Highlights
- •Circulating tumour cells (CTCs) count at baseline and day 28 is a strong prognostic factor in advanced gastric cancer.
- •CTC count at day 28 is also predictive of disease control.
- •Therefore, evolution of CTC count between baseline and D28 could help to early adjust treatment.
Abstract
Background
The identification of dynamic biomarkers in advanced gastric and oesogastric junction
adenocarcinoma (GOA) could help to tailor strategies for each patient. Enumeration
of circulating tumour cells (CTCs) is approved by the US Food and Drug Administration
in breast, colon and prostate cancer but is not in advanced GOA. Our study aims to
establish the optimal threshold and the clinical significance of CTC count in advanced
GOA before and during treatment.
Methods
One hundred six patients with untreated advanced GOA were included in the ancillary
study of the PRODIGE 17-ACCORD 20 trial. CTCs were detected in the peripheral blood
using the CellSearch system on day 0 (D0) and day 28 (D28). The prognostic value of
CTCs at D0 and D28 was analysed by testing several thresholds.
Results
At baseline, median CTC count was 1 (range, 0–415). While CTCs ≥1, 2 or 3 at D0 were
all significantly associated with worse overall survival (OS) and progression-free
survival (PFS), CTCs ≥2 were the optimal threshold, on D0 or D28. CTCs ≥2 at D28 were
also predictive of disease control. Taking into account both D0 and D28 CTC count
defined 3 groups (low/low, high/low and low-high/high) with significantly different
PFS (p = 0.0002) and OS (p = 0.003).
Conclusion
Quantification of CTCs at baseline and during treatment may be a useful prognostic
tool in advanced GOA, as it is associated with worse PFS and OS. A threshold ≥2 CTCs
seems to have the best discriminant value. Change in CTC count between baseline and
D28 could help to tailor treatment to each individual patient.
Keywords
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References
- Survival of metastatic gastric cancer: significance of age, sex and race/ethnicity.J Gastrointest Oncol. 2011; 2: 77-84https://doi.org/10.3978/j.issn.2078-6891.2010.025
- Signet-ring cell carcinoma of the stomach: impact on prognosis and specific therapeutic challenge.World J Gastroenterol. 2015; 21: 11428-11438https://doi.org/10.3748/wjg.v21.i40.11428
- Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial.Lancet Lond Engl. 2014; 383: 31-39https://doi.org/10.1016/S0140-6736(13)61719-5
- Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.Lancet Oncol. 2014; 15: 1224-1235https://doi.org/10.1016/S1470-2045(14)70420-6
- Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study.J Clin Oncol Off J Am Soc Clin Oncol. 2014; 32: 3520-3526https://doi.org/10.1200/JCO.2013.54.1011
- Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group.J Clin Oncol Off J Am Soc Clin Oncol. 2006; 24: 4991-4997https://doi.org/10.1200/JCO.2006.06.8429
- Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study.Ann Oncol Off J Eur Soc Med Oncol ESMO. 2015; 26: 149-156https://doi.org/10.1093/annonc/mdu496
- Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer.J Clin Oncol Off J Am Soc Clin Oncol. 2008; 26: 3213-3221https://doi.org/10.1200/JCO.2007.15.8923
- Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer.Clin Cancer Res Off J Am Assoc Cancer Res. 2008; 14: 6302-6309https://doi.org/10.1158/1078-0432.CCR-08-0872
- Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival.Clin Cancer Res Off J Am Assoc Cancer Res. 2006; 12: 4218-4224https://doi.org/10.1158/1078-0432.CCR-05-2821
- FOLFOX alone or combined to rilotumumab or panitumumab as first-line treatment in patients (pts) with advanced gastroesophageal adenocarcinoma (AGEA): an open-label, randomized phase II trial (PRODIGE 17 ACCORD 20 MEGA).J Clin Oncol. 2015; 33
- Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.Clin Cancer Res Off J Am Assoc Cancer Res. 2004; 10: 6897-6904https://doi.org/10.1158/1078-0432.CCR-04-0378
- Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer.J Clin Oncol Off J Am Soc Clin Oncol. 2005; 23: 1420-1430https://doi.org/10.1200/JCO.2005.08.140
- Index for rating diagnostic tests.Cancer. 1950; 3: 32-35
- New guidelines to evaluate the response to treatment in solid tumors. European organization for research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.J Natl Cancer Inst. 2000; 92: 205-216
- Circulating tumor cells as a surrogate marker for determining response to chemotherapy in patients with advanced gastric cancer.Cancer Sci. 2010; 101: 1067-1071https://doi.org/10.1111/j.1349-7006.2010.01492.x
- Circulating tumor cells as an independent predictor of survival in advanced gastric cancer.Ann Surg Oncol. 2015; 22: 3954-3961https://doi.org/10.1245/s10434-015-4483-6
- Dynamic monitoring of circulating tumour cells to evaluate therapeutic efficacy in advanced gastric cancer.Br J Cancer. 2016; 114: 138-145https://doi.org/10.1038/bjc.2015.417
- Different survival outcomes after curative R0-resection for Eastern Asian and European gastric cancer.Med Baltim. 2016; 95https://doi.org/10.1097/MD.0000000000004261
- A pilot study assessing the incidence and clinical significance of circulating tumor cells in esophagogastric cancers.Clin Colorectal Cancer. 2014; 13: 94-99https://doi.org/10.1016/j.clcc.2013.11.003
Article info
Publication history
Published online: April 26, 2017
Accepted:
March 28,
2017
Received in revised form:
March 22,
2017
Received:
February 22,
2017
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.