Retinoblastoma Biomarker Study

NCT00342797 | Completed

• 2 other identifiers: 999993033OH93-NC-N033
• Study Type: observational
• Target: 2,136
• Locations: 1 country
• Sites: 4

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.

Conditions

Retinoblastoma; Melanoma; Sarcoma

Keywords

second primary cancer; retinoblastoma; RB1 germline mutation; Natural History

Outcome Measures

Primary Outcomes (2)

• Mutation in RB1 gene

  Location of mutation in the RB1 gene

  once

• Subsequent Cancer

  Risk of subsequent cancer in relation to prior treatment and RB1 mutation

  At least one year after retinoblastoma

Study Arms (1)

Retinoblastoma cohort

Retinoblastoma patients treated at two hospitals in New York and one hospital in Boston from 1914-2006.

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114-3096, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Social Scientific Systems, Inc.

Durham, North Carolina, 27703, United States

Location

Related Publications (3)

• 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.

  PMID: 25185089 BACKGROUND

• 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.

  PMID: 30698734 BACKGROUND

• 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.

  PMID: 31622129 BACKGROUND

MeSH Terms

Conditions

Retinoblastoma; Melanoma; Sarcoma; Neoplasms, Second Primary

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue

Study Officials

• Lindsay M Morton, Ph.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2006
• First Posted: June 21, 2006
• Study Start: November 17, 1993
• Primary Completion: March 6, 2024
• Study Completion: March 6, 2024
• Last Updated: March 7, 2024

Record last verified: 2024-03

Locations

US (4)