title: Early tumour shrinkage as a prognostic factor and surrogate end-point in colorectal cancer: a systematic review and pooled-analysis.
abstract: OBJECTIVE
  Early tumour shrinkage (ETS), defined as a reduction of at least 20% in tumour size at first reassessment, has been recently investigated retrospectively in first-line trials of metastatic colorectal cancer (CRC), and appears to be associated with better outcomes. We have performed a systematic review and meta-analysis of published trials to evaluate the prognostic value of ETS in CRC in terms of overall survival (OS) and progression-free survival (PFS).
  
  
  METHODS
  An electronic search of the PubMed, SCOPUS, EMBASE, the Web of Science, and the Cochrane Central Register of Controlled Trial databases identified trials that compared outcomes of patients with or without ETS during first-line chemotherapy for metastatic CRC. The OS, reported as a hazard ratio (HR) with a 95% confidence interval (CI), was the primary outcome measure; the correlation coefficient (R) between ETS with median OS was also estimated.
  
  
  RESULTS
  Twenty-one trials from 10 publications were analysed. Overall, patients with ETS were associated with a better OS (HR, 0.58; 95% CI, 0.53 to 0.64; P<0.00001) and PFS (HR, 0.57; 95% CI, 0.47-0.69; P<0.00001) compared with patients who were early non-responders. However, ETS was poorly correlated with OS in terms of surrogacy (R=0.37; 95% CI - 0.31-0.78; P=0.28).
  
  
  CONCLUSIONS
  ETS is a good prognostic factor but an inappropriate surrogate for predicting outcome in CRC patients. These findings support ETS as prognostic tool in ascertaining earlier non-responders; however, its role as a surrogate end-point deserves further evaluation.
authors: Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: faupe@libero.it.
authors: Fausto
authors: F
authors: Petrelli
authors: Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133 Milan, Italy. Electronic address: filippo.pietrantonio@istitutotumori.mi.it.
authors: Filippo
authors: F
authors: Pietrantonio
authors: UO Oncologia Medica, Azienda Ospedaliero-Universitaria Pisana and Università di Pisa, via Roma 67, 56126 Pisa, Italy. Electronic address: chiaracremolini@gmail.com.
authors: Chiara
authors: C
authors: Cremolini
authors: Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133 Milan, Italy. Electronic address: maria.dibartolomeo@istitutotumori.mi.it.
authors: Maria
authors: M
authors: Di Bartolomeo
authors: Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: artefice2003@hotmail.com.
authors: Andrea
authors: A
authors: Coinu
authors: Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: lo.ve@tiscali.it.
authors: Veronica
authors: V
authors: Lonati
authors: Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133 Milan, Italy. Electronic address: filippo.debraud@istitutotumori.mi.it.
authors: Filippo
authors: F
authors: de Braud
authors: Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: lsandro.barni@ospedale.treviglio.bg.it.
authors: Sandro
authors: S
authors: Barni
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D006801:Humans; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor
keywords: Colorectal cancer; Early tumour shrinkage; First-line therapy; Overall survival; Prognostic factor