Annual Meeting Proceedings Part 1 - American Society of Clinical ...

232s Gastrointestinal (Colorectal) Cancer
3617 General Poster Session (Board #36F), Mon, 8:00 AM-12:00 PM
Relationship between genetic markers and quality of life (QOL) in stage III
colon cancer (CC) patients (pts) prior to adjuvant treatment (N0147).
Presenting Author: Jeff A. Sloan, Mayo Clinic, Rochester, MN
Background: In metastatic colorectal cancer (CRC), previous studies suggested
potential relationships between certain drug metabolizing (DM)
genes (DPYD, ERCC2, GSTP1 and TYMS) and QOL prior to receipt of
chemotherapy (Sloan, Plenary Session ASCO 2004). The current study is
the first to examine relationships between similar DM genes and QOL in
stage III CC pts. Methods: 1,583 CC pts on a randomized adjuvant stage III,
phase III trial received FOLFOX, FOLFIRI, or either �/- Cetuximab.
Genomic DNA and baseline QOL data via linear analogue self assessment
(LASA) scales with 4 QOL variables were obtained. 53 DM SNPs were
selected for known functional effect within potential regulatory sites.
Two-sample t-tests assessed differences in QOL between pts with variants
and wild-type status. Differences of at least 10 points on a 0-100 point
QOL score were considered clinically significant. Results: 14 relationships
between DM genes and QOL were detected at the nominal p � 0.05 level;
six of these were related to DPYD, ERCC2, GSTP1 and TYMS. Relationships
were also observed at the 0.05 level with polymorphisms of genes DPYS,
ERCC1, MGMT, MTHFR, OPRT and UGT1A1 based on unadjusted and
adjusted association tests. GSTP1 I105V and OPRT 5’UTR 28 A�G
markers differed on fatigue scores (p�0.04, 0.005, respectively). Variants
on MTHFR R594Q were associated with higher mental acuity scores
(p�0.02). These relationships remained after adjusting for age, gender,
race, T stage, PS, disease site, lymph nodes involved, and grade. The
robustness of the observed associations varied with the multiple comparison
adjustment method. Conclusions: Similar to the earlier study of stage IV
CRC, we observed a possible relationship in pts with Stage III CC with
regard to DM genes and QOL, although these relationships were more
modest than observed in Stage IV pts. These DM genes may be in linkage
disequilibrium with other genetic variants that more directly affect behavior
and QOL. Further genome wide association studies are needed to clarify
these relationships.
3619 General Poster Session (Board #36H), Mon, 8:00 AM-12:00 PM
Comparison of incidence and patterns of recurrence in colon cancer (Cca)
treated by sentinel lymph node (SLN) mapping (M) versus conventional surgery.
Presenting Author: Mohammed Saifullah Shaik, Hurley Medical Center/
Michigan State University, Flint, MI
Background: Recurrence of Cca patients (pts) depends on the initial stage at
diagnosis. SLNM upstages more pts than conventional surgery (Conv. Surg.) for
nodal metastasis, this might have an impact on the incidence and pattern of
recurrence. Hence comparative study was undertaken for recurrence in Cca pts
undergoing SLNM Vs Conv.Surg. Methods: Group (Gp) A pts underwent SLNM
with 1% Lymphazurin. The first 1-4 blue nodes were marked as SLNs followed by
standard oncologic resection. Gp B pts underwent Conv. Surg. Data was
collected for, TNM staging, Recurrence sites and follow up treatment. Minimum
follow up of all pts was 12 month, with mean follow up period 44 months for both
Gps. Results: There were 357 pts in GpA and 466 pts in GpB. For GpA pts, SLNM
was successful in 99.6% of pts with average (Avg.) SLN was 2.8/pts. Avg. no. of
LNs in GpA was 15.4/pts vs. 12.8/pt in GpB (p�0.001). For GpA pts, 46% was
LN �ve vs 34% in GpB . Excluding T0, Tis and M1 pts at diagnosis, recurrence
was calculated for 313 pts in GpA vs. 314 pts in GpB. An overall recurrence was
7.9% in GpA vs 22.2% (p�0.001) in GpB with distant mets being most common
in both Gps. Recurrence of LN �ve and LN –ve pts also were significantly lower
in GpA vs GpB (Table). The pattern of recurrence between the two Gps is shown
in the Table. Conclusions: SLNM upstages significantly more pts in Cca than
conv. surg. Even though pattern of recurrence was similar in both Gps, better
staging may have resulted in better treatment, reducing the recurrence in SLNM
Gp. Hence SLNM may be beneficial for Cca surgery.
Node �ve
Node -ve
Gp. A Gp. B
Gp. A Gp. B
(SLN) (Conv.)
(SLN) (Conv.)
T-Stage
1A. Incidence of recurrence
(# 112) (# 112) p°-value T-Stage (# 201) (# 202) p°-value
T-1 0 1 T-1 0 8
T-2 1 2 T-2 1 4
T-3 16 30 T-3 4 14
T-4 0 6 T-4 3 5
Total * 17 39 0.008 Total * 8 31 0.0005
(15%) (34.8%)
(4%) (15.3%)
1B. Patterns of recurrence. Gp. A Gp. B
Local 1 (4%) 5 (7.1%)
Regional (Reg) 4 (16%) 12 (17%)
Distant 20 (80%) 53 (76%)
Total number of recurrences Gp A Gp B
Local 1 (3%) 5 (6%)
Reg. lymph node and soft tissue 5 (15%) 16 (20%)
Liver 13 (35%) 31 (37.3%)
Lung 11 (30%) 10 (12%)
Bone 1 (3%) 4 (4.8%)
Peritoneum 0 (0%) 2 (2.4%)
* Pts with Tis/T0/M1 disease were excluded (Gp A�41; Gp B� 61); ° Chi-square test.
3618 General Poster Session (Board #36G), Mon, 8:00 AM-12:00 PM
Pharmacogenetic profiling for oxaliplatin-based adjuvant chemotherapy
(CT) benefit in stage II-III colon cancer (CC) patients: A GEMCAD study.
Presenting Author: Jaime Feliu, Department of Medical Oncology, La Paz
University Hospital, Madrid, Spain
Background: Identifying molecular biomarkers for tumour recurrence is
critical in successfully selecting early-stage CC patients who are more likely
to benefit from adjuvant CT. We tested whether single nucleotide polymorphisms
(SNP) within genes involved in biological pathways of interest for
CC progression and treatment resistance would predict the risk of recurrence
in stage II-III CC patients treated with oxaliplatin and fluoropyrimidines-based
adjuvant CT. Methods: Genomic DNA was extracted from
formalin-fixed paraffin-embedded samples from 202 surgically treated
high-risk stage II (29.7%) and stage III (70.29%) CC patients receiving
adjuvant CT (25.24% FOLFOX, 74.75% XELOX) from January 2004 to
December 2008. Minimum follow-up was 36 months. Genotyping was
performed for 62 SNPs in 31 genes using the MassARRAY (SEQUENOM)
technology. Our results were validated in an independent cohort of 177
stage II-III CC. Results: After a median follow-up of 51.4 months (7-96), 63
patients (31.18%) had experienced a relapse and 31 (15.34%) had died.
Three-year disease-free survival (DFS) and overall survival (OS) were
72.2% (�/-0.032) and 89.1% (�/-0.022), respectively. Multivariate
analysis showed that the risk of recurrence for patients with the E-selectine
rs3917412 G�A G/G genotype was higher than for those with any A allele
genotype [relative risk (RR): 2.02, 95% confidence interval (CI): 1.09-
3.73, p�0.024]. In haplotype analysis, patients harboring the E-selectine
rs3917412 G�A G/G and methylentetrahydrofolate reductase (MTHFR)
rs1801133 C�T T/T haplotype had a higher risk of developing tumor
recurrence compared to the E-selectine rs3917412 G�A any A and/or
MTHFR rs1801133 C�T any C haplotype (RR: 3.39, 95% CI, 1.51-7.62,
p�0.003). The ability to predict recurrence of this combined analysis was
independently validated in the second cohort (RR: 3.75, 95% CI, 1.32-
10.68, p�0.013). Conclusions: E-selectine and MTHFR SNPs were found
to be independent prognostic markers for stage II-III CC patients, suggesting
that this combined analysis provides additional prognostic information
to that offered by clinicopathologic variables.
3620 General Poster Session (Board #37A), Mon, 8:00 AM-12:00 PM
Effect of perioperative complications on recurrence and survival after
resection of hepatic colorectal metastases: Analysis of data from a
randomized controlled trial. Presenting Author: Camilo Correa-Gallego,
Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Perioperative outcomes such as blood loss, transfusions and
morbidity have been associated with cancer specific survival, but this is
unsupported by prospective data. Methods: Patients were derived from a
previously reported prospective randomized trial of acute normovolemic
hemodilution (ANH) versus standard management during major hepatectomy.
Patients with metastatic colorectal cancer (mCRC) were selected for
analysis. Chemotherapy and survival data were obtained from the medical
record. Disease extent was measured using a clinical risk scoring (CRS)
system. Log-rank test and Cox proportional hazard model were used to
evaluate recurrence free (RFS) and overall survival (OS). Results: This trial
enrolled 130 patients, 90 of whom had mCRC. Median follow up was 54 m;
median age was 53 yr; 56% were men. The CRS was �3 in 55% of
patients, and 57% had additional extrahepatic procedures. Morbidity and
mortality were 33% and 3%. Chemotherapy was split before and after
surgery in 70%; 10% received only preoperative and 19% only postoperative
treatment, which was initiated after a median time of 6 wks (IQR �
4-7). RFS and OS were 29 and 59 m. On multivariate analysis, (�)
resection margin, high CRS and perioperative complications predicted
shorter RFS and OS. Delayed initiation of postoperative chemotherapy (� 8
wks) while most common in patients with complications (37 vs 12%; p:
0.01), was not a significant predictor of shorter RFS or OS. Randomization
(ANH vs standard) was also not significant in this regard. (See Table.)
Conclusions: In this prospective randomized cohort, perioperative morbidity
was a highly significant independent predictor of cancer specific outcome,
associated with but not entirely explained by delayed initiation of chemotherapy.
Variables affecting overall (OS) and recurrence free (RFS) survival.
Median survival
Multivariate
months Univariate P P-HR
CRS (high vs low)
OS 32 vs 74 0.02 �0.01 – 3
RFS 21 vs 46 0.03 �0.01 –3
Margin (� vs -)
OS 34 vs 71 0.05 0.03 – 0.5
RFS 29 vs 32 0.2 0.04 – 0.5
Complications (Y vs N)
OS 27 vs 75 �0.01 �0.01 – 3.4
RFS 18 vs 60 �0.01 �0.01 – 3.5
Delayed chemotherapy (Y vs N)
OS 30 vs 75 0.06 0.06 – 3
RFS 29 vs 59 0.1 0.3
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