Retinoblastoma Patients Research Articles

Serum transforming growth factor-beta levels and severity of retinoblastoma in children

Background Transforming growth factor-? (TGF-?) expression contributes to the growth of retinoblastoma. TGF-? is produced or released by infiltrating cells such as lymphocytes and monocytes/macrophages. TGF-? levels are a potential marker of disease severity.
 Objective To assess the difference in serum TGF-? levels before chemotherapy in patients with retinoblastoma grades III and IV. 
 Methods This cross-sectional observational study was done at Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia from January to November 2019. Subjects were pediatric patients with grade III and IV retinoblastoma who had not undergone chemotherapy. Patients who met the inclusion criteria provided blood specimens for TGF-? testing. We analyzed the difference in serum TGF-? level between grade III and grade IV patients.
 Results We obtained 38 subjects, consisting of 13 grade III and 25 grade IV retinoblastoma patients. Mean TGF-? levels were in 1,061 ng/L in grade III and 988 ng/L in grade IV patients. The Mann-Whitney U test revealed no significant difference between the levels of TGF-?, retinoblastoma grade III and IV (P=0.655). However, TGF-? levels in both groups were markedly above the normal value (100 ng/L).
 Conclusion TGF-? levels are markedly increased in grade III and IV retinoblastoma patients. There was no significant difference in TGF-? level between grade III and IV patients. Our findings suggest that TGF-? plays an important role in tumor cell development. Further research on differences in TGF-? levels between late stages (grades III and IV) and early stages (grades I and II) of retinoblastoma to elucidate the role of TGF-? as a marker of retinoblastoma severity.

Clinical features and outcome of retinoblastoma at the Vietnam National Cancer Hospital.

To characterize the clinical features, treatment, and outcome of children diagnosed with retinoblastoma (RB) at Vietnam National Cancer Hospital. The study enrolled all RB patients newly diagnosed at Vietnam National Cancer Hospital from January 2018 to December 2022. The primary endpoint was overall survival (OS) and the eye salvage rate. In total, 139 patients were enrolled, 51.8% patients were male. Median age was 18.9months. Most patients presented with leukocoria (63.3%), followed by strabismus (14.4%), and 43.9% had bilateral disease. Of 200 eyes, 129 (64.5%) were classified as group E. Extraocular extension was noted in 10 of 139 patients (7.2%). About one-third of the patients lived more than 300 kilometers (km) away from these hospitals, and 17.3% of the patients belonged to minority groups, both of which were dominated by group E and extraocular or high-risk eyes at the time of consultation. Primary enucleation was done for 57 eyes (28.5%), and 51 of 61 patients (83.6%) received eye salvage therapy in bilateral RB group. At study closure, 127 children were alive at the last follow-up, 12 cases were confirmed dead. The 5-year OS and progression-free survival (PFS) rates were 90.3% and 85.9%, respectively. In particular, ethnic minority, distance to hospital more than 150km, and extraocular disease were significantly associated with higher mortality among children with RB treated in Vietnam National Cancer Hospital. There is a need to support for screening RB with early symptoms in grassroots medical facilities and raise awareness among patients' families through health education programs. Besides, caring and supporting treatment for patients from the ethnic minority and who live far from hospitals are also extremely necessary.

Automatic retinoblastoma screening and surveillance using deep learning.

Retinoblastoma is the most common intraocular malignancy in childhood. With the advanced management strategy, the globe salvage and overall survival have significantly improved, which proposes subsequent challenges regarding long-term surveillance and offspring screening. This study aimed to apply a deep learning algorithm to reduce the burden of follow-up and offspring screening. This cohort study includes retinoblastoma patients who visited Beijing Tongren Hospital fromMarch 2018 to January 2022 for deep learning algorism development. Clinical-suspected and treated retinoblastoma patients from February 2022 to June 2022 were prospectively collected for prospective validation. Images from the posterior pole and peripheral retina were collected, and reference standards were made according to the consensus of the multidisciplinary management team. A deep learning algorithm was trained to identify "normal fundus", "stable retinoblastoma" in which specific treatment is not required, and "active retinoblastoma" in which specific treatment is required. The performance of each classifier included sensitivity, specificity, accuracy, and cost-utility. A total of 36,623 images were included for developing the Deep Learning Assistant for Retinoblastoma Monitoring (DLA-RB) algorithm. In internal fivefold cross-validation, DLA-RB achieved an area under curve (AUC) of 0.998 (95% confidence interval [CI] 0.986-1.000) in distinguishing normal fundus and active retinoblastoma, and 0.940 (95%CI 0.851-0.996) in distinguishing stable and active retinoblastoma. From February 2022 to June 2022, 139 eyes of 103 patients were prospectively collected. In identifying active retinoblastoma tumours from all clinical-suspected patients and active retinoblastoma from all treated retinoblastoma patients, the AUC of DLA-RB reached 0.991 (95% CI 0.970-1.000), and 0.962 (95% CI 0.915-1.000), respectively. The combination between ophthalmologists and DLA-RB significantly improved the accuracy of competent ophthalmologists and residents regarding both binary tasks. Cost-utility analysis revealed DLA-RB-based diagnosis mode is cost-effective in both retinoblastoma diagnosis and active retinoblastoma identification. DLA-RB achieved high accuracy and sensitivity in identifying active retinoblastoma from the normal and stable retinoblastoma fundus. It can be used to surveil the activity of retinoblastoma during follow-up and screen high-risk offspring. Compared with referral procedures to ophthalmologic centres, DLA-RB-based screening and surveillance is cost-effective and can be incorporated within telemedicine programs. This study was registered on ClinicalTrials.gov (NCT05308043).

Eye-related quality of life and activities of daily living in pediatric retinoblastoma patients: A single-center, non-controlled, cross-sectional analysis.

Childhood retinoblastoma (RB) survivors are known to experience long-term morbidity; however, eye-related quality of life (QoL), which may significantly impact activities of daily living (ADL), has not been extensively studied in this population. The purpose of this cross-sectional study was to assess QoL and ADL morbidity among school-age RB survivors. The Pediatric Eye Questionnaire (PedEyeQ) and Roll Evaluation Activities of Life (REAL) were administered to childhood RB survivors between ages 5 and 17 followed at St. Louis Children's Hospital. Visual outcomes and demographic predictors of ADL and QoL were examined. Total 23 patients (mean age 9.6years) consented for participation in this study. All children experienced at least one domain on the PedEyeQ≤80%. Subjects and parents marked functional vision to be the most impacted domain with a median score of 82.5 and 83.4, respectively. Only 10.5% of participants scored above 75% on the ADL percentile rank. On multivariable analysis, decreased visual acuity (VA) was associated with worse "Child Functional" (odds ratio [OR] -59.2, p=.004) and "Parent Worry Function" (OR -66.5, p=.03) metrics. Decreased contrast sensitivity was associated with worse "Parent Impact" (OR 21.0, p = .02) and "Parent Worry Function" (OR 3.70, p=.04) metrics. Longer saccade horizontal latency was associated with a worse "Parent Worry Function" metric (OR 43.0, p=.009). On multivariable analysis, no variable was significantly associated with ADL. RB survivors have impaired QoL and ADL. Screening for such difficulties should strongly be considered for all RB patients. Additional studies may help predict morbidity based on visual metrics and demographic data.

Can Enhancement Pattern in Normal-Sized Optic Nerves on Magnetic Resonance Imaging Better Predict Tumor Invasion in Retinoblastoma Eyes?

Introduction: Optic nerve (ON) enhancement alone without ON thickening on contrast-enhanced magnetic resonance imaging (CE-MRI) can be associated with post-laminar optic nerve invasion (PLONI) in eyes with group E retinoblastoma. A few case reports and retrospective studies in the literature show a poor correlation between ON enhancement on MRI and ON invasion on histopathological examination (HPE). There is no universal consensus on the management of such cases. It is desirable that the presence and extent of a true ON invasion be reliably picked up before planning upfront enucleation in order to avoid stage II disease. Methods: In a prospective study conducted at a tertiary eye care center in North India, all retinoblastoma patients presenting with ON enhancement on imaging were evaluated. Demographic and imaging details, histopathological findings, and treatment details were recorded. The length and pattern of enhancement noted on MRI were correlated with histopathology. Follow-up was done till the end of the study period. Results: Six group E retinoblastoma eyes were evaluated. 3 eyes (50%) showed solid enhancement, 2 eyes (33.33%) had tram track pattern and 1 eye (16.66%) showed punctate enhancement pattern on CE-MRI. On histopathology, 5 (83.33%) cases showed PLONI and all 6 (100%) had ON head infiltration. The cut end of the ON was free in all cases. On correlating MRI and HPE, all eyes with solid enhancement pattern showed PLONI, of which 2/3 (66.6%) had diffuse ON infiltration. Only 50% of eyes with tram track patterns showed PLONI. The case which showed a punctate enhancement pattern showed focal infiltration by tumor cells with vacuolated cytoplasm on HPE. At the last follow-up, all patients were alive and free of disease. Conclusion: ON enhancement patterns may make it more predictive for PLONI on HPE. Solid enhancement pattern appears to correlate better with the extent of ON invasion on HPE, and longer lengths of solid ON enhancement may be considered for neoadjuvant chemotherapy rather than upfront enucleation.

Incidence and geographic distribution of retinoblastoma in Ethiopia

IntroductionRetinoblastoma is the most frequent intraocular malignancy of the eye in children, occurring in early childhood. Based on global estimates, Ethiopia is expected to observe over 200 new retinoblastoma cases per year, however without a cancer registry, this number is difficult to confirm. Therefore, the goal of the study was to determine the incidence and geographic distribution of retinoblastoma in Ethiopia.MethodsA retrospective medical chart review of clinically diagnosed new retinoblastoma patients between January 1, 2017 - December 31, 2020, in four public Ethiopian tertiary hospitals was performed. The incidence of retinoblastoma was calculated by a birth-cohort analysis.ResultsThere were 221 retinoblastoma patients observed in the study period. The incidence of retinoblastoma was found to be 1 in 52,156 live births. Incidence varied among different regions of Ethiopia.ConclusionThe incidence of retinoblastoma observed in this study is likely an underestimate. It is possible that patients were undercounted because they were seen outside of the 4 main retinoblastoma treatment facilities included in this facility, or they experienced barriers to accessing care. Our study suggests a need for a nationwide retinoblastoma registry and more retinoblastoma treatment centers in the country.

Angiographic analysis of ophthalmic artery flow direction in children undergoing chemosurgery for retinoblastoma compared to age-matched controls.

Catheter-based intra-arterial chemotherapy (IAC) has revolutionized the treatment of retinoblastoma (RB). Variability in ophthalmic artery (OA) flow, either retrograde from external carotid artery branches, or anterograde from the internal carotid artery, necessitates multiple IAC techniques. We evaluated the direction of OA flow and identify OA flow reversal events over the course of IAC treatment as well in comparison to OA flow direction in non-RB children. We performed a retrospective analysis of OA flow direction in all RB patients treated with IAC, along with an age-matched control group who underwent cerebral angiography at our center from 2014 to 2020. IAC was administered to a total of 18 eyes (15 patients). Initial anterograde OA flow was demonstrated in 66% (n = 12) of eyes. Five OA reversal events were identified (3/5 anterograde-to-retrograde). All five events were in patients receiving multiagent chemotherapy. No correlation was found between OA flow reversal events and the initial IAC technique. A control group of 88 angiograms representing 82 eyes (41 patients) was utilized. The anterograde flow was observed in 76 eyes (86.4%). Our control group included 19 patients with sequential angiograms. One OA flow reversal event was identified. OA flow direction is dynamic in IAC patients. Anterograde and retrograde OA directional switches do occur and may necessitate delivery technique variation. In our analysis, all OA flow reversal events were associated with multiagent chemotherapy regimens. Both anterograde and retrograde OA flow patterns were observed in our control cohort, suggesting bidirectional flow can occur in non-RB children.

Mental Wellbeing among Children with Cancer during COVID-19 Pandemic in Indonesia: A Cross-sectional Study

Abstract Introduction Coronavirus disease 2019 (COVID-19) has affected both physical and mental aspect of people worldwide, especially the high-risk group such as pediatric cancer patients. Children with cancer were considered both clinically and mentally vulnerable during this pandemic. They were also affected by the self-isolation, quarantine, and social distancing policy taken as a respond to public threat. Objectives To evaluate the impact of social distancing and health protocol during COVID-19 on the mental health profile of children with cancer in Indonesia. Methods A cross-sectional study evaluating the mental health of children with cancer during COVID-19 pandemic was conducted in Cipto Mangunkusumo Hospital, Jakarta, Indonesia from June to September 2020. An online questionnaire was used to collect demographics of parents and children, children's Strength and Difficulties Questionnaire (SDQ) score, and parents' Self-Reporting Questionnaire (SRQ). SDQ score consists of five subscales, including the emotional symptoms, conduct problems, hyperactivity, peer relationships problems and prosocial behavior. Cancer types were grouped into retinoblastoma, nonretinoblastoma (other solid tumors), and leukemia. Results There were 156 valid responses, consisting of 42 patients with retinoblastoma, 34 patients with nonretinoblastoma (other solid tumors), and 80 patients with leukemia. Pandemic-related lifestyle changes did not significantly impact emotional or behavioral problems. Children with normal total SDQ (odds ratio [OR]: 473, p = 0.001) and emotional scores (OR: 3.19, p = 0.07) had parents with normal SRQ scores (<6). Leukemia patients with shorter diagnosis period had worse hyperactivity score (p = 0.01). On the contrary, leukemia inpatients had better prosocial scores than outpatients (p = 0.03). More bilateral retinoblastoma patients (p = 0.04) with longer duration of cancer diagnosis (p = 0.03) faced peer problems. Conclusions Our study revealed that lifestyle changes during early COVID-19 pandemic were not major factors impacting emotional and behavioral problems in children with cancer. However, disease-related factors pose great challenges; thus, a holistic mental health support system should be available to both children and parents.

Rehabilitation of pediatric retinoblastoma patients with ocular prostheses and their subsequent modifications: A 15-year retrospective study.

Enucleation is a common treatment modality performed for pediatric retinoblastoma patients, and the resultant defects are reconstructed using an ocular prosthesis. The prostheses are modified or replaced periodically, as the child develops due to orbital growth and patient-error. The purpose of this report is to evaluate the replacement frequency of prostheses in the pediatric oncologic population. A retrospective review was completed by the two senior research investigators, of patients that had ocular prostheses fabricated following enucleation of their retinoblastoma from 2005 to 2019 (n=90). Data collected from the medical records of the patient included the pathology, date of surgery, date of prosthesis delivery, and the replacement schedule of the ocular prosthesis. During the 15-year study period, 78 enucleated observations (ocular prosthesis fabricated) were included for analysis. The median age of the patients at the time of delivery of their first ocular prosthesis was calculated to be 2.6 years (range 0.3-18 years). The median time to the first modification of the prosthesis was calculated to be 6 months. The time to modification of the ocular prosthesis was further stratified by age. Pediatric patients require modification of their ocular prostheses throughout their growth and development period. Ocular prostheses are reliable prostheses with predictable outcomes. This data is helpful to set an expectation among the patient, parent, and provider.

Novel point mutation and intronic mutations of <em>RB1</em> gene in retinoblastoma patients in Indonesia

BACKGROUND Retinoblastoma (RB) is an inherited disorder caused by the RB1 gene mutation in retinal cells or germline mutation. Identifying the specific mutation is crucial for prognosis, inheritance risk assessment, and treatment planning. This study aimed to identify the germline mutation in the RB1 gene in patients with RB and their parents from the eastern part of Indonesia.
 METHODS This observational analytic study recruited patients with RB and their parents between 2016 and 2018 at Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia. The normal control subjects were children from the outpatient clinic at the Department of Ophthalmology, Universitas Hasanuddin Hospital. Ophthalmic examinations and peripheral blood tests were performed in RB patients, their parents, and control subjects. Genomic DNA was isolated from blood leukocytes and amplified using conventional PCR. Hotspot exons 8, 10, 14, 17, and 22 were screened for mutations using the Sanger method.
 RESULTS There were 21 patients with RB (16 unilateral and 5 bilateral) and 14 normal subjects. Of the 184 variations detected in RB patients, 164 were also found in normal subjects. 19 intronic mutations in introns 10, 16, 17, and 21, and 1 novel missense mutation in exon 17 were identified. Parental testing revealed 8 substitutions in exon 17 and 5 intronic mutations in introns 16 and 17 of the parents. None of the variations in exons were passed to their children.
 CONCLUSIONS This study found a novel missense mutation in exon 17 of the RB1 gene.

Tumor Suppressor Role of INPP4B in Chemoresistant Retinoblastoma.

The chemotherapy of retinoblastoma (RB), a malignant ocular childhood disease, is often limited by the development of resistance against commonly used drugs. We identified inositol polyphosphate 4-phosphatase type II (INPP4B) as a differentially regulated gene in etoposide-resistant RB cell lines, potentially involved in the development of RB resistances. INPP4B is controversially discussed as a tumor suppressor and an oncogenic driver in various cancers, but its role in retinoblastoma in general and chemoresistant RB in particular is yet unknown. In the study presented, we investigated the expression of INPP4B in RB cell lines and patients and analyzed the effect of INPP4B overexpression on etoposide resistant RB cell growth in vitro and in vivo. INPP4B mRNA levels were significantly downregulated in RB cells lines compared to the healthy human retina, with even lower expression levels in etoposide-resistant compared to the sensitive cell lines. Besides, a significant increase in INPP4B expression was observed in chemotherapy-treated RB tumor patient samples compared to untreated tumors. INPP4B overexpression in etoposide-resistant RB cells resulted in a significant reduction in cell viability with reduced growth, proliferation, anchorage-independent growth, and in ovo tumor formation. Caspase-3/7-mediated apoptosis was concomitantly increased, suggesting a tumor suppressive role of INPP4B in chemoresistant RB cells. No changes in AKT signaling were discernible, but p-SGK3 levels increased following INPP4B overexpression, indicating a potential regulation of SGK3 signaling in etoposide-resistant RB cells. RNAseq analysis of INPP4B overexpressing, etoposide-resistant RB cell lines revealed differentially regulated genes involved in cancer progression, mirroring observed in vitro and in vivo effects of INPP4B overexpression and strengthening INPP4B's importance for cell growth control and tumorigenicity.

Referral patterns for retinoblastoma patients in Ethiopia

BackgroundIncreased lag time between the onset of symptoms and treatment of retinoblastoma (RB) is one of the factors contributing to delay in diagnosis. The aim of this study was to understand the referral patterns and lag times for RB patients who were treated at Menelik II Hospital in Addis Ababa, Ethiopia.MethodA single-center, cross- sectional study was conducted in January 2018. All new patients with a confirmed RB diagnosis who had presented to Menelik II Hospital from May 2015 to May 2017 were eligible. A questionnaire developed by the research team was administered to the patient’s caregiver by phone.ResultsThirty-eight patients were included in the study and completed the phone survey. Twenty-nine patients (76.3%) delayed seeing a health care provider for ≥ 3 months from the onset of symptoms, with the most common reason being the belief that it was not a problem (96.5%), followed by 73% saying it was too expensive. The majority of patients (37/38, 97.4%) visited at least 1 additional health care facility prior to reaching a RB treatment facility. The mean overall lag time from noticing the first symptom to treatment was 14.31 (range 0.25–62.25) months.ConclusionLack of knowledge and cost are major barriers to patients first seeking care for RB symptoms. Cost and travel distance are major barriers to seeing referred providers and receiving definitive treatment. Delays in care may be alleviated by public education, early screening, and public assistance programs.

Mutant-RB1 circulating tumor DNA in the blood of unilateral retinoblastoma patients: What happens during enucleation surgery: A pilot study.

Cell free DNA (cfDNA) and circulating tumor cell free DNA (ctDNA) from blood (plasma) are increasingly being used in oncology for diagnosis, monitoring response, identifying cancer causing mutations and detecting recurrences. Circulating tumor RB1 DNA (ctDNA) is found in the blood (plasma) of retinoblastoma patients at diagnosis before instituting treatment (naïve). We investigated ctDNA in naïve unilateral patients before enucleation and during enucleation (6 patients/ 8 mutations with specimens collected 5-40 minutes from severing the optic nerve) In our cohort, following transection the optic nerve, ctDNA RB1 VAF was measurably lower than pre-enucleation levels within five minutes, 50% less within 15 minutes and 90% less by 40 minutes.

Intra-arterial chemotherapy in refractory and advanced intraocular retinoblastoma.

To evaluate the efficacy of secondary and salvage intra-arterial chemotherapy (IAC) as a globe salvage treatment modality in advanced and refractory intraocular retinoblastoma. A retrospective chart review of advanced intraocular retinoblastoma (groups D and E International Classification of Retinoblastoma [ICRB] classification) patients refractory to intravenous chemotherapy (IVC) and undergoing IAC as the secondary and salvage treatment modality between December 2018 and June 2021 was carried out. All patients underwent the IAC procedure by super-selective ophthalmic artery catheterization and with triple-drug chemotherapeutic agents of melphalan, topotecan, and carboplatin. Data were collected about tumor regression, eye salvage, metastasis, and survival outcome at follow-up. Out of 13 patients, 12 patients received secondary IAC after being primarily treated with IVC and focal therapies and one patient received rescue IAC after recurrence following primary IAC. Mean number of IAC cycles administered was 2. Overall, globe salvage rate was 53.84%, with a mean follow-up of 17.53 months (range 6-37 months), three patients had enucleation for residual tumor or tumor recurrence. One patient developed metastasis post enucleation and two patients who were lost to follow-up after enucleation advice for residual tumor developed orbital tumor extension and eventually died of metastasis. Secondary triple-drug IAC following failure of IVC, along with other adjunct treatment modalities might a be a cost-effective option for eye salvage in advanced intraocular retinoblastoma patients who refuse enucleation, with a globe salvage rate of 53.84%. It can also be an effective approach to improve treatment compliance and can help in addressing the barrier of treatment refusal when enucleation is advised.

The role of EZH2 as a potential therapeutic target in retinoblastoma

Enhancer of zeste homolog 2 (EZH2) has been reported selectively expressed in postnatal human retinoblastoma (RB). While, the contribution of EZH2 in progression of RB and its clinical importance has not been clarified. Here, immunohistochemistry (IHC) was performed on tumor specimens from 53 RB patients. UNC1999 and GSK503, inhibitors targeting EZH2, were incubated with human RB cell line WERI-Rb-1 and Y79 to assess the role and mechanism of EZH2 in RB proliferation, metastasis and tumor glycolysis. Administration of UNC1999 in subcutaneous tumor model of RB was conducted. The results showed that highly expressed EZH2 in RB tissues was significantly associated with the poor overall survival. UNC1999 and GSK503 inhibited proliferation, migration, invasion and tumor glycolysis of RB. Results in mouse xenograft model confirmed the inhibitory effect of UNC1999 on tumor growth of RB and the regulation effect of EZH2 to STAT3/FoxO1 signaling pathway. Therefore, EZH2 is rewarding to study as a potential target for anti-RB treatment.

Association of choroidal invasion with retinoblastoma survival rates

To assess the impact of varying levels of choroidal invasion on survival from retinoblastoma. A retrospective nationwide analysis of retinoblastoma cases diagnosed between 2004-2016 using the Surveillance, Epidemiology, and End Results database was conducted. Overall survival, cause-specific survival, and all-cause mortality risk were assessed as primary outcomes. A total of 393 retinoblastoma patients were included, of whom 268 (68.2%) had no choroidal invasion, 91 (23.2%) had focal choroidal invasion, and 34 (8.7%) had massive choroidal invasion on enucleation. A total of 6 deaths occurred throughout an average follow-up period of 72.2 ± 47.1 months: 4 deaths were cancer related. Adjusted Cox regression demonstrated higher all-cause mortality in patients with massive choroidal invasion (HR, 41.29; 95% CI, 4.05-420.49; P = 0.002) relative to those without choroidal invasion; however, those with focal choroidal invasion (HR, 2.69; 95% CI, 0.17-43.09; P = 0.484) demonstrated no difference in all-cause mortality. On further stratification by level of optic nerve invasion (ONI), all cancer-related deaths (4/4) were found to have occurred in patients with massive choroidal invasion and concomitant postlaminar ONI (PLONI). Patients with massive choroidal invasion without PLONI demonstrated 5-year overall and cause-specific survival of 100%, whereas patients with massive choroidal invasion and PLONI demonstrated 5-year overall and cause-specific survival of 80.2%. All retinoblastoma-related deaths occurred in patients with both massive choroidal invasion and PLONI. These findings could not establish that massive choroidal invasion is an independent risk factor for poor outcome.

Retinoblastoma in the Southern Philippines: Clinical Outcomes of Retinoblastoma Patients in a Davao Tertiary Hospital

Background. Retinoblastoma is the most common intraocular cancer in childhood in the Philippines. Most datathough on demographics, clinical profile, treatment options, and outcomes in the country are from the NationalCapital Region.Objectives. This study aimed to describe the demographics, clinical profile, treatment done, and outcomes ofretinoblastoma patients seen in a public tertiary referral center in Davao from 2011-2020 to make available literature more representative of the status of retinoblastoma in the Philippines.Methods. An analytical cross-sectional study was conducted using the records of retinoblastoma patients seen in a tertiary government hospital located in Davao Region from January 2011 to December 2020.Results. There were 157 patients included in the analysis. Seventy-three (46%) were female with 44% coming from the Davao Region. One hundred seven (69%) patients had unilateral disease. Median age at initial consultation for patients with unilateral disease was significantly older than those with bilateral disease (p<0.003). Tumors were extraocular in 82 (40%) eyes. In the intraocular group, 36% of the eyes belonged to International Classification of Retinoblastoma (ICRB) Groups D and E. Enucleation was the most commonly performed treatment. Survival rate was 28%.This is the first report to provide epidemiologic and clinical data on retinoblastoma in the literature, including survival data, from Mindanao. Advanced stages and extraocular cases of retinoblastoma remain high. Delay of consultation contributed to the prognosis and clinical outcome of the disease.Conclusion. Advanced stages and extraocular cases of retinoblastoma remain significantly high in the country, even in Mindanao. treatment, outcomes, survival rate, Mindanao &nbsp

Clinical and histopathological study of retinoblastoma in bukavu from 01 january 2014 to 31th december 2020

Introduction: The aim of this study was to determine the histopathological and clinical characteristics of retinoblastoma in patients followed in Bukavu, Democratic Republic of Congo. Methods: It is a cross-sectional and analytical study that included 125 consecutives, exhaustively included subjects followed for retinoblastoma at CELPA ophthalmology clinic from January 2014 up to December 2020. Clinical and histopathological data were analyzed with Epi Info and SPSS 16.0 software. Results: A total of 7200 children aged 1-5 years old were consulted, including 125 cases of retinoblastoma, representing a frequency of 1.7%. The mean annual incidence was 13.8. The age group under 24 months predominated (54.4%), with a mean age of 24.6 months. The majority of patients had no family history of retinoblastoma (79.2%). Ocular protrusion and ocular pain were the most frequent complaints on admission (51.2%). The extraorbital form was found in 59.2% of patients. The average time period between the first symptoms and the consultation was 6 months, and the time period between the first consultation and the beginning of management was 14 days. 112 patients (89.6%) had received enucleation combined with chemotherapy. The survival rate observed after 3 years of follow-up was 40.8%. There was a signifcative association between evolution of the retiboblastoma and the delay between consultation and the management, clinical form and management, and the treatment mode both in bivariate and multivariate analysis (p<0.05, CI=95%). Extraorbital retinoblastoma (61.6%), endophytic (74.4%), with classic cytology showing Flexner-Wintersteiner rosettes (96.3%), numerous mitoses (98.4), necrosis and calcification (92%) dominated. Images of infiltration of the internal structures of the eye were observed (18.4%). Conclusion: Retinoblastoma, a highly malignant tumor of children, remains a real public health problem in Bukavu. Advanced and severe histological forms were the most frequent. Early diagnosis and treatment are essential to improve the prognosis. A survival rate of 40.8% obtained in our limited conditions is a beginning of success which could be improved with the involvement of all the disciplines concerned.

Seasonal Variation in the Diagnosis of Retinoblastoma

ABSTRACT Purpose To determine the seasonal variation in the diagnosis of retinoblastoma in a global sample of children and to investigate predictors of seasonal trends. Methods Data were collected through a global, multicenter, 1-year cross-sectional analysis that included all treatment- naïve retinoblastoma patients presenting to participating centers between January 1, 2017, and December 31, 2017. Due to variations in days per month, data were normalized to a 30-day/month calendar. Observed data were compared to a simulation study of expected results using a uniform distribution. Results Patient-level data were available for 4,351 children from 276 centers in 153 countries, of which 3,966 had a month of presentation recorded. There were relative peaks in disease presentation in January and July, with lower counts in November and December (p = .0015). No covariates were found to be significantly associated with the seasonal trend. Two covariates, patient age at presentation and extraocular tumor spread, showed a moderate association with month of presentation. Conclusion Our findings suggest seasonal trends in the presentation of retinoblastoma across the world. However, these trends do not appear to be related to income level of a country, climate, or other covariates. Any connection between seasonal variation of retinoblastoma presentation and retinoblastoma outcomes remains unclear or not present.

VCN‐01: from the preclinic to a phase I trial for refractory retinoblastoma patients

AbstractWhy do we propose an oncolytic adenovirus for the treatment of retinoblastoma?Physiopathology: Conventional chemotherapy‐independent Highly selective RB1 route (only infects E2F‐1‐high cells) Convenient local administration & low systemic spread Clinical availability of a GMP‐grade virus already evaluated by the AEMPS (Spanish Drug Agency) Security data available from adult treatment of refractory solid tumours Clinical translation to EudraCT: 2016–001060‐11 VCN‐01 is active for the treatment of chemo‐resistant retinoblastoma The distribution of the infective virus is restricted to the eye in mice and rabbits VCN‐01 intravitreal injection is both feasible and safe in rabbits Phase I Safety and Activity trial of the Oncolitic Adenovirus VCN‐01 for Patients With Refractory Retinoblastoma Single Site, Open Label With Dose Escalation To evaluate safety and Activity of intravitreal VCN‐01in Patients With Refractory Retinoblastoma Inclusion criteria Unilateral somatic mutation RBL Germinal mutation RBL active in only one eye (fellow eye non‐affected or enucleated) Rellapsed or refractory to systemic, intra‐arterial or intra‐vitreal chemotherapy Age: 1–12 yo Exclusion criteria Indication for immediate enucleation of the affected eye: glaucoma rubeosis iridis anterior chamber disease Conclusion.Phase I trial EudraCT: 2016–001060‐11 to include Patients with Reactivated or refractory RBL.