chemotherapy

Artificial larynx implant helps throat cancer patient breathe and speak

Source: www.ctvnews.ca
Author: staff

Sixteen months after receiving an artificial larynx, a 56-year-old French man suffering from throat cancer can now whisper and breathe normally. A report published this week in the New England Journal of Medicine considers this to be a significant first achievement.

Thanks to the implant, a 56-year-old throat cancer patient can now whisper and breathe normally. © ChrisChrisW / Istock.com

Thanks to the implant, a 56-year-old throat cancer patient can now whisper and breathe normally. © ChrisChrisW / Istock.com

This is the first time that doctors have observed a patient with the implant long term recover functions such as breathing and speaking after the complete removal of the larynx. Thanks to an artificial voice box, implanted in 2015 at France’s Strasbourg-Hautepierre university hospital, the 56-year-old Frenchman, who lives in Alsace, can now whisper in a comprehensible manner and breathe normally.

The patient has also recovered his sense of smell, which was damaged by the removal of the larynx. Other than the vocal cords, the larynx features an upper valve, called the epiglottis, which closes when food passes down the throat to prevent it from entering the windpipe.

The prosthetic larynx was developed by a French company called Protip Médical. It consists of a rigid titanium and silicone structure replacing the larynx and a removable titanium part that mimics the function of the epiglottis.

The only problem that remains unresolved in the implant is the function of the epiglottis. As a result, the patient coughs from time to time when eating, as food accidentally enters the windpipe. However, the surgeons still consider the functioning implant a highly satisfactory achievement.

The current procedure used to return voice function to throat cancer patients involves puncturing the throat to insert a valve allowing air to pass from the windpipe to the esophagus.

A few doubts remain about the long-term effectiveness of the implant. For example, blockages caused by dried out mucus and secretions from the lungs and nose could be a risk. Another concern is the risk of rejection, particularly in cancer patients who have undergone radiotherapy or chemotherapy treatments.

As for patient comfort, further testing will establish how the mobility of the patient’s neck is affected by the presence of a rigid tube in the throat.

“This implant is constantly evolving and the next patients will benefit from substantial improvements,” notably to improve the passage of food down the throat, said lead researcher Nihal Engin Vrana.

Each year more than 12,000 new cases of throat cancer are diagnosed in the U.S.. Larynx transplants remain extremely rare worldwide and are generally used in cases unrelated to cancer, which represent a small majority.

Source: The report is published in the New England Journal of Medicine.

January, 2017|Oral Cancer News|

Hog jowls and clementines: A bid to awaken cancer patients’ ruined sense of taste

Source: www.statnews.com
Author: Eric Boodman

The medicines were rich and strange, their active ingredients so particular they sounded fictional.

neurogastronomy_illustration_mollyferguson_121616-1600x900

Credit: Molly Ferguson for Stat

One regimen involved jowl bits from Red Wattle hogs; the pigs were bred from sows named Fart Blossom and Hildegard, and had spent the end of their lives gorging on acorns, hickory nuts, apples, and black walnuts. Another experimental drug included the flesh of the Ubatuba pepper, picked when it was red as a Santa suit, dried at precisely 90 degrees for five days, and then pulverized, seeds and all, into a fragrant, pinkish powder.

These concoctions were meant to be therapeutic — but they hadn’t been devised by pharmacologists or biochemists or even lab techs. Their inventors had no scientific training whatsoever: They were celebrity Montreal chef Frédéric Morin and renowned Atlanta pastry-maker Taria Camerino, who would be facing off in an unusual culinary duel. They’d been challenged to help solve a problem that most clinicians and neuroscientists aren’t able to — the impairment of taste in cancer patients who undergo chemotherapy and radiation.

This cook-off in the University of Kentucky’s demo kitchen was the opener for the second annual Neurogastronomy Symposium, which was born over a boozy, late-night chance encounter between neuropsychologist Dan Han and Morin in the chef’s restaurant. Together, they envisioned a conference that would combine neuroscience, agriculture, history, nutrition, medicine, and cooking — to understand the art and science of why we eat what we eat, and how we could change it for the better.

It isn’t your everyday scientific conference. It’s the kind of conference where invited neuroscientists and neurologists experience the flavor wheel of bourbon, sampling Woodford Reserve along with hazelnuts and then orange flesh to see how the liquor migrates into different parts of the palate. The kind of conference where a panel discussion on the science of taste includes a hip New York chef telling a roomful of dietitians that those with binge eating problems should “have sex! It will take your mind away from food.” The kind of conference where attendees suck lollipops designed to evoke the 1812 Overture.

You know, that kind of conference.

But behind the foodie fun is hard science and a real clinical conundrum. Killing cancer cells means killing healthy cells along with them. The poisons of chemo and the waves of radiation are especially good at taking apart the DNA of fast-dividing cells. That can help stop the out-of-control expansion of tumors. But the nerve cells in the nose and mouth replenish themselves quickly, and so they die, too.

The resulting changes in taste and smell might seem like a small price to pay for a lifesaving treatment. Yet one’s desire to get up in the morning can be intimately connected to one’s ability to enjoy food. Lose your ability to taste properly and your mental and physical health — which, for cancer patients, is already fragile — can suffer even more.

“Many people stop eating,” said Gary Beauchamp, a sensory perception researcher at the nonprofit Monell Chemical Senses Center in Philadelphia. “It is a potentially lethal effect.”

The loss of taste and smell is among the most common complaints of cancer patients. But those don’t necessarily bounce back even if you’re lucky enough to transition from patient to survivor.

“The hope is that some of those taste abilities will come back. We’re all different. Some regain it very quickly; others — like myself — might not at all,” said Barry Warner, a 59-year old who was treated for throat cancer seven years ago, and one of the cook-off’s taste-testers. “The bottom line is, if after a period of time, it doesn’t come back, it’s something you’ll have to adapt to. There isn’t going to be anything the same as it was.”

Most doctors hardly ask about this side effect, and when they do, they don’t have much to offer besides apologies and explanations. Their focus is keeping you alive.

“You have no resources to help you deal with the taste aspect,” Morin said in an interview with STAT about a week before he flew to the conference, as he drove to visit a friend with late-stage metastatic cancer. “Who is the next specialist you talk to? It’s the nutritionist: an accountant of nutrition, a bookkeeper of calories. They don’t become nutritionists because they relish the smell and taste of the skin of a roast chicken.”

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Camerino does a lot more than “relish” smells and tastes. By her own account, she lives through her sense of taste.

“I taste everything — like, everything,” she told STAT. “I taste colors, people, emotions, music … I can’t remember songs or movies, but I know what everything tastes like.”

That’s not just because she’s a celebrated pastry chef, who has devoted decades of her life to subtle differences in food. It’s also because she’s synesthetic. The unusual wiring of her brain makes her experience the world through her tongue. Sights and sounds conjure up complex flavors, allowing her to become a kind of mystical Willy Wonka, with top hat and plum velvet jacket swapped out in favor of big round glasses and snaking blue tattoos.

Camerino talks about the flavors she perceives the way some saints talk about God — as an experience accessible only through metaphor. And just as monks might interpret their visions through the lens of scripture, she uses her training in French patisserie, Japanese confectionery, and coastal Italian cooking to pinpoint what exactly it is she’s tasting at that moment — and, in some cases, to reproduce it.

When she was tasked with “profiling” the chef and television personality Andrew Zimmern in a cake, she was startled that the first thing to appear on her palate was prawn shell. “I was like, ‘Are you kidding?’” she said.

“How do I take a prawn shell and put it into a cake? You toast it. I toasted it low, for a long time, so it never burned and it didn’t become overly sharp, and then I ground it into a powder and I folded it into the cake batter, so all you got was the essence, nothing overwhelming.” The other flavors she had felt — green Szechuan peppercorns, bay leaves, miso, Asian pear — became accompanying syrups and jellies, until she was confident her cake perfectly embodied Zimmern’s spirit.

Sometimes, she’ll get flavors she’s never had before, and only through extensive research can she identify them. A band she was taste-profiling a few years ago conjured up a tang that turned out to be a Southeast Asian fruit called calamansi. A man she met around 2001 evoked a taste that turned out to be mare’s milk, as used in Tibetan and Mongolian cuisine. She is sure of it, even though she’s never tasted horse milk of any kind.

When Han, the neuropsychologist at the University of Kentucky, emailed to invite Camerino to the conference, she thought it was a joke. Like most people, she had never heard the term “neurogastronomy.” After all, it was only coined in 2011, in the title of a Yale neuroscientist’s book. She wasn’t sure that such a conference existed.

But after a back-and-forth by phone and email, she agreed. The arrangement had a fairy-tale ring to it: The woman for whom taste is everything would concoct a special dish that could rekindle patients’ pleasure in food.

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Barry Warner’s first hint of flavor began at least as early as 1957, in the months before he was born. His mother had grown up on a farm southeast of Louisville, where dinner came from the pigpen, the cowshed, and the vegetable patch. That kind of country cooking was what she learned and continued making into her adult years, and during her pregnancy, its fragrant particles filtered down though her digestive system and into her amniotic fluid, shaping what Warner would like once he was born.

He was raised among the rolling corn and tobacco farms of Nelson County, in a small town with a single stoplight. His parents weren’t farmers, but starting at 11 or 12, he helped neighbors to bale hay, loading it into trucks and stacking it in barns for the winter. He loved his mother’s cooking: cornbread sticks made in a cast-iron skillet, cooked cabbage, pork chops soft enough to cut with your fork.

But in 2009, eating became painful. “Every time I tried to extend my mouth wide enough to take a bite out of a sandwich or a hamburger, I had a burning sensation in my tongue,” he said. He went to see a friend, an oral surgeon who’d removed his wisdom teeth years before, and asked him to take a look.

“He thought it was cancer, but he didn’t tell me that and he didn’t tell my wife until he got confirmation,” Warner said. “I didn’t know about it until then.”

Throat cancer was one assault on his body and his ability to eat, but the treatment brought about many more. Five days a week, for seven weeks, he would be immobilized onto a steel table and inserted into a machine for radiation. He also got periodic rounds of chemo.

Those didn’t just dampen his ability to taste; they also left him without saliva and made him taste flavors that weren’t there.

“It really starts out when you’re undergoing chemotherapy, that metal taste you get,” said Warner. “It seems like no matter what you eat, the taste isn’t right.”

He could have been tasting the drugs in his bloodstream — but he could also have been experiencing what some call phantom flavors. Those phantoms, some scientists say, can be the product of a taste system that is no longer in control, like a trained horse gone crazy, bucking off its rider and reverting to a frenzy of kicks and twists.

“Taste has an interesting function beyond what you experience when you eat,” said Linda Bartoshuk, a taste perception expert at the University of Florida. “Nature wants you to eat, so the taste system can be used to turn off sensations that might interfere with your eating. Taste input actually turns down pain. How does taste do that? It does that by sending a lot if inhibitory messages in the brain.”

Take away those inhibitory messages, Bartoshuk said, and those unwanted sensations come roaring in.

Warner no longer tastes those stomach-turning flavors — but he can’t taste anything else either. He might be able to identify mashed potatoes, say, by the texture, and maybe a little by the smell. But beyond that, he wouldn’t be sure what he is eating.

Now, at the lunch before the cook-off, Warner took tiny bites of the squash-and-goat-cheese appetizer that was in front of him. Partially he was saving room for the two different regimens that were on their way to try to rekindle some of those lost gastronomic pleasures for him and a fellow survivor. But that is also just how he’s had to eat since treatment: slowly, mostly without talking, and with little enjoyment, forcing himself to take one small bite after another.

“I don’t really get hungry,” he said. “You might sit down at your meal thinking about how good it tastes. Instead, I’m counting how many bites it will take me to get through it. And you never think about how much eating is part of your social life. That changes dramatically.”

Warner has kept some of his habits anyway. He still drinks bourbon socially — a taste wired into him as a Kentuckian — and he can smell it, and feel the burn of the first sip. And he still drinks a cup of coffee every morning. But he can’t taste either one.

He doesn’t complain about these long-term side effects. “I am so grateful and indebted to the doctors that saved my life, I consider my hearing loss and my loss of taste just … collateral damage,” he said. “Seven years ago, when I was getting my diagnosis, the odds of me having this conversation were less than a flip of a coin.”

Still, part of him wishes that he could experience what he remembers of food and drink. He hopes he’ll wake up one day and be able to taste his coffee.

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Camerino has devoted herself to sweets, studying chocolate-making and practicing the way to twist a pastry bag so a spritz cookie has the perfect swirl. But suffering, loss, illness, pain — those, too, have distinct flavors for her.

She grew up in a poor, abusive household in Gainesville, Fla., with a heroin-addicted father. “Everything tasted like too-salty water, the kind that you gargle when you’re sick and you’re not supposed to drink,” she said.

She remembers a year when they ate little but white rice and packaged brown gravy. She remembers struggling through eating disorders without ever seeing a doctor. She remembers the smell of the Miller High Life her father drank. Yet she also remembers her mother getting a job at the African and Asian languages department at the University of Florida, being invited over and presented with foods she had never imagined. Those visits pushed her into studying linguistics.

It was only a chance encounter with a pastry magazine that made her switch course: “I was like, ‘That’s what I want to do. I want to create something that’s bite-sized that can change your perspective on life.’”

The invitation to the Neurogastronomy Symposium seemed like a perfect opportunity. And as with many of her concoctions, she would be guided by both her synesthesia and her culinary education. This time, though, the food would be a kind of medicine. “I’ve wanted to do something meaningful with this superpower,” she said.

She had been told next to nothing about the patients she would be cooking for. Instead, she both did external research — and turned inward. She began conjuring up the flavors evoked by cancer, by chemotherapy, by terrible pain. They were not so different from what she tasted during the long recovery from a motorcycle accident she had this summer: something acidic, a bit like blood, with an astringent metallic edge. She wasn’t surprised that this was the same taste that many cancer patients got when undergoing treatment.

“The first thing I wanted to do was dim that down. If I can gain control of the taste in their mouth, if I can get rid of it, I can give them some relief,” she said. “Blood or metal, the best way to compete with that would be citrus. I’m not using a really strong citrus: Clementines are sweet, they have a little more of a delicate flavor. The clementine will cut through — it will literally cut through — the blood and metallic taste, so now I have a pathway through into their experience.”

Yet she also knew that some patients didn’t have much sense of taste left at all, so she wanted flavors that, to her, produce vibrations felt beyond the mouth: basil and pistachio. “By using the basil, now I’m opening up from the top of the mouth to the top of the forehead, that’s where basil affects you, now I have their whole attention. And pistachio, it has a floral quality, it’s reminiscent of the Mediterranean, of the ocean.”

She wasn’t completely giving up on the mouth, though. She thought of how fat can fall soothingly on the palate, another sensation beyond taste. Butter was too heavy, too overpowering, she said. Instead she went with olive oil.

The medication she came up with would be delicate, fragrant, and not too sweet: a clementine upside-down cake with a dab of basil and pistachio pesto, crowned with a scoop of olive oil gelato.

She wasn’t sure how well it would work. She had never made it before, and had no plans to try it out before she arrived at the event. She knew nothing about these particular patients. Yet as she was preparing for the symposium, she became so excited about the idea of helping patients with taste loss that she even began to dream up a lozenge with the same goal.

“I’ve made people experience emotions by combining particular flavors,” she said. “If I’ve made them experience disappointment, satisfaction, joy, then it may be possible to activate certain parts of the brain and make them experience all of that even without their sense of taste.”

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The day of the challenge began snowy and gray. Two days before, fatty jowl bacon had been fetched from a long-bearded breeder of Red Wattle hogs, and driven 60 miles back to Lexington, for whatever taste-saving concoction Morin, the Montreal chef, had in mind. Now, the University of Kentucky chef-in-residence Bob Perry was picking up last-minute ingredients from the research farm where the Ubatuba peppers grow.

Morin, it turns out, hadn’t really planned his dish out in advance. He’d asked for some vegetables, wine, bacon, spices. He’d figure something out. Camerino, on the other hand, arrived at the university’s demo kitchen with her own ice cream maker and a duffel bag of tools — infrared thermometers, weird tweezers, Q-tips, an offset spatula, an elaborate assortment of spoons. She was going to bring her own olive oil, too, but thought that might be overkill.

Before they headed into the kitchen, the clinicians and scientists and chefs and sommeliers gathered around Warner and another cancer survivor named Erica Radhakrishnan like overeager medical students crowding around a rare and fascinating case. They peppered the two with questions. What was their most memorable meal? Are there textures you find comforting? Did you eat processed foods before? What about the savory taste, which the Japanese call umami?

Then, with whatever intel they could gather, the chefs began to cook. Morin peeled potatoes and fried bacon. Camerino cracked eggs with a single hit on the side of the bowl, a quick squeeze and a pull.

Camerino adjusted her recipe slightly, making room for local ingredients. She incorporated a sprinkle of Ubatuba paprika into a syrup for the cake; she used molasses boiled down from the green juice of sorghum grass instead of cane sugar.

She had been nervous when she arrived, but now she was in her element. She needs no timer to know exactly when something should come out of the oven, perfectly brown. She tasted a spoonful of the basil-pistachio pesto. “This is a trip to Sicily,” she said. “Your marriage is struggling, it’s winter, you’ve lost the ability to communicate … and you go to Sicily with your partner. That’s what this is.”

On the other side of the kitchen, Morin was breaking up the fractal patterns of Romanesco broccoli into tiny bits of chartreuse, as a topping for his potato soup. “If he does not taste anything, I also have a bottle of bourbon,” he muttered in Québécois French.

The kitchen began to fill with the smells of bacon and basil, a hint of curry, and the sweetness of cake. The dishes were ready. At the last second, Camerino spooned a glistening white ball of gelato onto the two desserts.

The chefs each came forward to introduce their dish. Then they pulled back toward the kitchen. And with everyone watching, Warner and Radhakrishnan took careful bites, rolling around first the soup and then the cake in their mouths. The chefs looked on, tense, as Warner primly wiped his moustache.

Both tasters complimented the moisture of the cake and the aromas of the soup, the way the spices enlivened the purée, the way the ice cream made it easier to swallow the cake. They would not reveal the winner until the next day, at the end of the conference, in an auditorium full of academics and clinicians.

But a few minutes later, when the room’s attention had moved elsewhere, Radhakrishnan, whose sense of taste has largely come back after two battles with breast cancer, turned to Warner.

“Barry, are you able to taste anything?” she asked, gesturing toward the cake.

There was a pause. Warner looked serious, like he was concentrating on a math problem. “No,” he said quietly.

It might have worked for Warner while he was undergoing chemo and tasting its metallic tang. Or it might have worked for someone else. Just as Warner’s pleasure in food had been shaped in complex ways — by his genes, by the country cooking he’d sampled in the womb and as a child, and then by those foods he’d grown to appreciate as an adult — his preferences were equally unique after he’d lost his sense of taste. After all, a loss is only a loss in relation to what came before.

To Camerino, the challenge was at once amazing and humbling. “I could have cried a lot — I cry really easily,” she said. The experiment only heightened her zeal: She is now working with a molecular sommelier to dream up four different lozenges for people with taste loss, and, for those without saliva, two aromatic sprays. She isn’t sure about the exact ingredients, but she is thinking citrus, basil, barley malt as a sweetener, and something reminiscent of anise.

Han hopes that these events for chefs and scientists can move from “fun preclinical challenges” to more rigorous research about what can actually help these patients and survivors. Morin is working on an app for cancer patients to share what helps for which kinds of taste loss, and there are other ideas in the works. “We’re doing very early studies to take stem cells to see if we could regrow the system,” said Beauchamp, the researcher from the Monell Center. “But we’re a long way from that.”

For now, Warner keeps to the regimen he’s turned to for seven years. He uses whomever he’s eating with as a timer for when he can stop making himself take bites. He smells coffee in the morning, sipping it as he heads into his sunroom to listen for birds. He feels that first burn of bourbon, and notices how it falls away with each subsequent sip.

December, 2016|Oral Cancer News|

Immunotherapy drug a ‘gamechanger’ for head and neck cancer

Source: www.theguardian.com
Author: staff

An immunotherapy drug hailed as a potential gamechanger in the treatment of cancer could soon offer new hope to patients with currently untreatable forms of the disease.

Nivolumab outperformed chemotherapy significantly in keeping relapsed head and neck cancer patients alive. Photograph: Alamy

Nivolumab outperformed chemotherapy significantly in keeping relapsed head and neck cancer patients alive. Photograph: Alamy

Nivolumab was found to extend the lives of relapsed patients diagnosed with head and neck cancers who had run out of therapy options. After a year of treatment, 36% of trial patients treated with the drug were still alive compared with 17% of those given standard chemotherapy.

Trial participants treated with nivolumab typically survived for 7.5 months, and some for longer. Middle-range survival for patients on chemotherapy was 5.1 months. The phase-three study, the last stage in the testing process before a new treatment is licensed, provided the first evidence of a drug improving survival in this group of patients.

Prof Kevin Harrington, from the Institute of Cancer Research, London, who led the British arm of the international trial, said: “Nivolumab could be a real gamechanger for patients with advanced head and neck cancer. This trial found that it can greatly extend life among a group of patients who have no existing treatment options, without worsening quality of life.

“Once it has relapsed or spread, head and neck cancer is extremely difficult to treat. So it’s great news that these results indicate we now have a new treatment that can significantly extend life, and I’m keen to see it enter the clinic as soon as possible.”

Before it can be offered on the NHS, the treatment will have to be approved by the European Medicines Agency and the National Institute for Health and Care Excellence (Nice), which vets new therapies in England and Wales for cost-effectiveness.

Of the 361 patients enrolled in the trial, 240 were given nivolumab while the remaining 121 received one of three different chemotherapies. UK patients were assigned the chemotherapy drug docetaxel, the only treatment currently approved for advanced head and neck cancer by Nice.

Patients whose tumours tested positive for the HPV virus, which is linked to cervical cancer and may be spread by oral sex, did especially well. They typically survived for 9.1 months, compared with 4.4 months when treated with chemotherapy. More than half of patients relapse within three to five years.

Nivolumab is one of a new class of antibody drugs called checkpoint inhibitors that help the immune system fight cancer. It works by blocking signals from tumour cells that stop the immune system attacking.

The drug is already licensed for the treatment of advanced melanoma skin cancer and non-small-cell lung cancer in the UK. However while Nice has backed its use on the NHS for melanoma it has so far refused to recommend making the drug freely available to lung cancer patients.

Prof Paul Workman, chief executive of the Institute of Cancer Research, said: “Nivolumab is one of a new wave of immunotherapies that are beginning to have an impact across cancer treatment. This phase-three clinical trial expands the repertoire of nivolumab even further, showing that it is the first treatment to have significant benefits in relapsed head and neck cancer.

“We hope regulators can work with the manufacturer to avoid delays in getting this drug to patients who have no effective treatment options left to them.”

October, 2016|Oral Cancer News|

Men with throat cancer will soon outnumber women with cervical cancer In The US

Source: www.houstonpublicmedia.org
Author: Carrie Feibel

The national increase in cases of oropharyngeal cancer related to the human papilloma virus is troubling, because there is no screening test to catch it early, like the Pap test for cervical cancer.

The oropharynx is the area of the throat behind the mouth, and includes the tonsils and the base of the tongue. Oropharyngeal cancer is increasing in both men and women, but for reasons that aren’t well understood, male patients are outnumbering female patients by five to one, according to Dr. Erich Sturgis, a head and neck surgeon at MD Anderson Cancer Center.

“It’s usually a man, and he notices it when he’s shaving. He notices a lump there,” Sturgis said. “That lump is actually the spread of the cancer from the tonsil or the base of the tongue to a lymph node. That means it’s already stage three at least.”

In the U.S., the number of oropharyngeal cancers caused by HPV are predicted to exceed the number of cervical cancers by 2020, Stugis said.

“With cervical cancer, we’ve seen declining numbers well before we had vaccination, and that’s due to the Pap smear being introduced back in the late 50s,” he said. “But we don’t have a screening mechanism for pharynx cancer.”

Research on an effective screening test for early-stage pharynx cancer is still underway. The reasons for the disproportionate effect on men are unknown. One theory is that people are engaging in more oral sex, but that doesn’t explain why men are more affected than women. Some suspect hormonal differences between men and women may be involved, and others hypothesize that it takes longer for women to “clear” the viral infection from their genitals, compared to men, according to Sturgis.

One of Sturgis’s patients, Bert Noojin, is an attorney in Alabama. He felt a little knot in his neck in early 2011. It took three trips to his primary care doctor, then a visit with an otolaryngologist before he was referred for a biopsy. Noojin was diagnosed with oropharyngeal cancer, but he still felt fine.

“It was still hard for me to believe I was sick in any way,” he recalled. “I didn’t even have a serious sore throat.”

After being diagnosed, Noojin came to MD Anderson Cancer Center in Houston for a second opinion and to pursue treatment. It was less than three months from when he first felt the knot, but an oncologist warned him the cancer was spreading fast.
“He said ‘Well, you need to start treatment right away’ and I said, ‘Well, do I have a week or 10 days to go home and get some things in order?’ and he said ‘No.’”

“He said ‘If you leave here, and you’re not part of our treatment plan when you leave here, I don’t think we’ll be able to help you.’ That is how far this disease had progressed, in such a very short time.”

The prognosis for HPV-related oropharyngeal cancer is good, especially compared to patients whose throat cancer is caused by heavy use of tobacco or alcohol, according to Sturgis. Between 75 and 80 percent of patients with the HPV-related type survive more than five years.

But the treatment is difficult, and can include “long-term swallowing problems, long-term problems with carotid artery narrowing, and long-term troubles with the teeth and jaw bone, and things that can cause a need for major surgeries later.”

In the summer of 2011, Noojin began chemotherapy and radiation at MD Anderson. He struggled with pain, nausea, and swallowing, and had to get a temporary feeding tube.

“Your throat just shuts down,” he said. “You’re burned on the inside. Just swallowing your own saliva, as an instinct, hurts.”

Noojin lost 45 pounds during treatment but feels lucky to have survived. He went back to his law practice in Alabama.

Noojin learned that cancers related to HPV, which is sexually transmitted, are cloaked in shame and guilt.

He experienced this first-hand when his marriage fell apart during his recovery. His wife was traumatized by the difficult months of treatment, he said. In addition, she irrationally blamed herself for giving him the virus, even though he was probably exposed many years earlier. He tried to comfort her and dispel her guilt, but they eventually divorced.

“I was married over two decades, but I was married previously, and she was married previously,” he said. “It just makes no sense for any of this to have a stigma.”

An estimated 80 percent of America women and 90 percent of men contract HPV at some point in their lives, usually when they’re young and first become sexually active. But the cancers caused by HPV can take years to develop.

“It’s a virus. It’s not anybody’s fault,” Noojin said.

He echoed the public health experts in calling for an end to the silence and shame, and a shift to a focus on prevention.

“All of what I went through, and all of what hundreds of thousands of men, and women, because of cervical cancer – what they have gone through is avoidable for the next many generations … if we just got serious about making sure our kids get vaccinated.”

The series of three shots can be given as early as age nine, but must be completed before the age of 26 to be effective. Currently, the completion rate for young women in the U.S. is less than 50 percent. Among young men, it’s less than 30 percent. That’s why experts warn these particular cancers will still be a problem decades from now.

September, 2016|Oral Cancer News|

Incisionless robotic surgery offers promising outcomes for oropharyngeal cancer patients

Source: medicalxpress.com
Author: press release, Henry Ford Health System

A new study from researchers at Henry Ford Hospital finds an incisionless robotic surgery – done alone or in conjunction with chemotherapy or radiation – may offer oropharyngeal cancer patients good outcomes and survival, without significant pain and disfigurement.

Patients with cancers of the base of tongue, tonsils, soft palate and pharynx who underwent TransOral Robotic Surgery, or TORS, as the first line of treatment experienced an average three-year survival from time of diagnosis.

Most notably, the study’s preliminary results reveal oropharyngeal cancer patients who are p16 negative – a marker for the human papilloma virus, or HPV, that affects how well cancer will respond to treatment – have good outcomes with TORS in combination with radiation and/or chemotherapy.

“For non-surgical patients, several studies have shown that p16 positive throat cancers, or HPV- related throat cancers, have better survival and less recurrence than p16 negative throat cancers,” says study lead author Tamer Ghanem, M.D., Ph.D., director of Head and Neck Oncology and Reconstructive Surgery Division in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford Hospital.

“Within our study, patients treated with robotic surgery had excellent results and survival, irrespective of their p16 status.”

Study results will be presented Sunday, Sept. 18 at the 2016 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) annual meeting in San Diego.

Led by Dr. Ghanem, Henry Ford Hospital in Detroit was among the first in the country to perform TORS using the da Vinci Surgical System. TORS offers patients an option to remove certain head and neck cancer tumors without visible scarring, while preserving speech and the ability to eat.

With TORS, surgeons can access tumors through the mouth using the slender operating arms of the da Vinci, thus not requiring an open skin incision.

Unlike traditional surgical approaches to head and neck cancer that require a large incision and long recovery, TORS patients are able to return to their normal lives only a few days after surgery without significant pain and disfigurement.

For the study, Dr. Ghanem and his colleagues wanted to take a closer look at the effectiveness of TORS for oropharyngeal cancer patients. They reviewed overall three-year survival, cancer control and metastasis, as well as the effect of p16 status on these variables.

The study included 53 Henry Ford oropharyngeal cancer patients who had TORS. Among them, 83 percent were male, 77 percent were Caucasian, and the mean age was 60.8 years. Thirty-seven percent had TORS alone, while more than 11 percent had TORS with radiation therapy, and more than half received chemotherapy and radiation therapy.

Thirty-seven percent had TORS alone, 11.4 percent received radiation therapy, and 50 percent received chemotherapy and radiation therapy. Eighty-one percent of patients had p16+ disease.

The study shows patients with a p16 negative marker had high survival (100 percent) and low cancer recurrence when TORS was the first line of treatment, as well as when TORS was followed by chemotherapy or radiation therapy.

The majority of patients (63 percent) were able to receive a lower dose of radiation after TORS, which reduces the risk of radiation side effects.

While Dr. Ghanem notes the study’s results are not enough to change clinical practice, it does demonstrate that TORS alone or in conjunction with adjuvant radiation or chemotherapy is an acceptable treatment option for oropharyngeal cancer patients regardless of p16 status.

September, 2016|Oral Cancer News|

Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Source: www.onclive.com
Author: Laura Panjwani

Robert-Ferris

Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD.

“Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.”

The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator’s choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN.

The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator’s choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act.

Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN.

OncLive: What were the updated findings from CheckMate-141 presented at ASCO?

Ferris: The data that were presented at the 2016 ASCO Annual Meeting were further evaluations and follow-up on some preliminary data—originally presented at the 2016 AACR Annual Meeting—that listed the OS results.

At ASCO, we recapped the primary endpoint of OS as an important endpoint for immunotherapies because response rate and progression-free survival may not be as accurate. Ultimately, the FDA and people at large want OS. In this study, OS was 36% at 1 year in the nivolumab-treated arm and 16.6% in the comparator arm, which was investigator’s choice of single-agent chemotherapy, consisting of methotrexate, docetaxel, or cetuximab. In this phase III randomized trial, nivolumab was given in a 2:1 randomization: 240 patients received nivolumab and 120 received investigator’s choice.

Also at ASCO, we presented further evaluations consisting of what the regimens are in the comparator arm. There was about 20% each of docetaxel and methotrexate and 12% of cetuximab. Approximately 60% of the patients had prior cetuximab exposure and we stratified by cetuximab as a prior therapy. We also demonstrated the ORR, which was 13.3% in the nivolumab-treated arm versus 5.8% in the investigator’s choice arm.

Therefore, there was an improvement in overall response, but the difference seemed more modest than the OS benefit—which was a doubling—with 20% more patients alive at 1 year. This reinforces the concept that perhaps response rate may not be the best endpoint. Progression-free survival (PFS) was double at 6 months, with about 20% in the nivolumab arm versus about 9.9% in the investigator’s choice arm. The median PFS was not different, but the 6-month PFS was twice as high. The time to response was about 2 months in each arm at the first assessment.

Your analysis also looked at biomarkers. Can you discuss these findings and their significance?

The p16 or HPV-positive group had a better hazard ratio for OS than the overall study population. The hazard ratio was .73 for the overall population, using a preplanned interim analysis. With the HPV-positive group, we had a hazard ratio of .55 and the HPV-negative group had a hazard ratio of .99. It is still favoring the nivolumab-treated patients but, with the curves separated earlier in the HPV-positive group, one could see the improvement with nivolumab at about 1 to 2 months. It took 7 or 8 months with the HPV-negative group to show a separation of the curves in favor of nivolumab.

We looked at PD-L1 levels, and PD-L1—using a 1% or above level—had an improvement in the PD-L1–positive patients in favor of nivolumab in terms of OS and ORR. When we looked at 5% and 10% thresholds of PD-L1, the OS did not seem to improve. Therefore, in all levels above 1%, the OS was similarly beneficial over the PD-L1 less-than-1% group. However, essentially all levels of PD-L1–positivity and PD-L1–negativity still favored nivolumab, but the benefit was more when its levels were greater than 1%.

We could combine HPV status with PD-L1 status and look at subsets; however, essentially every subset benefited, whether it was PD-L1–negative or positive. This indicates that, in this group of patients, who progress within 6 months of platinum-based therapy, that no current systemic therapeutic options benefit patients as well as nivolumab.

With regard to these findings, what are you most excited about?

Head and neck cancer is a difficult disease. Until recently, we didn’t know the impact of this enrichment for HPV-positive virus-induced subsets and we didn’t know if this was an immune responsive cancer. Clearly, it is. We have all of the hallmarks that we have seen for a bright future—based on the melanoma data—and a series of other cancers indicating response rates in the 15% to 20% range, suggesting that we now have a platform of the PD-1 pathway to combine with other checkpoints and to integrate earlier in disease with radiation and chemotherapy.

We have a demonstration of head and neck cancer as an immune-responsive cancer. We are beginning to get an idea of the biomarkers and starting to be able to segment patients who will benefit. Now, we have a large comparative trial with an OS endpoint and tissue to look at biomarkers to try and understand what the best future combinations will be.

What are some questions that you still hope to answer regarding nivolumab in head and neck cancer?

We have to get down deeper into the nonresponders. We should acknowledge that the majority of patients neither had a response nor benefited. Understanding who is more likely to benefit is useful, but we also need to understand the levels of alternative checkpoint receptors or other biomarkers of resistance.

We have sequential lymphocyte specimens from the peripheral blood, tissues, and serum so those are intensively under evaluation. There are interferon gamma signatures that have risen from the melanoma checkpoint field that will certainty be applied, as well.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

August, 2016|Oral Cancer News|

New study analyzes physical therapy for head and neck cancer survivors

Source: www.curetoday.com
Author: Andrew J. Roth

The aftermath of treatment for head and neck cancer can be particularly difficult, according to Ann Marie Flores. Flores, assistant professor, Department of Physical Therapy, Movement & Rehabilitation Science, Bouvé College of Health Sciences, Northeastern University, conducted a pre-pilot study looking at early physical therapy education for this patient population.

CURE interviewed Flores about her poster, which she presented at the 8th Biennial Cancer Survivorship Research Conference in Washington, DC.

Could you first give some background about this study? How did it come to be?
It was a spinoff of some studies that I began in breast cancer. I conducted a literature review of rehab needs of breast cancer survivors about 10 years ago and found that there was very little out there. Then, when I started a rehab oncology program at a previous institution, the patient population that were referred to the program tended to not be breast cancer patients, because they physically and functionally tend to do well in aggregate. Most of my patients referred were those with head and neck cancer. I went through the same process to look through literature critically to figure out what exists in terms of physical therapy and rehabilitation-based approaches. I’ve updated this over a long period of time and this poster is a systematic review of the quality of evidence. I combined this literature and data review with talking to a focus group of cancer survivors.

What did you find?
I asked the focus group if they needed more information and the answer was “Yes!” over and over again. The majority of comments I heard were exactly about physical therapy, self-care and efficacy—things we specialize in. They were also adamant about oral health and dental care, understanding salivary function, tongue motion, muscles and more. We also heard a lot about emotional and social support. So many of these survivors said they felt they were losing their mind because no one around them understood what they were going through after treatment.

It was very interesting to see the concordance of the systematic review results with our focus groups.

What is it about this population that you think creates such a need for information?
Head and neck cancer survivors make up about 4 percent of all cancer survivors. What many of these patients have are multimodality therapies, highly disfiguring surgeries, surgeries that contribute to high rates of disability. Many patients also get chemotherapy and radiation. These survivors can have impairments that can compromise key functions of life—breathing, eating and speaking.

Can these patients get the services they need? Where?
They should be able to, yes. I am a long-standing member of the American Physical Therapy Association and we have a task force that specializes in head and neck studies. We’ve published four studies looking at measuring physical therapy–related impairments that we can rehabilitate, such as shoulder dysfunction, trismus and lymphedema. With trismus, patients can’t open their mouths. Many patients with head and neck cancer have either had muscle tissue removed or have highly scarred jaw muscles. And with lymphedema, you can get that in any part of your body, including the head and neck. Many patients will have lymph fluid collect in the under part of their neck.

For a patient who has finished treatment and facing some of these issues, where should he/she go for support?
As a patient, I’d tell my doctor that I need a referral to a physical therapist. In fact, the next steps following on our research will be to pilot test our patient education materials to determine their clinical feasibility, acceptability, and impact on PT outcomes. We want to ensure that these materials are patient-centered and relevant across the survivorship trajectory.

Heading back to the office following head and neck cancer

Source: blogs.biomedcentral.com
Author: Daniel Caley

In Cancers of the Head & Neck launching today publishes the first study looking at disability and employment outcomes in patients with head and neck cancer related to the human papillomavirus (HPV). Dr Shrujal Baxi, Section Editor for survivorship and patient related outcomes and author of this study, explains more about their work in this Q&A:

The rates of patients diagnosed with HPV-related head and neck cancer is rising annually. By 2020, there will be more cases of HPV-related head and neck cancer than HPV-related cervical cancer in the United States. Numerous studies have shown that most patients with this diagnosis are likely to be cured of their disease, placing an increased emphasis on quality of life and non-cancer outcomes in this population of survivors. The majority of patients diagnosed with HPV-related head and neck cancer are working-age adults and employment is a serious issue both financially and psychologically.

How can treatment for head and neck cancer impact employment?
Treatment for head and neck cancer often involves a combination of chemotherapy and radiation given over a six to seven week period, often known as concurrent chemoradiation or combined modality chemoradiation. This process is considered toxic and can impact a patient’s ability to function normally including speaking, chewing, breathing and swallowing. Many patients require numerous supportive medications to get through treatment including narcotics for pain and anti-nausea medications. Patients can lose on average 10-15% of their weight within a few months and can suffer from severe fatigue and post-treatment depression.

Who was in your study?
We included 102 participants with HPV-related head and neck cancer treated with chemoradiation at our institution who were employed full-time for pay at the time of diagnosis.

How did the treatment impact employment?
97% of patients had to change their employment responsibilities in some way from reducing work, taking a break and then returning at a later date, or stopping altogether and not returning. There were 73 patients that stopped but eventually returned to work after treatment, and they required a median of 14.5 weeks to return. This is longer than the 12 weeks currently allowed according to the Family Medical Leave Act (FMLA).

Eight patients stopped working altogether and never went back. Eight patients stopped working during treatment and never returned to work. Aside from younger age predicting extra time off before returning to work, we did not find a patient, treatment or disease factor that accounted for needing extra time off.

What happened to these patients?
The majority of patients who returned to work continued. At nearly two years from completion of treatment, 85% of the original 102 patients were working for pay. Overall, survivors were doing very well in terms of quality of life with the majority not having any major limitations secondary to their treatment.

There were a group of survivors who were dissatisfied with their ability to work. Some were working but not satisfied with their abilities, while others were looking for work. Compared to those who were satisfied with their abilities, those that were unsatisfied were more likely to have more functional problems and more head and neck specific late toxicities from their treatment.

What does this mean for patients and providers?
I think that this study provides some guidance for patients and providers as they prepare for chemoradiation to treat HPV-related head and neck cancer. It is hopeful that most patients will return to work, but realistic expectations of ability to work will help in treatment planning. Employment is another reason why managing late toxicities remains an important aspect of optimal care for head and neck cancer survivors.

Type 2 diabetes drug could be beneficial for head and neck cancer patients

Source: www.eurekalert.org
Author: press release

Researchers at the University of Cincinnati (UC) College of Medicine have found that adding increasing doses of an approved Type 2 diabetes drug, metformin, to a chemotherapy and radiation treatment regimen in head and neck cancer patients is not well tolerated if escalated too quickly, but allowing slower escalation could be beneficial.

These findings are being presented via poster June 4 at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting: Collective Wisdom, being held June 3-7 in Chicago.

Trisha Wise-Draper, MD, PhD, assistant professor in the Division of Hematology Oncology at the UC College of Medicine, a member of both the Cincinnati Cancer Center and UC Cancer Institute and principal investigator on this study, says retrospective studies have shown improved outcomes in tumors treated with chemotherapy and radiation if they were also on metformin for diabetes.

“In head and neck squamous cell carcinoma, which develops in the mucous membranes of the mouth, nose and throat, diabetic patients taking a medication called metformin had better overall survival compared to those not on metformin when also treated with chemotherapy and radiation,” she says. “Additionally, pancreatic cancer patients treated with chemotherapy and metformin required higher doses of metformin–1,000 milligrams twice a day–to experience positive results.

“In basic science studies, metformin has been shown to stop mTOR, a molecular pathway present and active in this type of head and neck cancer, and pretreatment with metformin resulted in a decrease in the occurrence of oral cavity tumors in animal models. In this study, we wanted to see if the combination of escalating doses of metformin with the chemotherapy agent cisplatin and radiation for head and neck cancer tumors in non-diabetic patients would be effective.”

Wise-Draper says that metformin, which is an approved Type 2 diabetes medication, was provided by their investigational pharmacy. Metformin was administered orally in escalating doses for 7 to 14 days prior to starting the cisplatin and radiation and continued throughout standard treatment. Blood samples were collected before and after metformin treatment as well as during chemotherapy. Flow cytometry, a technique used to count cells, was used to detect the percent of circulating immune activated cells, and clinical laboratory tests including glucose, B12 and C-peptide (an amino acid that is important for controlling insulin) were performed.

“This is part of an ongoing clinical trial,” says Wise-Draper. “We found that eight patients with advanced head and neck cancer have been enrolled so far; we plan to have 30 total. Due to the relatively quick escalation of metformin, the patients’ tolerance was poor with higher doses of metformin when initiated 7 days prior to their chemotherapy and radiation therapy regimen.

“Therefore, the protocol was modified to allow slower escalation over 14 days. The most common toxicities observed included nausea (71 percent of patients) and vomiting (43 percent of patients), increase in creatinine (57 percent of patients), decreased white blood cell count (43 percent of patients) and pain when swallowing (43 percent of patients) with only nausea being directly attributed to metformin and the rest attributed to cisplatin and radiation.”

She adds that there wasn’t a substantial change in T cell or glucose levels with administration of metformin in the small sample of patients but that there were increased C-peptide levels in response to metformin administration.

“These results show that the combination of metformin and cisplatin and radiation was poorly tolerated when metformin was escalated quickly. However, there has been no significant increase in side effects thus far with the addition of metformin,” Wise-Draper says. “The trial is continuing with escalation of metformin over a longer period of time to provide more data; we will also try to increase our sample size.”

Note:
This research is being funded by the UC Cancer Institute. Wise-Draper cites no conflict of interest.

Checkpoint inhibitors seen to show potential of immunotherapy in several cancer studies

Source: immuno-oncologynews.com
Author: Magdalena Kegel

Several new checkpoint inhibitors — a class of immunotherapy drugs used in cancer — continue to show beneficial effects in numerous cancer types, according to data presented at the recent American Association for Cancer Research Annual Meeting in New Orleans.

Investigated checkpoint inhibitors confirmed earlier results showing evidence of efficacy in melanoma, and also suggested that this class of immunotherapies, which trigger a person’s immune system to attack cancer, might work in patients suffering from certain head and neck cancers.

One of the studies, CheckMate-141, exploring the checkpoint blocker nivolumab (Opdivo) in patients with squamous cell carcinoma of the head and neck, was stopped early after 36 percent of the 361 patients survived for one year — an increase of more than 100 percent compared to patients receiving other treatments.

Squamous cell carcinoma is usually treated with platinum-based chemotherapy, but the effects are often temporary as the cancer tends to return. Moreover, patients who fail to fully recover after chemotherapy are generally resistant to further treatment.

Maura Gillison from Ohio State University, who presented the CheckMate-141 data, said that no effective treatments have been approved for patients with this kind of cancer in over a decade. “I’ve treated head and neck cancers for more than twenty years, and this is the first time I’ve had a drug to go to for patients that have become resistant to first-line treatment,” she said in a press release.

Dr. Emma King, a Cancer Research UK-funded head and neck cancer expert, added that the findings are likely to have a “significant impact” for these cancer patients. “They also reinforce the important shift that we are seeing towards using immunotherapies for cancer treatment.”

“Before nivolumab can be used routinely to treat head and neck cancer in the UK, it will need to approved by the National Institute for Health and Clinical Excellence (NICE),” she added.

Nivolumab was investigated in the CheckMate-069 trial, where its efficiency in advanced melanoma was tested in combination with another checkpoint inhibitor, ipilimumab (Yervoy).

Data presented showed that 60 percent of patients on the combination therapy survived for two years. But the benefit can come with a high price, as severe side effects forced one-third of patients to stop the treatment.

“Both nivolumab and ipilimumab have changed survival expectations in advanced melanoma over the last few years, and these latest data show us that combining these two immunotherapies is an effective two-pronged attack against the cancer,” said Dr. James Larkin, a medical oncologist at the Royal Marsden Hospital.

Yet another study found nivolumab to increase five-year survival in advanced melanoma patients to one-third — again, a doubling compared to what can be achieved by conventional treatment.

Merkel cell carcinoma, a rare skin cancer linked to exposure to a common virus, was also among the cancer types showing benefits from checkpoint inhibitor treatment. Once the cancer spreads, no treatments are effective in holding it back. The checkpoint blocker pembrolizumab (Keytruda) caused tumors to shrink in about half of the 26 patients in the trial.

“The trial also suggests that patients whose Merkel cell carcinoma is linked to a virus may be more likely to benefit from this treatment, which fits with the idea that the more danger signals there are in a cancer, the easier it is for the immune system to recognise it,” said Peter Johnson, Cancer Research UK’s chief clinician.

Early data of checkpoint inhibition in liver and advanced bowel cancer, used in combination with radiofrequency ablation treatment, also showed promising results.