In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 7515-7515
Kurzfassung:
7515 Background: IFCT-0002 trial compared two perioperative CT regimens, CDDP-Gemcitabine vs.CBDCA-Paclitaxel in 528 stage I-II NSCLC patients. Paraffin-embedded post-chemo specimens were collected in the 490 non-complete responder patients for tissue expression studies of DNA-repair proteins. Methods: Surgical specimens were processed for immunohistochemistry as previously published. Variables were studied as continuous variables. Cut-off values were validated by bootstrap. Multivariate backward Cox regressions were used to adjust for patients’ characteristics associated with the corresponding outcome at p 〈 0.20 in univariate analysis. Discrimination of the proposed Cox models was estimated using the c-indexes corrected for over-optimism by a resampling procedure. Median follow-up was 72.0 months, 95%CI [69.7-73.5]. Results: ERCC1, MSH2, XRCC5/Ku80 and BRCA1 immunostainings were available in 413, 356, 396 and 221 specimens. Expressed as a continuous variable, only MSH2 staining score correlated with overall survival. XRCC5 showed no influence on survival. When dichotomised, low BRCA1 (under median value) and ERCC1 (ERCC1=0), while high MSH2 protein expression (over median value), adversely affected overall survival with respective adj. HRs of 1.56, 95%CI [1.05-2.32] , p=0.028 ; 1.37 95%CI [1.01-1.86], p=0.042 and 1.53, 95%CI [1.12-2.09] , p=0.007. No interaction was found between the attributed treatment and any of the 4 markers. High MSH2 and low ERCC1 variables were tested in 200 bootstrap multivariate Cox models and correlated with OS in respectively 87% and 78.5% (c-index=0.570), whereas stage predicted survival in only 49% of those theoretical samples. A prognostic score led to the definition of three groups of high-, intermediate- and low-risk of death with respective HRs of 2.83, 1.60 and 1. Median OS were respectively 28.3 months, 71.5 and not reached, 5-y survival rates were 34.2%, 54.8% and 66.3% (Log-Rank p 〈 0.0001). Conclusions: With a 6-year median follow-up, a prognostic score derived from multivariate Cox regression, validated by bootstraping, accurately discriminates a sub-group with high risk of death according to tumor expression of MSH2 and ERCC1.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.7515
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2013
ZDB Id:
2005181-5
