Cases Of Retinoblastoma Research Articles

Unilateral unifocal advanced intraocular retinoblastoma: is reasonable to adopt intra‐arterial chemotherapy as single therapeutic choice?

AbstractPurposeTo report the outcome of 30 naive unilateral unifocal retinoblastoma cases treated with intra‐arterial chemotherapy alone.MethodsFrom 2008 to 2019, 192 eyes affected with retinoblastoma have been treated with intra‐arterial chemotherapy (IAC). 100 out of 192 (52%) eyes were naive advanced unilateral unifocal retinoblastoma (Group B‐E). 30 out of 100 (30%) received intra‐arterial chemotherapy alone. All patients underwent genetic testing at diagnosis. MR was performed at diagnosis, during treatment (when necessary), 3 months after last infusion and annually to evaluate eyeball growth.ResultsTumor control and globe salvage was achieved in 100% of the reported cases (follow‐up ranged from 11 years to 9 months). New tumors or relapse have not been detected. No further local or systemic therapies were necessary. Procedure complications and local and systemic effects are reported. No intraocular or orbital tumor recurrence or metastatic disease have been observed observed.ConclusionsThe outcome will be correlated to genetic analysis, doses and drugs used (alone or in combination) and number of infusions received.

Molecular subgrouping of primary pineal parenchymal tumors reveals distinct subtypes correlated with clinical parameters and genetic alterations.

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.

Intra-arterial chemotherapy for retinoblastoma: an updated systematic review and meta-analysis

Background and purposeIntra-arterial chemotherapy for retinoblastoma has been adopted as a first-line treatment option by numerous tertiary centers. The effect of intra-arterial chemotherapy on future rates of metastatic disease as...

Эффект родительского происхождения мутации в гене RB1 при наследственной ретинобластоме с низкой пенетрантностью

Актуальность. При наследственной ретинобластоме герминальная мутация в одном из аллелей гена RB1 обусловливает предрасположенность к заболеванию и его семейную передачу. Наследственная ретинобластома манифестирует в более раннем возрасте по сравнению со спорадической формой и носит в большинстве случаев мультифокальный и билатеральный характер. Однако некоторые семьи с ретинобластомой (два и более носителя одинаковой герминальной мутации в родословной) демонстрируют более мягкий фенотип с неполной пенетрантностью (у части носителей герминальной мутации заболевание не развивается) и вариабельной экспрессивностью (одинаковая мутация у разных членов семьи может проявляться уни- или билатеральной формой заболевания). Выявление низкопенетрантных мутаций в гене RB1 и изучение характера их наследования способствует пониманию механизмов, лежащих в основе развития наследственной ретинобластомы с низкой пенетрантностью, и крайне важно как для дальнейшего расширения знаний о молекулярной генетике ретинобластомы, так и для медико-генетического консультирования и последующего клинического ведения семей с такой формой заболевания. Цель. Установить спектр генетических нарушений в гене RB1 у больных с наследственной ретинобластомой с неполной пенетрантностью и вариабельной экспрессивностью в выборке российских пациентов и определить влияние родительского происхождения мутации в RB1 на её фенотипическое проявление. Методы. Методом высокопроизводительного параллельного секвенирования проведено молекулярно-генетическое обследование 332 неродственных больных с ретинобластомой. Для верификации выявленных точковых мутаций и анализа их сегрегации в родословных использовали секвенирование по Сэнгеру. Результаты. В группе пациентов без семейного анамнеза ретинобластомы у 3,5% больных определен наследственный характер заболевания, при котором один из родителей являлся бессимптомным носителем герминальной мутации в гене RB1. Выявлено 10 низкопенетрантных мутаций в гене RB1 и установлен спектр мутаций, приводящих к развитию наследственной ретинобластомы с низкой пенетрантностью. В 91,7% случаев наследственной ретинобластомы с низкой пенетрантностью мутантный аллель получен пробандом от отца, у которого отсутствовали клинические признаки заболевания или наблюдалась более легкая форма. Выводы. Полученные результаты подтверждают ранее высказанные предположения, что низкопенетрантные герминальные мутации в гене RB1, унаследованные от отца, чаще приводят к развитию ретинобластомы, и в более тяжелой форме по сравнению с таковыми, унаследованными от матери. Background. In hereditary retinoblastoma, a germline mutation in one of the alleles of the RB1 gene causes a predisposition to the disease and its transmission within the pedigree. Hereditary retinoblastoma manifests at an earlier age compared with the sporadic form and in most cases is multifocal and bilateral. However, some families with retinoblastoma (two or more carriers of the same germline mutation in the pedigree) exhibit a milder phenotype with incomplete penetrance (some carriers of the germline mutation are asymptomatic) and variable expressivity (the same mutation in different family members may manifest as either a unilateral or bilateral form). Identification of low-penetrant mutations in the RB1 gene and studying their inheritance in pedigrees contributes to understanding the mechanisms underlying the development of retinoblastoma with low penetrance. It is extremely important both for further expansion of knowledge in the field of molecular genetics of retinoblastoma, and for competent genetic counseling and subsequent clinical management of families with this form of the disease. Objective. To establish the spectrum of genetic disorders in the RB1 gene in Russian patients with hereditary retinoblastoma with incomplete penetrance and variable expressivity and to determine the effect of the parental origin of the RB1 mutation on its phenotypic manifestation. Methods. Using high-performance parallel sequencing, a molecular genetic survey of 332 unrelated patients with retinoblastoma was performed. Sanger sequencing was used to verify the identified point mutations and analyze their segregation in pedigrees. Results. In the group of patients without a family history of retinoblastoma, in 3.5% the hereditary nature of the disease was determined, where one of the parents was an asymptomatic carrier of a germline mutation in the RB1 gene. Ten low-penetrant mutations in the RB1 gene were identified. In 91.7% of cases of hereditary retinoblastoma with low penetrance, the mutant allele was obtained by a proband from a father with no clinical signs of the disease or with a milder form. Conclusion. The results confirm the previously suggested assumptions that low-penetrant germline mutations in the RB1 gene inherited from the father more often lead to the development of retinoblastoma, and in a more severe form than those inherited from the mother.

Endovascular Super-Selective Intra-Arterial Chemotherapy for Retinoblastoma: Systematic Review and Institutional Experience

Abstract INTRODUCTION Selective intra-arterial delivery of chemotherapy (IAC) via microcatheter infusion into the ophthalmic artery has become an increasingly popular treatment modality to accomplish globe salvage in children with retinoblastoma. While previously limited to highly specialized centers, interest in and popularity of this treatment are growing. Here, we provide a comprehensive review of available data in addition to our own experience. METHODS Systematic literature review was conducted using PRISMA guidelines and 22 studies were identified that met inclusion criteria. In our own series, consecutive patients undergoing IAC for retinoblastoma were identified between January 2009 and December 2016. Pertinent data, including tumor grade, enucleation vs globe salvage, and both ocular and systemic adverse events were recorded. RESULTS In all1593 total eyes were treated as reported in 22 studies published between 2011 and 2019. Among those in which tumor staging data was available, 396 (27.6%) were less advanced (Reese–Ellsworth A-C, or International Classification I-III) and 997 (69.4%) were more advanced (D-E, IV-V). A total of 21 studies included data on systemic and/or ocular complications, which with few exceptions were transient and resulted in no permanent morbidity. A single permanent neurological complication occurred. Analysis of our institutional experience demonstrated a globe salvage rate of 73% (identical to pooled data from the literature). In 442 procedures, our ocular and systemic complication rates were 10.6% and 13.8%, respectively; virtually all were transient phenomena including orbital edema, myelosuppression, and and brief intraprocedural bronchospasm/bradycardia during drug delivery. CONCLUSION Although reported predominantly in retrospective series, a systematic review of outcomes in selective IAC for retinoblastoma demonstrates efficacy (73% globe salvage rate) with minimal morbidity, even in advanced disease. Our own results reflect a similar experience and taken together, provide strong evidence that this treatment modality is safe and effective. The data support adoption of this technique as first-line therapy for globe salvage in selected cases of retinoblastoma.

Primitive Ocular Cancers in the University Hospital of Brazzaville

Introduction: With the exception of retinoblastoma and melanoma of the uveal tract, primitive ocular cancers originate from the accessory structures of the eye, especially the eyelids and the conjunctiva. While in developed countries these cancers are mostly encountered after 60 years, in black Africa their prevalence has increased in young adults. Objective: To determine the epidemiological, clinical and histological profile of these tumors in the University Hospital of Brazzaville. Methodology: Mini analysis of nine (9) of our publications, published between 2015 and 2017, in the journals: East African Medical Journal, Health Science and Diseases, EC Ophthalmology, and Revue de Médecine et de Pharmacie. HIV serology has been systematically requested except for cases of retinoblastoma. Histological evidence was made in all cases. Results: 86 patients had been seen. Average age 31.2 years (2 years - 75 years), sex ratio equal to 1.08. Reasons for consultation: exophthalmia (44), mass (35%), leucocoria (20%) and palpebral wounds (1%). Affected structures: conjunctiva (38%), retina (35%) and eyelid (27%). Histological types: squamous cell carcinoma (55.5%), retinoblastoma (25.9%), basal cell carcinoma (8.5%), sebaceous carcinoma (5.5%), Kaposia’s sarcoma (3.5%) and acral melanoma lentiginous (1.1%). HIV serology was positive in 38% overall, but in 100% of conjunctival cancers. Conclusion: Primitive ocular cancers are dominated in children by retinoblastoma. In young adults, these are essentially opportunistic cancers in the context of HIV / AIDS.

Indications for Destructive Eye Surgeries among Children in a Tertiary Eye Care Center in North-Central Nigeria: A Ten Year Review

This study aimed to assess the indications for destructive eye surgeries (DES) among children and ascertain the proportion avoidable. The Eye theatre register was retrospectively reviewed. Data on children who had DES from 1st January 2008-31st December 2017 was retrieved. These included biodata; clinical presentation, diagnosis, indication and type of surgery, and outcome of management. The total number of paediatric ophthalmic surgeries within the study period was computed. The data were entered into Epi Info statistical software, version 3.4 for analysis. Descriptive and analytical statistics were applied, p-values < 0.05 were considered statistically significant. A total of 634 ophthalmic surgeries were performed on children within the study period, 50(7.9%) eyes of 49 children had destructive eye surgeries. Thirty-three (67.3%) were males and 16(32.7%) were females; M:F ratio was 2.1:1. The mean age was 6.7±5.0 years with a range of 1.7-11.7years (Mean±SD). Most, 27(55.1%) of the participants had evisceration, 15(30.6%) had enucleation while 7(14.3%) had exenteration. More males, 24(72.7%) had evisceration while more females 10(62.5%) had enucleation (Fisher’s exact test=13.8, p=0.001). The main indications for DES included tumour in 22(44%) eyes, trauma to eyes in 13(26%) and intractable infections in 8(16%) eyes. All the 15 eyes enucleated were confirmed cases of retinoblastoma. Seven (14.3%) persons had orbital exenteration of which 6(85.7%) were retinoblastoma. In all, 42(84%) destructive eye surgeries in this study were avoidable. There is a need for improved enforcement of the “Child’s Right Act” in our environment.

Indications for Destructive Eye Surgeries among Children in a Tertiary Eye Care Center in North-Central Nigeria: A Ten Year Review

This study aimed to assess the indications for destructive eye surgeries (DES) among children and ascertain the proportion avoidable. The Eye theatre register was retrospectively reviewed. Data on children who had DES from 1st January 2008-31st December 2017 was retrieved. These included biodata; clinical presentation, diagnosis, indication and type of surgery, and outcome of management. The total number of paediatric ophthalmic surgeries within the study period was computed. The data were entered into Epi Info statistical software, version 3.4 for analysis. Descriptive and analytical statistics were applied, p-values < 0.05 were considered statistically significant. A total of 634 ophthalmic surgeries were performed on children within the study period, 50(7.9%) eyes of 49 children had destructive eye surgeries. Thirty-three (67.3%) were males and 16(32.7%) were females; M:F ratio was 2.1:1. The mean age was 6.7±5.0 years with a range of 1.7-11.7years (Mean±SD). Most, 27(55.1%) of the participants had evisceration, 15(30.6%) had enucleation while 7(14.3%) had exenteration. More males, 24(72.7%) had evisceration while more females 10(62.5%) had enucleation (Fisher’s exact test=13.8, p=0.001). The main indications for DES included tumour in 22(44%) eyes, trauma to eyes in 13(26%) and intractable infections in 8(16%) eyes. All the 15 eyes enucleated were confirmed cases of retinoblastoma. Seven (14.3%) persons had orbital exenteration of which 6(85.7%) were retinoblastoma. In all, 42(84%) destructive eye surgeries in this study were avoidable. There is a need for improved enforcement of the “Child’s Right Act” in our environment.

Indications for Destructive Eye Surgeries among Children in a Tertiary Eye Care Center in North-Central Nigeria: A Ten Year Review

This study aimed to assess the indications for destructive eye surgeries (DES) among children and ascertain the proportion avoidable. The Eye theatre register was retrospectively reviewed. Data on children who had DES from 1st January 2008-31st December 2017 was retrieved. These included biodata; clinical presentation, diagnosis, indication and type of surgery, and outcome of management. The total number of paediatric ophthalmic surgeries within the study period was computed. The data were entered into Epi Info statistical software, version 3.4 for analysis. Descriptive and analytical statistics were applied, p-values < 0.05 were considered statistically significant. A total of 634 ophthalmic surgeries were performed on children within the study period, 50(7.9%) eyes of 49 children had destructive eye surgeries. Thirty-three (67.3%) were males and 16(32.7%) were females; M:F ratio was 2.1:1. The mean age was 6.7±5.0 years with a range of 1.7-11.7years (Mean±SD). Most, 27(55.1%) of the participants had evisceration, 15(30.6%) had enucleation while 7(14.3%) had exenteration. More males, 24(72.7%) had evisceration while more females 10(62.5%) had enucleation (Fisher’s exact test=13.8, p=0.001). The main indications for DES included tumour in 22(44%) eyes, trauma to eyes in 13(26%) and intractable infections in 8(16%) eyes. All the 15 eyes enucleated were confirmed cases of retinoblastoma. Seven (14.3%) persons had orbital exenteration of which 6(85.7%) were retinoblastoma. In all, 42(84%) destructive eye surgeries in this study were avoidable. There is a need for improved enforcement of the “Child’s Right Act” in our environment.

Episcleral brachytherapy for retinoblastoma

Background/AimsTo report visual outcomes, survival outcomes and complications following episcleral brachytherapy (EB) for retinoblastoma.MethodsRetrospective review of retinoblastoma cases treated with EB in a single institution. Survival outcomes were analysed using...

Human papillomavirus in ocular malignant tumours: a study from a tertiary eye care centre in North India

ObjectiveThe present study aims to detect the presence of human papillomavirus (HPV) in ocular malignant tumours, including retinoblastoma, eyelid squamous cell carcinoma (SCC), and sebaceous gland carcinoma (SGC), in the North Indian population. DesignProspective observational non randomized study. ParticipantsIn this study, 142 prospective cases of ocular malignant tumours (retinoblastoma, SGC, and SCC) were included. MethodsHPV was detected by multiplex PCR using PGMY09/11 primers in 142 patients with ocular malignancies. This was followed by genotyping using linear array (reverse hybridization). ResultsOf the 142 tumours studied, 72 were retinoblastoma, 30 SGC, and 40 SCC. The HPV genome was detected in 2.8% (4 of 142) of cases by multiplex PCR; all positive cases (4 of 40) were SCC. Genotyping revealed that all positives belonged to the high-risk HPV16 genotype. HPV-positive SCC patients had better disease-free survival. Retinoblastoma and SGC cases were negative for HPV. ConclusionsLow prevalence of HPV in ocular malignancies was observed in this study. The HPV genome was detected only in ocular squamous cell carcinoma cases and these patients were associated with better prognosis. HPV may not have a role in retinoblastoma and SGC in the North Indian population.

Demographics of Pediatric Orbital Lesions: A Tertiary Eye Center Experience in Saudi Arabia

Orbital lesions vary in their classification, incidence, and presentation depending on the age and geographic distribution. Such lesions in the pediatric age group have been studied extensively because of the possibility of faster progression of orbital involvement and the higher risk of morbidity in this age group in which vision is still developing. In Saudi Arabia, orbital lesions were studied over a 6-year period in the late 1980s, when retinoblastoma cases used to present late with orbital involvement. In this study, we revisited the same topic 20 years later aiming to find out the most recent prevalence of orbital lesions in a similar population of patients over a longer period (14 years) in the same eye center, and compare the current results to other reports worldwide. A total of 107 lesions from 106 patients were identified by tissue diagnosis, of which more than half of the lesions were benign cystic (being the most common), vasculogenic, and inflammatory in 63% [95% confidence interval (CI, 53.3–72.0)] of all biopsied lesions. Neoplasms accounted for 37% [95% CI (28.0–45.8)] with rhabdomyosarcoma being the most common, accounting for about one third of neoplasms, and no orbital cases of retinoblastoma were found. Our results demonstrated different distribution of orbital lesions in recent years reflecting the indirect effect of the improved health awareness and medical care in Saudi Arabia. This baseline demographic study is expected to be helpful for further clinical and prognostic studies with emphasis on pediatric orbital malignant lesions, their clinical presentation, management, and prognosis.

Retinoblastoma – Lessons Learned about Patterns of Care and Contributory Factors from 5 Years’ Experience in a Tertiary Care Center in Eastern India

Objectives: Retinoblastoma is the most common intraocular malignancy afflicting children worldwide. Even though there are enough data about the epidemiology of retinoblastoma in western population, there are only few reports from developing countries like India. In this retrospective study, we aimed to describe the epidemiological patterns, survival characteristics and prognostic factors of retinoblastoma.
 Materials and Methods: From medical records, we retrospectively analyzed the data of 68 children diagnosed in our hospital between January 2013 and December 2017 as having retinoblastoma. Data on sex, religion, laterality, age at diagnosis, presenting signs, family history, lag time for treatment, cause of such lag time and spread of tumor, treatment mode, and survival time were collected.
 Results: The median age of onset was 22 ± 19.73 months (range 2-92 months).The median patient age of onset of the unilateral cases was 23 ± 20.6 months, and that of the bilateral cases was 21 ±16.2 months. The median overall survival was 28.1±2.2 months. For unilateral cases, it was 30.1±2.5 months and for bilateral cases it was 19.7±2.9 months. The overall progression free survival (PFS) was 22.2±2.3 months. For unilateral cases, it was 24.18±2.7 months and for bilateral cases it was 13.9±2.9 months.
 4 cases of familial retinoblastoma were reported. Among the 13 bilateral cases, 3 were found to have pinealoblastoma too. On Cox regression analysis, age of onset below 36 months, diagnostic delay of less than 5 months and delay of treatment initiation (after diagnosis) less than 2 months were found to have significant effect on OS. The former two were found to have significant effect on PFS but not the latter (p<0.05 and HR>1).
 Conclusions: Almost 81% of patients presented at an advanced stage of the disease, the reason being accounted by diagnostic and therapeutic delay by virtue of a number of causes, the major one being eluded by apparently nonviolent yet ineffective alternative medicine practices. In spite of following the institutional protocols which are at par to the international guidelines, analysis shows much poorer survival in this study compared to those of developed countries. The cause might be such late presentation of the cases in already advanced stages of the disease.

Histopathologic findings after selective ophthalmic arterial injection of melphalan for retinoblastoma.

PURPOSE:The aim is to describe histopathologic observations in eyes enucleated after selective ophthalmic arterial injection (SOAI) of melphalan for retinoblastoma (RB).STUDY DESIGN:This is retrospective clinical study.PATIENTS AND METHODS:Histopathologic analysis of 14 eyes (13 patients) from May 2008 through January 2015 at Chang Gung Memorial Hospital.RESULTS:The eyes after SOAI were enucleated due to tumor viability (n = 7, 2 with vitreous hemorrhage), neovascular glaucoma (n = 4), lens drop to vitreous with total hyphema and elevated intraocular pressure (n = 1), retinal detachment (RD) progressed (n = 1), and persistent RD with phthisis change (n = 1). Almost all of the eyes showed vitreous seeding (n = 11 eyes) before treatment. After the treatment of SOAI, the histopathological examination revealed complete regression in four eyes with one was clinically diagnosed as viable tumor and progression, one with RD progression, and two as neovascular glaucoma. Six eyes showed invasion into the optic nerves, reaching the lamina cribrosa in five eyes, and six eyes with invasion into the choroid were observed. All of the cases with lamina cribrosa involvement showed tumor progression before enucleation, four cases with lamina cribrosa involvement expired later.CONCLUSION:Although some cases of RB can be controlled effectively with SOAI, but for refractory cases after SOAI, earlier decision of enucleation may be needed.

Contemporary management of retinoblastoma in the context of a low-resource country.

Retinoblastoma (RB) is the most common ocular cancer, and it typically presents before the age of 5 years in over 90% of cases. In high resource countries, RB patients tend to survive and retain their sight. This is not the case in low-resource countries because of late presentation and delayed intervention arising mostly from sociocultural and socioeconomic challenges. RB has no gender or racial predilection; the incidence is estimated as 1:16,000-1:18,000 live-births or 11/1 million children under 5 years. Most of the world's RB cases are found in Asia and Africa while most RB treatment centres are in America and Europe. RB is easy to detect by caregivers as a glowing white 'cat eye reflex' at night or when captured on camera. Health workers at primary care level can detect RB in early life if red reflex test and/or squint (Hirschberg) tests are deployed as part of wellness checks done especially during routine immunisation and well-baby clinics in the first 24 months of life. In most cases of RB, biopsies for histological confirmation are not required for diagnosis and treatment decisions to be made. Clinical information, ophthalmic evaluation and imaging modalities are typically used. There have been significant changes in the management of RB using various treatment modalities such as enucleation with orbital implant, use of chemotherapy delivered through intravenous, intravitreal, periocular and intra-arterial routes and targeted treatment with laser, cryotherapy and brachytherapy. Algorithm for management and development of the national RB program within the context of a low-resource country is presented from review of data extracted from Mendeley library, PubMed library, Google Scholar and One Network; full-text articles were mostly retrieved through the American Academy of Ophthalmology.

Results of Combined Chemotherapy and External Beam Radiotherapy for Unilateral Intra-Orbital Retinoblastoma—A Multi-Institutional Study from Mali

Retinoblastoma (RB) treatment aims at saving the life and preserving useful vision. In most low-income countries, because of delays in diagnosis, advanced disease presentation is quite common. This prospective study aimed at evaluating the treatment results of orbital RB with regards to overall survival rate of the patients treated with chemotherapy and radiotherapy. The study was performed from 01 November 2011 to 31 December 2015 in the paediatric oncology unit of Gabriel Touré Teaching Hospital, Bamako, Mali and The Institute of Tropical Ophthalmology of Africa (IOTA), Bamako, Mali. All intra-orbital non-metastatic RB cases not previously treated by chemotherapy or radiotherapy were included in this study. Fourteen patients were included into the study. Median age was 2 years, and sex ratio 2.5 (M = 10; F = 4). Right eye (n = 12, 85.7%) was more often affected than left eye (n = 2; 14.3%). Chemotherapy toxicities were mainly haematological including grade 3 anemia (n = 2; 7%) and grade 4 neutropenia (n = 3; 11%). Twelve patients (86%) were enucleated after neoadjuvant chemotherapy. Two patients (14%) abandoned treatment before enucleation. The IRSS pathology staging was: stage IIIa in 6 patients (50%), and stage II in six patients (50%). Six children (43%) received orbital radiotherapy at total dose of 45 Gy; Six children (43%) achieved complete remission; Overall survival rate was 48% at 4 years (95% CI: 22.5% - 74.4%). In conclusion, the therapeutic strategy based on neoadjuvant chemotherapy followed by enucleation, adjuvant chemotherapy and external beam radiotherapy, was beneficial in patients with stage III disease, achieving an event-free survival rate of 48%.

Analysis of the short-term curative effect of 356 cases of intraocular retinoblastoma in children.

ABSTRACTImportanceRetinoblastoma (Rb) is the most common primary malignant intraocular cancer in children. Systemic chemotherapy combined with local therapy is safe and effective for intraocular Rb.ObjectiveTo summarize the short‐term outcomes of patients with Rb to provide evidence for optimizing treatment protocols and improving therapeutic safety and efficacy.MethodsThe clinical data of 356 patients (486 eyes) with intraocular Rb admitted to our center from December 2009 to April 2017 were retrospectively analyzed. The measures included drug toxicity, eye‐preservation rate, and survival rate, with an emphasis on safety and short‐term efficacy. The date of last follow‐up was 30 November, 2017.ResultsThe patients comprised 226 unilateral Rb and 130 bilateral Rb. Enucleation before chemotherapy was performed in 72 patients. Among the 174 patients with unilateral Rb, enucleation after chemotherapy was performed in 80 patients (46.0%), and the eye was not enucleated in 89 (51.1%); 68 eyes were preserved (68/114, 59.6%) in Group D and 20 eyes (20/59, 33.8%) in Group E. Among the 220 eyes in patients with bilateral Rb, enucleation after chemotherapy was performed for 35 eyes; the eye‐preservation rate was 91.7% in Group C, 79.1% in Group D, and 52.1% in Group E. All patients developed grade II to IV myelosuppression after chemotherapy, among whom 18 patients (5%) requiring transfusion. Fourteen patients (3.9%) died of intracranial metastasis following self‐elected discontinuation of treatment (n = 7). Patients were followed up for a median of 47 (range, 1–96) months. The expected 5‐year overall survival rate was 95.3% (96.7% for unilateral Rb and 92.9% for bilateral Rb, P = 0.074).InterpretationThe VEC (vincristine, etoposide, and carboplatin) regimen with local treatment was safe for intraocular Rb. Intracranial metastasis remains the most common cause of Rb‐related death.

Comparing Incidence of Cataract Formation in Lens-Sparing Versus Whole-Eye Irradiation in Patients with Retinoblastoma

Retinoblastoma is the most common intraocular tumor in children with an incidence of about 300 cases per year. Thanks to treatment advances, the prognosis for retinoblastoma patients is excellent with a five-year overall survival rate of 95%. However, previous work has suggested that radiotherapy for patients with retinoblastoma results in a high risk of developing cataracts. Based on each patient’s individual stage at presentation, treatment plans were developed to either irradiate the whole eye or a smaller volume that excluded the lens. In this study, we investigated whether lens-sparing IMRT treatment plans resulted in a significantly lower incidence of post-radiation cataracts when compared to the whole-eye radiation treatment plans. We conducted a retrospective analysis of 66 patients (74 eyes) treated for retinoblastoma with IMRT at our institution from 1999-2015. Of these 66 patients, 7 patients were lost to follow-up, 1 patient died before meeting the 1-year minimum requirement of follow-up, and 2 patients received orbit radiation after bilateral enucleation. A total of 56 patients (35 males, 21 females) were included in our results. Two eyes were excluded for having cataracts prior to treatment and one orbit was excluded for receiving radiation after enucleation. Of the remaining 71 eyes, 57 eyes received whole-eye irradiation and 14 were treated with lens-sparing IMRT. Treatment groups did not differ significantly by age or sex but the whole-eye group had higher stage disease (p < .001). All patients were examined by ophthalmologists at our institution. We recorded the incidence of cataracts and enucleation post radiotherapy. Cataract incidence was reported as “cataract-free eye survival” and the percentage of eyes not enucleated was reported as “globe salvage rate”. Cataract-free eye survival was estimated as Kaplan-Meier survival curves. Five-year cataract-free eye survival was significantly higher (p < .001) for eyes treated with a lens-sparing approach (64.5%) than those treated with whole-eye irradiation (11.6%). There was no significant difference in 5-year globe salvage rates, which were 45/57 (78.9%) for whole-eye and 13/14 (92.9%) for lens-sparing patients. There was a significant difference (p = 0.005) in mean lens dose received by eyes that developed cataracts (33.8 Gy) versus eyes that remained cataract-free (21.7 Gy). Median follow-up time was 4 years for eyes that remained cataract-free. Patients treated with a lens-sparing technique were less likely to develop cataracts than patients treated with whole-eye irradiation. We did not find any difference in globe salvage rates between the two techniques. These findings suggest that a lens-sparing approach may reduce late effects compared to whole-eye irradiation for treatment of carefully selected cases of retinoblastoma. Whole-eye irradiation is recommended for advanced stages of disease complicated by retinal detachment or extensive vitreous seeding.

Outcome of Unilateral Intraocular Retinoblastoma

Background: retinoblastoma is the most common primary, malignant intraocular tumor of childhood, the aim of the study is to evaluate the outcome of management of 50 consecutive cases of unilateral retinoblastoma. Aims of the Work: to evaluate the outcome of management of unilateral retinoblastoma and to assess the risk of recurrence. Patients and Methods: prospective study of 50 consecutive cases with unilateral intraocular retinoblastoma. The management of cases was performed in the National eye center (Rod El Farag). Fundus examination was done under general anesthesia with RetCam 3. Management of cases according to the staging was group A: Focal treatment, TTT or cryotherapy, group B & C: chemotherapy with focal treatment, group D: If the patient has good visual potential (according to macular affection) Chemotherapy with focal treatment, if the patient has poor visual potential Enucleation, group E Enucleation. Results: as regard cases that managed with chemotherapy, there was 23 cases, 13 out of them treated with chemotherapy and transpupillary thermotherapy and showed complete regression, 10 cases showed initial regression with further new tumor recurrence after finishing chemotherapy, 5 cases was well managed by focal therapy, and another 5 cases failed to be controlled by focal therapy and Intra vitreal melphalan and ended by enucleation. As regard cases that was managed by enucleation, there was 32 cases, 27 out of them managed by primary enucleation, and 5 cases managed by secondary enucleation after failure of chemotherapy and focal therapy, 17 cases out of the enucleated eyes revealed presence of high risk pathological features, none of the cases developed local or metastatic tumors in the follow up period. Conclusion: retinal seeding, vitreous seeding are major predictive factors for tumor recurrence

Impact of yoga based lifestyle intervention on sperm oxidative DNA damage: study on fathers of non-familial sporadic heritable retinoblastoma patients

Sperm chromatin integrity is essential for fertilization, proper embryonic development and birth of healthy offspring. Sperm is highly vulnerable to oxidative damage to both nuclear and mitochondrial DNA due to minimal cytosolic anti-oxidants. Retinoblastoma is the most common childhood malignancy where the de novo germ line mutations are mainly inherited from paternal allele. The present study is planned as a case control study on the fathers of children affected with affected with non-familial sporadic heritable retinoblastoma to see the effect of yoga based lifestyle intervention on the decline in oxidative stress and oxidative DNA damage. A case control study with 75 fathers of children affected with non-familial sporadic heritable retinoblastoma cases and 50 fathers of healthy children were enrolled as healthy controls. Study duration was 6 months. Fathers of children affected with non-familial sporadic heritable retinoblastoma were enrolled in a yoga-based lifestyle intervention programme. Semen samples were collected at base line (day 0), after 1 month, 3 months and 6 months of yoga intervention. ROS, DNA fragmentation index (DFI) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels were estimated at base line (day 0), 1 month, 3 months and 6 months duration. ROS, DFI, 8-OHdG were also assessed in fathers of healthy children. Semen parameters were assessed as per the WHO, 2010 guidelines. The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels were significantly higher in fathers of children with non-familial sporadic heritable retinoblastoma as compared to fathers of healthy children. There was a reduction in mean DFI levels post yoga-based lifestyle intervention at 1 month (p=0.63), 3 months (p=0.046) and 6 months (p=0.032). Similarly, there was a reduction in seminal mean ROS levels at 1 month (p=0.74), 3 months (p=0.039) and 6 months (p=0.006). The levels of DNA oxidative base adduct i.e., 8-OHdG were also significantly reduced at 1 month (p=0.68), 3 months (p=0.043) and 6 months (p=0.022) with respect to its base line levels (day 0). Yoga-based simple lifestyle intervention meditation may significantly lower oxidative stress and oxidative DNA damage, and levels of mutagenic base 8-OHdG in the sperm DNA. Thus, yoga-based intervention is alternative and complementary treatment for maintaining/restoring sperm DNA integrity and hence, can reduce the prevalence of childhood cancers where poor sperm DNA integrity could be one of the reason.