Pathwork tissue of origin test confirms clinical validity

The Medical Technology Blog

Independent study of Pathwork tissue of origin test confirms clinical validity; “cost-effective for increasing cancer patient survival”

Results of a study conducted at Virginia Commonwealth University of the Pathwork Diagnostics’ Pathwork tissue of origin test have been published online in the American Journal of Clinical Pathology, in a paper entitled “Clinical verification of the performance of the Pathwork tissue of origin test: utility and limitations”. The Pathwork tissue of origin test is an FDA-cleared, Medicare-covered molecular diagnostic for identifying tissue of origin. It uses a tumour’s own genomic information to help pathologists and oncologists in the diagnosis of challenging cancer cases such as those that are metastatic or that have a complex clinical history.

In the study, the analytic and clinical performance of the tissue of origin test was examined in 43 poorly differentiated and undifferentiated tumour samples. Results showed 97 per cent (95 per cent confidence interval, 80.4 to 99.8 per cent) agreement between the tissue of origin test result and the reference diagnosis, which was determined on the basis of clinical correlations and immunohistochemical findings and was among the 15 tumour tissue types covered by the tissue of origin test.

The Pathwork tissue of origin test measures gene expression levels of 2,000 genes and uses algorithms to compare the tumour’s gene expression pattern with that of 15 tumour types, representing 58 morphologies and 90 per cent of all solid tumours. The test provides objective genomic information to help the physician diagnose what type of cancer the patient has. An accurate diagnosis allows oncologists to match therapy to the cancer.

In a related development, results from a study involving the Pathwork tissue of origin test have been presented at the American Association for Cancer Research – International Association for the Study of Lung Cancer joint conference on The Molecular Origins of Lung Cancer: Biology, Therapy and Personalised Medicine in San Diego, CA. The study, “Cost-effectiveness of gene-expression profiling for tumour-site origin”, was authored by John Hornberger, Irina Degtiar, Hialy Gutierrez, Ashwini Shewade, W David Henner, Shawn Becker and Stephen Raab.

The retrospective, observational study examined treatment changes made in patients by physicians who received tissue of origin test results. Changes in planned chemotherapy, surgery, radiation therapy, blood tests, imaging and referral to hospice care before and after test results were recorded. Estimates of the effect of changes in chemotherapy on survival were based on National Comprehensive Cancer Network (NCCN) and other treatment guidelines. Costs were estimated based on data from NCCN and Centers for Medicare and Medicaid Services fee schedules. Changes in overall survival, costs and cost per quality-adjusted life year (QALY) gained were estimated. In the study, use of chemotherapy regimens consistent with guidelines for the final tumour-site diagnosis increased from 42 per cent to 65 per cent. Overall survival was projected to increase from 15.9 months to 19.5 months, a mean gain of 3.6 months. The average increase in survival adjusted for quality of life was 2.7 months and the average cost per QALY gained was US$46,858.

Article source; Diagnostics Focus, edited by Sophie Bracken, medical news editor at Espicom Business Intelligence.


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JHU team uncover gene test to predict cancer in pancreatic cysts

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Welcome back to The Medical Technology Blog, todays article is taken from Espicom’s business publication Diagnostics Focus, please read on…

Johns Hopkins University (JHU) scientists have developed a gene-based test to distinguish harmless from precancerous pancreatic cysts, and which could eventually help some patients avoid needless surgery to remove the harmless variety. The investigators estimate that fluid-filled cysts are identified in more than a million patients each year, most of whom have undergone CT or MRI scans to evaluate non-specific symptoms, such as abdominal pain and swelling.

Dr Bert Vogelstein, co-director of the Ludwig Center at JHU and a Howard Hughes Medical Institute investigator, and his colleagues analysed precancerous cysts from 19 patients and searched for mutations in 169 cancer-causing genes. They found mutations in the KRAS gene, known for its prevalence in pancreatic cancers, and the GNAS gene, which had not previously been associated with pancreatic cancer. In both KRAS and GNAS, the mutations occur at a single coding spot in the DNA, the equivalent of a typo in a word within an entire encyclopaedia. KRAS and GNAS genes produce signalling proteins, relaying signals from the cell surface to areas within the cell.

The researchers then tested a total of 132 precancerous pancreatic cysts for mutations in KRAS and GNAS. The latter were found in more than half of the samples (87 of them), and KRAS mutations occurred in 107 samples. Nearly all (127) had mutations in GNAS, KRAS or both. The mutations occurred in large and small, high- and low-grade cysts, and in all major types of the most common precancerous pancreatic cysts. There were no major differences in age, gender or smoking history for people with GNAS or KRAS mutations in their cysts’ cells. Finally, the investigators tested tissue from pancreatic cancers that had developed in eight people with GNAS-mutated cysts. Seven of the eight had GNAS mutations in their cancer, as well as cells in the cysts.

GNAS and KRAS mutations were not found in benign cysts, although KRAS mutations did appear occasionally in a rare type of cyst with a relatively low potential to become cancerous. These rare, mostly benign cysts are less challenging to diagnose because of their location within the pancreas and type of patient, according to the investigators. Genetic analysis of the kind reported in the new study offers a new way to sort the potential of these cysts to cause malignant trouble.

The investigators caution that cyst fluid removal, an invasive procedure, also has its drawbacks and can cause bleeding, infection and inflammation in a very small percentage of patients. Further studies on a larger number of patients are expected to be done before the gene-based test can be widely offered. However, Vogelstein says that the technology for developing a gene-based test in this case is relatively straightforward because “the mutation occurs at one spot in both of the genes.”

Major funding for the study was provided by the Lustgarten Foundation, a private foundation that provides to funding pancreatic cancer research. Other funding was provided by the Virginia and D K Ludwig Fund for Cancer Research, the Sol Goldman Center for Pancreatic Cancer Research, the Joseph L Rabinowitz Fund, the Michael Rolfe Foundation, the Indiana Genomics Initiative of Indiana University, which is supported in part by Lilly Endowment., the J.C. Monastra Foundation, Swim Across America and the National Institutes of Health. JHU has filed a patent application on inventions described in the study.

Thanks to Lawrence Miller for this post, if you woul like more information like this, or to start your subscription please click on the link  Diagnostics Focus Newsletter

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HQ relocation brings Nuvilex closer to the action

The Medical Technology Blog

Nuvilex, a company that dedicates itself to the development of natural and biotechnology products, has made the canny decision to up sticks and move its corporate headquarters from Scottsdale, AZ, to Silver Spring, MD – only four miles from the FDA’s doorstep. Nuvilex is hoping that the move – which is in its final stages – will give the company immediate access to the FDA’s resources as the company pursues clinical development of its pancreatic cancer treatment technology, as well as other biotechnology developments in the future.

Not only is the company’s HQ in the FDA’s backyard, it is also only about ten miles away from the National Institutes of Health, and the National Cancer Institute – both major sources of funding grants and research collaborations. To explain the move, Nuvilex’ President and CEO, Dr Robert F Ryan, said the new location “..will facilitate our interactions with the FDA, an important part of our overall strategic planning, especially given our recent entry into biotechnology and our plans for expansion in this area”.

Nuvilex’ pancreatic cancer treatment is currently being geared-up for more clinical trials, and apparently, significant advances are in progress with the company’s live-cell encapsulation technology. Natural products in development include Gluten-Free Cinnergen and others to enhance a healthy lifestyle. The company is also developing products designed for cosmetic use, flu treatment and the use of heavy-metal-free tattoo inks. Future developments are planned for Citroxin and Oraphyte, Nuvilex’ antimicrobial and antinematodal agents.

This article was kindly provided by Sophie Bracken, editor of Drug Delivery Insight for Espicom.

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Results of a survey conducted at europacolon’s European CRC Patient Conference show that patients believe tests using blood samples would encourage more people to participate in regular screening for colorectal cancer.

The survey was jointly conducted by Epigenomics and europacolon, a European non-profit organisation dedicated to colorectal cancer. Of the participants in the survey, more than 50 per cent had previously heard of the possibility of colorectal cancer blood testing and more than 70 per cent thought that using a blood test would encourage more people to participate in regular screening for the condition. Some of the most often mentioned reasons that survey participants gave for preferring blood tests were ease-of-use and simplicity, not having to handle stool samples as necessary for conventional non-invasive testing, and overall fit with other routine blood tests.

In June, Quest Diagnostics, one of Epigenomics’ partners in the US, in collaboration with the non-profit organisation Colon Cancer Alliance, reported the results of a US national telephone survey of more than 1,300 men and women 50 years of age and older. In this survey, 31 per cent of the participants reported that they had never been screened for CRC. Of the respondents between 60 to 70 years of age that had previously participated in screening, 33 per cent stated that they had only been screened once in the past. These results highlight widespread lack of adherence to national guidelines in the US, which recommend regular screening by colonoscopy in combination with other tests for colorectal cancer for all men and women aged 50 and older. When asked about the option of a blood test, 78 per cent of the participants said that they were likely to take a blood test for colorectal cancer screening and 75 per cent said they were more likely to get screened more frequently if a blood test was offered to them.

According to Dr Jürgen Beck, Senior VP Medical Affairs of Epigenomics, the lack of widespread acceptance and regular use of conventional methods for the early detection of colorectal cancer, such as colonoscopy and stool tests, severely limits the potential of screening to reduce mortality from this common cancer. The two surveys in Europe and the US show the potential of blood-based screening as an approach to increase compliance. Epigenomics expects these findings to be substantiated further through studies into patient preferences and screening adherence that are ongoing at clinical centres in the US and Europe.

Epigenomics has developed an in vitro diagnostic blood test for the early detection of colorectal cancer, known as the Septin9 test. Alongside its partner, Abbott, the companies already market their respective first-generation CE-marked Septin9 tests in Europe, the Middle East, Asia/Pacific and further markets. Epigenomics is in the process of developing a second-generation Septin9 assay as a colorectal cancer screening test for the US and European markets. The company expects to submit this enhanced Septin9 colorectal cancer screening test, branded Epi proColon 2.0, to the FDA for regulatory review before the end of the year. Under licences from Epigenomics, Septin9 testing is currently offered in the US by Quest Diagnostics (ColoVantage) and ARUP Laboratories (Methylated Septin9 Test) as laboratory-developed tests aiding in the detection of colorectal cancer.

This article was provided by Sophie Sanderson, editor of Espicom’s newsletter Diagnostics Focus.

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Silence pours cash into development projects

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Last post on the Medical Technology blog before i shoot off on my hols, so no posts till i get back. Today’s article comes from Drug Delivery Insight, please read on…

Leading RNA interference (RNAi) company Silence Therapeutics has been busy lately. The UK-based firm tapped investors for nearly £6 million in funds last month, and has wasted no time in putting it to use. The company believes the funds, which were raised by both new and existing shareholders, will place it on a much improved financial footing.

The first slice of the funding was allocated to plan the closure of Silence’s US operations, which are located in Redwood City, CA. The US closure is expected to take place in the third quarter of this year, but the company’s German operations will remain open. As a result of the closure of the US base, Silence’s CEO, Phil Haworth, will step down once a replacement is found.

The second chunk of funding will be put towards Silence’s ongoing R&D efforts. The first portion will be used to complete the company’s ongoing Phase I trial of Atu027 for the treatment of advanced solid cancer, and is earmarked for completion during the second half of this year. Also, a Phase Ib trial of Atu027 in particular tumour types will be started in mid-2012. IND applications for Atu027 in solid will also be paid for by the funding in the second half of next year, and preclinical development will be stepped up for Silence’s Atu111 programme. The latter provides systematic delivery to the lung for treatment of pulmonary diseases.

Representing Silence’s most advanced drug candidate, Atu027 is a liposomal siRNA formulation targeting PKN3 for the treatment of advanced solid cancer that incorporats the company’s very own AtuPlex delivery technology. The company says it has proven its value by inhibiting the growth of blood vessels, thereby inhibiting blood supply to the tumour. Half-time results from the Phase I solid tumour trial of Atu027 are “encouraging”, as the drug has so far shown to be safe and well-tolerated. Silence hopes to finish the Phase I trial in the second half of this year, and release data before year-end.  The release of updated data from the trial was made at the recently-convened ASCO meeting in Chicago, IL.

Atu111, for the treatment of acute lung injury, is Silence’s most advanced candidate outside of the oncology field. It combines the company’s DACC drug-delivery system with AtuRNAi. The product’s target is being kept under wraps by Silence at the moment, but preclinical models using the DACC delivery system have shown sustained knockdown of up to three weeks in the lung endothelium.

As far as collaborative partners go, Silence is getting ready to start a Phase IIb trial for PF-‘655 in the second half of 2011, which is licensed to Quark Pharmaceuticals and Pfizer for the treatment of diabetic macular oedema.  Silence hopes Quark and Pfizer will report data from the trial later this year. Quark is also developing QPI-1002 for the treatment of delayed graft function and acute kidney injury in partnership with Novartis. In September 2010, quark kicked off a Phase II trial of QPI-1002 for the treatment of delayed graft function and plans to begin a second Phase II trial of the product in acute kidney injury during the course of this year.

Thanks to Sophie Bracken for this article, Sophie is editor of Drug Delivery Insight at Espicom Business Intelligence.

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Scientists use tumour’s ‘fingerprint’ to test for rare cancer

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Today’s article in the Medical Technology Blog is provided by Sophie Sanderson editor of Diagnostics Focus, please read on…

A team of researchers from the UK look to have come up with a ‘cheap and reliable’ diagnostic test for a rare form of cancer – hereditary leiomyomatosis and renal cell cancer (HLRCC) – which involves screening tumour samples for a particular molecular fingerprint unique to this cancer.

HLRCC is a disorder that causes the development of benign, but often painful tumours in the skin and, in females, in the uterus. Between one in six and one in ten people affected by the disorder will go on to develop an aggressive form of kidney cancer called papillary renal cell cancer. The disorder is caused by mutations, which may be inherited, in a gene responsible for the production of an enzyme known as fumarate hydratase (FH). This leads to an accumulation within cells of fumarate, which promotes the development of cancer cells. Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. HLRCC is said to follow an autosomal dominant inheritance pattern, in which a mutation happens in only one copy of the gene – meaning that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation.

Led by researchers at the Henry Wellcome Building for Molecular Physiology, University of Oxford, an international team of scientists claim to have identified a particular protein modification that is induced by FH deficiency (and hence an over-abundance of fumarate). This alteration is unique to this type of tumour and can be used as a biomarker – a biological ‘fingerprint’ to identify tumours caused by this mechanism.

For the first time, scientists are now in a position to screen for tumours caused by this rare, but often very serious condition using a test that is simple, cheap and reliable. The test for this protein modification offers great potential as it can be carried out in under two hours and will identify tumours with FH mutations. This approach is also said to be more cost-effective than genetic testing of all possible cases using DNA sequencing. When screening cases of papillary renal cell cancer using this new test, the researchers identified undiagnosed cases of HLRCC for genetic testing.

In the future, by applying this test in all cases of papillary renal cell cancer to identify people with FH mutations, families could receive advice on their own relative risks of developing the disorder and associated kidney cancer. Dr Lesley Walker, Director of cancer information at Cancer Research UK, reinforces the importance of this notion, stating that “…being able to identify other family members who are at risk so they can be monitored more closely is crucial to improving survival rates from this rare aggressive form of kidney cancer.” Tests like this could also help identify other patients with the same mutation, paving the way for the development of targeted treatments for specific groups of patients that could revolutionalise cancer treatment in the future.

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Todays article in the Medical Technology Blog is provided by Sophie Sanderson who is the editor of Diagnostics Focus, please read on…

A move to tackle the rates of lung cancer detection and survival by researchers in Germany seems to have led to an interesting new test that could potentially help save the lives of smokers in the future. The blood test, which is the result of work carried out by colleagues from the University of Cologne and University of Bonn, would make it easier to detect a lung tumour and improve the chances of survival.

The aim of the research was to develop a subsequent test that was not only able to differentiate lung cancer patients from healthy subjects, but also from persons with chronic lung diseases. The blood of over 200 smokers was studied, half of whom had lung cancer. Examining the research subjects’ blood using biochips for certain nucleic acids led to the finding of typical patters. Interestingly, over 480 molecules were recognised whose concentration in the blood changes when a person develops lung cancer. These nucleic acid molecules can be seen in the blood cells either in increased or decreased quantities and form in the body when certain genes are transcribed. In patients with lung cancer, a typical pattern emerges that can be detected with a measuring programme.

The stakes are huge and the development of a test for lung cancer offers huge potential. Lung cancer is already the second most common cancer in the UK, and in many cases the cause can often be linked back to smoking. Although people who have never smoked can also get lung cancer, nine out of ten cases are related to smoking. There are four different stages to lung cancer, going from stage I where the cancer is small and only in one area of the lung, to stage IV where the cancer has spread to another part of the body. Dr Joachim Schultze comments that “The prognosis for patients in stage III and IV is still very poor even today; even with the most modern therapies, the point of death can only be postponed.” When considering stage I lung cancer, it can be treated surgically and in most cases it can be cured, however, a tumour is detected in only about 15 per cent of all such cases.

It is anticipated that if a boost to the detection rates could be achieved with the use of a screening blood test, it could lead to an increase in survival rates. In the future, there is the potential for a lung cancer screening test to become part of routine practice. Whether this can be achieved remains to be seen, but for researchers the positive results will serve as an encouraging development.

Check out more articles like this by signing up to Espicom’s fortnightly publication Diagnostics Focus, thanks for reading.



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