Incidence and Mortality of Second Primary Cancers in Danish Patients With Retinoblastoma, 1943-2013

Abstract

Key Points Question Are heritability and treatment associated with the incidence of second primary cancer in Danish retinoblastoma survivors? Findings In this national cohort study of 323 patients in Denmark diagnosed with retinoblastoma, the incidence and mortality of second primary cancer were significantly higher in patients with heritable retinoblastoma vs patients with nonheritable retinoblastoma. The data did not show an increased risk in patients with heritable disease who were treated with external radiotherapy. Meaning The findings of this study suggest that patients with a genetic predisposition to retinoblastoma may be at greater greatest risk for developing second primary cancer later in life.

Impact of Laterality on Cumulative Survival in Patients Diagnosed with Retinoblastoma: A Retrospective Cohort Analysis of 1925 Cases in the Surveillance, Epidemiology, and End Results (SEER) Program

“… 15 Cumulative mortality from hereditary retinoblastoma survivors showcased increased mortality from consequent malignancies (25.5%, CI 20.8% to 30.2%) compared to nonhereditary retinoblastoma survivors (1.0%, CI 0.2% to 1.8%), 13 indicating genetic inheritance of relevant markers reduces survivorship compared to those with sporadic retinoblastomas. 14 Interestingly, while our current understanding of the RB1 mutation demonstrates preferential positive prediction of bilaterality, 16 this study showcased findings of germline abnormalities in 11% of sporadic unilateral retinoblastoma, indicating no preclusion of genetic testing in the presence of unilaterality. 15 This 2019 survival analysis showcased that out of 924 patients with nonhereditary retinoblastoma, none incurred bilateral origin.…”

“…15 Cumulative Preferred choice of therapeutic strategy for retinoblastoma is partially dependent on nature of laterality. 6,16 Clinical guidelines highlight preferentiality for intravenous chemotherapy with intermediate consideration for intraarterial chemotherapy and periocular chemotherapy for bilateral retinoblastomas. 6 In contrast, unilateral retinoblastomas demonstrate increased responsiveness to intraarterial chemotherapy; however, intermediate or minimal consideration for intravenous, periocular, and intravitreal chemotherapy remains.…”

Novel RB1 and MET Gene Mutations in a Case with Bilateral Retinoblastoma Followed by Multiple Metastatic Osteosarcoma

“…The cumulative mortality rate from second cancers at the age of 60 years was 34% among those with heritable Rb and 12% among those with nonheritable Rb. Sarcoma was the most common histological type of malignancy in patients with heritable Rb, and carcinoma was the most common type in nonheritable Rb [ 28 ].…”

“…Because of the expanding number of registered Rb cases [ 28 ], the publication of novel rare cases is very important to understand the molecular mechanism of this malignancy. To the best of our knowledge, this is the first report to detect this novel form of RB1 and synchronous MET gene mutation causing nonheritable bilateral retinoblastoma and consequential chondroblastic and osteoblastic osteosarcoma, the latter developing pulmonary metastases.…”

Subsequent Malignant Neoplasms in Retinoblastoma Survivors

“…Studies on four large cohort from the United Kingdom [ 9 , 40 , 41 ], the United States [ 12 , 42 , 43 , 44 , 45 , 46 , 47 ], The Netherlands [ 11 , 13 , 48 , 49 , 50 ] and recently Denmark [ 51 ] comprising of long-term Rb survivors have provided consistent data regarding the risk of SMNs. These studies are unique as they compare the SMN risk in Rb survivors to the risk of malignancy in the general population within each country.…”