Rationale and Objectives
To prospectively test the hypothesis that transcatheter intraarterial perfusion magnetic resonance imaging (TRIP-MRI) measured semiquantitative perfusion reductions during transcatheter arterial chemoembolization of hepatocellular carcinoma (HCC) are associated with tumor response.
Materials and Methods
Twenty-eight patients (mean age 63 years; range 47–87 years) with 29 tumors underwent chemoembolization in a combined magnetic resonance interventional radiology suite. Intraprocedural tumor perfusion reductions during chemoembolization were monitored using TRIP-MRI. Pre- and postchemoembolization semiquantitative area under the time-signal enhancement curve (AUC) tumor perfusion was measured. Mean tumor perfusion pre- and postchemoembolization were compared using a paired t -test. Imaging follow-up was performed 1–3 months after chemoembolization. We studied the relationship between short-term tumor imaging response and intraprocedural perfusion reductions using univariate and multivariate analysis.
Results
Intraprocedural AUC perfusion value decreased significantly after chemoembolization (342.1 vs. 158.6 arbitrary unit, P < .001). Twenty-six patients with 27 HCCs ( n = 27) had follow-up imaging at mean 39 days postchemoembolization. Favorable response was present in 67% of these treated tumors according to necrosis criteria. Fifteen of 16 (94%) tumors with 25%–75% perfusion reductions showed necrosis treatment response compared to only 3 of 11 (27%) tumors with perfusion reductions outside the above range ( P = .001). Multivariate logistic regression indicated that intraprocedural tumor perfusion reduction and Child-Pugh class were independent factors associated significantly with tumor response ( P = .012 and .047, respectively).
Conclusion
TRIP-MRI can successfully measure semiquantitative changes in HCC perfusion during chemoembolization. Intraprocedural tumor perfusion reductions are associated with future tumor response.
Early identification of tumor response to transcatheter arterial chemoembolization may facilitate efficient assessment of treatment efficacy, timing of repeat therapy, and patient prognosis. Radiological hepatocellular carcinoma (HCC) response assessment by conventional computed tomography (CT) or magnetic resonance imaging (MRI) typically occurs 1–3 months after chemoembolization. Although several studies have identified early vascular and cellular changes using dynamic-contrast enhanced (DCE) and diffusion-weighted (DW) MRI as potential markers for early tumor response assessment , few studies have explored intraprocedural functional imaging biomarkers that may objectively predict future tumor response at the time of chemoembolization procedures.
Intraprocedural MRI allows objective assessment of tumor functions during transcatheter liver-directed embolotherapies . We previously demonstrated that transcatheter intraarterial perfusion (TRIP)-MRI, which uses direct catheter-based intraarterial injections of gadolinium (Gd) contrast, may be clinically employed for intraprocedural monitoring and quantification of tumor perfusion changes during chemoembolization when performed in a combined MRI/digital subtraction angiography (DSA) unit (termed MR-IR suite) . TRIP-MRI serially monitors tumor contrast uptake during chemoembolization, providing reliable objective measurement of tumor perfusion before and after therapy .
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Materials and methods
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Clinical Setting and Patients Characteristics
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Table 1
Patient Demographic and Tumor Characteristics
Characteristic Patient Number ( n = 28) Gender Male 21 Female 7 Age (y) Mean ± standard deviation 62.7 ± 10.4 HCC etiology Alcoholic 5 Hepatitis B virus 1 Hepatitis C virus 13 Other 9 AFP >200 ng/mL 8 ≤200 ng/mL 20 Child-Pugh class A 16 B 12 ECOG performance status 0 9 1 19 AJCC stage 1 17 2 5 3 6 Okuda stage 1 9 2 18 3 1 CLIP stage 0 7 1 11 2 7 3 1 4 2 Tumor morphology Unifocal 18 Multifocal 10 Distribution Unilobar 22 Bilobar 6 Size of targeted lesion (cm) Mean ± standard deviation 4.0 ± 2.7 Diagnosis method Biopsy 11 Imaging 17
AFP, alpha fetoprotein; AJCC, American Joint Committee on Cancer; CLIP, Cancer of the Liver Italian Program; ECOG, Eastern Cooperative Oncology Group.
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MR-IR Suite
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Chemoembolization Procedures
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Intraprocedural MRI
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MRI Perfusion Data Analysis
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Tumor Response Evaluation
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Statistical Analysis
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Results
Intraprocedural TRIP-MRI
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Tumor Imaging Response
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Table 2
Tumor Imaging Response
Response CR PR SD PD WHO 0 0 25 2 Necrosis 7 11 7 2
CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease; WHO, World Health Organization.
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Association between Intraprocedural Tumor Perfusion Reduction and Tumor Response
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Table 3
Relationship Between Tumor Necrosis Imaging Response and MR Perfusion Reduction
Perfusion Reduction Necrosis Response CR PR SD PD Combined CR/PR Combined SD/PD <25% ( n = 6) 0 1 4 1 1 5 25%–50% ( n = 4) 0 4 0 0 4 0 50%–75% ( n = 12) 6 5 1 0 11 1 >75% ( n = 5) 1 1 1 2 2 3
CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.
Table 4
Analyses of Factors Associated with Tumor Response
Variable Necrosis Response_P_ -Value CR/PR ( n = 18, 67%) SD/PD ( n = 9, 23%) Univariate Analysis ∗ Multivariate Analysis † Perfusion reduction 0.001 0.012 25%–75% 15 (94%) 1 (6%) <25 or >75% 3 (27%) 8 (73%) Child-Pugh Class 0.004 0.047 A 13 (93%) 1 (7%) B 5 (38%) 8 (62%) Age (y) 1.000 ≤65 10 (67%) 5 (33%) >65 8 (67%) 4 (33%) Gender 0.653 Male 14 (70%) 6 (30%) Female 4 (57%) 3 (43%) Tumor size (cm) 0.683 ≤3.0 9 (75%) 3 (25%) >3.0 9 (60%) 6 (40%) Tumor number 0.692 1 10 (62.5%) 6 (37.5%) >1 8 (73%) 3 (27%) ECOG performance status 0.667 0 7 (78%) 2 (22%) > 0 11 (61%) 7 (39%) AJCC stage 0.683 1 9 (60%) 6 (40%) >1 9 (75%) 3 (25%) Serum AFP (ng/mL) 1.000 ≤200 13 (68%) 6 (32%) >200 5 (62.5%) 3 (37.5%) Serum bilirubin (mg/dL) 0.193 ≤1.3 8 (89%) 1 (11%) >1.3 10 (56%) 8 (44%)
AFP, alpha fetoprotein; AJCC, American Joint Committee on Cancer; CR, complete response; ECOG, Eastern Cooperative Oncology Group; PD, progressive disease; PR, partial response; SD, stable disease.
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Discussion
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