title: Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection: a pooled analysis of 3,313 patients.
abstract: Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging.
authors.affiliation: Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Radiology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Maas
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Nelemans
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Crane
authors.forename: Carlo
authors.initials: C
authors.lastname: Capirci
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Nash
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Kuo
authors.forename: Rob
authors.initials: R
authors.lastname: Glynne-Jones
authors.forename: Julio
authors.initials: J
authors.lastname: García-Aguilar
authors.forename: Javier
authors.initials: J
authors.lastname: Suárez
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Calvo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pucciarelli
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Biondo
authors.forename: George
authors.initials: G
authors.lastname: Theodoropoulos
authors.forename: Doenja M J
authors.initials: DM
authors.lastname: Lambregts
authors.forename: Regina G H
authors.initials: RG
authors.lastname: Beets-Tan
authors.forename: Geerard L
authors.initials: GL
authors.lastname: Beets
mesh_terms: D000368:Aged; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D066264:Datasets as Topic; D005260:Female; D013502:General Surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual / Q000628:therapy*; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: adjuvant chemotherapy; neoadjuvant treatment; rectal cancer; response; survival