title: No Increased Risk of Second Cancer After Radiotherapy in Patients Treated for Rectal or Endometrial Cancer in the Randomized TME, PORTEC-1, and PORTEC-2 Trials.
abstract: OBJECTIVE
  This study investigated the long-term probability of developing a second cancer in a large pooled cohort of patients treated with surgery with or without radiotherapy (RT).
  
  
  METHODS
  All second cancers diagnosed in patients included in the TME, PORTEC-1, and PORTEC-2 trials were analyzed. In the TME trial, patients with rectal cancer (n = 1,530) were randomly allocated to preoperative external-beam RT (EBRT; 25 Gy in five fractions) or no RT. In the PORTEC trials, patients with endometrial cancer were randomly assigned to postoperative EBRT (46 Gy in 2-Gy fractions) versus no RT (PORTEC-1; n = 714) or EBRT versus vaginal brachytherapy (VBT; PORTEC-2; n = 427).
  
  
  RESULTS
  A total of 2,554 patients were analyzed (median follow-up, 13.0 years; range 1.8 to 21.2 years). No differences were found in second cancer probability between patients who were treated without RT (10- and 15-year rates, 15.8% and 26.5%, respectively) and those treated with EBRT (10- and 15-year rates, 15.4% and 25.6%, respectively) or VBT (10-year rate, 14.9%). In the individual trials, no significant differences were found between treatment arms. All cancer survivors had a higher risk of developing a second cancer compared with an age- and sex-matched general population. The standardized incidence ratio for any second cancer was 2.98 (95% CI, 2.82 to 3.14).
  
  
  CONCLUSIONS
  In this pooled trial cohort of > 2,500 patients with pelvic cancers, those who underwent EBRT or VBT had no higher probability of developing a second cancer than patients who were treated with surgery alone. However, patients with rectal or endometrial cancer had an increased probability of developing a second cancer compared with the general population.
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Lisette M
authors.initials: LM
authors.lastname: Wiltink
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Remi A
authors.initials: RA
authors.lastname: Nout
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Marta
authors.initials: M
authors.lastname: Fiocco
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Elma
authors.initials: E
authors.lastname: Meershoek-Klein Kranenbarg
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Ina M
authors.initials: IM
authors.lastname: Jürgenliemk-Schulz
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Jobsen
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Harm J T
authors.initials: HJ
authors.lastname: Rutten
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.
authors.forename: Carien L
authors.initials: CL
authors.lastname: Creutzberg
authors.affiliation: Lisette M. Wiltink, Remi A. Nout, Marta Fiocco, Elma Meershoek-Klein Kranenbarg, Cornelis J.H. van de Velde, Carien L. Creutzberg, and Corrie A.M. Marijnen, Leiden University Medical Center, Leiden; Ina M. Jürgenliemk-Schulz, University Medical Center Utrecht, Utrecht; Jan J. Jobsen, Medisch Spectum Twente, Enschede; Iris D. Nagtegaal, Radboud University Medical Center, Nijmegen; and Harm J.T. Rutten, Catharina Hospital Eindhoven, Eindhoven, the Netherlands. marijnen@lumc.nl.
authors.forename: Corrie A M
authors.initials: CA
authors.lastname: Marijnen
mesh_terms: D000367:Age Factors; D016889:Endometrial Neoplasms / Q000150:complications / Q000532:radiotherapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016609:Neoplasms, Second Primary / Q000209:etiology*; D009426:Netherlands; D011336:Probability; D011878:Radiotherapy / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000150:complications / Q000532:radiotherapy*; D013997:Time Factors