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Neoadjuvant Chemotherapy First, Followed by Chemoradiation and Then Surgery, in the Management of Locally Advanced Rectal Cancer
A. Cercek, K. A. Goodman, C. Hajj, E. Weisberger, N. H. Segal, D. L. Reidy-Lagunes,
Z. K. Stadler, A. Wu ,M. R. Weiser, P. B. Paty, J. G. Guillem, G.M. Nash, L. K. F. Temple, J. Garcia-Aguilar, L. B. Saltz
Memorial Sloan-Kettering Cancer Center
Abstract
Background: Standard therapy for locally advanced rectal
Abstract
cancer (LARC) is pre-operative
chemo-radiotherapy (CRT)
and post-operative chemotherapy. To address earlier
systemic chemotherapy to target micrometastases. while
treating the primary tumor, we began offering FOLFOX as
initial treatment for patients with high-risk LARC.
Purpose: To report safety and efficacy of initial FOLFOX
before CRT on tumor downsizing and pathologic complete
response (pathCR) in LARC.
Patients and Methods: IRB waiver was obtained to
review records of stage II/III rectal cancer patients (pts)
treated at our institution between 2007 and 2012. Of
approximately 300 LARC pts treated with CRT, 61 received
FOLFOX as initial therapy.
Results: Of the 61 pts, 57 received induction FOLFOX
(median 7 cycles) then CRT, 4 pts had an excellent
response, declined CRT, and had TME. Twelve pts did not
undergo TME; 9 had a complete clinical response (CCR)
and were managed non-operatively; 1 declined despite
persistent tumor, 1 due to comorbidities, and 1 developed
metastatic disease. 22/61 patients (36%) had either
pathCR (n=13) or CCR (n=9). Of the 49 pts who
underwent TME, all had R0 resections, 23 (47%) had tumor
response >90%, including 13 (27%) pathCR. 28 pts
received all 8 cycles of FOLFOX, 8 had pathCR (29%) and
3 CCR (11%). There were no SAEs requiring delay in
treatment during FOLFOX or CRT.
Conclusion: FOLFOX and CRT before planned TME
results in substantial tumor regression, a high rate of
delivery of planned therapy, substantial rate of pathCRs
and the potential for non-operative management in select
patients.
Results
Results
Methods
• All patients completed all planned chemo and CRT
A waiver of authorization was obtained from the MSKCC
IRB to review an institutional database of colorectal cancer
patients. The electronic medical records were searched to
identify patients who met the following criteria:
a) presentation to Memorial Sloan-Kettering Cancer
Center with clinical (either MRI or ERUS) stage II/III
(T3/4, N1-2) rectal cancer between 2007 and 2012
b) No prior primary tumor-directed surgery, stenting or RT
c) Received induction chemotherapy with FOLFOX (5FU,
leucovorin and oxaliplatin) or CapeOx followed by
CRT (total dose if 5040cGY) then TME
d) Patients had interim imaging with either MRI or surgical
evaluation
e) Pathology reports were reviewed to assess complete
and partial response rates.
• There were no grade 4 toxicities or SAE
• Toxicities were consistent with those previously reported for
FOLFOX.
• Grade 3 toxicities from CRT included diarrhea (4%), fatigue
(1%) , nausea (1%) and neutropenia (1%).
• All patients achieved R0 resections
• No patients progressed in the primary on treatment
• Median follow up of 15.5 months (range 47.6mo- 10.7 mo)
Patient Characteristics
Baseline
Characteristics
Sex
Male
Female
Age, years
Average
Range
Performance
Status
(ECOG)
0
1
Initial
Diagnosis Stage
(MRI or ERUS)
T3N0
T3N1
T3N2
T4N0
T4N1
T4N2
• Of 61 patients 22 (36%) either had a pathCR (13) or
complete clinical response (9)
Number of
Patients
Total = 61
-33
28
-52
25-82
-54%
46%
--42
19
--69%
31%
7
24
23
1
4
2
%
8%
43%
39%
2%
6%
4%
• Of 49 patients who underwent TME
• 23 (47%) had tumor response > 90%
• 13 (27%) had pathCR
Results
Conclusions
Response to treatment
Total number of patients with TME N=49
Pathologic Complete
Response
13 (27%)
>90% treatment effect
23 (47%)
Node positive clinical
diagnosis
N=46
Node negative ypN0
30 (65%)
• FOLFOX and CRT before planned TME leads to substantial
tumor regression and rate of pathCRs
• The regimen is well tolerated and leads to a high rate of delivery
of all planned therapy
• Our recommended treatment schema includes interim imaging
with MRI and/or endorectal ultrasound to assess for response to
therapy
• This treatment strategy of completing all chemotherapy and
chemoradiotherapy before planned surgery offers the opportunity
for selective non-surgical management of locally advanced rectal
cancer.