title: Selection of appropriate end-points (pCR vs 2yDFS) for tailoring treatments with prediction models in locally advanced rectal cancer.
abstract: OBJECTIVE
  Personalized treatments based on predictions for patient outcome require early characterization of a rectal cancer patient's sensitivity to treatment. This study has two aims: (1) identify the main patterns of recurrence and response to the treatments (2) evaluate pathologic complete response (pCR) and two-year disease-free survival (2yDFS) for overall survival (OS) and their potential to be relevant intermediate endpoints to predict.
  
  
  METHODS
  Pooled and treatment subgroup analyses were performed on five large European rectal cancer trials (2795 patients), who all received long-course radiotherapy with or without concomitant and/or adjuvant chemotherapy. The ratio of distant metastasis (DM) and local recurrence (LR) rates was used to identify patient characteristics that increase the risk of recurrences.
  
  
  RESULTS
  The DM/LR ratio decreased to a plateau in the first 2 years, revealing it to be a critical follow-up period. According to the patterns of recurrences, three patient groups were identified: 5-15% had pCR and were disease free after 2 years (excellent prognosis), 65-75% had no pCR but were disease free (good prognosis) and 15-30% had neither pCR nor 2yDFS (poor prognosis).
  
  
  CONCLUSIONS
  Compared with pCR, 2yDFS is a stronger predictor of OS. To adapt treatment most efficiently, accurate prediction models should be developed for pCR to select patients for organ preservation and for 2yDFS to select patients for more intensified treatment strategies.
authors.affiliation: Department of Radiotherapy, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.affiliation: Department of Radiation Oncology (MAASTRO), University Medical Centre Maastricht, The Netherlands; Department of Knowledge Engineering, Maastricht University, The Netherlands. Electronic address: ruud.vanstiphout@maastro.nl.
authors.forename: Ruud G P M
authors.initials: RG
authors.lastname: van Stiphout
authors.affiliation: Department of Radiation Oncology (MAASTRO), University Medical Centre Maastricht, The Netherlands.
authors.forename: Guido
authors.initials: G
authors.lastname: Lammering
authors.affiliation: Bioimmagini e Scienze Radiologiche, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Gambacorta
authors.affiliation: Bioimmagini e Scienze Radiologiche, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Barba
authors.affiliation: Department of Surgical Oncology, Silesian Oncological Centre, Wroclaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bebenek
authors.affiliation: Department of Statistics, Faculté Médecine Dijon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of Radiotherapy, CHU Besançon, France.
authors.forename: Jean F
authors.initials: JF
authors.lastname: Bosset
authors.affiliation: Department of Radiotherapy, The Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bujko
authors.affiliation: Department of Radiotherapy, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cionini
authors.affiliation: Department of Radiotherapy, Centre Antoine Lacassagne, Nice, France.
authors.forename: Jean P
authors.initials: JP
authors.lastname: Gerard
authors.affiliation: Department of Radiotherapy and Oncology, University of Frankfurt, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.affiliation: Department of Radiotherapy, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Sainato
authors.affiliation: Department of Radiotherapy, University of Erlangen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
authors.affiliation: Department of Radiation Oncology, University of Texas MD Anderson Cancer Center Houston, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Minsky
authors.affiliation: Department of Statistics, EORTC Headquarters, Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Collette
authors.affiliation: Department of Radiation Oncology (MAASTRO), University Medical Centre Maastricht, The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D009364:Neoplasm Recurrence, Local / Q000473:pathology* / Q000628:therapy*; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000473:pathology* / Q000628:therapy*; D055815:Young Adult
keywords: Disease-free survival; Pathological complete response; Personalized treatment; Prediction models; Rectal cancer; Risk ratio