Comparative Accuracy of Intravenous Contrast-enhanced CT versus Noncontrast CT Plus Intravenous Contrast-enhanced CT in the Detection and Characterization of Patients with Hypervascular Liver Metastases

Rational and Objectives

To evaluate whether addition of nonenhanced computed tomography (NECT) to intravenous contrast-enhanced (CE) abdominal CT improves detection or characterization of hypervascular liver masses. Patients were referred for initial staging or follow-up with known breast, melanoma, neuroendocrine, or thyroid cancer.

Material and Methods

The literature was searched using the patient, intervention, comparison, and outcome (PICO) method. Retrieved articles were critically appraised and assigned a level of evidence based on the Oxford University Centre for Evidence-based Medicine hierarchy of validity for diagnostic studies.

Results

One thousand one hundred studies were reviewed; only 11 studies matched the PICO of our study and were appraised. Most of the appraised articles were published in the 1990s using older technology and contrast delivery. The retrieved diagnostic performance for characterization of liver metastases showed sensitivity/specificity of 97%/76% for NECT, 97%/75% for arterial CT, and 98%/76% for portal venous phase CT in patients with breast cancer; sensitivity of 96% (arterial and portal CT) versus 100% (NECT, arterial and portal CT) in patients with melanoma; and sensitivity of 43% (portal CT) versus 17% (NECT) in patients with neuroendocrine tumor. No primary study was found for performance of different CT protocols in patients with thyroid cancer. Available evidence showed radiologists reported more conspicuous liver masses on CECT compared to NECT in patients with breast or neuroendocrine cancer.

Conclusions

Based on existing evidence, NECT only adds a small incremental value to CECT for detection/characterization of hypervascular liver metastases. Addition of NECT increases patient’s exposure to radiation and the number of images available for interpretation.

The liver is a common site of metastatic disease because of the nature of its endothelial lining and dual blood supply. Metastatic disease in the liver is 18–40 times more common than primary liver malignancy .

Imaging of the liver is often started with intravenous contrast-enhanced computed tomography (CECT) achieved in two distinct phases following intravenous contrast injection: the arterial phase (starting 25–30 seconds after the initiation of contrast agent injection) and portal venous phase (started 60–70 seconds after the initiation of the bolus). A delayed phase (approximately 180 seconds after initial bolus) may occasionally be obtained . Nonenhanced CT (NECT) alone is insensitive for detection of hepatic masses and poor at characterization of these masses . However, in some institutions, imaging of liver also includes NECT (before intravenous contrast injection) in addition to CECT, for example, in renal cell carcinoma patients . Furthermore, it is possible that addition of NECT to CECT changes patient management by affecting radiologists’ confidence for characterization of liver masses or allows further characterization of significant incidental findings without additional imaging. The usefulness of imaging tests can vary significantly across institutions because of local radiological expertise, availability of equipment or personnel, and the training, experience, and biases of treating physicians and radiologists . At some institutions, arterial and portal phase CECT are used for hypervascular metastases (melanoma, neuroendocrine tumors [NET], thyroid carcinoma, and sometimes breast cancer ).

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Table 1

Search Strategy Using PICO-focused Keywords

Patients Intervention Comparison Outcome (Breast

Thyroid

Neuroendocrine

Carcinoid

Islet cell

Melanoma)

AND

(Cancer

Tumor

Mass

Carcinoma

Neoplasm) AND (Contrast-enhanced

Contrast

Enhanced

Contrast material

Intravenous contrast)

AND

(CT

Computed tomography) AND (Non-enhanced

Non-contrast

Without contrast)

AND

(Contrast-enhanced

Contrast

Enhanced

Contrast material

Intravenous contrast)

AND

(CT

Computed tomography) AND (Liver

Hepatic)

AND

(Mass

Metastasis

Lesion

Tumor)

AND

Outcome 1:

(Detection

Diagnosis

Characterization

Sensitivity

Specificity)

Outcome 2:

(Confidence level

Conspicuity)

Outcome 3:

(Incidental finding

Extrahepatic finding)

PICO, patient, investigation, comparison, and outcome.

Table 2

Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence

Adopted from Oxford Centre for Evidence-based Medicine website .

Question Step 1 (Level 1 ∗ ) Step 2 (Level 2 ∗ ) Step 3 (Level 3 ∗ ) Step 4 (Level 4 ∗ ) Step 5 (Level 5) Is this diagnostic or monitoring test accurate?

(Diagnosis) Systematic review of cross-sectional studies with consistently applied reference standard and blinding Individual cross-sectional studies with consistently applied reference standard and blinding Nonconsecutive studies or studies without consistently applied reference standards † Case–control studies or poor or nonindependent reference standard † Mechanism-based reasoning (expert opinion without explicit critical appraisal or based on physiology, bench research, or “first principles”)

PICO, patient, investigation, comparison, and outcome.

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Table 3

Included Studies Characteristics and Level of Evidence for Patients with Breast Cancer

Study Zimmerman et al. Sheafor et al. Frederick et al. Patten et al. DuBrow et al. Year 2000 1999 1997 1993 1990 Design Retrospective Retrospective Prospective Retrospective Retrospective No. of patients included 18 300 84 37 63 No. of patients with liver masses 18 79 44 9 63 No. of liver masses NR 387 105 NR NR Age range (y) 37–69 27–82 28–80 20–82 NR Consecutive recruitment NR Yes Yes Yes NR Initial staging or f/u NR Both NR Both NR Reference standard Malignancy criteria on CT and f/u with CT Histopathology, clinical or radiological f/u for 318 d Histopathology, comparison with previous or f/u imaging (CT or MRI) Histopathology, clinical or imaging f/u Histopathology, f/u by sequential imaging showing progression or regression, no f/u in patients with overwhelming liver involvement and other metastases CT protocol NECT, CECT (25, 70 s) NECT, CECT (20, 65 s) NECT, CECT (25,76 s) NECT, CECT (40 s) NECT, CECT (45 s) CT slice thickness (mm) 5 7 7 5 8–10 Contrast infusion Mechanical power injector (3 ml/s) Mechanical power injector (5 ml/s) Mechanical power injector (3 ml/s for 120 ml followed by 2 ml/s for 60 ml) Mechanical power injector (1.5 ml/s for 90 ml followed by 1 ml/s for 90 ml) Mechanical power injector (0.8–1 ml/s) or rapid drip infusion (rate NR) Comparison with other imaging None None None None None Blind interpretation NR Yes Yes NR NR NECT NR Sens (L): 97% Sens (L): 61% Sens (P): 77% Sens (P): 100% Spec (L): 76% Spec (L): 32% Arterial phase CECT NR Sens (L): 97% Sens (L): 59% NR NR Spec (L): 75% Spec (L): 61% Portal phase CECT NR Sens (L): 98% Sens (L): 85% Sens (P): 77% Sens (P): 95% Spec (L): 76% Spec (L): 83% Late-phase CECT NR NR NR NR NR Triple-phase CECT NR NR NR NR NR Combination of CECT and NECT NR NR NR Sens (P): 100% Sens (P): 100% Level of evidence ∗ 4 3 3 3 4

CECT, contrast-enhanced computed tomography; f/u, follow-up; L, lesions; MRI, magnetic resonance imagining; NECT, nonenhanced CT; NR, not reported; P, patient; Sens, sensitivity; Spec, specificity.

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Table 4

Included Studies Characteristics and Level of Evidence for Patients with Melanoma

Study Blake et al. Chomyn et al. Patten et al. Year 1999 1992 1993 Design Prospective Retrospective Retrospective No. of patients included 20 55 15 No. of patients with liver masses 13 16 3 No. of liver masses 57 89 NR Age range (y) 25–77 24–76 20–82 Consecutive recruitment NR NR Yes Initial Staging or f/u f/u NR Both Reference standard Histopathology, comparison with previous imaging Clinical presentation and presence of multiple liver masses or imaging f/u in 2–3 mo Histopathology, clinical or imaging f/u CT protocol NECT, CECT (25, 60, 240 s) NECT, CECT (portal phase) NECT, CECT (40 s) CT slice thickness (mm) 7 10 5 Contrast infusion Mechanical power injector (4 ml/s) Type of infusion not reported (1–2 ml/s for 50 ml followed by 1 ml/s for 100 ml) Mechanical power injector (1.5 ml/s for 90 ml followed by 1 ml/s for 90 ml) Comparison with other imaging None None None Blind interpretation NR NR NR NECT Sens (L): 72% Sens (L): 62% Sens (P): 100% Arterial phase CECT Sens (L): 84% NR NR Portal phase CECT Sens (L): 86% Sens (L): 100% Sens (P): 100% Late-phase CECT Sens (L): 53% NR NR Triple-phase CECT Sens (L): 96% NR NR Combination of CECT and NECT Sens (L): 100% Sens (L): 100% Sens (P): 100% Level of evidence ∗ 3 4 3

CECT, contrast-enhanced CT; f/u, follow-up; L, lesions; NECT, nonenhanced CT; NR, not reported; P, patient; Sens, sensitivity; Spec, specificity.

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Table 5

Included Studies Characteristics and Level of Evidence for Patients with Neuroendocrine Tumor

Study Rockall et al. Seemann et al. Paulson et al. Patten et al. Year 2009 2007 1998 1993 Design Prospective Prospective Retrospective Retrospective No. of patients included 11 31 58 14 No. of patients with liver masses 9 31 31 9 No. of liver masses 265 858 NR NR Age range (y) 36–76 38–83 24–78 20–82 Consecutive recruitment NR Yes Yes Yes Initial staging or f/u Both f/u Both Both Reference standard Both CT and MRI PET/CT Histopathology, focal mass on CT with positive scintigraphy Histopathology, clinical or imaging f/u CT protocol NECT, CECT (arterial, portal) NECT, CECT (35, 80 s) NECT, CECT (20,70 s) NECT, CECT (40 s) CT slice thickness (mm) 5 NR 7 5 Contrast infusion Type of infusion not reported (3–5 ml/s) Mechanical power injector (3 ml/s for 85 ml followed by 1.8 ml/s for 45 ml) Mechanical power injector (5 ml/s) Mechanical power injector (1.5 ml/s for 90 ml followed by 1 ml/s for 90 ml) Comparison with other imaging MRI PET/CT None None Blind interpretation Yes NR NR NR NECT Sens (L): 17% Sens (L): 29% NR Sens (P): 88% Arterial phase CECT Sens (L): 44% Sens (L): 45% NR NR Portal phase CECT Sens (L): 43% Sens (L): 74% NR Sens (P): 77% Late-phase CECT NR NR NR NR Triple-phase CECT NR NR NR NR Combination of CECT and NECT NR NR NR Sens (P): 100% Level of evidence ∗ 3 4 3 3

CECT, contrast-enhanced computed tomography; f/u, follow-up; L, lesions; MRI, magnetic resonance imaging; NECT, nonenhanced CT; NR, not reported; P, patient; PET, positron emission tomography; Sens, sensitivity; Spec, specificity.

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Breast Cancer

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Melanoma

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Neuroendocrine Cancer

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Thyroid Cancer

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Breast Cancer

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Melanoma

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Neuroendocrine Tumor

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Appendix 1 Description of studies not matching the PICO of current study

Breast Cancer

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Melanoma

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Neuroendocrine Tumor

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Comparative Accuracy of Intravenous Contrast-enhanced CT versus Noncontrast CT Plus Intravenous Contrast-enhanced CT in the Detection and Characterization of Patients with Hypervascular Liver Metastases

Rational and Objectives

Material and Methods

Results

Conclusions

Ask

Search

Appraise

Breast Cancer

Melanoma

Neuroendocrine Cancer

Thyroid Cancer

Apply

Breast Cancer

Melanoma

Neuroendocrine Tumor

Evaluate

Appendix 1

Description of studies not matching the PICO of current study

Breast Cancer

Melanoma

Neuroendocrine Tumor

References

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