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Prospective Validation Obtained in a Similar Group of Patients and with Similar High Throughput Biological Tests Failed to Confirm Signatures for Prediction of Response to Chemotherapy and Survival in Advanced NSCLC: A Prospective Study from the European Lung Cancer Working Party.

Berghmans T, Ameye L, Lafitte JJ, Colinet B, Cortot A, CsToth I, Holbrechts S, Lecomte J, Mascaux C, Meert AP, Paesmans M, Richez M, Scherpereel A, Tulippe C, Willems L, Dernies T, Leclercq N, Sculier JP, European Lung Cancer Working Par - Front Oncol (2015)

Bottom Line: No statistically significant differences were observed according to the main clinical characteristics, response rate (43 vs. 41%) or survival (median 25 vs. 29 months) between derivation and validation sets.However, these results could not be reproduced in an independent validation set.The role of miRNA and mRNA as predictive or prognostic factors remains a research topic and the use of high throughput technology in that context questionable.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.

ABSTRACT

Aim: Cisplatin doublets are standard 1st line treatment for advanced non-small cell lung cancer (NSCLC), without accurate predictor for response and survival, but important toxicity. Our aims were to identify predictive (for response) and prognostic (for survival) biological signatures in patients with NSCLC using messenger RNAs (mRNA) and miRNA expression.

Methods: Patients with pathologically proven untreated NSCLC, receiving 1st line cisplatin-vinorelbine and with an assessable lesion were eligible. A bronchial biopsy was lysed into Tripure Isolation Reagent on ice, snap frozen, and stored at -80°C. mRNA expression was analyzed using microarrays Agilent Technologies. miRNA expression was assessed using TaqMan Low Density Arrays (756 human miR panel, Applied Biosystems). Validation was performed by RT-PCR on the selected genes. Survival was measured from the registration date and response assessed by WHO criteria.

Results: Biopsies for transcriptomic analyses were obtained from 60 consecutive patients. No statistically significant differences were observed according to the main clinical characteristics, response rate (43 vs. 41%) or survival (median 25 vs. 29 months) between derivation and validation sets. In the derivation set (n = 38 patients), two mRNA and one miRNA predictive signatures for response were obtained. One mRNA and one miRNA prognostic signatures were derived from the first set, allowing an adequate distinction of patients with good and poor overall and progression-free survivals. None of these signatures could be validated in the validation set (n = 22 patients).

Conclusion: In this prospective study with advanced NSCLC treated with cisplatin-vinorelbine, we were able to derive with high throughput techniques predictive and prognostic signatures based on transcriptomic analyses. However, these results could not be reproduced in an independent validation set. The role of miRNA and mRNA as predictive or prognostic factors remains a research topic and the use of high throughput technology in that context questionable. The ClinicalTrials.gov study identifier is NCT00864266 (www.clinicaltrials.gov).

No MeSH data available.


Related in: MedlinePlus

Flow chart of the patients treated with cisplatin–vinorelbine for transcriptomic analysis.
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Figure 2: Flow chart of the patients treated with cisplatin–vinorelbine for transcriptomic analysis.

Mentions: Among 93 patients benefiting from chemotherapy, 76 did receive a combination of cisplatin (60 mg/m2 day 1) and vinorelbine (25 mg/m2 days 1 and 8). From these 76 patients (Figure 2), eight were not assessable for response and at the time of analysis, one patient was still under therapy and not yet assessed. Sixty-seven patients were evaluable for response but only 55 samples were adequate for performing microarrays (mRNA), the other 11 showing either insufficient quantity (n = 2), poor quality (n = 9), or unassessable for technological consideration (n = 1). The first 34 patients were included in the derivation group and the further 21 ones in the validation one. Sixty patients could be included in the miRNA analyses, the first 38 for the derivation group and the further consecutive 22 for the validation one. In seven cases, RNA was in insufficient quantity. The main characteristics of the patients are reported in the Table 1. No statistically significant differences were observed between the derivation and validation sets concerning clinical characteristics, response rate, or survival times.


Prospective Validation Obtained in a Similar Group of Patients and with Similar High Throughput Biological Tests Failed to Confirm Signatures for Prediction of Response to Chemotherapy and Survival in Advanced NSCLC: A Prospective Study from the European Lung Cancer Working Party.

Berghmans T, Ameye L, Lafitte JJ, Colinet B, Cortot A, CsToth I, Holbrechts S, Lecomte J, Mascaux C, Meert AP, Paesmans M, Richez M, Scherpereel A, Tulippe C, Willems L, Dernies T, Leclercq N, Sculier JP, European Lung Cancer Working Par - Front Oncol (2015)

Flow chart of the patients treated with cisplatin–vinorelbine for transcriptomic analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309174&req=5

Figure 2: Flow chart of the patients treated with cisplatin–vinorelbine for transcriptomic analysis.
Mentions: Among 93 patients benefiting from chemotherapy, 76 did receive a combination of cisplatin (60 mg/m2 day 1) and vinorelbine (25 mg/m2 days 1 and 8). From these 76 patients (Figure 2), eight were not assessable for response and at the time of analysis, one patient was still under therapy and not yet assessed. Sixty-seven patients were evaluable for response but only 55 samples were adequate for performing microarrays (mRNA), the other 11 showing either insufficient quantity (n = 2), poor quality (n = 9), or unassessable for technological consideration (n = 1). The first 34 patients were included in the derivation group and the further 21 ones in the validation one. Sixty patients could be included in the miRNA analyses, the first 38 for the derivation group and the further consecutive 22 for the validation one. In seven cases, RNA was in insufficient quantity. The main characteristics of the patients are reported in the Table 1. No statistically significant differences were observed between the derivation and validation sets concerning clinical characteristics, response rate, or survival times.

Bottom Line: No statistically significant differences were observed according to the main clinical characteristics, response rate (43 vs. 41%) or survival (median 25 vs. 29 months) between derivation and validation sets.However, these results could not be reproduced in an independent validation set.The role of miRNA and mRNA as predictive or prognostic factors remains a research topic and the use of high throughput technology in that context questionable.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care and Oncological Emergencies and Thoracic Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles , Brussels , Belgium.

ABSTRACT

Aim: Cisplatin doublets are standard 1st line treatment for advanced non-small cell lung cancer (NSCLC), without accurate predictor for response and survival, but important toxicity. Our aims were to identify predictive (for response) and prognostic (for survival) biological signatures in patients with NSCLC using messenger RNAs (mRNA) and miRNA expression.

Methods: Patients with pathologically proven untreated NSCLC, receiving 1st line cisplatin-vinorelbine and with an assessable lesion were eligible. A bronchial biopsy was lysed into Tripure Isolation Reagent on ice, snap frozen, and stored at -80°C. mRNA expression was analyzed using microarrays Agilent Technologies. miRNA expression was assessed using TaqMan Low Density Arrays (756 human miR panel, Applied Biosystems). Validation was performed by RT-PCR on the selected genes. Survival was measured from the registration date and response assessed by WHO criteria.

Results: Biopsies for transcriptomic analyses were obtained from 60 consecutive patients. No statistically significant differences were observed according to the main clinical characteristics, response rate (43 vs. 41%) or survival (median 25 vs. 29 months) between derivation and validation sets. In the derivation set (n = 38 patients), two mRNA and one miRNA predictive signatures for response were obtained. One mRNA and one miRNA prognostic signatures were derived from the first set, allowing an adequate distinction of patients with good and poor overall and progression-free survivals. None of these signatures could be validated in the validation set (n = 22 patients).

Conclusion: In this prospective study with advanced NSCLC treated with cisplatin-vinorelbine, we were able to derive with high throughput techniques predictive and prognostic signatures based on transcriptomic analyses. However, these results could not be reproduced in an independent validation set. The role of miRNA and mRNA as predictive or prognostic factors remains a research topic and the use of high throughput technology in that context questionable. The ClinicalTrials.gov study identifier is NCT00864266 (www.clinicaltrials.gov).

No MeSH data available.


Related in: MedlinePlus