Clinical trial NCT00342797: Retinoblastoma Biomarker Study
Official title: Retinoblastoma Biomarker Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Retinoblastoma
Melanoma
Sarcoma
Keywords: second primary cancer
retinoblastoma
RB1 germline mutation
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2006-06-21
Enrollment: 2136
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Survivors of retinoblastoma treated at hospitals in New York City and Boston between 1914-2006 and US residents.

Brief summary: Retinoblastoma is a rare pediatric ocular tumor caused by germline and/or somatic mutations in the tumor suppressor gene RB1. Survivors of retinoblastoma, particularly those with the hereditary form of the disease (germline RB1 mutations) are highly susceptible to developing additional malignancies, which are a major cause of morbidity and mortality. Since 1984, REB has followed a cohort of 2136 (including 1,995 one-year) retinoblastoma survivors to investigate the contributions of treatment and genetic risk factors to second cancer etiology. The last systematic follow-up for second cancer incidence and cause-specific mortality was completed in 2009. As the cohort ages, we now propose to conduct another interview survey to collect information on newly diagnosed second cancers. Additionally, we propose to expand collection of germline DNA for additional molecular studies in survivors. Retinoblastoma survivors have now entered adult ages when epithelial tumors would be expected to occur with greater frequency. Given that the somatic mutations in the RB1 pathway have been identified in several epithelial tumors (bladder, brain, breast, esophagus, liver, lung, prostate) in addition to sarcomas, it is important to collect new information on these epithelial tumors, and to investigate whether the previously identified high risks of sarcomas and melanoma will persist as the cohort ages. Additionally, our understanding of genetic susceptibility to second cancers is limited. Given that this is the only cohort of long-term survivors of retinoblastoma being followed in the U.S., combined with the leadership role of REB in the study of second cancers, continued follow-up of this cohort will provide unique clinical and epidemiologic data on the long-term cumulative risk of second cancers in this distinctive cohort of childhood cancer survivors.

Detailed description: Retinoblastoma is a rare pediatric ocular tumor caused by germline and/or somatic mutations in the tumor suppressor gene RB1. Survivors of retinoblastoma, particularly those with the hereditary form of the disease (germline RB1 mutations) are highly susceptible to developing additional malignancies, which are a major cause of morbidity and mortality. Since 1984, REB has followed a cohort of 2136 (including 1,995 one-year) retinoblastoma survivors to investigate the contributions of treatment and genetic risk factors to second cancer etiology. The last systematic follow-up for second cancer incidence and cause-specific mortality was completed in 2009. As the cohort ages, we now propose to conduct another interview survey to collect information on newly diagnosed second cancers. Additionally, we propose to expand collection of germline DNA for additional molecular studies in survivors. Retinoblastoma survivors have now entered adult ages when epithelial tumors would be expected to occur with greater frequency. Given that the somatic mutations in the RB1 pathway have been identified in several epithelial tumors (bladder, brain, breast, esophagus, liver, lung, prostate) in addition to sarcomas, it is important to collect new information on these epithelial tumors, and to investigate whether the previously identified high risks of sarcomas and melanoma will persist as the cohort ages. Additionally, our understanding of genetic susceptibility to second cancers is limited. Given that this is the only cohort of long-term survivors of retinoblastoma being followed in the U.S., combined with the leadership role of REB in the study of second cancers, continued follow-up of this cohort will provide unique clinical and epidemiologic data on the long-term cumulative risk of second cancers in this distinctive cohort of childhood cancer survivors.

Eligibility criteria: * INCLUSION CRITERIA:

Children treated for retroblastoma over the past 30-plus years.

Primary outcomes:
measure: Mutation in RB1 gene
timeFrame: once
measure: Subsequent Cancer
timeFrame: At least one year after retinoblastoma
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Cancer Institute (NCI)
state: Maryland
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Social Scientific Systems, Inc.
state: North Carolina
Study officials:
affiliation: National Cancer Institute (NCI)
name: Lindsay M Morton, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wong JR, Morton LM, Tucker MA, Abramson DH, Seddon JM, Sampson JN, Kleinerman RA. Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy. J Clin Oncol. 2014 Oct 10;32(29):3284-90. doi: 10.1200/JCO.2013.54.7844. Epub 2014 Sep 2.
citation: Kleinerman RA, Tucker MA, Sigel BS, Abramson DH, Seddon JM, Morton LM. Patterns of Cause-Specific Mortality Among 2053 Survivors of Retinoblastoma, 1914-2016. J Natl Cancer Inst. 2019 Sep 1;111(9):961-969. doi: 10.1093/jnci/djy227.
citation: Kleinerman RA, Schonfeld SJ, Sigel BS, Wong-Siegel JR, Gilbert ES, Abramson DH, Seddon JM, Tucker MA, Morton LM. Bone and Soft-Tissue Sarcoma Risk in Long-Term Survivors of Hereditary Retinoblastoma Treated With Radiation. J Clin Oncol. 2019 Dec 10;37(35):3436-3445. doi: 10.1200/JCO.19.01096. Epub 2019 Oct 17.