Kim Mi-Jung, Han Sae-Won, Lee Dae-Won, Cha Yongjun, Lee Kyung-Hun, Kim Tae-Yong, Oh Do-Youn, Kim Se Hyung, Im Seock-Ah, Bang Yung-Jue, Kim Tae-You
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Cancer Res Treat. 2016 Jul;48(3):990-7. doi: 10.4143/crt.2015.296. Epub 2016 Jan 14.
Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients.
Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells.
Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly.
Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.
脾肿大是奥沙利铂诱导的窦性阻塞综合征（SOS）的临床替代指标。我们研究了在接受辅助性5-氟尿嘧啶、亚叶酸钙和奥沙利铂（FOLFOX）治疗的结直肠癌（CRC）患者中脾肿大的发生情况及其与治疗结果和基因多态性的关系。
通过计算机断层扫描图像测量脾脏体积来确定脾肿大，这些图像是在CRC患者化疗开始前和辅助性FOLFOX治疗结束后获取的。使用外周血单个核细胞的DNA分析4个SOS相关基因（VEGFA、MMP9、NOS3和GSTP1）中的10个基因多态性。
在纳入的124例患者中，109例（87.9%）观察到脾脏大小增加。中位数变化为31%（范围为-42%至168%）。在化疗期间，与无脾肿大的患者相比，有脾肿大的患者血小板减少更严重（p<0.0001）。奥沙利铂的累积剂量和化疗期间的最低血小板计数是与脾肿大相关的临床因素。然而，未发现基因多态性与脾肿大的发生之间存在显著关联。无论是否发生脾肿大，无病生存期相似。
接受辅助性FOLFOX治疗的患者中经常观察到脾肿大，且导致更严重的血小板减少，但不影响治疗结果。所检测的基因多态性不能预测脾肿大的发生。
