title: Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer.
abstract: BACKGROUND
  Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear.
  
  
  METHODS
  Tumor attenuation as measured by Hounsfield units (HU) in contrast-enhanced computed tomography (CT) and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80) treated with regorafenib in a prospective study.
  
  
  RESULTS
  141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5%-20.7%). Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson's r = 0.37, p = 0.002). Among 53 patients with lung metastases, 17 (32.1%) developed cavitary changes. There were no differences in disease control rate, progression-free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD) according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50) and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13).
  
  
  CONCLUSIONS
  Regorafenib showed prominent anti-angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yoojoo
authors.initials: Y
authors.lastname: Lim
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 Radiology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jin Chul
authors.initials: JC
authors.lastname: Paeng
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Won
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Geyonggi-do, Korea.
authors.forename: Jee Hyun
authors.initials: JH
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.|Department of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010671:Phenylurea Compounds; D011725:Pyridines; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D011725:Pyridines; C559147:regorafenib