Retinoblastoma Biomarker Study

NCT ID: NCT00342797

Last Updated: 2024-03-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 2136 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1993-11-17
• Study Completion Date: 2024-03-06

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.

Conditions

Retinoblastoma; Melanoma; Sarcoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Retinoblastoma cohort

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lindsay M Morton, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Cancer Institute (NCI)

Bethesda, Maryland, United States

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Social Scientific Systems, Inc.

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 25185089 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30698734 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31622129 (View on PubMed)

Other Identifiers

OH93-NC-N033

Identifier Type: -

Identifier Source: secondary_id

999993033

Identifier Type: -

Identifier Source: org_study_id