181 results on '"Trilateral retinoblastoma"'
Search Results
2. Histopathology and molecular pathology of pediatric pineal parenchymal tumors.
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Vasiljevic, Alexandre
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MOLECULAR pathology , *PEDIATRIC pathology , *GENETIC disorders , *TUMORS in children , *CHILD patients - Abstract
Pineal parenchymal tumors in children are rare. They consist of two main types, pineoblastoma (PB) and pineal parenchymal tumor of intermediate differentiation (PPTID), which are World Health Organization (WHO) grade 4 and grade 2–3 respectively. PBs are divided into four distinct molecular groups: PB-miRNA1, PB-miRNA2, PB-RB1, and PB-MYC/FOXR2. PB-RB1 and PB-MYC/FOXR2 affect young children and are associated with a dismal prognosis. PB-miRNA1 and PB-miRNA2 groups affect older children and follow a more favorable course. They are characterized by mutually exclusive alterations in genes involved in miRNA biogenesis, including DICER1, DROSHA, and DGCR8. They may be sporadic or may represent one manifestation of DICER1 syndrome. PB-RB1 tumors show alterations in the RB1 gene and may develop in the setting of congenital retinoblastoma, a condition known as "trilateral retinoblastoma." In the pediatric population, PPTIDs typically affect adolescents. They are characterized by small in-frame insertions in the KBTBD4 gene which is involved in ubiquitination. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Tandem high‐dose chemotherapy followed by autologous stem cell transplantation: An infant with trilateral retinoblastoma.
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Toret, Ersin, Ozdemir, Zeynep Canan, Zengin Ersoy, Gizem, Oztunali, Cigdem, Bozkurt, Ceyhun, and Kebudi, Rejin
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STEM cell transplantation , *RETINOBLASTOMA , *MAGNETIC resonance imaging , *STRABISMUS , *CANCER chemotherapy , *INFANTS - Abstract
Background: Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Advanced RB, associated with exceedingly poor prognosis, requires more intensive multiagent chemotherapy than conventional regimens. Rescue of the bone marrow after intensive chemotherapy is achieved with stem cell transplantation. The sequential courses (tandem transplantation) of high‐dose chemotherapy followed by autologous stem cell transplantation allow for even greater dose intensity in consolidation with the potential to use different active chemotherapeutics at each transplant and have proven feasible and successful in treating children with recurrent/refractory solid tumors. Case Description: We report an infant with trilateral high‐risk RB who received tandem high‐dose chemotherapy (HDC) followed by autologous stem cell transplantation after the conventional chemotherapy. A 5‐month‐old female patient presented with strabismus, and the ophthalmoscopic examination showed intraocular tumoral lesions in both eyes. Magnetic resonance imaging (MRI) concluded the trilateral retinoblastoma diagnosis due to a tumoral mass in the optic chiasm. The follow‐up ophthalmologic examinations and the MRI detected stable disease after six cycles of multiagent chemotherapy. Conclusions: Rescue with autologous stem cell transplantation after HDC allows for an increase in chemotherapy intensity. Tandem transplantation provides the chance to perform different chemotherapeutics at each transplant and enables an increase in the chemotherapy intensity, thus providing a positive effect on disease‐free survival. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Asynchronous pineoblastoma is more likely after early diagnosis of retinoblastoma: a meta‐analysis.
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de Jong, Marcus C., Shaikh, Furqan, Gallie, Brenda, Kors, Wijnanda A., Jansen, Robin W., Dommering, Charlotte, de Graaf, Pim, Moll, Annette C., Dimaras, Helen, Shroff, Manohar, Kivelä, Tero T., and Soliman, Sameh E.
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EARLY diagnosis , *RETINOBLASTOMA , *MEDICAL screening , *MAGNETIC resonance imaging - Abstract
Purpose: To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening. Methods: We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta‐analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis. Results: Seventy‐nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs. Conclusions: An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma. [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
- View/download PDF
5. Trilateral Retinoblastoma
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Kim, Jonathan W., Dunkel, Ira J., Berry, Jesse L., editor, Kim, Jonathan W., editor, Damato, Bertil E., editor, and Singh, Arun D., editor
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- 2019
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6. Retinoblastoma with significant intravitreal haemorrhage: a rare presentation
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Rinkey Chaudhary, Saurabh Goyal, Tapendra Tiwari, and Rajaram Sharma
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medicine.medical_specialty ,genetic structures ,Trilateral retinoblastoma ,Retinoblastoma ,business.industry ,Retinal Neoplasms ,Intraocular tumour ,Infant ,First year of life ,Hemorrhage ,General Medicine ,medicine.disease ,eye diseases ,Neoplasm Seeding ,Ophthalmology ,Intravitreal Injections ,medicine ,Humans ,Presentation (obstetrics) ,business ,Antineoplastic Agents, Alkylating ,Melphalan ,Retrospective Studies - Abstract
Retinoblastoma is the most common intraocular tumour of the eye in children. It constitutes 11% of all cancers within the first year of life. In one-third of cases, it occurs bilaterally; usually, before 5 years of age without any gender predilection.[1 2][1] Trilateral retinoblastoma term is used
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- 2023
7. Modeling Developmental and Tumorigenic Aspects of Trilateral Retinoblastoma via Human Embryonic Stem Cells
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Yishai Avior, Elyad Lezmi, Dorit Yanuka, and Nissim Benvenisty
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human embryonic stem cells ,disease modeling ,trilateral retinoblastoma ,RB1 ,ZEB1 ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Human embryonic stem cells (hESCs) provide a platform for studying human development and understanding mechanisms underlying diseases. Retinoblastoma-1 (RB1) is a key regulator of cell cycling, of which biallelic inactivation initiates retinoblastoma, the most common congenital intraocular malignancy. We developed a model to study the role of RB1 in early development and tumor formation by generating RB1-null hESCs using CRISPR/Cas9. RB1−/− hESCs initiated extremely large teratomas, with neural expansions similar to those of trilateral retinoblastoma tumors, in which retinoblastoma is accompanied by intracranial neural tumors. Teratoma analysis further revealed a role for the transcription factor ZEB1 in RB1-mediated ectoderm differentiation. Furthermore, RB1−/− cells displayed mitochondrial dysfunction similar to poorly differentiated retinoblastomas. Screening more than 100 chemotherapies revealed an RB1–/–-specific cell sensitivity to carboplatin, exploiting their mitochondrial dysfunction. Together, our work provides a human pluripotent cell model for retinoblastoma and sheds light on developmental and tumorigenic roles of RB1.
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- 2017
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8. Trilateral retinoblastoma: A systematic review of 211 cases.
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Yamanaka, Ryuya, Hayano, Azusa, and Takashima, Yasuo
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META-analysis , *RETINOBLASTOMA , *BRAIN tumors , *STEM cell transplantation , *CENTRAL nervous system , *CANCER chemotherapy - Abstract
We conducted a systematic review of 72 studies to characterize trilateral retinoblastomas. Kaplan-Meier analysis was used to estimate survival, and statistical significance was assessed by using a log-rank test. We analyzed 211 cases of trilateral retinoblastomas. The average age of onset of retinoblastoma was 0.79 ± 1.38 years, and the average latency period between the onset of retinoblastomas and trilateral retinoblastomas was 1.49 ± 1.76 years. The brain tumors were found before the retinoblastoma diagnosis in 6 cases (3.1%), concurrently in 61 cases (32.1%), and after the retinoblastoma diagnosis in 123 cases (64.7%). Pineal tumors were found in 155 cases (73.4%) and sellar tumors in 46 cases (21.8%). The overall median survival was 10.3 months (95% CI, 8.5-13) and the 5-year survival rate was 15.7%. Central nervous system symptoms were variable and associated with shorter survival in univariate and multivariate analyses. The survival time in patients who received high-dose chemotherapy with stem cell transplant was significantly longer (p = 0.0067) than that of with or without conventional chemotherapy. Twelve long-term survivors were reported, and of these, six patients were treated with high-dose chemotherapy with stem cell transplant and six patients were treated with conventional chemotherapy. It is important that survivors continue to undergo regular medical surveillance in order to detect trilateral retinoblastoma at a potentially curative stage. Trilateral retinoblastoma patients with an irradiation history had shorter survival than those without irradiation history for retinoblastoma. High-dose chemotherapy should be considered as a potential treatment option for trilateral retinoblastomas. [ABSTRACT FROM AUTHOR]
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- 2019
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9. Prenatal diagnosis of bilateral retinoblastomas by multimodality fetal imaging: case report and review of the literature
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Theresa A. Grebe, Monique Riemann, Patricia Cornejo, Luís F. Gonçalves, Dawn Moncrief, and Aparna Ramasubramanian
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medicine.medical_specialty ,Trilateral retinoblastoma ,Offspring ,Retinal Neoplasms ,Enucleation ,Prenatal diagnosis ,Pineal Gland ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,Fetal mri ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Neuroectodermal tumor ,business.industry ,Retinoblastoma ,Ultrasound ,Infant ,medicine.disease ,Magnetic Resonance Imaging ,eye diseases ,030220 oncology & carcinogenesis ,Female ,Radiology ,business - Abstract
Retinoblastoma is the prototypic genetic tumor. Caused by mutations in the RB1 gene, retinoblastomas are heritable in 40% of the cases and, in such cases, tumors are bilateral in 80%, unilateral in 15%, and trilateral in 5% of the cases. Trilateral retinoblastoma is a term that describes bilateral retinoblastomas plus a midline suprasellar or pineal neuroectodermal tumor. Patients with a germline RB1 mutation have 45% chance of having an offspring with retinoblastoma. Prenatal diagnosis is important because the doubling time is fast, ranging from 7 to 15 days. Thus, late diagnosis during infancy is associated with larger tumors and increased risk of death, need for globe enucleation and vision loss. We report a case of bilateral retinoblastomas diagnosed by targeted high-resolution ultrasonography of the orbits at 32 weeks of gestation in a patient at risk. This report demonstrates the feasibility of accurately detecting even tiny retinoblastomas by ultrasound with current technology. We also review prenatally published cases to date and comment on the technical strengths and limitations of ultrasound and fetal MRI for prenatal diagnosis of retinoblastomas.
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- 2021
10. Clinical and magnetic resonance imaging features of 14 patients with trilateral retinoblastoma
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Dengbin Wang, Zhengrong Xia, Qiufeng Yin, Ming Liu, Xunda Ji, Shuxian Chen, Ting Gui, Yuhua Li, and Hui Zheng
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0303 health sciences ,Chemotherapy ,medicine.medical_specialty ,Trilateral retinoblastoma ,medicine.diagnostic_test ,Retinoblastoma ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Magnetic resonance imaging ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030221 ophthalmology & optometry ,medicine ,Volume reduction ,Effective diffusion coefficient ,Original Article ,Radiology, Nuclear Medicine and imaging ,Radiology ,Age of onset ,business ,030304 developmental biology - Abstract
BACKGROUND: Our study aimed to comprehensively investigate the age of onset, magnetic resonance imaging (MRI) features, and prognosis of children with trilateral retinoblastoma (TRB). METHODS: We included 14 patients with TRB diagnosed or followed up in our hospital. The age of onset and MRI features of the intraocular tumor and intracranial lesions were evaluated. A follow-up study was also conducted. RESULTS: A total of 11 participants were diagnosed with concurrent TRB at the age of 11.1±7.4 months, and 3 participants had late-onset TRB at age 37±19.1 months. The incidence of TRB with unilateral eye involvement was 7.1% (1/14). The intraocular tumors showed intense enhancement in contrast-enhanced T1-weighted images (WI) and significant diffusion restriction in diffusion WI (DWI) with an apparent diffusion coefficient (ADC) of (0.619±0.22)×10(−3) mm(2)/s. The intracranial lesions showed similar DWI aspects with an ADC value of (0.680±0.206)×10(−3) mm(2)/s. Therapeutically, 8 participants had a period of intraocular tumor stabilization and significant intracranial lesion volume reduction after chemotherapy, and 6 participants had given up treatment. Only 2 participants who simultaneously received high-dose chemotherapy and autologous hematopoietic stem cell rescue were still alive with no recurrence at 24 and 54 months of follow-up. The 1-, 2-, and 3-year overall survival (OS) rates were 80%, 18.75%, and 12.5%, respectively. CONCLUSIONS: Patients with unilateral or bilateral RB can develop TRB. The intraocular and intracranial tumors showed slightly different ADC values. High-dose chemotherapy, combined with stem cell rescue can significantly improve survival. A long term and scheduled follow-up before 60 months of age is necessary for screening later-onset TRB patients.
- Published
- 2021
11. A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma
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Kalle Nummi, Carol P. S. Lam, Phillipa Sharwood, Tero Kivelä, Brenda L. Gallie, Adriana Fandiño, Quah Boon Long, Vera Yarovaya, Guillermo Chantada, Sonia Moorthy, Jason C. S. Yam, Tatiana L Ushakova, Jaume Català, Matthew W. Wilson, Marco A. Ramirez-Ortiz, Winnie W. Y. Lau, Lorna Renner, Junyang Zhao, Ashwin Mallipatna, Chengyue Zhang, Ankit Singh Tomar, Vikas Khetan, V.G. Polyakov, Vera Adobea Essuman, Elizabeth Esparza-Aguiar, Suganeswari Ganesan, Jonathan W. Kim, Olga V Yugay, Genoveva Correa-Llano, Andrey A. Yarovoy, Paula Schaiquevich, Paul T. Finger, Elena Kotova, and Yacoub A. Yousef
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0303 health sciences ,medicine.medical_specialty ,Trilateral retinoblastoma ,business.industry ,Mortality rate ,Enucleation ,Cancer ,medicine.disease ,Confidence interval ,3. Good health ,Metastasis ,03 medical and health sciences ,Ophthalmology ,0302 clinical medicine ,Internal medicine ,030221 ophthalmology & optometry ,Medicine ,business ,Pathological ,030304 developmental biology ,Cancer staging - Abstract
Purpose To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). Design International, multicenter, registry-based retrospective case series. Participants A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. Main Outcome Measures Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan–Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. Results Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan–Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97–99) for cT1b and cT2a, 96% (95% CI, 95–97) for cT2b, 89% (95% CI, 88–90) for cT3 tumors, and 45% (95% CI, 31–59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P Conclusions Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.
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- 2020
12. Asynchronous pineoblastoma is more likely after early diagnosis of retinoblastoma : a meta-analysis
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Charlotte J. Dommering, Brenda L. Gallie, Helen Dimaras, Sameh E. Soliman, Tero Kivelä, Wijnanda A. Kors, Robin W. Jansen, Marcus C. de Jong, Manohar Shroff, Furqan Shaikh, Pim de Graaf, Annette C. Moll, HUS Head and Neck Center, Silmäklinikka, Helsinki University Hospital Area, Radiology and nuclear medicine, Pediatric surgery, CCA - Cancer Treatment and quality of life, Human genetics, Ophthalmology, ACS - Diabetes & metabolism, APH - Quality of Care, and APH - Health Behaviors & Chronic Diseases
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Pediatrics ,medicine.medical_specialty ,PNET ,MRI-BASED ASSESSMENT ,Trilateral retinoblastoma ,pineal gland ,Retinal Neoplasms ,Asymptomatic ,retinoblastoma ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,magnetic resonance imaging ,QUALITY ,In patient ,3125 Otorhinolaryngology, ophthalmology ,Stage (cooking) ,10. No inequality ,pineoblastoma ,Pineoblastoma ,AGED 0-5 YEARS ,medicine.diagnostic_test ,Brain Neoplasms ,Retinoblastoma ,business.industry ,Infant ,Magnetic resonance imaging ,General Medicine ,medicine.disease ,Ophthalmology ,Early Diagnosis ,TRILATERAL RETINOBLASTOMA ,PINEAL-GLAND ,Meta-analysis ,030221 ophthalmology & optometry ,medicine.symptom ,LARGE POPULATION ,business ,CONSENSUS ,Pinealoma ,030217 neurology & neurosurgery ,MRI - Abstract
PURPOSE: To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening.METHODS: We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta-analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis.RESULTS: Seventy-nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs.CONCLUSIONS: An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma.
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- 2022
13. Serial Case : Unilateral Dan Trilateral Retinoblastoma
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Hisbulloh HIsbulloh and Farah Hendara
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medicine.medical_specialty ,Trilateral retinoblastoma ,business.industry ,Ophthalmology ,Medicine ,business - Abstract
LATAR BELAKANG Retinoblastoma adalah tumor intraocular pada anak. Insidensi diperkirakan 1 dalam 15.000 pada 34.000 kelahiran. Retinoblastoma trilateral merupakan kombinasi yang jarang dari unilateral atau bilateral retinoblastoma dengan neoplasma intrakranial neuroblastik, biasanya ditemukan di daerah pineal atau daerah suprasellar. Dalam kasus retinoblastoma trilateral , prognosisnya buruk dengan tingkat kelangsugan hidup antara 9 sampai 13 bulan setelah diagnosis. LAPORAN KASUS Kasus 1, anak laki-laki berusia 1 tahun dengan keluhan leukokoria mata kanan, proptosis, kemerahan, kelopak mata bengkak dan juga memiliki riwayat perdarahan di mata kanan. Pemeriksaan CT scan menunjukkan lesi padat dengan kalsifikasi pada aspek posterior mata kiri (AP 1,32 x LL 1,72 x CC 0,7 cm). Kontras CT mata kanan menunjukkan massa jaringan lunak dengan kalsifikasi (AP 3,57 x LL 3,1 x CC 3,1 cm), meluas ke retrobulbar, saraf optik menebal dan massa parasellar yang enhance(AP 2,6 x LL 2,5 x CC 2,2 cm) Kasus 2, anak laki-laki berusia 2 tahun dengan keluhan mata kanan tampak plak putih yang semakin melebar. Pada pemeriksaan CT scan menunjukan lesi pada inhomogen irregular disertai kalsifikasi pada intra bulbus occuli kanan. PEMBAHASAN Retinoblastoma bisa terjadi baik unilateral bilateral, trilateral maupun quadrilateral. Pada kasus ini, pemeriksaan radiologi berperan untuk mendeteksi adanya tumor baik intra ocular maupun ekstra ocular. Diagnosis yang cepat dan tepat dengan menggunakan neuroimaging disertai penatalaksanaan yang agresif dapat menurunkan mortalitas pada pasien dengan retinoblastoma dan tumor intracranial. KESIMPULAN Diagnosis awal dan pengobatan terbukti penting dalam mengatasi perluasan tumor dan metastasis intracranial yang kemungkinan menyebabkan kematian. CT scan dan MRI sangat penting untuk diagnosis awal, perluasan, staging, rencana pengobatan dan follow up pasien retinoblastoma. Kata kunci : retinoblastoma, unilateral, trilateral, CT scan
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- 2020
14. Screening for Pineal Trilateral Retinoblastoma Revisited
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Furqan Shaikh, Wijnanda A. Kors, Brenda L. Gallie, Annette C. Moll, Tero Kivelä, Robin W. Jansen, Helen Dimaras, Pim de Graaf, Sameh E. Soliman, Marcus C. de Jong, and Jonas A. Castelijns
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Pineoblastoma ,endocrine system ,medicine.medical_specialty ,Pediatrics ,Trilateral retinoblastoma ,Retinoblastoma ,business.industry ,medicine.disease ,Intraocular Retinoblastoma ,Asymptomatic ,3. Good health ,03 medical and health sciences ,Ophthalmology ,0302 clinical medicine ,Interquartile range ,030220 oncology & carcinogenesis ,Epidemiology ,030221 ophthalmology & optometry ,medicine ,Pinealoblastoma ,medicine.symptom ,10. No inequality ,business - Abstract
Topic To determine the age up to which children are at risk of trilateral retinoblastoma (TRb) developing, whether its onset is linked to the age at which intraocular retinoblastomas develop, and the lead time from a detectable pineal TRb to symptoms. Clinical relevance Approximately 45% of patients with retinoblastoma—those with a germline RB1 pathogenic variant—are at risk of pineal TRb developing. Early detection and treatment are essential for survival. Current evidence is unclear regarding the usefulness of screening for pineal TRb and, if useful, the age up to which screening should be continued. Methods We conducted a study according to the Meta-analysis of Observational Studies in Epidemiology guidelines for reporting meta-analyses of observational studies. We searched PubMed and Embase between January 1, 1966, and February 27, 2019, for published literature. We considered articles reporting patients with TRb with survival and follow-up data. Inclusion of articles was performed separately and independently by 2 authors, and 2 authors also independently extracted the relevant data. They resolved discrepancies by consensus. Results One hundred thirty-eight patients with pineal TRb were included. Of 22 asymptomatic patients, 21 (95%) were diagnosed before the age of 40 months (median, 16 months; interquartile range, 9–29 months). Age at diagnosis of pineal TRb in patients diagnosed with retinoblastoma at 6 months or younger versus older than 6 months were comparable (P = 0.44), suggesting independence between the ages at diagnosis of intraocular retinoblastoma and pineal TRb. The laterality of intraocular retinoblastoma and its treatment were not associated with the age at which pineal TRb was diagnosed. The lead time from asymptomatic to symptomatic pineal TRb was approximately 1 year. By performing a screening magnetic resonance imaging scan every 6 months after the diagnosis of heritable retinoblastoma (median age, 6 months) until 36 months of age, at least 311 and 776 scans would be required to detect 1 case of asymptomatic pineal TRb and to save a single life, respectively. Conclusions Patients with retinoblastoma are at risk of pineal TRb developing for a shorter period than previously assumed, and the age at diagnosis of pineal TRb is independent of the age at diagnosis of retinoblastoma. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) level of evidence for these conclusions remains low.
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- 2020
15. A Potential Role For Apparent Diffusion Coefficient in the Diagnosis of Trilateral Retinoblastoma
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Jasmine H. Francis, Brian P. Marr, David H. Abramson, Sasan Karimi, Sameer Farouk Sait, Mark M. Souweidane, Ira J. Dunkel, Karim J Rebeiz, and Sofia Haque
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Male ,medicine.medical_specialty ,Trilateral retinoblastoma ,Retinal Neoplasms ,Neuroimaging ,Article ,03 medical and health sciences ,0302 clinical medicine ,Pineal Cyst ,Humans ,Medicine ,Effective diffusion coefficient ,Brain magnetic resonance imaging ,Bilateral retinoblastoma ,Retrospective Studies ,Extramural ,business.industry ,Retinoblastoma ,Infant ,Hematology ,medicine.disease ,body regions ,Diffusion Magnetic Resonance Imaging ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Female ,Radiology ,business ,030215 immunology - Abstract
We attempted to investigate the potential role for apparent diffusion coefficient (ADC) to diagnose trilateral retinoblastoma (TRb) by retrospectively reviewing brain magnetic resonance images of retinoblastoma patients. Observations: The median ADC measured 620.95 for TRb (n=6) and 1238.5 for normal pineal gland in bilateral retinoblastoma (n=8). Monitoring ADC trends aided in establishing the appropriate diagnoses in 3 patients (2 TRb, 1 benign pineal cyst). Conclusions: Our results provide baseline reference data and describe the importance of downward trending ADC which should prompt consideration of TRb. Unchanged high/nonrestricted values (>1000) may distinguish those with benign pineal tissue and obviate invasive neurosurgical procedures.
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- 2020
16. Retinoblastoma in Finland, 1964–2014: incidence and survival
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Tero Kivelä and Kalle Nummi
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Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Trilateral retinoblastoma ,Retinal Neoplasms ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cause of Death ,Epidemiology ,Humans ,Medicine ,Registries ,Family history ,Child ,Finland ,Retrospective Studies ,Cause of death ,business.industry ,Incidence ,Incidence (epidemiology) ,Mortality rate ,Infant, Newborn ,Retinoblastoma ,Infant ,Sensory Systems ,3. Good health ,Cancer registry ,Survival Rate ,Ophthalmology ,Child, Preschool ,030220 oncology & carcinogenesis ,030221 ophthalmology & optometry ,Female ,business ,Cohort study - Abstract
AimsTo determine the incidence of retinoblastoma (Rb) and subsequent survival in the Finnish population during five decades.MethodsThis retrospective observational cohort study comprised all patients with Rb born in Finland during 1964–2014 and diagnosed in 2018 (birth cohort analysis) or diagnosed in 1964–2014 (standard annual analysis), identified from the Finnish Cancer Registry and the national referral centre. We report age-adjusted incidences and survival according to cause of death.ResultsOf children born in 1964–2014, 205 developed Rb, whereas 204 Rbs were diagnosed during these years; 196 belonged to both cohorts. Altogether 80 (38%) of the 213 children had heritable Rb and 19 (9%) had familial disease. The sex ratio was 1.34, suggesting male preponderance. Birth cohort analysis showed a median incidence of 6.2 per 100 000 live births (1:16 130) and less variability as compared with standard annual analysis (12.1, 6.5 and 4.4 per million children 0–4, 0–9 and 0–14 years of age, respectively). The incidence of heritable Rb increased with time, reflecting the increase in familial tumours. Five-year mortality rates from Rb were 6.2% and 7.6% for non-heritable and heritable diseases, respectively, and 35-year mortality rates from second malignancies were 0% and 14.3%, respectively. Family history predicted improved survival, whereas the period of diagnosis did not.ConclusionThe incidence of familial Rb has increased, along with improvement in survival in Finland in 1964–2014, whereas the overall incidence of Rb was stable. Long-term risk of dying of second malignancies after heritable Rb was in line with other countries.
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- 2020
17. Magnetic Resonance Imaging Screening for Trilateral Retinoblastoma
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Ira J. Dunkel, Danielle Novetsky Friedman, Sofia Haque, Sana Qureshi, Mark M. Souweidane, David H. Abramson, and Jasmine H. Francis
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0303 health sciences ,medicine.medical_specialty ,medicine.diagnostic_test ,Trilateral retinoblastoma ,Retinoblastoma ,business.industry ,Incidence (epidemiology) ,Cancer ,Magnetic resonance imaging ,Gene mutation ,medicine.disease ,03 medical and health sciences ,Ophthalmology ,0302 clinical medicine ,Hereditary Retinoblastoma ,Cohort ,030221 ophthalmology & optometry ,medicine ,Radiology ,business ,030304 developmental biology - Abstract
Purpose Magnetic resonance imaging (MRI) has been used for baseline brain imaging and afterward as a screening tool for trilateral retinoblastoma (TRB), but there is no consensus on timing or frequency of screening worldwide. In this study, a cohort of hereditary retinoblastoma patients at increased risk for TRB was identified and the usefulness of aggressive neuroimaging was examined. Design Retrospective review of the medical records and MRI reports of patients with retinoblastoma treated at Memorial Sloan Kettering Cancer Center between January 1, 2006, and December 31, 2016. Participants Three hundred forty-nine total patients with retinoblastoma, including 215 hereditary retinoblastoma patients in the screening group. Methods We reviewed 804 MRI studies of the orbit or brain. Patient and disease characteristics, including laterality, family history, and gene mutation status were analyzed. The impression of every MRI was coded 1 to 5, each value representing a different abnormality. Main Outcome Measures We calculated the incidence of TRB in patients with germline disease as well as the incidence of screening MRI scans showing TRB. Results Among our hereditary retinoblastoma screening cohort (n=215) 4 patients with TRB were identified on screening MRI. All 4 patients showed bilateral disease, pineal gland tumors, and a latency period of at least 1 year. Three of the 4 were deceased by the end of the study. The incidence of TRB diagnosis was 1.9% (95% confidence interval [CI], 0.7%–4.9%). Of the 804 screening MRI scans performed on the screening cohort, 691 (86%) were unremarkable and 4 reported a lesion suspicious for TRB. The overall incidence of detecting TRB on screening MRI in the at-risk cohort was 0.5% (95% CI, 0.2%–1.3%) with a number needed to treat of 202. Conclusions All cases of TRB in our center during the study period developed before the patient was 3 years of age and after a total of only 4 lifetime MRIs. Overall survival from TRB was not improved as a result of screening, and many false-positive results required additional, subsequent MRI scans with anesthesia.
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- 2020
18. Molecular subgrouping of primary pineal parenchymal tumors reveals distinct subtypes correlated with clinical parameters and genetic alterations
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Stefan Rutkowski, David W. Ellison, Martin Mynarek, Martin U. Schuhmann, Martin Sill, Christian Thomas, Katja von Hoff, Damian Stichel, Martin Hasselblatt, Andreas von Deimling, Murat Iskar, Peter Lichter, Elke Pfaff, Matthias A. Karajannis, Petra Ketteler, Marc Zapatka, Marcel Kool, Jens Schittenhelm, Dietmar R. Lohmann, Felix Sahm, Marina Rhizova, Anna Kaufhold, Christian Aichmüller, Stefan M. Pfister, Andrey Korshunov, Matija Snuderl, David T.W. Jones, Andrea Wittmann, and Brent A. Orr
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Adult ,Male ,0301 basic medicine ,endocrine system ,Adolescent ,Trilateral retinoblastoma ,Medizin ,Context (language use) ,Biology ,medicine.disease_cause ,Pineal Gland ,Article ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine ,Humans ,Child ,Aged ,Aged, 80 and over ,Pineoblastoma ,Brain Neoplasms ,Retinoblastoma ,Pineocytoma ,Papillary tumor ,DNA Methylation ,Middle Aged ,medicine.disease ,MicroRNAs ,030104 developmental biology ,Case-Control Studies ,Mutation ,DNA methylation ,Cancer research ,Female ,Neurology (clinical) ,Carcinogenesis ,Pinealoma ,030217 neurology & neurosurgery - Abstract
Tumors of the pineal region comprise several different entities with distinct clinical and histopathological features. Whereas some entities predominantly affect adults, pineoblastoma (PB) constitutes a highly aggressive malignancy of childhood with a poor outcome. PBs mainly arise sporadically, but may also occur in the context of cancer predisposition syndromes including DICER1 and RB1 germline mutation. With this study, we investigate clinico-pathological subgroups of pineal tumors and further characterize their biological features. We performed genome-wide DNA methylation analysis in 195 tumors of the pineal region and 20 normal pineal gland controls. Copy-number profiles were obtained from DNA methylation data; gene panel sequencing was added for 93 tumors and analysis was further complemented by miRNA sequencing for 22 tumor samples. Unsupervised clustering based on DNA methylation profiling separated known subgroups, like pineocytoma, pineal parenchymal tumor of intermediate differentiation, papillary tumor of the pineal region and PB, and further distinct subtypes within these groups, including three subtypes within the core PB subgroup. The novel molecular subgroup Pin-RB includes cases of trilateral retinoblastoma as well as sporadic pineal tumors with RB1 alterations, and displays similarities with retinoblastoma. Distinct clinical associations discriminate the second novel molecular subgroup PB-MYC from other PB cases. Alterations within the miRNA processing pathway (affecting DROSHA, DGCR8 or DICER1) are found in about two thirds of cases in the three core PB subtypes. Methylation profiling revealed biologically distinct groups of pineal tumors with specific clinical and molecular features. Our findings provide a foundation for further clinical as well as molecular and functional characterization of PB and other pineal tumors, including the role of miRNA processing defects in oncogenesis.
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- 2019
19. Retinoblastoma.
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Ortiz, Michael V. and Dunkel, Ira J.
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RETINOBLASTOMA , *CHILDHOOD cancer , *SYMPTOMS in children , *CANCER genetics , *TUMOR classification , *CANCER chemotherapy - Abstract
Retinoblastoma is the most common primary intraocular malignancy of childhood. It typically presents with leukocoria or strabismus. In later stages of the disease, the child may exhibit proptosis, buphthalmos, or hypopyon. The pathognomonic molecular aberration is a loss of function mutation in the RB1 gene on chromosome 13q. The degree of tumor involvement within the eye is defined by its group. Grouping was historically done with Reese-Ellsworth System. Recent therapeutic advances have led to the development of a new grouping system, the International Classification of Retinoblastoma (ICRB). In cases of extraocular extension and metastatic disease, the degree of tumor involvement outside of the eye is defined by its stage. Retinoblastoma is staged using the International Retinoblastoma Staging System (IRSS). Children with intraocular retinoblastoma have an excellent overall and ocular survival. In order to avoid the morbidity of enucleation and external beam radiation, treatments for isolated intraocular retinoblastoma have progressively moved toward targeted local modalities. Patients with extraocular involvement, such as those with trilateral retinoblastoma, have a poorer prognosis. The majority of these higher stage patients are now able to be cured with combination chemotherapy. [ABSTRACT FROM AUTHOR]
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- 2016
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20. Magnetic resonance imaging based morphologic evaluation of the pineal gland for suspected pineoblastoma in retinoblastoma patients and age-matched controls.
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Pham, Thi Thai Hien, Siebert, Eberhard, Asbach, Patrick, Willerding, Gregor, and Erb-Eigner, Katharina
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MAGNETIC resonance imaging of the brain , *PINEAL gland physiology , *PINEAL gland tumors , *DISEASE susceptibility , *RETINOBLASTOMA , *AGE factors in disease - Abstract
Purpose The purpose of this study was to evaluate the morphologic magnetic resonance imaging (MRI) characteristics of the pineal gland in retinoblastoma (Rb) patients without and with pineoblastoma in comparison to age-matched controls to improve early identification of pineoblastomas (trilateral retinoblastoma, TRb). Methods and materials 80 patients with retinoblastoma and 80 age-matched controls who had undergone brain MRI were included in this retrospective institutional review board approved cohort study. Two readers analyzed the following MR characteristics of the pineal gland: signal intensity on T1- and T2-weighted images, enhancement pattern, delineation of the gland, presence of cystic component, size of pineal gland and size of pineal cysts, respectively. A third reader assessed all images for the presence or absence of pineoblastoma. Results 3 patients were positive (TRb cohort) and 77 negative for pineoblastoma (non-TRb cohort). The mean maximum diameter of the pineal gland was 6.4 mm in Rb patients and 6.3 mm in age-matched controls. The mean volume of the pineal gland in Rb patients was 93.1 mm 3 and was 87.6 mm 3 in age-matched controls. Considering all available MRI scans the mean maximum diameter of the pineal gland in TRb patients was 11.2 mm and the mean volume in TRb patients was 453.3 mm 3 . The third reader identified pineoblastomas with a sensitivity of 100% (3 of 3) and a specificity of 94% (72 of 77). Conclusion Our non-TRb patients did not show significant differences in the size of the pineal gland and pineal gland cysts compared to age-matched controls. The presented data can serve as a reference for the volume of normal pineal glands and pineal cysts in the diagnostic work-up of Rb patients with suspected pineoblastoma. [ABSTRACT FROM AUTHOR]
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- 2015
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21. Three Novel Cases of Trilateral Retinoblastoma: An Approach towards Genetic Diagnosis
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Renata Mendes de Freitas
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Proband ,medicine.medical_specialty ,medicine.diagnostic_test ,Trilateral retinoblastoma ,Intracranial tumor ,business.industry ,Retinoblastoma ,Magnetic resonance imaging ,medicine.disease ,eye diseases ,medicine ,Secondary tumors ,Multiplex ligation-dependent probe amplification ,Radiology ,business ,Genetic diagnosis - Abstract
The trilateral retinoblastoma is the heritable form of retinoblastoma associated with an intracranial tumor that most effect the pineal gland, as well as the suprasellar or intrasellar region of the brain. Because of this rarity, few works on the molecular genetics of this tumor has been reported being important the report of these cases associated with molecular studies. This work aims to alert health professionals to the early diagnosis of retinoblastoma, and to highlight the use of intracranial magnetic resonance imaging to track secondary tumors, including trilateral retinoblastoma. More than 50% of trilateral retinoblastoma is diagnosed at the time of retinoblastoma diagnosis by magnetic resonance imaging, suggesting that baseline screening for trilateral retinoblastoma might indeed be useful. In this paper, we present three cases of trilateral retinoblastoma with diagnosis obtained by magnetic resonance imaging and the molecular data found for each proband.
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- 2021
22. An In Utero Presentation of Trilateral Retinoblastoma
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Irina Belinsky, Jasmine H. Francis, Yandong Bian, and David H. Abramson
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Adult ,medicine.medical_specialty ,Pediatrics ,Trilateral retinoblastoma ,Biopsy ,Retinal Neoplasms ,MEDLINE ,Article ,Retina ,Pregnancy ,Ophthalmology ,medicine ,Humans ,Neoplasm Staging ,Ultrasonography ,Pineoblastoma ,business.industry ,Retinoblastoma ,Brain ,Second cancer ,Magnetic Resonance Imaging ,In utero ,Female ,Presentation (obstetrics) ,business ,Pregnancy Complications, Neoplastic - Published
- 2021
23. Intraarterielle Chemotherapie beim Retinoblastom : erste Erfahrungen eines deutschen Referenzzentrums
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Sophia Göricke, Tobias Kiefer, Nikolaos E. Bechrakis, Sabrina Schlüter, Norbert Bornfeld, Petra Ketteler, Saskia Ting, Dirk Geismar, and Eva Biewald
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medicine.medical_specialty ,genetic structures ,Trilateral retinoblastoma ,Retinal Neoplasms ,medicine.medical_treatment ,Medizin ,Disease ,Metastasis ,medicine.artery ,medicine ,Humans ,Prospective Studies ,Child ,Prospective cohort study ,Retrospective Studies ,Chemotherapy ,Retinoblastoma ,business.industry ,Infant ,Retrospective cohort study ,medicine.disease ,eye diseases ,Surgery ,Ophthalmology ,Ophthalmic artery ,Neoplasm Recurrence, Local ,business - Abstract
Adequate management of retinoblastoma requires a multidisciplinary and individual approach to treatment. Intraarterial chemotherapy (IAC) is one of the most commonly used treatment modalities, and enables supraselective application of chemotherapy via the ophthalmic artery and is now established in almost all treatment centres. However, published treatment success rates are heterogeneous. There are some unanswered issues regarding sight-threatening ocular complications and the long-term occurrence of secondary malignancies and metastatic disease. The objective of the present study is to analyse the results of a German national reference centre.Retrospective analysis of all children with an indication for at least one IAC from April 2010 to April 2020. IAC was used either as primary or recurrence therapy. Obligatory follow-up was at least 6 months.137 eyes of 127 children with an indication for IAC could be included. 12 eyes with a follow-up of less than 6 months and 37 eyes in which IAC was technically not feasible were excluded. In summary, 88 eyes of 79 children were finally analysed. Mean follow-up was 38 months, ranging from 7 to 117 months. In total, 195 procedures were completed. In 30 eyes (34.1%) IAC was conducted as primary and in 58 (65.9%) as secondary therapy. There was an initial IAC treatment response in 75 eyes (85.2%) with a recurrence-free rate of 61.3%. Eye salvage rate was 68.1% with 28 enucleated eyes in total. Ocular complications were observed in 36 eyes (40.9%), with 19 eyes (21.6%) showing severe sight-threatening and 11 eyes (12.5%) presenting minor non-sight-threatening toxic reactions. During follow-up, 1 child developed a secondary malignancy, 1 child developed metastasis and 1 child died as a consequence of trilateral retinoblastoma.In summary, IAC is a potent modality for retinoblastoma treatment and has been very successful, even in advanced disease and heavily pretreated eyes. However, ocular complications should be taken in consideration, especially when the only seeing eye is treated. Long term incidences of secondary malignancies and metastatic diseases should be further investigated in prospective studies.Das Retinoblastom, als häufigste intraokulare Tumorentität, bedarf einer interdisziplinären und individuellen Therapie. Die intraarterielle Chemotherapie (IAC) ermöglicht die supraselektive interventionelle Gabe eines Chemotherapeutikums über die A. ophthalmica und hat sich in den weltweiten Behandlungszentren zunehmend etabliert. Die publizierten Erfahrungen zwischen den verschiedenen Zentren sind teilweise sehr heterogen. Offen bleibt insbesondere der Stellenwert von visusbedrohenden okulären Nebenwirkungen und die Langzeitfolgen in Bezug auf Zweitmalignome oder Metastasen nach IAC. Ziel der vorgestellten Studie ist es, die Ergebnisse eines deutschen nationalen Referenzzentrums zu analysieren.Retrospektive Analyse aller Retinoblastomkinder, die im Zeitraum von April 2010 bis April 2020 die Indikation zu mindestens einer IAC als Primär- oder Rezidivtherapie erhielten. Das minimale Follow-up betrug 6 Monate.Es wurden 137 Augen von 127 Kindern mit der Indikation zur IAC eingeschlossen. 12 Augen wurden aufgrund eines Follow-ups von weniger als 6 Monaten ausgeschlossen, bei weiteren 37 war die IAC technisch nicht durchführbar. Es konnten folglich 88 Augen von 79 Kindern mit mindestens einer erfolgreichen IAC eingeschlossen werden. Das mittlere Follow-up betrug 38 Monate (7 – 117). Es wurden insgesamt 195 IACs durchgeführt, wobei die IAC bei 30 Augen (34,1%) als Primärtherapie und bei den übrigen 58 Augen (65,9%) als Sekundärtherapie durchgeführt wurde. In 75 Augen (85,2%) zeigte sich ein primäres Ansprechen auf die IAC mit einer Rezidivfreiheit von 61,3%. Die Bulbuserhaltungsrate lag mit 28 enukleierten Augen bei 68,1%. Bei 36 Augen (40,9%) kam es zu unterschiedlichen okulären Nebenwirkungen und Komplikationen. Bei 19 der 37 von Komplikationen betroffenen Augen (21,6%) traten visusrelevante und bei 11 Augen (12,5%) nicht visusrelevante toxische Reaktionen auf. Während des Follow-ups entwickelte 1 Kind ein Zweitmalignom, 1 Kind entwickelte Metastasen und 1 Kind verstarb an den Folgen eines trilateralen Retinoblastoms.Zusammenfassend stellt die IAC ein potentes Therapieverfahren zur Behandlung des Retinoblastoms dar, das auch bei fortgeschrittenen und vorbehandelten Befunden zum Bulbuserhalt eingesetzt werden kann. Dennoch sollten die okulären Komplikationen, insbesondere bei funktioneller Unicussituation, nicht außer Acht gelassen werden. Langzeitergebnisse in Bezug auf Zweitmalignome und Metastasenentwicklung stehen derzeit aus und sollten über prospektive Multicenterstudien analysiert und bewertet werden.
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- 2021
24. A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma Part I : Metastasis-Associated Mortality
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Amer Joint Comm Canc Ophthalmic On, Tomar, Ankit Singh, Finger, Paul T., Gallie, Brenda, Kivela, Tero T., Correa-Llano, Genoveva, HUS Head and Neck Center, Silmäklinikka, University of Helsinki, and Helsinki University Hospital Area
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RISK ,TRILATERAL RETINOBLASTOMA ,3125 Otorhinolaryngology, ophthalmology ,CLASSIFICATION ,SYSTEM ,EYE CANCER - Abstract
Purpose: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). Design: International, multicenter, registry-based retrospective case series. Participants: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. Main Outcome Measures: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the KaplaneMeier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. Results: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year KaplaneMeier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P
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- 2020
25. Clinical audit of retinoblastoma management: a retrospective single-institution study
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Jason Baoshan Hu, Furqan Shaikh, Sameh E. Soliman, Brenda L. Gallie, Kaitlyn Flegg, Wei Sim, Helen Dimaras, and Arunan Selvarajah
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Clinical audit ,medicine.medical_specialty ,Trilateral retinoblastoma ,Retinal Neoplasms ,Enucleation ,MEDLINE ,Eye Enucleation ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Child ,Retrospective Studies ,Clinical Audit ,Retinoblastoma ,business.industry ,General surgery ,Medical record ,Infant ,General Medicine ,medicine.disease ,Ophthalmology ,030221 ophthalmology & optometry ,business ,Complication - Abstract
Objective The primary aim of this study was to identify the frequency of death, metastasis, enucleation, and use of external beam radiation therapy (EBRT) among retinoblastoma patients. The secondary aim was to determine whether any events were associated with suboptimal clinical management to identify areas for clinical care improvement. Methods Patients diagnosed with retinoblastoma between January 1, 2000, and December 31, 2015, at The Hospital for Sick Children were included. Medical records of eligible patients underwent a comprehensive 2-part review. First, a chart review collected diagnostic details, treatment course, and occurrence of 4 events: death, metastasis, use of EBRT, and enucleation. Next, events were reviewed in detail, and a multidisciplinary committee reached consensus on cases managed suboptimally. Results The study included 209 patients (292 eyes). There were 8 deaths, 11 metastases, 177 enucleations (143 primary, 34 secondary), and 8 uses of EBRT. Thirteen patients were reviewed by the multidisciplinary committee, which confirmed that 5 of these patients had events associated with suboptimal clinical management. Three patients developed metastases leading to death (misdiagnosis and mismanagement of trilateral retinoblastoma [1], parental refusal of enucleation [1], and inaccurate histopathology after primary enucleation [1]). One patient developed extraocular extension related to scleral invasion following aggressive focal therapy. One patient underwent secondary enucleation for a Group B eye related to mismanagement of a treatment complication. Discussion Deaths, metastases, and enucleations with documented instances of suboptimal care highlighted a need to enhance medical team and patient communication, histopathology interpretation, laser treatment guidelines, and trilateral retinoblastoma management. Routine clinical audit of retinoblastoma management can identify areas for clinical practice change.
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- 2020
26. Screening for pineal trilateral retinoblastoma revisited: a meta-analysis
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de Jong, Marcus C, Kors, Wijnanda A, Moll, Annette C, de Graaf, Pim, Castelijns, Jonas A, Jansen, Robin W, Gallie, Brenda, Soliman, Sameh E, Shaikh, Furqan, Dimaras, Helen, Kivelä, Tero T, HUS Head and Neck Center, Silmäklinikka, Department of Ophthalmology and Otorhinolaryngology, University of Helsinki, and Helsinki University Hospital Area
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endocrine system ,AGED 0-5 YEARS ,MRI-BASED ASSESSMENT ,PINEALOBLASTOMA ,screening ,CHILDREN ,lead time ,eye diseases ,retinoblastoma ,period at risk ,HIGH-DOSE CHEMOTHERAPY ,GLAND ,STEM-CELL RESCUE ,trilateral retinoblastoma ,INTRAARTERIAL ,3125 Otorhinolaryngology, ophthalmology ,LARGE POPULATION ,pineoblastoma ,MRI - Abstract
TOPIC: To determine the age up to which children are at risk of trilateral retinoblastoma (TRb) developing, whether its onset is linked to the age at which intraocular retinoblastomas develop, and the lead time from a detectable pineal TRb to symptoms.CLINICAL RELEVANCE: Approximately 45% of patients with retinoblastoma-those with a germline RB1 pathogenic variant-are at risk of pineal TRb developing. Early detection and treatment are essential for survival. Current evidence is unclear regarding the usefulness of screening for pineal TRb and, if useful, the age up to which screening should be continued.METHODS: We conducted a study according to the Meta-analysis of Observational Studies in Epidemiology guidelines for reporting meta-analyses of observational studies. We searched PubMed and Embase between January 1, 1966, and February 27, 2019, for published literature. We considered articles reporting patients with TRb with survival and follow-up data. Inclusion of articles was performed separately and independently by 2 authors, and 2 authors also independently extracted the relevant data. They resolved discrepancies by consensus.RESULTS: One hundred thirty-eight patients with pineal TRb were included. Of 22 asymptomatic patients, 21 (95%) were diagnosed before the age of 40 months (median, 16 months; interquartile range, 9-29 months). Age at diagnosis of pineal TRb in patients diagnosed with retinoblastoma at 6 months or younger versus older than 6 months were comparable (P = 0.44), suggesting independence between the ages at diagnosis of intraocular retinoblastoma and pineal TRb. The laterality of intraocular retinoblastoma and its treatment were not associated with the age at which pineal TRb was diagnosed. The lead time from asymptomatic to symptomatic pineal TRb was approximately 1 year. By performing a screening magnetic resonance imaging scan every 6 months after the diagnosis of heritable retinoblastoma (median age, 6 months) until 36 months of age, at least 311 and 776 scans would be required to detect 1 case of asymptomatic pineal TRb and to save a single life, respectively.CONCLUSIONS: Patients with retinoblastoma are at risk of pineal TRb developing for a shorter period than previously assumed, and the age at diagnosis of pineal TRb is independent of the age at diagnosis of retinoblastoma. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) level of evidence for these conclusions remains low.
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- 2020
27. Orbital Pseudocellulitis: A Retinoblastoma-Associated Masquerade Syndrome
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Francesco Martino, Sonia De Francesco, Clelia Miracco, Maria Chiara Gelmi, Paolo Galluzzi, and Doris Hadjistilianou
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medicine.medical_specialty ,medicine.diagnostic_test ,Trilateral retinoblastoma ,genetic structures ,business.industry ,Retinoblastoma ,Leukocoria ,Physical examination ,medicine.disease ,eye diseases ,Buphthalmos ,Clinical Research ,Medicine ,Radiology ,sense organs ,Differential diagnosis ,Orbital cellulitis ,medicine.symptom ,business ,Sinusitis ,General Nursing - Abstract
Introduction: A masquerade syndrome is an atypical presentation of a neoplastic process that mimics an inflammatory condition. In this paper, we focus on orbital pseudocellulitis. Case Series: Our case series includes 5 retinoblastoma patients with orbital pseudocellulitis at presentation. In 3 patients the disease was bilateral, in 1 trilateral, and in 1 unilateral. The eyes with pseudocellulitis were enucleated, while the fellow eyes were treated conservatively, when affected. Four patients responded well to the therapy and showed remission of the tumor. The patient with trilateral retinoblastoma did not respond to therapy and died of disease. Discussion: Differential diagnosis with infectious orbital cellulitis is extremely important. Patients with orbital cellulitis present with fever, sinusitis, leukocytosis, and raised inflammatory markers, while ophthalmoscopic examination is negative and imaging studies show sinus involvement. On the contrary, patients with retinoblastoma do not show systemic inflammation, while ophthalmoscopic examination reveals leukocoria, buphthalmos, and an intraocular tumor mass associated with retinal detachment. Magnetic resonance imaging shows intralesional calcifications and soft tissue edema without sinus involvement. Histology confirms the diagnosis. Conclusions: Medical history, physical examination, and imaging studies are crucial in the diagnosis of retinoblastoma-associated orbital pseudocellulitis. Retinoblastoma should be excluded in all patients with signs of pre-septal orbital cellulitis through fundoscopy and/or imaging studies
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- 2020
28. Two novel cases of trilateral retinoblastoma: genetics and review of the literature.
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D’Elia, Gemma, Grotta, Simona, Del Bufalo, Francesca, De Ioris, Maria Antonietta, Surace, Cecilia, Sirleto, Pietro, Romanzo, Antonino, Cozza, Raffaele, Locatelli, Franco, and Angioni, Adriano
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RETINOBLASTOMA gene , *CHILDHOOD cancer , *GENETIC mutation , *INTRACRANIAL tumors , *LITERATURE reviews - Abstract
Retinoblastoma (RB) is the most common eye tumor in children; it originates from germline and/or somatic mutations that inactivate both alleles of the RB1 gene located on chromosome 13q14. Patients with unilateral or bilateral RB infrequently may develop an additional intracranial neuroblastic tumor, usually in the pineal gland, which characterizes the trilateral retinoblastoma (TRB) syndrome. The most common chromosomal abnormalities detected in TRB are deletions at 13q14, even if some rare cases of RB1 point mutations were described. In our report, we investigated two patients with TRB who showed a germline RB1 point mutation that has never been found to date and a large deletion involving RB1, respectively. Genetic data were compared to our in-house series and to current literature; these data suggested a role for other candidate regions in the pathogenesis of TRB. Moreover, our study highlights the need for new approaches allowing a multigenic analysis to clarify the genotype−phenotype correlation in TRB. [Copyright &y& Elsevier]
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- 2013
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29. Minimal disseminated disease evaluation and outcome in trilateral retinoblastoma
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Ana Vanesa Torbidoni, Guillermo L. Chantada, Viviana E. Laurent, Saipriya Iyer, Rosario Aschero, Irene Szijan, Claudia Sampor, Daniel Fernando Alonso, Daniel Alderete, and Jorge Rossi
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Male ,Oncology ,INTRACRANIAL TUMOR ,Medicina Clínica ,Disease ,Pineal Gland ,Oncología ,0302 clinical medicine ,Cerebrospinal fluid ,Risk Factors ,Antineoplastic Combined Chemotherapy Protocols ,NEUROBLASTIC TUMOR ,Potential impact ,Brain Neoplasms ,Systemic chemotherapy ,Hematopoietic Stem Cell Transplantation ,Retinoblastoma ,Cerebrospinal Fluid Proteins ,Magnetic Resonance Imaging ,Sensory Systems ,Retinoblastoma Binding Proteins ,medicine.anatomical_structure ,Child, Preschool ,030220 oncology & carcinogenesis ,N-Acetylgalactosaminyltransferases ,Minimal Disseminated Disease ,Female ,Pinealoma ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Trilateral retinoblastoma ,Retinal Neoplasms ,Ubiquitin-Protein Ligases ,Bone Marrow Cells ,Transplantation, Autologous ,LEPTOMENINGEAL DISSEMINATION ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Retrospective Studies ,Homeodomain Proteins ,business.industry ,BONE MARROW ,Infant ,Ophthalmology ,RB1 GENE ,Concomitant ,Trans-Activators ,030221 ophthalmology & optometry ,Bone marrow ,Neoplasm Recurrence, Local ,business - Abstract
Trilateral retinoblastoma (TRb) presents a management challenge, since intracranial tumours are seldom times resectable and quickly disseminate. However, there are no risk factors to predict the final outcome in each patient. Objective To evaluate minimal disseminated disease (MDD) in the bone marrow (BM) and the cerebrospinal fluid (CSF) at diagnosis and during follow-up and reviewing its potential impact in the outcome of patients with TRb. Methods and analysis We evaluated MDD in five patients with TRb, detecting the mRNA of CRX and/or GD2, in samples from BM and CSF, obtained at diagnosis, follow-up and relapse. Results Treatment involved intensive systemic chemotherapy in four patients, one did not receive this treatment and died of progression of the disease. Two patients underwent stem cell rescue. Three patients had leptomeningeal relapse and died. One patient remains disease-free for 84 months. RB1 mutations were identified in the five patients, all of them were null mutations. At diagnosis, one patient had tumour cells in the CSF, and none had the BM involved. Only one case of four presented MDD during follow-up in the CSF, without concomitant detection in the BM. On leptomeningeal relapse, no case had MDD in the BM. In all these cases, cells in the CSF were positive for GD2 and/or CRX. Conclusion CSF dissemination always concluded in the death of the patient, without concomitant systemic dissemination denoting the importance of increasing treatment directed to the CSF compartment. The MDD presence could indicate a forthcoming relapse. Fil: Torbidoni, Ana Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Laurent, Viviana Eunice. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Aschero, María del Rosario. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Iyer, Saipriya. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Rossi, Jorge. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Alderete, Daniel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Szijan, Irene. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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- 2018
30. Current Treatment of Bilateral Retinoblastoma: The Impact of Intraarterial and Intravitreous Chemotherapy
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Scott E. Brodie, David H. Abramson, Y. Pierre Gobin, Jasmine H. Francis, Nelli Roosipu, Ira J. Dunkel, and Ariana M. Levin
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Male ,Cancer Research ,genetic structures ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Eye ,PFS, progression-free survival (an event included any treatment with enucleation, external beam radiation and OAC following completion of initial treatment and was calculated from the initial treatment date) ,Ophthalmic Artery ,0302 clinical medicine ,EBR, external beam radiation ,ERG, electroretinogram ,medicine.diagnostic_test ,Retinoblastoma ,Complete blood count ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,030220 oncology & carcinogenesis ,Child, Preschool ,ReFS, recurrent event–free survival (an event was defined as recurrence if receiving any treatment, including focal. and calculated from the end date of the initial treatment to date of recurrence diagnosis) ,Female ,medicine.medical_specialty ,Original article ,Trilateral retinoblastoma ,Retinal Neoplasms ,Enucleation ,Antineoplastic Agents ,lcsh:RC254-282 ,Disease-Free Survival ,03 medical and health sciences ,medicine.artery ,OAC, ophthalmic artery chemosurgery ,medicine ,Electroretinography ,Humans ,Infusions, Intra-Arterial ,SPMs, second primary malignancies ,Retrospective Studies ,Chemotherapy ,business.industry ,Fundus photography ,Infant, Newborn ,Infant ,Retrospective cohort study ,medicine.disease ,eye diseases ,Surgery ,Ophthalmic artery ,030221 ophthalmology & optometry ,Neoplasm Recurrence, Local ,business - Abstract
PURPOSE: To evaluate the management and outcomes of naive bilateral retinoblastoma treated at a single-center over a 5-year period during the era of ophthalmic artery chemosurgery (OAC) and intravitreous chemotherapy. METHODS: Retrospective cohort study of 46 patients (92 eyes) with naive bilateral retinoblastoma treated at Memorial Sloan Kettering Cancer Center between January 2012 and February 2017. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response. Patient, ocular, ocular progression-free, ocular recurrent event–free, and second ocular survivals were assessed by Kaplan-Meier estimates. Retinal toxicity was evaluated by electroretinography. Snellen visual acuity and complete blood count metrics were recorded. RESULTS: Sixty-four eyes (70%) in 41 patients (89%) received ophthalmic artery chemosurgery as part of their treatment. Twenty-six patients (56%) received tandem OAC (bilateral simultaneous infusions). Seven eyes were primarily enucleated. No eye receiving initial OAC was enucleated. There was a single secondary enucleation in an eye initially treated with focal therapy with anterior chamber recurrence. The 3-year Kaplan-Meier estimates for overall ocular, secondary ocular (survival after treatment for recurrence), progression-free, and recurrent event–free survival were 91.3% [95% confidence interval (CI) 83.4-95.5], 98.7% (95% CI 91.3-99.8), 91.5% (95% CI 83.0-95.8), and 78.9% (95% CI 68.2-86.3), respectively. Overall and secondary ocular survivals were 100% for International Classification of Retinoblastoma (ICRB) groups A-C. Overall ocular survival was 91.5% (95% CI 70-97.8) for ICRB group D and 71.4% (95% CI 47.1-79.4) for group E. Secondary ocular survival was 95.4% (95% CI 71.8-99.3) for ICRB group D and 100% for group E. There were no treatment-related deaths, three patients developed trilateral retinoblastoma (one died), and one patient (who did not receive OAC) developed metastatic disease and is in remission at 32-month follow-up. CONCLUSION: The majority (89%) of bilateral retinoblastoma patients in the current era and at this center were treated with OAC. This has resulted in saving a historic number of eyes. A quarter of eyes developed recurrent disease (defined as recurrent disease requiring any treatment including focal), the majority of which occurred in the first year after treatment, and all but one was saved. There has been no compromise in patient survival.
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- 2018
31. Retinoblastoma, the visible CNS tumor: A review
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Helen Dimaras and Timothy W. Corson
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0301 basic medicine ,genetic structures ,medicine.diagnostic_test ,Trilateral retinoblastoma ,business.industry ,Retinoblastoma ,Cancer ,Magnetic resonance imaging ,medicine.disease ,Pediatric cancer ,eye diseases ,3. Good health ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,Neuroimaging ,Optical coherence tomography ,Neuroblastoma ,Cancer research ,medicine ,business ,030217 neurology & neurosurgery - Abstract
The pediatric ocular cancer retinoblastoma is the only central nervous system (CNS) tumor readily observed without specialized equipment: it can be seen by, and in, the naked eye. This accessibility enables unique imaging modalities. Here, we review this cancer for a neuroscience audience, highlighting these clinical and research imaging options, including fundus imaging, optical coherence tomography, ultrasound, and magnetic resonance imaging. We also discuss the subtype of retinoblastoma driven by the MYCN oncogene more commonly associated with neuroblastoma, and consider trilateral retinoblastoma, in which an intracranial tumor arises along with ocular tumors in patients with germline RB1 gene mutations. Retinoblastoma research and clinical care can offer insights applicable to CNS malignancies, and also benefit from approaches developed elsewhere in the CNS.
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- 2018
32. Diffusion-weighted imaging to assess treatment response in a child with trilateral retinoblastoma.
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Bonci, Gregory, Rosenblum, Marc, Gilheeney, Stephen, Dunkel, Ira, and Holodny, Andrei
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RETINOBLASTOMA , *DIFFUSION magnetic resonance imaging , *JUVENILE diseases , *NERVOUS system tumors , *DIFFUSION coefficients , *CANCER chemotherapy , *THERAPEUTICS - Abstract
Trilateral retinoblastoma (TRb) is a rare condition in which children with bilateral retinoblastoma develop primary midline intracranial neuroblastic tumors. The intracranial lesions are difficult to follow after treatment due to residual mass-like enhancement that may represent persistent tumor or treated disease. We highlight a case where close evaluation of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) characteristics accurately depicted the extent of treated disease versus residual tumor after chemotherapy. [ABSTRACT FROM AUTHOR]
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- 2013
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33. Quiste benigno de la glándula pineal en paciente con retinoblastoma bilateral: Reporte de caso y revisión de la literatura
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Vivas Giraldo, Jose Pablo, Giraldo Ochoa, Daniela, Gaviria Bravo, Martha Lía, Gonzalez Alviar, María Elena, Lopez Posada, Mariana, Vargas Vélez, Sergio Alberto, Vivas Giraldo, Jose Pablo, Giraldo Ochoa, Daniela, Gaviria Bravo, Martha Lía, Gonzalez Alviar, María Elena, Lopez Posada, Mariana, and Vargas Vélez, Sergio Alberto
- Abstract
Background: Patients with hereditary Retinoblastoma (RB) are at risk of developing other types of extraocular primary malignancies throughout life. Among these tumors, pinealoblastoma is a type of malignancy that appears in the pineal gland and can develop at any time from the diagnosis of bilateral retinoblastoma.Objective: To present an unusual case of a patient with a diagnosis of hereditary BR who developed a pineal cystStudy design: Case report.Case summary: We present in this article the case of a patient with a diagnosis of hereditary BR with remission who developed a pineal cyst during clinical follow-up. The cystic lesions of the pineal gland reported by magnetic resonance are infrequent in pediatric age, however its incidence is increased in patients with RB, which generates uncertainty about the possibility of the development of a primary pineal gland malignancy. The pathophysiological mechanism of pineal gland cysts in patients with hereditary RB is still unknown, but it could be related to a genetic alteration or to chemotherapy treatment that these patients receive for the primary intraocular tumor.Conclusion: The imaging characteristics are fundamental to differentiate between benign and malignant lesions of the pineal gland in patients with Hereditary Retinoblastoma and to make a close follow up., Introducción: Los pacientes con Retinoblastoma (RB) hereditario se encuentran en riesgo de desarrollar otros tipos de tumores malignos primarios extraoculares durante la vida. Dentro de estos tumores se encuentra el pinealoblastoma, un tipo de neoplasia maligna que aparece en la glándula pineal y que se puede desarrollar en cualquier momento del diagnóstico del retinoblastoma bilateral.Objetivo: Presentar un caso inusual de retinoblastoma (RB) hereditario tratado y en remisión quien desarrolló un quiste pineal benignoDiseño del estudio: Reporte de caso y revisión de literaturaResumen del caso: Presentamos un paciente con diagnóstico de RB hereditario tratado y en remisión quien desarrolló un quiste pineal benigno durante el seguimiento clínico. Las lesiones quísticas de la glándula pineal reportadas por resonancia magnética son infrecuentes en edad pediátrica, sin embargo, su incidencia se ve aumentada en pacientes con RB, lo que genera incertidumbre sobre la posibilidad de presentar una neoplasia maligna. Aún se desconoce el mecanismo fisiopatológico de la aparición de quistes de la glándula pineal en pacientes con RB hereditario, pero podría tener relación con la alteración genética o con el tratamiento quimioterápico que reciben los pacientes para el tumor primario intraocular.Conclusión: Las características imagenológicas son fundamentales para diferenciar entre lesiones benignas y malignas de la glándula pineal en pacientes con retinoblastoma hereditario y para hacer el estrecho seguimiento junto con el examen clínico.
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- 2019
34. Trilateral retinoblastoma: neuroimaging characteristics and value of routine brain screening on admission.
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Rodjan, Firazia, Graaf, Pim, Brisse, Hervé, Göricke, Sophia, Maeder, Philippe, Galluzzi, Paolo, Aerts, Isabelle, Alapetite, Claire, Desjardins, Laurence, Wieland, Regina, Popovic, Maja, Diezi, Manuel, Munier, Francis, Hadjistilianou, Theodora, Knol, Dirk, Moll, Annette, and Castelijns, Jonas
- Abstract
Trilateral retinoblastoma (TRb) is a rare disease associating intraocular retinoblastoma with intracranial primitive neuroectodermal tumor. Treatment is difficult and prognosis is poor. This multicenter study evaluates clinical findings and MR imaging characteristics of associated intracranial tumors in Rb patients. Clinical data of 17 patients (16 TRb and 1 quadrilateral Rb patients) included time intervals between Rb and TRb diagnosis and presence of baseline brain-imaging (BBI). Two reviewers reviewed all images individually and one reviewer per center evaluated their images. Consensus was reached during a joint scoring session. Studies were reviewed for tumor location, size and imaging characteristics (signal intensity (SI) on T1- and T2-weighted images, enhancement pattern and cystic appearance). Of 18 intracranial tumors, 78 % were located in the pineal gland and 22 % suprasellar. All tumors showed well-defined borders with mostly heterogenous enhancement (72 %) and isointense SI on T1- (78 %) and T2-weighted images (72 %) compared to gray matter. The majority of pineal TRbs showed a cystic component (57 %). TRb detected synchronously with the intraocular tumors on BBI ( n = 7) were significantly smaller ( P = 0.02), and mainly asymptomatic than TRb detected later on ( n = 10). Overall, 5-year-survival of TRb patients detected on BBI was 67 % (95 % CI 29-100 %) compared to 11 % (95 % CI 0-32 %) for the group with delayed diagnosis. TRb mainly develops in the pineal gland and frequently presents with a cystic appearance that could be misinterpreted as benign pineal cysts. Routine BBI in all newly diagnosed Rb patients can detect TRb at a subclinical stage. [ABSTRACT FROM AUTHOR]
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- 2012
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35. High-dose chemotherapy followed by autologous and allogeneic peripheral blood stem cell transplantation for recurrent disseminated trilateral retinoblastoma.
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Tsuruta, Toshihisa, Aihara, Yasuo, Kanno, Hitoshi, Kiyotani, Chikako, Maebayashi, Katsuya, Sakauchi, Masako, Osawa, Makiko, Fujii, Hisaichi, Kubo, Osami, and Okada, Yoshikazu
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CASE studies , *RETINOBLASTOMA , *STEM cell transplantation , *MENINGES , *DISEASE relapse , *DRUG therapy , *PATIENTS , *TUMORS - Abstract
Introduction: Trilateral retinoblastoma (TRb) is an intracranial neurogenic tumor associated with unilateral or bilateral retinoblastoma and has very poor prognosis. Patients typically die from leptomeningeal tumor dissemination. Case report: A 3-year-old girl who had been diagnosed with TRb had a disseminated relapse after a tumorectomy, cerebrospinal irradiation, and conventional chemotherapy. The disseminated tumor disappeared after the first autologous peripheral blood stem cell transplantation (PBSCT) with high-dose melphalan and thiotepa. During the second complete remission, a second autologous PBSCT with high-dose busulfan and melphalan was performed. Seven months after the first PBSCT, the second relapse occurred, and we subsequently performed an allogeneic PBSCT with myeloablative chemotherapy consisting of melphalan, thiotepa, and cyclophosphamide. The patient showed clinical improvement after the allogeneic PBSCT. Conclusion: Although high-dose chemotherapies have a curative effect for some patients with TRb, the prognoses of disseminated tumors are still poor. Further examination of the high-dose chemotherapy is necessary for the time, the conditioning drugs, and the hematopoietic stem cell sources. [ABSTRACT FROM AUTHOR]
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- 2011
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36. The Role of Complement Factor H in Age-related Macular Degeneration: A Review
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Donoso, Larry A., Vrabec, Tamara, and Kuivaniemi, Helena
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RETINAL degeneration , *IMMUNE system , *GLYCOPROTEINS , *GENETIC mutation , *INFLAMMATION , *NEUTROPHIL immunology , *NATURAL immunity - Abstract
Abstract: Factor H is a 155kDa sialic acid containing glycoprotein that plays an integral role in the regulation of the complement-mediated immune system that is involved in microbial defense, immune complex processing, and programmed cell death. These events take place primarily in fluid phase and on the cell surface and are particularly important in the context of distinguishing self from non-self. Activation of the complement system occurs within seconds and results in a proteolytic cascade eventually forming the membrane attack complex leading to cell lysis. Factor H protects host cells from injury resulting from unrestrained complement activation. Mutations and SNPs (single nucleotide polymorphisms) in Factor H have been implicated in a variety of human conditions including age-related macular degeneration (AMD), atypical hemolytic uremic syndrome, and membranoproliferative glomuleronephritis type II or dense deposit disease. It should not be surprising that these seemingly unrelated diseases involving mutations in Factor H may share common features. Because the immune process involves, in part, an inflammatory response and common or similar surface antigens, it is also not unexpected to observe features of inflammation, including deposition of bioactive complement fragments such as C3a and C5a, a cellular influx of immune related cells such as lymphocytes, and the potential for multiple organ involvement. We review recent developments in molecular genetics; SNPs, including Y402H; the three-dimensional structure; and mass spectroscopy of Factor H as it relates to the pathogenesis of eye disease. In addition, we discuss the concepts of molecular mimicry, sequestered or hidden antigens, and antigenic cross reactivity, and propose that AMD should not simply be considered to be an eye disease, but rather a systemic vascular disease where the eye has the ability to self regulate a local immune response. Identification of the initial event or inciting antigen has yet to be determined and will significantly advance the understanding of the pathogenesis of AMD. [Copyright &y& Elsevier]
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- 2010
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37. Trilateral retinoblastoma: an institutional experience and review of the literature.
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Jurkiewicz, Elżbieta, Pakuła-Kościesza, Iwona, Rutynowska, Olga, and Nowak, Katarzyna
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RETINOBLASTOMA , *LITERATURE reviews , *OCULAR tumors , *INTRACRANIAL tumors , *RETROSPECTIVE studies , *PEDIATRIC ophthalmology - Abstract
Retinoblastoma is the most common pediatric intraocular neoplasm. The association of uni- or bilateral retinoblastoma with synchronic or metachronic ectopic midline intracranial tumor [trilateral retinoblastoma (TRB)] is uncommon. MR examinations of 202 children with retinoblastoma treated at our institute were retrospectively reviewed. MR images and clinical data of children with TRB were evaluated for the patient’s age at diagnosis of the intracranial tumor and intraocular lesions, tumor size, signal characteristics, and further course in follow-up MR examinations. There were three patients with TRB in our group of patients. All three children had had a negative family history. Two of them had a primary midline intracranial tumor and intraocular lesions at the time of the first diagnosis. In the third case, the first diagnosis was intracranial midline primitive neuroectodermal tumor. Diagnosis of lesions in both eyes was confirmed in ophthalmologic examination 1 month later. In one case, the intracranial tumor was in the pineal region and, in the other two cases, in the sellar and suprasellar regions. There was no evidence of leptomeningeal spread of the tumors in any patient. Patients with uni- and bilateral intraocular tumors should receive brain screening by MR imaging. We also recommend that patients under the age of 4 years with midline tumors should be carefully diagnosed for ocular neoplasms. [ABSTRACT FROM AUTHOR]
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- 2010
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38. Trilateral Retinoblastoma with Pituitary-Hypothalamic Dysfunction.
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Dai, Shuan, Héon, Elise, Budning, Andrew, Dimaras, Helen, Doyle, John, Halliday, William, Drake, James, Gallie, Brenda L., and Chan, Helen S. L.
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PITUITARY diseases , *HYPOTHALAMUS diseases , *HYPOTHALAMIC-pituitary-adrenal axis , *DRUG therapy , *RETINA , *CANCER cells , *TUMORS - Abstract
Trilateral retinoblastoma is characterized by retinal tumors in one or both eyes, as well as tumors of the pineal gland or parasellar region of the brain. Here we describe a 4-month-old girl, presenting with pituitary dysfunction, hypothalamic overgrowth syndrome and central blindness, in addition to suprasellar and bilateral retinal tumors. Biopsy of the suprasellar tumor confirmed the diagnosis of trilateral retinoblastoma. After biopsy, cerebrospinal fluid (CSF) metastasis was discovered. Overgrowth persisted, but blindness and pituitary dysfunction resolved when the suprasellar tumor and CSF metastasis responded to cyclosporine-modulated systemic chemotherapy with intraventricular chemotherapy, consolidated with marrow-ablative chemotherapy and stem cell rescue of the bone marrow. Twenty months after diagnosis and 12 months after transplant, an unusual pattern of tumor recurrence was observed along the catheter of the Ommaya reservoir used for delivering intraventricular chemotherapy, which was also at the site of the previous suprasellar needle biopsy. Salvage therapy consisted of resection, stereotactic radiation, and further systemic and intraventricular chemotherapy. At 25 months after diagnosis, the patient was developing well and seeing better. However, she died 32 months after diagnosis despite the salvage therapy. This case highlights the possibility of tumor dissemination after needle biopsy of a suprasellar tumor. Biopsy may be avoided if a characteristic clinicoradiological picture of trilateral retinoblastoma is recognized. We recommend that if a pineal or suprasellar tumor is observed in a child, the eyes should be examined for retinoblastoma, thereby avoiding biopsies of the intracranial tumor, which may track difficult-to-treat tumor cells through the brain, and disseminate tumor cells into the CSF. [ABSTRACT FROM AUTHOR]
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- 2008
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39. Modeling Developmental and Tumorigenic Aspects of Trilateral Retinoblastoma via Human Embryonic Stem Cells
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Dorit Yanuka, Yishai Avior, Elyad Lezmi, and Nissim Benvenisty
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0301 basic medicine ,Trilateral retinoblastoma ,Carcinogenesis ,Retinal Neoplasms ,Ubiquitin-Protein Ligases ,Human Embryonic Stem Cells ,Cell ,Antineoplastic Agents ,Ectoderm ,Mice, SCID ,Biology ,Biochemistry ,Article ,Carboplatin ,Cell Line ,03 medical and health sciences ,Mice, Inbred NOD ,disease modeling ,Genetics ,medicine ,ZEB1 ,Animals ,Humans ,Induced pluripotent stem cell ,lcsh:QH301-705.5 ,Transcription factor ,lcsh:R5-920 ,Retinoblastoma ,Teratoma ,Zinc Finger E-box-Binding Homeobox 1 ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,Embryonic stem cell ,eye diseases ,Mitochondria ,Retinoblastoma Binding Proteins ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,trilateral retinoblastoma ,Cancer research ,CRISPR-Cas Systems ,lcsh:Medicine (General) ,RB1 ,Developmental Biology - Abstract
Summary Human embryonic stem cells (hESCs) provide a platform for studying human development and understanding mechanisms underlying diseases. Retinoblastoma-1 (RB1) is a key regulator of cell cycling, of which biallelic inactivation initiates retinoblastoma, the most common congenital intraocular malignancy. We developed a model to study the role of RB1 in early development and tumor formation by generating RB1-null hESCs using CRISPR/Cas9. RB1−/− hESCs initiated extremely large teratomas, with neural expansions similar to those of trilateral retinoblastoma tumors, in which retinoblastoma is accompanied by intracranial neural tumors. Teratoma analysis further revealed a role for the transcription factor ZEB1 in RB1-mediated ectoderm differentiation. Furthermore, RB1−/− cells displayed mitochondrial dysfunction similar to poorly differentiated retinoblastomas. Screening more than 100 chemotherapies revealed an RB1–/–-specific cell sensitivity to carboplatin, exploiting their mitochondrial dysfunction. Together, our work provides a human pluripotent cell model for retinoblastoma and sheds light on developmental and tumorigenic roles of RB1., Graphical Abstract, Highlights • RB1-null hESCs were generated using CRISPR/Cas9 • RB1−/− hESCs generate large, neural-enriched teratomas, possibly by ZEB1 activation • RB1 inactivation triggers aberrant mitochondrial abundance and function • Unbiased drug screening found that carboplatin specifically targets RB1-null cells, Retinoblastoma is the most common congenital intraocular malignancy, caused by retinoblastoma-1 (RB1) inactivation. In this paper, Benvenisty and colleagues used CRISPR/Cas9 to generate RB1−/− human embryonic stem cells, and utilized them to reveal cellular, developmental, and tumorigenic aspects of this mutation. Furthermore, they have used this model in a drug screening, identifying a chemotherapy specifically targeting these mutant cells.
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- 2017
40. Molecular genetics of pineal region neoplasms.
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Taylor, Michael, Mainprize, Todd, Squire, Jeremy, and Rutka, James
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A large variety of mass lesions have been reported in the region of the pineal gland. Pineal parenchymal tumors and germ cell tumors (GCTs) are especially characteristic of this region. Despite their rarity, a number of excellent studies on the cytogenetics and molecular genetics of pineal parenchymal tumors and pineal region GCTs have been published. These studies draw attention to a number of distinct genomic regions recurrently involved in the various subtypes of malignancies of the pineal gland. Outcomes for tumors in this location vary widely between patients and among differing histologies. Development of novel therapies for patients with poor prognoses will depend on the acquisition of a more detailed understanding of the molecular basis associated with the etiopathogenesis of these neoplasms. We review the literature on cytogenetics, familial syndromes, animal models and molecular genetics of pineal region neoplasms. [ABSTRACT FROM AUTHOR]
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- 2001
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41. Pineoblastoma in children less than six years of age: The Head Start I, II, and III experience
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Girish Dhall, Ira J. Dunkel, Mohammad H Abu-Arja, Jason Fangusaro, Tom B. Davidson, Sharon Gardner, Jonathan L. Finlay, Joseph Stanek, and Mohamed S. AbdelBaki
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Male ,medicine.medical_specialty ,Trilateral retinoblastoma ,medicine.medical_treatment ,Pineal Gland ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Adjuvant therapy ,Humans ,Prospective Studies ,Child ,Chemotherapy ,business.industry ,Brain Neoplasms ,Hazard ratio ,Induction chemotherapy ,Infant ,Consolidation Chemotherapy ,Hematology ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Surgery ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Head start ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,business ,Pinealoma ,Progressive disease ,030215 immunology ,Follow-Up Studies - Abstract
Background We report the outcomes of patients with pineoblastoma and trilateral retinoblastoma syndrome enrolled on the Head Start (HS) I-III trials. Methods Twenty-three children were enrolled prospectively between 1991 and 2009. Treatment included maximal surgical resection followed by five cycles of intensive chemotherapy and consolidation with marrow-ablative chemotherapy and autologous hematopoietic cell rescue (HDCx/AuHCR). Irradiation following consolidation was reserved for children over six years of age or those with residual tumor at the end of induction. Results Median age was 3.12 years (range, 0.44-5.72). Three patients withdrew from the study treatment and two patients experienced chemotherapy-related death. Eight patients experienced progressive disease (PD) during induction chemotherapy and did not proceed to HDCx/AuHCR. Ten patients received HDCx/AuHCR; eight experienced PD post-consolidation. Seven patients received craniospinal irradiation (CSI) with a median dose of 20.7 Gy (range, 18-36 Gy) with boost(s) (median dose 27 Gy; range, 18-36 Gy); three received CSI as adjuvant therapy (two post-HDCx/AuHCR) and four upon progression/recurrence. The five-year progression-free survival (PFS) and overall survival (OS) were 9.7% (95% confidence intervals [CI]: 2.6%-36.0%) and 13% (95% CI: 4.5%-37.5%), respectively. Only three patients survived beyond five years. Favorable OS prognostic factors were CSI (hazard ratio [HR] = 0.30 [0.11-0.86], P = 0.025) and HDCx/AuHCR (HR = 0.40 [0.16-0.99], P = 0.047). Conclusions Within the HS I-III trials, CSI and HDCx/AuHCR were statistically associated with improved survival. The high PD rate during later induction cycles and following consolidation chemotherapy warrants consideration of fewer induction cycles prior to consolidation and the potential intensification of consolidation with multiple cycles of marrow-ablative chemotherapy and irradiation.
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- 2019
42. PDCT-13. PINEOBLASTOMA IN CHILDREN: THE HEAD START EXPERIENCE
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Mohammad H Abu Arja, Thomas Davidson, Sharon Gardner, Zachary N Funk, Ira J. Dunkel, Jonathan L. Finlay, Joseph Stanek, Girish Dhall, Mohamed S. AbdelBaki, and Jason Fangusaro
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0301 basic medicine ,Pineoblastoma ,Oncology ,Cancer Research ,medicine.medical_specialty ,Trilateral retinoblastoma ,business.industry ,medicine.medical_treatment ,Chemotherapy regimen ,Craniospinal Irradiation ,Radiation therapy ,Progressive Neoplastic Disease ,03 medical and health sciences ,Abstracts ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Head start ,Adjuvant therapy ,Medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
BACKGROUND: Pineoblastoma is a rare malignant pineal region tumor, the optimal management of which in young children remains unclear. METHODS: We report the outcomes of 23 children with pineoblastoma prospectively enrolled on three sequential Head Start (HS) trials between 1990 and 2009. The HS treatment strategy included maximal surgical resection followed by five cycles of intensive induction chemotherapy and consolidation with marrow-ablative chemotherapy and autologous hematopoietic cell rescue (HDCx/AuHCR). Irradiation following recovery from consolidation was reserved for children over six years old or with residual tumor. RESULTS: Data on 23 children with pineoblastoma including two with trilateral retinoblastoma aged 0.44–5.72 (median 3.12) years were analyzed. Median overall survival (OS) was 12 months (95% CI: 7.6–29.7 months). The 3-year progression-free survival (PFS) and OS were 14.5% (95% CI: 5.1–41.2%) and 17.4% (95% CI: 7.1–42.4%), respectively. Three patients were long-term survivors beyond 5 years. Eight patients experienced progressive disease (PD) during induction chemotherapy, six following the fourth and fifth cycles. Ten patients proceeded to consolidation with HDCx/AuHCR; eight experienced PD post-consolidation. Seven patients received craniospinal irradiation with boost(s) (median dose 20.7 (18–36) Gy), three patients as adjuvant therapy and four upon progression/recurrence. Favorable prognostic factors were administration of radiotherapy (hazard ratio (HR) for OS=0.30 (0.11–0.86), p
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- 2018
43. LINC-36. TRILATERAL RETINOBLASTOMA: A REPORT OF FOUR CASES
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Ludi Dhyani Rahmartani
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Cancer Research ,Oncology ,Trilateral retinoblastoma ,business.industry ,Pediatric Neuro-Oncology in Asia and other Low/Middle Income Countries ,Cancer research ,AcademicSubjects/MED00300 ,Medicine ,AcademicSubjects/MED00310 ,Neurology (clinical) ,business ,eye diseases - Abstract
Retinoblastoma is the most common primary malignant intraocular cancer that usually develops in early childhood. About 5% of those patients are at risk of developing trilateral retinoblastoma (TRB). In developing countries, most of them came in the late stage; therefore, ocular and patient survival rates are lower than in developed countries. From 2015–2019, we found four cases of trilateral retinoblastoma. Two of them had bilateral retinoblastoma, and two had unilateral retinoblastoma. They all presented with leukocoria and had no family history of retinoblastoma. The mean age was 13.8 months (range 9–24 months of age). The diagnosis of trilateral retinoblastoma was made from initial head CT/MRI. They were treated conservatively with high dose VEC chemotherapy, and three of them have died during treatment. Trilateral retinoblastoma is usually fatal and needs multidisciplinary treatment care. In developing countries, it is important to evaluate distant metastasis. Head CT or MRI from the initial diagnosis to exclude the trilateral retinoblastoma.
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- 2020
44. Corrigendum to 'Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. 'Alive, with good vision and no comorbidity'' [Prog. Retina Eye Res. 73 (2019) 100764]
- Author
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David Cobrinik, Alexandre Moulin, Tero Kivelä, Susan Houghton, Francis L. Munier, Ciara Bergin, Yvan Vial, Paula Schaiquevich, Marie Claire Gaillard, Philippe Maeder, Christina Stathopoulos, Paul J. Dyson, Maja Beck-Popovic, Annette C. Moll, Dietmar R. Lohmann, Guillermo Chantada, Francesco Puccinelli, and Angel M. Carcaboso
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Oncology ,Melphalan ,medicine.medical_specialty ,Trilateral retinoblastoma ,Intraocular Retinoblastoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,030304 developmental biology ,0303 health sciences ,Retinoblastoma ,business.industry ,Uvea ,medicine.disease ,eye diseases ,Sensory Systems ,3. Good health ,Ophthalmology ,medicine.anatomical_structure ,030221 ophthalmology & optometry ,Differential diagnosis ,Phthisis bulbi ,business ,Unilateral Retinoblastoma ,medicine.drug - Abstract
The authors regret that Science Direct is not formatted to display the full content of the paper synopsis. This is now fixed with the publication of this corrigendum. List of contents 1. Introduction2. Epidemiology 2.1. Incidence2.2. Prevalence2.3. Predisposing factors for sporadic retinoblastoma3. Diagnosis 3.1. Presenting features3.2. Clinical examination and ancillary testing 3.2.1. Fundus documentation and fluorescein angiography3.2.2. Ultrasonic biomicroscopy (UBM)3.2.3. Optic coherence tomography (OCT)3.2.4. Magnetic Resonance Imaging (MRI)3.3. Classifications 3.3.1. Grouping of the eye at presentation (RE, IIRC, ICRB, COG, TNMH)3.3.2. Patient staging at presentation (IRSS, TNMH)3.3.3. Classification of retinoblastoma at relapse (RSU classification)3.4. Differential diagnosis3.5. Prenatal diagnosis of retinoblastoma3.6. Trilateral retinoblastoma 3.6.1. Incidence, early detection and screening3.6.2. Influence of the retinoblastoma treatment on the incidence of trilateral retinoblastoma3.6.3. Improved treatment of trilateral retinoblastoma: high-dose chemotherapy3.6.4. Differential diagnosis: pineal cysts3.7. Metastatic retinoblastoma 3.7.1. Diagnosis of metastatic retinoblastoma3.7.2. Treatment of metastatic retinoblastoma3.7.3. Influence of conservative retinoblastoma treatment in the occurrence of metastasis3.8. Second primary neoplasms 3.8.1. Incidence and mortality of second primary neoplasms3.8.2. Characteristics of secondary primary neoplasms3.8.3. Factors influencing the risk of secondary primary neoplasms 3.8.3.1. Genetic predisposition3.8.3.2. Influence of therapy3.8.3.2.1. Radiotherapy3.8.3.2.2. Chemotherapy3.8.4. Long-term follow-up in heritable retinoblastoma survivors 4. Retinoblastoma genesis 4.1. Mutational inactivation of the RB1 gene initiates retinoblastoma tumorigenesis4.2. Most retinoblastomas show more than two-hits4.3. RB1 mutations initiate tumorigenesis in the retinoblastoma cell-of-origin 4.3.1. First hints pointing towards a photoreceptor cell-of-origin4.3.2. Efforts to identify the retinoblastoma origin using genetically engineered mice4.3.3. Circumstantial and direct evidence for a cone precursor cell-of-origin4.3.4. Reconciling the cone precursor cell-of-origin with apparently contradictory observations4.4. Collaboration between RB1 inactivation and the cell-of-origin circuitry5. Retinoblastoma genetics and genetic counseling 5.1. Genetic presentations of retinoblastoma 5.1.1. Inherited heritable retinoblastoma (familial retinoblastoma) 5.1.1.1. Familial retinoblastoma with complete retinoblastoma5.1.1.2. Familial retinoblastoma with incomplete penetrance5.1.2. Isolated heritable retinoblastoma 5.1.2.1. Isolated bilateral retinoblastoma (full expressivity)5.1.2.2. Isolated retinoblastoma with genomic 13q14 deletion (reduced expressivity)5.1.3. Mosaic retinoblastoma5.1.4. Non-heritable retinoblastoma 5.1.4.1. Isolated unilateral retinoblastoma with somatic biallelic RB1 mutation5.1.4.2. Retinoblastoma without alterations of the RB1 gene 5.2. Genetic counseling and testing 5.2.1. Familial retinoblastoma5.2.2. Isolated bilateral retinoblastoma5.2.3. Isolated unilateral retinoblastoma 6. Clinical growth and seeding patterns 6.1. Retinoblastoma growth patterns 6.1.1. Classic growth patterns of primary retinoblastoma: endophytic, exophytic, mixed growth6.1.2. Rare variants of retinoblastoma 6.1.2.1. Cavitary retinoblastoma6.1.2.2. Diffuse infiltrating retinoblastoma6.1.2.3. Diffuse anterior retinoblastoma 6.2. Intra-ocular seeding 6.2.1. Vitreous seeding6.2.2. Retrohyaloid seeding6.2.3. Subretinal seeding6.2.4. Aqueous seeding 6.2.4.1. Prevalence of anterior chamber seeding6.2.4.2. Prevalence of anterior uvea invasion6.2.4.3. Invasion mechanisms of the aqueous humor 6.3. Retinoma/retinocytoma and phthisis bulbi 6.3.1. Prevalence and relationship with retinoblastoma6.3.2. Clinical features and risk of malignant transformation. 7. Conservative management of intraocular retinoblastoma 7.1. Pharmacokinetics 7.1.1. Intravenous drug delivery7.1.2. Intra-arterial drug delivery 7.1.2.1. Intraocular distribution of intra-arterial melphalan and topotecan7.1.2.2. Systemic adverse effects of intra-arterial delivered drugs7.1.3. Intravitreal drug delivery 7.1.3.1. Intraocular distribution of intravitreal melphalan7.1.3.2. Intraocular distribution of intravitreal topotecan7.1.4. Intracameral drug delivery7.1.5. Periocular drug delivery7.1.6. Suprachoroidal drug delivery7.2. Treatment modalities 7.2.1. Intravenous chemotherapy 7.2.1.1. Drug regimen and number of cycles7.2.1.2. Indications 7.2.1.2.1. Current indications7.2.1.2.2. Potential future indications 7.2.2. Treatment outcomes of intravenous chemotherapy 7.2.2.1. Relapse rate and role of consolidation by focal treatments7.2.2.2. Eye preservation without external beam radiotherapy7.2.3. Chemotherapy-related toxicity of intravenous chemotherapy 7.2.3.1. Expected toxicities7.2.3.2. Long-term toxicities7.2.4. Intra-arterial chemotherapy 7.2.4.1. Drug regimen and number of cycles7.2.4.2. Indications 7.2.4.2.1. Current indications7.2.4.2.2. Potential future indications7.2.4.3. Treatment outcomes 7.2.4.3.1. Recurrence rate and salvage therapy7.2.4.3.2. Eye preservation without external beam radiotherapy7.2.4.4. Adverse effects7.2.5. Intravitreal chemotherapy 7.2.5.1. Drug regimen and number of injections7.2.5.2. Safety7.2.5.3. Treatment outcomes7.2.5.4. Adverse effects7.2.6. Intracameral chemotherapy 7.2.6.1. Treatment outcomes7.2.6.2. Treatment-related adverse effects7.2.6.3. Potential alternatives to intracameral chemotherapy for aqueous seeding7.2.7. Periocular chemotherapy7.2.8. Focal treatments 7.2.8.1. Cryotherapy7.2.8.2. Hyperthermia7.2.8.3. Photocoagulation7.2.8.4. Brachytherapy 7.3. Disease and treatment-related complications 7.3.1. Amblyopia7.3.2. Cataract 7.3.2.1. Incidence7.3.2.2. Cataract surgery7.3.3. Rhegmatogenous retinal detachment 7.3.3.1. Incidence7.3.3.2. Surgical repair7.3.4. Secondary neovascularization7.3.5. Chorioretinal complications 7.3.5.1. Intravitreal melphalan-induced chorioretinopathy 7.3.5.1.1. Clinical presentation, classification system and incidence7.3.5.1.2. Risk factors associated with intravitreal melphalan-induced chorioretinopathy 7.3.5.1.2.1. Intravitreal concentration7.3.5.1.2.2. Para-vitreal injections7.3.5.1.2.3. Intraocular pigmentation7.3.5.1.2.4. Concomitant drug interactions 7.3.5.2. Choroidal occlusive vasculopathy 7.3.5.2.1. Clinical presentation, classification system and incidence.7.3.5.2.2. Factors associated with choroidal occlusive vasculopathy 7.4. Evaluation of quality of life8. Future directions and conclusion 8.1. Animal models8.2. Gene therapy8.3. Cell-of-origin targeted therapy8.4. Personalized therapy and liquid biopsy8.5. New drugs or combinations of drugs8.6. New Galenic formulation of known drugs8.7. Conclusion
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- 2020
45. Imaging in the trilateral retinoblastoma syndrome.
- Author
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Bagley, L., Hurst, R., Zimmerman, R., Shields, J., Shields, C., and Potter, P.
- Abstract
The medical records, CT, and MRI of ten children with trilateral retinoblastoma were reviewed. The intracranial pathology consisted of eight pineal neoplasms and two parasellar lesions, at least seven of the which were calcified. Two lesions demonstrated calcification only (no soft tissue mass) at initial presentation. Hydrocephalus was seen in eight cases, and concurrent or subsequent subarachnoid dissemination was documented in seven. Only one patient is known to be alive at the present time. The imaging features of the midline intracranial tumors mirror those of the ocular neoplasm. As calcification may be the only clue to the presence of the intracranial malignancy, close surveillance of high-risk patients with retinoblastoma with initial CT and follow-up MRI is suggested. [ABSTRACT FROM AUTHOR]
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- 1996
- Full Text
- View/download PDF
46. PEDT-04 SIX CASES OF RETINOBLASTOMA WITH CNS INVOLVEMENT
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Yoshiyuki Tsutsumi, Shinichi Tsujimoto, Keita Terashima, Kenichi Usami, Noriyuki Azuma, Masahiro Sugawa, Chikako Kiyotani, Takako Yosioka, Hideki Ogiwara, Hiroshi Fuji, Kyohei Isshiki, and Kimikazu Matsumoto
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Pathology ,medicine.medical_specialty ,Trilateral retinoblastoma ,business.industry ,Retinoblastoma ,medicine.medical_treatment ,Central nervous system ,medicine.disease ,Chemotherapy regimen ,Radiation therapy ,Abstracts ,Cerebrospinal fluid ,medicine.anatomical_structure ,Pediatric Clinical Trials/Therapeutic Studies (Pedt) ,medicine ,Optic nerve ,business ,Survival rate - Abstract
Although the survival rate of intraocular retinoblastoma (RB) is nearly 100%, the outcome of central nervous system (CNS) involvement or Trilateral retinoblastoma (TRb: very rare RB which associated with brain tumor) is dismal. We retrospectively reviewed our six cases of these rare tumors. Their ages at diagnosis are 0y3m-1y10m (median 1y3m) (Male 4, Female 2). Only one had RB family history. Their affected eyes were bilateral 2, unilateral 3 and no 1. Their CNS diseases were suprasellar tumor 3, pineal tumor 1 and cerebrospinal fluid (CSF) cytology positive 2. Two of the suprasellar tumor patients had spinal metastasis. Three of the six patients were TRb. One TRb patient was treated with chemotherapy and high-dose chemotherapy without radiotherapy. Although he suffered with secondary osteosarcoma seven years later, he got complete remission and alive 5 years more without any tumor recurrence. The second TRb patient was treated with chemotherapy and local radiotherapy but relapsed 20 months later. The third TRb patient was chemotherapy resistant. Two CSF positive patients had optic nerve invasion. One patient with chiasm invasion died 11 months later because of treatment resistance. The other patient with optic nerve invasion before optic canal had no CNS tumor nor CSF involvement at diagnosis. Chemotherapy before enucleation was given to avoid dissemination. However, CSF cytology became positive after enucleation and remained even with intensified chemotherapy. Finally, he got remission with radiotherapy and high-dose chemotherapy, and alive without disease for 3.8 years. The last patient had suprasellar genetically classified retinoblastoma tumor and cerebrospinal metastasis. This patient showed good chemotherapy response and is still under treatment. Even with "so called° fatal RB cases, some case could survive with intensified therapy. Data accumulation is necessary for better survival of these tumors.
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- 2019
47. An In Utero Presentation of Trilateral Retinoblastoma.
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Abramson DH, Bian Y, Belinsky I, and Francis JH
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- Adult, Biopsy, Brain pathology, Female, Humans, Magnetic Resonance Imaging, Pregnancy, Ultrasonography, Neoplasm Staging, Pregnancy Complications, Neoplastic, Retina diagnostic imaging, Retinal Neoplasms diagnosis, Retinoblastoma diagnosis
- Published
- 2021
- Full Text
- View/download PDF
48. Epidemiology and imaging of retinoblastoma
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de Jong, M.C. and de Jong, M.C.
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- 2017
49. Uniocular Trilateral Retinoblastoma with Spinal Metastases
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Geng-Yi Yong
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medicine.medical_specialty ,Trilateral retinoblastoma ,business.industry ,medicine ,Radiology ,Spinal metastases ,business - Published
- 2017
50. RB1 gene mutations in Argentine retinoblastoma patients. Implications for genetic counseling
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Irene Szijan, Diana Lidia Parma, Marcela Maria Ferrer, Leonela Natalia Luce, and Florencia Giliberto
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0301 basic medicine ,Male ,Physiology ,Ophthalmologic Tumors ,lcsh:Medicine ,Penetrance ,Medicina Clínica ,medicine.disease_cause ,Retinoblastoma Protein ,Oncología ,purl.org/becyt/ford/1 [https] ,Database and Informatics Methods ,0302 clinical medicine ,purl.org/becyt/ford/3.2 [https] ,Medicine and Health Sciences ,Medicine ,Blastomas ,lcsh:Science ,Frameshift Mutation ,Base Pairing ,Mutation ,Multidisciplinary ,Insertion Mutation ,biology ,Retinoblastoma ,Retinoblastoma protein ,Nonsense Mutation ,purl.org/becyt/ford/3.1 [https] ,Exons ,Bioquímica y Biología Molecular ,Pedigree ,Body Fluids ,Medicina Básica ,Treatment Outcome ,Blood ,Deletion Mutation ,Oncology ,030220 oncology & carcinogenesis ,Child, Preschool ,purl.org/becyt/ford/3 [https] ,Female ,Anatomy ,Unilateral Retinoblastoma ,Mutations ,CIENCIAS NATURALES Y EXACTAS ,Research Article ,Heterozygote ,CIENCIAS MÉDICAS Y DE LA SALUD ,Trilateral retinoblastoma ,Nonsense mutation ,Genética Humana ,Argentina ,Genetic Counseling ,Research and Analysis Methods ,Ciencias Biológicas ,03 medical and health sciences ,Germline mutation ,Genetics ,Humans ,purl.org/becyt/ford/1.6 [https] ,Base Sequence ,business.industry ,lcsh:R ,Infant, Newborn ,Infant ,Biology and Life Sciences ,Cancers and Neoplasms ,Rb1 Gene ,medicine.disease ,eye diseases ,030104 developmental biology ,Biological Databases ,Mutation Databases ,biology.protein ,Cancer research ,lcsh:Q ,business - Abstract
Retinoblastoma (RB) is an inherited childhood ocular cancer caused by mutations in the tumor suppressor RB1 gene. Identification of RB1 mutations is essential to assess the risk of developing retinoblastoma in the patients´ relatives. Retinoblastoma is a potentially curable cancer and an early diagnosis is critical for survival and eye preservation. Unilateral retinoblastoma is mostly non-heritable and results from two somatic mutations whereas bilateral retinoblastoma is heritable and results from one germline and one somatic mutation, both have high penetrance, 90%. The purpose of this study was to identify causative RB1 mutations in RB patients with different clinical presentations. A comprehensive approach was used to study a cohort of 34 patients with unilateral, bilateral and trilateral retinoblastoma. Blood and tumor DNA was analyzed by sequencing and multiplex ligation-dependent probe amplification (MLPA) assay. Validation of an insertion mutation was performed by cloning the PCR product. Most of the patients in our cohort had unilateral RB, eight patients had bilateral RB and one patient had a trilateral tumor with ocular and suprasellar/sellar locations. Other tumors in addition to retinoblastoma were also found in the affected families. One patient had two syndromes, retinoblastoma and schwannomatosis, and another RB patient had a father with a retinoma. Five out of the 25 unilateral RB patients carried germinal mutations (20%), which were mostly missense mutations. The bilateral and trilateral patients carried splice-site, nonsense and frameshift mutations as well as a whole RB1 gene deletion. Missense mutations were associated with mild phenotype: unilateral retinoblastoma, retinoma or no tumor. In this study we identified causative RB1 mutations in most bilateral RB patients and in some unilateral RB patients, including five novel mutations. These data are crucial for genetic counseling and confirm the need to perform complete genetic screening for RB1 mutations in both constitutional and tumor tissues. Fil: Parma, Diana Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Ferrer, Marcela Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Luce, Leonela Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Giliberto, Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Szijan, Irene. Universidad de Buenos Aires; Argentina
- Published
- 2017
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