Download - Anal Cancer Karin Haustermans
Anal Cancer Karin Haustermans Case study 47-year old (active
smoker, alcohol use, history of sexual high-risk behavior): 2006:
peri-anal condylomata acuminata (genital warts), high-grade
dysplasia 2012: presumed recurrence, re-resection elsewhere with
positive margins. However, pathology showed well-differentiated
SCC, incompletely resected. Clinical examination is highly suspect
for residual tumor near anal margin. CT from referring hospital
shows tumor in posterior anal canal, with a possible adenopathy
right inguinal. Further staging: cT1N0M0 T2-weighted MRI confirms
hypointense tumor (1.2 cm LL x 1.2 cm AP x 1.9 cm CC) in posterior
anal canal, with invasion of the internal & external sphincter.
No adenopathies. Diffusion-weighted MRI shows hyperintense lesion
in posterior anal canal on b1000 images, highly suggestive of
malignancy. FDG PET-CT: uptake limited to tumor in anal canal; cN0,
cM0. Treatment? 47-year old with cT1N0M0 well-differentiated SCC of
anal canal: Proposal in referring hospital: abdomino-perineal
resection (APR) with permanent colostomy. Second opinion at Leuven:
concomitant chemoradiotherapy. 45 1,8 Gy to pelvis posterior (Arc)
with concomitant 5-FU & MMC. Brachytherapy boost is scheduled
for 1 week after CRT (gap < 2w, OTT < 53d). Incidence and
risk factors
Rare disease Annual incidence: 1/ (USA) Incidence is increasing
over the last 25 years 5 year survival: +/- 60% Risk factors: HPV
(in 80% of the patients), HIV, (HSV) Immune suppression (transplant
recipients) Cigarette smoking Previous malignancies
(gynaecological, lymphoma, leukemia) Pretreatment evaluation
Medical history Symptoms (sphincter competence) Predisposing
factors (history of HPV and HIV infections) Associated disease
(CIN) Comorbidities possibly impacting on treatment Disease staging
To determine: Primary tumor : Nodes
Tumor location Tumor size Nodal involvement Distant Metastasis
Primary tumor : Clinical examination, preferably under anesthesia
Nodes Clinical examination Fine needle aspiration inguinal
Radiological TN staging: MRI M staging : CT Note : FDG-PET,
inguinal sentinel N biopsy : investigational FDG-PET/CT
comparison
Identification % T1-2 T3-4 N pelvis N inguinal CT 48 83 20 22 PET
86 100 37 FDG-PET > CT ~ 17 % Consequences T : better volume
definition N : tailoring RT volumes Cotter et al, IJROBP 2006 ;
Trautmann et al, MIB 2005 FDG-PET/MRI comparison
Bhuva et al, Annals of Oncology 2012 Methods: We looked at patients
treated radically for anal cancer at Mount Vernon Cancer Centre
(UK) between 2009 and Eighty-eight patients underwent treatment
according to data-based coding records of which 46 had positron
emission tomography (PET)/CT scans. Notes were unavailable for
three patients. We compared staging following conventional
modalities (DRE, MRI and CT) and PET/CT scans for these 43
patients. In 18 patients, the PET/CT stage differed from MRI. Of
these, 2 cases showed differences in T staging alone (both
upstaged), 13 showed a change in N staging alone (8 upstaged, 5
downstaged), 1 showed a change in T and N staging (T downstaged, N
upstaged) and 2 showed a change in M staging alone (upstaged)
(Figure 1). PET/CT altered the stage in 42% of patients but changes
in subsequent management were not implemented. All patients still
underwent radical chemoradiotherapy according to the planned
protocol. The majority of changes involved upstaging disease.
Treatment of localized anal cancer
Prior to mid-1980s: abdominoperineal resection as standard
treatment Nigro et al: XRT 30 Gy + 5 FU Mito C (3 patients) 2 AP
resection tumour sterilised 1 refusing surgery in complete clinical
remission No need for APR? Nigro et al, Dis Colon Rectum, Mid
eighties first phase III trials
Arm A Arm B US (RTOG8704) XRT+ 5 FU XRT+ 5 FU-Mito C EORTC 22861
XRT XRT + 5 FU-Mito C UKCCCR Approach of Nigro further evaluated in
3 fase III radomized controlled trials Patient
characteristics
US (RTOG 8704) Patient characteristics Treatment scheme NACT: No
CRT schedule: 45 -50,4Gy 5FU 1000 mg/m;D1-4, 29-32 +/- MMC 10mg/m;
D1&29 4-6 weeks gap If residual disease: 9 Gy
boost/5FU/cisplatin100 mg/m Glynne-Jones, IROBP 2011 US (RTOG-8704)
XRT+ 5 FU XRT + 5 FU-MMC p value Complete response 86%
92,2% Colostomy- free survival 59% 71% 0,014 Colostomy rate 22% 9%
0,002 DFS 51% 73% OS 78,1% 0,31 Glynne-Jones, IROBP 2011 Patient
characteristics
EORTC 22861 Patient characteristics Treatment scheme NACT: No CRT
scheme: 45 Gy/ 25 fx +/- 5FU 750 mg/m ; D1-5, 29-33 MMC 15mg/m; D1
6 weeks gap 15 Gy (CR) or 20 Gy boost (PR) Glynne-Jones, IROBP 2011
EORTC 22861 XRT XRT + 5 FU-MMC p value Colostomy-free
survival
Complete response 54% 80% Local Failure rate (5 years) 50% 32% 0,02
Colostomy free survival Increase by 32% (see graph) 0,03 DFS (5
years) Estimated improvement by 18% OS 58% 0,17 Glynne-Jones, IROBP
2011 Bartelink, J Clin Oncol May;15(5): (artikel niet beschikbaar
online, pas vanaf 1999 toegang, dus helaas ook geen mooiere figuur
gevonden) Colostomy-free survival Toxicities in phase III
trials
AcuteHaematologicalsignificant Diarrhoeasignificant
Skin/mucositissignificant Late ? Phase III Results: Summary
Local control Colostomy-free survival DFS Conclusions from early
randomised trials
CMT standard as first line treatment LeveI of Evidence I Needs
expertise Unsolved questions CRT for early stage (and very early)
RT doses Gap
Management of inguinal region Type and scheme of CT Optimizing RT
delivery Boost with brachytherapy ?
LF % Late tox Grade 4% RT alone 18-45 10-20 RT + brachy 17-20 2-15
Ref. Opzoeken, nergens gevonden, ik veronderstel nog niet
gepubliceerd... Gepresenteerd door Prof. JF Bosset (Salmon,
Eschwege, Schlienger, Papillon, Wagner, Allal, Peiffert) No pts
Sphincter necrosis OS/DFS/CFS RT CT 60 1 No RT+brachyCT 102 8
(Peignaux) Boost with brachytherapy ?
LOCAL RECURRENCE OVERALL SURVIVAL Hannoun-LeviIJROBP patients
(links) Fig. 2. Overall survival according to the boost technique:
brachytherapy (BCT) vs. external-beam radiotherapy (EBRT) (C).
(rechts) Fig. 3. Cumulative rate of local recurrence for the whole
population (A), regarding the boost technique: brachytherapy (BCT)
vs. external-beam radiotherapy (EBRT) (B) Hannoun-Levi, IJROBP 2011
Management of the inguinal region
Involvement % OverallT1-2T3-4 25< Risk increased T below dentate
line Pelvic nodes Anal margin involved Pic factor : 5-year survival
~ 50 % Management of inguinal region (CMT)
N negative ENI 36 Gy if T within 1 cm from anal margin Invasion of
anal margin Pelvic nodes involved N positive CMT 60 Gy CORS-03
study Ortholan, IJROBP 2012 CORS-3 study Ortholan, IJROBP 2012
Ortholan, IJROBP 2012
Fig. 4. Cumulated rate of inguinal recurrence (A), overall survival
(B), and disease-specific survival (C) curves according to
prophylactic inguinal irradiation (Kaplan-Meier method). Ortholan,
IJROBP 2012 Salvage surgery Note : delayed CR possible up to 4
months
if incomplete clinical response 16 weeks after CRT True cut biopsy
AP resection well-trained team Salvage surgery after failed
chemoradiation therapy has a reasonable chance of cure. Favorable
independent prognostic factors include recurrence ( vs.
persistence) after chemoradiation (when salvage is potentially
curative), absence of nodal disease at salvage, and negative
margins. Salvage inguinal lymph node dissection after failed
chemoradiation therapy also is potentially curative. Akbari. Dis
Colon Rect 2004 Tournier, Rangeard, Roohipour, Das
Predictors of outcome LRFT 4 cm N positive RT incomplete RT
interruption Early T response SurvivalT 4 cm Tournier, Rangeard,
Roohipour, Das Current schemes ENI : 36 Gy T doses : 50.4 no gap
59.4 gap (2 weeks)
CT : MMC Capecitabine 22861 and 22953 comparison of results 3 year
estimated rates (%)
Gap : is it detrimental? 22861 and comparison of results 3 year
estimated rates (%) Gap 6 wGap 2 w No patients Local control
Colostomy-free S Overall S Severe toxicity free S scheme considered
as new standard by EORTC Group Gap : is it detrimental ? No gap or
2 weeks 2w RT Gap (weeks)
5 y LF % 5 y CF % RTOG (T1-T4) 45 4-6 9 7 71 RTOG 9208 (T1-T4) 36 2
24 29 58 15 +5 EORTC (T2-T4) 6 32 72 EORTC (T2-T4) 35 12 80 2w No
gap or 2 weeks Gap : is it detrimental ? Pooled analysis RTOG 87-04
& RTOG 98-11
Links (Hannoun-Levi, IJROBP 2011)Cumulative rate of local regarding
the overall treatment time (