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YIJOM-4556; No of Pages 7

Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx


https://doi.org/10.1016/j.ijom.2020.09.025, available online at https://www.sciencedirect.com

Research Paper
Head and Neck Oncology

Correlation and accuracy of S. Y. Chin1, K. Kadir1, N. Ibrahim1,


K. Rahmat2
1
Department of Oral and Maxillofacial Clinical

contrast-enhanced computed Sciences, Faculty of Dentistry, University of


Malaya, Kuala Lumpur, Malaysia;
2
Department of Biomedical Imaging,
University Malaya Research Imaging Centre,

tomography in assessing depth Faculty of Medicine, University of Malaya,


Kuala Lumpur, Malaysia

of invasion of oral tongue


carcinoma
S.Y. Chin, K. Kadir, N. Ibrahim, K. Rahmat: Correlation and accuracy of contrast-
enhanced computed tomography in assessing depth of invasion of oral tongue
carcinoma. Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx. ã 2020 International
Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights
reserved.

Abstract. The aim of this study was to evaluate the correlation and accuracy of depth
of invasion (DOI) measurement from preoperative contrast-enhanced computed
tomography (CECT) scans in comparison to histopathological examination (HPE)
in oral tongue squamous cell carcinoma (OTSCC). Preoperative CT scans of 18
OTSCC patients were reviewed retrospectively by a single observer to measure the
DOI on axial and coronal sections; these were then compared to the HPE report.
Mean DOI was compared between CECT and HPE using repeated measures
ANOVA. The strength of correlation of CT-derived tumour depth was determined
using the intra-class correlation coefficient (ICC) followed by assessment of
accuracy by Bland–Altman plot. In general, the measurement of DOI was smaller
on CECT, with a mean difference of 0.743 mm on axial CT and 1.106 mm on
coronal CT. Regarding the correlation between CECT and HPE tumour depths, ICC
Keywords: Computed tomography; Depth of
was 0.956 for axial CT and 0.965 for coronal CT. Bland–Altman analysis showed invasion; Tongue cancer; Oral cancer staging;
that DOI from CECT and histopathological depth were in agreement with each Accuracy.
other. In conclusion, there was excellent correlation and accurate measurement of
DOI from CECT. Accepted for publication 30 September 2020

Introduction potency of a tumour.1 For oral cavity can- been reported that the 5-year disease-spe-
cer, DOI acts as an independent predictor of cific survival rate is significantly better in
Depth of invasion (DOI) is defined as the disease-specific survival and as a prognos- patients with a tumour DOI of less than
distance of tumour invasion from the tic indicator for occult cervical lymph node 4 mm (74.9%) when compared to those
original surface, which reflects the invasion involvement and distant metastasis.2,3 It has with a DOI of 4–9 mm (56.2%) or more

0901-5027/000001+07 ã 2020 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Chin SY, et al. Correlation and accuracy of contrast-enhanced computed tomography in assessing
depth of invasion of oral tongue carcinoma, Int J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.ijom.2020.09.025
YIJOM-4556; No of Pages 7

2 Chin et al.

Materials and methods


All patients diagnosed with OTSCC in the
Department of Oral and Maxillofacial
Clinical Sciences, University of Malaya
between January 1, 2009 and December
31, 2018, who had preoperative CECT
followed by curative surgery, were includ-
ed in this retrospective study. Patients with
recurrent cancer at the same site, a positive
tumour margin, or incomplete histopatho-
logical examination (HPE) report were
excluded from this study (Fig. 2). Patients
for whom the CECT slice thickness was
thicker than the recommended value of
Fig. 1. Depth of invasion versus tumour thickness: (a) endophytic tumour; (b) exophytic
tumour. The dashed line is a reference line drawn to connect the surface of the adjacent normal 3.0 mm16 and those with CECT taken
mucosa. The thin arrow represents the depth of invasion and the thick arrow represents the more than 1 month before surgery were
tumour thickness. Both depth of invasion and tumour thickness are measured perpendicular to also excluded. This research was approved
the reference line to the deepest-reaching front of the tumour. by the local institutional ethics commit-
tees (reference number DF OS1722/0050
(P); MREC number 2017106-5659).
Preoperative CECT was performed ei-
than 9 mm (17.4%).4 There is a marked which displays detailed anatomical struc- ther with a Siemens Somatom Definition
increase in cervical lymph node metastasis tures including intrinsic and extrinsic mus- AS+, Siemens Sensation 16, or Toshiba
when tumour invasion exceeds 4 mm,3,5 cles, the floor of the mouth, and the lingual Aquilion One, depending upon the centre
which is associated with a poor prognosis vascular bundle.14 Despite lesser soft tis- in which CECT was done. The imaging
and significantly higher mortality rate.6 In sue characterisation, the CT scan is more parameters were 512  512 matrix,
2017, DOI was incorporated into the eighth readily accessible and has a faster scan- 120 kV, with a slice thickness of less than
edition of the American Joint Committee on ning time, with high reproducibility and a 3 mm. The CT images were reviewed by a
Cancer (AJCC) tumour staging manual for shorter waiting time compared to MRI.15 single clinician (S.Y.C.) in oral and max-
oral cavity cancer. The CT scan may be useful to assess illofacial surgery, who underwent calibra-
Pathological DOI is measured from the tumour depth in oral cavity cancer when tion with the neuroradiologist (K.R.). The
basement membrane of the closest adja- MRI is unavailable or when it is contra- role of the neuroradiologist is invaluable
cent mucosa, dropping a ‘plumb line’ indicated for preoperative assessment. when detailed interpretation and reporting
from this plane to the deepest point of The aim of this study was to evaluate are required. Thus, five samples of CECT
tumour invasion.7 It is not the equivalent the correlation and accuracy of contrast- of tongue cancer were measured
of tumour thickness, which measures the enhanced CT (CECT) for the measure- independently by both observers before
maximal tumour dimension from the sur- ment of DOI in oral tongue squamous cell performing the measurements. Intra-class
face of a tumour to the point of deepest carcinoma (OTSCC) compared to histo- correlation coefficient (ICC) analysis
invasion.8–10 Unlike tumour thickness, pathological (HP) measurement. revealed a high level of agreement.
DOI remains the same regardless of the
pattern of tumour growth (Fig. 1); thus,
these two terms should not be used inter-
changeably.
As DOI is explicitly obtained from a
resected tumour specimen, numerous
studies have investigated the accuracy of
preoperative determination from imaging.
This information is valuable to the oncol-
ogical surgeon to precisely resect a tumour
and decide on elective neck dissection
based on the tumour depth calculated risk.
Magnetic resonance imaging (MRI)
assessment of DOI has shown excellent
correlation to histological depth, especial-
ly for larger-sized tumours.11,12
In head and neck cancer, assessments
using computed tomography (CT) and
MRI scans complement each other and
are currently the gold standard for
accurately evaluating the extension of
the primary tumour site.13 By principle,
the preferred choice of imaging for tongue
carcinoma is contrast-enhanced MRI, Fig. 2. Flow diagram of the study patient recruitment.

Please cite this article in press as: Chin SY, et al. Correlation and accuracy of contrast-enhanced computed tomography in assessing
depth of invasion of oral tongue carcinoma, Int J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.ijom.2020.09.025
YIJOM-4556; No of Pages 7

Correlation and accuracy of contrast-enhanced computed tomography in assessing depth of invasion of oral tongue
carcinoma 3
CECT measurement. The limits of agree-
ment (LoA) were calculated as the mean
difference  1.96 standard deviations
(SD). If the 95% CI of the measurement
difference was found to fall within the
respective LoA, this would indicate that
the CECT and HPE methods are in agree-
ment with each other and, therefore, that
the results may be used interchangeably.

Results
Eighteen patients with OTSCC were
Fig. 3. Measurement of depth of invasion on the CECT of a patient with oral tongue squamous included in this study. There were equal
cell carcinoma (exophytic tumour) at the left lateral border of the tongue: (a) axial CT; (b) numbers of male and female patients, and
coronal CT. The dotted line represents the reconstructed mucosal line joining the normal
mucosal surface on the adjacent sides of the lesion. The double-ended arrow is the tumour depth,
the mean age at diagnosis was 60.9 years
measured perpendicularly from the reconstructed mucosal line. (Table 1). The left lateral border of the
tongue was the most common tumour
site and the majority of patients were
diagnosed in the early stage of disease
(T1–T2).
DOI was measured from a reconstructed less than 0.05. Finally, the accuracy of The mean time interval from preopera-
mucosal line perpendicularly to the dee- CECT measurement of DOI was assessed tive CECT scan to surgery was 16.6 days
pest point of invasion. The evaluation was visually by plotting the difference between (range 7–31 days). All 18 CT scans were
performed on axial and coronal sections the measurements from CECT reading and available in axial sections; 12 (66.7%)
(Fig. 3) using the measurement tool pro- HPE reporting against the latter as the gold were in 0.8-mm slice thickness, one in
vided in the imaging software. To improve standard using a Bland–Altman plot.19 A 1.0-mm thickness, and the remaining five
visualisation of the lesion, the clinician positive value of difference would indicate in 3.0-mm thickness. However, only 14
manipulated the zoom factor, grey-scale that the CECT measurement was larger were reconstructed in coronal sections,
centre level, and the window width setting. than the HP measurement, whereas a almost all in 3.0-mm slice thickness and
Each CT slice of the oral tongue was negative value would indicate a smaller only one in 0.8-mm thickness.
examined carefully to obtain the maxi-
mum dimension of DOI in millimetres,
rounding to the nearest one decimal place.
The scan images were read on two Table 1. Demographic data of the OTSCC patients.
separate occasions, with an interval of at Frequency %
least 1 month, to minimise potential learn- Sex
ing effects.17 To avoid reading bias, the Male 9 50.0
clinician was blinded to the HP depth until Female 9 50.0
both CT readings for each sample were Age at diagnosis (years), median (range) 61 (34–81)
completed. Site of tongue cancer
The data analysis was performed using Right lateral border 6 33.3
IBM SPSS Statistics version 25.0 (IBM Left lateral border 11 61.1
Corp., Armonk, NY, USA). The ICC was Ventral surface 1 5.6
Clinical tumour stagea
used to assess the intra-observer reliability
T1 6 33.3
in the measurement of DOI on CECT. ICC T2 10 55.6
estimates and their 95% confidence T3 1 5.6
intervals (CI) were calculated based on T4 1 5.6
a single-measures, absolute-agreement, Clinical nodal stageb
two-way mixed-effects model. Measure- N0 13 72.2
ment reliability was interpreted as poor N1 3 16.7
(ICC <0.50), moderate (ICC 0.50–0.75), N2 2 11.1
good (ICC 0.75–0.90), or excellent N3 0 0
(ICC >0.90).18 Treatment
Resection of primary tumour only 7 38.9
The mean of the two CECT measure- Resection of primary tumour and ipsilateral ND 10 55.6
ments was used for further analysis. Re- Resection of primary tumour and bilateral ND 1 5.6
peated measures analysis of variance
OTSCC, oral tongue squamous cell carcinoma; ND, neck dissection.
(ANOVA) was used to calculate the mean a
Maximum tumour dimension: T1 = 2 cm or less; T2 = more than 2 cm but no greater than
difference between CECT and HP mea- 4 cm; T3 = more than 4 cm; T4 = more than 4 cm with involvement of adjacent structures.
surement, and its 95% CI. The strength of b
Nodal size and location: N1 = single ipsilateral lymph node measuring 3 cm or less;
correlation between the two measurement N2 = single ipsilateral lymph node more than 3 cm but no greater than 6 cm, or multiple
methods was analysed using the ICC. ipsilateral, bilateral, or contralateral lymph nodes less than 6 cm; N3 = lymph node measuring
Statistical significance was set at a P-value more than 6 cm.

Please cite this article in press as: Chin SY, et al. Correlation and accuracy of contrast-enhanced computed tomography in assessing
depth of invasion of oral tongue carcinoma, Int J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.ijom.2020.09.025
YIJOM-4556; No of Pages 7

4 Chin et al.

Table 2. Comparison of mean depth of invasion between contrast-enhanced computed tomography and histopathological measurement.a
Mean DOI (mm) Mean differenceb (mm) SE 95% CI P-valuec
Axial CT 9.26 0.743 0.505 2.129 to 0.643 0.495
Coronal CT 8.89 1.106 0.523 2.542 to 0.330 0.163
CI, confidence interval; CT, computed tomography; DOI, depth of invasion; SE, standard error.
a
Mean histopathological depth of invasion = 10.00  8.010 mm.
b
Paired difference [(CT) (histopathology)].
c
Adjustments for multiple comparisons: Bonferroni.

perpendicularly from a reference line join-


ing the tumour–mucosal junction on both
sides,1,5,6,9,20–22 radiological DOI has been
shown to be reproducible and to be the
optimal method for most cases.23
Most studies have observed that radio-
logical measurements were larger than the
HP measurement, with a reported tumour
shrinkage factor of 0.87–0.91.24,25 An
MRI study by Murakami et al. reported
that the radiological DOI was generally
2–3 mm larger than that of the pathologi-
cal DOI, with a mean difference of 2.3 mm
Fig. 4. Correlation of CECT with histopathological depth of invasion: (a) axial CT; (b) coronal (SD 3.2 mm) for axial MRI and 1.9 mm
CT.
(SD 2.1 mm) for coronal MRI.23 A recent
study by Baba et al. found that both CT
and MRI estimated larger than pathologi-
cal DOI; however the absolute value of
difference between radiological and path-
ological DOI was smaller by CT when
compared to MRI (median 2 mm vs
3.3 mm), although the difference between
the two imaging modalities was not sta-
tistically significant.26
In the current study, CT tumour depth
was on average 1–2 mm smaller than HP
depth. This finding confirms the results of
Locatello et al.,22 who reported CT-de-
rived DOI of 10.33 mm in the axial plane
and 9.10 mm in the coronal plane
Fig. 5. Bland–Altman plots comparing the agreement between CECT and histopathological (P = 0.06), with a mean pathological
measurements of the depth of invasion: (a) axial CT; (b) coronal CT. The solid line represents DOI of 11.25 mm. Similarly, a prospec-
the mean difference, the dotted lines indicate the 95% confidence interval, and the dashed lines
tive study by Alsaffar et al.12 found mean
are the limits of agreement (mean difference  1.96 standard deviations).
MRI tumour depth in OTSCC was
10.9 mm in comparison to mean patholog-
ical depth of 11.1 mm.
When the CECT measurement was re- measurements of these cases were 1, 2, The disparities of having either a larger
peated, the intra-observer reliability was and 3 mm, respectively. or smaller radiological DOI compared to
shown to be excellent for both axial Bland–Altman plots (Fig. 5) showed HPE in the different studies may be
(ICC = 0.996, P < 0.001) and coronal that the mean difference for axial CT explained by the different study designs
images (ICC = 0.999, P < 0.001). From was 0.72 mm (SD 2.072 mm) with and the effect of CT image quality versus
repeated measures ANOVA analysis 95% CI of 1.750 to 0.310 mm. Coronal specimen shrinkage. Studies with larger
(Table 2), axial and coronal CECT both CT showed a mean difference of radiological DOI than HP DOI excluded
yielded a smaller mean DOI than the HP 1.11 mm (SD 1.96 mm) and 95% CI many patients with no detectable tumours
depth, but there was no statistically sig- 2.236 to 0.023 mm. The 95% CI for both on CT or MRI, and also ill-defined
nificant difference. measurement differences were within tumours due to dental artefacts or patient
CT exhibited good to excellent correla- their respective LoA. motion, resulting in samples of larger-
tion with HP depth in both axial sized tumours.23,26
(ICC = 0.956, P < 0.001) and coronal Poorer soft tissue contrast in CT may
Discussion
planes (ICC = 0.965, P < 0.001) reduce the DOI measurement when com-
(Fig. 4). An interesting finding was that A standard radiological method for tumour pared to HPE. However, when combined
there were three cases of radiological DOI depth measurement in oral cavity cancer with specimen processing shrinkage and
recorded as 0 mm due to non-visible has yet to be established. By adopting the the effect of adjacent inflammation, CECT
tumour tissue in CT. Histopathological closest method to HPE of measuring has been shown to correspond better to HP

Please cite this article in press as: Chin SY, et al. Correlation and accuracy of contrast-enhanced computed tomography in assessing
depth of invasion of oral tongue carcinoma, Int J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.ijom.2020.09.025
YIJOM-4556; No of Pages 7

Correlation and accuracy of contrast-enhanced computed tomography in assessing depth of invasion of oral tongue
carcinoma 5
depth.26 The discrepancies may also be cancers with a DOI less than 4 mm were than 4 weeks (Spearman rho, r = 0.76)
attributed to the thinner slice thickness of not detectable on MRI.29 In this respect, when compared to 4–8 weeks
CT, ranging from 0.8 to 3 mm, compared CECT is comparable to MRI in detecting (r = 0.80), but was lower in those with
to a slice thickness of 3–5 mm for MRI in oral tongue lesions. an interval of more than 8 weeks
the published literature.23,27,28 In previous studies on the measurement (r = 0.62). Previous imaging studies have
The correlation of radiological DOI of DOI and tumour thickness, reading of included imaging taken 31 days to 8 weeks
with pathological DOI has been reported CT and MRI data was done by either before surgery, following their cancer
to be stronger for CT than for MRI (0.74, experienced head and neck radiolo- guidelines.22,24 In the present study, the
P < 0.001 vs 0.66, P > 0.001), revealing gists11,12 or oral and maxillofacial radiol- time interval of CT to surgery was restrict-
the superiority of using CT for pretreat- ogists.30 There was concordance between ed to within 1 month, in line with the
ment evaluation of radiological DOI.26 A these two groups in the determination of centre’s protocol. This time frame is clini-
wide variation of MRI tumour depth cor- tumour size from preoperative CT.30 In the cally realistic and justified the application
relation to histopathology has been current study, the CT measurements were of the study results in our clinical practice.
reported. Although the correlation has done by a clinician trained in oral and There were several limitations in this
been reported as excellent 0.91– maxillofacial surgery after a training ses- study. First, the relatively small sample
0.98,12,27 a good correlation with HPE sion on CT reading and calibration with a size in comparison to the total number of
was not shown for smaller tumour depths neuroradiologist. Although simple and OTSCC patients. This was largely attrib-
(<5 mm).12 Poor correlation between axi- straightforward, tumour DOI has frequent- uted to weaknesses in patient data storage,
al MRI and HPE (ICC = 0.265, P = 0.030) ly been missed out on the CT report, as the including CT scans. Second, the retrospec-
has been reported,23 with a fair correlation importance might not have been highlight- tive nature of this study meant that the
for coronal MRI (ICC = 0.583, ed to the radiologists. In the event of the quality of the CT scans was variable, as
P < 0.001). In the study by Park et al., CT report missing a DOI value, the oper- there was no existing standard protocol.
the oral tongue had the best correlation ating surgeon can perform the DOI mea- The detection of lesions was affected by
coefficient of 0.949 for histological and surement from the CT image prior to imaging reconstruction parameters such as
MRI DOI, when compared to 0.941 for surgery, provided the concept is well un- CT slice thickness and the reconstruction
tongue base cancers and 0.578 for tonsil derstood. Another advantage that was ob- algorithm, with lesions smaller than the
cancers.11 served in this study was that the surgeon slice thickness not visible on images
In the current study, measurements had information of the exact clinical loca- reconstructed with thick slice intervals.35
from CECT and HPE were in good agree- tion of the tumour on CT, which helped in Thin slices can depict more imaging
ment. Measurements of DOI from both the identification of the tumour mass, es- details than thicker ones, but they have
axial and coronal CECT were accurate pecially when the contrasted image was a higher noise level, making lesion bound-
when compared to histopathological mea- less clear. aries more difficult to identify and thereby
surement and these can be used inter- The disadvantages of CT are poor soft decreasing the reproducibility of measure-
changeably. Nevertheless, the results of tissue contrast, high radiation dose, and ment. Therefore, the reconstruction of CT
this study should be used carefully to the presence of amalgam streak artefacts scan images with the same slice
guide the decision on tumour resection that may interfere with the measurement thickness is important to reduce measure-
and elective neck dissection. of tumour depth. MRI involves non-ioniz- ment variability.35
The consistency of DOI measurement ing radiation and uses gadolinium chelates Further studies are needed to validate
from imaging and histopathology relies in as contrast agents, which are associated the results of this study. It is recommended
part on the parallelism of specimen gross- with a lower incidence of allergic/anaphy- that a prospective study involving differ-
ing to CT slices. Any difference in the lactic reactions and are less nephrotoxic in ent subsites of oral cancer is conducted,
direction of DOI measurement in these the doses used than the iodinated contrast with a larger sample size and standard
two modalities will contribute to discre- agents used in CT.31 In the present study, imaging protocol to improve image quali-
pancies in readings. In addition, the speci- whenever amalgam streak artefacts were ty. The latter should include the type of CT
men will have undergone distortion and encountered in the scan and overlapped machine, matrix size, field of view (FOV),
shrinkage following tumour resection. with the tumour depth assessment, the type of contrast material, and timing de-
These may lead to either an underestima- next slice with a clearer view of the tu- lay, which can influence the tumour depth
tion or overestimation of tumour depth. To mour was assessed. The presence of amal- measurement.36–38 The reading of CECT
overcome this, the surgeon may mark the gam streak artefacts can be overcome by by two observers, one from a surgical
specimen according to CT slicing prior to repeating the scan in an angled gantry background and one from a radiology
excision to serve as a guide for the pathol- along the line of the mandible, parallel background, would be beneficial to deter-
ogist when performing specimen grossing. to the plane containing the metal.32,33 mine the inter-observer reliability between
Another possible solution is to ensure However, this cannot be performed on differently experienced individuals.
axial and coronal CT slices are taken CT systems in which it is not possible In conclusion, the results of this study
parallel and perpendicular to the tongue to tilt the gantry; furthermore, it adds to showed that the measurement of DOI in
axis, respectively, as in pathological spec- the radiation dose and does not always preoperative CECT was comparable to
imen grossing. prevent important structures from being histopathology in OTSCC cases. CECT
The findings of this study showed that concealed by artefacts.34 measurement underestimated DOI by an
early superficial lesions (3 mm) could Weimar et al.25 assessed the impact of average of 1–2 mm against the gold stan-
not be examined in CECT, even when the imaging-to-surgery time interval on the dard of HP measurement. Excellent
slice thickness was less than the patholog- radiological–pathological tumour thick- correlation was found between these two
ical tumour depth, i.e. 0.8 mm. This is ness. They found that the correlation of modalities, with good agreement; thus
consistent with the findings of the MRI radiological to pathological tumour thick- CECT-derived tumour depth is accurate.
study by Baba et al., in which oral tongue ness was similar for a time interval of less We suggest that CECT may be utilised for

Please cite this article in press as: Chin SY, et al. Correlation and accuracy of contrast-enhanced computed tomography in assessing
depth of invasion of oral tongue carcinoma, Int J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.ijom.2020.09.025
YIJOM-4556; No of Pages 7

6 Chin et al.

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depth of invasion of oral tongue carcinoma, Int J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.ijom.2020.09.025
YIJOM-4556; No of Pages 7

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carcinoma 7
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senas AL, Lindell EP, Campeau NG, et al. the head and neck: improved conspicuity of 50603 Kuala Lumpur
CT dental artifact: comparison of an iterative squamous cell carcinoma on delayed scans. Malaysia
E-mail: kathreena@um.edu.my
metal artifact reduction technique with Am J Roentgenol 2001;176:1571–5.

Please cite this article in press as: Chin SY, et al. Correlation and accuracy of contrast-enhanced computed tomography in assessing
depth of invasion of oral tongue carcinoma, Int J Oral Maxillofac Surg (2020), https://doi.org/10.1016/j.ijom.2020.09.025

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