MR and CT imaging characteristics and ablation zone volumetry of locally advanced pancreatic cancer treated with irreversible electroporation
Eur Radiol
MR and CT imaging characteristics and ablation zone volumetry of locally advanced pancreatic cancer treated with irreversible electroporation
Laurien G. P. H. Vroomen 0 1 2 3 4
Hester J. Scheffer 0 1 2 3 4
Marleen C. A. M. Melenhorst 0 1 2 3 4
Marcus C. de Jong 0 1 2 3 4
Janneke E. van den Bergh 0 1 2 3 4
Cornelis van Kuijk 0 1 2 3 4
Foke van Delft 0 1 2 3 4
Geert Kazemier 0 1 2 3 4
Martijn R. Meijerink 0 1 2 3 4
0 Department of Gastroenterology and Hepatology, VU University Medical Center , Boelelaan 1117, 1081 HV Amsterdam , The Netherlands
1 Department of Radiology and Nuclear Medicine, VU University Medical Center , Boelelaan 1117, 1081 HV Amsterdam , The Netherlands
2 Laurien G. P. H. Vroomen
3 Abbreviations ADC AJCC ASA CA 19.9 ce CT DWI , USA
4 Department of Surgery, VU University Medical Center , Boelelaan 1117, 1081 HV Amsterdam , The Netherlands
Objectives To assess specific imaging characteristics after irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) with contrast-enhanced (ce)MRI and ceCT, and to explore the correlation of these characteristics with the development of recurrence. Methods Qualitative and quantitative analyses of imaging data were performed on 25 patients treated with percutaneous IRE for LAPC. Imaging characteristics of the ablation zone on ceCT and ceMRI were assessed over a 6-month follow-up period. Contrast ratio scores between pre- and post-treatment were compared. To detect early imaging markers for treatment failure, attenuation characteristics at 6 weeks were linked to the area of recurrence within 6 months. Results Post-IRE, diffusion-weighted imaging (DWI)-b800 signal intensities decreased in all cases (p < 0.05). Both ceMRI and ceCT revealed absent or decreased contrast
Pancreatic neoplasms; Ablation; Magnetic resonance imaging; Computed tomography; Tumour volume
-
Laurien G. P. H. Vroomen and Hester J. Scheffer contributed equally to
this work.
enhancement, with a hyperintense rim on ceMRI. Ablation
zone volume increase was noted on both modalities in the first
6 weeks, followed by a decrease (p < 0.05). In the patients
developing tumour recurrence (5/25), a focal DWI-b800
hyperintense spot at 6 weeks predated unequivocal recurrence on
CT.
Conclusion The most remarkable signal alterations after
pancreatic IRE were shown by DWI-b800 and ceMRI. These
early imaging characteristics may be useful to establish
technical success and predict treatment outcome.
Key Points
This study describes imaging characteristics after
irreversible electroporation (IRE) for pancreatic adenocarcinoma.
Familiarity with typical post-IRE imaging characteristics
helps to interpret ablation zones.
Post-IRE, no central and variable rim enhancement are
visible on contrast-enhanced imaging.
DWI-b800 may prove useful to predict early tumour
recurrence.
Post-IRE examinations reveal an initial volume increase
followed by a decrease.
apparent diffusion coefficient
American Joint Committee on Cancer
American Society of Anaesthesiologists
Cancer antigen 19.9
contrast-enhanced
computed tomography
diffusion-weighted imaging
18F-FDG
PET
IRE
LAPC
MRI
NPV
PPV
RECIST
ROI
SUVmax
WHO
Introduction
18F-fluorodeoxyglucose positron emission
tomography
Irreversible electroporation
Locally advanced pancreatic carcinoma
magnetic resonance imaging
negative predictive value
positive predictive value
Response Evaluation Criteria in Solid Tumours
region of interest
maximum standardized uptake value
World Health Organization
Patients with pancreatic cancer have a poor prognosis. For
nonmetastatic disease, the only curative opportunity is
surgical resection, and unfortunately, only 10–20 % of patients are
surgical candidates [
1
]. Up to 40 % of patients present with
nonmetastatic, but unresectable disease due to vascular
encasement (locally advanced pancreatic carcinoma [LAPC] or
American Joint Committee on Cancer [AJCC] stage III
disease) [
1, 2
]. In recent years, image-guided pancreatic tumour
ablation has gained increased interest when surgical options
are excluded. Nevertheless, thermal ablation techniques are
associated with substantial morbidity and mortality, due to
the proximity of large vessels, the pancreatic and common
bile duct, and the gastroduodenal wall [3]. Also, the
socalled heat-sink effect can impede complete ablation [
4
].
Recently, irreversible electroporation (IRE) has emerged as
a novel ablation technique that potentially circumvents the
abovementioned limitations. IRE induces an electric field
across cells to alter the cellular transmembrane potential.
After reaching a sufficiently high voltage, the phospholipid
bilayer structure of the cell membrane is permanently
disrupted, inducing apoptosis. It is hypothesized that IRE
leaves supporting tissue largely unaffected, preserving the
structure of large blood vessels and bile ducts [
5
]. Since IRE
relies on electrical energy, its efficacy is unaffected by the
heatsink effect. This suggests safer and more effective ablation of
neoplasms adjacent to large vessels or fragile structures [
6
].
Multiple studies have suggested the safety and feasibility of
pancreatic IRE [
7–9
], but only few have focused on ablation
zone imaging characteristics and volumetry post-IRE in the
clinical setting [
10–12
]. Familiarity with post-interventional
imaging is essential to determine ablation success and for
the detection of recurrence. Since isolated recurrence may be
favourable over distant metastasis for patients’ prognosis,
accurate imaging interpretation following IRE is of considerable
importance [
13
].
The purpose of the present study was to assess specific
imaging characteristics after percutaneous irreversible
electroporation (IRE) for locally advanced pancreatic carcinoma
(LAPC) with multiphasic contrast-enhanced (ce)MRI and
ceCT. Additionally, imaging features prognostic for local
recurrence were explored. The secondary aim was to quantify
tumour and ablation zone volumes.
Methods
Qualitative and quantitative analyses of imaging data were
performed on all patients treated with percutaneous IRE for
LAPC in the prospective PANFIRE-trial (Clinicaltrials.gov:
NCT01799044). All patients gave written informed consent.
The local institutional review board gave approval. Study
design and conduct were in accordance with the guidelines for
Good Clinical Practice.
Patients and tumours
Between January 2014 and June 2015, 25 patients (12 men, 13
women; median age, 61 years [range, 41-78]) with
histologically proven LAPC who met inclusion criteria were included.
Prior to study enrolment, all participants were discussed in the
multidisciplinary pancreatic tumour board. Inclusion criteria
were radiologic confirmation of LAPC stage III (axial
diameter ≤5 cm), American Society of Anaesthesiologists (ASA)
performance status 1-3, and adequate bone marrow, liver,
and renal function (Table 1A). Exclusion criteria were distant
metastases, history of epilepsy or ventricular arrhythmias, an
implanted stimulation device, and a metal biliary stent.
IRE procedure
All procedures were performed by an interventional
radiologist (MRM) under general anaesthesia as described
previously [
14
]. A ceCT, using multiplanar image
reconstruction, was made to define the three-dimensional tumour
measurements. Size and shape, including a 5-mm margin,
determined the number and configuration of the electrodes
(NanoKnife, AngioDynamics, Latham, NY, USA). Three
to six electrodes with an exposure length of 15 mm were
placed in the outer border or just outside the tumour under
CT-guidance. Ablation was performed between all
electrode pairs that were separated between 15-24 mm from
each other. For larger tumours, the needles were
repositioned for one or more overlapping ablations
(Table 2A). Per electrode pair a total of 100 pulses of
1500 V/cm and 90 μs were delivered. The AccuSync
cardiac synchronization device (Accusync Research Monitor,
Milford, CT, USA) was used to synchronize the electric
pulses with the patient’s electrocardiogram.
Imaging
CeMRI and ceCT scans were performed according to schedule
(Table 1). MRI was performed using a 1.5-Tesla MRI (Signa
HDxt, General Electric, Cleveland, OH, USA) with an
8channel phased array coil. Imaging protocol included
T2weighted fast-recovery fast spin echo images (matrix
320⨯224; field of view [FOV] 400 mm; slice thickness
7 mm), diffusion-weighted images (DWI) (b0, b50, and
b800 s/mm2; matrix 160⨯128; FOV 400 mm; slice thickness
8 mm) and breath-hold unenhanced and contrast-enhanced
T1-weighted three-dimensional fat-suppressed spoiled
gradient-echo images (matrix 256⨯256; FOV 350 mm; slice
thickness 3 mm; respectively, matrix 256⨯224; FOV 400 mm;
slice thickness 4.4 mm) in the arterial phase (20 s), portal
venous phase (60 s), and delayed phase (120 and 180 s) after
intravenous injection of gadolinium (Dotarem, Guerbet,
Villepinte, France) in a dose of 0.2 mL/kg at 3 mL/s. CT data
were acquired using a 64-row MDCT system (Siemens
Sensation, Erlangen, Germany). Scanning parameters were
120 kV, 180 mAs, and 380 mm FOV. CT was performed after
intravenous administration of a 100 mL bolus of non-ionic
iodinated contrast material (Xenetix 300, Guerbet,
Villepinte, France), at 4 mL/s with a scan delay of 40 s for
the pancreatic phase and 70 s for the portal venous phase.
Tumour and ablation zone evaluation
Two experienced abdominal radiologists (MCM and JEB)
interpreted the ceCT and ceMR images independently. Per
sequence, findings were graded systematically according to
the specific tumour and ablation zone imaging characteristics
compared to the surrounding healthy pancreatic parenchyma,
using a region of interest (ROI). MRI intensity was evaluated
on an ordinal 7-point scale (—/0/+++). CT density was
assessed on an ordinal 3-point scale (-/0/+). Furthermore, the
presence and configuration of periablational rim
enhancement, intralesional gas pockets, and blood residues was
evaluated. Discrepancies between the interpreters’ findings were
solved by consensus.
Radiologic response was evaluated through Response
Evaluation Criteria in Solid Tumours (RECIST) [
15
], in
which recurrence was defined as a focal or diffuse growing
mass within 1 cm of the ablated region compared to the new
baseline-scan at 6 weeks post-IRE, accompanied by a
substantial cancer antigen (CA) 19.9 rise (duplication compared to
baseline). Tumours recurring within 6 months were
considered early recurrences. Histopathologic confirmation was only
obtained if patients were eligible for retreatment. To detect
possible early imaging markers for treatment failure, a
reassessment of the recurrence area was performed.
Predicted and obtained treatment zone volumes
Tumour and ablation zone volumes were measured by
manually drawing the boundary of the tumour and ablation zone on
each portal venous ceCT and ceMRI DWI-b800 slice (Fig. 1).
The volume of the segmented lesion resulted from the sum of
all segmented slice surfaces, multiplied by the reconstruction
increment (caliper method) [
16
]. Patients who developed an
early recurrence were excluded from volumetric analysis.
Statistical analyses
Descriptive statistics were used to present results as
absolute numbers (normal distribution), median and range
(nonnormal distribution), or frequencies and percentages
(categorical variables). The two-tailed Wilcoxon signed-rank test
*After 3 months of follow-up, ceCT was
performed every 3 months
Fig. 1 Manually drawn boundary of tumour on (a) ceCT (portal venous
phase) and (b) DWI-b800 sequence
was performed to compare contrast ratio scores across
sequences between pre- and post-treatment. Statistical
analyses were performed using SPSS, version 20.0 (SPSS,
Chicago, IL, USA). The level of statistical significance
was set to p < 0.05. Interobserver-agreement was assessed
with k-statistics [
17
]. The prognostic accuracy of a focal
hyperintense spot on the 6-week follow-up DWI-b800 for
the development of recurrence within 6 months post-IRE
was determined with sensitivity, specificity, negative
predictive value (NPV), and positive predictive value (PPV).
Results
Twenty-five patients with a median age of 61 years (range
4178) were included for analysis. Tumours were located in the
pancreatic head (n = 18), body (n = 2), and uncinate process
(n = 5). Needle placement and pulse delivery was successfully
performed in all patients. Complications post-IRE were
oedematous pancreatitis (n = 1), duodenal wall ulcer directly
adjacent to the ablation zone (n = 1), new-onset biliary
obstruction (n = 3), cholangitis with infected biloma (n = 1), and
subtotal occlusion of the superior mesenteric artery (n = 1).
CeMR imaging
Complete MRI follow-up was accomplished in 21 patients.
Four patient were excluded from MR follow-up because of
claustrophobia. CeMRI tumour and ablation zone findings are
shown in Table 2. Interobserver agreement was substantial to
excellent on DWI-b800, precontrast T1- and postcontrast
T1weighted MRI and moderate to excellent on T2- and
postcontrast T1-weighted MRI (Table 3).
Prior to IRE, most tumours were markedly hyperintense on
T2-weighted images (71 %, n = 15) and on DWI-b800 (86 %,
n = 18) compared to surrounding normal pancreatic
parenchyma. Pancreatic tumours appeared hypointense in 86 % (n =
18) on both apparent diffusion coefficient (ADC) and arterial
1 day post-IRE
2 weeks post-IRE
6 weeks post-IRE
Values of κ=0.81–1.00 indicate excellent agreement, κ=0.61–0.80 indicates substan al agreement,
κ=0.41–0.60 indicates moderate agreement, κ=0.21–0.40 indicates fair agreement and κ≤0.20
indicates slight agreement [
17
].
Pre-IRE
1 day post-IRE
2 weeks post-IRE
6 weeks post-IRE
ceMRI
T2
DWI-b800
ADC
T1 precontrast
T1 arterial phase
T1 venous phase
ceCT
CT arterial phase
CT venous phase Pre-IRE
0.768
0.833
0.771
0.781
0.559
1.00
(—) IRE ablation zone plus rim-enhancement surrounding the treated
area on T1 sequence (portal venous phase) (m) Hyperintense (+) IRE
ablation zone plus hypointense rim enhancement surrounding the
treated area on T2 sequence (n) Hyperintense (+) IRE ablation zone on
DWI-b800 sequence (o) Isointense IRE ablation zone on ADC map.
6 weeks post-IRE: (p) Isointense IRE ablation zone on T1 sequence (q)
Hypointense (–) IRE ablation zone on T1 sequence (portal venous phase)
(r) Hyperintense (+) IRE ablation zone plus hypointense rim
enhancement surrounding the treated area on T2 sequence (s)
Hyperintense (+) IRE ablation zone on DWI-b800 (t) Isointense IRE
ablation zone on ADC map
Tumour and ablation zone signal densities on ceCT
phase T1-weighted MRI, and in 76 % (n = 16) on the portal
venous phase T1-weighted MRI.
Compared to original tumour intensity, one day post-IRE
DWI-b800 MRI signal intensities notably decreased in all
cases (p = 0.0002), accompanied by a subsequent ADC
increase (p = 0.0044). At two and 6-week follow-up, intensity
remained low on DWI-b800, in comparison with the initial
lesion (p = 0.0022 and p = 0.0023, respectively) and high on
ADC (p = 0.0010 and p = 0.0022, respectively). One day
postIRE, small areas of diffuse hyperintensity representing blood
residues were detected in all ablated areas on precontrast
T1weighted images. At this point, the ablation zone contrast
enhancement in the arterial and portal venous phase had
decreased in all lesions as compared to initial tumour intensity
(p = 0.0099 and p = <0.0001). In the portal venous phase, a
hyperintense rim surrounding the IRE ablation zone was
found in 71 % (n = 16) both 1 day and 2 weeks post-IRE,
and was less often identified at 6-week follow-up (29 %,
n = 6). At 2- and 6-week follow-up, tumour intensity remained
low for the arterial phase (p = 0.0004 and p = 0.033) and portal
venous phase (p = 0.0001 and p = 0.0009). On the
T2weighted sequences, ablation zone intensity during
followup did not significantly differ from the initial tumour intensity.
However, a remarkable hypointense rim surrounding the
ablation zone was observed in 52 % (n = 11) of patients 2 weeks
post-IRE on T2-weighted MRI. An example of typical MRI
features is shown in Fig. 2, corresponding to successfully
ablated tumours.
CeCT imaging
Differences between attenuation pre- and post-IRE in the
arterial and portal venous phase were not statistically
significant. Table 4 and Fig. 3 show the tumour and ablation zone
attenuation characteristics on ceCT. Interobserver agreement
was mostly substantial to excellent (Table 3). Compared to the
Fig. 3 Imaging findings during
follow-up on ceCT (a)
Isoattenuating tumour on ceCT
pre-IRE (b) CT-guided placement
of electrodes around the outer
border of the tumour (c)
Confirmation of correct electrode
configuration according to the
treatment plan with a
nonenhanced CT scan (d)
Hypoattenuating IRE ablation
zone with intralesional gas
pockets immediately after IRE (e)
Hypoattenuating IRE ablation
zone at 6 weeks of follow-up (f)
Hypoattenuating IRE ablation
zone at 3 months of follow-up
healthy pancreatic parenchyma the initial tumour appeared
either isodense (56 %) or hypodense in the arterial phase
(44 %) and hypodense (72 %) in the portal venous phase.
Immediately after IRE, intralesional and periablational gas
pockets were present in all cases. Post-IRE the ablation zones
were primarily hypodense in the arterial phase after 6 weeks
and 3 and 6 months (80 %, 52 %, and 56 %, respectively). In
the portal venous phase 76 % of the ablated areas were slightly
hypodense immediately post-IRE; at 6 weeks and 3- and
6month follow-up, ablation zones were hypodense in 92 %,
92 %, and 94 %, respectively.
Early recurrence
During a median follow-up period of 6 months (range 3-17),
five patients developed an early local recurrence at 2 (n = 1), 3
(n = 1), 5 (n = 2), and 6 (n = 1) months, detected on ceCT and
accompanied by a substantial CA 19.9 rise. Histopathologic
confirmation was obtained in one patient who was
subsequently retreated with IRE (Fig. 4). The four remaining
patients were considered unsuitable for retreatment because
of excessive disease progression. Targeted analysis of the
recurring areas revealed small hyperintense spots adjacent to the
overall decreased ablation zone intensity on DWI-b800,
which was low on ADC (Fig. 5). For this reason all DWI
and ADC exams were prospectively re-assessed for the
presence of these marginal spots by both reviewers (MCM and
JEB). Interobserver agreement was substantial (k = 0.674). In
4/5 patients a marginal spot showing diffusion restriction
correlated to early recurrence. In a fifth patient patchy
hyperintensity at 6 weeks evolved into extensive local
recurrence after 6 months. However, a marginal spot was also
identified in 3/16 patients without early relapse (sensitivity 100 %,
specificity 81 %, NPV 100 %, and PPV 63 %).
Tumour and ablation zone volumes
Ablation zones on both ceCT and DWI-b800 were difficult to
delineate from the surrounding pancreatic parenchyma due to
Fig. 4 The development of a
local recurrence. Red line =
duodenum. a CeCT pre-IRE
showing the initial tumour (white
arrowheads) that was treated with
IRE (b) MR DWI-b800 6 weeks
post-IRE showing new
hyperintensity around the
superior mesenteric artery (white
arrowheads) (c) CeCT 4 months
post-IRE showing evident local
recurrence (white arrowhead) (d)
re-IRE of the local recurrence
Fig. 5 DWI b800 MR images showing (a) a hyperintensity of the tumour
pre-IRE (arrows); (b) hypointensity of the ablated area with hyperintense
marginal spots and a lymph node at 6 weeks post-IRE
intralesional gas pockets, blood residues, and surrounding
tissue oedema.
CeMR imaging
The volume of one ablation zone prior to treatment and
6 weeks post-IRE could not be defined. Median tumour
volume 0-2 weeks prior to intervention was 19 mL (range 6-58).
One day post-IRE median ablation zone volume was 49 mL
(range 16-100). At 2 weeks of follow-up, median volume was
reduced to 16 mL (range 7-98). The median ablation zone
volume remained mostly stable at 6 weeks of follow-up
(14 mL, range 5-71) (Fig. 5).
CeCT imaging
Volumes prior to IRE (n = 2), immediately post-IRE (n = 8),
6 weeks post-IRE (n = 4), 3 months post-IRE (n = 1), and
6 months (n = 1) could not be precisely determined due to
poorly demarcated margins of the ablation zone. A median
tumour volume of 15 mL (range 4-98) was measured on
ceCT pre-IRE. Median ablation zone volume directly after
the intervention was 31 mL (range 19-150). On follow-up
examinations after 6 weeks, median volume had decreased
to 17 mL (range 2-59). Eventually, ablation zone volume
was equal to original tumour volume at 3 months of
followup (median 22 mL, range 4-78) and 6 months (median 28 ml,
range 8-64) (Fig. 6).
Discussion
Evaluation of tumour response after ablation is important to
define treatment success and to guide future therapy [
18
].
Knowledge of postinterventional MR and CT findings is
essential for accurate interpretation of the ablated area.
Familiarity with these characteristics prevents confusion
between normal or less typical postablational changes and
residual or recurrent disease. In addition, timely recognition of
IRE-related complications and vital tumour allows for
expedited management and possible retreatment. In this study, the
evolution of ablation zones based on ceMRI and ceCT was
reviewed over a follow-up period of 90 days.
In the liver, compared to the surrounding normal
parenchyma, a well-demarcated ablation zone is commonly visible on
CT and MRI post-IRE [
11, 19
]. Also, IRE ablation zones in
the liver depict a transient peripheral hyperenhancing rim [
11,
19
]. Since generally little healthy pancreatic tissue surrounds
the pancreatic tumour, in our study the ablation zone was often
ill-defined on MRI and especially on CT. Also, the presence of
more oedema within the ablation zone often impeded precise
ablation zone delineation.
Literature on post-IRE MRI is scarce and predominantly
involves the liver; imaging data of pancreatic IRE in humans
is not available yet. A reasonable explanation for the observed
hyperintense rim surrounding the ablation zone post-IRE is
reactive hyperaemia of oedematous inflammatory origin [
20,
21
]. However, it cannot be excluded that this rim still contains
residual disease and longer follow-up is needed to explore the
exact significance. The remarkable hypointense rim that we
found on T2 at 2 weeks suggests hemosiderin deposition [22]
resulting from degradation of the extravagated erythrocytes in
the periphery of the ablation zone [
23
].
Post-IRE, arterial and portal venous phase CT attenuation
decreased in nearly all patients. This decline in enhancement
is in line with the observed postcontrast MRI findings, which
may be indicative for accurate tumour therapy response [
24
].
The observed intralesional gas pockets may be caused by
electrolysis of water into hydrogen and oxygen caused by
the electric pulses [
23
], or by vaporization due to heat
development, or by a combination of these mechanisms.
Initial post-IRE examinations revealed a notable volume
increase on ceCT and ceMRI, followed by a decrease during
follow-up. The calculated volumes varied widely between
the two modalities, which is caused by the difficult ablation
zone delineation from surrounding structures. Studies
investigating the size and shape of the IRE ablation zone have
predominantly correlated imaging findings to histology in
animal studies. Overall, the radiological ablation zone size
as measured on CT and MRI-DWI correlates well with the
histological ablation zone [
20, 25, 26
]. In addition, studies
suggested that ablation zone size and shape depend on the
IRE parameters used and on the type of tissue ablated [
27
].
There is clear concordance between our findings and
preclinical and early clinical studies that describe a reduction of
the size of the ablated area over several weeks [
6, 11, 12,
20
], resulting from the clearance of cellular debris aided by
the preservation of larger vessels [
6, 20
].
The World Health Organization (WHO) criteria and
RECIST criteria, depend on decrease in tumour size [
28,
29
]. However, decrease in viable cell mass is not always
reflected by changes in tumour size [30]. Exclusive reliance
on tumour size does not, therefore, provide a complete
assessment of tumour response and may lead to inaccurate
conclusions [
29
]. A preferable method of post-IRE treatment
evaluation is to combine tumour and ablation zone sizes with
functional information such as alterations in enhancement
and diffusion [
31
].
CT is the standard imaging modality used for follow-up of
pancreatic cancer and has an accuracy of 93.5 % for detecting
locally recurrent tumour after pancreaticoduodenectomy
using RECIST [
32
]. Since all five patients showed
DWIb800 hyperintensity and low ADC values at the site of
eventual recurrence at 6 weeks, DWI-b800 and ADC may be
useful to predict early recurrence or incomplete ablation, similar
to imaging after hepatic ablation [
33
]. This may allow for
earlier retreatment. However, the presumed hemosiderin
deposition mentioned above may limit the capability of
DWIb800 to interpret the ablated area, in particular when the
treatment zone is small, as susceptibility effects may obscure small
areas of recurrence or create false-positives. Clearly, larger
numbers are needed to validate our finding. More on the
oncologic outcome of this trial will be published separately in the
near future.
18F-fluorodeoxyglucose positron emission tomography
(18F-FDG PET) CT has demonstrated better diagnostic
accuracy compared with ceCT [
34
] and even MRI (without
DWIb800) [
35
] in the diagnosis of pancreatic cancer. Also,
18FFDG PET is increasingly used to assess tissue response to
chemoradiation for LAPC. A recent study showed the
difference in maximum standardized uptake value (SUVmax)
preand post-chemoradiation for LAPC was an independent
predictor of clinical outcome.[
34
] In this study, 18F-FDG PET
was not performed, but the value of 18F-FDG PET as a
predictor for ablation success after pancreatic IRE should be
investigated in future studies.
The greatest limitation of this study was the sample size,
which precluded a meaningful quantitative data-analysis with
respect to recurrences, therefore, no multivariable analyses
were considered. Furthermore, histopathologic confirmation
of recurrence was obtained in only one patient. Given the lack
of clinical consequences and the associated risk of biopsy, no
histopathologic confirmation was obtained in the remaining
four patients. Another drawback was the often poorly
delineated ablation zone caused by a peri-ablational inflammatory
response, which renders the accuracy of the calculated
volumes uncertain, especially on CT.
In conclusion, the most remarkable signal alterations after
pancreatic IRE are shown by DWI-b800 and postcontrast
T1weighted MRI and these imaging characteristics may be
useful to predict complete ablation and early recurrence. Future
studies should elaborate whether imaging characteristics
postIRE can predict treatment outcome and stratify patients for
potential retreatment. Currently we are performing a
multicenter phase-III trial comparing IRE with stereotactic ablative
body radiotherapy after neoadjuvant FOLFIRINOX
(CROSSFIRE-study, registered at clinicaltrials.gov
NCT02791503). Within this study all pre- and post-IRE
images will be evaluated to validate present findings.
Acknowledgments The scientific guarantor of this publication is dr.
MR Meijerink. The authors of this manuscript declare relationships with
the following companies: The funding organizations had no involvement
in the design or conduct of this study, data management and analysis, or
manuscript preparation and review or authorization for submission. Dr.
M.R. Meijerink is paid consultant for AngioDynamics, the other authors
declare no conflict of interest. This study has received funding by The
PANFIRE-study was supported by a grant from the National Foundation
Against Cancer (NFtK, Amsterdam, the Netherlands) and the Foundation
for Image-Guided Cancer Therapy (SBBvK, Diemen, the Netherlands).
The needle electrodes were partially funded by Angiodynamics, Latham,
NY. MD de Jong kindly provided statistical advice for this manuscript.
Institutional Review Board approval was obtained. Written informed
consent was obtained from all subjects (patients) in this study. Methodology:
prospective, experimental, performed at one institution.
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