Tumor blood flow evaluation in one patient after initiation of atezolizumab + bevacizumab administration

Hamamatsu University School of Medicine
Drs. Satoshi Goshima, Shintaro Ichikawa, and Yukichi Tanahashi, Dept. of Diagnostic Radiology and Nuclear Medicine
Dr. Takashi Oba, Dept. of Radiology, Hamamatsu University Hospital

DATE : 2021

General
Introduction
Case explanation
Imaging findings
Photography protocol

General

1. Roles of contrast computed tomography (CT) in the abdominal region (especially for hepato-bili-ary-pancreatic diseases), and approaches to setting protocols

For any hepato-biliary-pancreatic disease, blood flow information obtained by multiphase imaging is indispensable for primary lesion detection, qualitative diagnosis, disease stage diagnosis, therapeutic efficacy determination, and postoperative complication screening⁽¹⁾. Patients with malignant tumors are often followed up after treatment, and contrast CT in the portal phase is then in general use.

Although contrast magnetic resonance imaging (MRI) with Gadoxetate disodium(Gd-EOB-DTPA) is recommended for detection of primary and metastatic liver cancer⁽¹⁾, there are difficulties with MRI throughput, etc., and contrast CT remains in frequent use in clinical practice.

Qualitative diagnosis of hepatocellular carcinoma (HCC) is made on the basis of wash-out and capsule dark staining in the portal and/or equilibrium phases, following from dark staining in the arterial phase. Optimization of the arterial phase is important, because detection of intra-lesional hypervolemia in not only hypervolemic HCC but also ischemic HCC enables treatment.

In addition, for localized treatments such as surgery, radiofrequency ablation, and transcatheter arterial embolization, elucidation of the relationship between the lesion and intrahepatic blood and lymphatic vessels is important for the treatment strategy. In gallbladder cancer, bile duct cancer, and pancreatic cancer, the dark staining pattern differs according to the proportions of tumor cell components and fibrous interstitial tissue components.
If the content of tumor cell components is high, dark staining in the arterial phase is often seen, whereas if the content of fibrous interstitial tissue components is high this leads to delayed dark staining in the equilibrium phase. Diagnosis in both the portal and equilibrium phases is necessary for determining the resection range and locating hepatic metastases. As there is a limit to the detection capacity of contrast CT for hepatic metastases, if signs suggesting hepatic metastases are detected by contrast CT in accordance with the appropriate imaging protocol, it is preferable to then be proactive in performing additional Gadoxetate disodium(Gd-EOB-DTPA) contrast MRI.

2. Features of the technology installed in the CT device

The device used with this patient, Revolution CT (GE Healthcare), is equipped with a detector that has 256 rows, each 0.625 mm wide. Using a garnet scintillator with luminescence sensitivity 100 times the conventional ratio, and a high-performance generator, scattered radiation was eliminated efficiently with a high-performance, three-dimensional collimator. Therefore, even with dual-energy imaging by ultrafast kV switching at 0.25 ms, high-performance image quality and high-precision quantitativity can be combined. In addition, by equipping the device with a GSI Xtream Smart Workflow, it is possible to perform simultaneous parallel calculations even during imaging, so that no problems occur during routine use even with dual-energy imaging. Furthermore, the device can be used for CT with a plane detector, and is also used in blood-flow analysis with Perfusion, 4D-DSA, etc. Having this high basic performance, the newly installed Deep Leaning image-reconstruction system enables favorable noise elimination even with dual-energy and low-voltage imaging, and its use in clinical practice is continuing to expand and become more widespread.

References

1. Japan Radiological Society (ed.): Diagnostic Imaging Guidelines, 2016.

Introduction

Patient’s background

Male; 70s; body weight: 57 kg; HCC

Assessment objectives

The patient had a history of surgery, transcatheter arterial chemoembolization (TACE), radiotherapy, and lenvatinib administration for HCC with chronic hepatitis B as a background condition. Some lesions were found to have deteriorated rapidly since the final TACE, so atezolizumab + bevacizumab administration was initiated. One week after initiation, hepatic dynamic CT was performed to evaluate tumor blood flow.

Contrast agent used

Iopromide 370 injection syringe, 92 mL

Case explanation

Atezolizumab + bevacizumab combination therapy is a novel treatment method, and in September 2020 it became the first immunotherapy to have been approved for unresectable HCC. With this patient, multiple hypervolemic HCC was found by CT before initiation of this treatment, and blood flow in the arterial phase was markedly reduced as little as 1 week after initiation, with only a fraction of the lesions remaining (Figs. 1, 3, 5 ➡). Dynamic CT using iopromide made it possible to clearly distinguish lesions in which blood flow continued from those in which it had ceased.

Imaging findings

Nodular early dark staining was found in the region showing low concentrations in the equilibrium phase (➡), and consideration was given to the possibility of a viable tumor remaining.

Fig. 1. Arterial phase

A wash-out region was found (➤), and it contained the nodular dark staining found in the arterial phase.

Fig. 2. Equilibrium phase

Nodular early dark staining was found in the region showing low concentrations in the equilibrium phase (➡), and consideration was given to the possibility of a viable tumor remaining.

Fig. 3. Arterial phase

A wash-out region was found (➤), and it contained the nodular dark staining found in the arterial phase.
A wash-out region (⇢) was found, not associated with the dark staining found in the arterial phase, and consideration was given to the possibility of it being the lesion remaining after elimination of a viable tumor.

Fig. 4. Equilibrium phase

Nodular early dark staining was found in the region showing low concentrations in the equilibrium phase (➡), and consideration was given to the possibility of a viable tumor remaining.

Fig. 5. Arterial phase

Fig. 6. Equilibrium phase

Photography protocol

Equipment used	CT device model	Revolution CT True Fidelity (version 2.0) with GSI Xtream (GE Healthcare Japan)
	Number of CT detector rows / number of slices	256 rows
	Workstation	AW Server (GE Healthcare Japan) and Vincent (Fujifilm Medical)

Automatic injector model and manufacturer	Dual Shot GX7 (Nemoto Kyorindo)	Indwelling needle size (G)	20G
Contrast agent name and concentration	Iopromide 370 injection syringe	Injection pressure limit	13kg/cm²

Contrast agent dose	600mgI/kg	Physiological saline solution dose	40mL	Scan timing	BT method (celiac artery), 80HU
Contrast agent injection time	30sec	Physiological saline solution injection speed	Same as contrast agent injection speed	Delay time	See table below

Imaging conditions	Imaging phase	Early arterial phase	Late arterial phase	Early portal phase	Portal phase	Equilibrium phase	Simple
	Tube voltage (kV)	GSI 80-140	GSI 80-140	GSI 80-140	GSI 80-140	GSI 80-140	100
	AEC	GSI Assist 14.8	GSI Assist 14.8	GSI Assist 14.8	GSI Assist 14.8	GSI Assist 14.8	Smart mA 14.8
	Beamwidth (mm)	80	80	80	80	80	80
	Imaging slice thickness (mm)	2.5	2.5	2.5	2.5	2.5	2.5
	Focal-spot size	Large	Large	Large	Large	Large	Large
	Scan mode	Helical	Helical	Helical	Helical	Helical	Helical
	Scan speed (s/rotation)	0.8	0.8	0.8	0.8	0.8	0.6
	Pitch	0.992	0.992	0.992	0.992	0.992	0.992
	Scan range	Upper abdomen	Upper abdomen	Upper abdomen	Upper abdomen to pelvis	Upper abdomen	Upper abdomen
	Imaging duration (s)	4.65	4.65	4.65	5.15	4.65	3.11
	Imaging direction	Head to foot	Head to foot	Head to foot	Head to foot	Head to foot	Head to foot

Reconstruction conditions		Early arterial phase	Late arterial phase	Early portal phase	Portal phase	Equilibrium phase	Simple
	Routine: Reconstructed slice thickness / interval (mm/mm)	2.5/2.5	2.5/2.5	2.5/2.5	2.5/2.5	2.5/2.5	ー
	Routine: Reconstruction function / iterative approximation method	Stnd/DL IR-M	Stnd/DL IR-M	Stnd/DL IR-M	Stnd/DL IR-M	Stnd/DL IR-M	ー
	3D / multiplanar reformation: Reconstructed slice thickness / interval (mm/mm)	3.0/3.0	3.0/3.0	3.0/3.0	3.0/3.0	3.0/3.0	ー
	3D / multiplanar reformation: Reconstruction function / iterative approximation method	Stnd/DLI R-M	Stnd/DLI R-M	Stnd/DLI R-M	Stnd/DLI R-M	Stnd/DLI R-M	ー

Contrast conditions		Early arterial phase	Late arterial phase	Early portal phase	Portal phase	Equilibrium phase	Simple
Contrast conditions	Delay time (s)	10	10	10	10	100	ー

Precautions for use (excerpt)

5. Administration to elderly people
This drug is excreted primarily by the kidneys, but in elderly patients renal function is often depressed, so high blood concentrations may persist. Therefore, it should be administered carefully, with minimization of the dose, etc., while monitoring the patient's condition.

*The case introduced is just one clinical case, so the results are not the same as for all cases.
*Please refer to the Package Insert for the effects and indications, dosage and administration method, and warnings, contraindications, and other precautions with use.