title: Early18F-FDG-PET/CT as a predictive marker for treatment response and survival in patients with metastatic colorectal cancer treated with irinotecan and cetuximab.
abstract: BACKGROUND
  To clarify if early reduction in standard uptake value (SUV) could predict metabolic response, radiologic response and overall survival (OS) in patients with metastatic colorectal cancer receiving third-line treatment.
  
  
  METHODS
  Patients were regardless of KRAS status, included in this phase II trial. They were treated with the monoclonal antibody, cetuximab, and the chemotherapeutic drug, irinotecan, every second week. A F18-fluorodeoxy glucose positron emission tomography/computed tomography (FDG-PET/CT) was scheduled before the first and second treatment, respectively, and then after every fourth treatment. Early metabolic response after one treatment and best overall metabolic response was calculated according to EORTC criteria (responders: ≥15% decrease in ∑SUVmax) and PERCIST (responders: ≥30% decrease in SULpeak). Best overall radiologic response was calculated according to RECIST 1.0.
  
  
  RESULTS
  By EORTC criteria, early metabolic response predicted partial metabolic response (PMR) with a high positive predictive value (PPV) of 0.875 and a high negative predictive value (NPV) of 0.714. Partial radiologic response was predicted with a low PPV of 0.368 but a high NPV of 1.0. By PERCIST, PMR was predicted with a high PPV of 0.826 and an intermediate NPV of 0.667 and partial radiologic response was predicted with a low PPV of 0.5 but a high NPV of 1.0. Median OS was nearly the same with the two criteria sets; 14.1 months for early metabolic responders and 9.9 months for non-responders using EORTC criteria and 13.5 and 10.1 months, respectively, using PERCIST.
  
  
  CONCLUSIONS
  With both EORTC criteria and PERCIST, early reduction in FDG uptake was predictive of a later partial metabolic and partial radiologic response to treatment. It was also predictive of significantly longer survival of early metabolic responders compared to non-responders. However, the sensitivities and specificities were not high enough to support clinical routine use.
authors.affiliation: a Department of Oncology , Copenhagen University Hospital Herlev , Herlev , Denmark.
authors.forename: Kristin
authors.initials: K
authors.lastname: Skougaard
authors.affiliation: a Department of Oncology , Copenhagen University Hospital Herlev , Herlev , Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Nielsen
authors.affiliation: a Department of Oncology , Copenhagen University Hospital Herlev , Herlev , Denmark.
authors.forename: Benny Vittrup
authors.initials: BV
authors.lastname: Jensen
authors.affiliation: b Department of Oncology , Odense University Hospital , Odense , Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Pfeiffer
authors.affiliation: c Department of Nuclear Medicine , Copenhagen University Hospital Herlev , Herlev , Denmark.
authors.forename: Helle Westergren
authors.initials: HW
authors.lastname: Hendel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068818:Cetuximab / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods; D011237:Predictive Value of Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000972:Antineoplastic Agents, Phytogenic; C117307:KRAS protein, human; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002166:Camptothecin