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Ophthalmology Apr 2024To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia.
PURPOSE
To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia.
DESIGN
Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter.
PARTICIPANTS
A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries.
INTERVENTIONS
Chemotherapy, radiotherapy, enucleation, and orbital exenteration.
MAIN OUTCOME MEASURES
Enucleation and death.
RESULTS
Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively.
CONCLUSIONS
At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia.
FINANCIAL DISCLOSURE(S)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Topics: Child; Humans; Male; Female; Infant; Child, Preschool; Retinoblastoma; Retinal Neoplasms; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Asia; Retrospective Studies; Eye Enucleation
PubMed: 37839559
DOI: 10.1016/j.ophtha.2023.10.015 -
Korean Journal of Ophthalmology : KJO Feb 2021To review the occurrence of new solitary tumors during and after intravenous chemotherapy against retinoblastoma.
PURPOSE
To review the occurrence of new solitary tumors during and after intravenous chemotherapy against retinoblastoma.
METHODS
From 115 eyes of 78 patients with a diagnosis of intraocular retinoblastoma who underwent intravenous chemotherapy and focal treatment without prior treatment, patient demographics, age at diagnosis, laterality, classification (Reese-Ellsworth and International Classification of Retinoblastoma), and treatment options were recorded. In addition, the occurrence of small tumors during and after chemotherapy was documented with a detailed review of medical records and fundus photographs.
RESULTS
Of a total of 115 eyes of 78 consecutive patients, new solitary tumors were observed in 50 eyes (50 / 115, 43%) of 40 patients (40 / 78, 51%). Multinominal logistic regression analyses showed that age at diagnosis (before 1 year) and vitreal seeding at diagnosis were linked to the development of isolated and miliary tumors, respectively. Kaplan-Meier analyses demonstrated that all small tumors developed with 20 months from the start of chemotherapy. Twenty-eight eyes (28 / 34, 82%) were salvaged with additional focal treatment in 34 eyes with isolated tumors.
CONCLUSIONS
Small tumors were observed during and after chemotherapy against retinoblastoma in patients who underwent intravenous chemotherapy and focal treatment. It is necessary to promptly identify and address small tumors for the preservation of eyeball and vision.
Topics: Antineoplastic Combined Chemotherapy Protocols; Eye Enucleation; Humans; Infant; Retinal Neoplasms; Retinoblastoma; Retrospective Studies
PubMed: 33596616
DOI: 10.3341/kjo.2020.0115 -
The Journal of International Medical... Jun 2021To identify key genes involved in occurrence and development of retinoblastoma.
OBJECTIVE
To identify key genes involved in occurrence and development of retinoblastoma.
METHODS
The microarray dataset, GSE5222, was downloaded from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between unilateral and bilateral retinoblastoma were identified and functional enrichment analysis performed. The protein-protein interaction (PPI) network was constructed and analysed by STRING and Cytoscape.
RESULTS
DEGs were mainly associated with activation of cysteine-type endopeptidase activity involved in apoptotic process and small molecule catabolic process. Seven genes (WAS, GNB3, PTGER1, TACR1, GPR143, NPFF and CDKN2A) were identified as HUB genes.
CONCLUSION
Our research provides more understanding of the mechanisms of the disease at a molecular level and may help in the identification of novel biomarkers for retinoblastoma.
Topics: Biomarkers, Tumor; Computational Biology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 34187205
DOI: 10.1177/03000605211022210 -
Indian Journal of Ophthalmology Feb 2023
Topics: Humans; Retinoblastoma; Developing Countries; Retinal Neoplasms; Melphalan
PubMed: 36727311
DOI: 10.4103/IJO.IJO_227_23 -
The Lancet. Child & Adolescent Health Sep 2023Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of...
BACKGROUND
Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of evidence from randomised controlled trials engendered controversy in the administration route of chemotherapy. We aimed to assess the efficacy and safety of intra-arterial chemotherapy compared with intravenous chemotherapy.
METHODS
This open-label, multicentre, randomised trial was done at six hospitals in China. Patients with new-onset unilateral group D or E retinoblastoma (poorly defined, large, or very large tumours, according to the International Intraocular Retinoblastoma Classification) without high-risk clinical factors were included. Patients were randomly assigned (1:1) to receive intra-arterial chemotherapy (injections of 0·5 mg/kg [or depending on age] melphalan with 20 mg carboplatin [first and third cycles] or with 1 mg topotecan [second and fourth cycles]) or intravenous chemotherapy (0·05 mg/kg [or 1·5 mg/m] vincristine, 5 mg/kg [or 150 mg/m] etoposide, and 18·6 mg/kg [or 560 mg/m] carboplatin for six cycles). After intra-arterial chemotherapy, patients received a subcutaneous injection of 0·1 mL nadroparin calcium twice at a 12 h interval. Both intra-arterial and intravenous chemotherapy cycles were completed every 4 weeks. No masking was done, except of independent statisticians, who were masked to the allocation information. The primary outcome was 2-year progression-free globe salvage rate, defined as the time from randomisation to tumour progression or enucleation, whichever occurred first, and was analysed by intention to treat. We also recorded predefined safety outcomes (myelosuppression and ophthalmic arterial stenosis or occlusion) and severe adverse events likely to be related to study treatment. The study is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-15006469, and is complete.
FINDINGS
Between June 1, 2015, and June 1, 2018, 234 patients with newly diagnosed retinoblastoma were screened and 143 eligible patients (median age 23·6 months [IQR 14·0-31·9]) were enrolled and randomly assigned to the intra-arterial chemotherapy group (n=72) or the intravenous chemotherapy group (n=71). At a median follow-up of 35·8 months (IQR 28·4-43·0), the 2-year progression-free globe salvage rate was 53% (38 of 72 patients) in the intra-arterial chemotherapy group and 27% (19 of 71 patients) in the intravenous chemotherapy group (risk ratio 1·97, 95% CI 1·27-3·07, p=0·0020). Myelosuppression was less common in the intra-arterial chemotherapy group than in the intravenous chemotherapy group (37 [51%] of 72 patients vs 50 [70%] of 71 patients; 0·73, 95% CI 0·56-0·96, p=0·021) and less severe (p=0·0070). In the intra-arterial chemotherapy group, two (3%) of 72 patients had ophthalmic artery occlusion and 13 (18%) patients had ophthalmic artery stenosis.
INTERPRETATION
Our findings show that intra-arterial chemotherapy could significantly improve the globe salvage rate in children with advanced unilateral retinoblastoma compared with intravenous chemotherapy, with mild systemic complications and no difference in overall survival rate. Intra-arterial chemotherapy could be an acceptable first-line treatment in children with advanced unilateral retinoblastoma.
FUNDING
Scientific Research Program of the National Health and Family Planning Commission of China, the Clinical Research Plan of Shanghai Hospital Development Center, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.
Topics: Humans; Child; Infant; Child, Preschool; Retinoblastoma; Carboplatin; Constriction, Pathologic; China; Retinal Neoplasms; Randomized Controlled Trials as Topic
PubMed: 37536351
DOI: 10.1016/S2352-4642(23)00141-4 -
Indian Journal of Ophthalmology Jul 2023Retinoblastoma is a retinal cancer that affects children and is the most prevalent intraocular tumor worldwide. Despite tremendous breakthroughs in our understanding of... (Review)
Review
Retinoblastoma is a retinal cancer that affects children and is the most prevalent intraocular tumor worldwide. Despite tremendous breakthroughs in our understanding of the fundamental mechanisms that regulate progression of retinoblastoma, the development of targeted therapeutics for retinoblastoma has lagged. Our review highlights the current developments in the genetic, epigenetic, transcriptomic, and proteomic landscapes of retinoblastoma. We also discuss their clinical relevance and potential implications for future therapeutic development, with the aim to create a frontline multimodal therapy for retinoblastoma.
Topics: Child; Humans; Retinoblastoma; Proteomics; Retinal Neoplasms; Combined Modality Therapy
PubMed: 37417104
DOI: 10.4103/IJO.IJO_3172_22 -
Pediatric Blood & Cancer May 2021Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid...
Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid Tumors (RECIST) provide radiological standards for assessment of solid tumors. However, no such guidelines exist for the evaluation of intraocular cancer, and ocular oncology clinical trials have largely relied on indirect measures of therapeutic response-such as progression-free survival-to evaluate the efficacy of treatment agents. Herein, we propose specific criteria for evaluating treatment response of retinoblastoma, the most common pediatric intraocular cancer, and emphasize a multimodal imaging approach for comprehensive assessment of retinoblastoma tumors in clinical trials.
Topics: Humans; Multimodal Imaging; Response Evaluation Criteria in Solid Tumors; Retinal Neoplasms; Retinoblastoma
PubMed: 33624399
DOI: 10.1002/pbc.28964 -
Biochimica Et Biophysica Acta. Gene... Sep 2023Retinoblastoma (RB) is a common malignancy that primarily affects pediatric populations. Although a well-known cause of RB is RB1 mutation, MYCN amplification can also...
Retinoblastoma (RB) is a common malignancy that primarily affects pediatric populations. Although a well-known cause of RB is RB1 mutation, MYCN amplification can also lead to the disease, which is a poor prognosis factor. Studies conducted in various tumor types have shown that MYCN inhibition is an effective approach to impede tumor growth. Various indirect approaches have been developed to overcome the difficulty of directly targeting MYCN, such as modulating the super enhancer (SE) upstream of MYCN. The drug used in this study to treat MYCN-amplified RB was THZ1, a CDK7 inhibitor that can effectively suppress transcription by interfering with the activity of SEs. The study findings confirmed the anticancer activity of THZ1 against RB in both in vitro and in vivo experiments. Therapy with THZ1 was found to affect numerous genes in RB according to the RNA-seq analysis. Moreover, the gene expression changes induced by THZ1 treatment were enriched in ribosome, endocytosis, cell cycle, apoptosis, etc. Furthermore, the combined analysis of ChIP-Seq and RNA-seq data suggested a potential role of SEs in regulating the expression of critical transcription factors, such as MYCN, OTX2, and SOX4. Moreover, ChIP-qPCR experiments were conducted to confirm the interaction between MYCN and SEs. In conclusion, THZ1 caused substantial changes in gene transcription in RB, resulting in inhibited cell proliferation, interference with the cell cycle, and increased apoptosis. The efficacy of THZ1 is positively correlated with the degree of MYCN amplification and is likely exerted by interfering with MYCN upstream SEs.
Topics: Child; Humans; N-Myc Proto-Oncogene Protein; Retinoblastoma; Cyclin-Dependent Kinase-Activating Kinase; Cyclin-Dependent Kinases; Retinal Neoplasms; SOXC Transcription Factors
PubMed: 37536559
DOI: 10.1016/j.bbagrm.2023.194964 -
Radiologie (Heidelberg, Germany) Dec 2022Retinoblastoma is the most common malignant eye tumor in children and is associated with tumor predisposition syndrome (RB1 mutation) in up to 40% of cases. Imaging is... (Review)
Review
BACKGROUND
Retinoblastoma is the most common malignant eye tumor in children and is associated with tumor predisposition syndrome (RB1 mutation) in up to 40% of cases. Imaging is an important part of the diagnostic workup of children with retinoblastoma both during the initial diagnosis and follow-up.
OBJECTIVES
The goal of this review is to present the current state-of-the-art regarding imaging of children with retinoblastoma, including technical background and diagnostic clues with a brief discussion of future prospects. In addition, we summarize the general clinical diagnostic workup and therapeutic options.
MATERIALS AND METHODS
Review of the literature and our own experience in the imaging of retinoblastoma.
CONCLUSION
High-resolution magnetic resonance imaging (MRI) is the imaging modality of choice in children with retinoblastoma for diagnosis (estimation of diagnosis/differential diagnosis, evaluation of local and intracranial tumor extension) and during follow-up. Despite the characteristic calcifications, computed tomography (CT) examinations are no longer indicated in these patients. Due to the high association with tumor predisposition syndrome, genetic counselling is recommended.
Topics: Child; Humans; Retinoblastoma; Retinal Neoplasms; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Eye Neoplasms
PubMed: 35969246
DOI: 10.1007/s00117-022-01052-0 -
Current Stem Cell Research & Therapy 2024The theory of cancer stem cells is a breakthrough discovery that offers exciting possibilities for comprehending the biological behavior of tumors. More and more... (Review)
Review
The theory of cancer stem cells is a breakthrough discovery that offers exciting possibilities for comprehending the biological behavior of tumors. More and more evidence suggests that retinoblastoma cancer stem cells promote tumor growth and are likely to be the origin of tumor formation, drug resistance, recurrence, and metastasis. At present, some progress has been made in the verification, biological behavior, and drug resistance mechanism of retinoblastoma cancer stem cells. This article aims to review the relevant research and explore future development direction.
Topics: Humans; Retinoblastoma; Neoplastic Stem Cells; Drug Resistance, Neoplasm; Animals; Retinal Neoplasms
PubMed: 37815190
DOI: 10.2174/011574888X252989230921065809