Download Neoadjuvant Therapy For CA Rectum

JHSGR
Neoadjuvant Therapy For Rectal Cancer
Dr Chris TL Cheng
Princess Margaret Hospital
Neoadjuvant Therapy for
Rectal Cancer
Background
Benefits of neoadjuvant therapy
Selection Criteria
Staging & CRM
Multidisciplinary Team (MDT) approach
Background
During the 1990s, TME and postoperative
adjuvant chemoradiotherapy (CRT) for
locally advanced rectal tumors was the
gold standard treatment regimen
High Local recurrence (LR) rates despite
the use of adjuvant CRT

investigators decided to test neoadjuvant
radiotherapy (RT) or CRT
Short course pre-op RT
Local
recurrence
Swedish (1997)
27% to 11%
rectal cancer trial (p<0.001)
(pre-TME)
Dutch TME trial
8.2% to 2.4%
(2001)
(p<0.001)
Survival
5-yr survival
48% to 58%
(p=0.004)
No difference
Pre-op radiotherapy
UK Medical Research Council (MRC
CR07) & National Cancer Institute of
Canada trial (NCIC-CTG C016)

Local recurrence at 3 years
Pre-op short course RT: 4.4%
Selective Post-op adjuvant chemoRT: 10.6%
Relative risk reduction 61% (p<0.0001)

No difference in overall survival
Sebag-Montefiore D et al. Preoperative radiotherapy versus selective postoperative
chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a
multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20.
Short course preop RT on local
recurrence
Relative risk reduction in LR
57%
Neoadjuvant RT Vs Neoadjuvant ChemoRT
Ceelen WP, Van Nieuwenhove Y, Fierens K. Preoperative chemoradiation
Chemotherapy
addition
to neoadjuvant
versus radiation alone in
for stage
II and III resectable
rectal cancer. Cochrane
Database
of Systematic Reviews
2009, Issue 1.response
Art. No.: CD006041. DOI:
RT
improves
complete
10.1002/14651858.CD006041.pub2
German rectal cancer study group
Neoadjuvant CRT Vs Adjuvant CRT
Local Recurrence
Overall Survival
Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative
chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351:1731– 40.
Neoadjuvant CRT has less
toxicities
Sauer R, Becker H, Hohenberger W, et al. Preoperative versus
postoperative chemoradiotherapy for rectal cancer. N Engl J
Med 2004; 351:1731– 40.
Local recurrence for locally advanced CA rectum
TME only
TME + adjuvant chemoRT
Neoadjuvant RT + TME
Neoadjuvant chemoRT + TME
Reduction in
local recurrence
Neoadjuvant ChemoRT is recommended for
locally advanced rectal cancer
Advantages of neoadjuvant CRT
apply to virgin, well-oxygenated tissue

more profound reduction of local recurrence
compared with postoperative CRT
downstage the tumor

make radical resection or sphincter preserving
surgery feasible
Selection Criteria
- T 3-4
- N +ve
- Predicted CRM ≤ 2mm
Accurate pre-op staging is important
for neoadjuvant therapy consideration
Meta-analysis on T and N staging
T
N
No accurate investigation for LN
EUS is operator dependent, cannot pass stenotic tumor, and
can only detect mesorectal lymph nodes
Bipat et al. Rectal cancer: local staging and assessment of lymph node involvement with
endoluminal US, CT, and MR imaging--a meta-analysis. Radiology 2004 Sep;232(3):773-83.
CRM (circumferential resection margin)
the distance from the edge of the tumor to
the margin of the resected specimen
a credible surrogate marker for local
recurrence (LR)
The prognostic value of CRM involvement
is independent of TNM classification.
CRM ≤ 2mm consider margin positive
MRI for CRM
MRI recommended for CRM assessment
MERCURY (Magnetic resonance imaging
and rectal cancer european equivalence)
study group


MRI and histopathologic assessments of
tumor spread equivalent to within 0.5 mm
Accurate measurement of the depth of
extramural tumor spread
Mercury Study Group. Extramural depth of tumor invasion at thin-section MR in patients
with rectal cancer: results of the MERCURY study. Radiology. 2007 Apr;243(1):132-9.
Surgeons
Radiologists
Multidisciplinary Team
Oncologists
Pathologists
Multidisciplinary team (MDT)
Discussion at the MDT meeting



Increases the proportion of patients receiving
neoadjuvant treatment
Improves local cancer control
Improves 5-year survival
Palmer G et al. Preoperative tumour staging with multidisciplinary team
assessment improves the outcome in locally advanced primary rectal cancer.
Colorectal Dis. 2010 Oct 19 ePub
Radiologists:
Standardized
MRI reporting by
specialist
gasterointestinal
radiologists
Oncologists
Long Vs Short Scheme CRT
Short scheme
Intensity 5 fractions of
500 cGy
Long scheme
4,500 to 5,060 cGy
daily during 4 weeks
Time
before
OT
Aim
3-4 days
4-6 weeks
Reduce local
recurrence
Downstage tumour and
secure threatened
CRM
Chemotherapy
Addition of chemotherapy to RT improves
complete pathologic remission up to 38%
Xeloda (Capecitabine): oral route
5-FU + Irinotecan/Oxaliplatin + RT

Downstaging 67-84%
Biological agents

Bevacizumab/Cetuximab
Pathologists
Quirke’s detailed reporting system for
rectal specimen



Completeness of mesorectal excision
Surgical audit
MRI audit
Quirke P. Training and quality assurance for rectal cancer: 20 years of data is enough.
Lancet Oncol 2003;4:695–702.
Quirke P, Durdey P, Dixon MF, et al. Local recurrence of rectal adenocarcinoma due to
inadequate surgical resection. Histopathological study of lateral tumour spread and
surgical excision. Lancet 1986;2:996 –9.
Re-staging after neoadjuvant CRT
After RT, both EUS and MRI offered poor
diagnostic performance in the assessment
of T and N stages
Mezzi G. et al. Endoscopic ultrasound and magnetic resonance imaging for restaging rectal cancer after radiotherapy.
World J Gastroenterol. 2009 Nov 28;15(44):5563-7.
Optimal time for operation
4-6 weeks is optimal
 Allows RT-induced tissue swelling or local
inflammation to subside.
 Allows time for tumor regression, which may
improve resectability and possibility of sphincter
preservation.
1)Lim S-BM et al. Optimal surgery time after preoperative chemoradiotherapy for locally
advanced rectal cancers. Ann Surg 2008; 248:243–251.
2)Veenhof AA et al. Preoperative radiation therapy for locally advanced rectal cancer: a
comparison between two different time intervals to surgery. Int J Colorectal Dis.
2007;22:507–513
Conclusion
For locally advanced rectal cancer:



Neoadjuvant ChemoRT
Accurate pre-op staging
Multidisciplinary team (MDT) approach
Thank you!