Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer

被引:1481
作者
Cohen, Steven J.
Punt, Cornelis J. A.
Iannotti, Nicholas
Saidman, Bruce H.
Sabbath, Kert D.
Gabrail, Nashat Y.
Picus, Joel
Morse, Michael
Mitchell, Edith
Miller, M. Craig
Doyle, Gerald V.
Tissing, Henk
Terstappen, Leon W. M. M.
Meropol, Neal J.
机构
[1] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA
[2] Med Oncol Associates, Kingston, NY USA
[3] Immunicon Corp, Huntingdon, PA USA
[4] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands
[5] Hematol Oncol Associates, Port St Lucie, FL USA
[6] Med Oncol & Hematol PC, New Haven, CT USA
[7] Union Hosp, Canton, OH USA
[8] Washington Univ, St Louis, MO USA
[9] Duke Univ, Med Ctr, Durham, NC USA
关键词
D O I
10.1200/JCO.2007.15.8923
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC. Patients and Methods In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third- line therapy. CTCs were measured using an immunomagnetic separation technique. Results Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P = .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P = .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors. Conclusion The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.
引用
收藏
页码:3213 / 3221
页数:9
相关论文
共 16 条
[1]   Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases [J].
Allard, WJ ;
Matera, J ;
Miller, MC ;
Repollet, M ;
Connelly, MC ;
Rao, C ;
Tibbe, AGJ ;
Uhr, JW ;
Terstappen, LWMM .
CLINICAL CANCER RESEARCH, 2004, 10 (20) :6897-6904
[2]   Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer [J].
Cohen, Steven J. ;
Alpaugh, R. Katherine ;
Gross, Steve ;
O'Hara, Shawn M. ;
Smirnov, Denis A. ;
Ferstappen, Leon W. M. M. ;
Allard, W. Jeffrey ;
Bilbee, Maryann ;
Cheng, Jonathan D. ;
Hoffman, John P. ;
Lewis, Nancy L. ;
Pellegrino, Ann ;
Rogatko, Andre ;
Sigurdson, Elin ;
Wang, Hao ;
Watson, James C. ;
Weiner, Louis M. ;
Meropol, Neal J. .
CLINICAL COLORECTAL CANCER, 2006, 6 (02) :125-132
[3]   Circulating tumor cells, disease progression, and survival in metastatic breast cancer [J].
Cristofanilli, M ;
Budd, GT ;
Ellis, MJ ;
Stopeck, A ;
Matera, J ;
Miller, MC ;
Reuben, JM ;
Doyle, GV ;
Allard, WJ ;
Terstappen, LWMM ;
Hayes, DF .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (08) :781-791
[4]   Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer [J].
Cunningham, D ;
Humblet, Y ;
Siena, S ;
Khayat, D ;
Bleiberg, H ;
Santoro, A ;
Bets, D ;
Mueser, M ;
Harstrick, A ;
Verslype, C ;
Chau, I ;
Van Cutsem, E .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (04) :337-345
[5]   Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor [J].
de Bono, Johann S. ;
Attard, Gerhardt ;
Adjei, Alex ;
Pollak, Michael N. ;
Fong, Peter C. ;
Haluska, Paul ;
Roberts, Luisa ;
Melvin, Carrie ;
Repollet, Madeline ;
Chianese, David ;
Connely, Mark ;
Terstappen, Leon W. M. M. ;
Gualberto, Antonio .
CLINICAL CANCER RESEARCH, 2007, 13 (12) :3611-3616
[6]  
ENGELL H C, 1955, Acta Chir Scand Suppl, V201, P1
[7]   The continuum of care: A paradigm for the management of metastatic colorectal cancer [J].
Goldberg, Richard M. ;
Rothenberg, Mace L. ;
Van Cutsem, Eric ;
Benson, Al B., III ;
Blanke, Charles D. ;
Diasio, Robert B. ;
Grothey, Axel ;
Lenz, Heinz-Josef ;
Meropol, Neal J. ;
Ramanathan, Ramesh K. ;
Becerra, Carlos H. Roberto ;
Wickham, Rita ;
Armstrong, Delma ;
Viele, Carol .
ONCOLOGIST, 2007, 12 (01) :38-50
[8]   Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment [J].
Grothey, A ;
Sargent, D ;
Goldberg, RM ;
Schmoll, HJ .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (07) :1209-1214
[9]   Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer [J].
Hurwitz, H ;
Fehrenbacher, L ;
Novotny, W ;
Cartwright, T ;
Hainsworth, J ;
Heim, W ;
Berlin, J ;
Baron, A ;
Griffing, S ;
Holmgren, E ;
Ferrara, N ;
Fyfe, G ;
Rogers, B ;
Ross, R ;
Kabbinavar, F .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (23) :2335-2342
[10]   Cancer statistics, 2007 [J].
Jemal, Ahmedin ;
Siegel, Rebecca ;
Ward, Elizabeth ;
Murray, Taylor ;
Xu, Jiaquan ;
Thun, Michael J. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2007, 57 (01) :43-66