Risk of third malignancies and death after a second malignancy in retinoblastoma survivors.
ABSTRACT Retinoblastoma patients have a strongly increased risk of second malignancies, and survivors with a third or subsequent malignancy are increasingly observed. However, it has not been examined whether survivors who developed a second malignancy have a greater risk of a subsequent malignancy. On the basis of the Dutch retinoblastoma registry, the risk of a third malignancy was compared with cancer risk in the Dutch population. Cox model analysis with a time-dependent covariate was used to compare the subsequent malignancy risk and survival among patients with and without a second malignancy. Risk of a third malignancy was increased 8-fold compared with the general population. The hazard ratio (HR) of a third malignancy after a second malignancy was more than 7-fold increased compared to the risk of a second malignancy after retinoblastoma. Radiotherapy increased the risk 3-fold. A third malignancy was associated with worse survival compared with survival of patients only diagnosed with a second malignancy (HR=5.0). Survivors of retinoblastoma who already developed a second primary malignancy have an even higher risk of subsequent primary malignancies than retinoblastoma survivors without a second malignancy. Treating physicians and patients should be aware of this higher risk.
- SourceAvailable from: InTechRetinoblastoma: An Update on Clinical, Genetic Counseling, Epidemiology and Molecular Tumor Biology, 03/2012; , ISBN: 978-953-51-0435-3
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ABSTRACT: We assessed risk, localization, and timing of third malignancies in Hodgkin lymphoma (HL) survivors. In a cohort of 3,122 5-year HL survivors, diagnosed before age 51 and treated between 1965-1995, we examined whether risk factors for second and third malignancies differ and whether the occurrence of a second malignancy affects the risk of a subsequent malignancy, using recurrent event analyses. After a median follow-up of 22.6 years, 832 patients developed a second malignancy and 126 patients a third one. The risk of a second malignancy was 4.7-fold (95% confidence interval (CI) 4.4-5.1) increased compared to risk in the general population; the standardized incidence ratio for a third malignancy after a second malignancy was 5.4 (95%CI 4.4-6.5). The 10-year cumulative incidence of any third malignancy was 17.1% among females and 9.2% among males (p=0.000). Compared to patients still free of a second malignancy, patients with a second malignancy had a higher risk to develop a subsequent malignancy. This risk depended on age, with hazard ratios of 2.2, 1.6 and 1.1 for patients aged <25, 25-34 and 35-50 years at HL treatment, respectively. In HL survivors who had a second malignancy, treating physicians should be aware of the increased risk of subsequent malignancies.Blood 04/2014; 124(3). DOI:10.1182/blood-2013-10-532184 · 9.78 Impact Factor
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ABSTRACT: Purpose Hereditary retinoblastoma (Rb) survivors have increased risk of subsequent malignant neoplasms (SMNs). Previous studies reported elevated radiotherapy (RT) -related SMN risks, but less is known about chemotherapy-related risks. Patients and Methods In a long-term follow-up study of 906 5-year hereditary Rb survivors diagnosed from 1914 to 1996 and observed through 2009, treatment-related SMN risks were quantified using cumulative incidence analyses and multivariable Cox proportional hazards regression models with age as the underlying time scale. Results Nearly 90% of Rb survivors were treated with RT, and almost 40% received alkylating agent (AA) containing chemotherapy (predominantly triethylenemelamine). Median follow-up time to first SMN diagnosis was 26.3 years. Overall SMN risk was not significantly elevated among survivors receiving AA plus RT versus RT without chemotherapy (hazard ratio [HR], 1.27; 95% Cl, 0.99 to 1.63). AA-related risks were significantly increased for subsequent bone tumors (HR, 1.60; 95% Cl, 1.03 to 2.49) and leiomyosarcoma (HR, 2.67; 95% Cl, 1.22 to 5.85) but not for melanoma (HR, 0.74; 95% Cl, 0.36 to 1.55) or epithelial tumors (HR, 0.89; 95% Cl, 0.48 to 1.64). Leiomyosarcoma risk was significantly increased for survivors who received AAs at age < 1 (HR, 5.17; 95% Cl, 1.76 to 15.17) but not for those receiving AAs at age >= 1 year (HR, 1.75; 95% Cl, 0.68 to 4.51). Development of leiomyosarcoma was significantly more common after AA plus RT versus RT (5.8% v 1.6% at age 40 years; P = .01). Conclusion This comprehensive quantification of SMN risk after chemotherapy and RT among hereditary Rb survivors also demonstrates an AA-related contribution to risk. Although triethylenemelamine is no longer prescribed, our findings warrant further follow-up to investigate potential SMN risks associated with current chemotherapies used for Rb. (C) 2014 by American Society of Clinical OncologyJournal of Clinical Oncology 09/2014; 32(29). DOI:10.1200/JCO.2013.54.7844 · 17.88 Impact Factor