Carcinoma rectum-radiotherapy perspective

Epidemiology
 Colorectal caner is the third most frequently diagnosed

cancer in the US men and women.

 108,070 new cases of colon cancer and 40,740 new cases

of rectal cancer in the US in 2008. Combined mortality for
colorectal cancer 49,960 in 2008.

 Worldwide approx. 1 million new cases p.a. are

diagnosed, with 529,000 deaths.

 Incidence rate in India is quite low about 2 to 8 per

100,000

 Median age- 7th decade but can occur any time in

adulthood
 Lifetime risk



1 in 10 for men
1 in 14 for women

Incidence in Large Bowel
• Cecum

14 %

• Ascending colon

10 %

• Transverse colon

12 %

• Descending colon

7%

• Sigmoid colon

25 %

• Rectosigmoid junct

0.9 %

• Rectum

23 %

Clinical Anatomy
 12-15 cm from anal

verge.

 Diameter
 4 cm (upper part)
 Dilated (lower part)

 Posterior part of the

lesser pelvis and in
front of lower three
pieces of sacrum and
the coccyx

 Begins at the

rectosigmoid junction,
at level of third sacral
vertebra

Clinical Anatomy
.

 Ends at the anorectal

junction, 2-3 cm in front of
and a little below the coccyx

 Taenia of the sigmoid colon

form a continuous outer
longitudinal layer of smooth
muscle

 Fatty omental appendices are

discontinued

Rectum is divided into 3
portions
 3 distinct intraluminal

curves ( Valves of
Houston)

Lower rectum : 3 – 6 cm from

the anal verge

Mid rectum: 6 cm to 8 -10cm

from anal verge
 Upper rectum: 8 cm to

12 -15cm from anal verge

Peritoneal Relations
 Superior 1/3rd of the rectum
 Covered by peritoneum on

the anterior
surfaces

and

lateral

 Middle 1/3rd of the rectum
 Covered by peritoneum on

the anterior surface

 Inferior 1/3rd of the rectum
 Devoid of peritoneum
 Close proximity to adjacent

structure including boney
pelvis.

Arterial Supply
 Superior rectal A – from

IMA; supplies upper
and middle rectum

 Middle rectal A- from

Internal iliac A.
(supplies lower rectum)

 Inferior rectal A- from

Internal pudendal A.

Venous Drainage
Superior rectal V- upper

& middle third rectum

Middle rectal V- lower

rectum and upper anal
canal

Inferior rectal vein- lower

anal canal

Nerve supply
 Sympathetic: L1-

L3, Hypogastric plexus

 ParaSympathetic: S2-S4

Lymphatic drainage
 Upper and middle rectum
 Pararectal

lymph
nodes,
located directly on the muscle
layer of the rectum
 Inferior mesenteric lymph
nodes, via the nodes along the
superior rectal vessels
 Lower rectum
 Sacral group of lymph nodes

or Internal iliac lymph nodes



NODAL GROUPS

Perirectal
Common iliac

Internal iliac
Paraortic

Aetiology
 Etiological agents
 Environmental & dietary factors
 Chemical carcinogenesis.

 Associated risk factors
 Male sex
 Family history of colorectal cancer
 Personal history of colorectal






cancer, ovary, endometrial, breast
Excessive BMI
Processed meat intake
Excessive alcohol intake
Low folate consumption
Neoplastic polyps.

 Hereditary Conditions (FAP, HNPCC)

Symptoms
 Asymptomatic
 Blood PR(60%)
 Change in bowel habit(43%) (diarrhoea, constipation,








narrow stool, incomplete evacuation, tenesmus)
Occult bleeding(23%)
Abdominal discomfort (20%)(pain, fullness, cramps,
bloating, vomiting)
Weight loss, tiredness
Back Pain
Urinary symptoms
Pelvic pain(5%) indicating nerve trunk involvement

Acute Presentations
 Intestinal obstruction
 Perforation
 Massive bleeding

Signs
 Pallor
 Abdominal mass
 PR mass
 Jaundice

 Nodular liver
 Ascites
 Rectal metastasis travel along portal drainage to liver via

superior rectal vein as well as systemic drainage to lung
via middle inferior rectal veins.

Signs

 Signs of primary cancer
 Abdominal tenderness and distension – large bowel obstruction
 Intra-abdominal mass

Digital rectal examination – most are in the lowest 12cm &
reached by examining finger
 Rigid sigmoidoscope

 Signs of metastasis and complications
 Signs of anaemia
 Hepatomegaly (mets)
 Monophonic wheeze

 Bone pain

WHO Classification of
Rectal Carcinoma
 Adenocarcinoma in situ / severe dysplasia
 Adenocarcinoma
 Mucinous (colloid) adenocarcinoma (>50% mucinous)

 Signet ring cell carcinoma (>50% signet ring cells)
 Squamous cell (epidermoid) carcinoma
 Adenosquamous carcinoma
 Small-cell (oat cell) carcinoma
 Medullary carcinoma
 Undifferentiated Carcinoma

Dukes classification
Dukes A: Invasion into but not through the
bowel wall



 Dukes B: Invasion through the bowel wall but
not involving lymph nodes


Dukes C: Involvement of lymph nodes



Dukes D: Widespread metastases

Modified astler coller
classification Stage A : Limited to mucosa

 Stage B1 : Extending into muscularis propria

penetrating through it; nodes not involved

but not

 Stage B2 : Penetrating through muscularis propria;

nodes not involved

 Stage C1 : Extending into muscularis propria but not

penetrating through it. Nodes involved

 Stage C2 : Penetrating through muscularis propria.

Nodes involved

 Stage D: Distant metastatic spread

TX
T0
Tis
T1
T2

TNM Classification

Primary tumor cannot be assessed
No evidence of primary tumor
Carcinoma in situ: intraepithelial or invasion of lamina propria
Tumor invades submucosa
Tumor invades muscularis propria

T3

Tumor invades through the muscularis propria into pericolorectal tissues

T4a

Tumor penetrates to the surface of the visceral peritoneum

T4b

Tumor directly invades or is adherent to other organs or structures
Tis

T1

T2 T3

T4

Mucosa
Muscularis mucosae
Submucosa

Muscularis propria

Subserosa
Serosa

Extension to an adjacent organ

Stage grouping
Stage
0
I
IIA
IIB

T
Tis
T1
T2
T3
T4

N
N0
N0
N0
N0
N0

M
M0
M0
M0
M0
M0

Dukes
A
A
B
B

MAC
A
B1
B2
B3

IIIA
IIIB
IIIC
IV

T1-2
T3-4
Any T
Any T

N1
N1
N2
Any
N

M0
M0
M0
M1

C
C
C
-

C1
C2/C3
C1/C2/C3
D

Stage 0 Rectal Cancer
 Known as ―cancer in
situ,‖ meaning cancer
is located in the
mucosa.

Stage I Rectal Cancer
 The cancer has grown
through the mucosa
and invaded the
muscularis (muscular
coat)

Stage II Rectal Cancer
 The cancer has grown

beyond the muscularis
of the colon or rectum
but has not spread to
lymph nodes

Stage III Rectal Cancer
 Cancer has spread to
the regional lymph
nodes (lymph nodes
near the colon and
rectum)

Stage IV Rectal Cancer
 Cancer has spread

outside of colon or
rectum to other areas of
the body

Prognostic factors
 Good prognostic

factors
 Old age
 Gender(F>M)
 Asymptomatic pts

 Polypoidal lesions
 Diploid

 Poor prognostic
factors










Obstruction
Perforation
Ulcerative lesion
Adjacent structures
involvement
Positive margins
LVSI
Signet cell carcinoma
High CEA
Tethered and fixed
cancer

Stage and Prognosis
Stage

5-year Survival (%)

0,1

Tis,T1;No;Mo

> 90

I
II

T2;No;Mo
T3-4;No;Mo

80-85
70-75

III

T2;N1-3;Mo

70-75

III

T3;N1-3;Mo

50-65

III
IV

T4;N1-2;Mo
M1

25-45
<3

Japanese Scientists train
Dogs to detect Colorectal
Cancer ( Gut, 2011)

Diagnostic Workup
 History—including family history of colorectal cancer
or polyps

 Physical examinations including DRE and complete
pelvic examination in women:
size, location, ulceration, mobile vs. tethered vs.
fixed, distance from anal verge and sphincter functions.

 Proctoscopy—including assessment of
mobility, minimum diameter of the lumen, and distance
from the anal verge

 Biopsy of the primary tumor

Diagnostic Evaluation

 General

Clinical features.
 Lab. Studies
Complete blood cell count
Blood chemistry profile
CEA
 Evaluation

Determination of Occult Blood

Digital Rectal Examination
Proctosigmoidoscopy
Flexible Fibreoptic Sigmoidoscopy & Colonoscopy.
Barium Enema
• Urologic Evaluation
• Other Imaging studies
• CT, USG, MRI, Chest X-ray, FDG- PET scan, Endorectal U/S.

Colonoscopy or barium
enema
To evaluate remainder of large bowel to rule out
synchronous tumor or presence of polyp syndrome.

Figure: Carcinoma of the rectum. Doublecontrast barium enema shows a long
segment of concentric luminal narrowing
(arrows) along the rectum with minimal
irregularity of the mucosal surface.

Transrectal Ultrasound
 Used for clinical staging.
 80-95% accurate in tumor






staging
70-75%
accurate
in
mesorectal lymph node
staging
Very good at demonstrating
layers of rectal wall
Use is limited to lesion < 14
cm
from
anus,
not
applicable for upper rectum,
for stenosing tumor
Very useful in determining
extension of disease into
anal canal (imp to plan
sphincter
preserving
surgery)

Figure.Endorectal ultrasound
of a T3 tumor of the
rectum, extension through the
muscularis propria, and into
perirectal fat.

EUS : Accuracy
EUS CT
Depth of infiltration T staging

91% 71%

N staging

87% 76%

CT Scan
 Part of routine workup of patients
 Useful in identifying enlarged pelvic lymph-nodes and

metastasis outside the pelvis than the extent or stage of
primary tumor

 Limited utility in small primary cancer
 Sensitivity 50-80%

 Specificity 30-80%

CT Scan
 Ability to detect pelvic and para-aortic lymph nodes

is higher than peri-rectal lymph nodes(75% to 87%
vs. 45%)
Accuracy
T stage

60-80%

Accuracy
N stage

60-75%

Liver met.

70-79%

Figure:
Rectal cancer with uterine
invasion. CT scan shows a large
heterogeneous rectal mass (M) with
compression and direct invasion into the
posterior wall of the uterus (U).

Figure: Mucinous adenocarcinoma of the
rectum. CT scan shows a large
heterogeneous mass (M) with areas of
cystic components. Note marked luminal
narrowing of the rectum (arrow).

Magnetic Resonance
Imaging (MRI)
 Greater accuracy in defining extent of rectal cancer

extension and also location & stage of tumor

 Helpful in lateral extension of disease, critical in

predicting circumferential margin for surgical excision.

 Different approaches (body coils, endorectal MRI &

phased array technique)

Figure: Normal rectal and perirectal
anatomy on high-resolution T2-weighted
MRI. Rectal mucosa (M), submucosa
(SM), and muscularis propria (PM) are
well discriminated. Mesorectal fascia
appears as a thin, low-signal-intensity
structure (arrowheads) and fuses with the
remnant of urogenital septum making
Denonvilliers fascia (arrows).

Figure: Mucinous adenocarcinoma of the
rectum. T2-weighted MRI shows high
signal intensity (arrowheads) of the cancer
lesion in right anterolateral side of the
rectal wall.

PET with FDG
 Shows promise as the most sensitive

study for the detection of metastatic
disease in the liver and elsewhere.
 Sensitivity of 97% and specificity of
76% in evaluating for recurrent
colorectal cancer.

cancer
rectum
prostate

Small bowel
bladder
pubic bone

Aims of treatment
 Local control

 Long-term survival
 Restoration of bowel continuity and Preservation
of anal sphincter.
 Bladder and sexual function and maintenance or
improvement in QOL.
 Careful preoperative screening is crucial in
determination of the location of lesion and its

depth of invasion

Treatment

Surgery

Chemotherapy

Radiotherapy

Treatment Overview
 Sx mainstay of treatment.
 After curative resection the 5 year survival drops
from 80% in stage I to about 40% in stage III
disease.

 Local recurrence remains a major site of failure
ranging from 5% in few selected series to about
40% in most reports.
 LF associated with devastating symptoms that
severely affects the QOL & difficult to salvage

Principles of surgical
management
 Removal of primary tumor with adequate margin.
 T/t of draining LN.
 Restoration of function
 ―En bloc‖ resection if necessary

PELVIC SUBSITES
Five subsites :predominant areas at risk for local
recurrence:
 Mesorectal subsite (MS),
 Posterior pelvic subsite (PPS)
 Lateral pelvic subsite (LPS)
 Inferior pelvic subsite (IPS)
 Anterior pelvic subsite (APS)

PATERN OF NODAL
RECURRENCE
 MS less common as it gets totally removed in
TME
 PPS most common site of nodal recurrence 22
to 49% in various series.
 LPS around 21%
 IPS around 3 to 11%
 APS around 5 to17%

Surgical procedures for
Rectal ca

 APR ( abdomino-perineal resection).
 LAR ( Low ant. Resection)

Radical

 Proctectomy & colo-anal anastomosis
 Local excision




Transanal excision
Post. Proctotomy
Non-Radical
Trans-anal endoscopic microsurgery(TEM).

 Ablative procedures

Endoscopic surgery
Fulguration

Local excision

 For superficially invasive (T1) tumors with low







likelihood of LN metastases
Total biopsy, with further T/t based on pathology
Tumors within 8 to 10 cm of anal verge,
Encompass less than 40% of circumference of bowel wall,
well or moderately well differentiated histology,
No pathological evidence of venous or lymphatic vessel
invasion on biopsy
With unfavorable pathology patient should undergo
total mesorectal excision with or without sphincterpreservation:
 Positive margin (or <2 mm), lymphovascular invasion,
 Poorly differentiated tumors, T2 lesion

Local Excision Techniques
 Transanal Excision.
 Post proctotomy.
 TEM
 Fulguration
 Endoscopic laser

 Staging of such lesions should be performed using EUS

to minimize likelihood of doing a local excision for T3
tumors.

LAR
 For tumors in upper/mid rectum allows
preservation of anal sphincter

 Join colon to low rectum
 Permanent colostomy if tumor too low
w

 Reduced ability to define distant
disease
 Difficulty localizing lesion

 OR time and costs

Abdomino-perineal
resection
 For tumors of distal rectum(lower 1/3rd) with distal edge

up to 6 cm from anal verge
 Associated with permanent colostomy and high
incidence of sexual and genitourinary dysfunction

Procedure

 Through combined abdominal and perineal
incisions, the anus, rectum, and sigmoid colon

are removed en bloc.
 Also called Miles Resection
 The proximal end of the bowel is exteriorized
through a separate stab wound as a
colostomy.
 The distal end is pushed into the hollow of the
sacrum and removed via perineum
 Performed to treat cancer of the lower
rectum—and diseases are too low for use of
stapling devices

Heavy purse string suture
around anus to occlude it

Colon and Rectum are
delivered through the
perineal resection

Total mesorectal excision
 Local failures are most often due to inadequate surgical

clearance of radial margins.

 Conventional resection violates the mesorectal circumference

during blunt dissection, leaving residual mesorectum.

 Excision of fascia enveloping the fat pad around the rectum

 TME involves precise dissection and removal of the entire

rectal mesentery as an intact unit.

 Local recurrence with conventional surgery averages approx.

25-30% vs. TME 4-7% by several groups (although several
series have higher recurrence)

Pelvic Exenteration
The surgeon removes the rectum as well as nearby organs such as the
bladder, prostate, or uterus if the cancer has spread to these organs.
A colostomy is needed after this operation. If the bladder is
removed, a urostomy (opening to collect urine) is needed.

High Anterior Resection

15 cm

Low Anterior Resection
Ultra-low Anterior Resection

Abdominoperineal Resection (APR)

Complications of Surgery
 Bleeding

 Infection
 Anastomotic Leakage
 Blood clots
 Anesthetic Risks

SUMMARY OF BOWEL FUNCTION IN THE 2 GROUPS
Non-Radiation
(59 Patients)
No. of bowel movements/day
Medican (range)
4
Clustering
5
Awoken at night for movement
Incontinence
None
Occasional
Frequent
Wear a pad
Perianal skin irritation
Regularly use Lomotil ± Imodium
Unable to differentiate stool from gas
Liquid consistency (sometimes or always)
Unable to defer defecation >15 min
Need to defecate again within 30 min
Bowel function different to preoperative

2 (1-7)
83%
3%
14%
14%
–
93%
7%
0%
10%
12%
5%
15%
5%
19%
37%
61%

Chemoradiotherapy
(41 Patients)

7 (1-20)
22%
42%
37%
46%
–
44%
39%
17%
41%
41%
58%
39%
29%
78%
88%
93%

p Value

<0.001
–
–
–
<0.001
<0.001
–
–
–
<0.001
<0.001
<0.001
0.009
0.001
<0.001
<0.001
0.001
JH012804

Adjuvant therapy

Chemotherapy

Radiation therapy
with or without
chemotherapy

Purpose of
Radio(chemo)therapy
 To lower local failure rates and improve
survival in resectable cancers
 To allow surgery in primarly inoperable cancers

 To facilitate a sphincter-preserving procedure
 To cure patients without surgery: very small
cancer or very high surgical risk

Chemotherapy agents







5Fu
Leucovorin
Oxaliplatin
Irinotecan
Bevacizumab
cetuximab

Combinations
 FOLFOX
 FOLFIRI
 Leucovorin/5FU
 Capecitabine
 NIGRO
 Bevacizumab in
combination with
the above regimens.

PREOPERATIVE CHEMORADIATION
 NSABP R-03 : improved DFS & OS
 German trial : improved locoregional control.
 REGIMENS :
 5- FU : 225 mg/ m2 – daily continous infusion
 Capecitabine : 825 mg/ m2 BD on days of radiation
 5- FU : 400 mg / m2 IV bolus + leucovorin 20 mg /m2

IV bolus for 4 days : wk 1 & wk 5.

POSTOPERATIVE CHEMORT :
 EORTC 22921 trial : improved DFS & OS.
 MOSAIC trial : Addition of oxaliplatin + 5- FU + leucovorin

.

REGIMENS :
 5-FU : bolus weekly regimen ( leucovorin 20 mg/m2 over 2
hrs : 5- FU 500 mg/ m2 bolus
 if no neoadjuvant chemoRT :
 Weekly Roswell Park regimen : 5-FU + leucovorin
( leucovorin 500 mg /m2 given over 2 hrs followed by 5-FU
bolus ) : weekly over 6 wks then 2 wks rest .
 mFOLFOX 6
 Capecitabine 1000 – 1250 mg/ m2 from day 1-14 ( 21 day
cycle )

Role of Radiotherapy
 Neo-adjuvant/Adjuvant RT in resectable Ca Rectum

pre-op
post-op

 RT in locally advanced rectal cancer

pre-op for down staging
IORT

 Definitive RT

unfit for surgery

 Palliative RT – Pain, bleeding etc.

ADVANTAGES OF PRE
OP CT+RT

•

Down staging, hence increased resectability

•

Decreased risk of dissemination during surgery.

•

Radiation more effective with tumour cells
highly vascular.

•

Less serious bowel toxicity due to easy
exclusion.

•

Possibility of increasing sphincter preservation
in borderline cases.

TARGET VOLUME
 Site of local involvement

 spread to other organ - sacrum, vagina or
prostate
 Whole of the sacrum
 Posterior margin should be beyond the sacrum
 Anterior border 2-3 cm anterior to the promontry
of sacrum to include common iliac LN

Positioning
 Prone position with belly

board

 Purpose is to displace

bowel superior and
anteriorly & bladder
anteriorly

 Bladder distension
 Blocks are used to spare

the posterior muscle and
soft tissues behind the
sacrum and small bowel.

Treatment energy
 PA portal with 6MV to decrease bladder dose
 Lateral portal requires 10/15 MV to increase depth

dose and decrease dose to hip joints

 30 degree wedges improves distribution

 Portals
 4 fields (AP, PA, two lateral fields)
 3 fields (PA, two lateral fields)
 2 fields(AP,PA-rarely used)

PA Borders – Pre Op
Case In most cases upper border


lies at L5-S1 junction to
cover Sacral promontary.
 Inferior margin should be 34 cm below inferior tumour
extent on sigmoidoscopy.
 For upper rectal Ca, inferior
border upto dentate line(
cover all mesorectum)
 Lateral border -1.5 cm
beyond the bony pelvic wall

Lateral portal
 Upper Border- L5-S1

 Lower Border 3-5 Cm below

inferior Tx extension

 Posterior border should be

atleast 1 cm behind sacral
convexity

 Anterior border at pubic

symphysis*(T3-T4)

Issues in Postoperative RT
of Rectum
 Increased risk of bowel toxicity
Adhesions
Bowel sags in pelvic cavity
Large portals
1.
2.

Anastomotic site in ANTERIOR RESECTION
Perineal scar in APR

PA Borders – Post Op
Case
 In case of APR, inferior border

should cover perineal scar
 8-30% scar recurrence if scar
not included in field
 While only 2% reoccur if scar
included in portal

Lateral Borders – Post Op
Case
 In case of APR, inferior border

should cover perineal scar

Dose Distribution: 3
Fields / 30w

Dose Distribution: 3 Fields
/ 45w

Portals- Two Fields : APPA
 Parallel opposing not commonly used
 High dose to bladder and bowel
 Used in palliative cases & when bladder or

anterior wall involved

Pre-Op radiotherapy
 Short course

25 Gy in 5 daily fractions of 5 Gy given in 1
week.
 Long course
 Phase 1
45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.


Phase 2 (optional)
5.4–9 Gy in 3–5 daily fractions of 1.8 Gy(2 lat. Fields)

Post-Op Radiotherapy
 Phase 1
 45 Gy in 25 daily fractions of 1.8 Gy given in 5 week

 Phase 2 (optional)
 5.4–9 Gy in 3–5 daily fractions of 1.8 Gy(2 lat. fields)

Palliative radiotherapy
 Phase 1

 45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.

 Phase 2 (optional)

 5.4–14.4 Gy in 3–8 daily fractions of 1.8 Gy(2 lat fields)
 A hypofractionated regimen can be used
 30–36 Gy in 5–6 fractions of 6 Gy once weekly given in 5–

6 weeks.

Dose limitations
 Small bowel- 45–50 Gy
 Femoral head and neck- 42 Gy
 Bladder -65 Gy
 Rectum- 60 Gy

TARGET VOLUMES
 CTVA: Defined to be the regions that would always be

treated for rectal cancer
 Internal iliac
 Pre-sacral
 Peri-rectal
 CTVB:


External iliac nodal region

 CTVC:



Inguinal nodal region

GUIDELINES

 Lower Pelvis:

The caudal extent minimum of 2 cm caudal to
gross disease, including coverage of the entire mesorectum
to the pelvic floor
Extension of CTVA does not need to go more than a few
millimeters beyond the levator muscles unless there is
radiographic evidence of extension into the ischiorectal
fossa
For very advanced anal or rectal cancers, extending
through the mesorectum or the levators, add ~1-2 cm
margin up to bone wherever the cancer extends beyond the
usual compartments
An MRI and/or PET/CT scan is strongly recommended in
such cases.

Mid pelvis
The posterior and lateral margins of CTVA should

extend to lateral pelvic sidewall musculature or, where
absent, the bone.
Anteriorly extend CTVA to ~1 cm into the posterior

bladder, to account for day-to-day variation in
bladder position.
Include the posterior portion of the internal

obturator vessels (which lie between the external and
internal iliacs in the mid pelvis) with CTVA.

Upper pelvis:
 Superior extent - the rectosigmoid junction or 2 cm

proximal to the superior extent of macroscopic disease
in the rectum/peri-rectal nodes.
 This defines how much of the distal large bowel

within CTVA.

 Properly cover the internal iliac and pre-sacral

regions.

 The most cephalad aspect of CTVA - the common

iliac vessels bifurcate into external/internal iliacs
(landmark: sacral promontory).

Indications for elective
irradiation (CTVB+CTVC)
Elective coverage of the inguinal and external iliac regions

should be routine for anal carcinoma.

For rectal carcinomas extending into gynecologic or

genitourinary structures, the external iliac region should be
added (i.e. elective nodal coverage = CTVA + CTVB for
these cases).
Include the external iliacs for rectal cancers that extend

into the anal canal.

Electively irradiate the inguinal nodal region for rectal

adenocarcinomas that extend to the anal verge or peri-anal

OAR
The femoral head and neck should be avoidance

structures.

The small and large bowel are important structures to

consider when planning treatment.

The entire abdominal contents need to be contoured up to

~ 1 cm above the PTV.

Absolute volume of bowel (in cc) is more important than

relative volume (in %).

IORT radiation therapy (IORT) delivers a
 Intra-operative
concentrated dose of radiation therapy to a tumor
bed during surgery

 Dose range from 1250-2000cGy.
 Patient must be a surgical candidate in order to be

eligible for IORT

 Reserved for pts. with early-stage disease.

 Maximum effect, while minimizing recurrence
 Delivered immediately after tumor is removed,
helping to destroy the microscopic tumor cells

that may be left behind
 The tumor site is typically at high risk for
recurrence & traditional RT requires a recovery
period after surgery, which leaves microscopic
disease in the body for longer
 Spares healthy tissues and organs
 Shortened treatment times
 IORT T/t itself takes about 4 to 5 min.

 A "boost" for traditional radiation pts.
 Patients who must receive additional radiation
therapy following surgery can receive a boost of
radiation during IORT
After they have recovered from the surgical
procedure, they can continue with their RT with
fewer complications.

Endocavitary Radiation
 Propagated initially by Papillon and Sischy
 High doses low energy radiation delivered using
50 KVp unit
 Initially utilised applicator cones of 2.4 – 2.9 cm
dia
 Later intra-luminal catheters were used after
development of after-loading techniques.
 Dose at 1 cm depth = 1/3 rd of surface dose
 Since, very small volume very high doses can be
tolerated
 Multiple treatment done till CR achieved

Treatment Recommendations
Stage

Rectal cancer

~5-year LF/OS

I

• TME with APR or LAR.
• If pT1-2N0, no adj. treatment.
• Local excision for favorable tumors (<3 cm
size, <30% circumference, within 8 cm of anal
verge, well-moderately differentiated; margin
>3 mm, no LVSI/PNI).
 favorable T1 lesions- observation.
 T2 lesions - adjuvant 5-FU/RT

<5% LF
90% OS

II and III
(locally
resectabl
e)

• Pre-op 5-FU/RT LAR/APR adjuvant 5FU-based therapy × 3 cycles (preferred)
• If surgery initially  then adjuvant 5-FU × 2
cycles  concurrent chemoRT  5-FU ×2
cycles

T3N0 and T1-2N1:
5–10% LF
80% OS
T4N0 and T3N1:
10–15% LF
60% OS
T4N1 and T3/4N2:
15–20% LF
40% OS

Stage

III
(T4/ Locally
unresectable
)

Rectal cancer

If obstructed, diverting colostomy or stent
placed  definitive treatment. 5-FU/RT 
resection if possible. Consider
IORT for microscopic disease (after 50 Gy
EBRT, give IORT 12.5–15 Gy) or
brachytherapy for macroscopic disease 
adjuvant 5-FU-based therapy*

IV

Individualized options, including combination
5-FU-based chemo alone, or chemo ± resection
± RT

Recurrent

Individualized options.
If no prior RT, then chemoRT  surgery ±
IORT or brachytherapy.
If prior RT, then chemo surgery ± IORT or
brachytherapy as appropriate.

~5-year LF/OS

Pre-op RT vs. surgery alone
Swedish Rectal Cancer Trial(NEJM 1997;336:980 ): 1168 patients
randomised to 25 Gy (5x5) PRT or no RT.
Surgery alone
Preop. RT
Rate of local recurrence 27%
11%
p<0.001
5-year overall survival 48%
58%
p=0.004

Dutch Colorectal Cancer Group (Kapiteijn E. NEJM
2001;345:638): 1861 patients randomised TME vs
PRT+TME
TME
PRT+TME
Recurrence rate 2.4%
8.2%
OS
ns
ns

Pre-op vs. post-op Chemo RT
Randomized trial of the German Rectal Cancer study Group (Sauer
R et al. N Engl J Med 2004;351:1731-40):
 cT3 or cT4 or node-positive rectal cancer
 50.4 Gy (1.8 Gy per day)
 5-FU: 1000 mg/m2 per day (d1-5) during 1. and 5. week

Preop CRT
Patients
5 y. OS
5 y. local relapse
G3,4 toxic effects

Postop CRT

N=415
76%
6%
27%

N=384
74% p=0.8
13% p=0.006
40% p=0.001

• Increase in sphincter-preserving surgery with preop Th.

• MRC CR07/NCIC-CTG C016 (Sebag-Montefiore et al.

2009): 1350 pt. with resectable rectal cancer randomized.
▫ 25 Gy/5# + Surgery (TME)
▫ Surgery (TME) + (45 Gy & 5 FU)

CRT
5 y. OS
5 y. local relapse
DFS

Preop RT

80.8%
4.4%
79.5%

Postop

78.7%
10.6%
74.5%

Polish Trial
• Polish Study (Br J Surg. 2006): 316 pts with resectable T3-

4 rectal cancer, no sphincter involvement, tumor palpable
on DRE (1999-2002).
– RT  short-course RT with 5 Gy/d x 5 days + Surgery
(TME)
– CRT  50.4 Gy (1.8 Gy /# over 5.5 weeks) + bolus 5-FU
325 mg/m²/d + LV x 5 days 1st and 5th wks of RT +
Surgery (TME)
Preop SCRT Preop LCRT

5 y. OS
5 y. local relapse
DFS

67.2%
9.0%
58.4%

66.2%
14.2%
55.6%

Post-op chemo, RT, and/or ChemoRT
 GITSG 7175 (Thomas and Lindblad, 1988): 227 patients with stage B2-C

rectal CA randomized postoperatively to:
 no adjuvant therapy vs.
 chemo alone vs.
 RT alone vs.
 concurrent chemoRT.
Result: Chemo-RT arm improved 5-year OS (54%) and LR(10%) over
observational arm OS (27%) & LR (25%).

 Mayo NCCTG 79-47-51 (NEJM 1991): 204 patients with T3/4 or

LN+(B2-C) randomized to
 post-op RT (45–50.4 Gy) vs.
 chemoRT (bolus 5-FU concurrent).
Result: Chemo-RT improved LF (25 14%), DFS, and OS (48 58%)
vs. RT alone.

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