2018

1. MANAGEMENT OF ANAL CANAL
TUMORS WITH EMPHASIS ON RT
PLANNING.
DR . SUMERA SABA
Moderator: DR. ARSHAD MANZOOR

2. INTRODUCTION
 Cancers of the anal region accounts Anal canal cancer most commonly
for 1% to 2% of all large bowel cancers develops in patients 50 to 60
and 4% of all anorectal carcinomas. Years of age.
I ) squamous cell carcinomas:75%-80% The corresponding 5-year relative
survival rates were:-
II) Adenocarcinomas :- 15%
I) 80.1% for localized disease,
 There is slight female predominance II) 60.7% for regional lymph nodes
with 1.7 cases per 100,000 women 29.4% for distant metastasis.
compared with 1.4 per 100,000 men
per year III) 55.4% for unstaged disease.

3. INTRODUCTION
ANATOMY
Anal canal extends from the
anorectal ring to
the anal verge (3-4cm).
REGIONS:-
 Intraanal lesions:- cannot be
Visualized or only slightly visualized
With gentle traction on the buttocks.
 Perianal lesions:-completely visible
------within a 5cm radius of anal
opening with gentle traction
 Skin lesion:-
---- outside of 5cm radius

5. ANATOMY

6.  Development:-
upper 15mm develops from  primitive ano rectal canal (distal part of
hindgut).
lower part below the pectinate line (lower 15+8cm)  ectodermal
invagination i-e proctodeum.
ARTERIAL SUPPLY :-
above pectinate line  superior rectal artery
below pectinate line  inferior rectal artery.
VENOUS SUPPLY :- veins of anal canal connects with both the systemic and
portal venous system .
veins from inf. Part of venous plexus communicate with systemic system via the
internal pudendal & internal iliac veins.
veins from the superior canal flows predominantly to inferior mesentric vein
then to portal system.

7.  Nerve supply :-
above pectinate line - supplied by autonomic nervous system.
(sympathetic by inf, hypogastric plexus L1, L2)
(parasympathetic by pelvic splanchic S2.S3.S4)
below pectinate line  supplied by somatic nerves .
( inf. rectal .S2,S3.S4)
SPHINCTERS:- internal sphincter contracts  symphathetic nerves
relaxed  parasymphathetic nerves
external sphincter :- supplied by inf. Rectal nerve & Perineal
branch of 4th sacral nerve.

8.  Lymphatic supply:-

9.  … Lymph nodes at Risk in Anal cancer

10. RISK FACTORS
 Most significant risk factors so far identified are:-
 sexually transmitted virus
 immuno supression
 tobacco smoking.

11. PATHOLOGY
 WHO classification of carcinoma of anus.
ANAL CANAL ANAL MARGIN
Squamous cell Malignant epithelial tumors:
Large cell keratinizing squamous cell carcinoma
Large cell non keratinizing ( transitional) gaint condyloma
Basaloid basal cell carcinoma
others.
Adenocarcinoma Bowen’ s disease
Rectal type Paget’ s disease
Anal gland type
Small cell carcinoma
Undiffrentaited
melenomas

12. PATHOLOGY
¶ primary anal melanoma is a rare
tumor that accounts for only 1%
0f all anal cancers. Anal melanoma
is similar to melanoma of skin and
is characterized by the distant
spread of disease
¶ Outcome is poor after WLE or APR
with just a 10% survival is most
series at 5-year follow up.

13. PATHWAYS OF TUMOR SPREAD
 Anal cancer tumor spread by
 direct extension to surrounding tissue
 Lymphatic dissemination to pelvic
and inguinal lymph nodes, or
 Hematogenous spread to distant
viscera .

14. PATHWAY OF TUMOR SPREAD
 LOCAL EXTENSION:- LYMPHATIC SPREAD
i. Sphincter muscle May occur early.
ii. Perianal connective tissue Overall lymph node spread is seen
iii. Rectum in 25% of cases at diagnosis.
iv. Perineum
v. pelvic wall Delayed inguinal lymph node
vi. Prostate metastasis is seen in approximately
vii. Vaginal septum 10% -25% of patient.
Anal-vaginal fistula is seen in <5% of cases.

15.  Distant metastasis is relatively rare , and extra
pelvic metastasis is seen in <10% of patients before
treatment.
Common sites of metastasis includes:-
 liver
 lung
 extrapelvic lymph nodes

16. PROGNOSTIC FACTOR
:Tumor related prognostic Factors for poorer OS included
 node-positive Cancer,
 large(>5cm) tumor diameter,
Tumor >5cm in diameter Regardless of nodal status , had a
higher colostomy rate and inferior DFS.
Patient related poor prognostic factors:-
 age >65yrs
 Poor Performance score
 Male gender
 Base line HB < 10g/l
 Presence of HIV infection/ AIDS
patient who continues to smoke tobacco are at greater risk of
local relapse .

17. CLINICAL PRESENTATION
 Bleeding Per Rectum. (45%)
 Perianal Pain (30%)
 Pruritus.
 A Palpable anal Mass
 anal discharge
 Change In Bowel Habits

18. WORKUP FOR ANAL CANAL CANCER
 PET imaging is useful in further evaluating
the extent of the primary tumor
and the presence of regional lymph nodal
metastasis and distant metastasis, as well
as in evaluating the response to therapy.
For patients with HIV risk factors,
a determination of HIV status should
be made before the initiation of
therapy.
Female patients should be subjected to a
gynecological examination to exclude
other HPV –associated cancers.
Counseling for loss of fertility for men
and women.
Under no circumstances should a formal lymph node dissection be carried out for initial evaluation
of suspicious nodes

19. AJCC TNM STAGING
 ..

20. 

21. MANAGEMENT OF ANAL CANAL CARCINOMA
 For a long time APR remained the standard of care for anal
cancer.
Papillon et al
 In the early 1960’s
 Introduced the concept --- long-term local control with
definitive radiation therapy.

22. Chemo radiotherapy:-
 Nigro et al. In 1974
 First demonstrated complete pathologic responses to
concurrent .
5-fluorouracil, Mitomycin C, and Radiation therapy
Nigro ND , Vaitkevicius VK, Considine B Jr. Combined therapy for
cancer of the anal canal : a preliminary report . Dis colon rectum
1974 ; 17 : 354-356

23. SURGERY
 Surgery is the principal treatment for Anal intraepithelial neoplasia but
retains only a limited place in the initial management of primary
invasive anal cancer.
Local excision;- Preserving ano rectal function is possible in
 well differentiated squamous cell ca.
 <2cm (T1).
 not invading sphincter .
 located distal to dentate line .
APR is still useful for local recurrence after conservation therapy &
for management of complication of conservation therapy.
.

24. RADIATION THERAPY
 Use of RT alone either as brachytherapy or EBRT has been
greatly reduced since the confirmation of improved outcome
with Concurrent chemo radiation.
 RT alone is given in patient who are unable to under go CCRT
( because of old age or any Contraindication for chemotherapy)

25. CONCURRENT CHEMORADIATION

26. Other Drug Radiation Combination:-
UKNCRIAS  phase II trail
RT (50.4Gy /28#-- 5.5week) + single MMC (12mg/m2 on D1) + oral
capcitabine ( 825mg/m2 BD with RT )
This schedule was well tolerated with acceptable compliance .
Results :- TRR after treatment was 90%.
EORTC phase II trail:-
RT ( 36Gy + 2week gap + 23Gy) + MMC/ 5FU or MMC/ CDDP
Results :- after 8week
ORR were 92% in MMC/CDDP vs 80% in MMC/5FU
Although greater compliance to full regimen was seen with
RT,MMC,and 5FU.

27. ROLE OF INDUCTION CHEMOTHERAPY
 NCCN :-
“ Induction chemotherapy preceding chemoradiation
may be beneficial in subset of patients with T4 cancer. 5-year
colostomy free survival rate was significantly better in T4 patient
who received induction 5-FU/ Cisplatin compared to those who
did not .(100% vs 38+/_16.4%. p=.ooo6) ˝

28. RADIATION THERAPY TECHNIQUES AND DOSES
 Anal region can be irradiated with various techniques due to complex
anatomy of this region & inguinal lymphatic.
 AIM :- to reduce the dose supplied to the genital organs, bladder, small
intestines and femur head , and to increase dose to primary tumor and
deep inguinal lymphatics .
we can use:
 AP/PA portal
 Wide anterior field – narrow posterior field
 4 field box technique.
 3DCRT
 IMRT
 Brachytherapy

29. RADIATION THERAPY
 Localization. Immobilization and Simulation.
 Immobilization and patient position.
• Supine with arm across the chest or prone in a belly board in an alpha-cradle or other
immobilization device , arms extended . If using the prone setup for primary field,
may consider supine positioning for the boost (which is typically away from small
bowel) so that desquamated patient may be positioned more comfortably.
Contrast agent and markers
I. Oral contrast to delineate the small bowel.
II. Barium enema to delineate the tumor.
III. IV contrast to delineate the tumor and LN.
IV. Anal marker to delineate the anus.
V. Wire to involved inguinal LN.
VI. Bladder should be moderately filled.

30.  Target volume definitions :
 GTV : primary tumor ,clinically positive LN seen on planning CT
(>1cm short axis diameter).
I. PET or MRI fusion typically aides in GTV delineation.
II. Colonoscopy / anoscopy reports may help determine tumor
location.
 CTV : LN at risk include common iliac, external iliac, internal
iliac, presacral, mesorectal , perianal, and inguinal.
I. CTV = 2.5cm expansion on primary tumor and 1cm expansion
on involved nodes.
 PTV :
PTV= CTV + 1cm

31.  Radiation therapy can be divided into three phases
 Entire pelvic field
 Cone down pelvic field
 Tumor bed only

32. INITIAL RADIATION FIELD (AP/PA) TO COVER THE
ENTIRE PELVIS
 ,,,,

33. RADIATION THERAPY
GUIDELINES:-
Whole pelvic field
Posterior-anterior:-
 Superior border: L5/S1 junction
 Lateral borders:- 1.5 cm lateral to the widest bony margin of the
true pelvic side walls. The lateral border extended to include the
lateral inguinal nodes. These nodes should be outlined with wire
in order to help identify them.
 inferior border:- minimum 2.5 cm below the anal verge or the
inferior extent of the primary tumor---- which ever is most
inferior.

34. GUIDELINES
laterals:-
Superior border:- same as posterior-anterior field.
Inferior border:- same as posterior-anterior field.
Posterior border:- 1-1.5cm behind the anterior
body sacral margin.
Anterior border:- posterior margin of the symphysis
pubis ( to treat only internal iliac nodes).
Blocking:-
Blocks are used to spare the posterior muscle and soft tissue behind
the sacrum, to reduce the amount of dose inferior to symphysis
pubis , and to decrease the amount of small bowel treated both
superiorly and anteriorly .

35. INGUINAL NODE INVOLVEMENT AT PRESENTATION

36.  InguinaL lymph nodes are potential site for metastatic
dissemination.
 Inguinal involvement is demonstrated to be a poor prognostic
factor.
 Benefit of prophylactic inguinal irradiation (PII) remains
questionable because of the potential serious long term wound
and lower extremity complications.

38. CONE DOWN FIELD BORDERS
Lower superior border to the bottom of S1 joint .
Inferior and lateral borders remain the same.

39. BOOST ( additional 9-14 Gy)
 Indicated for T2, T3,/ T4, N1,
 Use 2cm margin on GTV via AP/PA , 3 field ( opposed laterals and PA-
lowest anterior skin dose), or 4-field (AP/PA/laterals) approach.

40.  Inguinal nodes boost field:-
Nodes are situated 3-4cm below ant skin
surface.
Use CT scan image for verification of depth.
patient -- supine position
energy – electrons
portal - single anterior
sup. Border:- 2cm above ing ligament
inf. Borger :- 5cm below inguinal ligament
lateral border :- upto ASIS
Medial boder :- pubic tubercle

41.  GUIDELINES

42. VOLUMETRIC PLANNING GOALS
 95% of the PTV should receive at least 95% of the prescription dose.
 No portion of PTV should receive less then 85% of the prescription dose.
 99% of the CTV should receive at least 95% of the prescribed dose.
 0.1cc of the tissue is limited to 115% of the prescription dose.
 1.0cc of tissue ( or 5% of the PTV) is limited to 110% of the prescription dose.
 5cc of tissue ( 10% of the PTV ) is ideally limited to 105% of the prescription
dose.
 For external genitalia, attempt to limit
 50% to less than 20GY
 95% to less than 40Gy.
For iliac crest, may attempt to limit
 5o% to less than 30Gy
 95% to less than 50Gy

43. DOSE / FRACTIONAION ( NCCN)
 CTV to 45Gy / 1.8 Gy/fx.
 Field reduction to cone down after 30.4 Gy.
 T2,T3,T4, or N1 should receive an additional 9 to 14.4 Gy to the GTV via
boost field.
 T2 dose goal, 45 to 50.4 Gy.
 T3 dose goal , 54 Gy.
 T4 dose goal, 54- 59.4 Gy.
 Clinically negative inguinal LN should receive a minimum of 36 Gy,
measuring prescription depth on CT classically, 3cm has been used . (
this may under dose thicker patients.)

44. DOSE / FRACTIONAION ( NCCN)
 Clinically positive inguinal lymph node Should receive a minimum 45
Gy.
 Boost additional 5.4 to 9 Gy depending On size of LN and clinical
response.
 Clinically positive pelvic LN may be Boosted along with primary boost
field for an additional 5.4 TO 9 Gy above 45Gy CTV Dose depending
on LN size and clinical Response.

47. RTOG Ano rectal Target Volumes
Consensus Guidelines------- 2008 (RTOG 0529 protocol)
For Anal canal : Primary tumor
 GTV = All gross tumor + involved nodes ( clinical &
radiological )
 CTVA = 2cm proximal and caudad to gross disease. It should
include 2-2.5cm normal perianal skin around the anal verge.
it should include mesorectum, presacral and peri anorectal
tissue 2cm cephalad and caudad to gross disease.
1cm of posterior bladder/prostate/uterus.
 PTVA = 1cm expansion from CTVA in all directions ( trimmed
t0 3 -5mm to spare non target skin surface).
Dose to PTVA = 54-59.4 Gy

49. RTOG Anorectal Target Volumes
Consensus Guidelines for nodes------- 2008
 For anal canal : 3 elective nodal CTV
For nodes 8mm-1cm expansion around vessel ( ant.lat.= 1cm)
1) CTVa = internal illiac, presacral & perirectal nodes
2) CTVb = external iliac nodes
3) CTVc= inguinal nodes
Elective nodal CTV dose =45Gy

50.  CTVa ( internal iliac , presacral nodal regions)
Covers entire mesorectum, sup. From sacral promontary to
pelvic floor made by levator ani inferiorly .
Anterior surface of rectum posteriorly ( presacral),
iliopsoas /perirectal area laterally .
Mesorectum;- cylindrical , with cone shaped
tips in cranial and caudal direction . Starts at
level of sacral promontory at origin of
superior rectal artery & ending at the level
where leveter ani muscle inserts into the
rectal wall.

51.  CTVb ( for external iliac nodal regions )
cephalad;- upper end at SI joint ( division of common iliac
artery)
caudad- upper end of pubic rami ( bottom of internal iliac
artery )

52.  CTVc ( Inguinal nodal region)
 cephalad-: upper end of pubic
ramus, or at the inferior extent of
Internal obturator artery.
 Caudad : 2cm cuaded to
saphenous/Femoral junction
(SF junc. Lies at 4cm down & 4cm
lateral to pubic tubercle ,
LN is med. to vessel).

54.  ,,the

55. RTOG 0529: A phase 2 evaluation of dose- painted intensity
modulated radiation therapy in combination with 5FU and MMC
for the reduction of acute morbidity in carcinoma of anal canal.
Anal Cancer
Nodes
High risk node
DP-IMRT was associated with significant sparing of acute
grade 2+ hematogical and grade 3+ dermatologic and GIT
toxicity.

56. RTOG 0529 ( IMRT WITH 5FU and MMC)
VS . RTOG 98-11.
77% of patients experienced grade 2 or
higher gastrointestinal/ genitourinary
(GVGU) acute adverse event (AEs) that
were equal to that noted in the MMC
arm of RTOG 98-11(76%).
There were statistically significant
reduction in grade 3 or higher GVGU Aes
with IMRT , 21% vs 36% RTOG 98-11, and
grade 3 or higher dermatologic Aes, 21%
Vs 47% RTOG 98-11( p<.ooo1).
The use of IMRT with 5FU and MMC
resulted in significant reduction in grade 3+
dermatological and GU acute toxicity.

57. NORMAL TISSUE CONTOURING
No specific DVH recommendation for normal tissue by
RTOG, still investigation but
 Femoral head, iliac crest
 Small bowel up to 1cm beyond PTVA
 Large bowel including recto sigmoid
 Bladder
 External genitalia

58. DOSE PRESCRIPTION
 After target volume delineation, IMRT dose prescription as
follows:-
 PTVA ( primary)= 54-59 Gy
 CTV nodal = 45-54 Gy { 45Gy: uninvolved, 50Gy : < 3cm
54Gy : > 3cm) .
Dose constrains to normal tissue:-
Bladder 35 Gy < 50% vol
Large bowel 30 Gy <200cc vol
Small bowel 30 Gy < 200cc vol
Femoral head 30 y < 50% vol
Iliac crest 30 Gy < 50 % vol
External genitalia 20 Gy < 50% vol

59. BRACHYTHERAPY
Interstitial Brachytherapy is an ideal method by which to deliver conformal
radiation for anal cancer while sparing the surrounding normal structures
such as small intestine and bladder.
INDICATIONS:- as boost to EBRT / CCRT
 If Tumor volume does not exceed ½ circumference,
 5mm thick,
 5cm long i.e T1, T2, or small T3 lesion
Presence of lymph nodes in the rectal wall may not CI as long as they are located
in distal 8cm and responded well to CCRT.
Note;-
Brachytherapy alone is effective in controlling small lesions, but causes painful
reaction in half the patients and late necrosis in 10-15% , and therefore has to
be individualised.

60.  Target volume:-
It is the palpable & visible tumor with a safety margin of apparently normal
mucosa and skin of at least 5mm
To exactly localize target area – carefully DRE ( preferable EUA).
Timing of brachytherapy :-
2-8 week after External beam radiotherapy.
Sources and dose rate:-
Ir 192, HDR
Pre op instructions.
laxative 4-6 hrly , light low fiber diet, overnight fasting

61.  Technique:-
 Lithotomy position.
 Under GA / Spinal/ Epidural anesthesia.
 Foleys catheter.
 Use of template :-
 Papillon’s template
 Syed neblett template
 Modified syed template
 Modified anal template with an obturator.

62.  Implantation blindly by palpating the canal , done with stainless
steel needles 15cm long , 1.7-1.9mm diameter.
 The template is firmly sewn against the perineum .
 Needles are them implanted through the hole while a finger is
placed inside the lumen to verify that the needle do not penetrate
the lumen.
 Usually the needles are implanted 5mm beneath the anorectal
mucosa.
 Sometime it is difficult to insert needles in the recto vaginal
septum-- in that case it is easier to implant first in the RVS before
sewing the template to the perineum.
 Needles are inserted taking margin of 2-3 cm .

63.  A typical implant contain 5 needles spaced at 1cm, 5-7cm long
for a T1-T2 tumor and 6-7 needles , 7-8cm long for a small T3
tumor.
 In some cases if tumor is thicker than 1cm , 2 single plane
implant can be done.
 All needles are positioned at same depth and verification
made that needles do not retract when the patient’s legs are
retracted.
 Elastic tap dressing to fix the anal applicator – Y shaped

64.  Post implant ---- treatment planning
 CT film / orthogonal X rays.
 Catheter reconstruction.
 Target contouring.
 Prescription – 0.5 -1 cm from any chosen catheter.
 Check target coverage and dose to mucosa.
Dose -15-20 Gy @ 3 Gy / # twice daily at least 6 hrs apart.

65. Results
However problem with brachytherapy
22-27% -- sphincter necrosis
incontinence , stenosis , needing colostomy -10%
Hence newer approach---
Image guided brachy – TRUS guided brachy
to position the needles under image control
and assessing tumor extent
following by 3D planning and optimization.
no brachy brachy
Local control 61% 79%-83%
5 yr DFS 76% 82%

66. SIDE EFFECTS OF PELVIC RADIATION
 ,,,

67. SIDE EFFECTS OF PELVIC RADIATION

RADIATION FIELD
Radiation may hit the bladder
and rectum causing urinary
burning or frequency and
ano-rectal irritation and skin
burning.
High dose area.
In pre-menopausal women, radiation is likely to effect ovarian function and
should not be used if women is pregnant.

68. SIDE EFFECT OF TREATMENT
Early complication Late complication
Diarrhea Small bowel obustraction
Increased bowel frequency Persistent diarrhea
Dysuria Urinary incontinence
Dyspareunia
Acute proctitis Stricture
Malabsorption of fat, carbohydrate,
protien and bile salt.
Scrotol / perineal tenderness
impotence
Perineal dermatitis PIF

70. SALVAGE THERAPY FOR LOCAL RECURRENCE
 Most patient undergo an APR and a permanent colostomy is
established with creation of large pelvic floor defect.
 Tumors that invade local structure such as the vagina or prostate
should be resected with negative margins and often involves
multivisceral resection.
 The OS at 5 year following resection is in the range of 30% to
64%, with DFS rates in the range of 30% to 40%.
 The most important prognostic factor of survival after resection is
the status of the margin, and patients with negative margins (R0)
have up to 75% 5 year OS.

71.  Predictors of a poor OS outcome following surgery are
inguinal lymph node status, tumor size greater than 5cm,
adjacent organ involvement , male gender, and more
numerous co morbidities.

72. MANAGEMENT OF METASTATIC DISEASE
 Systemic chemotherapy for metastatic squamous cell
carcinoma of anus is generally similar to other metastatic
squamous histology , such as lung or head n neck cancer.
 Cisplatin & 5FU have been reported to achieve an 11%
complete response and 61% partial response rate.
 Hainsworth et al:- treated 60 patient with the combination of
carboplatin , paclitaxel & 5FU in a phase 2 study with an
overall response rate 90%.

74. Thank you