2011 Gastrointestinal Cancers Symposium

Gene Signature Test Predicts Colorectal Cancer Recurrence

ColoPrint, a microarray-based gene signature test, accurately identifi ed the risk of recurrence of colorectal cancer in patients with localized stage II disease, raising the potential of an exciting new prognostic tool for clinicians.

Robert Rosenberg, MD, an assistant professor at the University Hospital of the Technical University in Munich, and colleagues used ColoPrint to analyze the expression of 18 genes in tumor tissue from 233 patients who had undergone surgical resection for stage II or III colorectal cancer from 1987 to 2003.

Of the 135 stage II patients, ColoPrint identifi ed 73% as low risk; only 5% developed recurring cancer within 5 years or more. The test identifi ed the remaining 27% as high risk, and 20% of these patients developed cancer with a median follow-up of 97 months.

ABSTRACT 358.

IMRT Therapy Has Fewer Drawbacks

Intensity-modulated radiation therapy (IMRT) in combination with chemotherapy delivered the same results as conventional combination radiation therapy, but with fewer adverse effects in anal cancer patients, according to study results presented by Lisa Kachnic, MD, chair of radiation oncology at Boston University, Massachusetts.

Kachnic, the principal investigator of the phase II Radiation Therapy Oncology Group (RTOG) trial, said in a press release that IMRT plus 5-fl uorouracil and mitomycin-C chemotherapy was “associated with signifi cant sparing of grade 3 and higher dermatologic and gastrointestinal acute toxicity.”

In the RTOG 0529 study, 52 stage II and stage III patients were treated with IMRT plus the chemotherapy regimen for 2 years. At median follow-up of 26.7 months, the 2-year disease-free survival (DFS) rate was 77% and overall survival (OS) was 86%. Investigators said the 325-patient RTOG 9811 trial, where patients received conventional radiation, resulted in 75% DFS and 91% OS with greater acute toxicity.

ABSTRACT 368.

PET Testing Used as Prognostic Tool

Positron emission tomography (PET) testing after 2 weeks of chemotherapy and before surgery helped determine whether patients with locally advanced adenocarcinoma of the esophagogastric junction would benefi t from additional radiation, researchers reported.

The prospective study MUNICON II involved 56 patients who were divided into 2 groups based on their response to initial chemotherapy as measured by PET results. The 33 responders were given an additional 3 months of chemotherapy before surgery, while the 23 nonresponders were given radiation before surgery aimed at shrinking tumor size.

Of the responders, 27 patients (82%) underwent curative surgery and have not yet reached median event-free survival and median OS after 38 months. Among nonresponders, 16 patients (70%) underwent curative surgery; the median event-free survival and OS were 15.4 months and 18.3 months, respectively.

The trial outcomes were reported by lead researcher Florian Lordick, MD, PhD, director of the Department of Hematology and Oncology at Klinikum Braunschweig in Brunswick, Germany, and senior lecturer at Hannover Medical School. She said at a press conference that the study is the fi rst attempt to guide treatment based on early PET testing, but that it unfortunately shows the lack of salvage treatment for those without an early response.

ABSTRACT 3.

ISH Testing Poses Advantages in Evaluating HER2 Expression

A comparison of methods for assessing the expression of human epidermal growth factor receptor 2 (HER2) in gastric cancer determined that in-situ hybridization (ISH) yields the best results, Australian researchers reported in a poster presentation.

The question is an important one since up to 33% of advanced gastric cancer cases exhibit amplifi cation or overexpression of HER2, M. Priyanthi Kumarasinghe, PhD, a clinical pathologist at Queen Elizabeth II Medical Center in Perth, and colleagues noted. Studies have shown that the anti-HER2 monoclonal antibody trastuzumab improves survival in HER2-positive disease, making accurate and consistent testing crucial for the use of HER2 as a predictive marker in gastric cancer, they said.

And, although HER2 testing in breast cancer has become routine in Australia as part of a national program, pathologists have limited experience in the evaluation of HER2 expression in gastric cancer tissue.

To assess the status of HER2 testing for this population, Kumarasinghe and colleagues conducted an interlaboratory reproducibility study involving 9 reference laboratories. Each laboratory received a tissue microarray encompassing 100 prescreened samples from patients with gastric or gastroesophageal junction adenocarcinoma. The laboratories evaluated the specimens for HER2 expression by both immunohistochemistry (IHC) and ISH (chromogenic ISH [CISH], silver ISH [SISH], or fl uorescence ISH [FISH]).

The laboratories demonstrated good concordance for ISH evaluation, the research team reported. In contrast, only moderate agreement emerged from IHC staining, except for IHC3 specimens.

“The good concordance across laboratories for HER2 copy number . . . suggests that ISH is the optimal method for HER2 testing in gastric cancer,” Kumarasinghe said. “The agreement between laboratories on HER2 score of samples by IHC was moderate, likely due to discordance between laboratories on the assignment of IHC1 and IHC2 samples, suggesting the need for ISH confi rmation in these cases.”

For all levels of HER2 (IHC0-IHC3 ) expression, the laboratories had overall agreement of 68%. Grouping IHC0/1 together resulted in an overall accuracy of 84%, increasing to 92% when IHC3 was a separate category and the other 3 levels of expression were considered as 1.

Laboratories using CISH/SISH had good or very good concordance when HER2 expression was defi ned by copy number (κ = 0.81), but agreement declined when test results were defi ned by HER2:chromosome 17 ratio (κ = 0.69). Comparison of central FISH with CISH/SISH showed the best results when results were defi ned by HER2 copy number (κ = 0.90).

On the basis of their fi ndings, the investigators recommended the following testing algorithm for HER2 expression in gastric cancer:

• IHC alone is not suffi cient for determining HER2 status in gastric cancer.

• Use of the HER2/chr17 ratio in ISH should be restricted to equivocal cases.

ABSTRACT 15

• IHC should be used for initial evaluation, followed by single-probe ISH evaluation for specimens that exhibit