Positron emission tomography/computed tomography and biomarkers for early treatment response evaluation in metastatic colon cancer.
BACKGROUND
Treatment options for metastatic colon cancer (mCC) are widening. We prospectively evaluated serial 2-deoxy-2-[18F]fluoro-d-glucose positron-emission tomography/computed tomography (PET/CT) and measurements of tissue inhibitor of metalloproteinases-1 (TIMP-1), carcinoembryonic antigen (CEA), and liberated domain I of urokinase plasminogen activator receptor (uPAR(I)) for early assessment of treatment response in mCC patients.


METHODS
Thirty-three mCC patients scheduled for first-line chemotherapy with capecitabine and oxaliplatin (CAPOX) and bevacizumab participated; 27 were evaluated by PET/CT before treatment, after one and four treatment series. Morphological and metabolic response was independently assessed according to Response Evaluation Criteria in Solid Tumors and European Organization for Research and Treatment of Cancer PET criteria. Plasma TIMP-1, plasma uPAR(I), and serum CEA were determined.


RESULTS
Metabolic response after one treatment course predicted the ability of CAPOX and bevacizumab to induce morphological response after four treatment series with a sensitivity of 80%, specificity of 69%, and odds ratio of 13.9 (95% confidence interval [CI] 1.9; 182). Early metabolically stable or progressive disease was associated with shorter progression-free survival (hazard ratio [HR] = 3.2 [CI 1.3; 7.8]). Biomarker levels at early evaluation were associated with shorter OS (TIMP-1 per unit increase on a log-2-transformed ng/mL scale: HR = 2.6 [CI 1.4; 4.9]; uPAR(I) per 25 fmol/mL increase: HR = 1.5 [CI 1.1; 2.1]).


CONCLUSIONS
This monocentric study demonstrated predictive value of early metabolic PET response and prognostic value of TIMP-1 and uPAR(I) levels in mCC treated with CAPOX and bevacizumab. Results support investigation of PET/CT, TIMP-1, and uPAR(I) guided early treatment adaptation in mCC.
Departments of Clinical Physiology and Nuclear Medicine, Hematology and Oncology, Clinical Pathology, and Radiology, Næstved Hospital, Næstved, Denmark; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark; Department of Public Health, Core Biostatistics, University of Copenhagen, Copenhagen, Denmark; Institute of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark; Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark, and Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark.
Bodil E
BE
Engelmann
Annika
A
Loft
Andreas
A
Kjær
Hans J
HJ
Nielsen
Thomas A
TA
Gerds
Eric V
EV
Benzon
Nils
N
Brünner
Ib J
IJ
Christensen
Susanne H
SH
Hansson
Niels H
NH
Holländer
Michael H
MH
Kristensen
Johan
J
Löfgren
Elena
E
Markova
Carsten
C
Sloth
Liselotte
L
Højgaard
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D019788:Fluorodeoxyglucose F18; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed / Q000379:methods
D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D019275:Radiopharmaceuticals; D000077150:Oxaliplatin; D003841:Deoxycytidine; D019788:Fluorodeoxyglucose F18; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil
Carcinoembryonic antigen; Metastatic colon cancer; Positron-emission tomography; Tissue inhibitor of metalloproteinases-1; Treatment response evaluation; Urokinase plasminogen activator receptor domain I