radiation

Reducing Radiation Successfully Treats HPV-Positive Oropharynx Cancers and Minimizes Side Effects

Source: Yale Cancer Center, http://www.newswise.com/articles/reducing-radiation-successfully-treats-hpv-positive-oropharynx-cancers-and-minimizes-side-effects

Released: 12/26/2016

Newswise — Human papillomavirus-positive oropharynx cancers (cancers of the tonsils and back of the throat) are on rise. After radiation treatment, patients often experience severe, lifelong swallowing, eating, and nutritional issues. However, new clinical trial research shows reducing radiation for some patients with HPV-associated oropharyngeal squamous cell carcinomas can maintain high cure rates while sparing some of these late toxicities.

“We found there are some patients have very high cure rates with reduced doses of radiation,” said Barbara Burtness, MD, Professor of Medicine (Medical Oncology), Yale Cancer Center, Disease Research Team Leader for the Head and Neck Cancers Program at Smilow Cancer Hospital, and the chair of the ECOG-ACRIN head and neck committee. “Radiation dose reduction resulted in significantly improved swallowing and nutritional status,” she said.

The study, published in the December 26 issue of the Journal of Clinical Oncology, showed that patients treated with reduced radiation had less difficulty swallowing solids (40 percent versus 89 percent of patients treated with standard doses of radiation) or impaired nutrition (10 percent versus 44 percent of patients treated with regular doses of radiation).

“Today, many younger patients are presenting with HPV-associated squamous cell carcinoma of the oropharynx,” said Dr. Burtness. “And while traditional chemoradiation has demonstrated good tumor control and survival rates for patients, too often they encounter unpleasant outcomes that can include difficulty swallowing solid foods, impaired nutrition, aspiration and feeding tube dependence,” said Dr. Burtness. “Younger patients may have to deal with these side effects for decades after cancer treatment. We want to help improve our patients’ quality of life.”

The study included 80 patients from 16 ECOG-ACRIN Cancer Research Group sites who had stage three or four HPV-positive squamous cell carcinoma of the oropharynx, and were candidates for surgery. Eligible patients received three courses of induction chemotherapy with the drugs cisplatin, paclitaxel, and cetuximab. Patients with good clinical response then received reduced radiation.

Study results also showed that patients who had a history of smoking less than 10 packs of cigarettes a year had a very high disease control compared with heavy smokers.

 

Other authors on the paper include: Shanthi Marur (Johns Hopkins Medicine) and Anthony Cmelak (Vanderbilt University).

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

January, 2017|Oral Cancer News|

Why won’t our doctors face up to the dangers of radiotherapy?

Source: http://www.dailymail.co.uk/health/article-1089091/Why-wont-doctors-face-dangers-radiotherapy.html

Author: Isla Whitcroft

It’s a life-saver for thousands – but the side-effects can be devastating.

A year after he’d undergone treatment for cancer of the tonsils, Richard Wayman felt a painful tingling in his legs. Within weeks, the 59-year- old shopkeeper was struggling to walk. He was admitted to hospital, where doctors carried out scans, X-rays and tests.

‘The scans revealed lesions on my lungs, which raised fears that the cancer had spread, so I was admitted to another hospital for a biopsy and, as a result, contracted MRSA and pneumonia,’ recalls Richard, from Colchester in Essex.

‘From 11-and-a-half stone I went down to eight-and-a-half stone. I thought I was never going to get out of there.’

Finally, the lung lesions were diagnosed as a side-effect of the radiotherapy Richard had undergone for his cancer. However, his problems only got worse: a few weeks after a routine tooth extraction, the bone around the extraction started to crumble and become infected.

Within months he had an open weeping wound, running from his lower cheek through his jaw and into his mouth. The diagnosis: bone necrosis as a direct result of radiotherapy damage to the jaw.

Richard is one of the many thousands of cancer survivors who have developed terrible conditions as a result of the radiotherapy treatment that helped save them.

Around 4 to 5 per cent of all head and neck cancer patients suffer problems with swallowing or breathing, fistulas (open holes) in the jaw and gum, loss of taste and hearing.

But the problem is not unique to these cancers. Up to 10 per cent of breast cancer patients suffer radiation damage to their heart, lungs or the nerves to the arms (leading to loss of circulation and movement).

Every year, another 6,000 patients who’ve had pelvic radiotherapy treatment for conditions such as bowel cancer suffer long-term damage (including incontinence). A thousand of these patients go on to suffer even worse problems, such as intestinal failure or heavy bleeding.

It is clear that radiation damage is a significant health care issue. Yet, to date, there has been no national attempt to collate statistics that would enable any significant research work to begin.

Remarkably, it is not even officially classified as a specific medical condition; nor is there any definitive information on how to deal with it.

As a result, when it comes to treating the problems, patients can be offered a mix of options. Some are treated by a urologist, others are referred to a gastroenterologist, or an ear, nose and throat expert, while women often see a gynaecologist. This means many people will go undiagnosed for months and often years.

‘Until recently, radiotherapy damage has not been a priority in the treatment of cancer,’ says oncologist Paul Cornes, who runs clinics for patients with radiotherapy damage.

‘It is not a deliberate cover up; but in the past, cancer medicine was all about the treatment and giving patients a chance of life. Now we must address quality of life after cancer.’

Dr Sylvie Delanian, a radiologist and oncologist at the Hospital St Louis in Paris, is one of the few radiologists around the world to research and treat the condition. ‘Long-term radiotherapy damage is a taboo subject,’ she argues.

‘Radiologists are often frightened to discuss the matter with patients in case they refuse treatment. There is also the feeling that “we’ve saved your life, now go away and live with the side-effects”.’

Indeed, some hospitals seem to actively discourage discussion about the subject. While we were investigating this article, one London trust refused to allow Good Health to speak to their specialist, while another major cancer centre barred us from a conference on pelvic radiotherapy damage.

Radiotherapy is an incredibly successful method of treating cancer, increasing survival rates by around 50 per cent. It works by bombarding the tumour or tumour site with X-rays to kill the dividing cancer cells. In doing so, it inevitably affects surrounding healthy cells.

But areas such as the bowel, lung and jaw seem to be more susceptible to long-term damage. The precise reason is not clear, although it is thought that the mucus which lines the bowel and the delicate sacs in the lung are extremely vulnerable.

Long-term damage can appear as fibrosis (an overgrowing of healthy cells as they go into overdrive to repair the radiotherapy damage) or necrosis (the death of the tissue, causing open holes or fistulas).

Radiotherapy can also damage nerves, reducing blood circulation or causing breathing difficulties, with side-effects often not appearing for several years after treatment.

When Alan Warren was diagnosed with rectal cancer four years ago, it was, understandably, very worrying. The taxi driver and father-of-two underwent chemotherapy, then radiotherapy, to shrink the tumour, before it was removed along with several inches of his bowel.

‘My oncologist said I would be back working within four months. Fours years on, I’m still unable to work,’ says Alan, 55.

During those years, Alan, from Christchurch, Dorset, has suffered unimaginable pain. He has also suffered the indignity of urine leaking out through his back passage after he developed an internal fistula 12cm long, running from the top of his bladder to what was left of his lower bowel.

An operation to close the fistula failed. After that, the only option was a permanent catheter.

‘My problems were all blamed on scar tissue from the original cancer surgery, so I was referred to a urologist for treatment.

‘By chance, Alan’s wife Jackie, a nurse, came across an article on radiotherapy damage. ‘My urologist reluctantly admitted that I probably did have it,’ says Alan.

In the UK treatment tends towards cutting out the afflicted area if necessary – which often results in more scar tissue and pain. But there are other options.

Jervoise Andreyev, a gastroenterologist at the Royal Marsden, London, uses anti-diarrhoea medication, pelvic exercises, antibiotics and dietary changes to treat the problem if it’s in the pelvis.

Meanwhile, Dr Delanian uses a combination of three drugs: vitamin E, pentoxifylline (for vascular and circulatory problems) and clodronate (bone disorders).

Her success rates are impressive, with research to back these up going back over a decade. After contacting the radiotherapy damage action group RAGE, Alan and Jackie found out about Dr Delanian, and in October last year they visited her in Paris. Thanks to treatment, by January 2008 Alan’s fistula was gone and he was healed.

Richard Wayman also saw Dr Delanian. Six months later, the hole in his face healed.

The leg weakness and tingling have stabilised, too.

But despite the fact that some UK doctors are quietly following her method, it is not a mainstream treatment, and many of her patients find that in the UK they are refused the drugs she prescribes.

In 2006, the Royal Marsden carried out a trial into Delanian’s treatment on breast cancer patients, but announced that it failed to show any significant improvement.

Paul Cornes says: ‘Newer radiation therapies such as intensity modulated radiation therapy (IMRT) and proton beam therapy deliver more accurate beams with significantly lesser side-effects.

‘Unfortunately, IMRT is not yet widely available in the UK, and proton beam therapy is considered too expensive for the NHS.’

Dr Delanian adds: ‘Radiation is a great tool, but can also be very dangerous. As a profession, we should try to find a way to minimise the risk and deal with the effects.’

 

Originally posted:  

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

December, 2016|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|

Oral cancer in the crosshairs at San Antonio Dental School

Source: tpr.org
Author: Wendy Rigby

San Antonio researchers are working on a new therapy for a stealthy killer: oral cancer. Visits to the dentist are your number one protection against the disease. In a lab at the University of Texas Health Science Center at San Antonio, dental researcher Cara Gonzales, DDS, Ph.D., shared promising news on a new approach to healing.

“It was very exciting,” Gonzales said. “These patients have not had any new therapeutic options in 40 years.”

The discovery of a new gene that’s turned on in oral cancers gave Gonzales and her colleagues a new target at which to aim. It’s a gene that’s also found in lung cancers.

So-called nude mice are used in the oral cancer experiments. Webdt Rigby / Texas Public Radio

So-called nude mice are used in the oral cancer experiments.
Wendy Rigby / Texas Public Radio

Gonzales works in a sprawling space filled with lab equipment and cell lines used in many molecular biology projects. One of her research assistants brought in a cage of lab animals with some strange lumps on their backs.

“These are called nude mice because they don’t have a complete immune system,” Gonzales explained.

These mice are at the center of a successful experiment. First, scientists used human oral cancer cells to grow large tumors on the animals. They tried one oral cancer drug already on the market. Not much action. Then, they tried a lung cancer drug, also already approved by the Food and Drug Administration. Not that effective on its own. Finally, they used a combination of two drugs. What happened made the medical profession take notice.

“When we combined the two, then we saw a 50 percent reduction in the tumor volumes after 14 days,” Gonzales described.

That kind of success could help thousands of patients whose cancers aren’t caught until the later stage, patients like Paige Lewis of San Antonio who was only 35 when she got the results of a biopsy from her doctor.

“I walked in and she said the words I’ll never forget,” Lewis recalled. “‘Sweetie, it’s cancer.’”

Lewis had tried for a year to get various doctors and her dentist to examine and biopsy the strange spot under her tongue. But no one really thought she was at risk for the disease.

“I was told it’s most likely nothing because I’m young. I was only 35 years old. I was a female non-smoker, non-drinker,” Lewis said.

While smoking, drinking and age are big risk factors for oral cancer, so is the presence of the human papillomavirus in the body. Some cases, like Lewis’, are simply unexplained.

Since her cancer was so advanced, Lewis, a single mother of three children, faced a massive surgery and weeks of radiation. Paige still bears scars on her arm from a major surgery where doctors removed her tumor and rebuilt her tongue.

“They removed half of my tongue,” she described. “They harvested part of my arm in order to place a flap in my mouth. And then a part of my leg to cover part of my arm.”

Lewis spent 20 days in the intensive care unit. If her cancer had been detected earlier, or if doctors had the ability to shrink her tumor, her ordeal would have been less painful and less risky. Only slightly more than half of all oral cancer patients are alive five years after their treatment. Lewis is four years out.

U.T. Health Science Center researchers are trying to secure funding for human trials which may take place in San Antonio. The pills used in this new combination target tumors specifically, so patients would not suffer as many side effects as they do with conventional chemotherapy, side effects like hair loss and gastrointestinal issues.

Dr. Cara Gonzales’ oral cancer paper was published in the journal Oral Oncology.
“If we can find something that would treat these advanced tumors, we could potentially increase the survival rate of approximately 25 percent of all oral cancer patients,” Gonzales stated.

Lewis is coping well with the side effects of surgery and radiation, but it hasn’t been easy. “Cancer takes over your life during that period of time. And it affects every single person you know,” Lewis said. “All of this could have been avoided with an early diagnosis.”

An oral cancer screening at the dentist only takes two minutes, and checking for oral cancer should be part of a regular dental screening. Like Lewis and thousands of others, though, you may have to insist the hygienist or dentist examine your mouth, tongue and gums in detail. Having a medical professional look for signs and symptoms of the disease is still the best defense against oral cancer which claims an average of one American life every hour.

October, 2016|Oral Cancer News|

Particular HPV strain linked to improved prognosis for throat cancer

Source: medicalxpress.com
Author: provided by University of North Carolina Health Care

When it comes to cancer-causing viruses like human papillomavirus, or HPV, researchers are continuing to find that infection with one strain may be better than another.

In an analysis of survival data for patients with a particular type of head and neck cancer, researchers from the University of North Carolina Lineberger Comprehensive Cancer Center confirmed findings that a particular strain of HPV, a virus linked to a number of cancers, resulted in better overall survival for patients with oropharyngeal cancer than patients with other strains of the virus in their tumors.

They believe their findings, reported in the journal Oral Oncology, are particularly important as physicians move to lessen treatment intensity for patients with HPV-linked oropharyngeal cancer in clinical trials to try to spare them negative side effects of radiation or drugs. They also found that a test used widely to determine patients’ HPV status may not be sensitive enough to select patients for de-intensification.

“What we demonstrate in this study is that the type of HPV can help us to better determine a patient’s prognosis,” said the study’s senior author Jose P. Zevallos, MD, MPH, an associate member of UNC Lineberger and an associate professor in the UNC School of Medicine. “We think this is important because HPV positive patients do so well generally, and there’s been a huge move nationally to take treatment down a couple notches to limit morbidity and side effects. The risk is that if you de-intensify too much, and you happen to have a high-risk tumor because you have a different type of HPV, then this could be harmful to patients who don’t warrant it.”

The UNC study was based on an analysis of survival data for 238 patients in North Carolina diagnosed between January 2002 and February 2006 with oropharyngeal cancer, a type of head and neck cancer in the throat at the back of the mouth, as part of the Carolina Head and Neck Cancer Study, or CHANCE. The Centers for Disease Control and Prevention estimates that more than 15,600 cases of HPV-associated oropharyngeal cancer are diagnosed in the United States each year.

Previous studies have shown that patients with HPV-linked oropharyngeal cancer have higher survival and lower recurrence rates compared to those with HPV-negative oropharyngeal cancer. As those patients tend to respond better to treatment, researchers are studying whether patients with HPV-linked oropharyngeal cancer can receive less intensive treatment with good outcomes. The researchers point out, however, that there has been limited research that tracks outcomes for oropharyngeal cancer based on the particular strain of HPV that patients have.

Zevallos and his colleagues confirmed earlier findings that patients with oropharyngeal cancer tumors infected with HPV16 had improved overall survival. They also determined that patients whose cancer was infected with other HPV strains had similar survival rates as patients whose cancer did not have HPV at all.

They found that 71.4 percent of patients with HPV16-linked oropharyngeal cancer lived at least five years. Meanwhile, the five-year survival-rates for patients with other strains of the virus in their tumors, and for patients who were HPV-negative, were lower: 57 percent for patients with other types of HPV and 50 percent for HPV-negative patients.

Zevallos said the finding of a lower survival rate for patients positive for HPV strains other than HPV16 is important in that it indicates that those patients may not be good candidates for treatment de-intensification.

“The finding that non-HPV16 types are closer to the HPV-negative group in terms of survival differences suggests that those patients should definitely not be considered for anything other than standard aggressive therapy,” he said.

The researchers noted that additional research needs to be done in a larger sample size to rule out the possibility that characteristics other than HPV status are driving survival differences, and to clarify whether the patients found to have other HPV strains were not false-positives.

The also cautioned that based on their findings, a commonly used clinical test that measures for the presence of the p16 protein may not be specific enough to identify HPV-linked oropharyngeal cancer patients who are good candidates for treatment de-intensification. To determine whether patients had HPV-positive tumors, they compared the results of the p16 test with results of a more specific genetic test.

They found that 4.3 percent of the patients were positive for p16, but negative for HPV according to the genetic test. Another approximately 11 percent of p16-positive cases had HPV strains other than HPV16, according to the genetic tests. Zevallos said this is an important finding because patients whose cancer was not infected with HPV16 had a lower 5-year survival rate, meaning they would not be good candidates for treatment de-escalation.

Yet the researchers report that many of the clinical trials that de-intensify treatment use p16 expression alone to determine if a patient’s cancer is HPV-positive, and whether they should be considered for treatment de-intensification.

“Even though we rely almost exclusively around the country on p16 positivity as a surrogate for HPV16 presence, this sheds some light on the fact that maybe we should be considering HPV genotyping because of the survival differences we saw here,” Zevallos said.

September, 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|

Cancer-Preventing Vaccines Given To Less Than Half Of US Kids

Source: www.houstonpublicmedia.org
Author: Carrie Feibel

U.S. regulators approved a vaccine to protect against the human papilloma virus (HPV) in 2006, but cancer experts say misconceptions and stigma continue to hamper acceptance by both doctors and parents.

Eighty percent of Americans are exposed to the human papilloma virus in their lifetimes. Some strains of HPV can cause genital warts, but most people experience no symptoms and clear the virus from their systems within a year or two. But for an unlucky minority, the virus causes damage that, years later, leads to cervical cancer, throat cancer, and other types.

Researchers at MD Anderson are frustrated that ten years after the first vaccine arrived on the market, only 42 percent of U.S. girls, and 28 percent of boys, are getting the three-shot series.

The series can be given to girls and boys between the ages of 9 and 26, but the immune response is strongest at younger ages, before sexual activity begins.

n 2007, then-Texas governor Rick Perry proposed making the HPV vaccine mandatory for all preteen girls.  At the time, the vaccine was only approved and marketed for girls.

Dr. Lois Ramondetta, a cervical cancer specialist at MD Anderson, remembers the outcry.

“A lot of people felt that was the right idea, but the wrong way to go about it. Nobody really likes being told what to do, especially in Texas,” Ramondetta said. “I think there was a lot of backlash.”

Eventually, the legislature rejected Perry’s plan, even though it included an opt-out provision. Ramondetta said too many politicians focused on the fact that HPV is sexually transmitted. That had the unfortunate effect of skewing the conversation away from health care and into debates about morality and sexuality. She said the best and most accurate way to discuss the vaccine is to describe it as something that can prevent illness and death.

“I try to remove the whole concept of sexuality,” Ramondetta said. “When you’re talking about an infection that infects 80 percent of people, you’re really talking about something that is part of the human condition. Kind of like, it’s important to wash your hands because staph and strep are on all of us.”

Today, only Virginia, Rhode Island and Washington, D.C. mandate HPV vaccines.

“Our vaccination rates are really terrible right now,” Ramondetta said.

In Texas, only 41 percent of girls get all three of the required shots, and only 24 percent of boys.

hpv-kara-million-1200x788

Kara Million of League City finds those numbers upsetting.  Million survived two rounds of treatment for cervical cancer.

“Even if you had a chance that your kid could have any kind of cancer, and you could have given them two shots or three shots for it? To me, it’s a no-brainer,” Million said.

Million always got regular Pap tests. But she missed one appointment during a busy time following the birth of her second child. When she went back, it had been only 15 months since her last Pap test. But the doctor found cervical cancer, and it had already progressed to stage 3.

“That was a huge surprise,” Million recalled.

Million had chemotherapy and radiation at MD Anderson. But a year later the cancer returned.

The next step was surgery, a radical procedure called a total pelvic exenteration.

Million and her husband looked it up online.

“When I was reading it, I was just, like, ‘this is so barbaric, there is no way they are still doing this in this day and age,’” Million said. “‘For certain, in 2010 we have better surgeries to do than this.’”

But there weren’t better surgeries. This was her only option.

“I had a total hysterectomy; they pulled all the reproductive system out,” she explained. “They take your bladder out, they take part of your rectum, they take part of your colon, they take your vagina, all of that in your pelvic area comes out.”

The surgery took 13 hours, and left her with a permanent colostomy bag and urostomy bag.

“At that point, with two kids at that age – I think they were one-and-a-half and three – there’s no option. I’m a mom, so I’m going to do whatever it takes so they can have their mom.”

Most women survive cervical cancer if it’s caught early enough. But Million’s cancer was diagnosed at a later stage, where only a third of women make it past five years. She has already made it past that five-year anniversary, and she’s not wasting any time.

She now volunteers as a peer counselor at MD Anderson to other cervical cancer patients, and she urges parents to vaccinate their kids.

“If most of cervical cancer is caused by HPV, and now we have something that can help prevent what I went through, and what my friends went through, and the friends that I lost?” Million says, “I don’t understand why people don’t line up at the door to get their kids vaccinated for it.”

But Dr. Ramondetta said parents can’t consent to the vaccination if pediatricians or family doctors don’t offer it. And they’re not offering it nearly enough, she said.

Some doctors don’t know how to broach the topic, fearing it will lead to a difficult conversation about sexual behavior. Some mistakenly think boys don’t need it, although they do – not only to protect their partners from HPV, but to protect themselves against oropharyngeal and anal cancers, which are also caused by HPV.  Ramondetta added that some doctors incorrectly assume that giving the vaccine will promote promiscuity.

Ramondetta says extensive research actually shows it doesn’t.

“There should be this understanding of an ethical responsibility. That this is part of cancer screening and prevention, just like recommending mammograms and colonoscopies.”

In Texas, only 41 percent of girls get all three of the required shots, and only 24 percent of boys.

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

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.