Radiotherapy for Colo-rectal Cancer. Case 1 בן 58 גידול בגובה 9 ס"ם מפי הטבעת...
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Transcript of Radiotherapy for Colo-rectal Cancer. Case 1 בן 58 גידול בגובה 9 ס"ם מפי הטבעת...
Radiotherapy for Colo-rectal Cancer
Case 1
ס"ם מפי הטבעת9 גידול בגובה 58בן •
קולונוסקופיה – גידול צירקולרי, כמעט חוסם•
• TRUS T3 N0
TMEמועמד לניתוח •
טיפול??•
Staging
• Clinical– Rectal exam + rectoscopy– TRUS– Abdomino-pelvic CT– Chest X-ray– CEA?
• Pathological
Aim of adjuvant chemo-radiation
• 1o aim – overall survival• 2o aim - Loco-regional control
- Disease free survival
- Quality of life• Sphincter preservation
– Down-staging
• Long-term bowel function• Urinary function• Sexual function
Endoscopic ultrasound
Surgical Procedures for Rectal Cancer
• Radical– Abdominoperineal resection– Low anterior resection– Proctectomy and coloanal anastomosis– Total mesorectal excision
• Conservative– Transanal excision– Transanal endoscopic microsurgery
• Ablative procedures– Endoscopic laser Fulguration– Brachytherapy
Mesorectal resection
Low coloanal anastamosis
Radiotherapy for colo-rectal cancer• Rationale
– Local control– Survival– Down-staging
• Indications– Risk of local recurrence >10%– Radiotherapy can be safely delivered to site of highest risk
• Sites– Rectum– Cecum– Other sites - T4
Patterns of failure rectal cancer
• Pelvic failure rate– B2-C1 - 10-60% – C2 - 30-70%
• Patients undergoing 2nd look operation– Pelvic recurrence 92 % – Pelvic recurrence only 48% Gunderson 1974
Adjuvant radiotherapy for rectal cancer: a
systematic overview of 8,507 patients from 22
randomised trials. Lancet 2001;358:1291
risk of death from non-rectal cancer
causes and from rectal cancer from six trials
of preoperative radiotherapy
(biologically effective dose >30 Gy)
MRI evaluation of tumor response Sauer
Systematic overview Lancet 358:1291, 2001 radiotherapy dose-response
reduced death rate increased reduced
BED overall cancer specific non-cancer death local failure
Pre-op• <20 Gy 6% 11% 5% -20%• 20-30 Gy 1% 1% 15% 24%• >30 Gy 10% 22% 37% 57%
All pre-op 6% 13% 15% 46%
Post-op >35 Gy 5% 9% 12% 37%
Mesorectal resection
Rates of Overall Survival in 1805 Eligible Patients, TME study
TME study: local recurrence 2 years after complete resection2.4% in XRT & surgery and 8.2% in surgery alone (P<0.001)
Sphincter preservation
• Pre 1990 – 95% pts with low <6 cm tumors underwent AP
resection
• Post 1990: Pre-op XRT– Several series 80% sphincter preservation– 85-90% local control (3-4 yrs)– 75-90% good bowel function
Adjuvant radiotherapy for rectal cancer pre-operative
postoperative
• Staging clinical surgical
• Toxicity less more– Bowel may be trapped after surgery
• Surgery down-stagingreduced spillage
Relative reduction in local failure according to number of 5 Gy fractions. Size of symbols is proportional to the number of patients in trial. The 3 large trials are, from the top, te TME trial, Swedish Rectal Cancer trial and the Stockholm I trial.
Dose (5Gy fx studies)
Radiotherapy toxicity 5 Gy x 5 pre-op
• Stockholm trials– Trial 1 large AP/PA fields 8% post-op mortality (Cancer 66:49, 1990)
• 1 & 2 combined (Cancer 78:968, 1996)
– Thromboembolism RR 2– Pelvic/femoral fractures RR 3– Intestinal obstruction RR 1.5– Fistula RR 2.8
• Swedish trial (Dis Colon Rectum 41:543 1998)
– > 4 stools per day 20%– Emptying difficulties 52%– Incontinence of loose stool 50%
Radiotherapy volumes in trials using 5 * 5 Gy and postoperative mortality
Volume technique Energy given (J)
• Stockholm(+) Mid L2 2-beams 310• Uppsala Mid L3 3-beams 210–
250• SRCT Mid L4 3/4 beams 190• Stockholm II (+) (As SRCT, but no shields) 270• TME Mid L5 3/4 beams 140–170
Small bowel sparing using high-energy linear accelerator XRT
prone three-field treatment v AP/PA.
The small bowel (arrows) remains fixed in the pelvis, and cannot be excluded from the lateral fields.
Post-operative radiotherapy
The small bowel (arrows) is excluded from the lateral fields Note: place wire to exclude perineum or use anal marker
Pre-operative radiotherapy
Correlation between the volume of small bowel receiving 15 Gy (V15) and degree of acute small
bowel toxicity Baglan KL Int J Radiat Oncol Biol Phys 2002 52:176
.
Adjuvant versus Neoadjuvant Chemo-radiation for Rectal Cancer: Sauer NEJM 2004
• Phase III preop 45 Gy CRT v postop 45 Gy CRT
• Eligibility: T3/T4 or N+• 5−FU (1g/m2/d - 120h−CI) 1st and 5th week of XRT • Interval between CRT and surgery was 4−6 weeks• Techniques of surgery standardized and included TME
– Stratification was done according to surgeon
• 797 evaluable patients in 26 institutions
Adjuvant versus Neoadjuvant Chemo-radiation for Rectal Cancer: Sauer NEJM 2004
• Post-op Pre op
• 5−year pelvic recurrence 11% 7% (p = 0.02)
– 5−year distant recurrence 34% 30% (p = 0.52)
– disease−free survival 55% 59% (p = 0.23) – overall−survival 73% 78% (p =0.38)
• chronic anastomotic stenosis 8.5% 2.7% (p = 0.001)
– Acute grade 3 and 4 toxicity 31.7% 28.8% (p -n.s.)
• sphincter preservation 19% 39% (p = 0.004)– subgroup of 188 patients with low−lying tumors declared by surgeon prior to
randomization to require an AP resection
Adjuvant versus Neoadjuvant Chemo-radiation for Rectal Cancer: German Study
Sauer ASTRO 2003; local recurrence
Pre-operative 5-FU chemoradiation: commonly used in rectal cancer
• 5-FU-based chemoradiation has become part of pre-operative therapy for rectal cancer– More effective downstaging than XRT alone
• Historical controls
• Pivotal EORTC study now completed accrual
– 10–30% pCR rates
• With postoperative XRT protracted infusion of 5-FU improves survival versus bolus 5-FU
1O’Connell MJ et al. N Engl J Med 1994;331:502–7
EORTC study
Newer drugs in chemo-radiation of rectal cancer
• Indications:– Locally advanced T4– N+– May be overkill for T2-T3 N0
• Drugs– Oxaliplatin– Irinotecan (CPT-11)– Bevacizumab– EGFR inhibitors
NSABP R-04 rectal cancer trial
*Plus 5.4Gy for fixed tumours
Resectable rectal cancer, stage II–III
n=1 600
Capecitabine continuous throughout radiotherapy (50.4Gy*)
SURGERY
5-FU continuous infusion throughout
radiotherapy (50.4Gy*)
• Objectives – DFS– Recurrence rate– pCR– safety
Direct evidence that the VEGF-specific antibody bevacizumab
has antivascular effects in human rectal cancer. Willett Nat Med 2004
Case 2
עצירות כרונית54בת •
ס"ם מפי הטבעת (מעל 3גידול בגובה •הספינקטר)
•TRUS T2 N0
מסרבת כריתה ראדיקאלית•
טיפול??•
Sphincter preservation local therapy only
• Endocavity radiation Local failure – T1 3%– T2 33%– Local excision only– T1 0-33%– T2 0-43%– Local excision & XRT– T1 0-10%– T2 0-18%
Candidates for local therapy of rectal cancer
• Indications– Tumor <3 cm– Well differentiated– Submucosa or superficial muscularis
• Options– Transanal resection– Brachytherapy– External beam radiotherapy
Local therapy only – what about lymph nodes?
• Incidence of peri-rectal lymph nodes– T1 0-12%– T2 22-28%– T3 36%– Grade 1 0-4%– Grade 2 14-30%– Grade 3 50%