Outcome of second malignancies after retinoblastoma: a retrospective analysis of 25 patients treated at the Institut Curie

Aerts, Isabelle; Pacquement, Hélène; Doz, François; Mosseri, Véronique; Desjardins, Laurence; Sastre, Xavier; Michon, Jean; Rodriguez, José; Schlienger, P; Zucker, Jean‐Michel; Quintana, E.

doi:10.1016/j.ejca.2004.03.023

Cited by 87 publications

(86 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most of the reported cases occur in patients predisposed to bilateral retinoblastoma, a rare childhood cancer, linked to the germline inactivation of one allele of the tumour suppressor gene RB1. In this genetic background, the cumulative incidence of secondary tumours, mainly sarcomas, after radiotherapy may reach 38%, 50 years after diagnosis, whereas it does not exceed 21% in the absence of radiotherapy (Aerts et al, 2004;Kleinerman et al, 2005). We recently analysed the presence of TP53 mutations in a series of sarcomas developing in the irradiation field in patients treated by radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

RB1 and TP53 pathways in radiation-induced sarcomas

et al. 2007

View full text Add to dashboard Cite

The tumour suppressor genes, TP53 and RB1, and four genes involved in their regulation, INK4a, ARF, MDM2 and MDMX, were analysed in a series of 36 postradiotherapy radiation-induced sarcomas. One-third of the tumours developed in patients carrying a germline mutation of RB1 that predisposed them to retinoblastoma and radiation-induced sarcomas. The genetic inactivation of RB1 and/or TP53 genes was frequently observed in these sarcomas. These inactivations were owing to an interplay between point mutations and losses of large chromosome segments. Radiation-induced somatic mutations were observed in TP53, but not in RB1 or in the four other genes, indicating an early role of TP53 in the radio-sarcomagenesis. RB1 and TP53 genes were biallelically coinactivated in all sarcomas developing in the context of the predisposition, indicating that both genes played a major role in the formation of these sarcomas. In the absence of predisposition, TP53 was biallelically inactivated in one-third of the sarcomas, whereas at least one allele of RB1 was wild type. In both genetic contexts, the TP53 pathway was inactivated by genetic lesions and not by the activation of the ARF/MDM2/MDMX pathway, as recently shown in retinoblastomas. Together, these findings highlight the intricate tissue-and aetiologyspecific relationships between TP53 and RB1 pathways in tumorigenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

RB1 and TP53 pathways in radiation-induced sarcomas

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The increased risk of second malignancies conferred by radiation in this patient population is well established in epidemiologic studies (FlGURE 1) [3,6,20]. Long-term follow-up indicates that the risk of a second malignancy in patients with the germinal mutation who underwent radiation is 3.…”

Section: Impact On Incidencementioning

confidence: 84%

Genes and environment: effects on the development of second malignancies in retinoblastoma survivors

Schefler¹,

Kleinerman

Abramson³

2008

Expert Review of Ophthalmology

View full text Add to dashboard Cite

Although it is a rare cancer, retinoblastoma has served as an important model in our understanding of genetic cancer syndromes. All patients with a germinal rb1 mutation possess a risk of the development of second malignancies. Approximately 40-50% of all retinoblastoma cases are considered germinal cases and recent work has indicated that nearly all retinoblastoma patients probably demonstrate a degree of mosaicism for the rb1 mutation, and thus are at risk of secondary malignancies. The risk of the development of these cancers continues throughout the patients' lives due to the loss of a functional RB1 protein and its critical tumor suppressive function in all cells. These cancers can develop in diverse anatomic locations, including the skull and long bones, soft tissues, nasal cavity, skin, orbit, brain, breast and lung. Treatments used for retinoblastoma such as external-beam radiation and chemotherapy can have a significant impact on the risk for and pattern of development of these secondary cancers. Second malignancies are the leading cause of death in germinal retinoblastoma survivors in the USA and thus continue to be an important subject of study in this patient population. Second malignancies following the germinal form of retinoblastoma are the subject of this review.Keywords cancer risk; external-beam radiation; germinal hereditary; pinealoblastoma; radiation-induced neoplasm; retinoblastoma; sarcoma; second malignancy; Survivor Epidemiology: incidence & survivalDuring the mid-20th Century, as treatment regimens for retinoblastoma improved, the number of survivors and their offspring began to increase. Treatment approaches for retinoblastoma in developed countries are now so effective that in the USA, Europe, and developed countries throughout the world, the leading cause of death among retinoblastoma survivors is not retinoblastoma itself, but second malignancies [1]. The incidence of second malignancies in survivors of retinoblastoma who carry the rb1 mutation has been reviewed extensively [1][2][3][4][5][6][7][8][9][10][11][12][13]. Cumulative incidence reports of second malignancies have varied, at least in part because of the wide range in design and population size of these reports. Most large studies with adequate long-term follow-up have reported incidence rates of approximately 0.5-1 % per year when a constant risk of cancer development per year of survival is calculated based on reported cumulative risk rates [1,3,7,10,14]. The study with †

show abstract

“…This can be explained by multiple reasons: different radiotherapy techniques and dosages, different proportion of patients exposed, different chemotherapy protocols, the length of observation time, the size of cohort, the proportion between hereditary and sporadic Rb, follow-up, selection bias and choice of method for statistical analysis. (Aerts et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Mortality from second tumour among long-term survivors of retinoblastoma: a retrospective analysis of the Italian retinoblastoma registry

et al. 2006

View full text Add to dashboard Cite

Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1. 93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13

show abstract

Outcome of second malignancies after retinoblastoma: a retrospective analysis of 25 patients treated at the Institut Curie

Cited by 87 publications

References 28 publications

RB1 and TP53 pathways in radiation-induced sarcomas

RB1 and TP53 pathways in radiation-induced sarcomas

Genes and environment: effects on the development of second malignancies in retinoblastoma survivors

Mortality from second tumour among long-term survivors of retinoblastoma: a retrospective analysis of the Italian retinoblastoma registry

Contact Info

Product

Resources

About