Show simple item record

dc.contributor.authorGlynne-Jones, Ren_US
dc.contributor.authorSebag-Montefiore, Den_US
dc.contributor.authorMeadows, HMen_US
dc.contributor.authorCunningham, Den_US
dc.contributor.authorBegum, Ren_US
dc.contributor.authorAdab, Fen_US
dc.contributor.authorBenstead, Ken_US
dc.contributor.authorHarte, RJen_US
dc.contributor.authorStewart, Jen_US
dc.contributor.authorBeare, Sen_US
dc.contributor.authorHackshaw, Aen_US
dc.contributor.authorKadalayil, Len_US
dc.contributor.authorACT II study groupen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2017-03-24T13:57:19Z
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28209296en_US
dc.identifierS1470-2045(17)30071-2en_US
dc.identifier.citationLancet Oncol, 18 (3), pp. 347 - 356en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/489
dc.identifier.eissn1474-5488en_US
dc.identifier.doi10.1016/S1470-2045(17)30071-2en_US
dc.description.abstractBACKGROUND: Guidelines for anal cancer recommend assessment of response at 6-12 weeks after starting treatment. Using data from the ACT II trial, we determined the optimum timepoint to assess clinical tumour response after chemoradiotherapy. METHODS: The previously reported ACT II trial was a phase 3 randomised trial of patients of any age with newly diagnosed, histologically confirmed, squamous cell carcinoma of the anus without metastatic disease from 59 centres in the UK. We randomly assigned patients (by minimisation) to receive either intravenous mitomycin (one dose of 12 mg/m2 on day 1) or intravenous cisplatin (one dose of 60 mg/m2 on days 1 and 29), with intravenous fluorouracil (one dose of 1000 mg/m2 per day on days 1-4 and 29-32) and radiotherapy (50·4 Gy in 28 daily fractions); and also did a second randomisation after initial therapy to maintenance chemotherapy (fluorouracil and cisplatin) or no maintenance chemotherapy. The primary outcome was complete clinical response (the absence of primary and nodal tumour by clinical examination), in addition to overall survival and progression-free survival from time of randomisation. In this post-hoc analysis, we analysed complete clinical response at three timepoints: 11 weeks from the start of chemoradiotherapy (assessment 1), 18 weeks from the start of chemoradiotherapy (assessment 2), and 26 weeks from the start of chemoradiotherapy (assessment 3) as well as the overall and progression-free survival estimates of patients with complete clinical response or without complete clinical response at each assessment. We analysed both the overall trial population and a subgroup of patients who had attended each of the three assessments by modified intention-to-treat. This study is registered at controlled-trials.com, ISRCTN 26715889. FINDINGS: We enrolled 940 patients from June 4, 2001, until Dec 16, 2008. Complete clinical response was achieved in 492 (52%) of 940 patients at assessment 1 (11 weeks), 665 (71%) of patients at assessment 2 (18 weeks), and 730 (78%) of patients at assessment 3 (26 weeks). 691 patients attended all three assessments and in this subgroup, complete clinical response was reported in 441 (64%) patients at assessment 1, 556 (80%) at assessment 2, and 590 (85%) at assessments 3. 151 (72%) of the 209 patients who had not had a complete clinical response at assessment 1 had a complete clinical response by assessment 3. In the overall trial population of 940 patients, 5 year overall survival in patients who had a clinical response at assessments 1, 2, 3 was 83% (95% CI 79-86), 84% (81-87), and 87% (84-89), respectively and was 72% (66-78), 59% (49-67), and 46% (37-55) for patients who did not have a complete clinical response at assessments 1, 2, 3, respectively. In the subgroup of 691 patients, 5 year overall survival in patients who had a clinical response at assessment 1, 2, 3 was 85% (81-88), 86% (82-88), and 87% (84-90), respectively, and was 75% (68-80), 61% (50-70), and 48% (36-58) for patients who did not have a complete clinical response at assessment 1, 2, 3, respectively. Similarly, progression-free survival in both the overall trial population and the subgroup was longer in patients who had a complete clinical response, compared with patients who did not have a complete clinical response, at all three assessments. INTERPRETATION: Many patients who do not have a complete clinical response when assessed at 11 weeks after commencing chemoradiotherapy do in fact respond by 26 weeks, and the earlier assessment could lead to some patients having unnecessary surgery. Our data suggests that the optimum time for assessment of complete clinical response after chemoradiotherapy for patients with squamous cell carcinoma of the anus is 26 weeks from starting chemoradiotherapy. We suggest that guidelines should be revised to indicate that later assessment is acceptable. FUNDING: Cancer Research UK.en_US
dc.format.extent347 - 356en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAgeden_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectAnus Neoplasmsen_US
dc.subjectCarcinoma, Squamous Cellen_US
dc.subjectChemoradiotherapyen_US
dc.subjectCisplatinen_US
dc.subjectDose Fractionationen_US
dc.subjectFemaleen_US
dc.subjectFluorouracilen_US
dc.subjectFollow-Up Studiesen_US
dc.subjectHumansen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectMitomycinen_US
dc.subjectNeoplasm Recurrence, Localen_US
dc.subjectNeoplasm Stagingen_US
dc.subjectPrognosisen_US
dc.subjectRemission Inductionen_US
dc.subjectSurvival Rateen_US
dc.subjectTime Factorsen_US
dc.titleBest time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-11-15en_US
rioxxterms.versionofrecord10.1016/S1470-2045(17)30071-2en_US
rioxxterms.licenseref.startdate2016-11-15en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfLancet Oncolen_US
pubs.issue3en_US
pubs.notesNot knownen_US
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-statusPublisheden_US
pubs.volume18en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
dc.contributor.icrauthorCunningham, Daviden_US
dc.contributor.icrauthorMarsden,en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/