Key result
High persistence of Pt-(GpG) DNA adducts in circulating tumor cells exposed to cisplatin ex vivo significantly predicted partial response to platinum-based chemotherapy with 80% sensitivity and 83% specificity.
Why the study?
Does ex vivo Pt-(GpG) adduct persistence in circulating tumour cells predict response to platinum-based chemotherapy in patients with NSCLC?
Observational (n=11)
No
Does ex vivo Pt-(GpG) adduct persistence in circulating tumour cells predict response to platinum-based chemotherapy in patients with NSCLC?
Effect estimate: ROC AUC 0.817
Absolute Event Rate: 37.08% vs 3.11%
p-value: p=0.01
Assessing Pt-(GpG) adduct kinetics in circulating tumor cells ex vivo may serve as a predictive biomarker for response to platinum-based chemotherapy in NSCLC patients.
May support ex vivo CTC adduct testing to predict platinum response in NSCLC; leaves open prospective validation before clinical use.
BACKGROUND: Pt-(GpG) intrastrand crosslinks are the major DNA adducts induced by platinum-based anticancer drugs. In the cell lines and mouse models, the persistence of these lesions correlates significantly with cell damage. Here we studied Pt-(GpG) DNA adducts in circulating tumour cells (CTC) treated with cisplatin in medium upfront to systemic therapy from patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Blood was drawn before systemic treatment and the CD45/CD15-depleted fraction of mononuclear cells was exposed to cisplatin, verified for the presence of CTC by pan-cytokeratin (pCK) staining and immunoanalysed for the level of Pt-(GpG) in DNA. RESULTS: Immunostaining for pCK, CD45 and subsequently for Pt-(GpG) adducts in the cisplatin-exposed cells (ex vivo) at different time points depicted distinct differences for adduct persistence in CTC between responders vs non-responders. CONCLUSION: Pt-(GpG) adducts can be detected in CTC from NSCLC patients and assessing their kinetics may constitute a clinically feasible biomarker for response prediction and dose individualisation of platinum-based chemotherapy. This functional pre-therapeutic test might represent a more biological approach than measuring protein factors or other molecular markers.
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Nel et al. (2013) conducted an observational in Non-small-cell lung cancer (NSCLC) (n=11). Ex vivo cisplatin exposure and Pt-(GpG) adduct kinetics measurement vs. Stable disease (non-responders) was evaluated on Pt-(GpG) adduct persistence (AUC) in CTCs exposed to cisplatin ex vivo (ROC AUC 0.817, p=0.01). High persistence of Pt-(GpG) DNA adducts in circulating tumor cells exposed to cisplatin ex vivo significantly predicted partial response to platinum-based chemotherapy with 80% sensitivity and 83% specificity.
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