Anal and Rectal Cancers - ASTRO

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

� None
Disclosures

Learning Objectives
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 imageguidance
g for lower GI cancers
• List the challenges associated with management of
g g
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
Mesorectal fat
Peritoneal Reflection
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

644 Anal
SCC Patients
5-Year Rates
Disease Disease-free free Survival
Local Relapse
Colostomy
Distant Mets.
Overall Survival
RTOG 98 98-11 11
RT + MMC/5-FU
Cis/5-FU
RT + Cis/5-FU
C/F�RT C/F�RT+C/F C/F RT RT+MMC/F MMC/F
(%)
(%)
p
Ajani JA et al., JAMA 2008;299:1941-1921

RTOG 9811
Relapse l bby
TN Category
TN
No. Local Local-Regional Regional Distant Metastasis
C Category t
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 T2N1-3 95 37 40 22 31
T3N1 T3N1-3 47 27 58 12 32
T4N1 T4N1-3 25 14 64 4 17
Gunderson LL et al., ASTRO 2010

• AP/PA – RTOG
RT Technique
– 30 30.6 6 to t pelvis l i
– 45 Gy to true pelvis (drop superior
border to SI joints)
– 54 - 59 59.4 4 Gy to GTV + 22-3 3cm cm
margin for T3+ disease

Anal Cancer:
NCCN GGuidelines id li VVersion i 22.2012 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 Gy y( (N0-inguinal g nodes) )
IMRT may be used in the treatment
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=25 n=25
Posterior Posterior-anterior anterior field Lateral field
n=2

RTOG 0529: Dose Painted IMRT in
Anal Cancer (Kachnic et al )
Anal Cancer (Kachnic, et 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 Gyy 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 fxss over o 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
� Primary: Reduce combined grade 2+ GI/GU toxicities by
15%, as compared to 98-11 5FU/MMC arm (n=59 pts)
� Secondary: all AEs vs. 98-11
� Secondary: feasibility (< 5 cases with major deviations)
� Secondary: two year outcomes

CTV A includes:
• MMesorectallnodes d
– Perirectal
– “Presacral”
• Internal iliac nodes
CTV B includes:
• External iliac nodes
CTV C includes:
• Inguinal nodes
RTOG guidelines guidelines
Myerson RJ RJ, Kachnic LA LA, IJROBP IJROBP, 2009 2009.

RTOG 0529: IMRT vs. RTOG 9811
0529
(n=52)
9811-MMC-arm
(n=324)
Acute Morbidity # y
% %
≥ 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 Kachnic L et al al., ASTRO 2009; & Kachnic 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 � APR
• MMedian 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)
VVuong, PProc 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
Outcomes
IMRT
(%)
Conventional RT
(%)
P value
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

Preoperative 5FU
+5040cGy pelvic RT
German Rectal Cancer Study
Locally Advanced
Rectal Cancer
Surgery
Surgery Postoperative 5FU
+5580 cGy pelvic RT
Sauer Sauer, NEJM 2004

Standard Pelvic Fields for Rectal Cancer

Dosimetric Benefit of IMRT for Rectal
Cancer
• MMultiple lti l ddosimetric i t i studies t di hhave compared d
conventional fields (bony anatomy), 3DCRT,
33-field fi ld sIMRT, 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
cT3-4NxM0 or cTxN1-2M0
Preop for planned
resection
Radiation
capecitabine
it bi
+ oxaliplatin
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
+
Adjuvant
Chemo
FOLFOX
Surgery
LAR or or APR
APR

Rectal Cancer – Target Definition
• GTV: Primary y 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 MM, 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

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

Indications for IMRT for Rectal Cancer
• Low Rectal Tumors or T4 tumors
– Invading anal sphincter, cover inguinal nodes
– AAnterior 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
– AAquaplast l t/ / VVac-loc 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
– DDynamic i CContrast-Enhanced t t E 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 overall ll 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 rectal ltumors
• Consequence of rectal motion due to filling and
ddeformation f ti
• Data from studies of prostate gland motion using
cine cine-MRI MRI demonstrate
– Rectal motion and filling was a main determinant of
prostate p intra-fraction motion
• 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 of f 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 by y matching g bony y 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 anal l 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