RADIATION ONCOLOGIST IN THE MAKING

1. CARCINOMA ANAL CANAL
DR MEGHA PREM
JUNIOR RESIDENT
DEPARTMENT OF RADIATION
ONCOLOGY GMC CALICUT

2. ANATOMY
• Length =3-4 cm
• Posterior wall >anterior wall
• BEGINS : Rectum enters puborectalis sling at
apex of anal sphincter complex
• ENDS: Squamous mucosa blending with the
perianal skin palpable intersphincteric
groove / outermost boundary of the internal
sphincter muscle

3. • ANAL SPHINCTER COMPLEX :
Palpable as anorectal ring on DRE & approx 1-2
cm proximal to dentate line

6. The lumen has folds of mucous membrane(anal
columns) produced by arterial cavernous
bodies (anal cushions) in the submucosa.
The columns are connected to each other at
their distal end by valves by transverse folds
anal valves

7. • Perianal skin :hair bearing skin elsewhere
• Anal verge: skin blends with a pale colored
zone

10. Lymphatic drainage
 The major lymphatic pathways flow to three
lymph node systems.
 The perianal skin, the anal verge, and the canal
distal to the dentate line drain predominantly to
the superficial inguinal nodes, with some
communications to the femoral nodes and to the
external iliac systems.
10

11.  Lymphatics from around and above the dentate
line flow with those from the distal rectum to
the internal pudendal, hypogastric, and
obturator nodes of the internal iliac systems.
 The proximal canal drains to the perirectal and
superior hemorrhoidal nodes of the inferior
mesenteric system.
 Intramural system
11

14. • Sexually transmitted viruses
• Immunosupression
• Tobacco
• Sexual pratices
• Multiple sexual partners in
homo/heterosexual relationships
• Unprotected anal intercourse

15. • Compromise of CMI reduces bodys ability to
prevent/eliminate infection by viruses such
as HPV
• INFECTION WITH IATROGENIC
HIV SUPRESSION IN
ORGAN TRANSPLANT PTS

16. •
• ANAL CANCER IS NOT A DESIGNATED AIDS
DEFINING CONDITION

17. High risk HPV virus 16 , 18 , 31, 33, 35

18. • BENIGN CONDITIONS SUCH AS FISTULAE ,
FISSURES & HEMORHOIDS DO NOT
PREDISPOSE TO CANCER
• C/C ANAL INFLAMMATION d/t IBD ALSO NOT
A RF

19. CLINICAL FEATURES

20. • NON SPECIFIC
• BLEEDING &PAIN M/C
• Awareness of an anal mass
• Pruritus
• Anal discharge

21. NATURAL HISTORY
• Spreads mostly by direct extension &
lymphatic pathways
• Overall risk of LN involvement is 25%

22. • Pelvic LN mets – 30%
• Superior hemorrhoidal -25%
• Ext iliac, obturator /hypogastric-30%
• Inguinal -16%

23. • LN METS INCREASE WITH FREQUENCY IN
• WITH PROGRESSIVE ENLARGEMENT OF
PRIMARY CANCER

24. • Extrapelvic mets – lungs, liver & paraaortic
nodes
• Relapse after initial treatment is common in
area of primary tumor & pelvic ln
• LRR -30%
• DF -20%

25. • PERIANAL CANCER
• I/L INGUINAL LNS M/C SITE OF METS
• EXTRAPELVIC METS UNCOMMON

26. PATHOLOGY
• WHO CLASSIFICATION
• INTRAEPITHELIAL INVASIVE
• The terms basaloid, cloacognic &transitional
• all grouped as SCC
•

28. • THE OUTCOME OF ALL HISTOLOGIES ARE
POORER STAGE FOR STAGE THAN IT IS FOR
SCC

30. STAGING & WORKUP
• History & physical examination
• PRIMARY TUMOR EXTENT
• ANAL SPHINCTER COMPETENCE
• VAGIANL FISTULAS
• ANOGENITAL WARTS
• INGUINAL LN

31. • BIOPSY
• PROCTOSCOPY
• FNAC / excision biopsy of enlarged LN
clinicaly/ radiologicaly
• CERVICAL CANCER SCREENING- association of
anal cancer & HPV

32. HIV TESTING
•
• IDENTIFICATION OF HIV STATUS IMPROVES
CLINICAL OUTCOMES

33. •
• MRI MOST ACCURATE METHOD FOR
ASSESSING PRIMARY TUMOR & PELVIC
NODES

34. • Thoracic , abdominal & pelvic CT & pelvic MRI
• To identify lung/liver mets / enlarged LN
• SKELETAL STUDIES NOT INDICATED IN THE
ABSENCE OF FOCAL SYMPTOMS

35. • PET CT & INGUINAL SLNB to identify inguinal
ln mets & refine RT plans

36. •
PET CT CANNOT REPLACE DIAGNOSTIC CT
• RECTAL ULTRASOUND TO DETERMINE DEPTH
OF TUMOR INVASION IS NOT USED IN
STAGING

39. “Direct invasion of the rectal wall, perirectal skin,
subcutaneous tissue, or the sphincter muscle(s) is
not classified as T4.”
39

42. PROPHYLATIC VACCINES
• Routine use of 4 valent/9 valent vaccine in
boys 11-12 yrs & females 13-18 yrs
• Also in men who have sex with men who have
not been previously vaccinated

43. Prognostic factors
• TUMOR FACTORS
• D/s confined to the pelvis : T STATUS most
useful predictor of local control, sphincter
preservation, and survival
• MOST ADVERSE FACTOR IS PRESENCE OF
EXTRAPELVIC METASTASIS
43

44. • TUMOR FACTORS HAVE MOST PROGNOSTIC
VALUE
44

47. • PATIENT FACTORS
• NOT CONSISTENT
• Age, PS, baseline HB LEVEL & race
• Pts continuing to smoke
• HIV POSITIVE PTS : High viral load, low CD4
counts & AIDS prognostic of poor LC & OS
47

48. • EARLY RESPONSE & EXTENT OF RESPOMSE TO
CHEMORADIATION WERE CORRELATED WITH
SURVIVAL

49. Treatment
 Historically Abdominoperineal resection
(APR) was the primary treatment modality
 Local relapses were common
 5 year overall survival 40 – 60 %
 Now reserved as salvage for patients who fail
radiation or who had prior pelvic RT
49

53. United Kingdom Coordinating Committee for Cancer Research
(UKCCCR) ACT I (1987-1994)
577 patients with SCCof the anal canal or anal
margin
40%- T3/T4, 20% LN+, 2% extrapelvic metastases
53
• 45 Gy / 20-25 #RT alone
• 45 Gy / 20-25 #
• 5FU 1000 mg/m²/day,
CI for 4 days, 1st & final
weeks of RT
• Mitomycin 12 mg/m²
IV bolus day1
ChemoRT
Reassessed clinically 6 weeks
after treatment.
Primary tumor not regressed by
at least 50%  APR
Otherwise, the patients received
an additional 15 Gy in six
fractions by a perineal field or
25 Gy over 2 to 3 days by
iridium-192 implant

54. 3-Year Results
54
RT RTCT P value
Locoregional
control
39% 61% <.0001
Cause specific
survival
61% 72% o.o2
Overall survival 58% 65% o.25
There were six (2%) deaths due to treatment in the combined-modality arm and
two (0.7%) in the irradiation-alone arm. Acute toxicity, other than hematologic,
was considered comparable in each group

55. 55
RT RTCT
12 year LRC 41% 66%
Colostomy free
survival
20% 30%
Overall survival 27% 33%

56. EORTC
103 patients with advanced cancers of the
anal canal
85% - T3 or T4 cancers and 51% -abnormal nodes
56
• RT 45 Gy/25#RT alone
• RT 45 Gy/25#
• Chemo 5-FU (750 mg/m2/day for 5 days) in
weeks 1 and 5 of RT
• mitomycin (15 mg/m2) by bolus IV injection
on day 1 of the first course of 5-FU only.
ChemoRT
After 6 weeks,
boost irradiation
of 15 Gy (if CR)
or 20 Gy (if PR)
was given by
external-beam
or interstitial
irradiation

57. RT RTCT P value
Local control 50 68 SS
Colostomy free
survival
40 72 SS
Overall survival 65 70 NS
57
J Clin Oncol 1997;15:2040-2049.
Chemo RT improves local control and colostomy
free survival , no impact on overall survival, with
comparable toxicity

58. SHRINKING FIELD
• Treatment using at least two phases, where
latter phases use smaller fields than the
former phases.

59. • Shrinking fields are used when different volumes
within the patient are thought to contain different
quantities of tumour stem cells, in an effort to reduce
the volume of normal tissue treated to high dose.
• The initial fields distribute dose to all areas of concern,
up to the dose required in the areas thought to be at
'least risk'.
• Smaller fields are then used to increase the dose to the
smaller volume believed to be at higher risk.
• It is possible to have several phases with shrinking
fields between each

60. • Anal cancer may be treated with a three phase
technique:
• Phase I uses large fields to treat all the nodal
regions at risk (internal iliac, presacral, and
inguinal nodes) as well as any involved nodes and
the primary tumour
• Phase II constricts the fields to treat the involved
nodes and anal canal
• Phase III delivers the final few treatments to the
anal canal only

61. SIMULATION
• Supine with arms across chest
• Prone in a alpha cradle / other immobilization
devices
• Wires for inguinal LN
• Marker near growth
• Vaginal dilators
• Bladder moderately filled

62. • All patients will be treated with a daily dose of
1.8 Gy, 5 days per week to a dose of 45 Gy in
25 Fx in 5 to 6.5 weeks (< 10-day break, as
indicated, for skin intolerance)

63. • Patients with T3, T4, or N+ lesions or T2
lesions with residual disease after 45 Gy
should receive additional 10-14 Gy (2 Gy per
Fx) to a reduced field

65. RTOG 9811

66. AP PA
Upper border – L5-S1 junction (includes the common iliac,
upper presacral, and rectosigmoid nodes )
 This border moved down (after 30.6 Gy) to the
lower end of the sacroiliac joints (encompassing only the
perirectal, lower presacral, and internal iliac nodes and, if the volume is
sufficiently wide, the lower external iliac nodes) in order to lessen
the risk of radiation enteritis
Lower border
 3 cm below the anal verge or the inferior extent
of the primary tumor whichever is most inferior

69. Lateral borders
The position - depends on the desirability of treating a
continuous homogenous volume or the preference to
minimize irradiation of the femoral head and neck
Options include
1. Anterior and posterior fields of equal size encompassing
the inguinal nodes
69

70. . Anterior and posterior fields of equal size, but
restricted to include the medial borders of the pelvis
only (1.5 cm lateral to bony pelvis) and the inguinal
nodes being treated by anterior electron beams
matched to the photon fields

71. 4 FIELD
• The lateral border of the AP field shall include
the lateral inguinal nodes as determined by
bony landmarks
• The lateral border of the PA field shall extend
2 cm lateral to the greater sciatic notch

72. • If utilized, the target volume includes all areas
at risk (pelvis, anus plus margin, inguinal
nodes, external iliac nodes)
• AP and lateral fields should be shaped such
that the lateral inguinal nodes are included in
these fields. The inguinal nodes should not be
included in the PA field

73. Deliver 14.4 Gy/8 Fx for a total of 45 Gy at 1.8
Gy/day
After 30.6 Gy has been given to an initial pelvic
field

74. • the superior border shall be dropped to the
upper level of the greater sciatic notch
(inferior border of SI joints). The reduced
pelvic field shall be continued to 45 Gy at 1.8
Gy per day

75. • (For all T3, T4, and N+ patients or T2 patients
with residual disease after 45 Gy)

76. • After 45 Gy, boost fields shall be utilized to
encompass the original primary tumor volume
plus a 2.0 to 2.5 cm margin

77. • Treatment field options include reduced
multiple photon fields with the patient in
supine position (i.e., 4-field or PA and laterals
with wedges) or a direct photon or electron
perineal field with the patient in the lithotomy
position

78. • An additional 10-14 Gy (2 Gy per Fx) shall be
delivered (total 55-59 Gy). If pelvic nodes are
grossly involved, they should be included in
the final boost field if small bowel can be
avoided

79. Posterior Pelvis Techniques
• The anal canal and posterior pelvic nodes may be treated by multiple
beam techniques.
• The volume irradiated is reduced compared with that of whole-pelvis
techniques and dose to anterior perineum and external genitalia is less
• Commonly 3/4-field techniques, such as a direct posterior or AP-PA fields
and opposed lateral beams
79

80. 80

81. • Inguinal nodes receive only exit dose ( 30-40%
0f prescribed dose)
• Inguinal nodes boosted concurrently with
electron to bring dose up to 100% of
prescribed dose

82. Boost fields
 Target volume for boost field is the original primary tumor volume/node
plus a 2-2.5 cm margin
 Options include
1. External-beam therapy with a perineal field, or by multifield
techniques
2. Interstitial therapy
82

83. Brachytherapy
 Brachytherapy is used for boosting T1 - 2, and
small T3 tumors which have responded well to
chemoradiation.
Contraindications
 Insufficient tumour response after primary chemoradiotherapy
 Lesions involving more than the half the circumference of the anal canal,
because there is a higher risk of stenosis and necrosis,
 Lesions of which the proximal limit is not palpable and thus cannot be
implanted.
 T4 tumours (however, in T4 tumours extending into the anovaginal septum
and responding to external beam radiotherapy, brachytherapy is possible).
83

84.  A small acrylic template is used to space a
semicircle of hollow needles in place and are
after loaded with Ir-192 to deliver 15-20 Gy at 1
Gy/h to a depth of 0.5 cm as a boost to the anal
canal primary site
 A typical implant contains 5 radioactive lines
spaced at 1 cm, 5 - 7 cm long for a T1 - 2 tumor,
and 6-7 needles, 7 - 8 cm long for a small T3
tumor
84

85. CHEMOTHERAPY REGIMENS
• 5 FU +MITOMYCIN +RT
• Continuous infusion of 5FU 1000mg/m2/d IV
D1-4
• MITOMYCIN 10mg/m2 bolus d1 & d29

91. rtog

93. The primary tumor planning target volume
(PTV) receives 54 Gy (red colorwash), and the
elective nodes 45 Gy (blue colorwash). An
involved right-sided inguinal node was dose-
painted to 50.4 Gy (orange colorwash)

94. • GTV A = primary anal tumor(examination,
imaging & endoscopy)
• GTVN 50=metastatic nodal regions ≤3 cm
• GTVN 54 =metastatic nodal regions >3 cm
• CTV =2.5 -1 cm (manually edited to avoid
overlap into nontarget muscles or bone,
considered natural barriers to tumor
infiltration)

95. • Elective nodal CTVs (mesorectum, presacrum,
bilateral internal and external iliac, and
bilateral inguinal)
• PTV =CTV+1cm
• PTVs were not edited in any way except to
avoid overlap with the skin.

96. • Normal structures (small bowel, large bowel,
bladder, femoral heads, iliac bones, perianal
skin, genitalia) were also contoured, the bowel
as individual loops to 2 cm above the most
superior extent of the target CTVs

100. • Acute 3+ hematologic toxicity rates appear
similar across RTOG 9811 (62%), RTOG 0529
(58%) which suggests that pelvic bone marrow
is similarly suppressed by chemoradiation,
regardless of radiation approach

104. MMC vs CDDP

106. RESULTS
• THE REPLACEMENT OF MITOMYCIN WITH
CDDP IN CHEMORT DOES NOT AFFECT THE
RATE OF COMPLETE RESPONSE NOR DOES
ADMINISTRATION OF MAINTENANCE
THERAPY DECREASE THE RATE OF D/S
RECURRENCE

107. ROLE OF INDUCTION THERAPY
• ACCORD 03 NO BENEFIT OF INDUCTION CT
• A RECENT RETROSPECTIVE ANALYSIS
INDUCTION CT IS BENEFICIAL FOR T4 D/S

108. Evaluation of planned treatment breaks during radiation therapy
for anal cancer: update of RTOG 92-08.
 RTOG 92-08 began as a single arm, Phase II trial consisting of RT + 5-FU +
M with a mandatory 2-week break
 High rate of colostomy  trial re-opened in 1995  evaluated the same
treatment regimen without a mandatory treatment break
 Each cohort of RTOG 92-08, the mandatory treatment break and
continuous radiation schedule, were compared to Mitomycin-C arm of
RTOG 87-04.
The study was not designed to compare the two RTOG 92-08 cohorts to
each other
108
Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):114-8. Epub 2008 May 9.

109. RT+5FU+M
With mandatory
treatment break
RT+5FU+M
Without mandatory
treatment break
109
RTOG 92 08 cohorts (59.4 Gy)
Compared with Mitomycin arm
of RTOG 8704 (45 – 50.4 Gy)

110. Conclusion
 Late toxicity was low in both cohorts.
 5-year Disease Free Survival and Colostomy Free Survival in mandatory
treatment break arm - lower than reported on RTOG 87-04
 DFS and CFS in the no mandatory treatment break cohort were
comparable to other reported series.
 Treatment breaks in anal canal treatment should be kept to a minimum.
110

111. 111

112. 112

113. Role of surgery
• LOCAL EXCISION – 2 SITUATIONS
• SUPERFICIALLY INVASIVE ANAL CANCER : anal
cancer that has been completely excised with
≤3mm BM invasion & a max horizontal spread
of ≤7mm
• T1N0 WD perianal cancer MARGINS
RECOMMENDED 1CM

114. • CANCER IS AN ACCIDENT BUT NOT THE END
OF THE ROAD