Download Colon and Rectum

Anatomic Considerations
and Patterns of Spread
Rectum
 12 to 15 cm in length
 from the rectosigmoid junction to the puborectalis
ring
 upper third
 middle third (posterior border of the rectouterine
pouch or rectovesical space)
 lowest third no serosal barrier
Colonic nodal drainage
 consists of pericolic nodes and nodes in association
with the vascular supply to the colon (i.e., mesenteric
nodes
 rectal nodal drainage include the perirectal, presacral,
and internal iliac nodes .
Epidemiology, Molecular Cascade, Risk Factors, Hereditary Disease, and
Clinical Presentation
 The median age is in the seventh decade
 chemical carcinogens
 Environmental and dietary factors
Factors shown to increase the risk
 include increasing age,
 male sex,
rectal cancer
 excessive alcohol use
 family history of colorectal cancer,
 increasing height,
 increasing body mass index,
 processed meat intake
 low folate consumption.
 consumption of fruits and vegetables ?
 The role of chemopreventive agents (carotenoids, aspirin,
and other nonsteroidal anti-inflammatory drugs) ?
Biologic and genetic pathways of development of
colorectal cancer
 proto-oncogenes (mutations in the ras proto-
oncogene.)
 tumor suppressor genes (inactivation adenomatous
polyposis coli (APC) and P53)
Biology :microsatellite “instability”
 The majority of HNPCCas well as a minority of
sporadic colorectal cancers harbor microsatellite
“instability.”
 mutations in genes encoding enzymes that repair DNA
replication errors
 Studies have suggested that patients with tumors
possessing a high frequency of microsatellite
instability have a more favorable outcome and develop
fewer metastases
Colorectal cancer
 minimal or no symptoms
 Nonspecific
bowel habits, weakness, intermittent abdominal pain,
nausea, and vomiting.
The persistence of such symptoms as well as any
evidence of iron deficiency anemia should be
investigated
Clinical Presentation
 right colon
exophytic ,iron deficiency anemia
 left colon and sigmoid colon
deeply invasive, annular, and accompanied by
obstruction and rectal bleeding
 Rectal cancer frequently results in bleeding and
alterations in bowel habits.
 FIGURE 58.1. Idealized depiction of peritoneal
relationships in the colon and rectum. The transverse
and sigmoid colon are intraperitoneal, with a complete
peritoneal covering (serosa) and mesentery. The
ascending and descending colon are retroperitoneal,
lack a true mesentery, and usually do not have a
peritoneal covering posteriorly or laterally. The upper
rectum begins above the peritoneal reflection and has
peritoneum anteriorly and laterally. The lower half to
two thirds of the rectum is below the peritoneal
reflection (infraperitoneal).
Prevention and Early Detection
 Neoplastic polyps are precursors of colon cancers
 Most colorectal cancers arise from pre-existing polyps
 Patients with neoplastic polyps should be considered
at high risk for large bowel cancer, and polypectomy
may reduce this risk. With the availability of the
flexible colonoscope and endoscopic polypectomy,
polyps can be removed at a premalignant stage and
patients followed closely.
 The goal of screening is to detect preinvasive polyps or
early invasive cancer. The presence of polyps increases
the risk for cancer to approximately 15%. Data from
programs in which proctoscopy is performed annually
suggest that routinely scheduled polypectomy reduces
the development of subsequent bowel cancer by 80%
or more .
 The American Cancer Society has recommended
screening should begin at age 50 in the average risk
patient by either:
Annual fecal occult blood test and/or flexible
sigmoidoscopy every 5 years,
Double contrast barium enema every 5 years
Colonoscopy every 10 years
patients at high risk
 adenomatous polyps
 history of colorectal cancer
 first-degree relative with colorectal cancer or
adenomas
 inflammatory bowel disease
 family history or genetic testing
 Intensive surveillance is recommended for patients at
high risk
1. Computed tomography (CT) colonography
2. genetic fecal testing are being studied
Although screening methods can detect colorectal
cancer at an early stage, <40% of patients are
diagnosed with early disease, likely reflecting low
rates of disease awareness as well as the infrequency
of screening in eligible candidates
Pathology
 (>90%) adenocarcinomas
 Scc, carcinoid, leiomyosarcoma, and lymphoma.
 Most grading systems classify adenocarcinoma as well,
either moderately or poorly differentiated.
Pathways of Spread
 invade from mucosa through the bowel wall and
beyond, with involvement of lymphatic channels and
lymph nodes.
 Hematogenous spread can occur, primarily to the lung
and liver.
 There is little propensity for colon cancer to spread
longitudinally within the bowel wall, in contrast to
esophageal or gastric cancers
Patient Evaluation/Staging
 Pretreatment evaluation
1. pathological confirmation
2. colonoscopy ( synchronous primaries occurring in
3.
4.
5.
6.
7.
8.
3% to 5%)
CBC with LFT and CEA
abdominal and pelvic CT scan
CXR
(PET) scan
(MRI),
Ultrasound
‫‪(PET) scan‬‬
‫‪ ‬در مرحله بندی قبل عمل ارزشمند نیست اما در مرحله بندی بعد درمان‬
‫‪،‬عود یا شک به عود مفید است دویتا‬
‫‪ ‬در موارد الیگومتاستاز کاندید درمان شفاء دهند ه مفید است‪.‬پرز‬
Prognostic factors
 depth of tumor invasion into and beyond the bowel
wall
 the number of involved regional lymph nodes
 presence or absence of distant metastases
 The tumor, node, metastasis (TNM) system of the
American Joint Committee on Cancer can be used as a
clinical (preoperative) or postoperative staging system
Colorectal Tumor, Node, Metastasis Staging, 2002
 Tis
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Carcinoma in situ: Intraepithelial or invasion of
lamina propria
T1
Tumor invades submucosa
T2
Tumor invades muscularis propria
T3
Tumor invades through the muscularis propria
into the subserosa, or into non-peritonealized
pericolic or perirectal tissues
T4
Tumor directly invades other organs or
structuresa and/or perforates visceral peritoneum
(includes invasion of other segments of colon)
 Direct invasion in T4 includes invasion of other
segments of the colorectum by way of the serosa; for
example, invasion of the sigmoid by a carcinoma of the
cecum. Tumor that is adherent to other organs or
structures, macroscopically, is classified as T4.
However, if no tumor is present in the adhesion,
microscopically, the classification should be pT3
 N1
Metastasis in one to three regional lymph nodes
 N2
Metastasis in four or more regional lymph nodes
(Tumor nodules in the pericolonic adipose tissue
without evidence of residual lymph node are classified
as a regional lymph node metastases)
Therapy of Colon Cancer
Surgery
 based on the anatomy and mechanisms by which this
disease spreads.
 avoid cutting across tumor in intramural lymphatics,
 sufficient lengths of bowel must be resected
 Resection results in excellent cure rates
average 5-year survival
o 97% for T1N0
o 85% to 90% for T2N0
o 65% to 75% for T3–T4N0
o 50% (T3N+) and 35% (T4N+)
American Joint Committee on Cancer Stage Grouping
T
N
M
Dukes
MAC
Stage
I
T1
A
A
T2
A
B1
IIA
T3
B
B2
IIB
T4
B
B3
IIIA
T1-T2
N1
M0
C
C1
IIIB
T3-T4
N1
M0
C
C2/C3
IIIC
Any T
N2
M0
C
C1/C2/C3
IV
Any T
Any N
M1
-
D
Adjuvant Chemotherapy
 addition of 5FU (5-fluorouacil) and leucovorin improves

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survival for resected stage III patients
Capecitabine, an oral 5-FU prodrug, has demonstrated
similar overall and disease free survival rates to 5FU/leucovorin in patients with resected stage III colon
cancer
5-FU/leucororin/oxaliplatin in resected stage II or III colon
cancer patients showed improved disease-free
FU/LV/oxaliplatin as the new standard chemotherapeutic
regimen in the adjuvant treatment of completely resected,
high-risk colon cancer
The efficacy of agents such as bevacizumab and cetuximab
as adjuvant therapy is being investigated
Adjuvant Irradiation with or without Concurrent Chemotherapy
 The potential indications for adjuvant radiation therapy in
colon cancer are based on analyses of patterns of failure
following resection
 local failure in colon cancer also depends on anatomic
origin
1. ascending and descending colon
2. mid-sigmoid and mid-transverse colon
3. cecal, hepatic/splenic flexure, and proximal/distal
sigmoid tumors are variable depending on the amount of
mesentery present, tumor extension, and the adequacy of
radial margins.
 When colon cancers adhere to or invade adjacent
structures, local failure rates exceed 30% following surgery
alone.
 In summary, local failure occurs in patients with
colonic tumors where there are anatomic constraints
on radial resection margins, including tumors
adherent to or invading adjacent structures.
 To summarize, these studies have suggested that
operative bed failures in high-risk patients undergoing
resection alone are at least 30%, and that the risk of
local failure is reduced by the administration of
adjuvant radiation therapy.
 Irradiated patients included those with T4N0/N+,
T3N+ disease (excluding mid-sigmoid and midtransverse colon) and T3N0 patients with margins of
<1 cm.
(
surgery alone compared with CHRT (T3–4N0/N+ tumors
 radiation, with concurrent chemotherapy, usually with bolus 5-
FU (500 mg/m2/d) for 3 consecutive days during the first and last
weeks of radiation therapy. Radiation treatment to treat the
tumor bed with an approximate 3- to 5-cm margin to a total dose
of 45 Gy,
 Draining nodes were included if thought to be at high risk for
involvement. Local control rates in T4N0 and T4N+ patients
treated with radiation therapy were 93% and 72%, respectively
versus 69% and 47%, respectively in patients undergoing surgery
alone. Similarly, relapse-free survivals were 79% and 53%,
respectively in T4N0/T4N+ patients undergoing adjuvant
radiation, versus 63% and 38%, respectively undergoing surgery
alone.
 No significant outcome differences were observed in patients
with T3N0 and T3N+ lesions; however, there may be an element
of selection bias in the radiation group given most patients were
referred because of concerns of adequacy of local control
following surgery alone.
‫ در کنسر کولون‬CHRT
The rate of acute enteritis in patients receiving
irradiation and 5-FU was 16% versus 4% in patients
undergoing irradiation only.
2. Late bowel complication rates were not increased by
concomitant 5-FU administration.
3. with increasing numbers of nodes involved, survival
steadily decreased
4. There was a trend toward improved local control in
patientsreceiving 5-FU
1.
‫ در کنسر کولون‬CHRT ‫اندیکاسیون‬
 T4 tumors
 margin positive resection
 abscess/fistula formation
 FIGURE 58.2. Idealized postoperative
anteroposterior-posteroanterior irradiation fields of
extrapelvic colon cancer (tumor bed and nodal
regions). If treated preoperatively, lateral fields could
be added based on imaging with computed
tomography of the abdomen and colon radiograph. A:
Para-aortic nodes are at risk, in addition to tumor bed,
due to tumor adherence to posterior abdominal wall
with descending colon cancer. B: External and
common iliac nodes are at risk, in addition to tumor
bed, from proximal ascending colon cancer.
 local control rates in patients undergoing
intraoperative boost were 89% compared to 18%
undergoing external irradiation alone
 5-year survival
margin negative resection (66%)
microscopic residual (47%)
gross residual (23%).
 patients undergoing intraoperative boost
demonstrated improved survival (76% vs. 26%).
 A study from the University of Florida of patients with
locally advanced but completely resected colon cancers
receiving adjuvant radiation reported a local control
rate of 88%, similar to the 90% reported at the Mayo
Clinic in patients who had completely resected
tumors.
 there appeared to be a dose-response relationship to
local control.
The 5-year rate of local control was 96% for patients
receiving 50 to 55 Gy versus 76% for patients receiving
<50 Gy
To assess whether the addition of radiation therapy to adjuvant chemotherapy would result in superior survival and local regional failure rates in resected, high-risk colon cancer pat
 No definitive conclusions can be made regarding the
efficacy of postoperative irradiation with 5-FU and
levamisole based on this underpowered study with
many flaws; however, this study provides no data
supporting its routine use.
IOERT
 local failure
11% receiving IOERT plus EBRT versus 82% EBRT only
 5-year survival
76% for patients receiving IOERT 26% for patients
receiving EBRT alone]
metastatic disease
 5-FU–based chemo-therapy is usually administered.
 Recent prospective randomized trials have shown that
multiple agents improve survival in patients with
metastatic colorectal cancer.
irinotecan, 5-FU, leucovorin,
oxaliplatin
 Varying combinations of these drugs as well as other
novel agents remain the focus of ongoing investigation
in both the metastatic and nonmetastatic setting.
Palliative CHRT
 Palliative irradiation, sometimes in combination with
5-FU–based chemotherapy, is considered for patients
with specific symptoms referable to metastatic
disease—brain, bone, and other sites.
 The combination of radiation therapy and newer
agents (capecitabine, irinotecan, oxaliplatin,
bevacizumab, cetuximab) remains investigational
Techniques of Irradiation
 Field arrangement will vary depending on the site of the primary
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disease as well as areas judged to be at high risk for local recurrence
Patient positioning (supine, prone, decubitus) should be considered in
planning.
the right or left decubitus position for at least a portion of their
treatment, allowing displacement of the small bowel away from the
treatment field.
Immobilization devices may improve reproducibility.
It may be useful to compare films in both the decubitus and supine
positions to determine the actual amount of small bowel displacement.
CT-based planning may facilitate defining the tumor bed, determining
beam orientation, as well as estimating the volume of small bowel
included within the treatment fields.
Techniques of Irradiation
 total radiation dose
45 Gy in 25 fractions of 1.8 Gy per fraction (primary
tumor and at-risk tissues)
Reduced fields to 50 Gy
T4 tumors( a total dose of 54 to 60 Gy)
 Any treatment beyond 50 Gy mandates exclusion of all
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small bowel from the field.
Spinal cord dose should be limited to 45 Gy.
at least two thirds of one functional kidney should receive
no more than 18 to 20 Gy
at least two thirds of the total liver volume should not
receive more than 30 Gy.
In a Mayo Clinic analysis, small bowel obstruction rates
were lower when more than two treatment fields were
used, and attempts should be made to implement
multifield techniques, which may be aided by CT-based
planning
 primary tumor site :with a 4- to 5-cm margin proximally
and distally with 3- to 4-cm margin medially and laterally
to cover areas of potential residual disease.
 The nodal basins in the mesentery beyond surgical
margins are usually not treated as satisfactory margin
clearance is obtained in these sites. An exception to this
may be right colon tumors where both small bowel and
right colon are supplied by ileocolic vessels, limiting the
extent of resection.
 In some instances, treatment of the para-aortic nodes may
be indicated, particularly with extensive retroperitoneal
involvement by tumor. Treatment of proximal mesenteric
nodes may be appropriate if nodes adjacent to the surgical
or resection margin are involved.
 FIGURE 58.3. Idealized multiple-field preoperative or
postoperative irradiation technique for a sigmoid
colon cancer adherent to the bladder. Solid lines, large
field; interrupted lines, boost field. A:
Anteroposterior-posteroanterior. B: Paired laterals
Conclusion
 value of adjuvant postop CHRT for patients at high risk
for local relapse is unlikely to ever be addressed in a
definitive randomized trial. Treatment
recommendations should be made on a case-by-case
basis with existing data in the setting of an informed
consent.
 CHRT should be considered for patients with tumors
(a) invading adjoining structures, (b) those
complicated by perforation or fistula. and (c) where
incomplete resection is performed.
IOERT
 The use of intraoperative irradiation as a supplement to
EBRT in certain T4 tumors (i.e., those with uncertain
margins) may also be appropriate. For patients with tumors
adherent to or invading adjacent structures, the preferred
treatment sequence would be preoperative EBRT plus 5FU–based chemotherapy followed by resection with or
without IOERT and postoperative systemic therapy, based
on excellent results in preliminary IOERT reports from
both U.S. and European institutions.
CHRT →S± IOERT+CHT
A similar approach would be reasonable for patients with
locally recurrent cancers or with regional nodal relapse
Therapy of Rectal Cancer
 surgery had remained the primary treatment modality,
 local recurrence of disease (20% to 50%)
 Recent results of national cooperative group studies
and several European randomized trials indicate that a
multimodality treatment approach results in a
significantly better outcome than surgery alone.
Defining the True Rectum and Impact of Tumor Location
 12 to 15 cm from the anal verge. The true surgical rectum
begins at the anorectal ring, just proximal to the dentate
line .
 Tumors arising above the anorectal ring tend to
metastasize along the distribution of the middle rectal
vessels to the internal iliac lymph nodes as compared to
tumors that may extend into the anal canal, which spread
via nodes along the inferior rectal and external iliac
pathways
 Cancers that arise in the anal canal generally metastasize to
the lungs rather than the liver, .The prognosis of patients
worsens with more distal location of cancer, and these
differences persist even with the addition of adjunctive
therapy
 The proximal and distal rectum have historically been
defined by the level at which the peritoneum is
reflected along the anterior surface of the rectum
(usually at the level of S3)
 The middle valve of Hoston is a useful landmark that
can often be identified endoscopically (usually about 6
cm from the anorectal ring), and can be used to
differentiate proximal tumors from more distal lesions.
All tumors that can be digitally palpated are generally
considered distal cancers.
Prognostic Factors
 Location
 TNM
 Histopathological grade
 LVI
 Circumferential tumors
 ulceration
 Mobility
 Obstaction
 age, gender, and ethnicity(may be little)
Prognostic Factors
 Tumor extent as defined by the American Joint Committee
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on Cancer (AJCC) staging clearly remains the dominant
determinant of survival
age, gender, and ethnicity have little association with
outcome but may affect choice of therapy
Histopathological grade is of borderline significance,
however, and signet cell cancers have a particularly poor
outcome
LVI has been shown on univariate analysis to have a
negative impact on survival
Circumferential tumors or those with total or near total
obstruction (lumen <1 cm) respond very poorly, and
tumors with deep central ulceration are associated with a
high incidence of lymph node involvement
 Tumor mobility remains a key factor in both choice
and outcome of treatment
 Mobile cancers have a much more favorable outcome
as compared to tethered or fixed cancers.
 Tumor fixation is much more problematic in the distal
rectum as the confines of the bony pelvis inhibits the
surgeons ability to achieve adequate
 Distal rectal cancers require a more vigorous approach
to adjuvant therapy than proximal cancers.
 FIGURE 58.4. Lymphatics of the rectum
Imaging
 CTS
 EUS
 MRI
CTS
 CT appears to be much more useful in identifying enlarged
pelvic lymph nodes and metastasis outside the pelvis than the
extent or stage of the primary tumor
 Standard CT does not permit the visualization of the layers of
the rectal wall, and, therefore, its utility in the assessment of
small primary cancers is limited
 The sensitivity of CT scan is reported as 50% to 80% accurate,
with a 30% to 80% specificity (65% to 75% accurate for tumor
staging and 55% to 65% accurate in mesorectal lymph node
staging)
 The ability of CT scans for detecting distant metastasis,
including pelvic and para-aortic lymph nodes, is higher than for
detecting perirectal nodal involvement (75% to 87% vs. 45%)
 Any lymphadenopathy near the rectum seen on a CT scan should
be considered abnormal.
EUS
 more helpful in clinically stage rectal cancers
 80% to 95% accurate in tumor staging and 70% to 75%
accurate in mesorectal lymph node staging
 very good at T
 Its use is limited to lesions <14 cm from the anus and not
applicable for the upper rectum or for stenosing tumors.
EUS can also identify enlarged perirectal lymph nodes but
is not effective outside of the perirectum (76). One area
where EUS can be very useful is in determining extension
of disease into the anal canal, which is an area that is
poorly visualized on CT but of critical importance for
planning sphincter preserving surgical procedures
MRI
 greater accuracy in defining the extent of rectal cancer
extension and also determining the location and stage
of tumor .
 Different approaches to MRI have been explored
including the use of body coils, endorectal MRI and
phased array techniques. Although MRI appears to
have greater accuracy, it requires a significant learning
curve but is becoming a greater part of the standard
presurgical work-up for rectal cancer.
MRI ‫فوائد‬
 less operator dependent
 a larger field of view than EUS
 allows assessment for proximal tumors and stenotic
lesions
 detect involved lymph nodes on the basis of
characteristics other than size
 extent of lateral extension of disease
 They are all less accurate in predicting response after
neoadjuvant therapy with high rates of false positivity
and should be interpreted with caution in this setting
Treatment
Rectum
Surgery
 mainstay of curative treatment for carcinoma of the
rectum
1. limited surgery
2. LAR
3. APR
approach General principles of a surgical
 Removal of all gross and microscopic disease with
negative proximal, distal, and circumferential margins.
 Radical resection, this means removal of the adjacent
mesorectal tissue containing the regional lymphatics
and the superior hemorrhoidal artery pedicle.
 The surgeon's experience with resection of colorectal
cancer is an independent variable in the outcome of
treatment .
 Distal intramural spread of tumor is rare beyond 1.5
cm, and, therefore, a 2-cm distal margin is currently
considered acceptable, except in lesions that are poorly
differentiated or widely metastatic
Radial Margin
 86% local regional recurrence (with positive margins)
 only 3% local regional recurrence (without lateral
resection margin involvement).
 The mean surgical margin of resection has been
shown to decrease with increasing stage of disease
ranging from 14 mm for T1 cancers to 3 mm for T4
cancers, with a corresponding increase in local
recurrence from 0% to 75% .
Total Mesorectal Excision
 standard for all radical resections
 Sharp
 12 to 15 perirectal and pelvic lymph nodes
 Careful nerve sparring dissection
 more difficult with APR than LAR( higher anastomotic
leak rate) especially for low rectal lesions (15% to 17%)
 low rates of local recurrence (4% to 7%) and an
improvement in survival approaching 80% to 85% for
stage II and 65% to 70% for stage III disease
Abdominoperineal Resection
 gold standard for surgical resection of distal rectal
cancer and requires removal of the primary tumor
along with a complete proctectomy
 slightly higher morbidity and mortality than LAR
 a worse quality of life
 higher risk of positive margins
Low Anterior Resection
 performed not just for cancers of the upper third of
the rectum but also for middle and lower third cancers
 good anal sphincter continence prior to considering
sphincter-preserving options.
 LAR to APR have similar outcomes for local and
distant recurrence rates and survival as long as all
surgical margins are negative.
 The absence of a colostomy, while offering a better
quality of life with LAR, can be compromised with
bowel urgency and frequency or poor sphincter control
Local Excision
 tumors to be located <8 cm from the anal verge
 full thickness into the fat
 tumor be removed in one piece with at least a 1-cm
margin
 A primary closure
 to restrict local excision to patients with low-risk
tumors where the risk of recurrence is <10% (i.e., T1 or
favorable T2 cancers)
 T2 cancers need for further adjuvant therapy
RTOG) Protocol 89-02
 margins ≥3 mm, no LVI, no regional LN ≥2 cm by CT
scan, and be grade 1 or 2 to be eligible for observation.
T2 tumors with margins ≤3 mm received 59.4 to 65 Gy
with 5-FU (1,000 mg for meter squared on days 1 to 3 and
29 to 31)
 The risk of perirectal nodal metastasis and high
incidence of reported local failure rates for T2 cancers
following local excision alone indicate the need for
further adjuvant therapy
The Cancer and Leukemia Group B (CALGB)
 Although this study supports the use of adjuvant
radiation and chemotherapy for adverse T1 and
favorable T2 tumors, one should proceed with caution
given the high local failure rate.
local excision should be limited to
tumors:
 (<4 cm
 clinically T1 or T2,
 well to moderately differentiated
 involve <40% of the circumference of the rectum.
 These tumors are usually mobile, polypoid, not ulcerated,
and have favorable pathology including no lymphovascular
or blood-vascular invasion
Adjuvant Therapy
Postoperative
 surgery alone for T3 or T4 or node-positive patients :
a 25% local failure rate
40% to 50% overall survival,
 CHRT :
local failure rate of 10% to 15%
overall survival rate of 50% to 60%.
 5-FU/LV showed better relapse-free survival and
disease-free survival but not overall survival as
compared to MOF.
 The conclusions of the two NSABP trials were that
while postoperative radiation treatment did not appear
to improve overall survival, there was an improvement
in local control
Two trials GITSG
 this trial concluded a significant overall survival
advantage of nearly double for patients who had
combined modality treatment after surgical resection.
 the combined use of radiation and chemotherapy is
more effective than postoperative radiation alone, with
a greater potential for improved survival, and is
recommended.
 The bolus 5FU dose was 500 mg/m2 on day 1 to 5
during weeks 1 and 5, whereas the continuous infusion
5-FU was 225 mg/m2 per day
Favorable T3N0
 Sharp mesorectal excision with LAR or APR for T3N0
rectal cancers results in low local recurrences of <10%
without the use of adjuvant therapy.
 A limited subset of patients with T3N0 rectal cancer
may have an excellent outcome with surgery alone, but
there are no randomized data to support the omission
of adjuvant therapy for this group of patients at the
present time
Side Effects of Combined Chemoradiation
 acute side effects
nausea, vomiting, diarrhea , stomatitis with mucosal
ulceration , hematological toxicity
 Severe late toxicity
diarrhea, hand/foot syndrome ,Chronic bowel injury
(25% )
rectal urgency with frequent bowel movements
Treatment Technique for Postop Adjuvant Treatment
 areas at risk
 The presacral space, the primary tumor site, and (for
post-APR cases) the perineum.
 the internal iliac and distal common iliac nodes
 The external iliac nodes should be covered for lesions
extending to the dentate line.
Treatment Technique
 prone position
 full bladder
 the use of bowel-displacement techniques such as a
belly board (foam board table with a cutout to allow
the upper-abdominal contents to fall forward) or a
foam board mound designed to push the full bladder
posteriorly and cephalad
 The use of shaped lateral fields

 2D, a four-field [AP/PA]/right/left [R/L] lateral) or
three-field (PA/R/L lateral)
AP/PA
 superior port edge :L4/L5 (mid-L5 )
 distal port edge :5 cm below palpable tumor or 5 cm
below the best estimate of the preoperative tumor bed
and (if an APR has been performed) below the
perineum
 Lat :least a 1.5-cm margin on the pelvic brim
Lateral treatment portals
 entire sacrum posteriorly. A radiopaque marker should
be placed at the posterior aspect of the anus to make
certain that blocks in the posterior-inferior aspect of
the portal do not impinge on targeted portions of
anorectum.
 Ant at least 4 cm anterior to the rectum or all
macroscopic disease (determined by CT scan)
Dose
 4,500 cGy in 25 fractions of 180 cGy each
 An additional boost for patients receiving postoperative
radiation
 Small bowel must be excluded from the boost volume after
about 5,000 cGy. Typically, if small bowel cannot be
excluded, the boost dose is 540 cGy. If it can be excluded,
the usual boost dose is 900 cGy.
 (3D) treatment planning
The initial CTV should include macroscopic disease with
an approximately 2-cm margin in mesentery and within the
course of the large bowel(the initial CTV should include
rectal mesentery and nodal regions at risk)
 RT 3 to 6 weeks after surgery.
Neoadjuvant Therapy
Tumor down staging,
2. improved resectability
3. potential for expanded sphincter preservation
options in the distal rectum
 preoperative radiation results in improvement of both
local control and survival
1.
Neoadjuvant Chemoradiation
 45-50 Gy( 1.8 Gy)+ concurrent bolus 5-FU (350 mg/m2)
plus leucovorin on days 1 to 5 during weeks 1 to 5
 After surgery, four cycles of adjuvant chemotherapy
Capecitabine
 Capecitabine requires the presence of thymidine
phosphorylase (TP) for conversion to the active form
of 5-FU within the cells.
 Studies of capecitabine in combination with radiation
have shown similar response rates to 5FU,
 825 mg twice a day during the course of radiation
treatment.
 Acute toxicity of diarrhea, stomatitis, nausea, and
neutropenia are also somewhat less with capecitabine
than with 5-FU/leucovorin, however, the incidence of
hand/foot syndrome is higher with capecitabine .
 Ongoing phase III trials in the United States and
Europe are evaluating capecitabine and oxaliplatin
delivered neoadjuvantly with radiation therapy
 Doses of 46 Gy or 50 Gy were more effective than 40
Gy, but there was no difference between 46 or 50 Gy.
Similar results have been reported from other studies
as well.
Preoperative Versus Postoperative
 preoperative combined preoperative chemotherapy
and radiation therapy resulted in significantly less
local failures in the pelvis by half and also provided
twice the sphincter preservation. Importantly, there
was no difference in overall survival or disease-free
survival between the two arms
 FIGURE 58.5. A: AP portal of patient with T4 rectal
cancer. B: Lateral portal of a patient with T4 rectal
cancer.
Locally Advanced Rectal Cancer
 Clinical T4 tumors may not be resected completely
due to tumor fixation. Preoperative radiation
treatment is recommended to facilitate curative
resections.
IORT
 No IORT
metastases
less than T4 disease
adequate margins >1 cm
 IORT
Ten to 12.5 Gy for complete resection
12.5 to 15 Gy for microscopic residual
17.5 to 20 Gy for gross residual disease.
 The risk of peripheral neuropathy was 20% for doses >15
Gy. IORT improves local control, especially with a gross
total resection, but not survival for locally advanced rectal
cancer.
Reirradiation
 Recurrent rectal cancer is often approached the same
way as T4 disease with an aggressive treatment plan of
CHRTby surgery and then adjuvant CHT.
 IORT is considered
 The 5-year overall survival is approximately 20% .The
local control is about 40% in patients with no prior
radiation to 10% to 20% in patients who had prior
radiation.