title: Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib.
abstract: OBJECTIVE
  This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome.
  
  
  RESULTS
  A total of 40 patients were evaluable for PET image analysis. Among various PET parameters, total lesion glycolysis (TLG) measured in the same target lesions for RECIST 1.1 analysis were the most significant in predicting prognosis, with the lowest p-value observed in TLG calculated using the margin threshold of 40 % (TLG40 %). Further analysis using TLG40 %showed significantly longer overall survival (OS) in patients with lower baseline TLG40 %(<151.8) (p = 0.003, median 14.2 vs. 9.1 months in <151.8 and ≥151.8, respectively). Patients showing higher decrease in TLG40 %after treatment showed significantly longer progression-free survival (PFS) (p = 0.001, median 8.0 vs. 2.4 months in %ΔTLG40 %< -9.6 % and ≥ -9.6 %, respectively) and OS (p = 0.002, median 16.4 vs. 9.1 months in %ΔTLG40 %< -9.6 % and ≥ -9.6 %, respectively). The same cutoff could discriminate patients with longer survival among the patients who were under the stable disease category according to RECIST 1.1 (median PFS 8.4 vs. 6.8 months, p = 0.020; median OS 18.3 vs. 11.5 months, p = 0.049).
  
  
  CONCLUSIONS
  Measurement of TLG can predict treatment outcome of regorafenib in mCRC.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-ro, Jongno-gu, Seoul, 03080, South Korea.
authors.forename: Yoojoo
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehang-ro, Jongno-gu, Seoul, 03080, South Korea.
authors.forename: Ji-In
authors.initials: JI
authors.lastname: Bang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-ro, Jongno-gu, Seoul, 03080, South Korea. saewon1@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. saewon1@snu.ac.kr.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehang-ro, Jongno-gu, Seoul, 03080, South Korea. paengjc@snu.ac.kr.
authors.forename: Jin Chul
authors.initials: JC
authors.lastname: Paeng
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-ro, Jongno-gu, Seoul, 03080, South 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, South Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-ro, Jongno-gu, Seoul, 03080, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.|Department of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea.
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000072078:Positron Emission Tomography Computed Tomography; D011446:Prospective Studies; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D011725:Pyridines; D019788:Fluorodeoxyglucose F18; C559147:regorafenib
keywords: Biomarker; Fluorine-18 fluorodeoxyglucose positron-emission tomography; Metastatic colorectal cancer; Regorafenib