Cancer Drug Might Help Curb Severe COVID-19

Could a cancer drug spare hospital patients from the ravages of severe COVID-19?

Yale doctors think it can after giving the medication, known as tocilizumab, to severely ill patients back in March.

How does tocilizumab work? It has a long history of dampening the life-threatening immune system reactions cancer patients often experience while undergoing treatment. Since the same kind of dangerous response develops in many COVID-19 cases, the researchers thought the drug might make a difference for the sickest patients.

The result — while preliminary — appears to be a dramatically lower death rate among patients placed on mechanical ventilators.

How much lower? Among the first 239 COVID-19 patients treated at Yale New Haven Hospital, in Connecticut, during the early weeks of the pandemic, 153 were treated with tocilizumab, including all 48 patients who had been placed on ventilators. “Instead of survival rates of 10% to 50% reported elsewhere, it was 75% in [ventilated] patients treated with tocilizumab,” said study author Dr. Christina Price, Yale’s chief of clinical allergy and clinical immunology.

In addition, among those seriously ill patients who ultimately survived COVID-19, tocilizumab appears to have significantly shortened overall ventilation time. While hospitals around the country were having to keep patients hooked up for between 12 to 14 days, ventilations at Yale typically lasted only about five days.

How tocilizumab works against COVID-19

What accounts for its apparent success against COVID-19?

It all originates in the threat posed by a deadly immune system phenomenon known as “cytokine release syndrome” (CRS), an out-of-control inflammatory response that the virus triggers in some patients.

CRS is “when the body’s response to fighting the virus goes so unchecked it ends up being harmful, damaging the liver, the kidney, the lungs. You need an immune response. You can’t totally shut it down completely. But you can’t let it get out of control, which is what can happen to cancer patients undergoing treatment. And to COVID patients,” Price said.

The problem? “There were no [U.S. Food and Drug Administration]-approved medications for COVID in March,” she stressed.

Read more…

Using convalescent blood to treat COVID-19: The whys and hows

Some researchers and doctors have started using plasma from people recovering from COVID-19 to treat others who have developed the disease. Medical News Today spoke to Dr. Arturo Casadevall, from Johns Hopkins University, to learn more about this approach.

In the search for an effective treatment for COVID-19, an old method of fighting infectious diseases has recently resurfaced: transfusions with convalescent plasma. Plasma is a component of blood.

This method has a simple premise. The blood of people who have recovered from an infection contains antibodies. Antibodies are molecules that have learned to recognize and fight the pathogens, such as viruses, that have caused disease.

Doctors can separate plasma, one of the blood components that contain such antibodies, and administer it to people whose bodies are currently fighting an infectious disease. This can help their immune systems reject the pathogen more efficiently.

Recently, researchers and healthcare professionals have been looking into the possibility of using this method to treat people with COVID-19, the respiratory disease caused by the SARS-CoV-2 virus.

In the United States, a group of researchers and doctors from 57 institutions, including Johns Hopkins University, the Albert Einstein College of Medicine, and the Icahn School of Medicine at Mount Sinai, are investigating and applying convalescent plasma therapy for COVID-19.

This is a concerted initiative — called the “National COVID-19 Convalescent Plasma Project” — born after the publication of a viewpoint paper in The Journal of Clinical Investigation in March, 2020.

The paper argued for the potential merits of passive antibody therapy in the treatment of COVID-19. It was authored by immunologists Dr. Arturo Casadevall, chair of the Molecular Microbiology & Immunology Department at Johns Hopkins Bloomberg School of Public Health, and Dr. Liise-anne Pirofski, professor of Infectious Diseases in the Department of Medicine at the Albert Einstein College of Medicine.

To understand more about convalescent plasma therapy, its merits, its risks, and its current use in COVID-19 treatments, Medical News Today recently spoke to Dr. Casadevall.

Here is what he told us, alongside more information on the current state of convalescent plasma therapy.

A therapy ‘used for over 100 years’
So, where did the idea of using convalescent plasma, or passive antibody therapy, come from?

This notion was first introduced in the late 19th century when physiologist Emil von Behring and bacteriologist Kitasato Shibasaburou discovered that they could use antibodies present in serum — another blood component — to fight the bacterial infection diptheria.

Since then, doctors have used passive antibody therapy, on and off, at least since the 1930s to treat or prevent both bacterial and viral infections, including forms of pneumonia, meningitis, and measles.

When we asked him how the idea of using convalescent plasma therapy to treat COVID-19 came about, Dr. Casadevall told us: “I have worked on antibodies my entire life professional life […], and I knew that convalescent plasma — or sera […] — was being used for over 100 years.”

“In fact, the first Nobel Prize was given [to Behring] for the use of serum to treat diphtheria, so I knew the history.” This long history of successfully using this method against different infectious diseases suggested that it might also be effective against the disease caused by SARS-CoV-2.

“I knew that in epidemics when you don’t have a lot of things, […] the blood of those who recover can have antibodies that can be used [as treatment],” Dr. Casadevall explained.

“So it’s an old idea, it’s been around for a long time, and I think that my contribution was, in fact, to alert my friends, authorities, that this [therapy] could be used in this epidemic.”

Recent research has already shown that people who have contracted SARS-CoV-2 have developed antibodies that can react to the coronavirus.

“There [are] now multiple studies that have shown that when people recover from the virus, they have in their blood neutralizing antibodies that are able to kill the virus,” Dr. Casadevall also told MNT.

Although “[p]eople differ greatly in the amount of antibodies that they make — some make large amounts, some make small amounts — […] the good news is that most have [them],” he added.

Given the willingness of people who have recovered from COVID-19 to donate blood, the method seems feasible right now. In fact, some doctors are already using convalescent plasma therapy in some cases.

Settling the matter of safety
In the U.S., the National COVID-19 Convalescent Plasma Project have already been trialing this method as widely as possible.

Dr. Casadevall told MNT that “in the United States, we have close to 12,000” people who have received the convalescent plasma treatment for COVID-19.

Based on the data obtained from a little less than half of this cohort, Dr. Casadevall and his colleagues have concluded that this approach is safe for the patients receiving treatment — the first step necessary before ascertaining the method’s effectiveness.

The team has reported these findings in a preprint that they have made available online.

“[On May 14], we put out a paper on the first 5,000 [patients] showing that [this therapy] was relatively safe. That’s the first step,” Dr. Casadevall explained.

“You want to show safety. And then the question of efficacy will be coming in the next few weeks. Right now, the data [is] being analyzed. We are hopeful,” he also told MNT.

“And,” he added, “especially since [the] Italians are reporting already that the use of convalescent plasma was associated with a drop in mortality [due to COVID-19]. We are hopeful that similar insights [will] come from the analysis of the data in the United States.”

In Europe, the European Blood Alliance — a non-profit association — report that 20 countries have initiated the use of convalescent plasma in the treatment of COVID-19 or are considering it for the near future. These include Italy, Spain, and the United Kingdom, some of the European countries most aggressively hit by SARS-CoV-2.

Demonstrating this procedure’s safety is essential because of the risks inherent to the transfusion of blood or blood components.

There is also the issue that adding more liquid volume into a person’s vascular system could lead to a risky overload, Dr. Casadevall explained.

“The concerns when you give plasma [include the fact that] rarely, you can get a transfusion reaction, [and] rarely, you could have a volume overload. What do I mean by that? I mean that […] you’re putting volume into blood, and if it goes in too rapidly, it could [lead to an] overload [of the] cardiac system,” he said.

“So when we looked at the experience of the first 5,000 [patients], we were very reassured that we did not see any major problems.”

Worries and hopes going forward
While different centers in the U.S. are already using convalescent plasma in the treatment of COVID-19, Dr. Casadevall expressed a worry that the therapy is not as effective as it might be because most patients receive it too late in the course of the disease.

Aside from its use in clinical trials, the Food And Drug Administration (FDA) have approved the administration of this form of therapy only in emergency situations to patients in a severe stage of the disease, which may not be soon enough.

“Often, physicians are using the plasma on patients that are very ill, and we don’t really know whether that’s going to be as effective as if you gave it early in the course of the disease,” Dr. Casadevall pointed out.

“Here in the United States, patients have been treated when they’re intubated, but we think that is relatively late. Many physicians are trying to move it earlier, that is, when people begin to decompensate,” he added.

But even where there is a will, getting this treatment to the patients who need it sooner rather than later is not always straightforward. “Some of the problem […] is that it takes time,” Dr. Casadevall explained.

“Because let’s say the doctor orders plasma and people are getting worse. It sometimes takes a while for the plasma to arrive. Some hospitals have it on site, others have to get it from blood banking centers.”

Despite these obstacles, the use of convalescent plasma therapy is so attractive to healthcare practitioners because they can access it and use it now.

Unlike with vaccines, whose development takes time, or experimental medication, which needs to go through several different stages of testing before it can obtain formal approval, this approach allows doctors to use what is already there — the blood of those who have recovered from the illness — to treat hospitalized patients.

“People often get confused [about the difference between convalescent plasma therapy and some vaccines] because they both involve antibodies,” Dr. Casadevall told MNT.

But while vaccines also operate on the premise of stimulating a person’s immune system to block or kill the virus, they do not use “ready made” antibodies, and testing them for safety and efficacy could take a year or more.

“When you get plasma, someone else is giving you the antibodies, and you get them immediately,” Dr. Casadevall explains.

Going forward, he thinks that doctors could use this therapy alongside other options as they gradually become available.

“[C]onvalescent plasma provides something that can be used today with standard knowledge and standard procedures […] But we do hope that better options will be available in the future,” he reiterated.

Prostate cancer : Noninvasive urine test moves a step closer

Researchers have identified a unique molecular signature of prostate cancer in urine. This may pave the way for an accurate, noninvasive test for the condition.
The scientists — from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, MD — used RNA and other molecules in urine to differentiate between males with prostate cancer and those with nonmalignant prostate conditions or healthy prostates.

Prostate cancer is the second most common cancer among males in the United States, after skin cancer. Around 1 in 9 males will receive a diagnosis of this condition in their lifetime.

In the U.S. alone, almost 192,000 males will receive a diagnosis in 2020, and over 33,000 will die from the condition.

Flawed tests
Prostate cancer is highly treatable, especially if a doctor diagnoses it early. However, there are often no symptoms in the early stages, and existing screening tests are problematic.

For example, the widely used prostate-specific antigen (PSA) blood test is unreliable, giving a lot of false-positive results and not discriminating benign from aggressive forms of cancer.

As part of a regular health check, or if a male’s PSA levels are elevated, a doctor may perform a digital rectal examination (DRE). However, these tend to be quite invasive, which discourages many males from undergoing them.

Doctors recommend a biopsy if they find anything suspicious during a DRE. However, even a biopsy cannot provide a definitive test, and the procedure can be painful.

“A simple and noninvasive urine test for prostate cancer would be a significant step forward in diagnosis,” says senior study author Ranjan Perera. The study now appears in the journal Scientific Reports.

“Tissue biopsies are invasive and notoriously difficult because they often miss cancer cells, and existing tests, such as PSA […] elevation, are not very helpful in identifying cancer.”

According to the National Cancer Institute, only about 25% of males who undergo a biopsy following a positive PSA test actually have prostate cancer.

Dislodged cells
Male urine contains a small amount of cells shed from different parts of the urinary tract, including the prostate. Scientists can isolate, process, and analyze these cells using various molecular techniques.

Existing prostate urine tests involve a health professional first massaging the prostate to dislodge more of these cells. However, recent research suggests that this may be unnecessary. Indeed, males may actually be able to collect urine samples at home and mail them to a laboratory for testing.

For the new study, the researchers recruited 126 males. Of these, 64 had prostate cancer, 31 had nonmalignant prostate conditions (benign prostatic hyperplasia or prostatitis), and 31 had no cancer. They collected urine samples without first massaging the prostate.

Cells become cancerous partly as a result of genetic and metabolic changes that provide the energy boost they need to proliferate rapidly.

To identify a unique molecular signature of these changes in prostate cancer, the researchers sequenced RNA molecules and used mass spectrometry to measure metabolites in the samples.

“We discovered cancer-specific changes in urinary RNAs and metabolites that — if confirmed in a larger, separate group of patients — will allow us to develop a urinary test for prostate cancer in the future.”

– First study author Bongyong Lee, of Johns Hopkins All Children’s Hospital in St. Petersburg, FL

Unlike the PSA test, the RNA and metabolite profile that the researchers identified could distinguish between males with prostate cancer and those with nonmalignant prostate conditions.

The scientists write in their paper that a test based on their findings could also determine how advanced a cancer is.

However, they emphasize that this was a proof-of-principle study. Larger studies are necessary to validate the test before it is ready for clinical use.

They say that in the future, their findings might inspire new treatments for the condition based on the metabolic changes they identified.

Researchers identify potential coronavirus vaccine and therapy targets

Researchers show that antibodies that can neutralize the virus that causes SARS can reduce how well the new coronavirus infects cells in laboratory studies. They also use an approved drug to reduce virus entry into cells.

With global cases of COVID-19 surpassing 100,000, researchers are looking for ways to prevent new viral infections.

The new coronavirus, called SARS-CoV-2, has strong similarities to other viruses in the coronavirus family, particularly those that cause SARS and MERS.

Two new papers appeared recently in the journal Cell, investigating how SARS-CoV-2 infects cells.

So, how exactly does the virus gain entry to cells, and why is it important to know this?

Understanding the target molecules that facilitate viral entry into cells is paramount to identifying how to stop this process from happening.

Both papers report that SARS-CoV-2 makes use of the same mechanism for viral entry that the SARS virus (SARS-CoV) uses.

More importantly, both research teams looked at ways of disrupting this process, using an enzyme inhibitor and antibodies against the SARS virus.

Coronavirus infection route
The new coronavirus, SARS-CoV-2, is a type of virus called an enveloped RNA virus.

This means that its genetic material is encoded in single-stranded RNA molecules surrounded by a cell membrane taken from the cell that it last infected.

When enveloped viruses infect a cell, they do this using a two-stage process.

The first step involves making a connection with a receptor on the surface of the target cell. The second is fusion with a cell membrane, either on the surface of the cell or at an internal location.

In the case of coronaviruses, the first step requires that specific proteins in the viral envelope, called spike (S) proteins, undergo a biochemical modification. This step is called S protein priming.

The enzymes responsible for S protein priming are potential therapeutic targets as inhibiting their mechanism may prevent a virus from being able to enter a cell.

“Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets,” write the authors one of the new papers in Cell.

The senior study author is Stefan Pöhlmann, a professor for Infection Biology at Georg-August-University and Head of the Infection Biology Unit of the German Primate Center, both in Göttingen in Germany.

Pöhlmann and his colleagues show evidence that the SARS-CoV-2 S protein binds to the same receptor as the SARS virus S protein. The receptor is called angiotensin-converting enzyme 2 or ACE2.

In fact, an earlier paper in the journal Nature had already implicated ACE2 as the receptor that allows SARS-CoV-2 to infect cells.

In addition to providing further evidence of ACE2’s role, Pöhlmann and the team also saw that, like SARS-CoV, the new coronavirus S protein uses an enzyme called TMPRSS2 for S protein priming.

Importantly, they showed that “camostat mesylate, an inhibitor of TMPRSS2, blocks SARS-CoV-2 infection of lung cells.”

Camostat mesylate is a drug approved in Japan for the treatment of pancreatitis. The authors explain in the paper:

Towards a SARS-CoV-2 vaccine
Pöhlmann and his colleagues also studied whether antibodies made by people who had a previous diagnosis of SARS would prevent SARS-CoV-2 virus entry into cells.

They found that antibodies against the SARS-CoV S protein reduced how well a laboratory model virus with the SARS-CoV-2 S protein could infect cells. They also saw similar results with antibodies against S proteins made in rabbits.

“Although confirmation with infectious virus is pending, our results indicate that neutralizing antibody responses raised against SARS-S could offer some protection against SARS-CoV-2 infection, which may have implications for outbreak control,” the team writes in the paper.

Yet, Pöhlmann and his colleagues are not the only ones studying the potential to use antibodies to SARS as a vaccine for SARS-CoV-2.

David Veesler, an assistant professor in Biochemistry at the University of Washington in Seattle, provides more evidence that the virus enters target cells via ACE2 in a paper published in Cell.

Along with his colleagues, he also studied antibodies against SARS S protein fragments to identify potential vaccines.

The team showed that antibody serum from four different mice could reduce infection with a laboratory model virus containing the SARS-CoV-2 S by 90%.

But before a much-needed SARS-CoV-2 vaccine is available, more testing is required.

Clinical trials to show the safety and efficacy will form the basis of developing these vaccine candidates into safe products to use.

In Europe, the European Medicines Agency announced last month that it was taking “concrete actions to accelerate the development and availability of medicinal products for the treatment and prevention of the new coronavirus.”

Meanwhile, in the United States, the Department of Health and Human Services is collaborating with Janssen Research and Development, part of pharmaceutical company Johnson & Johnson, to develop a vaccine against SARS-CoV-2. A clinical trial, sponsored by the National Institute of Allergy and Infectious Diseases using a novel type of RNA-based vaccine, is also underway.

Antibiotics discovered that kill bacteria in a new way

A new group of antibiotics with a unique approach to attacking bacteria has been discovered, making it a promising clinical candidate in the fight against antimicrobial resistance.

The newly-found corbomycin and the lesser-known complestatin have a never-before-seen way to kill bacteria, which is achieved by blocking the function of the bacterial cell wall. The discovery comes from a family of antibiotics called glycopeptides that are produced by soil bacteria.

The researchers also demonstrated in mice that these new antibiotics can block infections caused by the drug resistant Staphylococcus aureus which is a group of bacteria that can cause many serious infections.

The findings were published in Nature today.

“Bacteria have a wall around the outside of their cells that gives them shape and is a source of strength,” said study first author Beth Culp, a PhD candidate in biochemistry and biomedical sciences at McMaster.

“Antibiotics like penicillin kill bacteria by preventing building of the wall, but the antibiotics that we found actually work by doing the opposite — they prevent the wall from being broken down. This is critical for cell to divide.

“In order for a cell to grow, it has to divide and expand. If you completely block the breakdown of the wall, it is like it is trapped in a prison, and can’t expand or grow.”

Looking at the family tree of known members of the glycopeptides, researchers studied the genes of those lacking known resistance mechanisms, with the idea they might be an antibiotic demonstrating a different way to attack bacteria.

“We hypothesized that if the genes that made these antibiotics were different, maybe the way they killed the bacteria was also different,” said Culp.

The group confirmed that the bacterial wall was the site of action of these new antibiotics using cell imaging techniques in collaboration with Yves Brun and his team from the Université de Montréal.

Culp said: “This approach can be applied to other antibiotics and help us discover new ones with different mechanisms of action. We found one completely new antibiotic in this study, but since then, we’ve found a few others in the same family that have this same new mechanism.”

The team is led by professor Gerry Wright of the David Braley Centre for Antibiotic Discovery within the Michael G. DeGroote Institute for Infectious Disease Research at McMaster.

The research was funded by the Canadian Institutes of Health Research and the Ontario Research Fund.

Scientists breach brain barriers to attack tumors

The brain is a sort of fortress, equipped with barriers designed to keep out dangerous pathogens. But protection comes at a cost: These barriers interfere with the immune system when faced with dire threats such glioblastoma, a deadly brain tumor for which there are few effective treatments.

Yale researchers have found a novel way to circumvent the brain’s natural defenses when they’re counterproductive by slipping immune system rescuers through the fortresses’ drainage system, they report Jan. 15 in the journal Nature.

“People had thought there was very little the immune system could do to combat brain tumors,” said senior corresponding author Akiko Iwasaki. “There has been no way for glioblastoma patients to benefit from immunotherapy.”

Iwasaki is the Waldemar Von Zedtwitz Professor of Immunobiology and professor of molecular, cellular, and developmental biology and an investigator for the Howard Hughes Medical Institute.

While the brain itself has no direct way for disposing of cellular waste, tiny vessels lining the interior of the skull collect tissue waste and dispose of it through the body’s lymphatic system, which filters toxins and waste from the body. It is this disposal system that researchers exploited in the new study.

These vessels form shortly after birth, spurred in part by the gene known as vascular endothelial growth factor C, or VEGF-C.

Yale’s Jean-Leon Thomas, associate professor of neurology at Yale and senior co-corresponding author of the paper, wondered whether VEGF-C might increase immune response if lymphatic drainage was increased. And lead author Eric Song, a student working in Iwasaki’s lab, wanted to see if VEGF-C could specifically be used to increase the immune system’s surveillance of glioblastoma tumors. Together, the team investigated whether introducing VEGF-C through this drainage system would specifically target brain tumors.

The team introduced VEGF C into the cerebrospinal fluid of mice with glioblastoma and observed an increased level of T cell response to tumors in the brain. When combined with immune system checkpoint inhibitors commonly used in immunotherapy, the VEGF-C treatment significantly extended survival of the mice. In other words, the introduction of VEGF-C, in conjunction with cancer immunotherapy drugs, was apparently sufficient to target brain tumors.

“These results are remarkable,” Iwasaki said. “We would like to bring this treatment to glioblastoma patients. The prognosis with current therapies of surgery and chemotherapy is still so bleak.”

The study was primarily funded by the Howard Hughes Medical Institute and the National Institutes of Health.

Other Yale authors are Tianyang Mao, Huiping Dong, Ligia Simoes,Braga Boisserand, and Marcus Bosenberg. Salli Antila and Kari Alitalo of the University of Helsinki are also authors.

Revolutionising radiotherapy: making a cornerstone cancer treatment more personal and powerful

“We have a very powerful treatment which contributes to the cure of cancer in around a third of patients treated,” says Professor David Sebag-Montefiore from the University of Leeds of radiotherapy, a cornerstone of cancer treatment in the UK.

But there’s always room for improvement. “Some of the radiotherapy we give today isn’t doing a good enough job.”

We want more people to reap the benefits of this tried and tested treatment, so we’re investing £56 million to launch the Cancer Research UK Radiation Research Network (CRUK RadNet). This will support radiotherapy research in seven specialist institutes across the UK and aims to propel radiotherapy into the future.

It’s money to develop new tech, harness the power of existing ones, apply approaches like artificial intelligence (AI) and to help scientists really understand what’s going on when cancer cells are hit by radiotherapy beams, so we can use drugs to boost their cancer-killing effects.

“Because radiotherapy is an effective treatment across such a broad range of cancers it’s clearly a job that can’t be achieved in one centre alone,” says Sebag-Montefiore. This new initiative hopes to make use of the different expertise from each research station involved, bringing in knowledge from scientists who have never worked in radiotherapy before. “This network will allow us to focus along the breath of cancer research and actually make a big impact.”

Although radiotherapy has become extremely advanced in the last couple of decades and comes in many high-tech forms, there are still plenty of questions around how it’s effects can be maximised to benefit more people and how to reduce side effects of the treatment.

Here are just three of a number of research areas CRUK RadNet hopes to get answers for.

How does radiotherapy affect the tumour microenvironment?

Radiotherapy works by damaging the DNA of cancer cells. “These fatal DNA breaks mean the cancer cells can’t divide,” says Sebag-Montefiore.

But cancer cells aren’t just quietly hanging out by themselves. They’re sitting in a busy environment of blood cells, immune cells and healthy tissues, all of whom are likely to be interacting.

The full extent of the influence these cells have on each other is still unclear, but clues from the clinic suggest that the immune system plays an important role in mopping up cancer cells after radiotherapy, even after they’ve spread to other parts of the body.

“Clinically we are now starting to see situations in people who have incurable cancer that has spread, where irradiating the primary tumour improves their survival,” says Sebag-Montefiore. It’s a positive benefit that scientists are still working to understand.

One theory is that radiation causes cancer cells to break down and release their contents, which creates lots of interesting molecules for the immune system to detect and home in on. The energised immune cells then move around the body looking for cancer cells displaying these same molecules. And when they find them, they kill them, which may explain why tumours that are distant from where the cancer first started shrink.

Figuring out what’s going on in and around a tumour when it’s being irradiated could point to ways to enhance treatment and may even help radiotherapy work for those who currently don’t respond to it. For example, immunotherapies could give immune cells the boost they need to turn against tumours. Or, giving patients drugs that stop cancer cells repairing their DNA alongside radiotherapy might give the cancer an extra blow.

Sebag-Montefiore says there is clearly a substantial piece of work needed to understand the environment that the radiotherapy beams operate in and are also creating. Learning more about this will help us “know how to best to harness the microenvironment and have maximum impact”.

“This is a significant part of the work that will be done in CRUK RadNet.”

How could AI improve radiotherapy?

Every day we hear of new ways that AI is improving everything from how we shop to healthcare. Now Sebag-Montefiore and his team in Leeds, alongside researchers across the CRUK RadNet network, are exploring how it can be used to help cancer treatment.

“In Leeds, we think we can harness AI to actually improve how radiotherapy is given to patients.”

Computer programmes may help them deliver a highly targeted radiotherapy called SABR more accurately, sparing healthy cells. “Both the tumour and the organ we target during treatment move so we apply a safety margin around the tumour to make sure we hit the whole tumour. At the moment this margin is pretty much the same for every patient.”

But the money from CRUK RadNet will allow them to develop algorithms that could work out the exact area the radiotherapy beam will need to cover for each patient. The team hope to use AI to analyse MRI scans from a range of cancers that are in areas of the body that move a lot, like the liver.

“We could analyse those scans with AI to build up a personalised picture of the actual movement,” which means more precise treatment and fewer side effects.

Why do cancer cells become resistant to radiotherapy?

Unfortunately, radiotherapy doesn’t work on everyone.

“We need to understand why radiotherapy isn’t as effective as it could be in some patients,” says Sebag-Montefiore.

“Within all cancers we can identify some groups of patients where radiotherapy resistance is a major barrier to the cure of cancer.”

This may be someone whose cancer initially responds well to treatment but then it stops working. Or, in a few cases, radiotherapy might have no affect at all.

CRUK RadNet members are investigating resistance from a number of angles, looking at ways to overcome the fact that radiotherapy can’t destroy certain cancers. They’re particularly focusing on the cancer types where survival is still depressingly low, like pancreatic cancer and brain tumours.

For instance, a team in Manchester are delving into how radiotherapy changes the biology of cancer cells and how this may contribute to them standing firm against its powerful beams.

A community effort

Sebag-Montefiore is keen to get going. “The last 10 years have seen significant progress in radiotherapy research, but we can do better.”

He says the network now needs to make sure they work with the whole UK radiotherapy community to make sure they do the best science. Because for Sebag-Montefiore, the potential impact of the network is huge.

“CRUK RadNet is a fantastic investment because it gives us a great chance in improving radiotherapy cure rates and reduce side effects further to ensure patients are getting the best possible treatment.”

Good noise, bad noise: White noise improves hearing

Noise is not the same as noise — and even a quiet environment does not have the same effect as white noise. With a background of continuous white noise, hearing pure sounds becomes even more precise, as researchers from the University of Basel have shown in a study in Cell Reports. Their findings could be applied to the further development of cochlear implants.

Despite the importance of hearing in human communication, we still understand very little of how acoustic signals are perceived and how they are processed to allow us to make sense of them. One thing is clear though: the more precisely we can distinguish sound patterns, the better our hearing is. But how does the brain manage to distinguish between relevant and less relevant information — especially in an environment with background noise?

Exploring the “auditory brain”

Researchers led by Prof. Dr. Tania Rinaldi Barkat from the Department of Biomedicine at the University of Basel have investigated the neuronal foundation of sound perception and sound discrimination in a challenging sound environment. The focus was on research into the auditory cortex — the “auditory brain,” that is, the area of the brain that processes acoustic stimuli. The resulting activity patterns stem from measurements in a mouse brain.

As is well known, the distinction between sounds becomes more difficult the closer they are in the frequency spectrum. Initially, the researchers assumed that additional noise could make such a hearing task even more difficult. However, the opposite was observed: The team was able to demonstrate that the brain’s ability to distinguish subtle tone differences improved when white noise was added to the background. Compared to a quiet environment, the noise thus facilitated auditory perception.

Noise reduces neuronal activity

The data of the research group showed that white noise significantly inhibited the activity of the nerve cells in the auditory cortex. Paradoxically, this suppression of the neuronal excitation led to a more precise perception of the pure tones. “We found that less overlap occurred between populations of neurons during two separate tone representations,” explains Professor Tania Barkat. “As a result, the overall reduction in neuronal activity produced a more distinct tone representation.”

To confirm that the auditory cortex and not another area of the brain was responsible for the change in sound perception, the researchers used the light-controlled technique optogenetic. Their findings could possibly be used to improve auditory perception in situations where sounds are difficult to distinguish. According to Barkat, it is conceivable that cochlear implants could be stimulated with an effect similar to white noise in order to improve the frequency resolution and thus the hearing result of their users.

Measuring up: how does the UK compare internationally on cancer survival?

Our ambition is that 3 in 4 people will survive their cancer by 2034. And while cancer outcomes may differ from country to country, the goal of improving cancer survival is one that’s reflected across the world.

A good way for countries to monitor their progress in improving cancer care is by comparing how many people get cancer (incidence), how many survive (survival) and how many die from their cancer (mortality) to see how they measure up. If survival is higher, and incidence and mortality are lower, it’s clear that a country is on the right track.

“No one country manages cancer perfectly,” says John Butler, a consultant specialising in gynaecological cancer surgery. “ But international studies enable countries to learn lessons from one another to with the aim of improving their own cancer policies.”

And in the latest study, published in Lancet Oncology by the International Cancer Benchmarking Partnership, some promising trends have emerged. Survival has improved for the 7 cancer types studied in all countries between 1995 and 2014.

But the figures also underline how much progress still needs to be made in the UK to equal the best outcomes globally. With the exception of ovarian and oesophageal, the UK has the lowest survival figures for the cancers studied.

What do the latest figures show?

Big, international studies like this are a task for the International Cancer Benchmarking Partnership (ICBP). Led by clinicians, researchers and policymakers from around the world, the team compare trends in cancer survival, incidence and mortality rates across 7 countries with similar healthcare systems: UK, Australia, Canada, New Zealand, Denmark, Norway and Ireland. Something that’s never been done before.

Comparisons like this can be tricky – mainly because countries collect and record data in slightly different ways, something the ICBP is looking at in more detail. But despite the challenges, the latest figures from the ICBP are the best available and will only get better as more analysis is done.

The team has been collecting data from 7 cancer types – ovary, lung, colon, rectum, pancreas, oesophagus and stomach – since 1995.

And the latest figures, covering 1995 to 2014, reveal some stark differences in cancer survival between countries. Generally, cancer survival is higher in Australia, Canada and Norway than in Denmark, Ireland, New Zealand and the UK.

Similar trends can be seen for individual cancer types, like lung cancer. From the graphs we can see that Australia has the highest lung cancer survival, and Ireland has made the greatest increase in survival over time. But despite big improvements in lung cancer survival, the UK remains bottom of the list for this cancer type.

Why is the UK lagging behind?

There are many, complex reasons that could explain why we have lower survival compared to other countries.

Butler, the lead clinical advisor for ICBP, says there are some factors that will affect survival in all cancer types. “The UK health system is under great pressure, with increasing demands on cancer diagnostics and more urgent referrals”. And that could affect survival figures. Diagnosing and treating cancer early gives patients the best chance of surviving their cancer, but it relies on having enough NHS staff and funding in place to make this a reality – something the NHS doesn’t currently have.

But there are also more specific reasons that may explain differences between countries for some cancers.
Take ovarian cancer for example. Patients diagnosed in the UK appear to be diagnosed at similar stages to other countries, but survival is lower. This suggests there could be improvements in how these patients are treated.

And as Butler elaborated, this is amplified in older patients.

Older patients are more likely to have other health problems, which often make it more challenging to perform surgery or deliver chemotherapy. More is needed to be done to understand these patients’ complex needs and improve treatments for them, as we’ve blogged about before, as well as to understand why this is an issue particularly for the UK.

But when looking at survival as a whole, it’s useful to consider where we started. In 1995, the UK had some of the lowest survival estimates of the seven countries studied. This means that even though we have made improvements in certain cancers, we’re starting from a lower baseline. Which makes it that much harder for us to catch up with the countries who have higher survival.

And it’s where comparing our progress to other countries can help.

What can we learn from other countries?

Denmark was in a similar place to the UK with their survival in 1995. But as Jesper Fisker, chief executive officer of the Danish Cancer Society, told us “There’s been great progress in Danish cancer survival – which is the result of massive efforts and investments in the cancer field over the past 20 years”.

They’ve also made major strides towards centralising their cancer services, meaning cancer patients are treated in fewer, more specialised centres, with the best clinicians for their cancer type.

And it’s paid off – Denmark has seen real improvements in cancer survival – such as increasing their 1-year survival of lung cancer from 27.5% to 46.2% (from 1995-1999 to 2010-2014). The UK has made similar efforts to improve cancer services, with some success, but much more needs to be done.

And it’s not quite as straightforward as it sounds. While Denmark has made big improvements overall, this has not been universal for every cancer type. The same is true for all the countries studied and it’s something the ICBP is working to understand. They’re looking into variations in access people have to diagnostic tests, scans and treatment, as well as differences in healthcare systems that could help to explain the disparity.

Progress for the UK

On the bright side, the UK has made particularly good progress in increasing cancer survival in rectal, ovarian, and oesophageal cancers.

For example, from 1995 to 1999, 48 in 100 patients were estimated to survive their rectal cancer for at least 5 years. This has now increased to 62 in 100 patients for 2010-2014, only 8.7% behind Australia, who had the highest rectal cancer survival of the countries studied.

Butler called the progress “encouraging” and said there were lots of factors that could be behind the improvements. England produced its first national cancer plan in 2000 and appointed a national cancer director, who helps provide advice and leadership for our cancer services. Since then there’s been more guidance and greater scrutiny of how cancer services are performing, as well as more funding.

There’s also been a move towards cancers being treated in specialised centres, where there will be more relevant cancer expertise.

How can the UK catch up?

But despite the improvements, there’s clearly more work to be done in the UK.

For Butler, investigations into how well cancer services are performing could be a good way to start. For example, national audits in the UK for lung cancer have increased the number of people having surgery, as well as the number of specialised lung cancer surgeons. Replicating this approach could help the NHS direct its efforts to improve outcomes for other types of cancer.

And while the UK government have introduced a range of policies between 1995 and 2014 to improve cancer services and speed up diagnosis and treatment, these have added to the strain on NHS services.

It’s crucial that investment into cancer services is increased to match the ever-growing demand. As Butler told us, “one of the biggest challenges the UK faces is capacity of diagnostic services.”

Trump signs order aimed at development of better flu vaccines

Reporting By Deena Beasley; Editing by Sonya Hepinstall

(Reuters) – U.S. President Donald Trump on Thursday signed an executive order aimed at spurring the development of better vaccines to protect against seasonal influenza as well as a potential pandemic flu outbreak.

The order does not allocate additional funding for now, but calls for an evaluation of current flu vaccine manufacturing abilities and a task force report including cost estimates, administration officials said on a call with reporters.
Each year the seasonal flu, which can kill tens of thousands of Americans, costs the United States about $50 billion, including lost productivity, one administration official said. A serious flu pandemic would push those costs to between $1.8 billion and $3.8 billion, he said.

Manufacturers such as GlaxoSmithKline Plc and Sanofi SA make millions of doses of flu vaccine for the U.S. market alone, growing the virus in chicken eggs. Usually the doses, which protect against strains that experts predicted the previous February, are ready in time and in sufficient quantity for the winter flu season.
But if the strain that appears during flu season was not the one experts forecast, the vaccines might not work. The appearance of H1N1 swine flu in 2009-2010 took experts by surprise, and the flu was already on its second wave before a vaccine was ready; an estimated 61 million people in the U.S. got swine flu and thousands died.

The Department of Health and Human Services will coordinate government efforts to modernize influenza vaccine production. The focus will be on recombinant technologies to quickly produce reliable vaccines as well as “universal” vaccines that would elicit immunity against parts of the virus that do not change from year to year.