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ORIGINAL RESEARCH
Locally Advanced Rectal
Carcinoma Treated with
Preoperative Chemotherapy and
Radiation Therapy: Preliminary
Analysis of Diffusion-weighted MR
Imaging for Early Detection of Tumor
Histopathologic Downstaging1
Ying-Shi Sun, MD
Xiao-Peng Zhang, MD
Lei Tang, MD
Jia-Fu Ji, MD
Jin Gu, MD
Yong Cai, MD
Xiao-Yan Zhang, MD
1
From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Departments
of Radiology (Y.S.S., X.P.Z., L.T., X.Y.Z.), Surgery (J.F.J.,
J.G.), and Radiotherapy (Y.C.), Peking University School
of Oncology, Beijing Cancer Hospital and Institute, No. 52
Fu Cheng Road, Hai Dian District, Beijing 100142, China.
Received December 16, 2008; revision requested February
10, 2009; revision received April 23; accepted June 3;
final version accepted July 28. Supported by the National
Basic Research Program of China (973 Program) (grant no.
2006CB705706) and Natural Science Foundation of Beijing,
China (grant no. 7072018). Address correspondence to
X.P.Z. (e-mail: [email protected] ).
Purpose:
To determine whether changes in apparent diffusion coefficients (ADCs) of rectal carcinoma obtained 1 week after the beginning of chemotherapy and radiation therapy
(CRT) correlate with tumor histopathologic downstaging
after preoperative CRT.
Materials and
Methods:
This prospective study was approved by an institutional
review board; informed consent was obtained from all
patients. Thirty-seven patients (mean age, 54.7 years; 13
women, 24 men) with primary rectal carcinoma who
were undergoing preoperative CRT were recruited for
the study. Diffusion-weighted (DW) magnetic resonance
(MR) imaging was performed with a 1.5-T MR imager in
all patients before therapy, at the end of the 1st and 2nd
week of therapy, and before surgery. Tumor ADCs were calculated. Linear mixed-effects modeling was applied to analyze change in ADCs and volumes following treatment.
Results:
Patients were assigned to the tumor downstaged group
(n = 17) or the tumor nondownstaged group (n = 20) on
the basis of histopathologic examination results following
surgery. Before CRT, the mean tumor ADC in the downstaged group was lower than that in the nondownstaged
group (1.07 3 1023mm2/sec 6 0.13 [standard deviation] vs
1.19 3 1023mm2/sec 6 0.15, F = 6.91, P = .013). At the end
of the 1st week of CRT, the mean tumor ADC increased
significantly from 1.0 7 3 1023mm2/sec 6 0.13 to 1.32 3
1023mm2/sec 6 0.16 (F = 37.63, P , .001) in the downstaged group, but there was no significant ADC increase
in the nondownstaged group (F = 1.18, P = .291). The mean
percentage of tumor ADC change in the downstaged group
was significantly higher than that in the nondownstaged
group at each time point (F = 18.39, P , .001).
Conclusion:
Early increase of mean tumor ADC and low pretherapy mean
ADC in rectal carcinoma correlate with good response to
CRT. DW MR imaging is a promising noninvasive technique
for helping predict and monitor early therapeutic response
in patients with rectal carcinoma who are undergoing CRT.
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Radiology: Volume 254: Number 1—January 2010
GASTROINTESTINAL IMAGING: Tumor Downstaging of Rectal Carcinoma after Therapy
T
umor (T category) downstaging
(1) and complete pathologic response after preoperative chemotherapy and radiation therapy (CRT)
followed by definitive surgical resection
for advanced rectal cancer resulted
in decreased local recurrence and
improved disease-free survival (2).
Advanced rectal cancers that show T
category downstaging and complete
pathologic response after CRT may represent subgroups that are characterized
by better biologic behavior (3). However, in locally advanced rectal cancer,
preoperative CRT has shown a significant individual variation of response;
about 9%–25% of patients would show
complete pathologic response to longcourse CRT, about 54%–75% of patients would show downstaging of tumor (4,5), and others would show no
response. Therefore, early detection
and assessment of the response would
be beneficial to patient treatment before or at an early stage of CRT, so
that those showing no response can
be identified early so that treatment
may be intensified. Currently, monitoring the response to therapy is usually
achieved by monitoring the tumor size
at computed tomography (CT) or magnetic resonance (MR) imaging, which
includes measurement of tumor length,
area, and volume (6–8). However, those
evaluations are performed at the later
stages of CRT, because changes in size
are not apparent early during therapy.
Diffusion-weighted (DW) MR imaging is a noninvasive method to obtain information about microscopic structures
through the detection of water proton
mobility in biologic tissue (9,10). In recent years, researchers have used this
technique to determine the therapeutic
efficacy of CRT in tumors such as breast
cancer, glioma, liver tumor, prostate
carcinoma, and rectal cancer (11–26).
Preclinical and clinical data indicate a
number of potential roles of DW MR
imaging in predicting suitable therapies
and monitoring response to conventional
and novel therapies. DW MR imaging
as a quantitative biomarker is able to
assess response to antineoplastic treatments that cause tumor cell destruction and/or the obliteration of tumor
microvessels (27).
The application of DW MR imaging for the prediction and monitoring
of disease response in colorectal cancer has been previously investigated
for both primary disease (25,28) and
metastatic disease to the liver (29,30).
However, the application of DW MR
imaging to evaluate early response
of the primary rectal carcinoma to
CRT has, to our knowledge, not been
previously reported. The purpose of
this study was to determine whether
changes in ADCs of rectal carcinoma
obtained 1 week after the beginning
of CRT correlate with tumor histopathologic downstaging after preoperative CRT.
Advances in Knowledge
n During long-course chemotherapy
and radiation therapy (CRT) for
rectal cancer, the mean percentage of tumor apparent diffusion
coefficient (ADC) increase was
significantly different in the
tumor downstaged group and the
nondownstaged groups, (F =
18.39, P , .001), and this
greater increase in ADC in
downstaged lesions could be
identified as early as 1 week after
initiating CRT (24.3% vs 3.7%).
n A low pretherapy mean tumor
ADC appears to predict a good
response to CRT.
Radiology: Volume 254: Number 1—January 2010
n
Implications for Patient Care
n Early temporal changes in ADCs
and pretherapy ADCs measured
at diffusion-weighted (DW) MR
imaging can potentially depict
patients with locally advanced
rectal carcinomas that are resistant to preoperative CRT, which
allows for prompt modification in
treatment protocols.
n DW MR imaging seems to be a
promising noninvasive technique
for helping predict and monitor
therapeutic response in patients
with rectal carcinoma who are
undergoing CRT.
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Sun et al
Materials and Methods
Patients
This prospective study was approved
by our institutional review board, and
informed consent was obtained from
all patients. Patients who were scheduled to undergo preoperative CRT were
eligible to be included in this study.
Inclusion criteria were the same as the
criteria for patients undergoing preoperative CRT in our hospital; tumor
was clinical stage T3 and could be
any N stage without evidence of distant metastases. The exclusion criteria
were: (a) previous CRT for primary rectal carcinoma or tumor in other organ
(n = 0), (b) contraindication to MR
imaging examination (n = 0), (c) premature discontinuation of CRT (n = 4),
(d) delayed (more than 8 months after
CRT) or canceled surgery (n = 5), or
(e) discontinued MR imaging examinations during therapy (n = 7).
The initial T stage was assessed by using pelvic MR imaging and/or intrarectal
ultrasonography (US), and the presence
of distant metastases was assessed with
abdominal CT and chest radiography.
A total of 53 consecutive patients
who met the study criteria were recruited
from our clinics between December
2005 and November 2008; however, 16
patients subsequently withdrew or were
withdrawn because of discontinued MR
imaging examinations during therapy,
Published online before print
10.1148/radiol.2541082230
Radiology 2010; 254:170–178
Abbreviations:
ADC = apparent diffusion coefficient
CRT = chemotherapy and radiation therapy
DW = diffusion weighted
Author contributions:
Guarantors of integrity of entire study, all authors; study
concepts/study design or data acquisition or data analysis/
interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors;
manuscript final version approval, all authors; literature
research, Y.S.S., X.P.Z., L.T., X.Y.Z.; clinical studies, Y.S.S.,
X.P.Z., J.F.J., J.G., Y.C.; statistical analysis, Y.S.S., X.P.Z.,
L.T., X.Y.Z.; and manuscript editing, Y.S.S., X.P.Z., X.Y.Z.
Authors stated no financial relationship to disclose.
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GASTROINTESTINAL IMAGING: Tumor Downstaging of Rectal Carcinoma after Therapy
discontinued preoperative CRT, or delayed or canceled surgery.
A total of 37 patients (mean age,
54.7 years; age range, 24–79 years;
13 women [mean age, 54.0 years; age
range, 33–72 years], 24 men [mean
age, 55.1 years; age range, 24–79
years]) with rectal carcinoma histologically confirmed with biopsy results
were examined by using DW MR imaging at four time points: 2–5 days
before CRT, at the end of the 1st week
of CRT, at the end of the 2nd week of
CRT, and 1–4 days before surgery. Surgery was performed 2–4 weeks following
the end of CRT. Patient histopathologic
evaluation is summarized in Table 1.
MR Imaging Technique
All patients were examined with a 1.5-T
MR whole-body imager (Signa EchoSpeed Plus with EXCITE; GE Medical
Systems, Milwaukee, Wis) with a 33
mT/m maximum gradient capability and
equipped with an eight-channel phasedarray body coil.
Before DW MR imaging, T2-weighted
images in sagittal, coronal, and trans-
verse orientations (perpendicular to
the long axis of the rectum covering
the whole tumor) were obtained in
all patients by using a fast spin-echo
sequence (for sagittal and coronal images: echo time msec/repetition time
msec, 100/5000; field of view, 240–360
mm; matrix size, 256 3 256; section
thickness, 4 mm; intersection gap,
0 mm; number of signals acquired,
four; echo train length, 15; no fat
saturation; bandwidth, 22.73 kHz)
(for transverse images: 100/5000;
field of view, 160–180 mm; matrix
size, 256 3 256; section thickness,
3 mm; intersection gap, 0 mm; number
of signals acquired, four; echo train
length, 16; no fat saturation; bandwidth, 20.83 kHz).
Axial DW MR images were obtained by using a DW MR echo-planar
sequence (66.6/6000; field of view,
360 mm; matrix size, 128 3 128; section
thickness, 5 mm; intersection gap, 1 mm;
number of signals acquired, eight; receiver bandwidth, 250 kHz.). DW MR
images and ADC maps were acquired
by using b values of 0 and 1000 sec/
Table 1
Histopathologic Evaluation in 37 Patients with Rectal Carcinoma
Histopathologic Evaluation
Downstaged
Group (n = 17)
Nondownstaged
Group (n = 20)
Distance from tumor to the anal verge (cm)
,4
4–6
7–9
1
7
9
2
9
9
3
11
2
1
0
2
10
4
3
1
6
9
2
4
10
6
2
13
2
0
0
0
0
0
0
10
7
3
Histopathologic diagnosis
Well-differentiated adenocarcinoma
Moderately differentiated adenocarcinoma
Poorly differentiated adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Pre-CRT clinical stage
T3N0M0
T3N1M0
T3N2M0
Postoperative histopathologic stage
T0N0M0 (complete pathologic response)
T2N0M0
T2N1M0
T3N0M0
T3N1M0
T3N2M0
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Sun et al
mm2 applied in directions x, y, and z.
The array spatial sensitivity encoding
technique (factor of two) was used to
reduce the distortion of echo-planar
imaging. All DW MR imaging was performed during free breathing. The imaging time of one DW MR imaging sequence was 160 seconds.
Anisodamine (20 mg) (Minsheng
Pharmaceutical Group, Hangzhou, China)
was injected intramuscularly to reduce
bowel motility when contraindications
had been excluded.
MR Image Analysis
Representative T2-weighted MR images, DW MR images, and ADC maps
during treatment are shown in Figure 1.
The image quality of DW MR imaging
was sufficient to identify the tumor region in all patients.
MR images were analyzed in consensus by two experienced radiologists
(Y.S.S. and X.P.Z., with 10 and 15 years
of experience in clinical MR imaging,
respectively) who were blinded to the
therapeutic response and were working
together on a workstation (AW4.2; GE
Medical Systems).
ADCs were measured on the workstation. We manually contoured along
the edge of the tumor as a region of
interest, section by section in thicknesses of 5 mm, and avoided distortion
and artifact regions. Regions of interest
were drawn on DW MR images with a
b value of 1000 sec/mm2. The size of
the regions of interest of one section
was not less than 20 voxels. The number of imaging sections of the tumors
in all patients ranged from three to 10,
depending on the size of the tumor. The
mean ADC of the whole tumor was derived from the mean of all voxel ADCs
within each region of interest recorded
for the entire lesion because of the
heterogeneous nature of lesions and was
calculated by using homemade software
based on Functool (GE Medical Systems)
software.
MR volumetric evaluations were performed during therapy. On T2-weighted
MR images, the tumor outline was traced
manually on each individual section.
The volumes of lesions were calculated
by summing all of the cross-sectional
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GASTROINTESTINAL IMAGING: Tumor Downstaging of Rectal Carcinoma after Therapy
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Figure 1
Figure 1: Images in 45-year-old man with rectal cancer. T category downstaged after CRT. (a) Axial fast spin-echo T2-weighted MR images at four
time points. (b) Axial DW MR images with b = 1000 sec/mm2 at four time
points. (c) Resulting axial ADC maps calculated from different DW images
at four time points. Outlines indicate tumor region. Tumor mean ADCs were
0.998 3 1023 mm2/sec before therapy, 1.21 3 1023 mm2/sec at week 1,
1.31 3 1023 mm2/sec at week 2, and 1.25 3 1023 mm2/sec before
surgery. The ADC of the tumor showed a clear shift to higher values at the
end of the 1st week of CRT. At the end of the 2nd week of CRT, the ADC
showed a slight shift, and the ADC was reduced after CRT.
volumes of the entire lesion on the workstation.
Treatment Technique
All patients underwent preoperative
CRT. Three-dimensional conformal
radiation therapy was given at a dose
of 2.0 Gy per day, 5 days per week, for
4 weeks, with a total radiation dose of
40 Gy. In addition, capecitabine (Xeloda; Roche Pharmaceuticals, Shanhai,
China) was administered orally at a
dose of 2000 mg/m2 per day, 7 days per
week, for 4 weeks. Total mesorectal excision was performed within 2–4 weeks
after completion of preoperative CRT.
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n
Histopathologic Evaluation
After surgery, the resected specimens
were staged according to the International Union Against Cancer ypTNM
staging system (1).
Irradiated cancer and harvested
mesorectal lymph nodes were submitted for microscopic analysis. Hematoxylin-eosin–stained slices were prepared, and an experienced pathologist
reviewed specimens for all patients.
Proximal, distal, and circumferential
resection margins were evaluated. A
careful search of the mesorectum was
performed to identify as many lymph
nodes as possible.
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Statistical Analysis
All patients were assigned to one of
two groups, the tumor downstaged
or the tumor nondownstaged group.
Tumor downstaging was assessed by
comparing the pre-CRT clinical stage
(cT stage) with the postoperative
histopathologic stage (ypT stage). T
downstaging was defined when ypT was
lower than cT.
All statistical analyses were performed by using software (SAS, version
8.0; SAS Institute, Cary, NC). Pre- and
posttreatment ADCs, volume, percentage of changes in the ADC, and percentage rate of tumor volume reduction
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GASTROINTESTINAL IMAGING: Tumor Downstaging of Rectal Carcinoma after Therapy
Sun et al
Table 2
Mean Tumor ADC of Downstaged and Nondownstaged Groups at Four Time Points
Time Point
Pretherapy
Week 1
Week 2
Presurgery
Downstaged Group
(n = 17) (3 1023 mm2/sec)
Nondownstaged Group
(n = 20) (3 1023 mm2/sec)
95% Confidence Interval*
F Value
P Value
1.07 6 0.13
1.32 6 0.16
1.36 6 0.11
1.30 6 0.09
1.19 6 0.15
1.22 6 0.12
1.30 6 0.14
1.28 6 0.13
20.22, 20.03
0.01, 0.19
20.02, 0.15
20.05, 0.10
6.91
4.88
2.34
0.35
.013
.034
.136
.558
Note.—Unless otherwise indicated, data are means 6 standard deviations.
* Confidence intervals are for the difference between the two groups.
Figure 2
Figure 2: Graph shows four lines that correspond to the mean tumor ADC
and tumor volume time courses during CRT of the tumor ( T ) downstaged and
nondownstaged groups. Graph illustrates a maximum increased slope of ADC at
week 1 in the downstaged group, which did not appear in the nondownstaged
group. The decreased slope of tumor volume was not significantly different
between the two groups.
of downstaged and nondownstaged
tumors were analyzed by using linear
mixed-effects modeling (31). The ADC
and volume were the dependent variables, whereas the independent variables were subject (random factor),
group (fixed factor), and time (a numeric variable). The model was fitted
by an unstructured covariance matrix.
We compared the difference between
the two groups at each time. Correlations were assessed by calculating the
Spearman rank coefficient.
174
Two-tailed P values were used, and
a statistically significant difference was
declared if the P value was less than the
a level of .05.
Results
Following surgery, disease in 17 patients was downstaged, and disease in
20 patients was not downstaged following CRT. Tumor ADCs of all 37 patients are summarized in Table 2 and
Figure 2.
During CRT, the difference of the
mean tumor ADC in the two groups
was significant at each time point (F =
30.19, P , .001). The evolution of the
ADCs in the two groups was significantly
different (F = 8.86, P , .001).
Before CRT, the mean tumor ADC
in the downstaged group (mean ADC,
1.07 3 1023 mm2/sec 6 0.13; 95% confidence interval: 1.01 3 1023 mm2/sec,
1.14 3 1023 mm2/sec) was lower than
that in the nondownstaged group (mean
ADC, 1.19 3 1023 mm2/sec 6 0.15;
95% confidence interval: 1.12 3 1023
mm2/sec, 1.26 3 1023 mm2/sec) (F =
6.91, P = .013).
As shown in Figure 2, at the end
of the 1st week of CRT, the mean tumor ADC increased significantly in the
downstaged group (mean ADC, 1.32 3
1023 mm2/sec 6 0.16; 95% confidence
interval: 1.24 3 1023 mm2/sec, 1.41 3
1023 mm2/sec) (F = 37.63, P , .001);
although a slight increase in mean tumor
ADC was identified in the nondownstaged group, this change was not statistically significant (mean ADC, 1.22 3
1023 mm2/sec 6 0.12; 95% confidence
interval: 1.17 3 1023 mm2/sec, 1.28 3
1023 mm2/sec) (F = 1.18, P = .291).
At the end of the 2nd week of CRT,
further increase in ADCs were seen
in the downstaged group (F = 63.37,
P , .001) and the nondownstaged group
(F = 10.95, P = .004). These values were
significantly different from pretherapy
values. Before surgery, the ADC decreased slightly in both groups.
The mean percentage of tumor
ADC change was significantly different
in the two groups (F = 18.39, P , .001)
(Fig 3). The mean percentage of change in
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Sun et al
Table 3
Mean Tumor Volume of Downstaged and Nondownstaged Groups at Four Time Points
Time Point
Pretherapy
Week 1
Week 2
Presurgery
Downstaged
Group (n = 17) (cm3)
Nondownstaged
Group (n = 20) (cm3)
95% Confidence Interval*
F Value
P Value
9.14 6 5.12
8.57 6 4.99
6.05 6 3.66
2.77 6 2.42
15.61 6 10.78
12.37 6 6.32
9.48 6 6.39
6.94 6 7.31
212.11, 20.82
27.55, 20.06
26.90, 0.04
27.83, 20.50
5.40
4.25
4.03
5.32
.026
.047
.053
.027
Note.—Unless otherwise indicated, data are means 6 standard deviations.
* Confidence intervals are for the difference between the two groups.
Figure 4
Figure 3
Figure 3: Box-and-whisker plot shows percentage of change for ADCs in
tumor ( T ) downstaged and nondownstaged groups after treatment (week 1,
week 2, and preoperation). In downstaged group, medians (lines through boxes)
are lower than those of nondownstaged group. 䊊 = outlier.
tumor ADC in the downstaged group
was higher than that in the nondownstaged group at each time point (week
1, 24.3% vs 3.7%; week 2, 28.2% vs
9.8%; presurgery, 23.0% vs 9.5%).
There was a significant difference
between the mean tumor volume of the
two groups before treatment (F = 5.40,
P = .026) (Table 3, Fig 2). The absolute tumor volume in the downstaged
group was significantly lower than that
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n
Figure 4: Box-and-whisker plot shows percentage of change for tumor
volume in tumor ( T ) downstaged and nondownstaged groups after treatment
(week 1, week 2, and preoperation). Medians (lines through boxes) between
downstaged and nondownstaged groups are not significantly different.
䊊 = outlier, ⴱ = extreme value.
in the nondownstaged group (F = 5.37,
P = .022), and the difference of tumor
volume at each time was significant
(F = 37.29, P , .001) (Table 3). However,
the evolution of tumor volume in the
two groups was not significantly different (F = 1.62, P = .190) (Table 3). The
mean percentage rate of tumor volume
reduction was not significantly different
in the two groups (F = 1.21, P = .276)
(Fig 4).
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There was no correlation between
the ADCs and tumor volume before
CRT (r = 0.178; P = .292).
Discussion
Tumor downstaging after preoperative
CRT is an important prognostic factor in
tumor local recurrence rate and 5-year
survival rate for patients with primary
rectal carcinoma (32,33). In our study, a
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GASTROINTESTINAL IMAGING: Tumor Downstaging of Rectal Carcinoma after Therapy
therapy response was defined according
to whether preoperative CRT resulted
in any T category downstaging.
Our results showed that at the end
of the 1st week after beginning CRT,
significant increases in tumor ADCs
occurred only in the downstaged group.
This is consistent with the results of preclinical animal and cell studies. Animal
models of breast cancer (11), sarcoma
(34), glioma (14,35), liver tumor (18),
and prostate cancer (19) have all shown
an increase in ADC following a number
of different therapeutic modalities. It is
believed that increases in ADCs are a
consequence of cellular damage leading to necrosis (14,34). Another reason
for the increase in ADCs seen within
1 week is tumor edema caused by the
massive release of vascular endothelial growth factor within hours of even
the first fraction of radiation therapy.
That would lead to increased vascular
permeability and increased interstitial
volume, which would increase ADCs. In
addition, clinical studies of rectal cancer (26), breast cancer (36), and breast
metastases in the liver (24) have shown
comparable ADC responses in human
patients. This response occurs within
days of initiating therapy and appears
to be a universal response to therapy,
regardless of pathologic categorization
of tumor.
In our study, slight increases of tumor ADCs were observed in the nondownstaged group at the end of the 1st
week of CRT as well. The values continued to increase during the 2nd week
of CRT and reached a statistically significant difference from that of before
CRT. When we compared the rate of
increase in ADCs in the downstaged
group with that in the nondownstaged
group at three time points (week 1,
week 2, and presurgery), we found
that the percentage of changes of the
tumor ADCs in the downstaged group
were significantly greater than those in
the nondownstaged group at all three
time points. We believe it was not that
the tumors in the nondownstaged group
were not affected by preoperative CRT,
because the tumor volume in that group
decreased after CRT, but the degree
of tumor sensitivity to CRT was lower
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Sun et al
than that in the downstaged group. The
possible explanation of this phenomenon is that the tumor cell necrosis
achieved with CRT in the downstaged
group significantly exceeded that in the
nondownstaged group. So, the difference of elevation of the ADCs after the
start of CRT reflected mainly the different sensitivity of the tumor cells to CRT
in the two groups.
The percentage of increase of tumor ADCs was significantly higher in
the downstaged group than in the nondownstaged group at the end of the 1st
week of CRT. However, reduction of the
tumor volume in both groups emerged,
and the reduction rates were not significantly different at week 1 and week 2.
We postulate, therefore, that an early
(week 1) increase of ADC may be a
suitable marker of tumor downstage
due to CRT that may be more reliable
than measurements of tumor volume
in rectal carcinoma. However, the cutoff value of the percentage of increase
of ADC needs further study.
Dzik-Jurasz et al (25) reported that
at pretreatment, a responder group
had statistically lower ADCs of rectal
tumor than a nonresponder group. We
obtained results similar to those reported
by Dzik-Jurasz et al, as those rectal
tumors with lower pretherapy ADCs
were more likely to be downstaged
after CRT. But DeVries et al (28), on
the other hand, found that the mean
ADCs in patients who responded well
to therapy were almost identical to
those who did not respond. However,
by using histogram analysis, they
found that an ADC histogram showed
a higher relative fraction of high
ADCs in the therapy nonresponder
group than in the responder group.
This suggests the potential limitation
of using summary mean or median
ADCs in some instances to evaluate
treatment response.
The reduction of mean tumor ADCs
occurred in all patients after CRT,
mainly because CRT led to interstitial
fibrosis, and radiation-induced inflammation regressed gradually.
Tumor volume measurement is widely
used for antitumor therapy response,
including for rectal carcinoma. The rec-
tum is a hollow viscus with irregular
morphology, so it is difficult to measure
the tumor volume located in the rectum. To date, the correlation between
rectal tumor histopathologic downstaging after CRT and tumor volume reduction remains controversial (6,37). Our
study showed that the tumor volumes
decreased obviously after CRT in both
groups. However, the difference of the
tumor volume reduction rate was not
statistically significant. Thus, it is unreliable to judge tumor downstaging by the
volume decrease or the reduction rate
of tumor volume in rectal carcinoma
at early stages of CRT.
Our study had several limitations.
First, the size of the patient group in
this study was relatively small and not
enough to get optimal threshold value
for predicting tumor downstaging.
Second, the identification of tumor
downstaging was based on a comparison between initial clinical T staging and postoperative pathohistologic
T staging, which could have induced
an inadvertent bias, because the tumor pre-CRT clinical stage would have
been underestimated or overestimated
in view of the inherent limitations of MR
imaging and US. Third, T3 stage in rectal cancer represents a heterogeneous
group. In patients with T3 disease, a
depth of extramural disease extension
of 5 mm or greater has been found
to be an independent poor predictor
of outcome and disease recurrence
(38). In addition, disease involvement
of the potential circumferential margin is also a poor prognostic factor.
Unfortunately, these factors were not
taken into consideration in this study
because of the small size of the patient group. Fourth, the images were
analyzed by consensus between two
reviewers, so the interobserver variability of ADC measurements was not
tested. Additionally, as there is considerable variability in reported ADCs, it
is unclear whether these results will be
reproducible in other centers, and, at
present, each center may need to establish its own reference values.
In conclusion, 1 week after beginning CRT, a significant increase of
mean tumor ADCs and low pretherapy
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GASTROINTESTINAL IMAGING: Tumor Downstaging of Rectal Carcinoma after Therapy
mean ADCs in rectal carcinomas have
the potential to help predict tumor
downstaging after CRT. DW MR imaging is a promising noninvasive technique for helping predict and detect
therapeutic response in patients with
rectal carcinoma who are undergoing
CRT.
Acknowledgments: We thank Hao Shen, MS, for
the programming software in the study, Yu Sun,
PhD, for histopathologic evaluation and Yong
Cui, PhD, for valuable assistance in data analysis
and manuscript preparation.
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