Project description:Background: The JBR.10 trial demonstrated significant survival benefit from adjuvant cisplatin/vinorelbine (ACT) in stage IB-II NSCLC (HR 0.69, p=0.04), but stage IB patients did not derive significant benefit (HR: 0.94, p= 0.79). We hypothesized that expression profiling could identify stage-independent subgroups of patients who might benefit from adjuvant chemotherapy. Methods: Gene expression profiling was conducted on mRNA isolated from frozen JBR.10 tumor samples (either from patients under observation [OBS], or treated with ACT). The minimum gene set that selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified and this gene signature was used to classify patients into high and low risk for death after surgery, and predict ACT effect. The prognostic gene signature was additionally tested on ACT patients and publicly available microarray datasets. Results: A 15-gene signature separated OBS patients into equal high and low risk subgroups with significantly different prognoses (HR 15.02, 95% CI 5.12-44.04, p=0.0001). The signature was prognostic in both stage IB and II. It was also predictive of improved survival following ACT treatment in high-risk patients (HR 0.33, 95% CI 0.17-0.63, p=0.0005), but not in low risk patients (HR 3.67, 95% CI 1.22-11.06, p=0.0133; interaction p=0.0001). The prognostic effect of the signature was validated in two independent gene expression datasets of 169 stage I-II adenocarcinoma and 106 squamous cell carcinoma patients. Conclusions: This microarray-based 15-gene prognostic expression signature is stage and histology independent and may select early stage NSCLC patients who are most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine. Keywords: Expression profiling by microarray; prognosis prediction 90 samples

2010-09-09 | E-GEOD-14814 | biostudies-arrayexpress

Randomised study of adjuvant chemotherapy for completely resected p-stage I-IIIA non-small cell lung cancer.

Project description: Not available

| S-EPMC2360551 | biostudies-other

Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non-Small-Cell Lung Cancer

Project description:Purpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT. Patients and Methods: Gene expression profiling was conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation [OBS], 71 ACT). The minimum gene set that was selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified. The prognostic value of this gene signature was tested in four independent published microarray data sets and by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). Results: A 15-gene signature separated OBS patients into high-risk and low-risk subgroups with significantly different survival (hazard ratio [HR], 15.02; 95% CI, 5.12 to 44.04; P .001; stage I HR, 13.31; P .001; stage II HR, 13.47; P .001). The prognostic effect was verified in the same 62 OBS patients where gene expression was assessed by qPCR. Furthermore, it was validated consistently in four separate microarray data sets (total 356 stage IB to II patients without adjuvant treatment) and additional JBR.10 OBS patients by qPCR (n 19). The signature was also predictive of improved survival after ACT in JBR.10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P .0005), but not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133; interaction P .001). Significant interaction between risk groups and ACT was verified by qPCR. Conclusion: This 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.

2010-09-09 | GSE14814 | GEO

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer.

Project description: Not available

| S-EPMC4570139 | biostudies-literature

Significance of TP53 mutations as predictive markers of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer.

Project description: Not available

| S-EPMC5528648 | biostudies-literature