.

Preclinical models in ophthalmic oncology-a narrative review

Objective:This review serves as a comprehensive description and summary of currently available preclinical models of three tumors in ophthalmic oncology:conjunctival melanoma(CM),uveal melanoma(UM),and retinoblastoma.Background:Malignant melanomas are the most common tumors of the eye in adults,most often localized in the uvea and conjunctiva.Although the primary tumor can be successfully eliminated in many cases,nearly one in two UMs-and one in three CMs-are fatal to the patient due to metastasis.Effective therapies for metastatic uveal and CMs are unfortunately still not available,so there is an urgent need for new therapeutic strategies to improve prognosis quoad vitam and prolong the survival of melanoma patients.Another widely known tumor of the eye is retinoblastoma,which is the most common pediatric ocular malignancy,occurring in approximately 1 in 15,000-18,000 live births.Overall,it is considered well treatable,with a survival rate of approximately 90%at 3 years,although fatal if untreated.For a long time,enucleation was also considered the treatment of choice,with bilateral cases having one eye irradiated and the eye with the more advanced tumor removed.Since the 1990s,however,systemic chemotherapy has been predominantly used to preserve the quality of life and vision of young patients,although the cellular activity of the retinoblastoma often remains after treatment with chemotherapeutic agents.Prognosis of the disease is immensely depending on the stage and time of diagnosis and is varying between countries due to different developmental status of health care systems.Methods:We review recent advances in the available literature on established preclinical models in CM,UM,and retinoblastoma.In addition,we discuss the advantages and limitations of these models and provide an overview of current alternatives to animal testing in preclinical studies.Conclusions:In the case of all three diseases,further research is needed for improved therapeutic options.Animal models in particular are indispensable for cancer research in order to mimic the extremely complex processes of human carcinogenesis,physiology and progression.Certainly,animal studies do not easily translate to human diseases due to biological differences and limitations.However,they continue to serve as the primary source and link between in vitro testing and clinical studies in patients.In order to minimize animal experiments and possibly even replace them in the future,alternatives such as 3D cell cultures and in silico predictions are useful and insightful additions and require further development.Still,no currently available preclinical model can be fully translated to some of here described diseases.Nevertheless,they all provide essential insights and knowledge that should be of use in the future for better understanding and pursuit of new therapeutic strategies.