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Clinical significance of early circulating tumor cells (CTC) changes, analyzed by AdnaTest, in patients (pts) receiving first-line methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy (CT) for metastatic urothelial cancer (UC)

Date

09 Oct 2016

Session

Poster display

Presenters

Emanuela Fina

Citation

Annals of Oncology (2016) 27 (6): 266-295. 10.1093/annonc/mdw373

Authors

E. Fina1, A. Necchi2, P. Giannatempo2, M. Colecchia3, D. Raggi2, M.G. Daidone1, V. Cappelletti1

Author affiliations

  • 1 Experimental Oncology And Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 2 Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3 Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
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Background

The therapeutic paradigm of metastatic UC is rapidly shifting due to the advent of new promising targeted therapies or immunotherapies. Liquid biopsies and the early identification of reliable predictive and prognostic factors in the treatment course may be a key to optimize the available standard therapies.

Methods

5 mL of whole blood from pts receiving first-line MVAC were collected at baseline (t0) and after 2 cycles (t2). Samples were processed by immunomagnetic beads (AdnaTest ProstateCancerSelect kit) and the expression of EPCAM, MUC1 and ERBB2 was studied using multiplex-PCR. CTC positivity and cutoffs, obtained by ROC curve analysis in healthy donors, were: ≥1 positive marker among EPCAM (≥0.40 ng/µl), MUC1 (≥0.10 ng/µl) and ERBB2 (≥0.20 ng/µl). CTC variation (t0/t2) was split in favorable (+/-, -/-, -/+) and unfavorable group (+/+) due to small numbers. Univariable analyses were undertaken for progression-free (PFS) and overall survival (OS). Multivariable analyses with bivariable associations with clinical factors were also done to improve understanding of effects.

Results

Among the 31 analyzed pts, 17 (54.8%) were CTC+ at t0 and no association was found with any baseline pt and tumor characteristic, as well as with CTC status and objective response to MVAC. Unfavorable CTC trend was observed in 10/26 (38.5%) cases. CTC dynamic changes better predicted for 3-year (3y) PFS and OS probability compared to CTC status assessed at single time points. Unfavorable trend was univariably detrimental on both 3y PFS probability (10% vs 49.2%, p = 0.006) and 3y OS probability (20% vs 63.5%, p = 0.017). Significance was maintained after adjusting for liver metastases (p = 0.031 and p = 0.025 for PFS and OS) and MSKCC risk score (p = 0.014 and 0.025).

Conclusions

We proposed a novel technique to early assess CTC status in metastatic UC receiving MVAC CT. Early CTC changes may be useful to improve our prognostic ability. Pending validation, these results may lead to improved trial designs and to refine the sequence of conventional CT options in the clinical setting.

Clinical trial identification

None

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale dei Tumori

Funding

Fondazione IRCCS Istituto Nazionale dei Tumori

Disclosure

All authors have declared no conflicts of interest.

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