Blood test that finds 50 types of cancer is accurate enough to be rolled out

Author: Nadeem Badshah

A simple blood test that can detect more than 50 types of cancer before any clinical signs or symptoms of the disease emerge in a person is accurate enough to be rolled out as a screening test, according to scientists.

The test, which is also being piloted by NHS England in the autumn, is aimed at people at higher risk of the disease including patients aged 50 or older. It is able to identify many types of the disease that are difficult to diagnose in the early stages such as head and neck, ovarian, pancreatic, oesophageal and some blood cancers.

Scientists said their findings, published in the journal Annals of Oncology, show that the test accurately detects cancer often before any signs or symptoms appear, while having a very low false positive rate.

The test, developed by US-based company Grail, looks for chemical changes in fragments of genetic code – cell-free DNA (cfDNA) – that leak from tumours into the bloodstream.

The Guardian first reported on the test last year and how it had been developed using a machine learning algorithm – a type of artificial intelligence. It works by examining the DNA that is shed by tumours and found circulating in the blood. More specifically, it focuses on chemical changes to this DNA, known as methylation patterns.

Now the latest study has revealed the test has an impressively high level of accuracy. Scientists analysed the performance of the test in 2,823 people with the disease and 1,254 people without.

It correctly identified when cancer was present in 51.5% of cases, across all stages of the disease, and wrongly detected cancer in only 0.5% of cases.

In solid tumours that do not have any screening options – such as oesophageal, liver and pancreatic cancers – the ability to generate a positive test result was twice as high (65.6%) as that for solid tumours that do have screening options such as breast, bowel, cervical and prostate cancers.

Meanwhile, the overall ability to generate a positive test result in cancers of the blood, such as lymphoma and myeloma, was 55.1%. The test correctly also identified the tissue in which the cancer was located in the body in 88.7% of cases.

Dr Eric Klein, chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic in the US and first author on the research, said: “Finding cancer early, when treatment is more likely to be successful, is one of the most significant opportunities we have to reduce the burden of cancer.

“These data suggest that, if used alongside existing screening tests, the multi-cancer detection test could have a profound impact on how cancer is detected and, ultimately, on public health.”

Dr Marco Gerlinger, from the Institute of Cancer Research in London and consultant medical oncologist at the Royal Marsden NHS foundation trust, said: “This new study shows impressive results for a simple blood test that can detect multiple cancer types.

“False positives are low which is important as this will avoid misdiagnoses. For some of the most common tumour types such as bowel or lung cancer, the test even picked up cancers that were very small, at a stage where many of them could potentially be cured.

“The study was done in patients whose cancer was already diagnosed based on other tests and this screening technology still needs to be tested in actual screening trials before routine use.

“But it already allows a glance at early cancer detection in the future which will almost certainly be built around liquid biopsy tests, which detect cancer DNA in the bloodstream.”

Meanwhile, the results of the NHS pilot of the test, which will include 140,000 participants, are expected by 2023.

Prof Peter Johnson, national NHS clinical director for cancer, said: “This latest study provides further evidence that blood tests like this could help the NHS meet its ambitious target of finding three-quarters of cancers at an early stage, when they have the highest chance of cure.

“The data is encouraging and we are working with Grail on studies to see how this test will perform in clinics across the NHS, which will be starting very soon.”

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Marine Corps corporal gets 3D-printed teeth with jaw reconstruction

Author: Ed Adamczyk

A Marine Corps member is the first recipient of the Defense Department’s first jaw reconstruction using 3D-printed teeth, the Pentagon said on Friday. A tumor prompted the removal of most of Cpl. Jaden Murry’s jaw in a November 2020 surgery. Murry is a member of Logistics Battalion 7, Marine Corps Air Ground Combat Center at Twentynine Palms, Calif.

The jaw was reconstructed using a portion of his fibula, or lower leg bone, but his lower teeth were made using a digital model, which was then printed into a physical replacement bridge and inserted in the new jaw. The surgery was conducted by a multi-department team of surgical specialists at the Naval Medical Center in San Diego.

“All of the providers worked as a team to keep his recovery on track,” Lt. Cmdr. Daniel Hammer, maxillofacial surgical oncologist and reconstructive surgeon, said in a press release.

“We were able to safely remove his tracheostomy tube [inserted in a patient’s neck when there are concerns about postoperative breathing] within a week of the surgery, and it was then we knew he was making strides in the right direction.”

Murry is recovering in the Naval Center’s Wounded Warrior Battalion, and on a diet of soft foods. A final prosthetic set of teeth will be available to him in about two months.

“Since his surgery, [OMFS specialists and I] see Jaden twice weekly for check-ups, and we’re guiding his healing process,” Hammer said in December. “To see him swallowing, speaking, walking and not using a tracheostomy tube one week post-surgery was a huge victory, both for [Murry] and for us.”

The success is also a part of a program developed by the U.S. Armed Forces Institute of Regenerative Medicine whose researchers work to use the body’s natural healing powers, in this case through the fibula transfer to the jaw, to improve head and face reconstruction.

Murry said that he is eager to resume his Marine Corps duties.

“I really look forward to getting back to a healthy mindset and working out, running and bodybuilding,” he said, adding that he will seek pizza when he again can eat solid food.

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A challenge to chew on: eating and drinking after cancer treatment

Author: Dara Chadwick, Heal

Exercise has always been part of Scott Wieskamp’s life. But after cancer treatment, the longtime runner and marathoner added a new element to his training regimen — exercises to strengthen and maintain his swallowing muscles.

“Every day while I’m driving to work, I open my mouth like I’m yawning to stretch all my facial muscles as much as I can,” says Wieskamp, 62, who lives just outside Lincoln, Nebraska. “I take my tongue and put it under the back of my lower teeth and push as hard as I can to exercise my tongue muscles. There’s about half a dozen things I do for a few minutes every day.”

Four years ago, Wieskamp was treated for oral cancer caused by the human papillomavirus. The aggressive treatment, which included 39 radiation sessions and several doses of the chemotherapy drug cisplatin, knocked out the cancer. But it also left Wieskamp unable to eat, and he lost 15 pounds in a matter of weeks.

“As you get radiation in the neck and throat area, it becomes painful to swallow,” he says. “I quit doing all that. I quit eating, quit swallowing — I couldn’t even drink.”

Because he was unable to get adequate nutrition, his doctors inserted a feeding tube so Wieskamp wouldn’t have to swallow. The tube stayed in place throughout his two months of treatment and for about a month after, he says.

Although his nutrition improved, Wieskamp says he was left with another problem: His muscles “forgot” how to swallow.

“I had to go to a speech-language pathologist to help me learn how to swallow again,” he says. “It was scary, painful and frustrating.”

Wieskamp’s swallowing challenges aren’t uncommon. After treatment, survivors of cancer may experience not only difficulty swallowing but also dry mouth and changes in taste, smell, digestion or bowel habits. Any of these changes can make eating and drinking a struggle, which then makes it difficult to get adequate nourishment.

When you’re not getting the nutrients you need, it’s hard for the body to regain strength and rebuild cells, according to Rachel Wong, an oncology dietitian at the Georgetown Lombardi Comprehensive Cancer Center at MedStar Georgetown University Hospital in Washington, D.C.

“Patients can experience delayed healing and recovery caused by poor nutrition post treatment” she says. “A rapid decline in weight from inadequate nutrition often results in both fat and muscle loss, causing significant fatigue and weakness, which can greatly impact one’s ability to accomplish tasks and resume a normal way of living.”

“It can be possible that patients find delayed healing and delayed recovery because of poor nutrition post treatment,” she further explains. “If you’ve lost a lot of weight and you’ve lost muscle, you may sleep a lot during the day.”

Eating challenges can also make it tough for survivors of cancer to enjoy time with family and friends, Wieskamp says. After treatment, he didn’t look forward to social occasions like he used to. “People say, ‘Hey, let’s meet for coffee’ or ‘Let’s have family over and we’ll have a meal,’” he says. “Our lives revolve around food.”

Some types of cancer require treatments that are more likely to affect how people eat and drink. According to Dr. David G. Pfister, medical oncologist and chief of the Head and Neck Oncology Service at Memorial Sloan Kettering Cancer Center in New York City, treatments for cancers of the head and neck pose particular challenges because they can affect swallowing, taste and smell.

For example, surgery in certain areas of the head and neck can disrupt structures used in swallowing, such as the throat and tongue. In addition, oral mucositis — mouth pain, sores and infection — can develop after radiation and chemo- therapy. Some survivors experience damage or changes to their salivary glands, which can make the mouth exceptionally dry. This can also predispose them to dental problems.

Jean DiNapoli, 62, of Newburgh, New York, says trying to swallow after completing 30 rounds of radiation for oropharyngeal cancer (a type of cancer found in an area of the throat called the oropharynx) was like “swallowing glass.” She also experienced mouth sores and thrush, a yeast infection that develops in the mouth, along with significant dry mouth.

DiNapoli, who is now seven years post treatment, says she lost about 35 pounds immediately following radiation.

“I could have gotten a feeding tube, but I really didn’t want it,” she says. “I didn’t want my muscles to atrophy.”

Pfister says the decision to place a feeding tube is one that doctors make carefully. “Not that long ago, when significant swelling, pain and weight loss were expected, we would prophylactically put in a feeding tube to get patients over the hump, so to speak,” he says. But doctors found that people would soon start taking all their calories through the tube, leading to the exact problem DiNapoli feared — muscle atrophy.

“Your swallowing muscles are like any other muscle. If you don’t use it, you lose it,” Pfister says, adding that it’s critical to make swallowing therapy a routine part of treatment along with good pain control. “We evaluate every patient in an individualized way. (Although) there clearly are settings where we put in a feeding tube, we’re more selective.”

After her treatment ended, DiNapoli worked with a speech pathologist once a week for a couple of months to regain strength in her tongue muscles and improve her ability to swallow. “I did different exercises, such as swallowing with my tongue between my teeth,” she says. “I also had the help of a good nutritionist.”

Registered dietitian nutritionists trained in mitigating the impact of cancer treatments can help survivors find new ways not only to get nourishment but also to enjoy food again. Annette Goldberg, a senior nutritionist at Dana-Farber Cancer Institute in Boston, says choosing the tools to help individuals bring their symptoms under control can be a bit of a puzzle. It depends on factors such as their overall health prior to treatment, the type of cancer and treatment they had, and the social support system they have.

“Sometimes I’ll ask patients if they live alone, and they’ll wonder why I’m asking that question,” she says. “I want to make sure they have the proper support. If you’re not feeling well, you don’t want to do anything.” That includes cooking, she says.

Maureen Gardner, a clinical oncology nutritionist at Florida Cancer Specialists & Research Institute in Tampa, says survivors who’ve had cancers in the gastrointestinal (GI) tract or treatment for any cancer in areas near the GI tract — such as prostate, ovarian or uterine cancer — may experience ongoing effects on how food is digested and eliminated. Some survivors may experience weight gain, such as breast cancer survivors who are on long-term hormone therapies or those who have entered menopause. Other people may experience ongoing diarrhea or dumping syndrome — when food moves too quickly from the stomach to the small intestine — after being treated for GI cancers.

Gardner says dietary changes, both in what and how patients eat, can help manage eating challenges after cancer treatment ends. If you have dry mouth, try to:

• Focus on hydration. In addition to drinking water, Goldberg recommends keeping your mouth clean and avoiding toothpastes and mouthwashes that are too harsh.

• Boost saliva production. Tart foods can stimulate the salivary glands, Goldberg notes. Adding tart lemon juice to water or chewing a strong sugarless mint gum can help.

• Add soft, moist foods to your diet. Wong recommends adding extra sauces or broth or even cream to casserole-type dishes or when having drier foods like meat, potatoes and rice.

“Drinking fluids along with your meals can certainly help improve the moisture content in the mouth and make swallowing easier,” Wong says. “Just having a glass of water, juice or any type of liquid in between each bite can really help get the food down.”

DiNapoli says she drank lots of water to relieve her dry mouth. She also tried different lozenges, mouthwashes and gels. “I still use XyliMelts,” she says. “I put (one) in my mouth at night and it slowly dissolves.”

Some survivors experience changes in taste and smell that affect the way they experience food. “I lost my sense of taste right after radiation,” DiNapoli says. “Everything tasted like paste. But then my sense of taste came back so strong that spicy food was overly spicy. And my sense of smell is stronger.”

“I tell patients that your taste buds and smell will constantly change,” Wong says, encouraging people to keep a running list of things that work well and things that don’t. “In my experience, a list of what works gives you the motivation to keep trying new things.”

If you’ve had changes in taste and smell that affect how you experience food, try experimenting with seasonings. Adding spices such as basil, pepper or dill can make food more sweet, savory or salty and improve its flavor. Wong also recommends adding different types of sauces, such as ranch, barbecue, or sweet and sour to help bring out the flavor in foods and add some moisture.

If you’re experiencing ongoing GI symptoms such as diarrhea, Goldberg recommends talking to your doctor or nutritionist about supplements that might help, such as banana flakes. “It’s a product that’s made from dehydrated bananas, which contain several soluble fibers including pectin. The soluble fiber absorbs fluid to help firm the stool,” she says. “A combination of foods, maybe some supplements and working with your care team can help.”

Although eating and drinking can be difficult during active treatment and the weeks immediately after, strengthening exercises and dietary changes can help most people overcome these challenges with time. Addressing issues right from the start can help the healing process, Wong says.

“Getting guidance from a dietitian can impact how patients recover after their treatment,” she says, adding that it’s important for doctors to talk with patients about challenges they might experience. She also recommends resources such as the American Institute for Cancer Research and the American Cancer Society for advice on managing eating challenges after treatment.

Support groups — both online and in person — can also help. DiNapoli and Wieskamp are members of an organization called Support for People with Oral and Head and Neck Cancer (SPOHNC). Both say SPOHNC has been incredibly helpful as they’ve healed.

“I would tell most people that I’m 100% normal, but I’m not 100% the same,” Wieskamp says. “My brain has had to learn that things that used to taste one way taste a little different today. But I’m only one person. You could probably interview 20 people and they may have 20 different answers.”

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Public urged to help cancer researchers by playing online game

Author: staff

Scientists have turned to the public to help with their latest cancer research in the form of an online citizen science game. The game is designed to train a computer algorithm to recognise oral cancers in medical images.

AcCELLerate tasks users with tracing the outline of a series of fluorescent dye-stained tongue images which become increasingly complex, using their computer mouse or finger on a smartphone.

It is designed to train a computer algorithm to recognise oral cancers in medical images, improving its ability to differentiate between healthy and cancerous cells.

“I’m really excited that the public will be contributing to my work on oral cancer,” said Dr Priyanka Bhosale, from King’s College London’s Centre for Stem Cells and Regenerative Medicine.

“The outcomes of the public training the AI will help me assess tumour tissue samples in a faster and more reliable way.”

It is hoped the tool can be used to advance research into other cancers.

The game forms part of the Royal Society Summer Science 2021 event and can be found at

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RowanSOM researcher begins human trials for cancer treatment drug

Author: news release

Could a targeted therapy derived from a plant used medicinally in China for centuries offer the next breakthrough in cancer treatment? Dr. Gary Goldberg, associate professor in the Department of Molecular Biology at Rowan University School of Osteopathic Medicine (RowanSOM), is undertaking a human clinical trial to find out.

Goldberg and his team are collaborating with a group at the Rutgers New Jersey Medical School headed by Dr. Mahnaz Fatazadeh, professor at Rutgers School of Dental Medicine, to test a new drug candidate called MASL. This novel compound has been trademarked and licensed from Rowan University by Sentrimed, a company founded by Goldberg. MASL is derived from Maackia amurensis, a legume tree native to the Amur River valley, which flows through parts of Russia and China.

The MASL human trial marks a milestone for RowanSOM, Goldberg noted.

“Coming up with a new drug and taking it to a clinical trial is an excellent example of investigator-initiated research from bench to bedside,” said Goldberg. “It has taken a lot of collaboration and work to get to this point.”

The FDA considers MASL an investigational new drug.

“This is a unique Phase I trial,” Goldberg said. “This study integrates investigation of patient safety, along with potential efficacy and proof of concept mechanistic studies.”

Goldberg and his team began the ongoing human trial, involving 20 cancer patients, in fall 2020. While MASL has the potential to treat many kinds of cancer, this trial will test MASL’s effects on oral cancer.

“Oral cancer is a horrible disease,” Goldberg said. “It kills as many people in this country as melanoma. In addition, survivors can suffer from decreased quality of life resulting from disfigurement and other consequences of surgery required for effective treatment.”

Since oral cancer causes lesions in the mouth, Goldberg and his team are administering MASL topically, with an oral lozenge, and systemically, as the compound enters the circulatory system after digestion.

Goldberg and his team aim to target cancer cells using specific proteins. Commonly used cancer treatments attack rapidly dividing cells, but not all of these cells are cancerous. This results in collateral damage, leading to a weakened immune system, as well as injury to digestive and other tissues.

MASL is different because, instead of harming all cells that divide rapidly—even normal and healthy ones—it targets the podoplanin (PDPN) protein receptor expressed on the surface of cancer cells.

Proteins are key in targeted cancer treatments, but thousands of proteins are turned on in the body of a cancer patient. Just a tiny fraction of these proteins are necessary for cancer to thrive.

“The most aggressive cancers tend to express high levels of PDPN,” Goldberg explained, including the vast majority of aggressive oral cancers. A normal cell may only have a little of this protein, but abnormal cells have a lot of it.

MASL’s potential goes beyond stopping the growth and spread of cancer cells, possibly even preventing precancerous lesions from turning malignant.

“The PDPN receptor offers exceptional opportunities as a powerful sentinel cancer biomarker and functionally relevant chemotherapeutic target,” Goldberg added.

Goldberg’s students have been heavily involved in developing knowledge of the basic science behind the drug’s efficacy, publishing findings in peer-reviewed journals and assisting directly with the human trial.

“I have seen firsthand the tumor-suppressive effects MASL has in cell culture and animal models,” said Stephanie Sheehan, a sixth-year Ph.D. student of cell and molecular biology who has assisted Goldberg in purifying, profiling and validating MASL in the lab for five years. “I am grateful this noninvasive and nontoxic therapy is being brought to patients.”

Learning about such cancer research drew seventh-year Ph.D. student Edward P. Retzbach to graduate school.

“As I learned more about MASL and the mechanisms behind how it worked, my interest grew,” Retzbach said. “For most preclinical and biomedical research, you don’t get to see the effects for a long time, so it is pretty great to actually see it happen in real time.”

Funding for Goldberg’s research has come from multiple organizations, including the National Institutes of Health, the Osteopathic Heritage Foundation, the N.J. Health Foundation, the Camden Health Research Initiative and the Northarvest Bean Growers Association, as well as Sentrimed and charitable donations.

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World’s first research centre for recurrent head and neck cancer

Author: Jasmine Jackson

The Royal Marsden NHS FT have launched the world’s first research centre for recurrent head and neck cancer, as a result of funding from the Royal Marsden Cancer Charity. It hopes to accelerate research into the disease, which will be carried out by a world-class team of clinicians and researchers.

The International Centre for Recurrent Head & Neck Cancer (IReC) also aims to improve patient outcomes in the UK and beyond, in the curative treatment, palliation, and supportive care of recurrent head and neck cancer.

The IReC announced a series of initiatives to help achieve these goals, including:

  • A national registry to improve understanding around recurrent head and neck cancer, whist capturing the different ways it is treated across the UK.
  • A tissue biobank to support laboratory and translational research.
  • An International Referral Centre to offer rapid second opinions for patients being treated in the UK and internationally.

This will also include the funding of three PhD research fellows, trial managers, a clinical trial nurse and a data manager, to increase research capacity.

Head and neck cancer is the 8th most common cancer in the UK, with more than 12,000 diagnoses each year. After treatment, it is estimated that between 20% and 40% of head and neck cancers will return, and in England, between 28% and 67% survive for five years or more.

IReC Director Professor Vinidh Paleri, Consultant Head and Neck Surgeon at The Royal Marsden, said: “Treating recurrent head and neck cancer is incredibly challenging as these patients have already been treated, often with surgery and radiotherapy, which can cause anatomical changes, scarring, and impaired healing. This means successfully treating the disease requires access to multi-specialty expertise, the latest drugs and surgical technology.

“However, patients with recurrent head and neck cancer in the UK face inconsistent access to treatment, with many treated palliatively not curatively. We also don’t know enough about the disease’s incidence or outcomes as national databases do not provide this information in detail, unlike for primary cancers.

“Through IReC, we aim to transform the treatment and care of recurrent head and neck cancer. From building a better understanding of how the disease is managed across the UK through a national registry, to funding research into novel treatments and minimally invasive surgery, our work will drive better outcomes for patients at The Royal Marsden and across the world.”

The IReC aims to launch more UK and international based projects over the next 10 years, to improve outcomes for patients. Part of this plan includes creating an international network of centres to roll out clinical trials quickly, and a genomics hub to enhance diagnostics and offer personalised treatment.

Charles Wilson, former Booker CEO and the founding donor of IReC, said: “Having been diagnosed with throat cancer three years ago, it is a privilege to support Professor Vinidh Paleri and his amazing team in helping found the International Centre for Recurrent Head & Neck Cancer.

“The need is great and the analytical, surgical and clinical expertise at The Royal Marsden is mind-blowing. The research could make a huge difference to patients around the world.”

The Royal Marsden’s Head and Neck Unit has been recognised as one of the largest of its kind in Europe and over the last two decades has helped pioneer numerous advances in the management of recurrent head and neck cancer.

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‘Vaccine for cancer’ trial begins in Liverpool and this is how it works

Author: Jonathan Humphries, Public Interest Reporter

The first human trials for a groundbreaking ‘vaccine for cancer’ have begun in Liverpool with the first patients recruited.

A team of cancer researchers from Liverpool Head & Neck Centre, The Clatterbridge Cancer Centre, Liverpool University Hospitals and the University of Liverpool are trialling new vaccines that aim to harness a patients own immune system to fight cancer.

Head and neck cancers, which include mouth, throat, tongue and sinus cancers, are particularly difficult to treat and carry a high risk of returning even after successful treatment.

The first UK patient has now been recruited in Liverpool and vaccine production has begun at the Transgene laboratory in France.

More patients will be recruited in coming months, with the aim of administering the first vaccine in a few months, when the usual treatment has been completed.

The Transgene trial will involve around 30 people who have just completed treatment for advanced, but still operable, HPV-negative (not linked to human papilloma virus) squamous cell carcinoma of the head and neck (SCCHN).

How does the vaccine work?

Head and neck cancer can involve many different kinds of gene mutations resulting in the production of new proteins, called ‘neoantigens’, that vary widely between patients.

The Transgene trial aims to produce individualised ‘therapeutic vaccines’, designed to trigger an immune response to the new antigen produced by a particular gene mutation linked to each patient’s own head and neck cancer.

Chief Investigator for the UK trial, Professor Christian Ottensmeier, a Consultant Medical Oncologist at The Clatterbridge Cancer Centre and Professor of Immuno-Oncology at the University of Liverpool, explained the process.

He said: “Cancer develops because of faulty cells.

“Cells in the body are constantly reproducing and sometimes a bit of the genetic code in a cell doesn’t get copied correctly. The new cells develop with faulty genetic code.

“Most of the time, this doesn’t matter because the faulty code doesn’t do anything important.

“Occasionally, however, the faulty code is important. If the body doesn’t spot the error, these faulty cells can continue to reproduce and the person develops cancer.

“The immune system is very good at recognising anything unusual such as viruses and bacteria, and the T-cells trigger antibodies to attack and destroy them.

“Cancer cells can be very good at hiding from the immune system because, apart from the faulty bit of genetic code, they are very similar to healthy cells.

“We are creating a cancer vaccine for each patient by turning the faulty genetic code into an Achilles heel for treatment.

“We already know that the vaccine technology is very effective at waking up the immune system. We hope this means that if the patient develops cells with the same faulty code in the future, their immune system will recognise them straight away and develop antibodies to destroy them before they develop into cancer.”

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Cancer survivors’ tongues less sensitive to tastes than those of healthy peers

Author: University of Illinois at Urbana-Champaign, News Bureau

Most survivors of squamous cell head and neck cancers report that their sense of taste is dulled, changed or lost during radiation treatment, causing them to lose interest in eating and diminishing their quality of life.

In a study of taste and smell dysfunction with 40 cancer survivors, scientists at the University of Illinois Urbana-Champaign found that the tips of these individuals’ tongues were significantly less sensitive to bitter, salty or sweet tastes than peers in the control group who had never been diagnosed with cancer.

In a paper published in the journal Chemical Senses, the U. of I. team said this diminished taste sensitivity suggested that the taste buds on the front two-thirds of the cancer survivors’ tongues or a branch of the chorda tympani facial nerve, which carries signals from the tip of the tongue to the brain, may have been damaged during radiation therapy.

“While most studies suggest that patients’ ability to taste recovers within a few months of treatment, patients report that they continue to experience taste dysfunction for years after treatment ends,” said M. Yanina Pepino, a professor of food science and human nutrition at the U. of I. “Our primary goal in this study was to test the hypothesis that radiation therapy is associated with long-term alterations in patients’ senses of smell and taste.”

While undergoing radiation and/or chemotherapy, head and neck cancer patients may lose taste buds, triggering a transient reduction in their ability to taste – a condition called hypogeusia – or their perception of tastes may be altered, a condition called dysgeusia that can also occur when nerves are damaged during cancer surgery, she said.

“Taste buds’ average lifespan of about 10 days enables rapid recovery from injury if the stem cells are preserved, yet it also makes the short-lived and long-lived cells within taste buds particularly vulnerable to the direct cytotoxic and anti-proliferative effects of chemotherapy and radiotherapy,” Pepino said.

Prior studies that explored taste loss and perception in these patients showed mixed results. Many of these studies involved “whole mouth” experiments that may not have detected regional damage to the taste buds at the front of the tongue or to the chorda tympani section of the facial nerve, said graduate student Raul Alfaro, the lead author of the study.

The U. of I. team assessed participants’ smell and taste functions separately and explored whether sensory interactions between taste and retronasal odors – aromas from food and beverages that are perceived in the oral cavity while eating or drinking – differed for the cancer survivors and the people in the control group.

The team assessed participants’ ability to taste regionally by applying cotton swabs soaked in flavored solutions to the tips of their tongues.

They also evaluated participants’ whole-mouth taste function by having them swish solutions around in their mouths for five seconds and spit them out. For this test, the participants were presented with nine cups of liquids that contained both taste and smell sensory components. The cups contained two concentrations of strawberry extract in a sucrose solution, lemon extract in citric acid, salt in a vegetable broth and caffeinated instant coffee. They also received one cup of deionized water.

After sipping each sample, participants were asked to identify its taste quality – sweet, salty, bitter, umami (savory) or no sensation – and to rate the smell and taste intensity of the sample on a scale that ranged from “no sensation” to “strongest of any kind.”

Participants tasted the samples twice – once wearing a nose clip and once without – to determine whether their taste perception differed when the nose clip blocked their retronasal olfactory cues.

When participants’ sense of taste was assessed using the whole-mouth test with or without the nose clip, they similarly rated the taste and smell of nearly all of the samples.

However, when participants’ sense of taste was assessed regionally at the tip of the tongue, the cancer survivors were more likely to respond they did not perceive a taste or to misidentify the taste quality – such as bitter, salty or sweet – of multiple samples.

“Although the results from the whole-mouth taste test suggested that head and neck cancer survivors’ taste function was normal and well preserved, results from the regional tests indicated that they had some deficits,” Pepino said. “Subtle taste dysfunction in the tip of the tongue persisted for several months after they completed their oncology treatments.

“Taste dysfunction at the tip of the tongue might sound unimportant; however, there is an elegant cross-talk between the nerves that conveys signals from the tip and the back of the tongue, such that taste signals in the tip of the tongue inhibit signaling from the back. This system allows taste intensity to remain constant in the whole mouth, even when taste signaling coming from the tip of the tongue is reduced. However, reduced signal input can also lead to phantom tastes, metallic taste and other oral symptoms.”

Additional co-authors of the study were food science and human nutrition professor Anna E. Arthur, who is also the Sylvia D. Stroup Scholar in Nutrition and Cancer, and an oncology dietitian with the Carle Cancer Center; Dr. Kalika P. Sarma, a radiation oncologist at Carle Foundation Hospital and a clinical assistant professor in the Carle Illinois College of Medicine; and then-research fellow Sylvia L. Crowder.

The work was supported by grants from the U.S. Department of Agriculture National Institute of Food and Agriculture, the Academy of Nutrition and Dietetics, and the Division of Nutritional Sciences at the U. of I.

Crowder’s work on the project was supported by a Carle Illinois Cancer Scholars for Translational and Applied Research Fellowship, as well as a grant from the National Cancer Institute.

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‘On the rise:’ Immunotherapy options for head and neck cancer

Author: Kristie L. Kahl

On behalf of the Head and Neck Cancer Alliance, Dr. Michael Moore spoke with CURE® about emerging therapies that potentially offer exciting new options for the future.

Although rates of head and neck cancer have risen, in part because of the human papillomavirus (HPV), emerging therapies such as targeted agents and immunotherapies are paving the way for future treatment of the disease, according to Dr. Michael Moore.

“I would say (immunotherapy) is probably one of the more exciting parts of what we’ve learned about head and neck cancer in recent years,” he told CURE® as a part of its “Speaking Out” video series.

On behalf of the Head and Neck Cancer Alliance, CURE® spoke with Moore, associate professor of otolaryngology-head and neck surgery and chief of head and neck surgery at Indiana University School of Medicine in Indianapolis, about targeted therapies, immunotherapy and how clinical trials are leading the way for future treatments.

How have genomics and targeted therapies played a role in head and neck cancer treatment?

Well, I would say it’s an emerging role. And it’s not used as commonly in head-neck cancer as it is in some other areas. So molecular testing or targeted therapies essentially are looking at a very specific part of the tumor to see if we can develop a specific drug that will target just that; (the goal is to) weaken the cancer’s defense — that is one way to say it — and try to very specifically treat that cancer in a way that will give us the best chance of getting rid of it and potentially try to limit the side effects related to the treatments. This has become a little bit more common now that the ability to analyze these tumors has become more widely available across the country. But still, the majority of these types of treatment approaches will be in the context of a clinical trial.

Do we have any currently approved targeted therapies for head and neck cancer?

That’s a great question. I think these are kind of different and are emerging all the time. There are ones that are focused on very specific mutations, such as what’s called the BRAF mutation, which is one that can be present in melanoma or certain aggressive cancers, such as thyroid cancer. And other ones will target things like tyrosine kinase inhibitors that have a more focused route to try to combat these tumors. And then there are ones that will be discussed a little later, such as immuno-oncology drugs that focus on the program cell death ligand and the receptor to try to turn the body’s immune system back on. Another example is what’s called Erbitux (cetuximab), which is focusing on a specific receptor on cancer cells, really trying to exploit this particular difference in cancer cells compared with normal tissue to try to give the best chance of getting rid of the tumor, but minimizing the side effects of the treatment.
What role has immunotherapy had in head and neck cancer treatment?

Cancer has a way of almost turning off the local immune system. It blocks many of the local immune responses to it. Normally, the body would say, “Yeah, that’s not part of our normal tissue, we want to get rid of it.” And some cancers have a way of blocking that. These immunotherapies have a way of almost inhibiting that blockage, if you will, or turning the immune system back on and allowing your own body’s immune system to fight these tumors. These can be incredibly effective. The challenge is if they’re only effective in a small minority of cancers. And so, when they do work, they can work extremely well and can give really good and long-lasting results. But in a high percentage of patients, the responses are much more modest or (patients) may not even respond at all.

Can you discuss the currently available immunotherapies for head and neck cancer?

There are two. Opdivo (nivolumab) is one that can be used in patients who have not responded or progressed despite standard therapy, including recent treatment with chemotherapy, including cisplatin. And then Keytruda (pembrolizumab) is another similar amino therapy that can be used and has actually achieved approval for use in the primary setting. When cancer comes back in an area that can’t be treated with either definitive surgery or definitive radiation therapy, you can use that as a next avenue for treatment. These are the two (Food and Drug Administration)-approved drugs that are out there. They also have ongoing studies where they’re being combined with other standard-of- care, primary treatments for head and neck cancer. I think in the next five to 10 years, they’ll likely be integrated much more on the front end of cancer therapy, rather than just offering them to those who don’t have other treatment options.

How do clinical trials help to advance these therapies, and why should patients consider joining one?

These are really what allows us to make our cancer treatment better. We constantly are. It’s not just going out and experimenting on people but, rather, we’re comparing these treatments to see how we can improve on the current standard approach to therapy. If you were to look back 50 to 60 years ago, all we had were big, morbid surgeries that people were put through and possibly adding radiation therapy. And then we added cisplatin, which is a drug that can be effective in enhancing the effects of radiation therapy. Now, as we add these other treatments, such as immunotherapy and other targeted therapies, the only way we know if they have any advantage over what we have to offer, currently, is to compare them in a clinical trial.

And with these clinical trials, those who have designed them have been very thoughtful in trying to do so in a way that compares them and then looks to see: Does that give us a benefit in getting rid of the cancer or curing the cancer, or at a minimum, slowing it down or giving a longer life? And/or does it give better quality of life or reduce the level of side effects? That’s what many of these clinical trials are. Some are adding new agents to see if those work better than other ones. For example, in the HPV-related cancer, some of the clinical trials are saying these respond fairly well to treatment. Can we actually back off on the severity of treatment, give them just as good of a cancer cure but (with) fewer long-term side effects? I think they’re critical as the only way we’re going to figure out how best to manage these types of cancers.

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Personalized 3D-printed shields protect healthy tissue during radiotherapy

Author: Jigar Dubal

Personalized 3D-printed devices for radioprotection of anatomical sites at high risk of radiation toxicity: intra-oral device (A), oesophageal device (B) and rectal device (C) generated from patient CT images. The area for protection is highlighted in red. (Courtesy: CC BY 4.0/Adv. Sci. 10.1002/advs.202100510)

One of the primary goals of radiation therapy is to deliver a large radiation dose to cancer cells whilst minimizing normal tissue toxicity. However, most cancer patients undergoing such treatments are likely to experience some side effects caused by irradiation of healthy tissue. The extent of this damage is dependent on the treatment location, with the most common toxicities involving the oral cavity and gastrointestinal tract.

Materials with a high atomic number (Z), often known as radiation-attenuating materials, can be used to shield normal tissue from radiation. However, integrating such materials into current patient treatment protocols has proven difficult due to the inability to rapidly create personalized shielding devices.

James Byrne and colleagues at Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital and MIT have addressed this need. The team has developed 3D-printed radiation shields, based on patient CT scans, incorporating radiation-attenuating materials to reduce the toxicity to healthy tissue.

Producing personalized 3D-printed shielding
Before a patient undergoes radiotherapy, they undergo CT scans to provide anatomical information that is used to plan their treatment. Byrne and his colleagues utilize these CT images to design personalized radio-protective devices, which they produce through 3D printing.

To determine the most appropriate shielding materials for the device, the researchers tested various elements and alloys, including liquids, with a high Z number. They characterized these materials by measuring their relative mass attenuation coefficients. From this, the team determined that elemental materials demonstrated greater radiation shielding than alloys or composites, and that mercury largely outperformed all other liquids. They then incorporated the high-Z materials into the personalized 3D-printed devices. The devices were made such that the shielding material could be removed to reduce artefacts during CT imaging and replaced prior to treatment.

To evaluate the device’s ability to shield healthy tissue from radiation, the team treated 14 rats with single-dose irradiation, half with and half without radio-protective devices in place, and examined the incidence of toxicities such as oral mucositis and proctitis.

The group also simulated clinical radiation treatments by modelling the radio-protective devices in the treatment planning software. The dose distributions with and without shielding were compared to evaluate the dosimetric impact of the device. The researchers simulated treatments of prostate and head-and-neck cancer patients, selecting the appropriate positioning of the device based on the regions of increased radiation exposure.

Evaluation of radio-protective devices
Histopathological analysis revealed that only one of seven rats with radio-protective devices in place during treatment suffered ulceration on the surface of the tongue. In contrast, all seven control rats, with no device in place, experienced extensive ulcerations on the tongue surface.

The clinical simulations identified that using radio-protective devices during prostate cancer treatment could reduce the dose to healthy tissue by 15% without reducing the dose delivered to the tumour. For the head-and-neck cancer treatment, the dose absorbed by inner-cheek tissue was reduced by 30%.

The results clearly show that the radio-protective devices may improve patient comfort throughout the course of treatment. “Our results support the feasibility of personalized devices for reduction of radiation dose and associated side effects” claims Byrne.

Future clinical implementation
The benefits of using 3D-printed radio-protective devices in the clinic are clear. “This personalized approach could be applicable to a variety of cancers that respond to radiation therapy,” says Byrne.

The researchers acknowledge that full clinical translation of 3D-printed shielding devices will require further development. “Given the small sample size of our dosimetric studies, further investigation in larger cohorts is needed to validate these approaches,” they say.

The researchers publish their findings in Advanced Science.

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