title: Identifying an early indicator of drug efficacy in patients with metastatic colorectal cancer-a prospective evaluation of circulating tumor cells, 18F-fluorodeoxyglucose positron-emission tomography and the RECIST criteria.
abstract: BACKGROUND
  This study investigated the predictive and prognostic significance of assessing early drug response with both positron-emission computerized tomography (PET-CT) and circulating tumor cells (CTCs) in patients receiving first-line chemotherapy for metastatic colorectal cancer.
  
  
  METHODS
  Eligible patients had PET-CT and CTC analysis at baseline and 4-6 weeks after starting chemotherapy, and then a CT scan at 10-12 weeks to assess the Response Evaluation Criteria In Solid Tumors (RECIST) response. Early response was defined as achieving a dual-endpoint consisting of PET-CT (30% drop in the sum of maximum standard uptake values-SUVmax-of target lesions) and CTC response (CTC < 3 cells/7.5 ml blood) at 4-6 weeks after starting chemotherapy.
  
  
  RESULTS
  About 84 patients were enrolled with a median follow-up of 32.9 months (95% confidence interval, CI, 24.5 months-not reached, NR), and 70 patients (84.3%) completed all assessments. Achieving an early response based on the dual-endpoint was independently associated with progression-free survival (hazard ratio, HR = 0.452, 95% CI 0.267-0.765). The median progression-free survival of early responders was 7.41 months (95% CI, 6.05-9.11) compared with 5.37 months (95% CI, 4.68-6.24) in non-responders (log-rank, P = 0.0167). RECIST response at 10 weeks was independently associated with overall survival (OS) (HR = 0.484, 95% CI, 0.275-0.852). Early response based on the dual-endpoint could predict the subsequent RECIST response with a sensitivity, specificity and positive predictive value of 64%, 70% and 74%, respectively.
  
  
  CONCLUSIONS
  Early response based on both PET-CT and CTC analysis has prognostic and probably predictive significance in patients undergoing first-line chemotherapy for metastatic colorectal cancer. Its utility as a new tool for assessing early drug response should be further validated.
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Clinical Oncology, Sir Y K Pao Centre for Cancer, Hong Kong Cancer Institute.
authors.forename: B
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Diagnostic and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR.
authors.forename: A D
authors.initials: AD
authors.lastname: King
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Clinical Oncology, Sir Y K Pao Centre for Cancer, Hong Kong Cancer Institute.
authors.forename: L
authors.initials: L
authors.lastname: Leung
authors.affiliation: Department of Diagnostic and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Clinical Oncology, Sir Y K Pao Centre for Cancer, Hong Kong Cancer Institute.
authors.forename: A
authors.initials: A
authors.lastname: Poon
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Clinical Oncology, Sir Y K Pao Centre for Cancer, Hong Kong Cancer Institute.
authors.forename: W M
authors.initials: WM
authors.lastname: Ho
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Clinical Oncology, Sir Y K Pao Centre for Cancer, Hong Kong Cancer Institute.
authors.forename: F
authors.initials: F
authors.lastname: Mo
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Clinical Oncology, Sir Y K Pao Centre for Cancer, Hong Kong Cancer Institute.
authors.forename: C M L
authors.initials: CML
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Clinical Oncology, Sir Y K Pao Centre for Cancer, Hong Kong Cancer Institute.
authors.forename: A T C
authors.initials: ATC
authors.lastname: Chan
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong SAR, China.
authors.forename: S C C
authors.initials: SCC
authors.lastname: Wong
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D066066:Response Evaluation Criteria in Solid Tumors; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: circulating tumor cells; colorectal cancer; positron-emission tomography