title: Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPIDO trial.
abstract: BACKGROUND
  Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer.
  
  
  METHODS
  Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life.
  
  
  CONCLUSIONS
  Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01558921.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Surgical Gastroenterology, Karolinska University Hospital, Solna P9:03, SE 171 76 Stockholm, Sweden. per.nilsson@karolinska.se
authors.forename: Per J
authors.initials: PJ
authors.lastname: Nilsson
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van Etten
authors.forename: Geke A P
authors.initials: GA
authors.lastname: Hospers
authors.forename: Lars
authors.initials: L
authors.lastname: Påhlman
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Regina G H
authors.initials: RG
authors.lastname: Beets-Tan
authors.forename: Lennart
authors.initials: L
authors.lastname: Blomqvist
authors.forename: Jannet C
authors.initials: JC
authors.lastname: Beukema
authors.forename: Ellen
authors.initials: E
authors.lastname: Kapiteijn
authors.forename: Corrie A M
authors.initials: CA
authors.lastname: Marijnen
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
authors.forename: Theo
authors.initials: T
authors.lastname: Wiggers
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods*; D011878:Radiotherapy / Q000379:methods*; D012004:Rectal Neoplasms / Q000628:therapy*; D012107:Research Design