Radiation Alone for Solid Tumors and the Questionable Development of Therapy-Related Myelodysplastic Syndromes
Menée aux Etats-Unis auprès de 10 924 patients atteints d'un cancer de la prostate diagnostiqué de 1986 à 2011 et traité par radiothérapie, cette étude de cohorte rétrospective évalue l'association entre une exposition à des rayonnements ionisants thérapeutiques et le risque ultérieur de syndromes myélodysplasiques
In this issue of the Journal, Mukherjee and colleagues at the Cleveland Clinic report that prostate cancer patients receiving radiation therapy (RT) at their center are no more likely to develop a therapy-related myelodysplastic syndrome than patients undergoing radiation-free radical prostatectomy (1). To properly frame the importance of this finding, it is important to understand several discoveries leading up to this report.
In 2008, the World Health Organization created the descriptive entity “therapy-related myeloid neoplasms” (t-MNs), which encompasses such conditions as therapy-related myelodysplastic syndrome (MDS) and therapy-related acute myeloid leukemia (AML) based on the following observations: 1) approximately 30% of all MDS cases and 10% to 30% of all AML cases arise after chemotherapy and/or RT for an antecedent cancer; 2) t-MNs harbor distinct chromosome and genetic abnormalities; and 3) patients with t-MNs had worse clinical outcomes compared with patients with de novo MDS or AML (2).
But not all therapies trigger a t-MN clone. Systemically administered alkylating agents and topoisomerase II inhibitors are known carcinogens of hematopoiesis. After these chemotherapies, secondary MDS and AML clones often harbor unfavorable cytogenetic abnormalities. Alkylating agents induce loss of all or part of chromosomes 5 or 7, in addition to deletions or mutations in the P53 tumor suppressor gene. Topoisomerase II inhibitors cause gene rearrangements involving MLL and RUNX1/AML1 genes. These unfavorable genetic abnormalities portend a short survival time.
However, t-MN incidence …
Journal of the National Cancer Institute , éditorial, 2014