Researchers Uncover Major Clue In Predicting Response To Immunotherapy

Researchers at Memorial Sloan Kettering Cancer Center in New York have discovered that cancer cells with high numbers of faults in their DNA are more likely to respond to immune checkpoint inhibitors (ICI), a major class of immunotherapy drugs, which includes Keytruda.

The study, published today in Nature Genetics adds important pieces to the puzzle as to why some cancer patients respond to immunotherapy whereas others do not. The researchers measured ‘tumor mutation burden (TMB)’, essentially counting how many DNA faults a tumor contains by looking for errors in the DNA sequence.

“People assume that TMB is important in predicting response to immunotherapy in all cancers, but up until now, all we’ve had is data from small studies and clinical trials on mostly lung cancers and melanoma,” said Luc Morris, MD, surgical oncologist at Memorial Sloan Kettering Cancer Center and one of the lead authors of the paper.

The researchers studied the DNA of 1,662 patients with advanced cancer (classified as stage IV or metastatic disease) treated with one or more of several FDA-approved ICI drugs and DNA from 5,371 patients with advanced cancer who had not had ICI. They used a tool called MSK-IMPACT, which looks at just 3% of the coding-regions in DNA, but is correlated to the number of mutations in the genome.

“Is TMB associated with likelihood that immunotherapy has benefit? Is this true in all cancers? We wanted to find out whether TMB had broad applicability,” said Morris.

The researchers found that if they took the 20% of cancers in their data with the most mutations, these people responded better to ICI than those with lower numbers of mutations in their tumors.

However, this correlation did not hold true for all tumors, for example, in people with a type of brain cancer called glioma, those with TMB in the top 20% did no better on ICI than those with lower TMB. Also in breast cancer there was no conclusive evidence that a higher TMB predicted response to ICI, although the study included relatively few breast cancer patients as ICI is not currently widely used for the disease.

Researchers don’t exactly know why high numbers of mutations make cancers more susceptible to immunotherapy, but they do have a very plausible theory. They think that the more mutated a cell is, the more likely it is to produce incorrect, mangled proteins. These displayed on the cell surface are called neoantigens and they are so far from what would be considered normal, the immune system identifies them as foreign and attacks the cells.

This is not a unique study in concept, with previous research on a smaller number of cancers of specific types, notably lung and melanoma, indicating that TMB is likely predictive of immunotherapy response. However, it is the largest and most comprehensive study to date, providing the most persuasive evidence that this is true for a greater number of cancer types.

“Only in lung cancer is TMB being used in a clinical trial. Hopefully this data will give us permission to include it in future clinical trials on other cancer types,” said Morris.

However, some patients with high TMB don’t respond to ICI at all, so there is still work to be done to figure out why high TMB is not a universal predictor of response to ICI.

“TMB by itself is not going to give you a high confidence in predicting whether a patient is going to respond to immunotherapy or not. It is one biomarker for response, but a number of other factors are important. I would not suggest you take the data from this paper and apply it to a patient in the clinic,” said Morris.

Print Friendly, PDF & Email
January, 2019|Oral Cancer News|

New app gives throat cancer patients their voice back

Source: www.straitstimes.com
Author: staff

Throat cancer patient Vlastimil Gular can say what he wants in his own voice thanks to technology that uses past recordings of his voice to create synthetic speech that can be played on his mobile phone via an app. Photo: AFP

Vlastimil Gular’s life took an unwelcome turn a year ago: minor surgery on his vocal cords revealed throat cancer, which led to the loss of his larynx and with it, his voice.

But the 51-year-old father of four is still chatting away using his own voice rather than the tinny timbre of a robot, thanks to an innovative app developed by two Czech universities.

“I find this very useful,” Mr Gular told AFP, using the app to type in what he wanted to say, in his own voice, via a mobile phone.

“I’m not very good at using the voice prosthesis,” he added, pointing at the hole the size of a large coin in his throat.

This small silicon device implanted in the throat allows people to speak by pressing the hole with their fingers to regulate airflow through the prosthesis and so create sound.

But Mr Gular prefers the new hi-tech voice app.

It was developed for patients set to lose their voice due to a laryngectomy, or removal of the larynx, a typical procedure for advanced stages of throat cancer.

The joint project of the University of West Bohemia in Pilsen, Prague’s Charles University and two private companies – CertiCon and SpeechTech – kicked off nearly two years ago.

The technology uses recordings of a patient’s voice to create synthetic speech that can be played on their mobile phones, tablets or laptops via the app.

Ideally, patients need to record more than 10,000 sentences to provide scientists with enough material to produce their synthetic voice.

“We edit together individual sounds of speech so we need a lot of sentences,” said Dr Jindrich Matousek, an expert on text-to-speech synthesis, speech modelling and acoustics who heads the project at the Pilsen university.

A Matter of Weeks
But there are drawbacks: Patients facing laryngectomies usually have little time or energy to do the recordings in the wake of a diagnosis that requires swift treatment.

“It’s usually a matter of weeks,” said Dr Barbora Repova, a doctor at the Motol University Hospital, working on the project for Charles University.

“The patients also have to tackle issues like their economic situation, their lives are turned upside down, and the last thing they want to do is to make the recording,” she told AFP.

To address these difficulties, scientists came up with a more streamlined method for the app, which is supported by the Technology Agency of the Czech Republic.

Working with fewer sentences – ideally 3,500 but as few as 300 – this method uses advanced statistical models such as artificial neural networks.

“You use speech models with certain parameters to generate synthesised speech,” said Dr Matousek.

“Having more data is still better, but you can achieve decent quality with less data of a given voice.”

The sentences are carefully selected and individual sounds have to be recorded several times, as they are pronounced differently next to different sounds or at the beginning and end of a word or sentence, he added.

So far, the Pilsen university has recorded 10 to 15 patients, according to Dr Matousek.

Besides Czech, the Pilsen scientists have also created synthesised speech samples in English, Russian and Slovak.

Baby Dinosaurs
Mr Gular – an upholsterer who lost his job due to his handicap – managed to record 477 sentences over the three weeks between his diagnosis and the operation.

But he was stressed and less than satisfied with the quality of his voice.

“Throat cancer patients often suffer from some form of dysphonia (hoarseness) before the surgery, so in combination with a limited speech sample, it makes the voice sound unnatural,” said Dr Repova.

In a studio at the Pilsen university meanwhile, entrepreneur Jana Huttova is recording outlandish phrases.

The 34-year-old mother of three faces the risk of losing her voice to minor throat surgery – an operation on her parathyroid gland.

“The Chechens have always preferred a dagger-like Kalashnikov,” she says, reading from the text before her.

“I have small kids and I want them to hear my own voice, not a robot,” Ms Huttova said.

Then she moved on to her next sentence: “We were attacked by a tyrannosaur’s baby dinosaurs.”

Connected to the Brain
Dr Matousek believes that in the future, patients will be able to use the app to record their voice at home using a specialised website to guide them through the process.

And he hopes that one day it will go even further.

“The ultimate vision is a miniature device connected to the brain, to the nerves linked to speech – then patients could control the device with their thoughts,” he said.

This kind of advanced solution is a very long way off, said Dr Repova.

“But look at cochlear implants – 40 years ago when they started, we had no idea how it would develop, how widely they would end up being used,” she said, referring to the inner-ear implants used to tackle severe deafness.

“A happy end would be a device implanted in the throat that could talk with the patient’s own voice,” she told AFP.

“It’s realistic: it may not come in a year or even in 10 years, but it’s realistic and we’re on the way.”

Print Friendly, PDF & Email
January, 2019|Oral Cancer News|

Living well with a feeding tube

Source: health.usnews.com
Author: Lisa Esposito, Staff Writer

Nearyly 450,000 Americans with swallowing or digestive problems manage tube feedings – also called home enteral nutrition – on their own. Some have temporary feeding tubes, while others leave the hospital with feeding tubes surgically placed for the foreseeable future.

Veteran users or “tubies” accept long-term feeding tubes as the best or only way to nourish themselves. Many resume school, work and social lives that were once threatened by severe weight loss and malnutrition. For them, getting a feeding tube means getting their active lives back.

Feeding Tube Benefits
Feeding tubes can prevent weight loss, boost energy and bolster your immune system. They also offer important health benefits for people coping with the following health issues:

Tube feeding for chronic swallowing challenges. For people with chronic health conditions that can cause swallowing difficulties, it helps keep them well-nourished. Neurologic conditions such as Parkinson’s disease, stroke or amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) can impair nerves, affecting swallowing ability.

Tube feeding for oral and throat cancer. Inability to swallow food because of cancer of the mouth or throat is a major contributor to people receiving one, says Lisa Epp, a registered dietitian nutritionist with Mayo Clinic in Rochester, Minnesota.

Tube feeding for nutrition during recovery. A patient who has a short-term eating problem likely to eventually resolve, such as someone recovering from a surgery, brain injury or stroke, may benefit from having one.

Tube feeding for gastric problems. Gastric problems in which the stomach doesn’t empty well or a part of the intestine doesn’t work are the third major cause for feeding tubes, Epp says. Less commonly, trauma and paralysis impair the ability to swallow.

Tube feeding for kids with impaired eating ability. In kids, genetic and other disorders that affect their development can compromise their ability to swallow and eat. Premature infants, toddlers diagnosed with failure to thrive and kids with congenital heart defects, cerebral palsy, cystic fibrosis, GI tract malformations or gastroesophageal reflux disease (GERD) may be candidates for feeding tubes.

When children are barely able to eat because of chronic illness, feeding tubes must be considered, Epp says. If children can’t have needed surgery or chemotherapy because their bodies are weakened by malnutrition, parents have to make that difficult choice.

“Getting better nutrition is going to help them be stronger, increase their immune system and help children grow to their potential, whatever that potential can be,” Epp says. As for adult patients, she adds, “The No. 1 thing I hear when people come back at six-week and three-month visits is, ‘Why didn’t I do this sooner?'”

Maintaining a healthy body weight while tube feeding. Even though they can eat a certain amount of food, some people with gastric conditions can’t take in enough to maintain their health.

“An important consideration is if a patient is continuing to lose weight,” says Arlene Escuro, a dietitian and nutrition therapy specialist at the Center for Human Nutrition in the Digestive Disease and Surgery Institute at Cleveland Clinic. “The key is if they have a functional GI tract. We do have patients with a GI dysfunction (who are) able to take some food by mouth, but it’s not sufficient to sustain their nutrition, so they will need to continue on with the home tube-feeding regimen.”

Types of feeding tubes
Feeding tubes can be temporary or longstanding. Nasal tubes and gastric tubes are the two main types.

A nasal tube, which is usually temporary, is nonsurgical. Nasogastric tubes enter the body through one nostril and run down into the stomach. Another nasal tube, called a nasoduodenal tube, goes into the small intestine, or duodenum. A nasojejunal feeding tube goes into a farther part of the small intestine, the jejunum.

A gastrostomy tube, or G-tube, is often the choice for people who need longer-term feeding tubes. Surgeons use an endoscope to place the G-tube directly into the stomach. The surgery creates a stoma, a visible opening that connects to the feeding tube outside the body. The feeding tube allows people to take specialized liquid nutrition directly into their stomach.

Gastrostomy tubes are often referred to simply as PEGs. Specifically, PEG means percutaneous endoscopic gastrostomy. The visible portion of the feeding tube is permanently attached. However, people can transition to other options.

With buttons or low-profile feeding tubes, there’s no long outer tube attached to the stomach. Instead, users attach extension sets only when needed for feedings, water or medication. The button closure lies nearly flat against the stomach.

However, buttons aren’t the best option for everyone, Epp says. For instance, people who stay on a pump with continuous feeding throughout the day often prefer a tube, which can feel more secure.

Patients and families need to be fully informed of risks as well as benefits before a feeding tube is placed. Doctors evaluate a patient’s medical history to assess his or her individual risk and determine if there are any contraindications, or reasons against, having this procedure.

A variety of intestinal and esophageal conditions, a history of gastric bleeding, previous abdominal surgery and intractable diabetes are among the possible contraindications for G-tube feedings, according to comprehensive, evidence-based guidelines developed by the Cystic Fibrosis Foundation.

Mechanical risks involve tube malfunctions. For example, the tube can get blocked so feeding can’t get through, or it may become dislodged or fall out. It must then be replaced in a hospital.

Skin problems include redness and irritation around a patient’s stoma because of moisture build-up from the stomach or feeding leakage. “There’s also a risk of infection through the stoma site where (users) had a gastrostomy tube, a PEG tube, placed,” Escuro says.

Gastric side effects can develop as well. “GI complications could be diarrhea, constipation or under-hydration,” Escuro says. “Our goal when we have these patients, as we transition them from hospital to home, is to prevent readmissions and tube-feeding related complications.”

Tube Feeding Schedules
Feeding schedules range from episodic feedings at standard mealtimes to continuous feeding regimens.

“We make the regimen very individualized, as much as possible, so it will not interfere with patients’ lives,” Escuro says. Bolus or syringe feedings are larger feedings spread throughout the day like regular meals. It takes about 15 to 20 minutes to administer the formula, Escuro says, usually taken three to four times a day. “Basically, it’s like eating breakfast, lunch, dinner and a snack.”

Other patients go home with a pump for 24-hour feedings. “The reason for the pump feeding is that the feeding tube is placed in their small bowel,” Escuro says. “We don’t really recommend doing bolus feedings in the small intestine, just because it’s such a small reservoir, where most people will not tolerate bolus feedings.”

Pump feedings can be gradually spaced out for some people. “If they go home on continuous feeding when they’re hooked up to a feeding pump, we try to cycle their feedings, eventually.” Escuro says. “So from 24 hours we will gradually cycle them to 20 hours to 18, 16 and to 12 hours or so. If it’s in the stomach, we can transition a patient to bolus feedings.”

Eventually, some patients are weaned off feeding tubes altogether.

Managing a Feeding Tube
Learning how to manage and become comfortable with home tube feeding ideally starts before patients leave the hospital.

At Cleveland Clinic, patients and family caregivers start home enteral feeding education, which includes hands-on practice, before discharge. After discharge, Escuro says, patients with PEGs receive care from a home health nurse to check the stoma site and make sure it’s healing properly. In addition, a home care dietitian follows up to make sure patients are doing well.

Still, for a patient coming home with a tube placed in his or her stomach, the responsibility can seem overwhelming. Through practice, they master the following steps to successfully manage the feeding tube:

  • Prepare the tube feeding
  • Gather supplies
  • Position for feeding
  • Check residual contents
  • Run continuous/cyclic tube feeding
  • Infuse a bolus tube feeding
  • Clean skin around tube site
  • Clean tube feeding equipment
  • Troubleshoot or report problems

Not Best for Everyone
A feeding tube is not always the right choice. For example, people with severe Alzheimer’s disease in later stages often have trouble eating and drinking. However, a feeding tube might not be for the best, according to Choosing Wisely, an initiative focused on avoiding unnecessary medical tests, treatments and procedures.

A frail older adult with Alzheimer’s could be at greater risk of complications such as pneumonia or pressure sores on the skin. They may lose the human contact of being fed by hand as well as the sensation of tasting food.

“Don’t recommend percutaneous feeding tubes (PEGs) in patients with advanced dementia – instead, offer oral assisted feeding,” tops a list of recommendations for physicians regarding quality of life for older adults from the American Geriatrics Society.

<u>Feeding Tube Food</u>
Commercial tube-feeding formulas are available to meet users’ individual nutritional needs. However, just as consumers of traditional food want more natural, less-processed options including plenty of fruits and vegetables, a similar movement is afoot among feeding tube users.

Blenderized whole foods, either made at home or commercially, are choices for patients who feel they can tolerate them better or who simply want to eat what others do. “It’s basically joining the family during mealtime and getting the same food, but it’s just blenderized,” Escuro says.

Expense is an issue. Users must work with insurers to cover ongoing costs of feeding supplies, particularly the food itself. While insurance usually covers the surgical placement, people pay at least a portion for tube-feeding formulas out of pocket.

<u>Resources for People With Feeding Tubes</u>
In addition to turning to their health care teams, people on home enteral nutritional can go online for expertise, advice and peer support.

The Feeding Tube Awareness Foundation is a nonprofit group whose mission is to support parents of children who are tube-fed.

Print Friendly, PDF & Email
January, 2019|Oral Cancer News|

CDC: Top HPV-Associated Cancer Is Now Oropharyngeal

Date: 08/23/18
Source: medscape.com
Author: Nick Mulcahy

Oropharyngeal squamous cell carcinoma (SCC) is now the most common HPV-associated cancer in the United States, according to a new report from the Centers for Disease Control and Prevention (CDC) that covers the years 1999 to 2015.

During that period, cervical cancer dropped from being the top HPV-associated cancer and oropharyngeal SCC took its place.

The transition happened because cervical carcinoma incidence rates decreased 1.6% per year, and oropharyngeal SCC incidence rates increased 2.7% per year among men and 0.8% per year among women.

In 2015, there were a total of 11,788 cervical cancers compared with 18,917 oropharyngeal SCCs.

The decline in cervical cancer is a “continued trend since the 1950s as a result of cancer screening,” write the report authors, led by Elizabeth Van Dyne, MD, MPH, an epidemic intelligence service officer at the CDC.

The uptick in oropharyngeal SCC could be due in part to “changing sexual behaviors,” including unprotected oral sex, especially among white men, who report having the highest number of sexual partners and performing oral sex at a younger age compared with other racial/ethnic groups, the authors say.

Oropharyngeal SCCs include those at the base of tongue, pharyngeal tonsils, anterior and posterior tonsillar pillars, glos­sotonsillar sulci, anterior surface of soft palate and uvula, and lateral and posterior pharyngeal walls.

The new report was published August 24 in the Morbidity and Mortality Weekly Report.

The study authors defined HPV-associated cancer as “an invasive malignancy in which HPV DNA was frequently found in special studies.” In other words, the new study data reveal the total number of certain cancers that are associated with — but not necessarily caused by — HPV.

A total of 30,115 new cases of HPV-associated cancers were reported in 1999 and 43,371 in 2015.

Overall, the rate of HPV-associated cancers dropped among women (change, –0.4%) during the study period and rose among men (change, 2.4%).

The CDC analyzed data from their National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program for all years from 1999 to 2015. “These data cover approximately 97.8% of the US population,” say the authors.

However, these two population-based cancer registries have a limitation: They tally invasive cancers but not the HPV status of cancers.

The authors point out HPV causes cervical cancer and “some oropharyngeal, vulvar, vaginal, penile, and anal cancers.”

Table. Annual Change in Type of Cancer From 1999 to 2015

Cancer Type Average Annual Change (%)
Cervical –1.6
Vaginal –0.6
Oropharyngeal in men 2.7
Oropharyngeal in women 0.8
Anal in men 2.1
Anal in women 2.9
Vulvar 1.3

Penile cancer rates remained stable during the study period.

The study authors say that the public health implication of the study is that HPV vaccination “can prevent infection with the HPV types most strongly associated with cancer.”

Print Friendly, PDF & Email
January, 2019|Oral Cancer News|

Five Things To Look Out For In Cancer Research In 2019

Date: 12/28/18
Source: Forbes.com
Author: Victoria Forster

2018 was a remarkable year for cancer research, with great strides made in diagnosing and treating various types of cancer as well as important breakthroughs looking at the health of cancer survivors. What can we expect to see from cancer research in 2019? As a cancer research scientist, here are the top five topics that I’ll be looking out for.

1. Immunotherapy. Who will respond, who won’t respond and why?

Immunotherapy is now seemingly everywhere, with several therapies approved for various cancer types, including CAR T-cells and immune checkpoint inhibitors and several more in development such as tumor infiltrating lymphocyte (TIL) therapy. TILs successfully cleared all tumors from a woman with metastatic breast cancer, in a research breakthrough which was one of the most reported in 2018.

Over 2,500 trials are now registered worldwide, but as the use of immunotherapy grows, there are still major questions to be answered. One particularly important to the use of immune-checkpoint blocking drugs such as those which target PD-1 or CTLA-4 is ‘why do some patients respond whereas others do not?’ Several research teams worldwide are currently grappling with this question, which is unlikely to have a single, clear answer, but I expect to see much more research published on this in 2019, which will hopefully start to benefit patients by identifying who will and won’t respond to these expensive drugs.

2. Liquid biopsy tests. More clarity on precisely what they do and more evidence that they do it accurately.

The liquid biopsy industry has exploded in 2018, perhaps unsurprising given the market is expected to be worth over $2 billion annually by 2022. The promise is that eventually, we should be able to diagnose cancer with a simple blood test, earlier, more cheaply and even more accurately than we currently do and even use these tests to monitor response to cancer treatment and when and if a tumor returns.  As a cancer research scientist, the number of research papers, presentations at top conferences and news releases by the dozens of companies currently developing these technologies can make it a little overwhelming to figure out what is going on.

In 2018, two of the top liquid biopsy tests on the market had their efficacy called into question with researchers from Johns Hopkins suggesting that the two competing tests gave different results with the same patient samples. A claim which was then challenged by representatives from both companies.

Liquid biopsy tests undoubtedly have huge potential and may indeed live up to their hype, but currently, the field is a little messy and difficult to understand for scientists, patients and oncologists who are not specialists. The American Society for Clinical Oncology (ASCO) issued a statement in March of this year essentially concluding that for most liquid biopsy tests there is currently not enough evidence to recommend their use in either the diagnosis or monitoring of cancer. Hopefully, 2019 brings greater clarity about how these tests can fit into the diagnosis and care of people with cancer and ASCO will be able to review their stance accordingly.

3. More focus on the side-effects of cancer treatment.

As a cancer survivor myself and an advocate for more research into what happens to cancer survivors past the ‘all clear,’ 2018 has been a remarkable year for research into the numerous and often disabling side-effects cancer survivors experience. For decades, cancer research has understandably been mainly focused on making sure as many people survive the disease as possible, but now with millions of cancer survivors in the world, a new research field looking at what actually happens to cancer survivors as a result of their treatments is growing at considerable speed.

From a study which hopes to have found a solution to male infertility after childhood cancer treatment to work showing that some women with early-stage breast cancer can have less radiotherapy without compromising their chance of survival, 2018 was a good year for cancer survivorship research. The highlight, in my opinion, was work from Stanford University scientists that may have figured out why ‘chemo brain’ happens, one of the most commonly-reported side-effects that cancer survivors experience. Even better, the scientists suggest that it may be treatable.

4. Cancer and the microbiome.

The microbiome has been one of the most talked about topics in medicine in 2018 and shows no sign of slowing down. Amidst the predictable flurry of supplements, fad-diets and blog posts giving scientifically-questionable advice telling you how to cherish and nurture your own gut flora, plenty of solid, evidence-backed research has been published showing that the microbiome is potentially involved in multiple sclerosis, inflammatory bowel disease and even Alzheimer’s disease. But what about cancer?

There are already several studies published showing that the microbiome can influence the response to chemotherapy drugs and even in some cases cause the production of toxic breakdown products of the drug. Earlier this month, work published in Nature Communications showed how a particular bacterial strain common in the human microbiome could influence the immune system to drive the progression of a currently incurable type of blood cancer called multiple myeloma. The study raised the possibility that targeting these bacteria with drugs could halt or slow the disease.

5. Organoids, the new secret weapon in personalized cancer medicine.

Back in November 2017, I wrote about how organoids, tiny lab-grown organs made from patient tissue samples would revolutionize the treatment of cancer by allowing researchers to test drugs on patient tumors before deciding which to give the patient. Several pharmaceutical and biotechnology companies have large-scale programs to commercially develop these technologies for using organoids in drug screening for patients and the increasing accessibility of organoid growing kits from companies which supply academic and hospital research laboratories mean research papers are coming out thick and fast.

But, organoids are by no means a perfect way to test new drugs yet. For example, it is easy and quick to make organoids from certain tumor types-such as colorectal, but very difficult from others such as brain tumors. Organoids grown in the lab also don’t have a blood supply, nor are they connected to other body systems which may influence the response of a patient to anti-cancer drugs. But researchers are making progress in organoid development all of the time, figuring out better ways to make and culture them so they more accurately reflect the tumor they were originally made from.  Expect to see them playing an increasing role in designing personalized medicine approaches for cancer patients as well as being involved in more lab-based cancer breakthroughs.

Print Friendly, PDF & Email
January, 2019|Oral Cancer News|

Hospitals required to post all prices online beginning January 1

Date: 12/26/18
Source: KATV
Author: Associated Press

 

Medicare will require hospitals to post their standard prices online and make electronic medical records more readily available to patients, officials said Tuesday.

The program is also starting a comprehensive review of how it will pay for costly new forms of immunotherapy to battle cancer.

Seema Verma, head of the Centers for Medicare and Medicaid Services, said the new requirement for online prices reflects the Trump administration’s ongoing efforts to encourage patients to become better-educated decision makers in their own care.

“We are just beginning on price transparency,” said Verma. “We know that hospitals have this information and we’re asking them to post what they have online.”

Hospitals are required to disclose prices publicly, but the latest change would put that information online in machine-readable format that can be easily processed by computers. It may still prove to be confusing to consumers, since standard rates are like list prices and don’t reflect what insurers and government programs pay.

Patients concerned about their potential out-of-pocket costs from a hospitalization would still be advised to consult with their insurer. Most insurance plans nowadays have an annual limit on how much patients must pay in copays and deductibles — although traditional Medicare does not.

Likewise, many health care providers already make computerized records available to patients, but starting in 2021 Medicare would base part of a hospital’s payments on how good a job they do.

Using electronic medical records remains a cumbersome task, and the Trump administration has invited technology companies to design secure apps that would let patients access their records from all their providers instead of having to go to different portals.

Verma also announced Medicare is starting a comprehensive review of how it will pay for a costly new form of immunotherapy called CAR-T. It’s gene therapy that turbocharges a patient’s own immune system cells to attack cancer.

Immune system T cells are filtered from the patient’s own blood and reprogrammed to target and kill cancer cells that had managed to evade them. Hundreds of millions of copies of the revved-up cells are then returned to the patient’s blood to take on the cancer.

Though only a couple of such treatments have been approved for blood cancers, the cost can exceed $370,000 per patient.

“It’s a new area for the agency,” said Verma. “We haven’t seen drugs priced at this level and we’re having to think about our strategy.”

Print Friendly, PDF & Email
January, 2019|Oral Cancer News|

The US surgeon general just issued a rare advisory about e-cigs like the Juul — here’s why vaping is so dangerous

In a rare national advisory, the top US public health official warned Americans of the dangers of e-cigarettes like the Juul, a popular device that lets users inhale nicotine vapor without burning tobacco.

US Surgeon General Jerome Adams said in the advisory on Tuesday that e-cigs like the Juul are a particular danger to kids and teens and called for fresh measures to halt their rising popularity.

“We need to protect our kids from all tobacco products, including all shapes and sizes of e-cigarettes,” Adams said in a statement, adding, “We must take action now to protect the health of our nation’s young people.”

The advisory singles out Juul multiple times, saying the sleek devices are popular among teens because they’re easy to conceal and don’t emit much odor. It tells parents, health professionals, and teachers to be on the lookout for all forms of nicotine-delivery devices, including e-cigs.

Adams’ announcement comes on the heels of warnings from several other federal agencies about a rise in e-cig use, including from the Centers for Disease Control and Prevention and the Food and Drug Administration.

In November, after new CDC data pointed to a 78% increase in e-cig use among high-school students, FDA Commissioner Scott Gottliebannounced moves to further restrict sales of e-cigarettes to prevent them from getting into the hands of young people. That included a crackdown on flavored offerings, which researchers say appeal strongly to young people.

Several days before the FDA’s announcement, Juul Labs, the Silicon Valley startup behind the most popular e-cig in the US, temporarily halted sales of its flavored varieties in stores until they agreed to adopt the company’s new age restrictions and a stronger system for making sure customers are at least 21 years old.

‘E-cigarettes and youth don’t mix’

Though smoking conventional cigarettes is uniquely deadly, and vaping appears to be somewhat healthier (especially for adults looking to switch), public health experts are concerned about how e-cigarettes affect young people.

Because of their runaway popularity, e-cigs could create a new generation of Americans hooked on nicotine, one of the world’s most addictive substances and the key ingredient in e-cigs like the Juul, these experts warn. Their concern comes in part from a host of studies suggesting that teens who vape are significantly more likely to go on to smoke regular cigarettes than teens who never vape.

This finding could be related to the way nicotine affects the developing brains of young people. Though the research on e-cigs is still limited because the devices are so new, researchers have a wealth of data on the negative effects of nicotine on teens who start smoking early.

In brain-imaging studies of adolescents who started smoking in their teens, researchers have found signs of reduced activity in the prefrontal cortex, the part of the brain tied to planning and decision-making. The same teens performed worse on memory and attention tasks than teens who didn’t smoke.

Nicholas Chadi, a clinical pediatrics fellow at Boston Children’s Hospital, spoke about the Juul at the American Society of Addiction Medicine’s annual conference this spring. He described some anecdotal effects of nicotine vaping that he’d seen among teens in and around his hospital.

“After only a few months of using nicotine,” the teens “describe cravings, sometimes intense ones,” Chadi said, adding that “after only a few hundred cigarettes — or whatever the equivalent amount of vaping pods — some start showing irritability or shakiness when they stop.”

Most e-cigs contain toxic metals, and using them may increase the risk of a heart attack

Beyond the effects of e-cigs on the developing brain, a host of health issues related to e-cigs is beginning to emerge.

This spring, scientists looked at the compounds in several popular brands of e-cigs aside from the Juul and found some of the same toxic metals that are in conventional cigarettes, such as lead.

A study published this month found that people who vape tended to have high concentrations of some of these toxic chemicals in their bodies.

In another study published this summer, scientists concluded that there was substantial evidence tying daily e-cig use to an increased risk of a heart attack. And this fall, a small study with rats suggested that vaping could have a negative effect on wound healing that’s similar to the effect of regular cigarettes.

But many teens may not be aware of these health risks. Researchers say that could be because so little research has focused on the Juul, which has captured a nearly 80% market share in the US.

So for a study published in October, researchers from Stanford University’s School of Medicine surveyed young people who vaped and asked them whether they used the Juul or another e-cigarette.

From their sample of 445 high-school students, the researchers observed that teens who used the Juul tended to say they vaped more frequently compared with those who used other devices. Juul users also appeared to be less aware of how addictive the devices could be, compared with teens who used other e-cigs.

“I was surprised and concerned that so many youths were using Juul more frequently than other products,” Bonnie Halpern-Felsher, a professor of pediatrics who was a lead author of the study, said in a statement.

“We need to help them understand the risks of addiction,” she added. “This is not a combustible cigarette, but it still contains an enormous amount of nicotine — at least as much as a pack of cigarettes.”

Print Friendly, PDF & Email
December, 2018|Oral Cancer News|

HPV discovery raises hope for new cervical cancer treatments

Source: www.eurekalert.org
Author: press release – University of Virginia Health Syste

Researchers at the University of Virginia School of Medicine have made a discovery about human papillomavirus (HPV) that could lead to new treatments for cervical cancer and other cancers caused by the virus.

HPV is responsible for nearly all cases of cervical cancer and 95 percent of anal cancers. It is the most common sexually transmitted disease, infecting more than 79 million Americans. Most have no idea that are infected or that they could be spreading it.

“Human papillomavirus causes a lot of cancers. Literally thousands upon thousands of people get cervical cancer and die from it all over the world. Cancers of the mouth and anal cancers are also caused by human papillomaviruses,” said UVA researcher Anindya Dutta, PhD, of the UVA Cancer Center. “Now there’s a vaccine for HPV, so we’re hopeful the incidences will decrease. But that vaccine is not available all around the world, and because of religious sensitivity, not everybody is taking it. The vaccine is expensive, so I think the human papillomavirus cancers are here to stay. They’re not going to disappear. So we need new therapies.”

HPV and Cancer
HPV has been a stubborn foe for scientists, even though researchers have a solid grasp of how it causes cancer: by producing proteins that shut down healthy cells’ natural ability to prevent tumors. Blocking one of those proteins, called oncoprotein E6, seemed like an obvious solution, but decades of attempts to do so have proved unsuccessful.

Dutta and his colleagues, however, have found a new way forward. They have determined that the virus takes the help of a protein present in our cells, an enzyme called USP46, which becomes essential for HPV-induced tumor formation and growth. And USP46 enzyme promises to be very susceptible to drugs. Dutta calls it “eminently druggable.”

“It’s an enzyme, and because it’s an enzyme, it has a small pocket essential for its activity, and because drug companies are very good at producing small chemicals that will jam that pocket and make enzymes like USP46 inactive,” said Dutta, chairman of UVA’s Department of Biochemistry and Molecular Genetics. “So we are very excited by this possibility that by inactivating USP46 we’ll have a way to treat HPV-caused cancers.”

Curiously, HPV uses USP46 for an activity that is opposite to what the oncoprotein E6 was known to do. E6 has been known for more than two decades to recruit another cellular enzyme to degrade the cell’s tumor suppressor, while Dutta’s new finding shows that E6 uses USP46 to stabilize other cellular proteins and prevent them from being degraded. Both activities of E6 are critical to the growth of cancer.

The researchers note that enzyme USP46 is specific to HPV strains that cause cancer. It is not used by other strains of HPV that do not cause cancer, they report.

Notes:
(1) The researchers have published their findings in the scientific journal Molecular Cell. The team included Shashi Kiran, Ashraf Dar, Samarendra K. Singh, Kyung Yong Lee and Dutta. All are from UVA’s Department of Biochemistry and Molecular Genetics.

(2)The work was supported by the National Institutes of Health, grant R01 GM084465.

Print Friendly, PDF & Email
December, 2018|Oral Cancer News|

Tobacco 21 — its time has come

Source: vtdigger.org
Author: Nevin Zablotsky, DMD

As we approach the holiday season I am reminded of the gifts of love we share with our families, as well as the New Year’s resolutions we make and try to keep after Jan. 1 history.

I am a periodontist having practiced in Burlington and South Burlington for the past 40 years. In that time I have treated patients that have been severely compromised by tobacco. Some have lost teeth from advanced periodontal disease and some have lost parts of their tongue and jaw due to oral cancer, leaving them significantly compromised functionally as well as well as emotionally. I have had to advise teenagers and their families that their tobacco chewing habit had caused significant enough changes in their mouth to warrant a biopsy of the involved area. This caused great stress to them as they waited a week to find out the results. Some may think that it takes many years for tobacco use to compromise one’s health, but teenagers can die a horrible death from tobacco use if they are one of the unlucky ones who is genetically predisposed to oral cancer.

Over the years, I have traveled throughout Vermont teaching about tobacco and nicotine addiction to elementary, junior and senior high school students. I feel that I have a good sense of what kids are thinking about these subjects. The elementary school students seem to understand that cigarettes are bad for them. When one talks to the middle school kids, there are some that are beginning to think that cigarettes and smokeless tobacco use is cool, and when speaking to high school students, there is a larger percentage of them that have begun to use a variety of these products, ranging from cigarettes and cigars, to hookahs, to a variety of e-cigarettes, with the newest product, Juul, going viral. This product has become so much of a problem local schools have sent letters to parents warning them of its sudden increase in usage .

It is legal for anyone over 18 to purchase all of these tobacco and nicotine products. Here are some facts to chew on.

About 95 percent of adult smokers begin smoking before they turn 21. Two-thirds of 10th grade students and nearly half of eighth grade students say it is easy to get cigarettes. More 18- and 19-year-olds using in high school means younger kids have daily contact with students who can legally purchase tobacco products.

I am often told that when one reaches the age of 18 they are mature enough to vote, or join the military, so therefore they are mature enough to decide on using tobacco products.

Tobacco use costs the military about $1.6 billion annually in lost productivity and health care expenses tied to respiratory problems, cardiovascular disease and slower healing, according to the Department of Defense data. That’s expected to climb to $19 billion during the next 10 years and result in 175,000 premature deaths. The Air Force bans tobacco in recreation facilities, and the Navy banned tobacco on all submarines. The Vermont National Guard also stated that they would abide by Tobacco 21 legislation if it passed, again citing readiness and fitness.

An argument has been made that tobacco retailers’ businesses will be irreparably harmed if tobacco 21 is implemented. Studies show that its impact over the first 5-8 years will be between one quarter and one half of a percent.

Vermont law does not allow the sale of alcohol to anyone under 21, and the new marijuana law passed last year also restricts its usage to those over 21. Given the proven health risks of tobacco use, why does the present law allow tobacco usage at age 18?

It has been calculated that 10,000 kids now under 18 and alive in Vermont will ultimately die prematurely from the smoking habit they began in their teenage years.

Six states have passed tobacco 21 legislation. This includes Massachusetts and Maine, with New York likely to join this group. Do we really want kids coming from our surrounding states coming here to get their cigarettes or e-cigarettes?

Even Altria and R.J. Reynolds, two of the largest tobacco companies in the world have stated that the age of sale should be 21.

So as we approach the new year I want to appeal to our representatives, to resolve to pass tobacco 21 in the 2019 legislative session, and remind them about how much suffering they can prevent. The decisions they make will have major consequences for generations to come. What a great resolution to keep. What a great holiday gift for us all.

Note: This commentary is by Nevin Zablotsky, DMD, a retired periodontist who practiced in South Burlington and the Coalition for a Tobacco Free Vermont.

Print Friendly, PDF & Email
December, 2018|Oral Cancer News|

Oral cancer prognostic signature identified

Source: www.eurekalert.org
Author: press release

Researchers in Brazil have identified a correlation between oral cancer progression and the abundance of certain proteins present in tumor tissue and saliva. The discovery offers a parameter for predicting progression of the disease – whether cervical lymph node metastasis is present, for example – and points to a strategy for overcoming the limitations of clinical and imaging exams. It could also help guide the choice of an ideal treatment for each patient.

The study began in the discovery phase with a proteomic analysis of tissue from different tumor areas using 120 microdissected samples. In the verification phase, prognostic signatures were confirmed in approximately 800 tissue samples by immunohistochemistry and in 120 samples by targeted proteomics.

The study was supported by São Paulo Research Foundation – FAPESP and conducted at the National Energy and Materials Research Center (CNPEM) in partnership with the São Paulo State Cancer Institute (ICESP), the University of Campinas’s Piracicaba Dental School (FOP-UNICAMP), the Institute of Computing from the same university, the University of São Paulo’s Mathematics and Computer Science Institute (ICMC) in São Carlos, and the Dental School of the West Paraná University (UNIOESTE), in addition to other institutions in Brazil and abroad.

“The data led to robust results that are highly promising as guides to defining the severity of the disease. We suggested potential markers of the disease in the first phase of the study and verified these markers in the second phase, enhancing the reliability of the findings and showing that these markers are effective in classifying patients with cervical lymph node metastasis,” said Adriana Franco Paes Leme, a researcher at CNPEM’s National Bioscience Laboratory (LNBio) and the corresponding author of the article published in Nature Communications.

Mouth cancer, also known as oral squamous cell carcinoma (OSCC), is the most common type of malignant head and neck tumor. Prevalence and mortality are high, with some 300,000 new cases diagnosed per year worldwide and 145,000 deaths. Although it is relatively easy to detect, typically when a dentist notices an oral lesion, the disease is usually diagnosed when it is already at an advanced stage.

“We worked on the study for five years until we achieved this breakthrough,” Paes Leme told. “It was divided into two phases. In the first, we used discovery proteomics to identify and quantify tumor tissue proteins. The second phase of the study consisted of analyses using immunohistochemistry and targeted proteomics, for when you know precisely which proteins you want to quantify.”

Proteomics focuses on the identification, localization and functional analysis of the proteins in a sample, which may consist of tissue or cells, for example. The proteins are quantified, post-translational modifications are detected, and their activity and interactions are assessed.

Bioinformatics and machine learning
The study funded by FAPESP had two phases. In the first phase, the researchers used laser microdissection and proteomics to map the proteins in mouth cancer tissue and correlate them with the clinical characteristics of patients. This analysis permitted the identification of several proteins, such as CSTB, NDRG1, LTA4H, PGK1, COL6A1, ITGAV, and MB, with differing levels of abundance depending on tumor area and links to key clinical outcomes.

In the second phase, after identifying and quantifying proteins in the 120-odd tumor tissue samples, the researchers deployed two protein verification strategies.

“One strategy consisted of gauging the abundance of the selected proteins in independent tissue samples using immunohistochemistry with antibodies. The other consisted of monitoring the same preselected targets in patients’ saliva,” Paes Leme said.

Saliva was chosen because this cancer is located in the mouth, where proteins could be secreted by neoplastic cells. “Saliva is a promising source of markers, as well as being a fluid obtained by noninvasive collection,” she explained. “We verified the proteins in saliva from 40 patients. Technical triplicates were analyzed to achieve the highest possible confidence level for the results in this phase of the study.”

After analyzing the saliva samples, the researchers used bioinformatics and machine learning techniques to arrive at prognostic signatures, verifying which of the proteins or peptides selected in the first phase could distinguish between patients with and without cervical lymph node metastasis.

“In addition, we had valuable information about the clinical evolution of the patients who took part in the study as volunteers by donating samples of their saliva,” Paes Leme said.

From this result, it was possible to identify three specific peptides – LTA4H, COL6A1, and CSTB – that can be used as a signature to classify patients with and without cervical lymph node metastasis, offering the potential to help doctors overcome the limitations of clinical exams and guide personalized treatment strategies.

Affordable biosensors
The scientists are now working on a new study designed to use translational techniques to build affordable biosensors capable of detecting prognostic signatures in patients’ saliva.

Peptides currently have to be identified and quantified by mass spectrometry and proteomics, which are costly techniques and not often available in clinics and hospitals.

“We want to develop a simpler and cheaper method that can easily be used by health professionals to assess the progression of the disease on the basis of tests that can be performed in a dentist’s or doctor’s office, or in clinical labs. In the study we’ve just published, we were able to identify this prognostic signature by mass spectrometry. We now plan to develop a biosensor with a focus on the use of this signature so that it can be adopted for clinical use and help guide treatment decisions”, Paes Leme said.

Print Friendly, PDF & Email
December, 2018|Oral Cancer News|