The Daily Sign-Out

Comments on CAP Proposed Revision to Stomach Cancer Protocol

Comments are now available for viewing concerning proposed revisions to CAP Stomach Cancer Protocol.  It's obvious that those who reviewed the protocol and offered their comments gave this matter careful consideration.

Comment Period for Revision to CAP Cancer Protocol for Stomach

The CAP has announced the opening of a comment period for revisions to the Stomach Cancer Protocol.

Prior to the release of the revised Stomach Cancer Protocol, the College of American Pathologists (CAP) will host a public comment period. You can review the revisions and submit feedback online. The public comment period will run through November 4, 2011. Please note that comments are not instantly available for review and will be posted on a weekly basis.

 

The Protocol for the Examination of Specimens from Patients with Carcinoma of the Stomach has been revised to:

 

• Update the histologic type section in response to new histologic classification from the World Health Organization in 2010
• Clarify the reporting of margin status by adding elements for reporting lateral mucosal margins from endoscopic mucosal resection specimens
• Add optional elements for reporting in situ and immunohistochemical studies of HER2

So here's your chance.  This is an important update and, I think, the College really needs to hear from those of us "in the trenches" as it were who are signing these cases out daily.  I don't think that HER2 testing should be optional but I'll be putting my comments in on that.

Trastumuzab approved for treatment of HER2-positive

from primeLines:

"On December 17, 2009, Roche’s trastuzumab (Herceptin^®) received a positive recommendation from the European Medicines Agency (EMEA) for use in combination with standard chemotherapy for the treatment of previously untreated patients with HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction. The positive opinion for this new indication was issued in record time due to high unmet medical need and data from the ToGA trial (my emphasis), which demonstrated an increase in overall survival (OS) for patients with advanced HER2-positive gastric cancer who received trastuzumab plus chemotherapy (intravenous fluorouracil or capecitabine and cisplatin) compared to chemotherapy alone."

I have done the immunostain for HER2 routinely on the last few gastric adenocarcinomas diagnosed since I blogged about the ToGA trial and HER2 in gastric cancer last year.  The rapidity of this recommendation is similar to what occurred with cetuximab/panitumumab in colorectal cancer with wild-type KRAS.

I have not seen any guidelines regarding grading of the IHC stain nor recommendations regarding reflex FISH but have used the same criteria as for reporting HER2 by IHC in breast.  I must add that this is not considered "standard-of-care" at this point and that this has been initiated by me not our local oncologists.  This would be a good topic to discuss at your hospital's tumor board or cancer grand rounds.  I recently had a case of a gastroesophageal junction adenocarcinoma in which I did do HER2, so it is of note that this is approved for GEJ tumors as well.

Novel classification for gastric cancer using pathways

A multi-institutional study published online on Oct. 1 in PLoS Genetics examined 301 gastric carcinomas using gene expression profiles and a pathway prediction model to identify major oncogenic pathways involved in gastric cancer and relate expression of these pathways to patient survival.  They found proliferation/stem cell-related, Wnt/beta-catenin, and NF-kappaB pathways are deregulated in over 70% of the gastric cancers they studied.  Furthermore, the found patterns of pathway co-activation associated with survival.  This is a free access paper so please download and read.

Reading the "Materials and Methods" of this paper is worthwhile in itself because the strategy the authors used is well-conceived and explained.  More importantly, this study demonstrates the feasibility of using gene expression profiles to perform in silico experiments to make pathway predictions as a basis for in vitro experiments--another example of "systems thinking" in pathology and oncology.

ASCO 2009--Herceptin in Gastric Cancer

As a follow-up to my previous post on HER2 in gastric cancer, here is a summary of the new results from the ToGA trial presented at ASCO 2009 which have been called "practice-changing."

This multinational study was conducted in 594 patients with HER2-positive disease, of nearly 4000 patients with advanced gastric cancer, screened for HER2 expression by both FISH and IHC.  All patients received chemotherapy (mostly cisplatin and capecitabine) and half were randomized to receive trastuzumab.  This trial was stopped early, after 17 months, because of the benefit seen.

The improvement in overall survival was 2.7 months, from 11.1 months in the chemotherapy group to 13.8 months in the trastuzumab group (hazard ratio, 0.74, P = .0046).  In addition, trastuzumab improved all of the secondary end points, including progression-free survival (increased from 5.2 months to 6.7 months; P = .002) and overall response rate (increased from 34.5% to 47%; P = .0017).

Two additional points of interest to pathologists:

As I noted before, this study demonstrates that HER2 overexpression varies with the site of the tumor and histology. Although overall, 22% of patients were HER2-positive, overexpression was found in 35% of those with tumors at the EG junction and 33% of those with intestinal pathology, but only 6% of those with diffuse pathology.

Also, when the criteria in the ToGA trial for HER2-positive gastric cancer are limited to those used for breast cancer (i.e., FISH-positive and/or IHC-3+, as recommended in 2007 ASCO/CAP guidelines), only 256 patients would have been included in the trial, but in these patients, the magnitude of benefit was even greater, with overall survival improved from 12.3 months to 17.89 months (hazard ratio, 0.58).

See my previous post for a reference on a modified HercepTest scoring system pertinent for gastric cancer.  Meanwhile, I think we should expect HER2 testing to be routine for gastric carcinoma, especially in GEJ and intestinal type tumors.

HER2 in gastric cancer

I was listening to a preview of the 2009 ASCO Conference (starting on May 29) on Medscape and one of the anticipated studies being presented is the results of the ToGA trial, a multi-center, international phase III trial evaluating the combination of trastuzumab with standard 5FU plus cisplatin chemotherapy in advanced HER2 positive gastric cancer.  Update to follow but meanwhile. . .

There is a nice review of the subject in Annals of Oncology, 2008;19:1523-1529 by Gravalos and Jimeno.  Preliminary data from this trial reported at ASCO 2007 in an abstract the HER2-positive rate in gastric cancer is about 24% (about what it is in breast cancer) and similar concordance between IHC and FISH (87%) but that there is a marked difference in HER2 expression by histologic type (36% intestinal, 7% diffuse).  I expect to see requests for HER2 testing on gastric cancer specimens and to start performing this routinely.  Of interest to pathologists is that there is a modified HercepTest scoring system that is more appropriate for gastric cancer compared to breast cancer of which we should be aware (Hofmann F, Stoss O, Shi D, et al.  Histopathology  2008;52:797-805).  Also, it is notable that there is a high concordance between surgically resected specimens and prior biopsy specimens so it is not necessary to repeat HER2 IHC.