Digital Pathology and Personalized Medicine News and Discussion

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Thomas Grogan of Roche Ventana Medical Systems Provides Pathologists Predictions about Anatomic Pathology

Posted on Friday, April 30, 2010

Being an employee of Definiens, I am very encouraged by Dr. Grogan’s predictions. Definiens for years has been on the forefront of quantitative, multiplexed analysis of localized biomarkers, as well as morphological quantification of individual cells. This was the purpose of the development of Definiens Tissue Studio, which facilitates translational research towards these ends. The Definiens XD platform facilitates the deployment of Definiens technology in the clinical setting:  Clarient (breast cancer IHC algorithms) and Aureon (prostate cancer H&E and immunofluorescence algorithms for morphology and biomarker localization and expression, respectively) are two examples. Going forwards, Definiens Tissue Studio (for translational research) and Definiens XD platform (for CLIA or 510K diagnostics) together will facilitate points 1, 2, 4, and 5 below:

More multiplex and multi-analyte testing lies ahead for clinical pathology laboratories.

Several experts predict that clinical pathology laboratories will see the use of multiplex assays and multi-analyte diagnoses increase significantly in the near future. As this happens, both the science and the operations of clinical laboratories and pathology practices will grow in sophistication and complexity.

This week at the Executive War College on Laboratory and Pathology Management in New Orleans, Louisiana, almost 600 pathology and laboratory leaders gathered from 12 nations across the globe. During Wednesday’s general session, Thomas M. Grogan, M.D., Founder and Chief Scientific Advisor of Roche Ventana Medical Systems laid out his vision of how surgical pathology will evolve in the future.

Grogan organized his predictions around six key areas of science which are experiencing rapid refinement and will contribute to new capabilities within anatomic pathology. He characterized each as a forward move “beyond” the current status quo:

* First, beyond diagnosis to therapeutics. Grogan noted that new lab testing technologies give pathologists more precise understanding about the disease being studied. In turn, that additional knowledge makes it possible to pathologists to identify which therapies will be most appropriate for the patient.

* Second, beyond single-analyte diagnosis to widespread use of multiplexing. This is appropriate because both clinicians and patients want more sophisticated knowledge about the tissue, the disease, and the most appropriate therapies.

* Third, Beyond protein to “gene + protein” assays. Grogan provided several cases to illustrate how the standard of practice for selected types of cancers now requires more than just protein analysis. To provide a more sophisticated understanding of the patient’s disease, pathologists will evaluate the specimen using both protein and genetic assays.

* Fourth, Beyond qualitative to quantitative assays. This is a steady shift away from “yes or no” assays in favor of lab tests which provide more detailed information about the cancer being diagnosed. It is this richer set of data which the clinician can use to identify therapies likely to be effective, to monitor the patient, and to predict recurrence of the disease.

* Fifth, Beyond informatics to cellular informatics. This relates to the detailed understanding of cells, including individually and collectively, along with their functional and spatial relationships within the tissue. He emphasized the importance of morphological context.

* Sixth, Beyond written reports to electronic patient-centric reports. On this point, Grogan emphasized the need for pathologists to be more consultative and to contribute to the creation of an integrated report which incorporates all the relevant clinical data for the physician and the patient.

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Phase III Study Supports Ability of VeriStrat to Stratify NSCLC Patients for Tarceva Treatment

Posted on Friday, April 30, 2010

Results from a phase III trial presented today suggest that Biodesix’s VeriStrat proteomics-based test may be able to predict which patients may benefit from treatment with Tarceva (erlotinib) for non-small cell lung cancer, Biodesix said.

At the Second European Lung Cancer Conference in Switzerland, David Carbone, professor of medicine and cancer biology at the Vanderbilt University School of Medicine, presented data that applied the VeriStrat test to a group of 441 patients and classified them either as “VeriStrat Good,” meaning they are likely to benefit from erlotinib therapy; or “VeriStrat Poor,” meaning they are likely to “derive little therapeutic benefit.”.

The 441 patients come from a total of 729 patients who are involved in NCIC Clinical Trials Group study BR.21, a phase III multicenter trial of erlotinib versus placebo in previously treated patients with NSCLC.

The study, which was funded by Biodesix, found that VeriStrat Good patients had a median survival of 10.5 months compared to VeriStrat Poor patients who had a median survival of 4 months.

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Approval of Provenge marks beginning of new era in cancer treatment

Posted on Friday, April 30, 2010

From Dana Farber Cancer Institute

Today’s announcement that the U.S. Food and Drug Administration has approved Provenge, a new form of therapy for some prostate cancer patients, marks the beginning of an era in which patients’ own immune systems become part of the standard therapeutic arsenal against cancer, say Dana-Farber Cancer Institute investigators who led a study of the treatment’s effectiveness in patients.

The study – the results of which were presented most recently at the 2010 Genitourinary American Society of Clinical Oncology‘s annual meeting – is the first large, controlled clinical trial to show that an immune system-based therapy can extend the lives of cancer patients, according to the trial’s leader, Philip Kantoff, MD, of Dana-Farber.

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New Study Demonstrates Patients With High-Risk MammaPrint Profile Benefit From Chemotherapy

Posted on Thursday, April 29, 2010

HUNTINGTON BEACH, California, and AMSTERDAM, April 29, 2010 /PRNewswire/ — Today, at the 11th Annual Meeting of the American Society of Breast Surgeons, Agendia, a world leader in molecular cancer diagnostics, announced that Breast Cancer Research and Treatment has published an important study demonstrating the benefit of adjuvant chemotherapy for patients with a high-risk of breast cancer recurrence according to the MammaPrint test. The ASBS meeting takes places April 28 – May 2, 2010, at the Bellagio in Las Vegas, where you can meet the Agendia team at booth # 314.

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Dendreon’s Clean Bill Of Health

Posted on Thursday, April 29, 2010

Via Forbes.com

One of the most controversial biotechnology companies of the past decade is poised to become one of the most successful.

The Food and Drug Administration announced it is approving Dendreon’s Provenge, a cell therapy that primes patients’ immune systems to fight off prostate cancer cells. The positive verdict came three years after the agency rejected Provenge in its first attempt at approval. Dendreon did another big study and convinced the agency that its cancer vaccine works.

The approval is a major milestone for Dendreon, the tiny biotechnology company that developed the treatment based on basic research that occurred at Stanford University. Dendreon shares, which have risen more than 200% in the past year, blasted up another 6% to $45 when news of the approval crossed the wire. Then they were halted. When trading restarted, shares were up 31%, to $52.

Update:

Provenge to cost $93K for full course of treatment

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ASCP 2010 Annual Meeting Digital Pathology Course Offerings

Posted on Thursday, April 29, 2010

From Digital Pathology Blog

Keith Kaplan: The upcoming ASCP Annual Meeting will feature several sesssions discussing Pathology 2.0, digital pathology, including telepathology and image analysis and personalized healthcare.

Looks like an excellent faculty for these sessions.  The meeting will take place in San Francisco between October 27-31, 2010.

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Breakthrough Method Predicts Risk of Invasive Breast Cancer

Posted on Thursday, April 29, 2010

From Science Daily

For the first time, scientists have discovered a way to predict whether women with ductal carcinoma in situ (DCIS) — the most common form of non-invasive breast cancer — are at risk of developing more invasive tumors in later years.

As a result of the finding, women with DCIS will have the opportunity to be more selective about their treatment, according to the scientists.

“Women will have much more information, so they can better know their risk of developing invasive cancer,” said lead author Karla Kerlikowske, MD. “It will lead to a more personalized approach to treatment. As many as 44 percent of patients with DCIS may not require any further treatment, and can rely instead on surveillance.”

The study was led by researchers at the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, and is reported online by the Journal of the National Cancer Institute.

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OSI Pharmaceuticals Announces That Tarceva® Received Approval in the European Union for Maintenance Use in Advanced Non-Small Cell Lung Cancer – Yahoo! Finance

Posted on Thursday, April 29, 2010

MELVILLE, N.Y.–(BUSINESS WIRE)–OSI Pharmaceuticals, Inc. (Nasdaq: OSIP – News) announced today that its international partner for Tarceva® (erlotinib), Roche, received approval from the European Commission for Tarceva as a monotherapy maintenance treatment in patients with advanced non-small cell lung cancer (NSCLC) whose disease remains largely unchanged (stable disease) after platinum-based initial chemotherapy.

“We are pleased that the European health authorities recognize Tarceva as a valuable option for lung cancer patients and their physicians when used in the first-line maintenance setting,” said Colin Goddard, Ph.D., Chief Executive Officer of OSI Pharmaceuticals. “We look forward to working with our partner, Roche, to advance the robust Tarceva lifecycle program, which includes evaluating Tarceva in the adjuvant setting and as a first-line treatment for advanced NSCLC patients with an activating EGFR mutation as well as branching into other disease settings including liver cancer.”

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Personalized Medicine for Cancer Patients in a New Technology Era

Posted on Wednesday, April 28, 2010

Definiens classification of NSCLC uising Definiens Developer XD. Acinar regions are in brown; white space, yellow; papillary regions, purple. Approaches like this may one day lead to more effective cancer grading and treatment. H&E image courtesy of MD Anderson.

ScienceDaily (Apr. 16, 2010) — Published online in Nature, a paper authored by over 200 members of the International Cancer Genome Consortium (ICGC) describes the beginnings of a Brave New World, a new era of personalised medicine for cancer patients.

Formed in 2008, the consortium brings together leading cancer researchers from around the world, working together to catalogue the genetic changes of the 50 most common cancers — 500 genomes from each cancer type — and make the results freely available on the internet.

“Given the tremendous potential for relatively low-cost genomic sequencing to reveal clinically useful information, we anticipate that in the not so distant future, partial or full cancer genomes will routinely be sequenced as part of the clinical evaluation of cancer patients,” say the authors in the paper.

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FDA makes changes for medical device advisory committees

Posted on Wednesday, April 28, 2010

The FDA’s Center for Devices and Radiological Health (CDRH) is making several changes to the way its expert panels review and discuss information at panel meetings on devices under premarket review during public hearings.

According to a news release from the agency, the changes are a result of an increasing number of medical device advisory panel meetings in recent years. Among the noted changes will be in regard to staffing issues, voting procedure and panel deliberations, as well as other issues related to information presentation and flow of discussion. This year, the FDA believes it will surpass the 17 meetings held in regard to 20 topics in 2009, prompting the need for change, said the agency, as increased activity has created challenges for the operation of panel meetings.

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HER2/neu Marker in Breast Cancer Guidelines and Recommendations

Posted on Wednesday, April 28, 2010

Definiens classificaiton of Her2 stained breast tumor cells using Definiens Tissue Studio. High intensity cells, dark red; medium intensity, orange; low intensity, yellow.

Recommendations of the HER2/neu Advisory Committee, Ontario, Canada:

The testing laboratory must have an established immunohistochemistry program with sufficient volume to maintain technical/professional knowledge and skill. (The UK guidelines recommend performance of 250 IHC and, if applicable, 100 FISH tests per year1). For Ontario, we recommend a minimum of 20 HER2/neu IHC tests per month or 240 HER2/neu tests per year.

The laboratory must have a quality assurance improvement program that provides for the required quality control and uses quality indicators to determine whether performance is meeting the quality standard.

At least one pathologist from each centre, involved in the reading and interpretation of immunohistochemical preparations in situ hybridization for HER2/neu, must complete appropriate training.

Quality Assurance Requirements – To be read in conjunction with the Testing Algorithm Schematic

It is recommended that tissue be fixed with 10% phosphate buffered formalin (4% formaldehyde), pH 7.0. The optimal fixation time is 8 to 48 hours.

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Biomarker Studies Could Realize Goal of More Effective and Personalized Cancer Medicine

Posted on Wednesday, April 28, 2010

By Katie Moisse @ Scientific American

When President Richard Nixon launched the war on cancer in his January 1971 State of the Union, he called for “the same kind of concentrated effort that split the atom and took man to the moon.” Yet nearly 40 years and $100 billion in federally funded cancer research later, it seems the lunar landing was a much less daunting task.

Although much has been learned about the biology of cancer, the overall survival rate among people who have it has improved only slightly, according to a commentary published April 21 in Science Translational Medicine. The authors of the commentary argue that developing strategies to match new and existing drugs with the tumor characteristics of individual patients is a crucial step toward greater success in cancer treatment—an effort known as personalized medicine. “We have reached a juncture where talking about personalized cancer medicine and the importance of incorporating these goals into clinical trials is no longer sufficient,” they wrote.

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Subtle changes in PTEN protein levels increase chances of developing cancer

Posted on Wednesday, April 28, 2010

Subtle gene changes may increase cancer susceptibility

A US study has found that even subtle changes in the levels of PTEN, a protein that blocks cancer development, may significantly increase a person's chances of developing cancer.

Scientists already knew that losing one or both copies of the gene which contains the information to make PTEN can increase the chance of developing tumours.

But the latest study from Beth Israel Deaconess Medical Centre (BIDMC) indicates that even tiny changes – which don’t mean fully inactivating the genes – may play an important role.

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Biomarkers key to better cancer trials

Posted on Tuesday, April 27, 2010

Definiens classification of breast tumor sub-cellular structures using Definiens Tissue Studio. Nuclei, dark blue; cytoplasm, light blue; membrane, red.

By John Carroll @ Fierce Biotech

Joseph Nevins, director of the of the Duke Institute for Genome Sciences and Policy’s Center for Applied Genomics & Technology, believes it’s time to radically change the way that cancer drugs are developed if we expect to see a new generation of personalized therapies. Because of the complexity of cancer–breast cancer, he speculates, could be broken down into 15 different types of cancers – tissue samples should be collected from patients going through clinical trials so that more effective biomarkers can be developed to match a new treatment with a patient.

via Biomarkers key to better cancer trials – FierceBiotech.

Reform to increase U.S. healthcare spending about $311B

Posted on Tuesday, April 27, 2010

HealthImaging.com has an interesting article about the new U.S. health care reform bill. Unfortunately, we now learn that the bill will actually add expense to the ballooning US national debt. I would be very interested to hear opinions from the pathology community about the health care reform bill and its intended and unintended consequences. Good or bad? Both? Leave a comment below…

President Obama’s health care reform plan is estimated to increase the overall national health expenditures under the health reform act by a total of $311 billion over the next decade, according to a report last week from Richard Foster, chief actuary of the Centers for Medicare & Medicaid Services (CMS).

According to the April 22 memorandum from the Office of the Actuary, this figure primarily reflects the net impact of greater utilization of healthcare services by individuals becoming newly covered, lower prices paid to health providers for the subset of those individuals who become covered by Medicaid and lower payments and payment updates for Medicare services.

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Avastin: Time for a Predictive Test

Posted on Monday, April 26, 2010

By Patricia F. Dimond, Ph.D. @ GEN

The expanded use of Avastin (bevacizumab) into the first-line setting, adjuvant therapy, as well as into additional advanced cancers is a high-stakes proposition for Roche. The drug is currently used to treat advanced colon, breast, lung, and kidney cancers. In the past year, however, Phase III trials have failed to show its potential in late-stage prostate, advanced stomach, or early-stage colon cancers.

A test to identify potential responders to Avastin and/or to monitor therapy results and disease progression would prove extremely valuable for Roche’s development plans. It would also spare those patients who would not see a response to the drug from the side effects associated with it. The therapy has been linked to arterial clots, heart attacks, stroke, and bowel perforations.

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New Study of How Digital Pathology Enabled by Web 2.0 Functions Boosts Productivity and Adds Clinical Value

Posted on Sunday, April 25, 2010

By Justin Clark @ Dark Daily

Pathologists using digital scanning and digital pathology systems can now utilize latest-generation Web 2.0 functionality to enhance productivity and increase compensation. That’s the message in a newly-published White Paper, “Pathology Innovators Use Web 2.0 to Boost Productivity and Create Clinical Value.”

Already, the first digital pathology products that incorporate Web 2.0 functions are available and in use at a number of innovative pathology laboratories. The distinction between Web 1.0 and Web 2.0 is important. Web 1.0 was a passive interface between web pages and the user. Web 2.0 is a responsive, interactive interface between the web page and the user. Thus, when Web 2.0 functions are incorporated into digital pathology systems and pathology workflow, significant productivity and quality gains result.

The White Paper “Pathology Innovators Use Web 2.0 to Boost Productivity and Create Clinical Value” is tailored to the needs of any pathologist or lab professional looking to fully modernize their laboratory. Published by The Dark Report and Dark Daily, it is available free to laboratory professionals as a PDF download here.

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Novartis to Pay $45M Up Front in Cancer Collaboration with Array BioPharma

Posted on Sunday, April 25, 2010

Array BioPharma inked a deal with Novartis for the worldwide development of the small molecule MEK inhibitor ARRY-162, currently in a Phase I cancer trial. The agreement also covers its back-up, ARRY-300, and other MEK inhibitors. Array will initially receive $45 million comprising an upfront and milestone fee.

The firm is eligible to get an additional $422 million if certain clinical, regulatory, and commercial milestones are achieved. Array plans on co-developing ARRY-162 in one or more indications and funding a portion of development costs.

Array will earn double-digit royalties on sales of approved drugs outside of the U.S. and a higher royalty rate for U.S. sales if it meets co-funding obligations. Array also has a co-detailing right in the U.S. for approved drugs.

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News: Ventana to Work on Companion Diagnostic for Clovis’ Phase II Lipid-Conjugated Gemcitabine.

Posted on Sunday, April 25, 2010

Ventana Medical Systems is to develop a companion diagnostic for use in ongoing clinical trials of Clovis Oncology’s lead anticancer candidate, Phase II-stage CO-101. The human equilibrative nucleoside transporter 1 (hENT1) immunohistochemistry assay will be leveraged to identify patients with low level tumor expression of the hENT1 protein. Clovis says that if CO-101 development is successful and submitted for registration in major markets, Ventana will also submit the hENT1 assay for PMA as a Class III device.

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Pfizer halts Sutent testing for liver cancer

Posted on Sunday, April 25, 2010

Pfizer halts Sutent testing for liver cancer

By Tracy Staton

Created Apr 23 2010 – 9:36am

Pfizer’s bid for broader use of its cancer drug Sutent has hit another wall. The company stopped a late-stage trial of the drug as a treatment for liver cancer, saying that it wasn’t as effective as Bayer’s Nexavar in this indication. In addition, patients on Sutent were more likely to suffer serious side effects.

The company calls the trial’s outcome disappointing and says the result “does not diminish our confidence in Sutent for the treatment of patients” with kidney cancer and gastrointestinal stromal tumors. “We … are working with investigators to better understand these trial results and their implications for clinical practice,” SVP Mace Rothenberg says in a statement.

This is Pfizer’s second setback on Sutent in as many months. The company said in March that Sutent didn’t perform against advanced breast cancer [1] as well as it had hoped. Pfizer is continuing to test Sutent against other cancer types, including non-small cell lung cancer and prostate cancer.

via Pfizer halts Sutent testing for liver cancer.