Imaging Biomarkers of Tumor Response in Neuroendocrine Liver Metastases Treated with Transarterial Chemoembolization: Can Enhancing Tumor Burden of the Whole Liver Help Predict Patient Survival?
Purpose To investigate whether whole-liver enhancing tumor burden [ETB] can serve as an imaging biomarker and help predict survival better than World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) methods in patients with multifocal, bilobar neuroendocrine liver metastases (NELM) after the first transarterial chemoembolization (TACE) procedure. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 51 patients (mean age, 57.8 years ± 13.2; range, 13.5-85.8 years) with multifocal, bilobar NELM treated with TACE. The largest area (WHO), longest diameter (RECIST), longest enhancing diameter (mRECIST), largest enhancing area (EASL), and largest enhancing volume (ETB) were measured at baseline and after the first TACE on contrast material-enhanced magnetic resonance images. With three-dimensional software, ETB was measured as more than 2 standard deviations the signal intensity of a region of interest in normal liver. Response was assessed with WHO, RECIST, mRECIST, and EASL methods according to their respective criteria. For ETB response, a decrease in enhancement of at least 30%, 50%, and 65% was analyzed by using the Akaike information criterion. Survival analysis included Kaplan-Meier curves and Cox regressions. Results Treatment response occurred in 5.9% (WHO criteria), 2.0% (RECIST), 25.5% (mRECIST), and 23.5% (EASL criteria) of patients. With 30%, 50%, and 65% cutoffs, ETB response was seen in 60.8%, 39.2%, and 21.6% of patients, respectively, and was the only biomarker associated with a survival difference between responders and nonresponders (45.0 months vs 10.0 months, 84.3 months vs 16.7 months, and 85.2 months vs 21.2 months, respectively; P < .01 for all). The 50% cutoff provided the best survival model (hazard ratio [HR]: 0.2; 95% confidence interval [CI]: 0.1, 0.4). At multivariate analysis, ETB response was an independent predictor of survival (HR: 0.2; 95% CI: 0.1, 0.6). Conclusion Volumetric ETB is an early treatment response biomarker and surrogate for survival in patients with multifocal, bilobar NELM after the first TACE procedure.©RSNA, 2016.
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Sonia
S
Sahu
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Ruediger
R
Schernthaner
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Roberto
R
Ardon
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Julius
J
Chapiro
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Yan
Y
Zhao
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Jae Ho
JH
Sohn
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Florian
F
Fleckenstein
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
MingDe
0000-0001-7641-2595
M
Lin
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Jean-François
JF
Geschwind
From the Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, Md (S.S., R.S., Y.Z., J.H.S., F.F., J.F.G., R.D.); Department of Radiology, Yale University School of Medicine, 330 Cedar St, TE 2-230, New Haven, CT 06520 (S.S., R.S., J.C., Y.Z., J.H.S., F.F., J.F.G., R.D.); Medisys, Philips Research, Suresnes, France (R.A.); and U/S Imaging and Interventions (UII), Philips Research North America, Cambridge, Mass (M.L.).
Rafael
R
Duran
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries; D015415:Biomarkers; D016461:Chemoembolization, Therapeutic / Q000379:methods; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality* / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D066066:Response Evaluation Criteria in Solid Tumors; D012189:Retrospective Studies; D015996:Survival Rate; D047368:Tumor Burden; D055815:Young Adult
D015415:Biomarkers