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Multimodality therapy for rectal cancer
Multimodality therapy for rectal cancer
Carlo AscheleOncologia Medica B
Istituto Nazionale per la Ricerca sul Cancro - Genova
Carlo AscheleOncologia Medica B
Istituto Nazionale per la Ricerca sul Cancro - Genova
Highlights in the management of gastrointestinal cancerRoma - May 21-22, 2010
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LOCAL FAILURE AND SITE OF RECTAL CANCER
tumor odds 95%site ratio c.i.
upper 0.43 0.24-0.77third
middle/lower 1.0third
p=0.004
Hermanek, 1995
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EFFECT OF RT ON LOCAL FAILURE AND SITE OF RECTAL CANCER
Dutch TME trial
cm from 2-y LR, % anal verge RT+TME TME p
0-5 5.8 10 0.05
5-10 1.0 10.1 <0.001
10-15 1.3 3.8 0.17
NEJM, 2001
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• SOTTO LA RIFLESSIONE PERITONEALE
• ENTRO 12 CM DALLA RIMA ANALE
età-sesso-altezza-peso-condizioni ginecologiche ed ostetriche
(nord vs sud europa)anteriore vs posteriore
INTERVENTO- RETTOSCOPIA (STR RIGIDO)-RMN
CHI?
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Locally advanced rectal cancerLocally advanced rectal cancer
• perirectal fat penetration
• adjacent organ invasion
• lymphnode infiltration
• mesorectal fascia (CRM) involvement
TRUS - CT scan - MRI
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Tx neoadiuvante del carcinoma del rettoTx neoadiuvante del carcinoma del retto
Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach
Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach
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Tx neoadiuvante del carcinoma del rettoTx neoadiuvante del carcinoma del retto
Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach
Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach
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IMPACT OF POST-OP CMTT3 and/or N+
IMPACT OF POST-OP CMTT3 and/or N+
local failure, % 5-y survival, %
GITSG 7175 11 54
Mayo/NCCTG 79-47-51 14 5386-47-51 9-11 60-70 (4-y)
INT 0114 14 64
NSABP R-02 9 62-65
Compared to surgery alone: ~ 50 ~ 15-25
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Copyright © American Society of Clinical Oncology
Gunderson, L. L. et al. J Clin Oncol; 22:1785-1796 2004
(NCCTG 794751, 864751; NSABP R01, R02; INT 0114. N=3791)
LOCALLY ADVANCED RECTAL CANCER. IMPACT OF ADJUVANT CMT ON
SURVIVAL
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Post-op chemoradiationPost-op chemoradiation
Compliance 46-76 %
Acute toxicity 26-53 %
(grade III-IV)
Long-term toxicity 46-56 %
NCCTG 79-4751 / 86-4751; GITSG 7175 ; NSABP R02; CAO/ARO/AIO 94
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CAO/ARO/AIO-94
R
50.4 GyCI FU TME FU x 4 cy
TME FU x 4 cy50.4 GyCI FU
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Post-op Pre-op p5-y outcome (n=394) (n=405)
Survival % 74 76 0.80 LF % 13 6 0.006
acute toxicity 40 27 0.001chronic toxicity 24 14 0.01
NEJM 2004
CAO/ARO/AIO-94CAO/ARO/AIO-94
TME SURGERY
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CAO/ARO/AIO-94
declared to sphincter-saving require APR surgery
Post 78 19 % (15/78)
Pre 116 39 % (45/116)
p 0.004
NEJM 2004
PRE-OP CHEMORADIATION: IMPACT ON SPHINCTER SAVING
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Standard treatment of locally advanced rectal cancer
Standard treatment of locally advanced rectal cancer
TME
45-50.4 Gy
CT
RT
T3-4 and/or N+
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Pre-op RT vs. surgery alone:Risk of local recurrence in phase III trials
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Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT
Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT
pCR, %
RT RT + CT
EORTC 5 14
FFCD 3 10
Bosset, NEJM 2006; Gerard, JCO 2006
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Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT
Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT
5-y LR, %
RT RT + CT
EORTC 17 8
FFCD 16 8
Bosset, NEJM 2006; Gerard, JCO 2006
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NSABP R-04
RT + Capecitabine +/- oxaliplatin
S
RT + CI 5-FU +/- oxaliplatin
R
N=1460
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R
RT 50.4 GyFU 225 mg/m2/day PVI OXA 60 mg/m2 weekly x 6
RT 50.4 GyFU 225 mg/m2/day PVI
TME
6-8wks
n=747
n=598
STAR-01
ACCORD
ypT0(N0)
16%
16%
p=0.94
R
RT 50 GyCAPE 1600 mg/m2/day
OXA 50 mg/m2 weekly x 5
RT 45 GyCAPE 1600 mg/m2/day
TME
6-8wks
14%
19%
p=0.11
ASCO ‘09
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Standard treatment of locally advanced rectal cancer
Standard treatment of locally advanced rectal cancer
TME
45-50.4 Gy
CT
RT
T3-4 and/or N+
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5–10%5–10%
Blunt dissection Blunt dissection TME TME
LR 20–40%LR 20–40%
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Fascial plane In mesorectum In/on muscularis
Dataset for colorectal cancer (2° edition), RCOP, 2007
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SURGERY QUALITY:EFFECT OF THE PLANE OF SURGERY ON
LOCAL RECURRENCE
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Circumferential resection margin
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Copyright © American Society of Clinical Oncology
Nagtegaal, I. D. et al. J Clin Oncol; 26:303-312 2008
LOCAL RECURRENCE AND CRM
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Standard treatment of locally advanced rectal cancer
Standard treatment of locally advanced rectal cancer
TME
45-50.4 Gy
CT
RT
T3-4 and/or N+
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FU-based adjuvant chemotherapy in rectal cancer patients. QUASAR
study (n=948). survival
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n = 3239
Effect of FU-based adjuvant chemotherapy in colon and rectal cancer patients. QUASAR studyRecurrence
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Effect of adjuvant FU-based chemotherapy in rectal cancer
patients included in the QUASAR studyRecurrence at any timen = 948
Lancet 2008; 371: 1503
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CAO/ARO/AIO-94
R
50.4 GyCI FU TME FU x 4 cy
TME FU x 4 cy50.4 GyCI FU
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Gunderson, L. L. et al. J Clin Oncol; 22:1785-1796 2004
(NCCTG 794751, 864751; NSABP R01, R02; INT 0114. N=3791)
LOCALLY ADVANCED RECTAL CANCER. IMPACT OF ADJUVANT CMT ON
SURVIVAL
Surg +/- RT
+ Adj Chemo
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ECOG 5204
* RT + bolus or CI FU ± LV, or Cape
or NSABPR 04
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JCO, 2007
Effect of adjuvant chemotherapy in pts with good and poor response to pre-op treatment
DF
S
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Tx neoadiuvante del carcinoma del rettoTx neoadiuvante del carcinoma del retto
Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach
Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach
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Standard treatment of locally advanced rectal cancer
Standard treatment of locally advanced rectal cancer
TME
45-50.4 Gy
CT
RT
Optimal for every LARC patient?
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n=188 (TRUS 130 / MRI 58)
22 % node + after pre-op CRT
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n 3-y LR 5-y LR
routine pre 674 4% 5%
selective post 676 11% 12 %
HR=0.39 (95% CI 0.27-0.58); p<0.0001
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MERKEL et al 2001
• pT3<5mm, N any
T2 and early T3 tumours <5mm have 85-90% 5 year cancer specific survival.
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STANDARD vs SELECTIVE APPROACH STANDARD vs SELECTIVE APPROACH
• almeno 7-8 cm dalla rima anale• infiltrazione grasso < 5 mm (MERCURY)• non evidenza di linfonodi patologici• margine radiale atteso di almeno 2 mm• chirurgo dedicato
• TME con mesoretto integro e CRM -• pT3a-bN0 (almeno 12 linfonodi negativi) • G1-G2
patients’ preference
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Rectal cancer:adjuvant / neoadjuvant treatment
Rectal cancer:adjuvant / neoadjuvant treatment
SURGEON
MEDICAL ONCOLOGIST
RADIOTHERAPIST
CUREQOL
PATHOLOGIST
STOMA THERAPIST NURSE
RADIOLOGIST