dc.contributor.author | Fontana, E | |
dc.contributor.author | Nyamundanda, G | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Tu, D | |
dc.contributor.author | Cheang, MCU | |
dc.contributor.author | Jonker, DJ | |
dc.contributor.author | Siu, LL | |
dc.contributor.author | Sclafani, F | |
dc.contributor.author | Eason, K | |
dc.contributor.author | Ragulan, C | |
dc.contributor.author | Bali, MA | |
dc.contributor.author | Hulkki-Wilson, S | |
dc.contributor.author | Loree, JM | |
dc.contributor.author | Waring, PM | |
dc.contributor.author | Giordano, M | |
dc.contributor.author | Lawrence, P | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Begum, R | |
dc.contributor.author | Shapiro, JD | |
dc.contributor.author | Price, TJ | |
dc.contributor.author | Cremolini, C | |
dc.contributor.author | Starling, N | |
dc.contributor.author | Pietrantonio, F | |
dc.contributor.author | Trusolino, L | |
dc.contributor.author | O'Callaghan, CJ | |
dc.contributor.author | Sadanandam, A | |
dc.date.accessioned | 2020-11-03T15:04:21Z | |
dc.date.issued | 2020-09-29 | |
dc.identifier.citation | JCO precision oncology, 2020, 4 | |
dc.identifier.issn | 2473-4284 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4207 | |
dc.identifier.eissn | 2473-4284 | |
dc.identifier.doi | 10.1200/po.20.00050 | |
dc.description.abstract | PURPOSE: Metastatic colorectal cancers (mCRCs) assigned to the transit-amplifying (TA) CRCAssigner subtype are more sensitive to anti-epidermal growth factor receptor (EGFR) therapy. We evaluated the association between the intratumoral presence of TA signature (TA-high/TA-low, dubbed as TA-ness classification) and outcomes in CRCs treated with anti-EGFR therapy. PATIENTS AND METHODS: The TA-ness classes were defined in a discovery cohort (n = 84) and independently validated in a clinical trial (CO.20; cetuximab monotherapy arm; n = 121) and other samples using an established NanoString-based gene expression assay. Progression-free survival (PFS), overall survival (OS), and disease control rate (DCR) according to TA-ness classification were assessed by univariate and multivariate analyses. RESULTS: The TA-ness was measured in 772 samples from 712 patients. Patients (treated with anti-EGFR therapy) with TA-high tumors had significantly longer PFS (discovery hazard ratio [HR], 0.40; 95% CI, 0.25 to 0.64; P < .001; validation HR, 0.65; 95% CI, 0.45 to 0.93; P = .018), longer OS (discovery HR, 0.48; 95% CI, 0.29 to 0.78; P = .003; validation HR, 0.67; 95% CI, 0.46 to 0.98; P = .04), and higher DCR (discovery odds ratio [OR]; 14.8; 95% CI, 4.30 to 59.54; P < .001; validation OR, 4.35; 95% CI, 2.00 to 9.09; P < .001). TA-ness classification and its association with anti-EGFR therapy outcomes were further confirmed using publicly available data (n = 80) from metastatic samples (PFS P < .001) and patient-derived xenografts (P = .042). In an exploratory analysis of 55 patients with RAS/BRAF wild-type and left-sided tumors, TA-high class was significantly associated with longer PFS and trend toward higher response rate (PFS HR, 0.53; 95% CI, 0.28 to 1.00; P = .049; OR, 5.88; 95% CI, 0.71 to 4.55; P = .09; response rate 33% in TA-high and 7.7% in TA-low). CONCLUSION: TA-ness classification is associated with prognosis in patients with mCRC treated with anti-EGFR therapy and may further help understanding the value of sidedness in patients with RAS/BRAF wild-type tumors. | |
dc.format | Electronic-eCollection | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Intratumoral Transcriptome Heterogeneity Is Associated With Patient Prognosis and Sidedness in Patients With Colorectal Cancer Treated With Anti-EGFR Therapy From the CO.20 Trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-08-06 | |
rioxxterms.versionofrecord | 10.1200/po.20.00050 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | JCO precision oncology | |
pubs.notes | Not 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/Genomic Analysis – Clinical Trials | |
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/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
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/Genomic Analysis – Clinical Trials | |
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/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 4 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Genomic Analysis – Clinical Trials | |
icr.researchteam | Medicine (RMH Smith Cunningham) | |
icr.researchteam | Systems and Precision Cancer Medicine | |
dc.contributor.icrauthor | Cheang, Chon | |
dc.contributor.icrauthor | Ragulan, Chanthirika | |