Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06367530
Status:
RECRUITING
Last Update Posted:
2024-04-16
First Post:
2024-04-04
Brief Title:
Trilateral Retinoblastoma Incidence and Outcomes
Sponsor:
Amsterdam UMC location VUmc
Organization:
Amsterdam UMC location VUmc
Study Overview
Official Title:
Global Survey of Trilateral Retinoblastoma Incidence and Outcomes
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GS-TRIO
Brief Summary:
Patients with heritable retinoblastoma are at risk to develop an intracranial brain tumor which is often fatal The investigators intend to look at the incidence and survival of trilateral retinoblastoma which is a brain tumor that can either be located in the pineal gland or elsewhere in the brain in retinoblastoma patients globally All retinoblastoma patients from participating centers will be included The investigators hypothesize that the apparent incidence of trilateral retinoblastoma especially the usually later diagnosed pineal trilateral retinoblastoma in low-income countries will be lower because of low chances of surviving the ocular tumors at about 50 and also because of possible under-diagnosis Therefore as retinoblastoma care improves in low-income countries the incidence of pineal trilateral retinoblastoma might go up Knowledge about incidence and survival can help improve health practices in parts of the world where this might be needed Therefore this global study firstly aims 1 to evaluate survival after trilateral retinoblastoma and factors influencing survival and 2 to evaluate incidence of trilateral retinoblastoma by country income level The study will run from 2024 through 2027
Detailed Description:
This study will adhere to the Strengthening the Reporting of Observational Studies in Epidemiology STROBE statement for cohort studies and to the Guidelines for Accurate and Transparent Health Estimates Reporting GATHER statement The study is designed as a prospective cohort study of retinoblastoma patients diagnosed in one year from as many as possible worldwide treatment centers The methods of patient recruitment are partly similar to previous global retinoblastoma studies Data will be extracted from a the Global Retinoblastoma study follows up patients who will present with retinoblastoma in 2024-2027
All unique trilateral retinoblastoma patients cases and all other retinoblastoma patients controls with will be included in the incidence analysis For survival analysis follow-up data will be required
After initial submission of case data by participating centers three years after the start of the study information on follow-up metastasis eye globe salvage laterality diagnosis of trilateral retinoblastoma and survival outcome will be available At a later stage participating centers that reported trilateral retinoblastoma cases will be contacted again for additional information All trilateral retinoblastoma patients will be included in the analysis regardless if additional information is provided
The investigators will request the following additional data
location pineal supra-parasellar other location eg 3rd ventricle
treatment for trilateral retinoblastoma
if not clear from initial report cause of death trilateral retinoblastoma side effect of treatment other
details on germline RB1 mutation
country of residence
family history of retinoblastoma
was patient symptomatic or asymptomatic when trilateral retinoblastoma was diagnosed if symptomatic what where the symptoms If asymptomatic how was the tumor diagnosed
information on trilateral retinoblastoma confirmation eg biopsy CSF treatment response disease progression
treatment for trilateral retinoblastoma
was the treatment with intent to cure active treatment or was the intent palliative
maximum diameter mm of tumor
wat trilateral retinoblastoma metastasized at the time of diagnosis
was this case published if yes where
also missing data during the initial submission phase will be requested again
If feasible additionally all centers that will also be asked if they can retrospectively provide data on trilateral retinoblastoma patients of whom retinoblastoma was not diagnosed in 2024 and were diagnosed with trilateral retinoblastoma in the years 2020 through 2027
Outcome measures
Incidence and risk factors of developing trilateral retinoblastoma will be analyzed in the following manner cases and controls who were diagnosed with retinoblastoma in 2024
overall incidence of pineal and non-pineal trilateral retinoblastoma in all retinoblastoma patients bilateral retinoblastoma patients and heritable retinoblastoma patients all patients with wither bi- or trilateral retinoblastoma familial retinoblastoma or a proven germline RB1 mutation will be considered heritable
estimate possible under-diagnosis of trilateral retinoblastoma in lower-income countries
potential modifiers of incidence risk of developing trilateral retinoblastoma will be analyzed pineal versus non-pineal trilateral retinoblastoma age at diagnosis of retinoblastoma eg lt or 12 months old country income level
Survival analysis of trilateral retinoblastoma alone all cases who were diagnosed with trilateral retinoblastoma in the years 2024 through 2027
overall and trilateral retinoblastoma specific survival will be analyzed
potential predictors of survival eg pineal versus non-pineal trilateral retinoblastoma tumor size previous treatment for retinoblastoma treatment for trilateral retinoblastoma symptomatic versus asymptomatic RB1 mutation active treatment metastastic disease country income level
Survival analysis of trilateral retinoblastoma in the entire retinoblastoma cohort cases and controls who were diagnosed with retinoblastoma in 2024-2027
trilateral retinoblastoma mortality versus other-cause mortality also stratified by country income level and al versus non-pineal trilateral retinoblastoma
event-free survival with an event defined as trilateral retinoblastoma diagnosis also stratified by country income level and al versus non-pineal trilateral retinoblastoma
event-free survival will be analyzed for potential predictors age at diagnosis of retinoblastoma previous systemic chemotherapy previous external beam radiotherapy country income level
Other analyses all cases who were diagnosed with trilateral retinoblastoma in the years 2024 through 2027
verify independence between the age at diagnosis of retinoblastoma and trilateral retinoblastoma
verify the period that retinoblastoma patients are at risk to develop trilateral retinoblastoma
whether trilateral retinoblastoma is usually diagnosed at a later date if the diagnosis of retinoblastoma was before the age of 12 months
evaluate and more precisely estimate of the previously estimated lead time between symptomatic and asymptomatic trilateral retinoblastoma of about 1 year
The income level of a country will be determined by the at the time most recent World Population Prospects by the Department of Economic and Social Affairs of the United Nations
Statistical analysis
Incidence will be reported as proportions with 95 exact binomial confidence intervals Cumulative incidence of trilateral retinoblastoma curves will be created accounting for death from other causes without diagnosis of trilateral retinoblastoma
Overall survival all-cause mortality disease specific survival and event free survival were performed An event is defined as being diagnosed with trilateral retinoblastoma
The Kaplan-Meier product-limit method and the log rank test will be used to analyze survival data A Cox proportional hazards model will be employed to analyze potential predictors factors Schoenfeld residuals will be used to check the proportionality assumption of the model
The investigators each case with a unique identifier for stratification based on the center to account for heterogeneity between these centers
In case of subgroup analyses original P-values will presented as well as adjusted p-values corrected for multiple hypothesis testing according to Bonferronis method
All unique trilateral retinoblastoma patients cases and all other retinoblastoma patients controls with will be included in the incidence analysis For survival analysis follow-up data will be required
After initial submission of case data by participating centers three years after the start of the study information on follow-up metastasis eye globe salvage laterality diagnosis of trilateral retinoblastoma and survival outcome will be available At a later stage participating centers that reported trilateral retinoblastoma cases will be contacted again for additional information All trilateral retinoblastoma patients will be included in the analysis regardless if additional information is provided
The investigators will request the following additional data
location pineal supra-parasellar other location eg 3rd ventricle
treatment for trilateral retinoblastoma
if not clear from initial report cause of death trilateral retinoblastoma side effect of treatment other
details on germline RB1 mutation
country of residence
family history of retinoblastoma
was patient symptomatic or asymptomatic when trilateral retinoblastoma was diagnosed if symptomatic what where the symptoms If asymptomatic how was the tumor diagnosed
information on trilateral retinoblastoma confirmation eg biopsy CSF treatment response disease progression
treatment for trilateral retinoblastoma
was the treatment with intent to cure active treatment or was the intent palliative
maximum diameter mm of tumor
wat trilateral retinoblastoma metastasized at the time of diagnosis
was this case published if yes where
also missing data during the initial submission phase will be requested again
If feasible additionally all centers that will also be asked if they can retrospectively provide data on trilateral retinoblastoma patients of whom retinoblastoma was not diagnosed in 2024 and were diagnosed with trilateral retinoblastoma in the years 2020 through 2027
Outcome measures
Incidence and risk factors of developing trilateral retinoblastoma will be analyzed in the following manner cases and controls who were diagnosed with retinoblastoma in 2024
overall incidence of pineal and non-pineal trilateral retinoblastoma in all retinoblastoma patients bilateral retinoblastoma patients and heritable retinoblastoma patients all patients with wither bi- or trilateral retinoblastoma familial retinoblastoma or a proven germline RB1 mutation will be considered heritable
estimate possible under-diagnosis of trilateral retinoblastoma in lower-income countries
potential modifiers of incidence risk of developing trilateral retinoblastoma will be analyzed pineal versus non-pineal trilateral retinoblastoma age at diagnosis of retinoblastoma eg lt or 12 months old country income level
Survival analysis of trilateral retinoblastoma alone all cases who were diagnosed with trilateral retinoblastoma in the years 2024 through 2027
overall and trilateral retinoblastoma specific survival will be analyzed
potential predictors of survival eg pineal versus non-pineal trilateral retinoblastoma tumor size previous treatment for retinoblastoma treatment for trilateral retinoblastoma symptomatic versus asymptomatic RB1 mutation active treatment metastastic disease country income level
Survival analysis of trilateral retinoblastoma in the entire retinoblastoma cohort cases and controls who were diagnosed with retinoblastoma in 2024-2027
trilateral retinoblastoma mortality versus other-cause mortality also stratified by country income level and al versus non-pineal trilateral retinoblastoma
event-free survival with an event defined as trilateral retinoblastoma diagnosis also stratified by country income level and al versus non-pineal trilateral retinoblastoma
event-free survival will be analyzed for potential predictors age at diagnosis of retinoblastoma previous systemic chemotherapy previous external beam radiotherapy country income level
Other analyses all cases who were diagnosed with trilateral retinoblastoma in the years 2024 through 2027
verify independence between the age at diagnosis of retinoblastoma and trilateral retinoblastoma
verify the period that retinoblastoma patients are at risk to develop trilateral retinoblastoma
whether trilateral retinoblastoma is usually diagnosed at a later date if the diagnosis of retinoblastoma was before the age of 12 months
evaluate and more precisely estimate of the previously estimated lead time between symptomatic and asymptomatic trilateral retinoblastoma of about 1 year
The income level of a country will be determined by the at the time most recent World Population Prospects by the Department of Economic and Social Affairs of the United Nations
Statistical analysis
Incidence will be reported as proportions with 95 exact binomial confidence intervals Cumulative incidence of trilateral retinoblastoma curves will be created accounting for death from other causes without diagnosis of trilateral retinoblastoma
Overall survival all-cause mortality disease specific survival and event free survival were performed An event is defined as being diagnosed with trilateral retinoblastoma
The Kaplan-Meier product-limit method and the log rank test will be used to analyze survival data A Cox proportional hazards model will be employed to analyze potential predictors factors Schoenfeld residuals will be used to check the proportionality assumption of the model
The investigators each case with a unique identifier for stratification based on the center to account for heterogeneity between these centers
In case of subgroup analyses original P-values will presented as well as adjusted p-values corrected for multiple hypothesis testing according to Bonferronis method
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None