Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX

Abstract

PurposeSplenomegaly 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.Materials and MethodsSplenomegaly 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.ResultsOf 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.ConclusionSplenomegaly 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.

Splenomegaly in Colon Cancer During Adjuvant Oxaliplatin-based Chemotherapy

“…Splenomegaly was determined higher in patients who did not receive dose reduction during chemotherapy in our study, which can be explained by the increase in cumulative oxaliplatin dosage received by patients whose dosages were not reduced. Kim et al have shown that splenomegaly developed more in patients receiving full-dose oxaliplatin than those receiving dose reductions, which is similar to our study [10].…”

“…Kim et al have investigated the association between splenomegaly development in patients with colorectal cancer and thrombocytopenia receiving adjuvant FOLFOX therapy similar to ours. The authors have reported that thrombocyte count was lower both during the chemotherapy period and after in patients developing splenomegaly [10]. Moreover, it has also been shown that thrombocytopenia developing in splenomegaly patients was more severe than in those who did not develop splenomegaly [10].…”

“…[12,16]. Splenomegaly is 24% in the study by Overman and 37.9% in the study by Kim et al [9][10]. The reason is that the different rates of splenomegaly development might be due to the various techniques used in SV measurement.…”

“…Studies have shown the relation between splenomegaly that develop in patients receiving oxaliplatin and thrombocytopenia [9][10]12]. Overman et al have determined a strong correlation between splenomegaly development in patients receiving oxaliplatin and thrombocytopenia [9].…”

“…The authors have reported that thrombocyte count was lower both during the chemotherapy period and after in patients developing splenomegaly [10]. Moreover, it has also been shown that thrombocytopenia developing in splenomegaly patients was more severe than in those who did not develop splenomegaly [10]. Jung et al have reported in colorectal cancer patients receiving FOLFOX4 a correlation between splenomegaly development and thrombocytopenia and emphasized that the correlation became more prominent after 6 cycles of chemotherapy [12].…”