Incidence of therapy-related leukemia following chemoradiotherapy for esophageal cancer

Abstract

e15663 Background: The combination of chemotherapy and concurrent radiotherapy (CRT) has recognized as a curative alternative for several stage of esophageal cancer. On the other hands, a sufficiently long survival time has increased treatment-related late toxicities. However, the frequency and the pathogenesis of secondary malignancies that is the most serious late-onset complication are still unclear. Methods: From July 2000 to March 2008, 348 patients with esophageal squamous cell carcinoma underwent CRT. All patients received chemotherapy consisting with nedaplatin (80 mg/m2, div day1) and fluorouracil (700 mg/m2, ci day 1–5) and concurrent long T field irradiation (2 Gy daily, up to 30 Gy). A hundred patients received a single course as the neoadjuvant setting. Two cycles of CRT as the definitive or palliative setting were administered in 248 patients. Median and average follow-up durations are 8 and 21 months (1 to 92), respectively. Results: Four patients, who achieved CR after CRT, developed leukemia. Case1, 60-yo-male, developed overt acute myeloid leukemia (AML) from myelodysplastic syndrome 48 months after CRT. Cytogenetic analysis showed complicated abnormalities including deletion 5q. Case2, 64-yo-male, developed AML M0 with t(9;22)(q34;q11) 44 months after CRT. Case3, 72-yo-male, developed Burkitt leukemia with t(8;14)(q24;q32) 19 months after CRT. Case4, 65-yo-male, developed myeloid crisis of chronic myelogenous leukemia with complicated abnormalities including t(9;22)(q34;q11) 48 months after CRT. Case 1 and 3 had localized disease and received single course of neoadjuvant CRT. Case 2 and 4 had advance disease and received 2 courses of CRT. All patients eventually died of leukemia. Conclusions: Since platinum and fluorouracil have shown relatively low chance of secondary neoplasm, our data demonstrates that the concurrent radiotherapy which involves massive bone marrow tissue may increase the risk of leukomogenesis. To this end, atypical cytogenetic abnormalities seen in the present cases give a new insight into the biology of therapy-related leukemia. Notably, this is the first report presenting the incidence of secondary leukemia by nedaplatin. No significant financial relationships to disclose.