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doi:10.1016/j.ijrobp.2005.12.

027
CLINICAL INVESTIGATION Rectum
MRI IDENTIFIED PROGNOSTIC FEATURES OF TUMORS IN DISTAL
SIGMOID, RECTOSIGMOID, AND UPPER RECTUM: TREATMENT WITH
RADIOTHERAPY AND CHEMOTHERAPY
SARAH BURTON, M.R.C.S.,* GINA BROWN, F.R.C.R.,

IAN DANIELS, F.R.C.S.,

ANDY NORMAN, B.SC.,

IAN SWIFT, F.R.C.S.,* MUTI ABULAFI, F.R.C.S.,*


ANDY WOTHERSPOON, M.R.C.PATH.,

AND DIANA TAIT, F.R.C.R.

*Division of Colorectal Surgery, Mayday University Hospital, Croydon, UK;



Academic Department of Radiology, and
Departments of

Medical Statistics and Computing,

Histopathology, and

Clinical Oncology, Royal Marsden Hospital, Sutton,
Surrey, UK;

Division of Colorectal Surgery, Epsom and St. Helier NHS Trust, Epsom, UK
Purpose: Neoadjuvant therapy is traditionally reserved for locally advanced mid and low rectal cancers. In
tumors above this level, the need for adjuvant treatment is based on poor histopathologic features, but this
approach has potential disadvantages. The aim of this study was to determine whether magnetic resonance
imaging (MRI) could accurately stage tumors of the distal sigmoid, rectosigmoid, and upper rectum and help
direct preoperative treatment.
Materials and Methods: A total of 75 patients with distal sigmoid, rectosigmoid, and upper rectal tumors were
assessed preoperatively by MRI. If tumor extended beyond the planned surgical resection plane, chemoradio-
therapy was offered.
Results: Of the 75 patients, 57 (76%) underwent primary surgery. Agreement between the MRI prognosis and
histopathologic ndings was 84% (95% condence interval [CI], 72.692.7%). The other 18 patients underwent
neoadjuvant chemoradiotherapy for poor prognostic features with predicted surgical resection margin involve-
ment. The histopathologic examination conrmed tumor downstaging in 9 of the 18 patients who underwent
chemoradiotherapy. The 3-year survival rate in the good prognosis group (91%; 95% CI, 77.197.3%) was not
signicantly different from that of the chemoradiotherapy group (81.4%; 95% CI, 52.493.6%). The poor
prognosis group undergoing primary surgery had signicantly worse survival (62.2%; 95% CI, 30.382.8%,
p < 0.03).
Conclusion: Our ndings indicate that tumors of the distal sigmoid, rectosigmoid, and upper rectum can be
staged accurately using high spatial resolution MRI and that those with poor prognostic disease may benet from
preoperative therapy. 2006 Elsevier Inc.
MRI staging, Colorectal cancer, Neoadjuvant chemotherapy, Preoperative radiotherapy.
INTRODUCTION
The denitions of rectal cancer vary, but the most accepted
denition is that of tumor arising within 15 cm of the anal
verge as measured by rigid sigmoidoscopy (1). Many publica-
tions have subdivided the site of rectal cancer into thirds
upper (1015 cm), middle (510 cm), and low (5 cm)
for the purposes of analysis (2, 3). Such subdivision has
allowed the identication of different prognostic groups of
rectal cancer patients. Low rectal cancers appear to have a
poorer prognosis, which may reect the difculty in achieving
a negative circumferential resection margin (CRM) with such
tumors (4). The Dutch Total Mesorectal Excision Surgery
(TME) trial concluded that upper third rectal cancers did not
gain signicant benet from short-course radiotherapy (5).
This has translated into the belief that tumors of the distal
sigmoid, rectosigmoid, and upper rectum do not benet from a
preoperative treatment strategy.
In the management of such tumors, it is standard practice
to offer these patients only adjuvant postoperative therapy if
the histologic assessment identies poor prognostic features
(6). However, this approach has some disadvantages, with
inherent delays in beginning therapy owing to surgical
complications and patient convalescence (6). This can result
in poor compliance and completion rates in the postopera-
tive period (7). The preoperative identication of known
poor prognostic features such as circumferential margin
involvement, peritoneal involvement, nodal disease, and
extramural vascular invasion (EMV) (810) could render
these patients eligible for preoperative treatment strategies.
In tumors of the distal sigmoid, rectosigmoid, and upper
Reprint requests to: Gina Brown, F.R.C.R., Department of
Radiology, Downs Road, Sutton, Surrey SM2 5PT, United King-
dom. Tel: (44) 208-661-3964; Fax: (44) 208-661-3506; E-
mail: gina.brown@rmh.nhs.uk
Received Sept 15, 2005, and in revised form Dec 15, 2005.
Accepted for publication Dec 15, 2005.
Int. J. Radiation Oncology Biol. Phys., Vol. 65, No. 2, pp. 445451, 2006
Copyright 2006 Elsevier Inc.
Printed in the USA. All rights reserved
0360-3016/06/$see front matter
445
rectum, the adjacent small bowel is the critical normal tissue
and its tolerance prohibits treatment in the adjuvant setting
(11) of a potentially large target volume, namely the peri-
toneal cavity. However, justication exists for considering
neoadjuvant radiotherapy in primarily unresectable tumors
of the distal sigmoid, rectosigmoid, and upper rectum. High
spatial resolution magnetic resonance imaging (MRI) is
very accurate in assessing such poor prognostic factors in
rectal cancer patients (12). We investigated extending its
potential use in distal sigmoid, rectosigmoid, and upper
rectal tumors.
METHODS AND MATERIALS
Data were collected retrospectively on all upper rectal, rectosig-
moid, and distal sigmoid cancer patients referred for MRI after
presenting to our unit between January 1999 and December 2002.
The local ethics review board of the participating institutions
approved the study. None of the patients included in this study had
distant metastatic disease at presentation. The tumor site was
dened prospectively according to the distance from the anal verge
to the tumors lowest limit as measured by MRI in the sagittal
plane (Table 1).
Our denitions were based on our interpretation of the current
published data. A study to determine the level of the peritoneal
reection found the mean anterior height from the anal verge to be
9 cm in women and 9.7 cm in men (13). We therefore dened the
lower limit of upper rectal cancers as 10 cm (i.e., above the level
of the peritoneal reection). In 2000, U.S. guidelines were issued
indicating that a cancer should only be classied as rectal if it was
12 cm from the anal verge on rigid proctoscopy (14). This was
based on evidence that the local recurrence rate in tumors 12 cm
was 9.6% compared with 30.1% and 30.7% for mid and low rectal
cancers, respectively, and was more consistent with a colonic
pattern of local failure (15). Hence, we used 12 cm to dene our
rectosigmoid group. The Association of Coloproctologists (Great
Britain and Ireland) have dened rectal cancer as any tumor 15
cm. Therefore, we used 15 cm as our denition of the lower limit
for distal sigmoid cancers.
MRI technique
All patients underwent preoperative MRI of the pelvis according
to the protocol described below. Only T
2
-weighted sequences were
used. MRI was performed on a 1.5-T scanner (Siemens, Erlangen,
Germany) with a four-element pelvic phased array wrap-around
surface coil at any of the involved hospitals. All patients were
imaged in the supine position. Neither intravenous antiperistaltic
agents nor contrast agents were administered. A coronal localizing
image was obtained to select the axial and sagittal images with a
T
2
-weighted fast spin echo (FSE) sequence (TR 3000 ms, TE
128 ms, echo-train length [ETL] 16, 5 mm thickness, four signal
averages, scan duration 35 min). The sagittal images were used to
plan 3-mm oblique high spatial resolution axial images. The im-
ages were acquired in a plane orthogonal to the tumor and rectal
wall using a T
2
-weighted FSE sequence (TR 3000, TE 128 ms,
256 256 matrix, ETL 16, eld of view 1618 cm). Depending
on the tumor length, the scan duration was between 6 and 12 min.
All MRI scans were prospectively reviewed by a single radiol-
ogist for T stage, depth of extramural invasion, N stage, presence
of extramural venous invasion, and CRM or surgical resection
margin status.
A preoperative treatment strategy of 12 weeks of neoadjuvant
chemoradiotherapy was only offered to patients with MRI-pre-
dicted positive CRMs or surgical resection margins (i.e., tumor
beyond the planned resection planebladder, pelvic side walls, or
other adjacent organ), and these patients were enrolled in phase II
trials (16). The presence of other poor prognostic features on MRI
was reported but did not change the patients planned treatment.
All the remaining patients proceeded with the traditional approach
of primary surgery (1721) (Table 2).
Chemoradiotherapy technique
Patients received a protracted venous infusion of 5-uorouracil
(300 mg/m
2
body surface area/d for 12 weeks) with intravenous
Table 1. Denitions of tumor site
Tumor site Distance from anal verge (cm)
Upper rectum 10 to 12
Rectosigmoid 12 to 15
Distal sigmoid 15
Table 2. Treatment allocation of rectal cancers according to MRI features (these criteria were
extended to tumors of distal sigmoid, rectosigmoid, and upper rectum)
Prognostic group MRI features Treatment strategy
Good T1-T2, T3 5 mm, N0-N1, no EMV, potentially
CRM negative
Primary surgery
Bad T3 5 mm, T4, N2, EMV present, potentially
CRM negative
Primary surgery
T4 invading adjacent organs and/or potentially
CRM positive
Preoperative
chemoradiotherapy
Abbreviations: EMV extramural invasion; CRM circumferential resection margin.
Our local staging stratication was based on evidence of 5-year survival rates of 85% for rectal
cancer patients with T3 tumors 5 mm depth of extramural spread vs. 54% survival for tumors with
T3 5 mm spread (24).
Peritoneal involvement is a known poor prognostic factor for both rectal and colon cancers (25,
26).
Increasing percentage of nodal disease reduces overall survival in colorectal cancer (27).
EMV has been shown to be an independent poor prognostic factor in colorectal cancer (8, 28).
446 I. J. Radiation Oncology Biology Physics Volume 65, Number 2, 2006
bolus injection of mitomycin C (7 mg/m
2
body surface area every
6 weeks). Starting on Week 13, the 5-uorouracil dose was re-
duced to 200 mg/m
2
body surface area/d, and concomitant pelvic
radiotherapy (45 Gy in 25 fractions) was begun, followed by a
5.49-Gy boost to the tumor bed (16). Patients were treated in the
prone position with a full bladder. Both maneuvers have been
shown to decrease the volume of small bowel. Patients underwent
CT treatment planning, using diagnostic MRI scans to aid in
localization of the target volume. The small bowel was maximally
excluded using customized blocking techniques (2224). Surgery
was planned for 6 weeks after chemoradiotherapy.
Histopathologic technique
All resections were performed with curative intent, and his-
topathologic examinations were performed according to the Royal
College of Pathologists guidelines (25). The CRM was dened in
upper rectal cancers as positive if tumor was within 1 mm of the
surgical resection margin. In cases of an apparent histopathologi-
cally complete response after chemoradiotherapy, multiple blocks
throughout the whole rectum were obtained, and all cases consid-
ered for postoperative therapy were reviewed centrally. The T stage,
N stage, presence of EMV, CRM status, and depth of extramural
invasion were documented.
Data were collected on prognostic features identied on MRI
and correlated with the prognostic features identied on histologic
examination.
Cancer-specic survival data were collected for the different
prognostic groups. The date of death or last follow-up appointment
were used as the endpoints for the survival curves.
Statistical analysis
The kappa test was used to compare each MRI-predicted poor
prognostic feature with the histopathologic ndings to determine
the accuracy. We calculated the 95% condence intervals using the
binomial distribution. Survival was analyzed using the Kaplan-
Meier methods, and the logrank test was used to detect any
differences between the survival curves.
RESULTS
A total of 75 patients were included in the study, with a
median age of 65 years (range, 3786 years); 41 patients
(54%) were men. The tumors were evenly distributed
among the three sites, with 25 (33%) dened as upper third
rectal tumors, 24 (32%) as rectosigmoid, and 26 (35%) as
distal sigmoid tumors (Table 3). On the basis of the MRI-
determined criteria (Table 1), 18 of the 75 patients under-
went neoadjuvant chemoradiotherapy to downstage the tumor
before surgical resection. The remaining 57 patients pro-
ceeded to primary surgical resection. The proportion of
tumors undergoing each therapy differed according to site,
with 16 (64%) of 25 upper third rectal tumors undergoing
primary surgery compared with 19 (79%) of 24 rectosig-
moid tumors and 23 (85%) of 26 distal sigmoid tumors
(Table 3).
The median lymph node count after resection was 12
(range, 638). Of 18 patients in the primary surgery group
with poor prognostic disease on histologic examination, 17
were offered postoperative chemotherapy, and only 2 pa-
tients refused further treatment.
MRI agreement
The agreement between MRI and the histologic ndings
for each prognostic variable was determined by correlating
the MRI prediction against the nal histologic outcome.
In the primary surgery patients (n 57), the T stage agree-
ment was 63%, with a weighted kappa agreement of 0.596
(Table 4). Nodal staging by MRI criteria was accurate in
65% of cases (37 of 57; Table 5). However, in the surgery-
alone patients, if the prognostic features were grouped into
good or bad according to the criteria in Table 2, the agree-
ment of the MRI prediction of prognosis was 84.5% (range,
Table 3. Treatment allocation and tumor site
Tumor site
Patients
(n)
Surgery
alone (n)
Chemoradiotherapy
(n)
Upper third rectal 25 (33) 16 (64) 9 (36)
Rectosigmoid 24 (32) 19 (79) 5 (21)
Distal sigmoid 26 (35) 22 (85) 4 (15)
Total 75 (100) 57 (76) 18 (24)
Data in parentheses are percentages.
Table 4. Correlation of MRI predicted T stage with nal
histologic ndings in patients undergoing primary surgery
MRI predicted T stage
Final histologic T stage
T1-T2 T3 T4
T1-T2 14 8 0
T3 5 18 6
T4 0 2 4
Agreement 63%; weighted kappa with quadratic (FleissCohen)
weights 0.59.
Table 5. Correlation of MRI-predicted N stage with nal
histologic ndings in patients undergoing primary surgery
MRI
Histopathologic nding
Node negative Node positive
Node negative 23 9
Node positive 11 14
Agreement 65%; kappa 0.28.
Table 6. Correlation of MRI-predicted prognosis with nal
histologic prognosis in patients undergoing primary surgery
MRI-predicted prognosis
Final histologic prognosis
Good Poor Totals
Good 35 5 40
Poor 4 13 17
Totals 39 18 57
Agreement for MRI prediction of prognosis 84% (95% CI,
72.692.7%, kappa 0.63); sensitivity 90%, specicity 72%, posi-
tive predictive value 88%, and negative predictive value 76%.
447 Preoperative treatment of distal sigmoid and rectosigmoid cancers S. BURTON et al.
72.692.7%), with a kappa agreement of 0.64 (Table 6).
The sensitivity was 90%, with a specicity of 74%.
The MRI prediction of the presence or absence of extra-
mural vascular invasion was accurate in 41 (72%) of 57
cases, with a negative predictive value of 84% (Table 7).
Of the 57 patients, 3 had MRI-predicted involved CRMs,
with only 1 case conrmed on histologic examination in
the primary surgery group. The original MRI reports for
these patients suggested that the margins were not at risk;
hence, their allocation to primary surgery. MRI showed a
96% (55 of 57) accuracy for correctly identifying the CRM
status.
Effect of chemoradiotherapy
Eighteen patients underwent neoadjuvant chemoradio-
therapy. All 18 patients had potentially involved CRMs or
invasion of adjacent organs as determined by MRI and
proceeded to chemoradiotherapy to downstage or downsize
their tumor (Fig. 1). Of the 18 cases, 15 were predicted to be
CRM positive on MRI. Of these, the tumor of 13 patients
was successfully downstaged by chemoradiotherapy to neg-
ative margins as conrmed by histologic examination, with
5 patients having a complete pathologic response (Table 8).
The remaining 8 patients demonstrated brosis extending
from the tumor edge to the circumferential margins on
histologic examination, consistent with tumor shrinkage in
response to the neoadjuvant treatment (Fig. 2). All 3 cases
with posttreatment persistent adjacent organ invasion on
MRI were conrmed as such on histopathologic examina-
tion. The 2 patients with positive margins were in the
rectosigmoid group.
Of the 18 patients with a predicted poor prognosis on
initial MRI who underwent chemoradiotherapy before sur-
gery, the disease of 9 (50%) was successfully converted to
a good prognosis (Figs. 1 and 3). The effect of chemora-
diotherapy on the International Union Against Cancer stage
showed that the number of Stage III tumors was reduced
from 16 (89%) to 7 (39%), with a complete pathologic
response in 28% (Table 8).
Survival
The 3-year cancer-specic survival rate was 92% (95%
condence interval [CI], 77.197.3%) for the good progno-
sis tumors, 62.2% (95% CI, 30.382.8%) for the bad prog-
nosis tumors that underwent primary surgery, and 81.4%
(95% CI, 52.493.6%) for the poor prognosis tumors that
underwent neoadjuvant therapy before surgery (Fig. 4).
The difference in the 3-year survival rate between the
good prognosis group and bad prognosis group undergoing
surgery alone was statistically signicant (p 0.03). No
signicant difference could be demonstrated between sur-
vival in the good prognosis group and the neoadjuvant
chemoradiotherapy group.
DISCUSSION
In rectal cancer, neoadjuvant chemotherapy is increas-
ingly being combined with radiotherapy for the dual pur-
pose of enhancing radiosensitivity of the tumor and reduc-
ing local recurrence (6, 16). Such neoadjuvant therapies
have yet to be explored in the region of the rectosigmoid
and sigmoid colon. However, local recurrence rates as great
as 30% in distal sigmoid, rectosigmoid, and upper rectal
cancers have been reported (26) and therefore support a
proposal for neoadjuvant therapies.
The avoidance of radiotherapy in tumors of the distal
Table 7. Correlation of MRI-predicted EMV with nal
histologic ndings in patients undergoing primary surgery
MRI-predicted EMV
Final histologic EMV
Absent Present
Absent 31 6
Present 10 10
Agreement 72% (41/57), kappa 0.354, positive predictive value
84%.
Pts undergoing
chemoradiotherapy
18
MRI predicted CRM+ve
15
Histological CRM
negative
3
Histological CRM
positive
2
Good
prognosis
2
Bad
prognosis
6
Bad
prognosis
2
MRI predicted organ
invasion
3
Histological CRM
negative
13
Good
prognosis
7
Bad
prognosis
1
Fig. 1. Actual treatment allocation according to MRI prognostic
factors and outcomes on nal histologic examination. MRI
magnetic resonance imaging; Pts patients; CRM circumfer-
ential resection margin; ve positive.
Table 8. Downstaging effect of chemoradiotherapy
UICC stage
Pretreatment
MRI-predicted
stage (n)
Posttreatment
pathologic
stage (n)
Stage 0, T0N0 0 5
Stage I, T1-T2N0 0 0
Stage II, T3-T4N0 2 6
Stage III, any T, N1-N2 16 7
Total 18 18
Abbreviation: UICC International Union Against Cancer.
448 I. J. Radiation Oncology Biology Physics Volume 65, Number 2, 2006
sigmoid, rectosigmoid, and upper rectum is based on sound
radiotherapeutic principles concerning normal tissue toxic-
ity issues and the aim of encompassing an anatomically
dened compartment, relating to patterns of tumor spread,
at the target volume. These two principles are critically
interconnected, because the size of the target volume will
affect the volume of normal tissue irradiated. However, the
target volume can be conned to the area of surgical dif-
culty and does not necessarily need to encompass the re-
gional lymph nodes. Sufcient evidence has shown an in-
creased incidence of bowel toxicity in the postoperative
compared with the preoperative setting, making this a more
appealing proposition than irradiating an ill-dened postop-
erative area at risk (11, 27).
Our study has shown that preoperative MRI can accu-
rately stratify tumors of the distal sigmoid, rectosigmoid,
and upper rectum into prognostic groups. Agreement of the
T and N stage of the distal sigmoid, rectosigmoid, and upper
third rectal tumors was 63% and 65%, respectively. Al-
though the T and N stage of the more proximal rectal and
sigmoid tumors using MRI is less accurate than the 8590%
rate achieved with MRI of rectal cancers alone (12), we
have shown that by identifying either locally extensive
disease or disease encroaching on the potential resection
margin, we can distinguish between good and poor progno-
sis tumors with 84.5% accuracy.
Magnetic resonance imaging prediction of the presence
or absence of EMV, a known poor prognostic factor in
rectal and colon cancer (9, 10), was correct in 72% of cases.
Pathologic studies have shown that EMV predicts for poor
survival and development of systemic failure (9, 10). Thus,
the accurate prediction of this feature may be of benet in
Fig. 2. Evidence of upper third rectal tumor downstaging from involved margin to negative margin with neoadjuvant
chemoradiotherapy. (a) Tumor extending to mesorectal fascia and thus to potential surgical resection margin (arrow).
Preoperative chemoradiotherapy was given to enable tumor regression from potential resection margins. (b) Scans after
treatment showed extensive low signal intensity where tumor had been, with regression away from margin and
corresponding to brosis (arrow). (c) Surgical specimen conrmed brosis at circumferential margins but no viable
tumor (arrow). (Figure appears in color online.)
Fig. 3. (a) Example of locally advanced distal sigmoid cancer before chemoradiotherapy. Consecutive oblique coronal
T
2
-weighted fast spin echo images (TR 4000, TE 101, echo train length 11) through extensive sigmoid tumor invading
bladder dome. On the basis of these magnetic resonance imaging ndings, patient was offered intensive preoperative
chemoradiotherapy. (b) Example of locally advanced distal sigmoid tumor in same patient after chemoradiotherapy.
Oblique coronal T
2
-weighted fast spin echo images (TR 4000, TE 101, echo train length 11) through sigmoid tumor after
chemoradiotherapy showing marked tumor regression. Tumor was more readily resectable.
449 Preoperative treatment of distal sigmoid and rectosigmoid cancers S. BURTON et al.
future preoperative stratication of high-risk patients with
rectosigmoid and distal sigmoid cancer.
Tumors of the distal sigmoid, rectosigmoid, and upper
rectum are more difcult to stage than mid and lower rectal
tumors, possibly because of the technical challenge of ob-
taining true axial images through the tortuous rectosigmoid
junction. Future developments in software, particularly
three-dimensional T
2
-weighted high spatial resolution im-
ages, may improve visualization of these areas to increase
the accuracy of T and N staging.
The CRM status is used as a surrogate marker for local
recurrence and poor survival in rectal cancers (28). Using
MRI, our predicted CRM positive rate was 20% (15 of 75)
for tumors above the peritoneal reection. However, after
chemoradiotherapy in selected high-risk patients, our histo-
logic CRM positive rate was reduced to 4% (3 of 75). Also,
MRI was 96% accurate in predicting the margin status in the
primary surgery group. One limitation of our study was that
we have relied on the extent of brosis to indicate the
original tumor extent. Although it could not be proved, the
brotic stroma extending to the CRMs in the treated cases
supports the view that the reduction in positive CRM rate
was probably an effect of chemoradiotherapy rather than
overstaging by MRI. The International Union Against Can-
cer TNM stage was decreased in 9 of 16 patients undergoing
neoadjuvant therapy, with 5 patients having a complete
pathologic response. This translated into a point estimate of
the 3-year survival rate for patients with poor prognosis
disease undergoing chemoradiotherapy of 81.4% (95% CI,
52.493.6%), not signicantly different from the survival
rate of patients with good prognosis disease (91%; 95% CI,
77.197.3%). However, the difference in the point estimate
of the 3-year survival between those with good and bad
prognosis disease undergoing primary surgery was signi-
cant (p 0.03), even though most bad prognosis tumor
patients proceeded to postoperative chemotherapy. It seems
unlikely that additional survival benet could be achieved
with neoadjuvant therapy in the good prognosis group of
patients. However, such therapy appears to have made a
difference in the survival of patients with poor prognostic
features with initially unresectable disease, and this sug-
gests that a similar benet could potentially be demon-
strated in those with tumors above the peritoneal reection
and resectable poor prognosis disease.
CONCLUSION
Our results indicate that routine MRI-based preoperative
assessment of tumors in the distal sigmoid, rectosigmoid,
and upper rectum may be an effective method for identify-
ing patients with high-risk features. Whether such patients
benet from preoperative identication and treatment using
neoadjuvant chemoradiotherapy needs to be tested prospec-
tively. Although some centers already treat upper rectal and
rectosigmoid tumors with neoadjuvant chemoradiotherapy,
the potential to extend this approach to distal sigmoid tu-
mors is an exciting prospect.
REFERENCES
1. Association of Coloproctology of Great Britain and Ireland.
Guidelines for the management of colorectal cancer. London:
ACPGBI; 2001.
2. Marijnen CA, Kapiteijn E, van de Velde CJ, et al. Acute side
effects and complications after short-term preoperative radio-
therapy combined with total mesorectal excision in primary
0
20
40
60
80
100
0 1 2 3 4 5
Time since initial presentation (years)
P
r
o
b
a
b
i
l
i
t
y

o
f

s
u
r
v
i
v
a
l

(
%
)
Good
Bad (No CRT)
Bad (CRT)
Fig. 4. Cancer-specic survival curves for good prognosis tumors, bad prognosis tumors, and tumors treated with
neoadjuvant therapy. CRT chemoradiotherapy. (Figure appears in color online.)
450 I. J. Radiation Oncology Biology Physics Volume 65, Number 2, 2006
rectal cancer: Report of a multicenter randomized trial. J Clin
Oncol 2002;20:817825.
3. Nagtegaal ID, van de Velde CJ, van der Worp E, et al.
Macroscopic evaluation of rectal cancer resection specimen:
Clinical signicance of the pathologist in quality control.
J Clin Oncol 2002;20:17291734.
4. Bonadeo FA, Vaccaro CA, Benati ML, et al. Rectal cancer:
Local recurrence after surgery without radiotherapy. Dis Co-
lon Rectum 2001;44:374379.
5. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative
radiotherapy combined with total mesorectal excision for re-
sectable rectal cancer. N Engl J Med 2001;345:638646.
6. Chawla AK, Kachnic LA, Clark JW, et al. Combined modality
therapy for rectal and colon cancer. Semin Oncol 2003;30:
101112.
7. Pahlman L, Glimelius B. Pre- or postoperative radiotherapy in
rectal and rectosigmoid carcinoma: Report from a randomized
multicenter trial. Ann Surg 1990;211:187195.
8. Mulcahy HE, Toner M, Patchett SE, et al. Identifying stage B
colorectal cancer patients at high risk of tumor recurrence and
death. Dis Colon Rectum 1997;40:326331.
9. Shepherd NA, Saraga EP, Love SB, et al. Prognostic factors in
colonic cancer. Histopathology 1989;14:613620.
10. Newland RC, Dent OF, Lyttle MN, et al. Pathologic determi-
nants of survival associated with colorectal cancer with lymph
node metastases: A multivariate analysis of 579 patients.
Cancer 1994;73:20762082.
11. Frykholm GJ, Glimelius B, Pahlman L. Preoperative or post-
operative irradiation in adenocarcinoma of the rectum: Final
treatment results of a randomized trial and an evaluation of
late secondary effects. Dis Colon Rectum 1993;36:564572.
12. Brown G, Radcliffe AG, Newcombe RG, et al. Preoperative
assessment of prognostic factors in rectal cancer using high-
resolution magnetic resonance imaging. Br J Surg 2003;90:
355364.
13. Narajian MM, Belzer GE, Cogbill TH, et al. Determination of
the peritoneal reection using intraoperative proctoscopy. Dis
Colon Rectum 2004;47:20802085.
14. Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for
colon and rectal cancer surgery. J Natl Cancer Inst 2001;93:
583596.
15. Pilipshen SJ, Heilweil M, Quan SH, et al. Patterns of pelvic
recurrence following denitive resections of rectal cancer.
Cancer 1984;53:13541362.
16. Chau I, Allen M, Cunningham D, et al. Neoadjuvant systemic
uorouracil and mitomycin C prior to synchronous chemora-
diation is an effective strategy in locally advanced rectal
cancer. Br J Cancer 2003;88:10171024.
17. Merkel S, Mansmann U, Papadopoulos T, et al. The prognos-
tic inhomogeneity of colorectal carcinomas stage III: A pro-
posal for subdivision of stage III. Cancer 2001;92:2754
2759.
18. Shepherd NA, Baxter KJ, Love SB. Inuence of local perito-
neal involvement on pelvic recurrence and prognosis in rectal
cancer. J Clin Pathol 1995;48:849855.
19. Shepherd NA, Baxter KJ, Love SB. The prognostic impor-
tance of peritoneal involvement in colonic cancer: A prospec-
tive evaluation. Gastroenterology 1997;112:10961102.
20. Stocchi L, Nelson H, Sargent DJ, et al. Impact of surgical and
pathologic variables in rectal cancer: A United States commu-
nity and cooperative group report. J Clin Oncol 2001;19:
38953902.
21. Conroy T, Guillemin F, Stines J, et al. [Diagnosis and staging
of colorectal cancers]. Rev Prat 1994;44:27062713.
22. Gallagher MJ, Brereton HD, Rostock RA, et al. A prospective
study of treatment techniques to minimize the volume of
pelvic small bowel with reduction of acute and late effects
associated with pelvic irradiation. Int J Radiat Oncol Biol
Phys 1986;12:15651573.
23. Shanahan TG, Mehta MP, Bertelrud KL, et al. Minimization
of small bowel volume within treatment elds utilizing cus-
tomized belly boards. Int J Radiat Oncol Biol Phys 1990;
19:469476.
24. Koelbl O, Richter S, Flentje M. Inuence of patient position-
ing on dosevolume histogram and normal tissue complica-
tion probability for small bowel and bladder in patients re-
ceiving pelvic irradiation: A prospective study using a 3D
planning system and a radiobiological model. Int J Radiat
Oncol Biol Phys 1999;45:11931198.
25. Quirke P, Williams GT. Minimum data set for colorectal
cancer histopathology reports. London: Royal College of Pa-
thologists; 1998.
26. Willett C, Tepper JE, Cohen A, et al. Local failure following
curative resection of colonic adenocarcinoma. Int J Radiat
Oncol Biol Phys 1984;10:645651.
27. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus
postoperative chemoradiotherapy for rectal cancer. N Engl
J Med 2004;351:17311740.
28. Nagtegaal ID, Marijnen CA, Kranenbarg EK, et al. Circum-
ferential margin involvement is still an important predictor of
local recurrence in rectal carcinoma: Not one millimeter but
two millimeters is the limit. Am J Surg Pathol 2002;26:350
357.
451 Preoperative treatment of distal sigmoid and rectosigmoid cancers S. BURTON et al.