1. What is the most appropriate therapy for a 50 year old patient with T3N+ rectal cancer and isolated resectable liver metastases?
Systemic chemotherapy->chemoradiation->surgery
Bruce Minsky

2. GCR-3 Randomized Phase II
· 108 pts
CAPOX RT
Surgery
CAPOX
CAPOX RT
CAPOX
Surgery
Fernandez-Martos et al. JCO 2010

3. GCR-3 Randomized Phase II
Induction Standard p
% pCR
% Gr
toxicity
% received
all 4 cycles
Fernandez-Martos et al. JCO 2010

4. Delayed Surgery 1593 Pts, 2009-2011 Dutch surgical colorectal audit
Preop CMT ( Gy + Cap TME
Sloothaak et al, Br J Surg 2013

5. 5 Gy x 5 + Induction CT
50 pts resectable/abatable M1 (84% liver, 10% lung, 6% both)
T2: 8%, T3: 76%, T4: 16%
5 G x wks CAPOX/Bev x wks Surg+ RFA
Total
72% R0 resection (all sites) % 2-Yr recurrence
80% 2-Yr survival
Pelvis
26% pCR
2/36 local recurrence at a median of 32 months
Exp arm of RAPIDO phase III
Van Dijk et al. Ann Oncol 2013

6. 5 Gy x 5 + Induction CT · 44 evaluable pts · cT3-4, any N, any M
· 5 Gy x 5 mFOLFOX6 x 4
· 30% ypT0, 32% ypN0
Myerson et al, ASCO GI 2012

7. 5 Gy x 5 + Concurrent CT ∙ 73 pts, cT3-4 rectal cancer
∙ 5 Gy x 5 (IMRT) + modified Mayo (400/20) x 5
∙ Surgery: 4-8 weeks
∙ pCR: 1.4%
∙ Gr 3+
Toxicity: 38%
Yeo et al, IJROBP 2013

8. Stockholm III Trial Dose Surgery 25 Gy 1 wk 25 Gy delayed
cT3, < 15 anal verge
Dose Surgery
25 Gy 1 wk
25 Gy delayed
50 Gy delayed

9. Stockholm III Trial % Postop Tox 25 Gy-I 25 Gy-D 50 Gy-D
Anast leak
Wound infect
Abd infec
Total (p=0.01)
Pettersson et al, Br J Surg 2013

10. Phase II Randomized Trial: Post CMT Chemotherapy
· 144 pts stage II/III rectal cancer
∙ CI5-FU Gy
%Postop
Rx %pCR Comp
CMT Surg (6 wks)
(6 wks)
CMT mFOLFOX6 Surg
if cResponse (11 wks)
(p=NS)
Garcia-Aguilar et al, Ann Surg 2011

11. Preop CMT + Bevacizumab
%Grade 3+
Series # Preop %pCR Toxicity
Brown 26 FOLFOX
Bev/50.4
Austria 8 Cape/Bev
· Both trials stopped early due to toxicity
Dipetrillo et al, IJROBP 2012
Resch et al. Radiother Oncol 2012

12. Radiation Dose Escalation
Phase III randomized
248 pts, cT3-4
50.4 pelvic RT + UFT/LV
HDR: 5 Gy x 1 cm
cPR R0 (T3) TRG+2 Surg Comp
HDR
* *
None
* p = ss
Jakobsen et al Proc ASCO 2011

13. Conclusions • Induction CT does not compromise RT
• Improved survival of pts with liver mets =
increased chance of local recurrence
• Short course RT or ChemoRT: both
reasonable but need to weigh benefits
vs. risks (rapid return to CT vs. toxicity)