Early Detection of Recurrence in Patients With Locally Advanced Non-Small-Cell Lung Cancer via Circulating Tumor Cell Analysis.
CTC
LA-NSCLC
Lung cancer
Prospective trial
Radiation oncology
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
17
01
2019
revised:
29
03
2019
accepted:
19
04
2019
pubmed:
22
6
2019
medline:
9
4
2020
entrez:
22
6
2019
Statut:
ppublish
Résumé
Assays to identify circulating tumor cells (CTCs) might allow for noninvasive and sequential monitoring of lung cancer. We investigated whether serial CTC analysis could complement conventional imaging for detecting recurrences after treatment in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Patients with LA-NSCLC (stage II-III) who definitively received concurrent chemoradiation were prospectively enrolled, with CTCs from peripheral blood samples identified using an adenoviral probe that detects elevated telomerase activity present in nearly all lung cancer cells. A "detectable" CTC level was defined as 1.3 green flourescent protein-positive cells per milliliter of collected blood. Samples were obtained before, during (at weeks 2, 4, and 6), and after treatment (post-radiation therapy [RT]; at months 1, 3, 6, 12, 18, and 24). Forty-eight patients were enrolled. At a median follow-up of 10.9 months, 22 (46%) patients had disease recurrence at a median time of 7.6 months post-RT (range, 1.3-32.0 months). Of the 20 of 22 patients for whom post-RT samples were obtained, 15 (75%) had an increase in CTC counts post-RT. In 10 of these 15 patients, CTCs were undetectable on initial post-RT draw but were then detected again before radiographic detection of recurrence, with a median lead time of 6.2 months and mean lead time of 6.1 months (range, 0.1-12.0 months) between CTC count increase and radiographic evidence of recurrence. One patient with an early recurrence (4.7 months) had persistently elevated detectable CTC levels during and after treatment. These results indicate that longitudinal CTC monitoring in patients with LA-NSCLC treated with chemoradiation is feasible, and that detectable CTC levels in many patients meaningfully precede radiologic evidence of disease recurrence.
Sections du résumé
BACKGROUND
Assays to identify circulating tumor cells (CTCs) might allow for noninvasive and sequential monitoring of lung cancer. We investigated whether serial CTC analysis could complement conventional imaging for detecting recurrences after treatment in patients with locally advanced non-small-cell lung cancer (LA-NSCLC).
PATIENTS AND METHODS
Patients with LA-NSCLC (stage II-III) who definitively received concurrent chemoradiation were prospectively enrolled, with CTCs from peripheral blood samples identified using an adenoviral probe that detects elevated telomerase activity present in nearly all lung cancer cells. A "detectable" CTC level was defined as 1.3 green flourescent protein-positive cells per milliliter of collected blood. Samples were obtained before, during (at weeks 2, 4, and 6), and after treatment (post-radiation therapy [RT]; at months 1, 3, 6, 12, 18, and 24).
RESULTS
Forty-eight patients were enrolled. At a median follow-up of 10.9 months, 22 (46%) patients had disease recurrence at a median time of 7.6 months post-RT (range, 1.3-32.0 months). Of the 20 of 22 patients for whom post-RT samples were obtained, 15 (75%) had an increase in CTC counts post-RT. In 10 of these 15 patients, CTCs were undetectable on initial post-RT draw but were then detected again before radiographic detection of recurrence, with a median lead time of 6.2 months and mean lead time of 6.1 months (range, 0.1-12.0 months) between CTC count increase and radiographic evidence of recurrence. One patient with an early recurrence (4.7 months) had persistently elevated detectable CTC levels during and after treatment.
CONCLUSION
These results indicate that longitudinal CTC monitoring in patients with LA-NSCLC treated with chemoradiation is feasible, and that detectable CTC levels in many patients meaningfully precede radiologic evidence of disease recurrence.
Identifiants
pubmed: 31221522
pii: S1525-7304(19)30102-0
doi: 10.1016/j.cllc.2019.04.011
pmc: PMC6703908
mid: NIHMS1528565
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
384-390.e2Subventions
Organisme : NCI NIH HHS
ID : R01 CA201071
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
Trends Mol Med. 2006 Mar;12(3):130-9
pubmed: 16488189
Cancers (Basel). 2014 Jan 15;6(1):128-42
pubmed: 24434542
Ann Transl Med. 2014 Nov;2(11):107
pubmed: 25489581
Transl Lung Cancer Res. 2016 Oct;5(5):466-482
pubmed: 27826528
JAMA Oncol. 2015 Jun;1(3):394
pubmed: 26181190
Mol Oncol. 2016 Dec;10(10):1595-1602
pubmed: 27856179
Curr Oncol. 2017 Apr;24(2):103-110
pubmed: 28490924
J Mol Diagn. 2015 May;17(3):209-24
pubmed: 25908243
Drugs Today (Barc). 2004 Aug;40(8):697-710
pubmed: 15510241
PLoS One. 2012;7(7):e41052
pubmed: 22829910
J Clin Oncol. 2015 Mar 20;33(9):1008-14
pubmed: 25667291
Transl Lung Cancer Res. 2017 Dec;6(6):713-715
pubmed: 29218273
Cancer. 2015 Jan 1;121(1):139-49
pubmed: 25241991
Lancet Oncol. 2015 Feb;16(2):187-99
pubmed: 25601342
J Thorac Dis. 2018 Aug;10(Suppl 21):S2522-S2536
pubmed: 30206496
N Engl J Med. 2017 Nov 16;377(20):1919-1929
pubmed: 28885881
J Thorac Oncol. 2017 Feb;12(2):281-292
pubmed: 27826034
Oncol Rep. 2014 Nov;32(5):1772-8
pubmed: 25176113
Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):328-33
pubmed: 17869659
J Thorac Dis. 2011 Sep;3(3):197-204
pubmed: 22263088
Oncologist. 2016 Jan;21(1):84-94
pubmed: 26614709
Am J Respir Crit Care Med. 2017 May 1;195(9):1150-1160
pubmed: 28459327
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402