title: Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Mi-Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Radiology and Institute of Radiation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Se Hyung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D060005:Genotyping Techniques / Q000379:methods; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006498:Hepatectomy / Q000009:adverse effects; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods; D013163:Splenomegaly / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000235:genetics*; D013921:Thrombocytopenia / Q000097:blood* / Q000139:chemically induced / Q000235:genetics; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D009944:Organoplatinum Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D002955:Leucovorin; D005472:Fluorouracil
keywords: Colorectal neoplasms; Genetic polymorphism; Oxaliplatin; Sinusoidal obstruction syndrome; Splenomegaly