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

230s Gastrointestinal (Colorectal) Cancer
3609 General Poster Session (Board #35F), Mon, 8:00 AM-12:00 PM
Reappraisal of the risks and benefits of major liver resection in patients
with initially unresectable colorectal liver metastases. Presenting Author:
Francois Cauchy, HBP Surgery, Hôpital Beaujon, Clichy, France
Background: Improvements in both surgical technique and efficacy of
chemotherapy have increased the rate of resection for patients with initially
unresectable colorectal liver metastases (IU-CRLM). We aimed to evaluate
the short and long-term outcomes of major hepatectomy for such patients.
Methods: From 2000 to 2011, 257 patients underwent major hepatectomy
for CRLM. Seventy-eight (30%) of these patients were considered IU and
required portal vein occlusion and/or �12 cycles or change in induction
chemotherapy regimen to achieve resectability. Results: IU patients had
respectively more lesions (5.6 vs.3.6, p�0.001), more frequently bilobar
(70% vs.50% p�0.008) and synchronous (83.3% vs.70%, p�0.027)
than initially resectable (IR) patients. Post-operative mortality (12.8%
vs.1.7%, p�0.001) and major complications (46.2% vs.22.3%,
p�0.0001) were higher in IU patients. An associated metabolic syndrome
(HR 5.2, CI 1.2-21.9, p�0.025), high grade sinusoidal lesions (HR 2.4, CI
1.1-5.8, p�0.044) and the need for vascular reconstruction (HR 6.3, CI
1.2-34.4, p�0.032) were significant risk factors for major morbidity in IU
patients. Significantly fewer IU patients received adjuvant chemotherapy in
case of major postoperative complications compared to IR patients (47%
vs. 83%, p�0.001). Overall 5-year survival was significantly lower in IU
than in IR patients (26% vs.55%, p�0.032) and all IU patients had tumor
recurrence within 3 years. The absence of adjuvant chemotherapy and
tumor size �5 cm were the only factors associated with poor survival in
multivariate analysis for IU patients. Conclusions: IU-CRLM patients
requiring major liver resection displayed higher morbidity and mortality
rates than IR ones, therefore compromising both short and long-term
outcomes. Multimodal strategy should be reassessed in the presence of
metabolic syndrome, sinusoidal lesions or major vascular involvement.
3611 General Poster Session (Board #35H), Mon, 8:00 AM-12:00 PM
Clinical utility of the preoperative Glasgow prognostic score in patients
undergoing potentially curative resection for colorectal cancer. Presenting
Author: Donald C. Mcmillan, Department of Surgery, University of Glasgow,
Glasgow, United Kingdom
Background: There is now good evidence that, in addition to TNM stage, the
pre-operative combination of the standardised measurements of C-reactive
protein and albumin, the Glasgow Prognostic Score (mGPS) provides
valuable prognostic information. The aim of the present study was to
examine the clinical application of the pre-operative mGPS in a large
mature cohort of patients undergoing potentially curative resection for
colorectal cancer. Methods: From a prospectively maintained database,
consecutive patients (n� 797) with histologically proven colorectal cancer
who were considered to have undergone potentially curative resection
between January 1997 and December 2010 in a single surgical unit at the
Royal Infirmary, Glasgow were included in the study. Results: Patients with
an elevated mGPS were more likely to be older (p�0.001), female
(p�0.05), have colonic tumours (�0.001), present as an emergency
(p�0.001), had higher TNM stage (p�0.05) and more likely to die of their
disease (p�0.01). The median follow-up was 66 months and using 3 year
cancer-specific mortality as an endpoint, the area under the receiver
operator curve was 0.652 (95% CI, 0.591–0.714; p�0.001) for the
mGPS and 0.668 (95% CI, 0.610–0.727; p�0.001) for TNM stage. The
cancer-specific survival, at 3 years, varied between 86% and 64%
according to the mGPS and between 88% and 72% according to TNM
stage. The cancer-specific survival, at 3 years, in patients with a mGPS 0
was 91% and 81% for TNM stage II and III respectively. The cancerspecific
survival, at 3 years, in patients with a mGPS 1 was 89% and 66%
for TNM stage II and III respectively. The cancer-specific survival, at 3
years, in patients with a mGPS 2 was 77% and 43% for TNM stage II and III
respectively. Conclusions: The results of the present study show the clinical
utility of the pre-operative mGPS in predicting cancer specific survival of
potentially curative surgery for colorectal cancer.
3610 General Poster Session (Board #35G), Mon, 8:00 AM-12:00 PM
A population-based study of the effect of FDG PET/CT in the management
of liver-limited colorectal adenocarcinoma (CRC) metastases. Presenting
Author: Maria Yi Ho, Division of Medical Oncology, British Columbia Cancer
Agency, Vancouver, BC, Canada
Background: PET/CT scans are publically funded in British Columbia for
staging in liver limited metastatic CRC. However, past studies have been
equivocal about the utility of PET/CT as some report as high as a 20-30%
change in management while others report �10% change in management.
Our primary objective was to assess the effect of the addition of PET/CT to
CT scanning for the management of liver limited colorectal cancer.
Methods: Patients who underwent PET/CT scan for de novo liver limited
metastatic disease from 2005-2011 in the province of British Columbia
were identified using the PET/CT database. Patients recently completed or
currently on chemotherapy were excluded. We determined the concordance
rates between CT and PET/CT scans with respect to the extra-hepatic
disease, the number of lesions in the liver and the location of liver lesions.
Results: 349 patients were identified. The most common indications for
PET/CT scans after an initial CT scan were: detection of extrahepatic
disease (77%), confirmation of the malignant nature of the liver lesions
(8%) and the extent of extrahepatic disease (15%). PET/CT and CT were
discordant in 39% of cases for the extent of metastatic disease. PET/CT
revealed extrahepatic disease in 27% of the cases for which CT only
detected liver limited disease. In contrast, 13% of patients were downstaged
when CT liver lesions were demonstrated not to be FDG avid.
Concordance of PET/CT and CT scans on the number and location of liver
lesions was 52% and 85%, respectively. PET/CT revealed additional
number of liver lesions and multilobar disease in 26% and 12% of cases,
respectively. Furthermore, the median time between PET/CT and CT were
64.3 days and 64.1 days for concordant and discordant cases (p�0.88).
Conclusions: PET/CT scans provided additional information compared to CT
scans which could have implications for surgical management. Our study
supports the utility and public funding of PET/CT in addition to CT in
patients with potentially surgically curable metastatic CRC involving the
liver.
3612 General Poster Session (Board #36A), Mon, 8:00 AM-12:00 PM
Does multiple mutational analysis of the EGFR pathway have a prognostic
role in advanced colorectal cancer (CRC)? Presenting Author: Luisa Foltran,
Azienda Ospedaliero-Universitaria, Udine, Italy
Background: BRAF mutation is widely recognised as a strong negative
prognostic factor in advanced CRC, while the prognostic value of KRAS
mutations in codons 12-13 remains controversial. Exploring mutations in
other downstream components of the EGFR pathway may have an impact
on survival. Methods: A consecutive cohort of 201 metastatic CRC patients
treated with systemic chemotherapy were analysed for KRAS (12-13-61-
146), BRAF, PIK3CA and NRAS genotypes by pyrosequencing on PyroMark-
TMQ96 ID instrument (Qiagen, Germany) with commercially available kits
Anti-EGFR MoAb response (Diatech Pharmacogenetics, Italy). Accurate
microdissection guaranteed more than 70% of cancer cells for each
sample. For the purpose of the survival analysis 4 categories were created:
(1) KRAS mutated (codons 12-13 only); (2) BRAF mutated; (3) any of
KRAS codons 61-146, PIK3CA or NRAS mutations; (4) all-wild type.
Log-rank and Cox proportional tests were applied for statistical analysis.
Results: KRAS mutations were present in 96 (47.8%) patients: 86 (42.8%)
were in codons 12-13. BRAF mutations were found in 11 (5.5%) samples
while PIK3CA and NRAS in 33 (16.4%) and 7 (3.5%), respectively. All
mutations were mutually exclusive except for 24 (11.9%) patients with
concomitant KRAS/PIK3CA mutations. Median survivals for different
categories are shown. Patients harbouring BRAF mutation had the worst
outcome (p�0.0006). Mutations of any codon of KRAS (12-13-61-146)
also negatively impacted on survival (p�0.026), while the all wild-type
(KRAS/BRAF/PIK3CA/NRAS) patients had the longest survival (p�0.002).
Conclusions: This study suggests the usefulness for early molecular profiling
for advanced CRC patients. Mutational analysis of all EGFR pathway
components may identify different prognostic subgroups. This information
may drive treatment selection in clinical practice and stratification in
clinical trials.
Mutational status
Median survival
(months)
HR for death
(95% CI)
BRAF mutation 5.1 4.5 (2.1-9.7)
KRAS mutation 12-13 only 15.8 1.56 (1.1-2.3)
Any of KRAS 61-146 /NRAS/ PIK3CA mutation 14.7 1.8 (1.1-3.3)
All W-T (reference category) 22.2 1
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