Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy.

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% CI, 0.99 to 1.63). AA-related risks were significantly increased for subsequent bone tumors (HR, 1.60; 95% CI, 1.03 to 2.49) and leiomyosarcoma (HR, 2.67; 95% CI, 1.22 to 5.85) but not for melanoma (HR, 0.74; 95% CI, 0.36 to 1.55) or epithelial tumors (HR, 0.89; 95% CI, 0.48 to 1.64). Leiomyosarcoma risk was significantly increased for survivors who received AAs at age < 1 (HR, 5.17; 95% CI, 1.76 to 15.17) but not for those receiving AAs at age ≥ 1 year (HR, 1.75; 95% CI, 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.

• Authors: Jeannette R Wong, Lindsay M Morton, Margaret A Tucker, David H Abramson, Johanna M Seddon, Joshua N Sampson, Ruth A Kleinerman
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 29 Pg. 3284-90 (Oct 10 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25185089 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Intramural)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Antineoplastic Agents, Alkylating
• Triethylenemelamine

Topics

• Antineoplastic Agents, Alkylating (adverse effects)
• Child, Preschool
• Female
• Follow-Up Studies
• Humans
• Infant
• Longitudinal Studies
• Male
• Neoplasms, Second Primary (epidemiology)
• Retinal Neoplasms (drug therapy, genetics, pathology, radiotherapy)
• Retinoblastoma (drug therapy, genetics, pathology, radiotherapy)
• Retrospective Studies
• Risk
• Survival Rate
• Survivors
• Triethylenemelamine (adverse effects)
• United States (epidemiology)