Once uveal melanoma (UM) has distant metastasis, the median survival time of the patient is less than 12 months. There is currently a lack of standard treatment for metastatic UM. In recent years, immunotherapy is splendid in the field of oncology. Immune checkpoint therapy, cancer vaccine therapy and T cell adoptive therapy have been applied to UM therapy. However, most of the clinical effects are limited and the survival benefit is not high. The recent early research results of the new immunotherapeutic drug IMCgp100 are encouraging.
Objective To observe the different clinical response patterns of uveal melanoma (UM) patients after external scleral plaque radiotherapy (PRT), and to investigate the risk factors of secondary enucleation after treatment failure. MethodsA single-centre retrospective study. Demographic baseline characteristics and clinical data were collected from 465 UM patients treated with 125I external scleral PRT at Beijing Tongren Hospital from March 2011 to September 2017. Among them, 217 were male and 248 were female, tumor all occurred monocularly. The mean age of subjects was 46.7±12.1 years. Reasons for secondary enucleation included local tumor treatment failure, glaucoma, scleral necrosis and patient request. Tumor grading was based on the grading standards established by the American Joint Committee on Cancer (AJCC). The pattern of tumor response after PRT was classified as degenerated type, growth type, stable type or other types according to literature criteria. The median follow-up time after PRT was 59 months to observe tumor changes. Complete follow-up records of 3 or more color doppler ultrasound imaging (CDI) was available in 245 cases. A t-test was performed to compare the patient's age, intraocular pressure, best corrected visual acuity, tumor thickness and maximum basal diameter before treatment; a chi-square test was performed to compare the patient's gender, AJCC T classification of the tumor, whether the ciliary body was involved, presence of subretinal fluid, optic disc invasion and vitreous hemorrhage, tumor shape and location. Kaplan-Meier survival analysis was used to estimate the cumulative probability of secondary enucleation after extra-scleral PRT. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the relationship between tumor characteristics and secondary enucleation after extra-scleral PRT. ResultsAmong 465 patients, eecondary enucleation was performed on 78 (16.8%, 78/465) patients during the follow-up period. The 1, 3 and 5 year secondary enucleation rates were 5.4%, 9.3% and 17.1%, respectively. Eye preservation was successful in 387 cases (83.2%, 387/465). Patients treated by secondary enucleation had a larger maximum basal diameter of tumor, a higher proportion of irregular and diffuse morphology, a cumulative macular involved and a higher AJCC T classification, the difference was statistically significant (P＜0.05). There were 115, 76, 27, and 27 cases of degenerated type, stable type, growth type, and other type, respectively. The tumor thickness of the growth type and other types was significantly smaller than that of the degenerated type and the stable type, and the difference was statistically significant (P＜0.05). Univariate Cox analysis showed that the maximum basal diameter of the tumor (HR=1.19), tumor thickness (HR=1.08), AJCC T classification (HR=1.90), growth type response pattern (relative to degenerated type response pattern) (HR=4.20) was associated with failure of eye preservation (P＜0.05). In the multivariate Cox analysis, the largest tumor basal diameter (HR=1.24) and the growth type response pattern (relative to the degenerated type response pattern) (HR=4.59) were still associated with failure of eye preservation (P＜0.05). ConclusionsThe tumor thickness of UM patients with growing and other response patterns after PRT is smaller before treatment; the maximum basal diameter of the tumor and the growing response pattern are independent risk factors for secondary enucleation.
Uveal melanoma (UM) is one of the most common primary intraocular malignancy in adults. The incidence of UM is lower in Asia than in Europe and the United States, however, the age of onset of UM patients in Asia is earlier than in the European and American populations. With the improvement of economic living standards in recent years, UM as a rare intraocular tumor has been gradually recognized by the public. In the past 10 years, the research of UM in China has been characterized by a large number and rapid development. Among them, the direction of molecular genetics represented by non-coding RNA, the frontier development of potential anticancer drugs for UM and Chinese traditional medicines are the research hotspots for scholars in China. In the past 10 years, China has made a relatively complete understanding and research progress on the pathogenesis, diagnosis and treatment of UM. On the other hand, compared with European and American countries, China still lacks in frontier research such as immunotherapy. With the further efforts of Chinese ophthalmology researchers and research teams, and with the further development of scientific research in my country, it is believed that the mechanism affecting tumors can be further elucidated, providing more possibilities for treatment and improving the prognosis of UM patients in China.
Uveal melanoma (UM) is an aggressive and lethal tumor in the eye. The complexity and heterogeneity of UM and its microenvironment leads to a lack of strategies for early prevention and treatment of metastases. Single-cell sequencing technologies provide critical insights into deciphering the complexity of intratumor heterogeneity and the microenvironment by enabling genomic, transcriptomic, and epigenetic analysis at the single-cell level. With the help of bioinformatics analysis combined with artificial intelligence algorithms, molecular indicator systems related to prognosis as well as therapeutic targets can be found, which can provide a basis for guiding the selection of clinical treatment plans. However, the single-cell sequencing technology also has certain limitations, such as high sample requirements, expensive and time-consuming sequencing. It is believed that with the improvement of science and technology and the update of analytical methods, these shortcomings can be gradually solved, and this rare tumor will eventually be overcome in the future, and the goal of long-term survival of UM patients will be achieved.
Inherited retinal diseases (IRD) are a group of genetic disorders with high genetic and clinical heterogeneity. Patients with IRD may have their clinical diagnosis confirmed by genetic testing. Over the past 30 years, rapid advances in molecular genetics have raised the disease-causing gene variant detection rate and the accuracy of genetic testing, which provide hope to patients. The genetic diagnosis of patients with IRD is complicated due to the overlapping clinical phenotypes, and the fact that different variants lead to different phenotypes and severity even of the same gene. It is very important to overall evaluate the clinical phenotype of patients, precisely select genetic testing methods, and reasonably define disease-causing genes and variants during genetic diagnosis, which can guide the patient's subsequent treatment and provide genetic counseling.
Inherited retinal diseases (IRD) are a group of genetic disorders with high genetic and clinical heterogeneity. Genetic diagnosis has become one essential method for patients with IRD in their clinical management. So far, about 30% of the patients with IRD cannot get molecular diagnosis (no pathogenic variant detected or only mono-allele variant identified in AR genes) using target or whole exome sequencing. Most missing heritability or variants for these patients were variants located in no-coding regions (deep intron or promoter regions) and structure variants of the known IRD genes. It is more challenge to reveal this kind of missing variants, which need using whole genome sequencing combined with other cellular or molecular assays.