Anal and Rectal Cancers:

Anatomy, Contouring and

Considerations for IMRT
Planning
Karyn
y A. Goodman,, MD
Associate Attending Radiation Oncologist
Memorial Sloan
Sloan-Kettering
Kettering Cancer Center
 Disclosures

ƒ None
 Learning Objectives
• Describe the challenges and outcomes in IMRT for
the lower GI sites (anal and rectal cancers)

• Discuss the role of IMRT planning and routine image-

gguidance for lower GI cancers

• List the challenges

g associated with management
g of
motion and deformation in treating lower GI cancers
 Outline
• Pelvic Anatomy and Nodal Drainage Patterns
• Contouring and planning recommendations
for IMRT in the treatment of Anal Cancer
• IMRT in Rectal Cancer
• IGRT and motion issues in the treatment of
pelvic tumors
Anatomy of the Rectum and Anus
Peritoneal Reflection

Mesorectal fat

12-15 cm
 Anatomy

Mesorectal Fascia Mesorectal Fascia

• T2 axial images
• Mesorectal fascial involvement associated with higher risk of
positive circumferential resection margin
Nodal Drainage Patterns
 Nodal Anatomy

Superior Hemorrhoidal Vessels Mesorectal Nodes

Courtesy of Corinne Winston, MD

 Nodal Anatomy

External Iliac Nodes Inguinal Nodes Great Saphenous Vein

Internal Iliac Nodes

Courtesy of Corinne Winston, MD

Nodal Anatomy
Nodal Anatomy
 Outline
• Pelvic Anatomy and Nodal Drainage Patterns
• Contouring and planning recommendations
for IMRT in the treatment of Anal Cancer
• IMRT in Rectal Cancer
• IGRT and motion issues in the treatment of
pelvic tumors
 RTOG 98
98-11
11
RT + MMC/5-FU
644 Anal
SCC Patients Cis/5-FU RT + Cis/5-FU

C/FÆRT+C/F
C/FÆRT C/F RT+MMC/F
RT MMC/F
5-Year Rates p
(%) (%)
Disease free Survival
Disease-free
Local Relapse
Colostomy
Distant Mets.
Overall Survival
Ajani JA et al., JAMA 2008;299:1941-1921
 RTOG 9811
Relapse
l b
by TN Category
TN No. Local-Regional
Local- Distant Metastasis
C t
Category Pt
Pts TF(#) 5yr(%) TF(#) 5yr(%)

T2N0 302 50 19 31 12

T3N0 115 25 22 12 14

T4N0 31 13 50 5 21

T2N1--3
T2N1 95 37 40 22 31

T3N1--3
T3N1 47 27 58 12 32

T4N1--3
T4N1 25 14 64 4 17

Gunderson LL et al., ASTRO 2010

 RT Technique
• AP/PA – RTOG
– 30
30.6
6 to
t pelvis
l i
– 45 Gy to true pelvis (drop superior
border to SI joints)
– 54 - 59.4
59 4 Gy to GTV + 22-3
3 cm
margin for T3+ disease
 Anal Cancer:
NCCN G
Guidelines
id li V
Version
i 2 2.2012
2012

RT Guidelines:
45 Gy for T1/T2,
T1/T2
9-14 Gy boost for T3/T4
Field reduction after
30.6 Gy (bottom of sacroiliacal
joints)
36 Gyy (N0-inguinal
( g nodes))

IMRT may be used in the treatment

of patients with anal cancer
 180 patients

45 locoregional persistence or failure

28 local-only 7 local and regional 10 regional only

Local Recurrences in Relation to
Conventional Pelvic Fields
n=2
n=2

n=25 n=25

Posterior anterior field

Posterior-anterior Lateral field
 RTOG 0529: Dose Painted IMRT in
(Kachnic et al.)
Anal Cancer (Kachnic, al )
Mitomycin-C 10 mg/m² IV bolus on
days 1 & 29 IMRT
5-FU 1000 mg/m²/day by CI on
days
y 1-4 & 29-32 IMRT
T2 and above
*HIV pts eligible DP-IMRT
T2N0: 50.4 Gyy tumor;; 42 Gy
y elective
nodes in 28 fxs over 5.5 weeks
T3N0 or T4N0: 54 Gy tumor; 45 Gy
elective
e ect e nodes
odes in 30 fxs
soover
e 6
weeks
N+: 50.4 Gy < 3 cm or 54 Gy > 3 cm
ASTRO 2009,
2009 2010 in 30 fxs over 6 weeks
 Study Endpoints
ƒ Primary: Reduce combined grade 2+ GI/GU toxicities by
15%, as compared to 98-11 5FU/MMC arm (n=59 pts)

ƒ Secondary: all AEs vs. 98-11

ƒ Secondary: feasibility (< 5 cases with major deviations)

ƒ Secondary: two year outcomes

 RTOG guidelines
CTV A includes:
• Mesorectal
M l nodes
d
– Perirectal
– “Presacral”
• Internal iliac nodes
CTV B includes:
• External iliac nodes
CTV C includes:
• Inguinal nodes
Myerson RJ
RJ, Kachnic LA
LA, IJROBP
IJROBP, 2009
2009.
 RTOG 0529: IMRT vs. RTOG 9811
0529 9811-MMC-arm
(n=52) (n=324)
Acute Morbidityy# % %
≥ Grade 3 GI/GU AE 22* 36*
≥ Grade 3 skin AE 20* 47*

Endpoint& 2y-% 2y-%

Local-Regional Failure 20 23
Colostomy Failure 8 10
Overall Survival 88 91
Disease-Free Survival 77 71
Colostomy-Free Survival 86 84
Distant Failure 15 10
#Kachnic al., ASTRO 2009; &Kachnic L et al
L et al al., ASTRO 2010
Ng M, Int J Radiat Oncol Biol Phys, 2012
Ng M, Int J Radiat Oncol Biol Phys, 2012
Ng M, Int J Radiat Oncol Biol Phys, 2012
Contouring Guidelines

Ng M,
M Int J Radiat Oncol Biol Phys,
Phys 2012
IMRT plan for Anal Cancer
Comparison of APPA v. IMRT Fields

AP/PA (left) and IMRT (right). Inguinal nodes highlighted in pink, PTV in red. Isodose lines: 5400 cGy blue, 5250 cGy yellow,
5000 cGy cyan, 4725 cGy green, 4500 cGy magenta, 4275 cGy orange, 2500 cGy pink.
 IMRT for Anal Cancer
• 17 patients treated with definitive CMT
• 9 field IMRT plans
• Compared to AP/PA plans in 7 patients
• IMRT reduced mean and threshold doses to
small bowel
bowel, bladder,
bladder genitalia
• 3/17 patients failed Æ APR
• Median
M di f/ f/u 20
20.3
3 months
th
• 2 yr OS, DFS, CFS: 91%, 65%, 82%
Milano, IJROBP, 2005
Milano, IJROBP, 2005
 Multicenter Experience
• 53 patients Anal SCC
SCC, 3 academic centers
• Definitive chemoradiation (5-FU-based
chemo)
• Median f/u = 14.5 mos
• 18 month OS, CFS, freedom from LF: 93%,
84%, 84%

Salama, J Clin Oncol, 2007

 Multicenter Experience
• 42% had a treatment break
– median of 4 days
• 15% had acute grade 3 GI toxicity
– 34% Grade 3-4 toxicity on RTOG 98-11

Salama, J Clin Oncol, 2007

 Potential Limitations of IMRT
• Highly conformal fields with steep dose fall off
may underdose nodal regions at risk
• Potential for higher regional failure rates
• Cautionary report from McGill
– 66 pts treated for anal SCC (40-3DCRT, 26 IMRT)
– Increased Grade 3+ BM toxicity in IMRT grp (42% v
17.5%)
– 1 yr LR rate: 28.6% (IMRT) v. 15.2% (3DCRT)
V
Vuong, P
Proc ASCO,
ASCO 2008
 Propensity Score Analysis
• 223 Anal SCC patients treated from 1991-2010
• 45 – IMRT, 178 – conventional RT
• Median follow-up: 5 yrs (6.1 yrs - CRT, 2.3 yrs - IMRT)
• Patients treated with IMRT had significantly higher N
stage and were less likely to receive induction chemo
3-year IMRT Conventional RT P value
Outcomes (%) (%)
LRFS 87 79 .20
20
DMFS 86 88 .62
CFS 96 89 .10
10
OS 89 86 .91
DasGupta, Submitted, 2012
 Simulation Set-up
Set up
CT Simulation
– Prone (or supine)
– Aquaplast / Vac-loc Bag (or equivalent)
– Full Bladder
– IV Contrast + SB contrast
– Anal Marker
Marker; Wire around
aro nd Distal Extent
E tent of Disease;
Disease
Vaginal Marker
– PET-CT simulation if available or fuse diagnostic
g
PET
 Outline
• Pelvic Anatomy and Nodal Drainage Patterns
• Contouring and planning recommendations
for IMRT in the treatment of Anal Cancer
• IMRT in Rectal Cancer
• IGRT and motion issues in the treatment of
pelvic tumors
 German Rectal Cancer Study

Locally Advanced
Rectal Cancer

Preoperative 5FU Surgery

+5040cGy pelvic RT

Surgery Postoperative 5FU

+5580 cGy pelvic RT

Sauer NEJM 2004

Sauer,
Standard Pelvic Fields for Rectal Cancer
Dosimetric Benefit of IMRT for Rectal
Cancer
• M
Multiple
lti l dosimetric
d i t i studies
t di hhave compared d
conventional fields (bony anatomy), 3DCRT,
3 fi ld sIMRT,
3-field IMRT multi-field
lti fi ld IMRT planning
l i
• Target coverage and bowel volume
irradiated better for all plans compared to
conventional Urbano M, IJROBP, 2006
Callister M, Proc ASTRO, 2006
Guerrero Urbano MT, IJROBP 2006
Arbea L, Radiat Oncol, 2010
Tho LM,
LM IJROBP.
IJROBP 2006
 RTOG 0822 Phase II Rectal IMRT Trial

Adjuvant
cT3-4NxM0 or cTxN1-2M0 Chemo
Preop for planned
resection FOLFOX

capecitabine
it bi
Radiation + Surgery
+ oxaliplatin
LAR or APR
Pelvic IMRT: 45 Gy in 25 fx
3D-CRT boost: 5.4 Gy in 3 fx to total dose of
50.4 Gy in 28 fx
 Rectal Cancer – Target Definition
• GTV: Primaryy tumor + involved nodes
– As defined on physical exam, ERUS, MRI, CT, and/or
PET
– Include tumor +entire rectal circumference at that
level
• CTV: Elective nodal regions
– Standard: Peri-rectal, internal iliac, and superior
hemorrhoidal (CTVA)
– For T4 tumors extending anteriorly: include external
iliac (CTVA + B)
– For tumors invading anal canal: include inguinal and
external iliac (CTVA+B+C)

Myerson RJ, Kachnic LA, IJROBP, 2009.

 RTOG 0822
• Primary endpoint: Comparison of Grade 2+ GI
toxicity
i i to RTOG 0247 ((non-IMRT)
IMRT)
• 68 analyzable patients
• 90% T3, 55% N+
• 51% Grade 2+ GI toxicity compared to 58% on
RTOG 0247 (NS)
• Only 5 (7%) had unacceptable CTV

Garafalo M,
M ASTRO 2011
 IMRT v. CRT
• 92 rectal cancer pts
treated from 2004-2009
• 61 – CRT,
CRT 31 – IMRT
• 45/50.4 Gy for CRT
• 45/50 Gy for IMRT using
an integrated boost

Samuelian JM,
JM IJROBP
IJROBP, 2012
 IMRT v. CRT
IMRT CRT P
(%) (%) value
Grade 2+ 48 62 .006
GI toxicity
t i it
Grade 2+ 23 30 .62
Diarrhea
Grade 2+ 10 38 .10
enteritis
pCR 19 28 NS

Samuelian JM, IJROBP, 2012

Indications for IMRT for Rectal Cancer
• Low Rectal Tumors or T4 tumors
– Invading anal sphincter, cover inguinal nodes
– Anterior
A t i T4 extension,
t i cover external
t l ili
iliac nodes
d
• Post-operative chemoradiation
– Minimize bowel dose since bowel falls into
pelvis
• Recurrent colon cancer in the pelvis
Indications for IMRT for Rectal Cancer
 Rectal Cancer - Radiation Techniques
CT Simulation
– Supine (thin) or Prone
– Belly Board / Bowel Compression if Prone
– A
Aquaplast
l t / Vac-loc
V l B Bag ((or equivalent)
i l t)
– Full Bladder
– Oral (SB Follow Through) +/- IV Contrast
– Anal marker; consider vaginal marker
– ≤ 3mm Slice Thickness
– Use Multiple Fields
– Consider IMRT for Select Cases (nodal burden, small bowel
issues)
 Outline
• Pelvic Anatomy and Nodal Drainage Patterns
• Contouring and planning recommendations
for IMRT in the treatment of Anal Cancer
• IMRT in Rectal Cancer
• IGRT and motion issues in the treatment of
pelvic tumors
 IGRT and Motion Issues
• Improvements in pelvic imaging
– EUS, CT, MRI, PET
• Rectal Motion
– Day-to-day variation in rectal filling
Rectal Protocol CT
Rectal MRI

Mercury Study group, British Medical Journal, 2006

 Rectal MRI
• Studies have validated use of MRI to:
– measure depth of extramural spread accurately
– Predict circumferential resection margin (CRM)
positivity
iti it when
h ttumor iis ≤ 1 mm from
f mesorectal
t l
fascia on MRI
– Assess tumor and nodal response to pre-
pre
operative chemoradiation
• Good correlation with pathology
p gy
measurements in resection specimens
Brown G, Radiology, 1999; Beets-Tan R; Lancet, 2001; Mercury Study group, Radiology, 2007;
Mercury Study group, British Medical Journal, 2006.
MRI to Risk Stratify Rectal Cancer
 Impact on Management

Tumor abuts mesorectal fascia T4 Bladder invasion

 MRI as a Biomarker
• Regression of tumor microvasculature is an
early surrogate marker for treatment response
• New MRI techniques can assess these changes
non-invasively
– Dynamic
D i C
Contrast-Enhanced
t tE h d IImaging
i (DCE)
– Diffusion-Weighted Imaging (DWI)
Functional MR Imaging for Rectal
Cancer
Axial T2 anatomic image DCE-MRI Ktrans Map

DWI-MRI ADC Map

Dzik-Jurasz ASK, Br J Radiol, 2005

PET for Treatment Planning
 Impact of PET on RT Planning
• Evaluate interobserver variability in
contouring rectal cancer cases
• Rectal cancer volumes contoured by 4
radiation oncologists at Stanford
– CT alone
l
– CT + PET
Impact of PET on RT Planning

Patel, TCRT, 2007

 Impact of PET on RT Planning
• 20 rectal cancer,
cancer 3 anal cancer patients
• PET altered treatment volume in 17%
• PET altered
l d overallll treatment plan
l iin 2
25%
%
– Detection of distant metastases in rectal cancer
patients

Anderson, IJROBP, 2007

 Rectal Tumor Motion
• IMRT for rectal cancer limited by uncertainty in
targeting
i rectall tumors
• Consequence of rectal motion due to filling and
d f
deformation
ti
• Data from studies of prostate gland motion using
cine MRI demonstrate
cine-MRI
– Rectal motion and filling was a main determinant of
prostate intra-fraction motion
p
• Inter-fraction motion for rectal tumors may be
even greater Ghilezan M, IJROBP, 2005
 Rectal CBCT Study
• On-board CBCT can be used to quantify
degree of rectal motion and volume change
during RT
• CBCT to measure accuracy and d precision off a
simulated IMRT treatment delivery model
• 9 patients (8 rectal, 1 anal cancer) underwent
> 1 CBCT during a course of RT
• Co-registered to respective simulation CT
scan byy matchingg bonyy anatomyy
 Serial CT Scans

Max RL Mean RL Max AP Mean AP

Centroid
motion (cm) 2.6 0.71 3.77 0.97
 Degree of Rectal Deformation
• IMRT plans generated for 8 rectal cases and
forward calculations were applied to the
subsequent CBCT scans
• 7 of 8 patients had adequate rectal coverage
with
ith IMRT plan
l using
i 15 mm margin i ddespite
it
rectal motion and deformation
 Recommendations for IGRT for Pelvic
Radiotherapy
d h
• Immobilization is essential
essential, even with 3DCRT
due to sacral rotation
– Aquaplast mold,
mold vacbag
• Daily image guidance is necessary for highly
conformal pelvic fields due to rectal motion
– Daily KV
– Daily
l CBCT?
– Fiducials
 Conclusions
• IMRT reduces toxicity associated with pelvic
radiotherapy
di th ffor anall cancer and
d with
ith
appropriate contouring, results in excellent
local control
• IMRT for rectal cancer has not been shown to
reduce toxicity but may be beneficial in select
cases
• Incorporating better imaging into planning
pelvic radiotherapy may allow for more
targeted treatments
Thank you