onco_new_pubblication_mozart

We are excited to announce the publication of our latest research, 

"Next-generation sequencing-based evaluation of the actionable landscape of genomic alterations in solid tumors: the 'MOZART' prospective observational study,"

. The study highlights the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment.

For more details, the full study is available 

Oncologica new publication: “MOZART” prospective observational study on genomic alterations in solid tumors

new-hope-against-battle-with-cancer

For international travellers, taking their PCR test swab is only the beginning of the Coronavirus PCR test journey. 

In a meeting with Robert Courts MP, Minister for Aviation, Maritime & Security, Oncologica® explained the genetic science and logistics applied daily to thousands of PCR test swabs to determine positive or negative results.

Furthermore, the genomic sequencing of travellers’ positive PCR test results is vital for identifying high-risk COVID-19 variants of concern, to alert NHS Test and Trace and help prevent high-risk virus variants from entering the UK population across our borders.

To help guide the Minister through the PCR swab test journey, Oncologica® presented a video specially created to outline the keys stages of genomic testing and the impact this data driven approach is having on identifying and curbing high-risk variant transmission via incoming international travellers.

YouTube video player

Step 1: The Coronafocus Covid-19 PCR Test Self-Swab Kit

A lot of work happens before PCR swab tests arrive for processing at Oncologica®’s specialist genomic testing laboratory. Travellers across the world first order PCR test kits online at 

 helps link travellers to government travel testing rules and details when kits are dispatched to coincide with PCR test date requirements. Coronafocus self-swab PCR test kits can be used for Pretravel-Fit to Fly, Day 2 Green list country and Day 2 Day 8 Amber list country arrivals and for Day 5 Amber list Test to Release certificates.

The COVID19 PCR test kits are dispatched by courier to customers and each kit includes a packaged self-sample swab, liquid tube with a unique barcode, sealable bag, swab instructions and a prepaid Royal Mail tracked return envelope(s). Travellers receive instructions electronically when placing their orders, explaining how to register and activate their PCR travel test kit by inputting the date and the time the swab was taken into the online customer dashboard prior to return of their kits to the lab for analysis.

Travellers can drop the PCR tests in the tracked return envelopes into Royal Mail priority post boxes located in every town or village , return the PCR sample(s) by hand to the 24/7 Oncologica® lab or contract their own private courier.

When a swab is returned to Oncologica®, scientists prepare the samples for COVID-19 PCR testing. They log the swab into the system with the unique sample number which tracks the PCR swab sample through the process and ensures that names are not directly on display.

The scientists prepare the samples for the Polymerase Chain Reaction (PCR). This checks whether the virus’s genetic information is present in the sample. The swab gets placed in a chemical solution that breaks apart and releases nucleic acids — the RNA whose unique sequences help identify the presence of the virus in a sample.

Coronavirus is a single-stranded RNA virus and needs to be converted into DNA using specific enzymes to enable the PCR process.

The PCR testing technique copies the genetic information and flags any matches with viral sequences.

We are all familiar with the DNA double helix. Each strand is made up of building blocks called nucleotides. PCR breaks these apart, into single strands in the solution. Then, strands of DNA that are custom-built to match the virus’s unique genetic sequences are introduced. If there is viral DNA in the sample, these primer strands will naturally latch onto the complementary strands. In this way, each strand of matching viral DNA gets doubled. The series of events keeps repeating to increase the amount of viral DNA, so that even tiny amounts of virus in the swab sample create copies.

When DNA primers bind with viral strands in the sample, they activate fluorescent signals that help track these genetic matches. In duplicating the viral DNA, every new strand of DNA creates a little light. The PCR doubles the strands in every cycle for exponential growth and light creation. The light cannot be seen by the human eye and is read by the PCR instrument. If a sample includes the virus, then the DNA primer strands bind, and lights accumulate to a level that signifies a positive test.

Oncologica® have capacity to process up-to 40,000 PCR test swabs daily.  COVID-19 PCR swab test results are very specific and sensitive and are accessed via the online customer dashboard usually within 24 hours from booking the swab sample into the laboratory. This is to ensure individuals follow government guidelines to protect their health and prevent virus transmission to families and the wider public.

The UK’s Test and Sequence strategy requires any positive PCR test samples to be sequenced in government-accredited labs. Oncologica® is a leader in COVID-19 PCR testing and sequencing.

Our highly trained scientific and medical team use state of the art high-volume PCR and sequencing instrumentation to support the demands of the international travel testing programme.

The Integrated PCR testing and genomic sequencing strategy is pivotal in identifying emerging high-risk variants on a global scale. These variants can cross our borders rapidly, so sequencing them effectively detects and alerts NHS Test and Trace to emerging strains to help prevent them becoming prevalent in the population.  Sequencing is also important in monitoring vaccine efficacy, informing new vaccines designs and for protection from future escalating outbreaks.

Oncologica® PCR test options are detailed 

Oncologica® video follows COVID-19 PCR swab through genomic lab test

oncologica-new-paper-brain-cancer-biomarkers-v2

Glioblastoma, the most aggressive form of brain cancer is commonly treated with surgery, radiation, and chemotherapy. However, a newly published study from the research team at Oncologica the world-leading genetic cancer testing laboratory based in Cambridge UK, explains how their genetic sequencing research into predictive glioblastoma biomarkers can empower patients and doctors with DNA blueprints to make better targeted therapy decisions. This could lead to improved treatment outcomes beyond the current survival rate of 7% within five years of diagnosis.

The latest anti-cancer targeted therapies and immunotherapies are directed at the genetic DNA mutations that underlie the development and progression of brain cancer. The latest targeted cancer medicines offer great advantages over standard therapeutic approaches as they directly attack the cancer cells but leave normal cells relatively undisturbed. These new genomic targeted drugs have greater specificity and reduce toxic effects for patients compared to conventional chemotherapy.

The fast implementation of these targeted therapies into routine clinical practice has been constrained by a lack of comprehensive genetic screening for these DNA mutations at diagnosis. Furthermore, the processing of tissue biopsies using formaldehyde and wax embedding for diagnosis, results in fragmentation of the DNA test which makes analysis for mutations a challenge.

In Oncologica’s newly published study Oncologica shows how semiconductor biomarker sequencing can be used to accurately screen the fragmented DNA and RNA from routine glioblastoma biopsy/resection samples. This enables comprehensive DNA profiling to be undertaken in the routine initial diagnostic workflow to link detected mutations to a broad range of potential genomic targeted therapies and immunotherapies, rather than wait to see if standard treatments fail to control the disease.

“We are continually researching new ways to improve the genetic test options at initial diagnosis to provide valuable personalised data to aid targeted cancer treatments” said Dr Marco Loddo, Co-Founder and Scientific Director of Oncologica.

“We hope our data will help inform oncologists about the broad range of potential therapies that are now available and that this will translate into improved clinical outcomes for glioblastoma patients in the future said Professor Gareth Williams, Co-Founder and Medical Director at Oncologica.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245817

Learn more about our Oncofocus genetic test for all solid tumour types

 https://oncologica.com/cancer-tests/oncofocus/

Oncologica new research on detection of brain cancer biomarkers by genomic sequencing to improve survival rates

oncologica-rapid-identification-of-variants

The emergence of Covid-19 variants are a potential threat to the successful global vaccination programmes. Like all viruses, SARS-CoV-2 evolves over time through the acquisition of random mutations in its genome which is an innate characteristic of viral replication. Mutations have the potential to increase the virulence of the virus by for example increasing the transmissibility and/or the severity of the disease.

Of more concern is for the variant to evade the protective immunity generated by previous infection or by vaccination. At least three designated “variants of concern” have been reported including B.1.1.7 (Kent) which was first identified in the UK and drove a surge in cases, B.1.351 (South Africa), which was first identified in South Africa, and P.1 (Brazil), which was first identified in travellers from Brazil who were tested at a Japanese airport.

This threat is being mitigated though Covid-19 sequencing for people who test Covid-19 positive following PCR/antigen swab testing.

Rapid sequencing of swab positive cases enables immediate mobilization of NHS Track and Trace services to prevent the spread of high risk variants in the community.

Test and sequence has been introduced for international travellers arriving in the UK. All international arrivals must undertake PCR Covid-19 testing and quarantine for 10 days. The PCR test is required on or before day 2 and on or after day 8 of their quarantine period. For variant surveillance Covid-19 sequencing is required for cases testing positive.

Testing and sequencing needs to be completed in a short time window (72hours) so that the information can be effectively actioned, namely identifying and isolating individuals carrying high risk Covid-19 variants. To achieve this rapid reporting time Oncologica® has established Coronofocus (

 ), an integrated Test and Sequence platform to combine high capacity PCR testing with SARS-CoV-2 variant identification. Notably Oncologica® utilises semiconductor sequencing technology that enables >99% coverage of the viral coding sequence enabling the precise identification of Covid-19 variants.

Coronafocus provides an effective solution to rapid test and sequence demands and is helping contribute to the UK surveillance programme which is preventing the spread of variants that can potentially circumvent vaccine immunity.

https://www.gov.uk/government/publications/covid-19-surveillance

 Oncologica®’s Coronafocus COVID-19 Test and Sequence platform enables rapid identification of variants of concern

mutations-matter

At least half of patients with cholangiocarcinoma have mutations in their tumors that may be treatable with targeted drugs or immunotherapies that are either experimental or approved for other cancer types. These are available through clinical trials.

Yet when surveyed, half of patients with this diagnosis said their tumor tissue hadn’t undergone molecular profiling to determine if those mutations were present. Why not? Most said they hadn’t known about this kind of testing.

) — which supports and advocates for those with this rare cancer that affects the bile ducts — is determined to make sure everyone with the disease learns about and has access to genetic profiling and clinical trial partici­pation. The foundation is working toward that goal through its new program called Mutations Matter, funded with a $125,000 grant from Bayer Pharmaceuticals.

), educational videos and targeted email campaigns, the foundation plans to tell both patients and doctors why this testing should be done as soon as possible after a cholangiocarcinoma diagnosis.

“Profiling needs to be done immediately, so you can plan what you want to do next if it progresses,” Stacie Lindsey, president of the foundation, said in a presentation at the organization’s annual conference, held Jan. 30 in Salt Lake City, Utah. “Cholangiocarcinoma is the most highly targetable among gastrointestinal cancers,” she added — it expresses the most mutations that are potentially treatable with drugs already approved to treat other types of cancer.

The gap in knowledge on this topic lies mainly in the fact that 85 percent of patients with cholangiocarcinoma are treated outside major academic cancer centers, where both tumor profiling and access to clinical trials are standard, Lindsey said. In community treatment settings, she said, oncologists who treat cholangiocarcinoma tend to be generalists rather than gastrointestinal specialists, tumor profiling may be limited or discouraged, and access to clinical trials may be restricted or not offered.

When it comes to a rare cancer like cholangiocarcinoma, the fact that just 5 percent of adults with cancer participate in clinical trials is “tricky,” she said, because insufficient enrollment can lead to studies being canceled or pharma­ceutical companies and academia failing to invest in them.

The foundation conducted its survey of 132 patients and their profiling histories a year and a half ago, when the immunotherapy Keytruda (pembrolizumab) was approved for all solid tumors that are considered micro­satellite instability-high, meaning that they have trouble repairing their own DNA when it’s damaged. About 3 percent of patients with cholangiocarcinoma have that status and are eligible for the treatment, but they can’t know that unless their tumor tissue is profiled, Lindsey said.

Of the half of respondents who said that their tumors had been profiled, 62 percent noted that the test results had influenced their treatment decisions.

Lindsey cited 51-year-old survivor Matt Reidy as an example. He had his tumor profiled, and when Keytruda was approved two years later, it turned out he was eligible to take the drug.

“I started Keytruda, and within four months I had a complete response,” Reidy is quoted as saying on the Mutations Matter website. “I continued the therapy for 18 months total, and three years after starting, I remain cancer-free and consider myself cured.”

Lindsey said the foundation is running Mutations Matter with help from a variety of partners.

Komodo Health gathers data on where patients are being treated and how, to pinpoint where education is most needed. If hot spots are found at sites within the country, the foundation can wage email campaigns targeted to community oncologists there. Digital communications company DMD is in charge of those targeted email efforts, and public relations experts at EIN Communications created a communications plan and are reaching out to media.

It was D2 Creative that made the simple, digestible videos — called “illuminations” — that are available in six languages and aimed at patients and doctors. The Cholangiocarcinoma Foundation has established a blueprint for outreach to other nonprofit organizations that might benefit from sharing the videos with their members, Lindsey said.

Finally, Perthera Inc., a health care artificial intelligence company, is acting as a concierge for patients, facilitating genetic profiling for each and then generating a free report, including a list of potentially relevant clinical trials and how to contact them. Perthera is offering its services at no cost during the program’s first year, which began in June 2018.

Mutations Matter: Cholangiocarcinoma Tumor Profiling Awareness

high-capacity-pcr-testing

The Covid-19 pandemic has had major impact on the social and economic activities of the United Kingdom and has resulted in many deaths. The two major initiatives to address the pandemic has been the establishment of high capacity Covid-19 testing coupled to track and trace and the development of vaccines. Oncologica® has contributed to the pandemic by establishing an integrated Covid-19 test and sequencing platform that is being used to control the spread of the disease across the community and also assess the impact of the vaccines in relation to the different Covid-19 variants.

During the early stage of the pandemic Oncologica® initiated Covid-19 PCR/antigen testing for the protection of vulnerable immunocompromised cancer patients. Since May 2020 Oncologica® has contributed to the national testing efforts as part of the volunteer Covid-19 Testing Network to support the DHSC Covid-19 National Testing Programme covering care homes, local authorities, schools and symptomatic testing across test sites.

Oncologica® has now extended its testing more broadly to support businesses, offices, factories, educational institutions, healthcare and transport (aviation, shipping and railway networks).

To date we have undertaken over 600,000 Covid-19 tests. Our contribution to the UK national efforts to address the Covid-19 pandemic was recently recognised by our shortlisting, as part of the Covid-19 Testing Network [CTN], for the Special Covid-19 UK Response Project Award 

https://www.pmi.org.uk/awards2020-special-COVID-19-award

Oncologica® has been listed as an approved government provider for general testing and for the test to release scheme. Following the latest Government requirements for international arrivals Oncologica® now provides genomic sequencing of positive cases in compliance with the new guidelines.

To facilitate the release of lockdown, to aid economic recovery and to enable people to travel we have now increased Covid-19 testing capacity to 40,000 tests/day and optimised our testing workflow to provide the rapid reporting of results with a 12 hour turnaround time.

Oncologica® launches an integrated Test and Sequence platform to combine high capacity PCR testing with SARS-CoV-2 variant identification

lung-cancer-driver-discovery

Lung adenocarcinoma, the most aggressive subtype of non-small cell lung cancer (NSCLC), comprises nearly 40 percent of lung cancer diagnoses. The KRAS gene is the most significant driver of this cancer, and is also found in some pleural mesothelioma cases. Researchers have been stymied by this tough gene that nearly always fights off treatments building resistance to the drugs. Now, researchers report they have found a “genetic promoter” that drives this type of cancer and could lead to a new anti-cancer therapy.

Researchers from the Mayo Clinic report that the Ect2 gene (Epithelial Cell Transforming 2) is responsible for cytokinesis, cell division, in normal, healthy cells. However, they found that Ect2 was not needed for cytokinesis in lung adenocarcinoma cells, leading them to uncover the other function Ect2 serves in cancerous cells. They found that Ect2 boosts ribosomes, which “manufacture proteins from messenger RNA instructions.”

“Ect2 drives increased synthesis of ribosomal RNA, which in turn gives rise to increased ribosomes,” said Alan Fields, Ph.D., senior author on the paper and a cancer biologist in the Department of Cancer Biology at Mayo Clinic’s Florida campus, in a Jan. 19 press release. “While it’s been known for a long time that tumor cells have elevated ribosome levels, this paper is the first to show that Ect2 supports tumor cell growth by stimulating ribosome biogenesis.”

Pleural mesothelioma is a serious cancer affecting the lining of the lungs that occurs in individuals previously exposed to airborne asbestos fibers. Asbestos is a known carcinogen and is also proven to cause lung cancer and asbestosis, a chronic lung disease. While there are some differences between pleural mesothelioma and lung cancer, such as the fact that mesothelioma displays as a large mass of interlocked tumors whereas lung cancer is characterized by more distinct, individual tumors, the treatments are often similar.

“KRAS-mediated lung adenocarcinoma is a particularly deadly form of lung cancer, in part because attempts to directly target KRAS therapeutically have not been successful in the clinic,” says the study’s lead author, Verline Justilien, Ph.D., an assistant professor in the Department of Cancer Biology at Mayo Clinic’s Florida campus.

“Our current findings reveal a potential novel therapeutic strategy for treating mutant KRAS lung adenocarcinoma cells in which Ect2 is overexpressed,” Dr. Justilien said.

The American Cancer Society estimates about 222,500 new cases of lung cancer and nearly 155,870 deaths from lung cancer in the U.S. in 2017. Close to 3,000 Americans will be diagnosed with mesothelioma this year with nearly the same number dying from the terminal cancer.

Lung Cancer Driver Discovery May Lead to Novel Therapy for Some Mesothelioma Patients

cross-border-travel

With many people ditching staycations for trips overseas, the risk of traveller related introduction of high-risk COVID19 variants into the UK is a major issue surrounding European and international holiday travel. The UK government day 2 and day 8 covid international testing programme to mitigate this risk is one of the most stringent travel testing initiatives globally. PCR testing and genomic sequencing for UK arrivals coupled with successful vaccine rollout is proving key to safe overseas travel.

In a landmark paper investigating cross border COVID transmission, published online in EClinical Medicine by the The Lancet publication, Prof Williams and Dr Loddo of Oncologica® show data indicating that although vaccines are having a big impact, there is still a high prevalence of high risk SARS-CoV-2 variants entering the UK which could potentially undermine the vaccination programme gains.

The Oncologica® genomic laboratory uses very sensitive PCR testing techniques coupled with fast semiconductor sequencing technology, which enables the precise identification of variants of concern. In this study relating to 203,065 passengers’ tests, around 2 in every 100 travellers were found to have infection involving a broad range of COVID variants. The low sensitivity of pre-embarkation lateral flow testing may contribute to the high prevalence observed in travellers.

The UK government’s day 2 day 8 stringent PCR travel testing programme highlights the importance of monitoring cross border transmission, and the crucial role it is playing in protecting the integrity of the UK national vaccine programme against the import of high-risk variants with immunity evading properties.

The adoption of similar PCR COVID testing strategies in many countries is gaining importance globally as the numbers of new cases of SARS-CoV-2 has nearly doubled over the last 2 months. Therefore, the chances for the emergence of new high risk COVID-19 variants is potentially high.

The study also shows that two doses of the vaccine are highly effective at reducing asymptomatic infection. However, a significant proportion of fully immunized travellers harboured active COVID SARS-CoV-2 infection and there was no difference in the amount of virus particles, referred to as viral load, when comparing vaccinated versus non-vaccinated individuals.

The data indicates that vaccine passports or immunity certificates alone may not be adequate, and need to be supported by Covid PCR testing and sequencing.  Interestingly the measurable amount of virus of the Delta variant was found in the Oncologica® study to be 21-fold higher compared to the Kent variant and this supports the higher transmissibility of this variant now the most dominant in the UK.

Combining rigorous travel PCR testing and sequencing together with vaccination is likely to provide the best opportunity for safe international travel vital for the economy and leisure travel.  Such public health COVID detection measures combined with national NHS track and trace will enable normal activities to resume until the goal of global vaccination is achieved.

COVID vaccination, PCR testing and variant sequencing: The key to safe cross-border travel

mutation-targeted-therapy

Patients with previously treated advanced non-small cell lung cancer (NSCLC) lived more than twice as long without disease progression when treated with a drug that targets a key resistance mutation versus standard chemotherapy, investigators reported.

Treatment with the oral tyrosine kinase inhibitor (TKI) osimertinib (Tagrisso) led to a median progression-free survival (PFS) of 10.1 months as compared with 4.4 months for patients who received standard chemotherapy. A subgroup of patients with brain metastases also lived twice as long without disease progression when treated with the anti-EGFR/T790M agent.

Osimertinib also was better tolerated, associated with a 50% lower incidence of grade ≥3 toxicity than with chemotherapy, 

, of the Chinese University of Hong Kong, and co-authors reported in the 

“In this trial, we found that patients with T790M-positive advanced non-small cell lung cancer who received osimertinib had better response rates and a longer duration of progression-free survival than did those receiving platinum therapy plus pemetrexed after first-line EGFR-TKI therapy,” the authors concluded. “The progression-free survival benefit with osimertinib was observed across all predefined subgroups, with hazard ratios of less than 0.50, including in patients with asymptomatic CNS metastases.

“In five prespecified measures of patient-reported symptoms, osimertinib had better results than platinum-pemetrexed.”

The trial began before the emergence of immunotherapy, such as anti-PD1/PD-L1 agents, and more research is needed to evaluate the potential role of immunotherapy in patients with EGFR-positive NSCLC, the authors added.

The published results confirmed findings 

 at the European Lung Cancer Conference. The FDA approved osimertinib for NSCLC in December 2015.

EGFR-TKIs have evolved into standard first-line therapy for advanced NSCLC. Despite initially high response rates, most tumors progress within about a year after starting treatment. About 60% of progressive disease results from development of the T790M point mutation in 

. The mutation reduces binding of first- and second-generation EGFR-TKIs to EGFR protein, reducing the drugs’ inhibition of downstream signaling, the authors noted.

Osimertinib targets both EGFR and T790M and has activity in the CNS. In a 

, treatment with osimertinib resulted a 61% objective response rate and median PFS of 9.6 months in patients with T790M-positive NSCLC. Two 

involving more than 400 patients yielded similar results, leading to the randomized, phase III 

Investigators at 126 sites enrolled patients who had disease progression after initial EGFR-TKI therapy and presence of the T790M variant, confirmed by the cobas EGFR mutation test (Roche Molecular Diagnostics). All patients provided blood samples at baseline to screening for T790M in circulating tumor DNA.

The patients were randomized 2:1 to daily osimertinib or four cycles of chemotherapy. Patients who remained progression free after completing the planned chemotherapy could continue maintenance treatment with pemetrexed.

The trial had a primary endpoint of investigator-assessed PFS. Data analysis included 419 patients, who had a median follow-up of 8.3 months. The results showed that a 70% reduction in the hazard for progression or death among patients randomized to osimertinib (HR 0.30, 95% CI 0.22-0.41, 

<0.001). Objective response rates were 71% with osimertinib and 31% with chemotherapy (

The estimated 6-month PFS was 69% in the osimertinib arm and 37% in the chemotherapy arm. At 12 months, the estimated proportions of patients who were alive and disease free were 44% with osimertinib and 10% with chemotherapy.

About a third of the patients had asymptomatic brain metastasis at enrollment. Median PFS in that subgroup was 8.5 months with osimertinib and 4.2 months with chemotherapy, representing a 68% reduction in the hazard (HR 0.32, 95% CI 0.21-0.49).

The study population included 172 patients who tested positive for the T790M mutation by both tumor and plasma assessment. Median PFS in the subgroup was 8.2 months with osimertinib and 4.2 months with chemotherapy. Response rates were 77% with osimertinib and 39% with chemotherapy.

The incidence of grade ≥3 adverse events was 23% with osimertinib and 47% with chemotherapy. The most commonly reported adverse events with osimertinib (any grade) were diarrhea (41%), rash (34%), dry skin (23%), and paronychia (22%). Interstitial lung disease-like adverse events occurred in 4% of the osimertinib group (one death) and QT-interval prolongation in 4%.

Third-generation EGFR-TKIs, such as osimertinib, have shown considerable promise for overcoming resistance issues that have limited the efficacy of first- and second-generation agents, the author of a recent review noted. Osimertinib demonstrated 200-fold greater selectivity for the mutation-associated proteins T790M and L858R as compared with wild-type EGFR in studies involving patients with NSCLC that had progressed on first-line EGFR-TKI therapy.

The increased selectivity of osimertinib for T790M also resulted in a more favorable safety profile compared with second-generation EGFR-TKIs, development of which has been held back by dose-limiting toxicity, 

, of Zhongda Hospital in Nanjing, China, wrote in 

Mutation-Targeted Therapy Slows Lung Cancer (NSCLC)

harnessing-our-own-immune-system

Immunotherapy, in which the body’s own immune system is harnessed to kill cancer cells in patients with advanced disease, is proving a powerful treatment in around 15% of cancer patients. Importantly this type of treatment can be used to treat a broad range of different tumour types including lung, breast and bladder cancers and melanoma.

The patients who are likely to respond to such treatment can be identified by analyzing the tumour biopsy with a special stain called the PD-L1 test. Tests which are able to identify a patient likely to respond to a particular treatment are called companion diagnostic CDx assays. Oncologica®, in collaboration with AstraZeneca, has recently completed a study involving the participation of internationally recognised pathologists to assess the performance of one of these tests, called the VENTANA PD-L1 (SP263) Assay in lung cancer.

Preliminary findings were presented at the ESMO 2018 congress in Munich, Germany. The study has now been completed and the findings recently published in the Journal of Thoracic Oncology, a leading journal in the field of lung cancer. We have shown that assessment of tumour cell (TC) scores by expert pathologists is highly reproducible in lung tumour samples using the VENTANA PD-L1 (SP263) Assay, thus building confidence in the performance of this test as a companion diagnostic for anti-PD-L1 immunotherapy.

This will help ensure that patients who may benefit from immunotherapy are correctly identified.

Immunotherapy: an anti-cancer treatment based on harnessing our own immune system to attack cancer cells

immunotherapy-less-toxic-and-prolongs-life

An immunotherapy drug that could save some cancer patients from the ordeal of extreme chemotherapy may also help them live longer, researchers say.

In a trial, pembrolizumab kept head and neck cancers at bay for an average of two years – five times longer than under chemotherapy. The patients also suffered far fewer side-effects.

Cases of head and neck cancers are rising in the UK and most are diagnosed late, when they are harder to treat.

Derek Kitcherside, 70, from Leicestershire, believes he wouldn’t be here without pembrolizumab.

He was diagnosed with cancer of the voicebox in 2011. When he started coughing up blood three years later, after receiving standard treatment, he was told the cancer had spread to his lungs and was probably incurable.

Derek asked to go on a drug trial and travelled to London every three weeks for two years for treatment with pembrolizumab.

“My tumour was shrinking all the time and I felt a bit better every time I went,” he said. “It made a huge difference to my life.”

Regular scans show the disease is now stable and the tumour is still getting smaller.

“I’m very pleased I can get on with my life,” Derek said.

“I don’t think I’d be here without it.”

It is a treatment that does not kill cancer cells itself but instead stimulates the body’s immune system to attack them. Pembrolizumab is already being used to treat a wide range of advanced cancers, including melanoma – a type of skin cancer that spreads easily.

Experts believe the drug has the potential to treat many more.

Normally, immunotherapy is used after standard treatments like chemotherapy have failed but this trial, in 882 patients from 37 countries, suggests it should be used earlier – and for some people it should be the go-to option.

The drug is given to patients regularly through a drip when their cancer has returned or spread, and is considered incurable.

It is kinder, safer and can keep patients alive for longer, the study in The Lancet found.

In people with advanced head and neck cancer who responded to the drug – one in four – their cancer shrank or stabilised for an average of 23 months.

By comparison, although more patients (36%) responded positively to standard chemotherapy treatment, the improvements lasted on average for only four and a half months.

Those with larger, more aggressive tumours were given the drug in combination with chemotherapy to help slow progress of the disease – which was kept in check for an average of seven months.

The trick is identifying people with tumours that will respond, says Prof Kevin Harrington, oncologist at The Royal Marsden NHS Founation Trust and professor of biological cancer therapies at the Institute of Cancer Research, who led the study,

A test for the presence of immune marker PD-L1 in the tumour means doctors can work this out.

Prof Harrington says approximately 85% of people with advanced or relapsed head and neck cancer would be eligible for pembrolizumab – around 1,300 patients a year.

At the moment, the recommended treatment is a toxic combination of chemotherapy and antibody therapy, which often makes people feel very sick.

The extreme treatment can also cause damage to the kidneys, hands and feet.

Patients given the immunotherapy drug experienced far fewer side-effects.

“It’s more sensible and less toxic – patients live longer and feel better,” says Prof Harrington.

“This study is very exciting”, says Prof Paul Workman, from the Institute of Cancer Research.

“Firstly because it shows that immunotherapy can have dramatic benefits for some patients with head and neck cancer when used as a first-line treatment, and secondly because the researchers have devised a test for picking out who is most likely to benefit.”

He said all new drugs coming on to the market should be accompanied by a test to target their uses as precisely as possible.

In the US and the EU, pembrolizumab has been approved for use on its own and with chemotherapy for advanced head and neck cancer, but not yet in the UK.

The National Institute for Heath Care and Excellence is currently appraising pembrolizumab and it could be approved for use on the NHS by next summer.

Cancer immunotherapy drug “less toxic and prolongs life”

revolution-in-cancer-treatment-has-begun

Chemotherapy is no longer the only option against cancer,

 there are now more than 600 targeted therapies available to treat solid tumours. 

Targeted therapies are the cornerstone of personalized medicine, 

a form of medicine that uses information about a person’s DNA profile to treat cancer.

The Oncofocus® test can identify new treatment options in 85% of patients

 who have supposedly exhausted standard treatments protocols.

St Vincent’s Hospital and Blackrock clinic, Dublin

Oncologica® Ltd Senior Commercial Manager

Oncofocus® Cancer Test and targeted therapies. The Revolution in cancer treatment has begun.

detection-of-biomarkers-in-glioblastoma

Glioblastoma is the most aggressive form of brain cancer, with debilitating symptoms including seizures, memory loss, difficulties in language processing, muscle weakness and visual changes. The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival with the five year survival rate being around 7%.

The exponential increase in modern anti-cancer agents called targeted therapies and immunotherapies are directed at the genetic DNA mutations that underlie the development and progression of cancer. Targeted agents therefore offer the great advantage that they directly attack the cancer cells but leave normal cell relatively undisturbed. Targeted agents therefore show increased specificity and reduced toxicity when compared with conventional chemotherapy.

One of the hurdles to the implementation of targeted therapies into routine clinical practice has been lack of comprehensive genetic screening for these therapy linked DNA mutations at diagnosis. The processing of the tissue biopsies using formaldehyde and wax embedding for diagnosis results in fragmentation of the DNA which makes analysis for mutations a challenge.

In our recent study we show that semiconductor sequencing can be used to robustly screen the fragmented DNA and RNA from routine glioblastoma biopsy/resection samples. This enables comprehensive DNA profiling to be undertaken as part of the routine diagnostic workflow allowing linkage of detected mutations to a broad range of potential targeted therapies and immunotherapies that can be considered should standard treatment protocols fail to control the disease.

https://www.biorxiv.org/content/10.1101/2021.01.11.426191v1

Utilisation of semiconductor sequencing for the detection of predictive biomarkers in glioblastoma

most-precise-treatments

Molecular genetic testing identified the most precise treatments

Genetic testing not only provides information regarding the chance of developing a particular disease but is also crucial in identifying the most effective anti-cancer therapy for each individual patient suffering from any solid tumour. Thus the battle against the tumour is tailored.

Genetic tests are basically of two types: the first is the predictive one, which allows asymptomatic people to reveal all the hidden secrets of their DNA and to quantify their risks of falling ill with certain diseases, cancer in particular, especially tumours of breast and ovary, colorectal and prostate and other diseases such as juvenile Alzheimer’s and cardiovascular diseases. The second type of test is aimed at people already suffering from cancer, a precision cancer test that is able to identify the most effective cancer therapy, especially biological, for each individual patient suffering from any solid tumour. From the routine paraffin blocks containing the excised or biopsied tumour tissues of the individual patient, stored in the pathology archive of the treating hospital, a piece of this material is sent to the precision oncology laboratory, for example Oncologica® UK, based in Cambridge, UK. Here the sample is analysed using the Oncofocus® test and within 10 – 15 days the report is issued which provides Oncologists with the linkage between the identified genetic mutations and the targeted drugs approved by the major world organizations as well as those undergoing clinical trials and additionally the immunological drugs that have recently entered clinical practice.

There is now a major change in direction regarding the method used for treatment selection in cancer. This modern approach, rather than recommending treatments based solely on the fact that the individual has a specific type of cancer, such as lung, breast, colorectal, etc., instead bases therapy selection by examining the disease at a molecular level. The best way to treat cancer with modern anti-cancer drugs is therefore “agnostic of cancer type”, meaning regardless of the type of cancer a patient may have developed. This is an approach that has been approved by the US Food and Drug Administration (FDA) and that has been adopted by many other countries such as Australia.

These “tumour-agnostic” therapies are beginning to show promising results in the clinical setting, helping patients with a wide variety of different tumours types that have previously been difficult to treat using conventional drugs, especially those patients in second line after the failure of first line treatment. In the tumour center of the Tirelli Medical Group (

) based in Pordenone we have already treated a hundred patients with this therapeutic strategy based on the recommendations of the American Food and Drug Administration (FDA) with often surprisingly favourable results.

Notably this is in keeping with a study recently published in the journal “Oncotarget” by a group of Stanford University in California showing that the use of therapy based on precision oncology (e.g. Oncofocus® Test) improves the survival of refractory cancer patients while decreasing the costs of treatment.

Mutations that play a fundamental role in the development of neoplasms have been called “driver” mutations since they are able to confer a growth advantage in the affected cells. Approximately 350 driver genes involved in cancer development have been identified in human tumours. Investigations by massive sequencing have shown that tumours exhibit numerous mutations, most of which are not drivers but “passengers”, i.e. not involved in tumour development but randomly occurring and selected by rapid neoplastic growth.

Knowing the genetic drivers, that is those genetic alterations that are the basis of tumour cell multiplication, means that it is possible to develop precision treatments that specifically and in a completely new way address the choice of biological and immunological drugs.

At the moment, oncologists have limited information in trying to find the right anti-cancer drug for their patient. There are in fact more than 300 anti-cancer drugs and hundreds of different types of cancer, each of these also possesses different genetic mutations that respond differently to therapies, it follows that, even for a good oncologist the chances of finding an effective drug mix can be low.

The use of genetic testing of the tumour biopsy sample is able to help the oncologist in making the right choice by increasing the probability of prescribing an effective drug. Immunological therapy is also identified through this type of testing. Prof. Riccardo Dolcetti, who is a professor of oncological medicine at the University of Queensland in Australia and who has been at the Cancer Institute of Aviano for a long time, tells me that there genetic testing on the tumour tissue is done following diagnosis in the major tumour types (e.g. lung, breast, colorectal, prostate, etc.) but that they also carry out genetic testing on the tumour biopsy taken following relapse if feasible. At the Tirelli Medical Group of Pordenone we carry out genetic testing only in cases of tumoural relapse, that is in patients in whom the first line therapy has failed, even though testing could take place at diagnosis to identify the best treatment available.

Even though the clinical implementation of genetic testing is still not such as to be used in routine clinical practice, it may be in the near future according to what was recently reported in the “New England Journal of Medicine”. The first so-called tumour histology-independent treatment, that is “agnostic of cancer type” was recently recommended by the European for approval in relation to the drug called Larotrectinib. This is a drug that targets a specific genetic mutation called NTRK i.e. the gene coding for the neurotropic tyrosine kinase receptor. Larotrectinib is indicated for the treatment of all pediatric and adult solid tumours that have the NTRK mutation regardless of their tumour type, i.e. whether it is breast, lung, colon, melanoma, etc.

This drug was approved in November 2018 in the United States and is considered an example of a targeted drug that radically changes the approach to cancer treatment. The data that have been recently published in the “New England Journal of Medicine” show an overall response of 76% which is quite unusual for patients heavily pre-treated with conventional therapies who have subsequently been administered Larotrectinib. This genetic alteration can be found in lung, colon, breast, thyroid and melanoma tumours.

Director of Tumor Center, Chronic Fatigue, Fibromyalgia and Oxygen-Ozone Therapy,

Tirelli Medical Group Clinic of Pordenone.

The most precise treatments with genetic tests

brother-diagnosed-with-incurable-brain-tumour

​Sherrie Hewson was due on stage when her phone rang with shattering news.

The Coronation Street ­favourite’s beloved elder brother Brett had been diagnosed with an incurable brain tumour. He was given 18 months to live. Sherrie, 68, burst into floods of tears in her dressing room.

The actress, who played stroppy hotel manager Joyce Temple-Savage in Benidorm, was about to appear in a stage version of the ITV sitcom.

In the months that followed Sherrie would turn her life upside down to help Brett fight the killer disease and to be by his side.

She said: “I wouldn’t take it in. I think it was my way of dealing with it because I knew I was due on stage and because I just didn’t want to believe it.

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