Rectum Adenocarcinoma Quality of conformal radiotherapy Impact for the surgeon P. Scalliet & K. Haustermans Fifth Belgian Surgical Week May 6th, 2004, Oostende
SOR rectum adenocarcinoma Indication of radiotherapy Decreases local relapse by 3/4. A local recurrence is a major threat to QoL. Better anal preservation. Secundary dissemination is prevented. Survival is perhaps improved.
Low dose Overall mortality with and without radiotherapy (pre-op or post-op op). (Lancet,, 2001) high dose 0.5 % P = 0.9 9.8 % P = 0.04 5.4 % P = 0.06
Effect of RT on risk of isolated local relapse in 11 trials pre-op op. and 7 trials post-op op. subgroup analysis par sous-groupes according tp BED. (Lancet,, 2001)
Non-rectal cancer death was increased in RT series (pre- and post-op op). It is thought to be technique dependant (Lancet,, 2001) 51.9 % 43.6 % 2p = 0.00002 17.9 % 14.6 % 2p = 0.001
Swedish Rectal Cancer Trial Preop RT Surgery P - value Local Failure 12 % 27 % < 0.001 5-Yr Survival 58 % 48 % 0.04 NEJM, 1997
Analyse critique de la méta-analyse analyse The Swedish trial cannot be considered optimal regarding the surgical technique (and pathology?). Is RT only good enough to compensate for lousy surgery?
CKVO 95 04 TME + RT Trial 5 x 5 Gy TME T1-3 TME * * = postop 50 Gy if margins positive
CKVO 95 04 TME + RT Trial
Results of multivariate analysis of local recurrence among the 1748 eligible patients with a macroscopically complete resection (N Eng J Med, 2001, 345: 638) variable Hazard ratio P value (95% CI) Treatment group <0.001 RT + surgery 1.00 < 0.001 Surgery 3.41 (2.05-5.7) Distance from 0.03 anal verge 10.1-15 cm 1.00 5.1-10 cm 2.13 (1.13-4.01) 0.02 Š 5 cm 2.78 (1.22-6.31) 0.02 TNM stage <0.001 Stage I 1.00 Stage II 3.44 (1.26-9.39) 0.02 Stage III 9.69 (3.89-24.2) <0.001 Stage IV 16.2 (5.4-48.6) <0.001 Type of resection is not a significant parameter
CKVO 95-04 RT + S S p Overall post-op complications 48 % 41 % 0.008 Blood loss 1100 ml 1000 ml <0.001 Mortality 4 % 3.3 % ns. Median operating 180 min 180 min ns. time Median hospital stay 15 d 14 d ns. Marijnen et al, JCO 2002, 20: 817
CKVO 95 04 TME + RT Trial (update( update) % LF % 4y survival % DM TME 11.3 63.5 28.2 RT + TME 5.8 64.3 25.5
Early morbidity CKVO 95-04 14 patients had to stop preop RT due to neurotoxicity Blood loss 1000 ml (RT-TME) vs 900 ml (TME) (p<0.001) Perineal wound complications 26 % (RT-TME) vs 18 % (TME) (p=0.05)
The Lyon experience 13 times 3 Gy Short Interval Long Interval Clinical response 53.1% 71.7% (p= 0.007) Path Downstaging 10.3% 26% (p= 0.005) SphincterSS 68% 76% (p= 0.27) Francois et al, JCO 1999
German study: RESULTS Preop CRT Postop CRT At randomisation deemed suitable for APER = 75/313 At randomisation deemed suitable for APER = 74/315 Sphincter sparing procedures = 35% Sphincter sparing procedures = 19% ASTRO 2003
Interval between radiation and surgery Repopulation of tumor cells within surgical margins is not relevant Repopulation of tumor cells outside surgical margins is not relevant as any number of surviving clonogens beyond future surgical margins is recurrence from day 0 Downsizing during the interval will make surgery easier WAIT till regression!
Selection of patients!
Rectum adenocarcinoma : conformal 3D radiotherapy technique (3D-CRT) bladder tumour (CTVt) node (CTVn) margin (PTV) Organ and tumour identification On each CT slice (30-80)
Clinical target volume : mesorectum (1) 1 2 3 4
Clinical target volume (2) 5 6 7 8
Clinical target volume (3) 9 10 Site of recurrence ANT POST Le CTV is enlarged toward iliacal nodal drainage CTV is longer posteriorly peritoneum mesorectum
rectum adenocarcinoma Small bowel bladder PTV reconstruction 3D Anal canal spared
Rectum Adenocarcinoma Critical structure Complication Dose limits Contour 3D Hip Ankylosis 45 Gy Necrosis of femoral head Bladder Radiation cystitis 50 y on 100% 60 Gy on 50% 70 Gy <20% Small bowel Radiation ileitis (*) 50 Gy on 250cc 45 Gy > 250cc Nervous plexus Plexitis (pain, 60 Gy incontinence) Blood vessels Arterial stenosis 60 Gy (*) potentially lethal
Rectum adenocarcinoma Megavoltage radiation beams
Rectum adenocarcinoma: : 3 or 4 beams beam eye s view Anterior beam Mutlileaf collimator Anal canal and perineal skin are preserved
Rectum adenocarcinoma Lateral beam Anal canal is preserved
Summary : total mesorectal radiotherapy mesorectum CRM mesorectum CRM distal margin