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