Download - Anal cancer 2008
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Anal cancerAnal cancer20082008
Anal cancerAnal cancer20082008
John Northover
St Mark’s Hospital
M62 course, 2008
John Northover
St Mark’s Hospital
M62 course, 2008
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Anal cancer update
The disease
• Rare - 1% of bowel cancers
• First GI tumour to become ‘non-surgical’ II
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Anal cancer update
Peak of development activity - 1990s
Viral aetiology and treatment
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Anal cancer update
The development of therapy
• Surgery alone
• Radiotherapy alone
• Combined modality therapy
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Anal cancer update
Surgical results, St Mark’s
Abdominoperineal excision:
• Margin, 72 cases, 5YS = 55%• Canal, 123 cases, 5YS = 58%
Pinna-Pintor et al, 1989
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Anal cancer update
Radiotherapy results
• 72 patients:
• 67% 5 year survival
• 75% anal function retained
Papillon et al, 1985
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Anal cancer update
The coming of combined therapy
• Nigro began in 1974
• Three inoperable cases
• Complete remissions
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Anal cancer update
Optimum non-surgical therapy?
RADIOTHERAPY ALONE
or
CHEMO plus RADIOTHERAPY
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Anal cancer update
ACT I trial - patient entry
Randomised 577 patients
331 surgeons, 162 radiotherapists
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Anal cancer update
UKCCCR trial - side effects
Radiotherapy alone Chemoradiotherapy
62% 65%
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Anal cancer update
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5 6time (yrs)
% e
ven
t fr
ee
CMTRadiotherapy
ACT I - Local treatment failure
111/285125/283
P<0.001, RR=0.57 (0.45, 0.73)
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Anal cancer update
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5 6time (yrs)
Cau
se-s
pecifi
c s
urv
ival
CMTRadiotherapy
ACT I - Deaths from anal cancer
P=0.02, RR=0.71 (0.53, 0.95)
77/285105/283
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Anal cancer update
ACT I - Disease at death
RT CM
Locoregional only 48 38
Distant ± LR 48 29
Other 7 4
TOTAL 105 77
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Anal cancer updateSurgical salvage ACT I
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Anal cancer updateSurgical salvage ACT I
• 265/577 (46%) local failures
• 143/265 (54%) radical surgery
• 10/143 (7%) no cancer in specimen
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Anal cancer updateSurgical salvage ACT I
• 67/133 (50%) alive at 2.1 years
• 58/133 (44%) further pelvic rec.
• Perineal wound healing -median 2 m.
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Anal cancer updateSurgical salvage ACT I - ARE
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5 6time (yrs)
% e
ven
t fr
ee
CMTRadiotherapy
P>0.5 , RR=0.89 (0.54, 1.47)
22/4051/89
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Anal cancer updateLessons from ACT I
• CMT established
• High local failure rate (33%)
• Less distant spread with CMT
• Surgical salvage disappointing
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Anal cancer updateACT II - the questions
• Better primary chemotherapy?
• 5FU + MMC
• 5FU + CDDP
• “Adjuvant” therapy?
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Anal cancer updateACT II Trial - Protocol
No maintenance
5FU & MMCRADIOTHERAPY
Maintenance5fu & CDDP
5FU & MMC RADIOTHERAPY
No Maintenance
5FU & CDDPRADIOTHERAPY
Maintenance5FU & CDDP
5FU & CDDPRADIOTHERAPY
Confimed anal cancer
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Anal cancer update
Intra-epithelial neoplasia
Normal AIN I AIN II AIN III
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Anal cancer update
The main target
AIN III
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Anal cancer update
AIN - why does it matter?
• Premalignant
• Multifocal
• High risk groups
• Increasing incidence
• Anal ca. incidence rising
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Anal cancer update
Aetiology of AIN
• HPV infection
• Mainly types 16, 18, 32, 33
• Integrates into genome
• Genetic instability
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Anal cancer update
High risk groups
• Immune deficiency
• Pathological - HIV
• Therapeutic - transplant recipients
• MSM
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Anal cancer update
Relative prevalence of AIN
• ‘Normal’ haemorrhoidectomy:
• 3 in 8153 specimens (0.04%) Lemarchand 2004
• HIV+ men:
• 20 in 103 men (19.4%) Kreuter 2005
x500 INCIDENCE
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• ± universal HPV infection (95%)
• Majority have AIN (81%)
• HAART does not protectPalefsky 2005
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Anal cancer update
Risks in other groups
MSW
MSS
WSN
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Anal cancer update
Men who have Sex with Women
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Anal cancer update
Men who have Sex with Sheep
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Anal cancer update
Women who have Sex with Nobody
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Anal cancer updateSymptoms
• None
• Pruritus
• Bleeding
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Anal cancer updateAnoscopy
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Anal cancer update
Aceto-white lesions
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Anal cancer update
Diagnosis of AIN III
Corkscrew vessels (AIN III)Corkscrew vessels (AIN III)
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Anal cancer update
Risk of progression
Nottingham study
• 35 patients AIN III
• FU 63m (14-120)
• 28 immune competent - no Ca
• 6 immune deficient - 3 (50%) CaScholefield et al 2005
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Anal cancer update
Surveillance - in known cases?
• AIN I/II• None in immune competent
• 6-12m in immune deficient?
• AIN III• 6-12m in all - or immune def. only?
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Anal cancer update
Should there be screening?
• High risk groups• MSM, HIV+ ??
• What marker lesion?• HPV type, AIN stage?
• What tests?• Anoscopy, HPV type, histology?
• What intervention?
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Anal cancer update
Should there be screening?
• x20 anal cancer in MSM
• AIN highly prevalent
• ? Natural history
• ? Improved outcomes
• Rx morbidity and recurrence
CASE NOT MADE
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Anal cancer update
Medical management
Surgery:• may be difficult (cf cervix)• high recurrence rate
Medical:• Imiquimod• Vaccination
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Anal cancer update
Medical management
Imiquimod
• Introduced 1997• Cytokine induction• Stimulates cellular immunity• Approved for anogenital warts• ? Role in neoplasia (VIN)
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Anal cancer update
Surgical options
• LE ± graft ± faecal diversion
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Anal cancer update
Surgical options
• LE ± graft ± faecal diversion
• Recurrence rates
• Surgical morbidity
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Anal cancer update
Excision and Thiersch graft
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Anal cancer update
Excision and Thiersch graft
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Anal cancer update
Excision and Thiersch graft
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Anal cancer update
Excision and advancement flaps
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Anal cancerAnal cancer20082008
Anal cancerAnal cancer20082008
John Northover
St Mark’s Hospital
M62 course, 2008
John Northover
St Mark’s Hospital
M62 course, 2008