168O - Quantification of cell free DNA as a prognostic factor in advanced NSCLC

Date 29 September 2012
Event ESMO Congress 2012
Session Biomarkers in lung cancer
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Anneli Dowler Nygaard
Authors A. Dowler Nygaard1, K.G. Spindler2, R. Andersen3, N. Pallisgaard3, A. Jakobsen4
  • 1Department Of Oncology, Vejle Hospital, 7100 - Vejle/DK
  • 2Oncology, Vejle Hospital, 7100 - Vejle/DK
  • 3Department Of Clinical Biochemistry, Vejle Hospital Sygehus Lillebaelt, Vejle Sygehus, Vejle, DENMARK, 7100 - Vejle/DK
  • 4Department Og Oncology, Vejle Hospital, 7100 - Vejle/DK

Abstract

Purpose

To investigate the prognostic importance of baseline circulating cell free DNA (cfDNA) in plasma from patients with advanced Non Small Cell Lung Cancer (NSCLC) prior to first-line chemotherapy.

Material and methods

The inclusion criteria were; histopathologically verified advanced NSCLC, indication for first-line chemotherapy and performance status (PS) 0-2. Treatment comprised carboplatin (area under the curve (AUC)5) iv day 1, and vinorelbine 30 mg/m2 iv day 1 and 60mg/m2 po day 8, q3w. A maximum of six courses was given. Plasma was obtained from a pre-treatment EDTA blood-sample. The number of cfDNA alleles at baseline was assessed by an in-house quantitative polymerase chain reaction (qPCR).

Results

A total of 246 patients were included, all receiving at least 1 course (median: 4). The overall response rate was 26%. The number of cfDNA alleles ranged from 480 to 1048500 per ml with a median value of 3200 and a 75th percentile of 6040 alleles per ml. The progression free survival (PFS) by intention to treat (ITT) was 5.4 months and the overall survival (OS) 8.9 months. The baseline level of cfDNA was strongly correlated to outcome. The median PFS was 2.9 months in patients with high levels (> the 75th percentile) compared to 5.7 months in patients with low levels (< the 75th percentile) (HR: 1.83; 95% CI 1.29-2.59; p < 0.0001). The median OS was 4.9 and 10.3 months, respectively (HR: 2.11; 95% CI 1.47-3.0; p < 0.0001). High levels of cfDNA were significantly associated with poor performance status (PS = 2), but neither age, gender, stage, histology nor number of metastases showed any correlation to the cfDNA-level. A multivariate Cox regression analysis confirmed an independent prognostic value of cfDNA in both PFS (p = 0.0002) and OS (p < 0.0001). PS also remained an independent prognostic marker (p = 0.0003 (PFS) and p = 0.002 (OS)).

Conclusion

High levels of cfDNA seem to have a strong prognostic influence as estimated by both PFS and OS in patients with newly diagnosed advanced NSCLC. Combined with PS it outlines a group of patients with minimal or no benefit of chemotherapy, though further investigations are warranted.

Disclosure

All authors have declared no conflicts of interest.