It is well known that retinoblastoma survivors typically enjoy long productive lives. This study investigated whether survivors of bilateral or unilateral retinoblastoma experienced higher rates of depression, anxiety, or other psychosocial conditions. Overall, the investigators reported that most do not have poorer psychosocial functioning compared with their peers without childhood cancer. Findings were similar for bilateral and unilateral survivors.
Ford JS, Chou JF, Sklar CA, Oeffinger KC, Friedman DN, McCabe M, Robison LL, Kleinerman RA, Li Y, Marr BP, Abramson DH, Dunkel IJ. Psychosocial outcomes in adult survivors of retinoblastoma. J Clin Oncol, 2015 Sept; 33. [Abstract]
We know that retinoblastoma survivors have an increased risk of breast cancer. We carried out a study to evaluate whether radiotherapy used to treat retinoblastoma may contribute to the higher risk in RB survivors. We combined data from the RB Follow-up Study with data from a similar effort in the United Kingdom. We found past radiotherapy RB was not related to breast cancer in hereditary patients. However, past radiotherapy was related to breast cancer in non-hereditary RB survivors. Our study was small, but we think that the RB1 germline mutation in hereditary survivors may have a stronger influence than radiotherapy on their risk for breast cancer.
Little MP, Schaeffer ML, Reulen RC, Abramson DH, Stovall M, Weathers R, de Vathaire F, Diallo I, Seddon JM, Hawkins MM, Tucker MA, Kleinerman RA. Breast cancer risk after radiotherapy for heritable and non-heritable retinoblastoma: a US-UK study. Br J Cancer 2014, May; 110: 2623-2632. [Abstract]
Retinoblastoma treatment has changed considerably over the past few decades with a trend towards less use of radiotherapy, to reduce second cancer risk that we and others had previously reported, and greater use of chemotherapy. However, less is known about risks of second cancers associated with chemotherapy. We noted significantly elevated risks for bone cancer and leiomyosarcoma, a common type of soft tissue sarcoma, following alkylating agent chemotherapy and radiotherapy combined, compared to radiotherapy alone in hereditary RB survivors. Excess risks for both of these second cancers persisted for decades.
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; 32 (29):3284-3290. [Abstract]
This study evaluated whether the risk of developing a second cancer among long-term survivors of retinoblastoma was different for those with a family history of disease, and bilateral versus unilateral disease. Overall, retinoblastoma survivors with bilateral disease and an inherited germline mutation were at slightly higher risk of developing a second cancer compared to those with a sporadic mutation. In particular the researchers note elevated risk for melanoma. These results emphasize the need for regular skin cancer screenings among survivors.
Kleinerman RA, Yu CL, Little MP, Li Y, Abramson D, Seddon J, Tucker MA. Variation of second cancer risk by family history of retinoblastoma among long-term survivors. J Clin Oncol 2012, 309(9):950-957. [Abstract]
Leiomyosarcoma is the most common type of soft-tissue sarcoma (cancer of the smooth muscle). Adult survivors of hereditary retinoblastoma are at increased risk for this cancer. Some adult female survivors have been diagnosed with this rare type of soft tissue cancer in the uterus. Although this type of cancer is rare, female survivors should be aware of this risk that begins in their childbearing years.
Francis JH, Kleinerman RA, Seddon JM, Abramson DH. Increased risk of secondary uterine leiomyosarcoma in hereditary retinoblastoma. Gynecol Oncol 2012 Feb;124(2):254-9. [Abstract]
Some inherited diseases are related to the older age of fathers. Using a sample of parents of retinoblastoma survivors, we studied the ages of mothers and fathers at the birth of the child with retinoblastoma. We found that the average age of fathers and mothers of a child with retinoblastoma that was not inherited from a parent, was older compared to parents of a child that inherited retinoblastoma from a parent.
Mills MB, Hudgins L, Balise RR, Abramson DH, Kleinerman RA. Mutation risk associated with paternal and maternal age in a cohort of retinoblastoma survivors. Hum Genet 2011 Dec 28. [Abstract]
One of the most common adverse effects of radiotherapy to the eye in childhood is the formation of cataracts later in life. This study investigated the risk for having a cataract removed. Nearly all cataracts that were removed within 30 years after diagnosis of retinoblastoma were associated with radiotherapy. More than 75% of the eyes treated with two or more radiation treatments had a cataract removed. These results emphasize the importance of regular eye examinations for retinoblastoma survivors, particularly those who were treated with radiation.
Chodick G, Kleinerman RA, Stovall M, Abramson DH, Seddon JM, Smith SA, Tucker MA. Risk of cataract extraction among adult retinoblastoma survivors. Arch Ophthalmol 2009 Nov;127(11):1500-4. [Abstract]
This study confirmed the observation of our earlier mortality study (published in 1993) of an increased risk of death from second cancers for survivors of hereditary retinoblastoma, especially those treated with radiotherapy. Increased risks were noted for cancers of the bone, soft tissue, brain, lung and uterus (mainly sarcomas). Nonhereditary retinoblastoma survivors experienced no increased risk of death from second cancers. Also, there was no evidence that retinoblastoma survivors were at greater risk of death from non-cancer causes than the general population. This study suggests screening programs for early detection and treatment of second cancers among hereditary retinoblastoma survivors.
Yu CL, Tucker MA, Abramson DH, Furukawa K, Seddon JM, Stovall M, Fraumeni JF Jr, Kleinerman RA. Cause-specific mortality in long-term survivors of retinoblastoma. J Natl Cancer Inst 2009 Apr 15;101(8):581-91. [Abstract]
In this first report of cancer screening behavior among survivors of retinoblastoma, adult survivors were asked about their use of mammograms, testicular self examinations, Pap tests, magnetic resonance imaging (MRI) and computed tomography (CT) scans. Their screening practices for breast, cervical and testicular cancers were similar to national rates. A higher proportion of survivors with the hereditary form of retinoblastoma, compared with nonhereditary, reported having undergone an MRI or CT scan in the past 5 years. Survivors of hereditary retinoblastoma should be encouraged to maintain, if not increase, their current screening practices to ensure early detection of second cancers.
Sheen V, Tucker MA, Abramson DH, Seddon JM, Kleinerman RA. Cancer screening practices in adult survivors of retinoblastoma at risk of second cancers. Cancer, 2008;113:424-441. [Abstract]
Previously, researchers have observed an increased risk of soft tissue sarcomas (cancers of the smooth muscle) among survivors of the hereditary retinoblastoma. This was the first study designed to investigate which subtypes of soft tissue sarcomas pose the greatest risk. Of the six soft tissue sarcoma subtypes evaluated, leiomyosarcoma was the most common and many were diagnosed 35 years after treatment for retinoblastoma. Almost all soft tissue sarcomas were diagnosed in patients who received radiation, although some of these sarcomas developed outside the radiation field. This study adds to the mounting evidence that survivors of hereditary retinoblastoma are at risk of soft tissue sarcomas and should undergo medical surveillance for sarcomas throughout their adult life.
Kleinerman RA, Tucker MA, Abramson DH, Seddon JM, Tarone RE, Fraumeni JF Jr. Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. JNCI, 2007;99:24-31. [Abstract]
Earlier studies have reported a significantly increased risk of lung cancer among hereditary retinoblastoma survivors. Adult survivors of hereditary and nonhereditary retinoblastoma were interviewed about their tobacco use. Hereditary survivors smoke less frequently than nonhereditary survivors but have a higher risk of lung cancer than nonhereditary survivors. Smoking does not entirely account for the increased risk of lung cancer among hereditary retinoblastoma survivors, but likely increases an already-elevated risk. Smoking prevention education and smoking cessation programs should be encouraged to minimize the risk of lung cancer among retinoblastoma survivors.
Foster MC, Kleinerman RA, Abramson DH, Seddon JM, Tarone RE, Tucker MA. Tobacco use in adult long-term survivors of retinoblastoma. Cancer Epidemiol Biomarkers Prev 2006;15:1464-8. [Abstract]
The follow-up of a large cohort of retinoblastoma survivors was extended with an additional 7 years of data to calculate the risk of additional cancers after treatment of retinoblastoma. Survivors of hereditary retinoblastoma had an overall increased risk of second cancers compared to nonhereditary retinoblastoma survivors and radiotherapy for retinoblastoma further increased this risk. One in three hereditary retinoblastoma survivors had developed a second cancer by 50 years after retinoblastoma diagnosis. The most common second cancers were cancer of the bone, soft tissues, brain, nasal cavities and melanoma. Radiotherapy further increased the risk of tumors. The study recommends careful, lifelong medical screening for hereditary retinoblastoma survivors, particularly those who were treated with radiotherapy.
Kleinerman RA, Tucker MA, Tarone RE, Abramson DH, Seddon JM, Stovall M, Li FP, Fraumeni JF Jr. Risk of new cancers following radiotherapy in long-term survivors of retinoblastoma: An extended follow-up. J Clin Oncol 2005;23:2272-2279. [Abstract]
Several case series and reports have provided suggestive evidence that lung cancer risk is increased in patients with hereditary retinoblastoma. This study found that hereditary retinoblastoma survivors have an increased risk of death from lung cancer. Because smoking rates in retinoblastoma survivors were not higher than the national average and no lung cancer deaths were reported in nonhereditary retinoblastoma survivors, the reported excess of lung cancer suggests that carriers of RB1 mutations may be highly susceptible to smoking-induced lung cancers. The study concluded that survivors who had hereditary retinoblastoma, in particular, should be targeted for smoking cessation.
Kleinerman RA, Tarone RE, Abramson DH, Seddon J, Li FP, Tucker MA. Hereditary retinoblastoma patients and risk of lung cancer. JNCI 2000:92; 2037-39. [Abstract]
Based on an observation of increased lipomas (benign tumors of fatty tissue) in retinoblastoma survivors, this study evaluated data from a large cohort of survivors to better understand the association between mutations in the RB1 gene and lipomas. Risk of lipoma was six times higher in the hereditary compared to nonhereditary retinoblastoma survivors. Additionally, a larger proportion of survivors of survivors with both hereditary retinoblastoma and a lipoma developed a second cancer compared with hereditary retinoblastoma survivors without a lipoma. The study concluded that hereditary retinoblastoma survivors are predisposed to lipomas due to the mutation in their RB1 gene and that they should undergo regular medical surveillance that includes skin examinations.
Li FP, Abramson DH, Tarone RE, Kleinerman RA, Fraumeni JF Jr, Boice JD Jr. Hereditary retinoblastoma, lipoma and second primary cancers. J Natl Cancer Inst 1997;89:83-4. [Abstract]
This study evaluated the risk of second cancers in a large cohort of retinoblastoma survivors followed for a median of 20 years. Researchers found that hereditary retinoblastoma survivors had a very high risk of second cancers compared to nonhereditary survivors. This was the first study to show an increase in soft tissue sarcomas and bone cancers in relation to increasing dose from radiotherapy used to treat retinoblastoma. This study concluded that genetic predisposition has a substantial impact on the risk of second cancers, which is increased by radiotherapy. The study also recommended that retinoblastoma patients should be examined throughout their adult life for second cancers.
Wong FL, Boice JD Jr, Abramson DH, Tarone RE, Kleinerman RA, Stovall M, Goldman MB, Seddon JM, Tarbell N, Fraumeni JF Jr, Li FP. Cancer incidence after retinoblastoma: radiation dose and sarcoma risk. JAMA 1997;1262-7. [Abstract]
In this study, we quantified the risk of death from second cancers among long-term survivors of retinoblastoma diagnosed from 1914 through 1984. We found that those with a germline mutations of the RB1 gene had a higher risk of death from second cancers, in particular bone cancers, soft tissue sarcomas, melanoma and brain cancers. Death due to second cancers was more common among those treated with radiotherapy. Our study concludes that careful, life-long cancer screening is important for all retinoblastoma survivors.
Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, et al. Mortality from second tumors among long-term survivors of retinoblastoma. J Natl Cancer Inst 1993;85:1121-8. [Abstract]