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dc.contributor.authorSclafani, F
dc.contributor.authorBrown, G
dc.contributor.authorCunningham, D
dc.contributor.authorWotherspoon, A
dc.contributor.authorTait, D
dc.contributor.authorPeckitt, C
dc.contributor.authorEvans, J
dc.contributor.authorYu, S
dc.contributor.authorSena Teixeira Mendes, L
dc.contributor.authorTabernero, J
dc.contributor.authorGlimelius, B
dc.contributor.authorCervantes, A
dc.contributor.authorThomas, J
dc.contributor.authorBegum, R
dc.contributor.authorOates, J
dc.contributor.authorChau, I
dc.date.accessioned2017-08-16T14:40:45Z
dc.date.issued2016-08
dc.identifier.citationAnnals of oncology : official journal of the European Society for Medical Oncology, 2016, 27 (8), pp. 1557 - 1565
dc.identifier.issn0923-7534
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/784
dc.identifier.eissn1569-8041
dc.identifier.doi10.1093/annonc/mdw215
dc.description.abstractBackground EXPERT and EXPERT-C were phase II clinical trials of neoadjuvant chemotherapy (NACT) followed by chemoradiotherapy (CRT) in high-risk, locally advanced rectal cancer (LARC).Design We pooled individual patient data from these trials. The primary objective was overall survival (OS) in the intention-to-treat (ITT) population. Prognostic factors were also analysed.Results A total of 269 patients were included. Of these, 91.1% completed NACT, 88.1% completed CRT and 240 (89.2%) underwent curative surgery (R0/R1). After a median follow-up of 71.9 months, 5-year progression-free survival (PFS) and OS were 66.4% and 73.3%, respectively. In the group of R0/R1 resection patients, 5-year relapse-free survival (RFS) and OS were 71.6% and 77.2%, respectively, with local recurrence occurring in 5.5% and distant metastases in 20.6% of cases. Significant prognostic factors after multivariate analyses included age, tumour grade and MRI extramural venous invasion (mrEMVI) at baseline, MRI tumour regression grade (mrTRG) after CRT, ypT stage after surgery and adherence to study treatment. mrTRG after NACT was associated with PFS (P = 0.002) and OS (P = 0.018) and appeared to stratify patients based on the incremental benefit from sequential CRT. Among the outcome measures considered, in the subgroup of R0/R1 resection patients, ypT and ypStage had the highest predictive accuracy for RFS (concordance index: 0.6238 and 0.6252, respectively) and OS (concordance index: 0.6094 and 0.6132, respectively).Conclusions Administering NACT before CRT could be a potential strategy for high-risk LARC. In this setting, mrTRG after CRT is an independent prognostic factor, while mrTRG after NACT should be tested as a parameter for treatment selection in trials of NACT ± CRT. ypT stage may be a valuable surrogate end point for future phase II trials investigating intensified neoadjuvant treatments in similar patient populations.
dc.formatPrint-Electronic
dc.format.extent1557 - 1565
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectHumans
dc.subjectRectal Neoplasms
dc.subjectNeoplasm Recurrence, Local
dc.subjectMagnetic Resonance Imaging
dc.subjectDisease-Free Survival
dc.subjectTreatment Outcome
dc.subjectNeoadjuvant Therapy
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectKaplan-Meier Estimate
dc.subjectChemoradiotherapy
dc.titlePAN-EX: a pooled analysis of two trials of neoadjuvant chemotherapy followed by chemoradiotherapy in MRI-defined, locally advanced rectal cancer.
dc.typeJournal Article
dcterms.dateAccepted2016-05-13
rioxxterms.versionofrecord10.1093/annonc/mdw215
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAnnals of oncology : official journal of the European Society for Medical Oncology
pubs.issue8
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume27en_US
pubs.embargo.termsNot known
icr.researchteamMedicine (RMH Smith Cunningham)en_US
dc.contributor.icrauthorCunningham, Daviden
dc.contributor.icrauthorChau, Ianen


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