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SWOG 0356: High gene-expression ERCC1 levels predicted poorer survival

2011 Gastrointestinal Cancers Symposium

SAN FRANCISCO — Patients with stage II to III esophageal adenocarcinoma who had elevated levels of ERCC1 gene expression had inferior 2-year PFS and OS.

All 90 patients in the phase 2 molecular correlative study were assigned oxaliplatin plus infusion 5-FU and external beam radiation before surgery.

Researchers sought to determine whether intratumoral gene-expression levels in drug metabolism (DPD, GSTPi, TS and TP) and DNA repair (ERCC1 and XPD) predicted clinical outcome. They then tested whether a specific pattern of 12 polymorphisms in eight genes and DNA repair predicted outcomes.

ERCC1 gene-expression cutoff was <1.7 x 10-3.

“When we looked at progression-free survival by ERCC1 levels using the predefined cutoff of 1.7, there was a highest risk for recurrence in the high ERCC1 group, with the hazard ratio nearly reaching three,” said Pierre O. Bohanes, MD, an oncology fellow at the University of Southern California Norris Comprehensive Cancer Center.

Bohanes presented the results Thursday at the 2011 Gastrointestinal Cancers Symposium.

“The median progression-free survival in the high ERCC1 group was 14.8 months and was not reached in the low ERCC1 group,” he said.

In univariate analysis, 2-year PFS was 17% for patients with high ERCC1 gene expression vs. 67% for those with low gene expression (HR=2.97; 95% CI, 1.37-6.45). Two-year OS was 72% for patients with low ERCC1 gene expression compared with 37% for high ERCC1 gene-expression levels (HR=2.32; 95% CI, 1.01-5.31). Median OS was 22.4 months in the high ERCC1 group and was not reached in the low gene-expression group.

Bohanes said ERCC1 gene-expression levels were not associated with complete pathologic response.

None of the other gene-expression levels tested showed a significant association with survival, and none of the tested polymorphisms showed any association with survival. – by Jason Harris

For more information:

Disclosure: Dr. Bohanes reported no relevant financial disclosures.

Twitter Follow HemOncToday.com on Twitter.

2011 Gastrointestinal Cancers Symposium

SAN FRANCISCO — Patients with stage II to III esophageal adenocarcinoma who had elevated levels of ERCC1 gene expression had inferior 2-year PFS and OS.

All 90 patients in the phase 2 molecular correlative study were assigned oxaliplatin plus infusion 5-FU and external beam radiation before surgery.

Researchers sought to determine whether intratumoral gene-expression levels in drug metabolism (DPD, GSTPi, TS and TP) and DNA repair (ERCC1 and XPD) predicted clinical outcome. They then tested whether a specific pattern of 12 polymorphisms in eight genes and DNA repair predicted outcomes.

ERCC1 gene-expression cutoff was <1.7 x 10-3.

“When we looked at progression-free survival by ERCC1 levels using the predefined cutoff of 1.7, there was a highest risk for recurrence in the high ERCC1 group, with the hazard ratio nearly reaching three,” said Pierre O. Bohanes, MD, an oncology fellow at the University of Southern California Norris Comprehensive Cancer Center.

Bohanes presented the results Thursday at the 2011 Gastrointestinal Cancers Symposium.

“The median progression-free survival in the high ERCC1 group was 14.8 months and was not reached in the low ERCC1 group,” he said.

In univariate analysis, 2-year PFS was 17% for patients with high ERCC1 gene expression vs. 67% for those with low gene expression (HR=2.97; 95% CI, 1.37-6.45). Two-year OS was 72% for patients with low ERCC1 gene expression compared with 37% for high ERCC1 gene-expression levels (HR=2.32; 95% CI, 1.01-5.31). Median OS was 22.4 months in the high ERCC1 group and was not reached in the low gene-expression group.

Bohanes said ERCC1 gene-expression levels were not associated with complete pathologic response.

None of the other gene-expression levels tested showed a significant association with survival, and none of the tested polymorphisms showed any association with survival. – by Jason Harris

For more information:

Disclosure: Dr. Bohanes reported no relevant financial disclosures.

Twitter Follow HemOncToday.com on Twitter.

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