radiation

Study: Healthy diet may avert nutritional problems in head, neck cancer patients

Source: news.illinois.edu
Author: Sharita Forrest

At least 90% of head and neck cancer patients develop symptoms that affect their ability or desire to eat, because of either the tumor itself or the surgery or radiation used to treat it. These problems, called nutrition impact symptoms, have wide-ranging negative effects on patients’ physical and mental health and quality of life.

However, patients who eat foods high in antioxidants and other micronutrients prior to diagnosis may reduce their risks of developing chronic nutrition impact symptoms up to one year after being diagnosed with head or neck cancer, according to a recent study led by researchers at the University of Illinois.

The scientists analyzed the dietary patterns of 336 adults with newly diagnosed head and neck cancers and these patients’ problems with eating, swallowing and inflammation of the digestive tract. This painful inflammatory condition, called mucositis, is a common side effect of radiation treatment and chemotherapy.

The mitigating effects of a healthy diet were particularly significant in people who had never smoked and in patients who were underweight or normal weight at diagnosis, who often experience the greatest eating and digestive problems during treatment, said Sylvia L. Crowder, the paper’s first author.

Crowder is a research fellow in the Cancer Scholars for Translational and Applied Research program, a collaborative initiative of the U. of I. and Carle Foundation Hospital in Urbana, Illinois.

“While previous work has established that the presence of nutrition impact symptoms is associated with decreased food intake and weight loss, no studies have examined how pre-treatment dietary intake may influence the presence of these symptoms later in the course of the disease,” Crowder said.

In the early 2000s, researchers hypothesized that consuming antioxidant supplements might protect patients’ normal cells from damage during radiotherapy, enabling them to better tolerate treatment and higher dosages.

Accordingly, prior research by Anna E. Arthur, a professor of food science and human nutrition at the U. of I. and the current study’s corresponding author, indicated that eating a diet of whole foods abundant in antioxidants and phytochemicals improved recurrence and survival rates in head and neck cancer patients.

Like Arthur’s prior research, the new study was conducted with patients of the University of Michigan Head and Neck Specialized Program of Excellence.

Data on patients’ tumor sites, stages and treatment were obtained from their medical records. More than half of these patients had stage 4 tumors at diagnosis.

Prior to starting cancer treatment and again one year post-diagnosis, the patients completed a questionnaire on their diet, tobacco and alcohol use, and quality of life. Patients reported whether they experienced any of seven nutrition impact symptoms – such as pain or difficulty chewing, tasting or swallowing foods and liquids – and rated on a five-point scale how bothersome each symptom was.

In analyzing the patients’ eating habits, the scientists found that they followed either of two major dietary patterns – the Western pattern, which included high amounts of red and processed meats, fried foods and sugar; or the prudent pattern, which included healthier fare such as fruits and vegetables, fish and whole grains.

Patients who ate healthier at diagnosis reported fewer problems with chewing, swallowing and mucositis one year after treatment, the scientists found.

“While the origin and development of nutrition impact symptoms are complex and varied, they generally share one common mechanism – cell damage due to inflammation,” said Arthur, who is also an oncology dietitian with the Carle Cancer Center. “The prudent dietary pattern has the potential to reduce inflammation and affect the biological processes involved in the pathogenesis of these symptoms.”

The scientists hypothesized that some patients may begin eating healthier after being diagnosed with cancer, potentially counteracting the pro-inflammatory effects of their previous dietary habits.

Reverse causation was possible too, they hypothesized – patients’ lack of symptoms may have enabled them to consume a broader range of foods, including healthier whole foods, before their cancer was discovered.

Notes:
Alison M. Mondul, Laura S. Rozek, Dr. Gregory T. Wolf and Katie R. Zarins, all of the University of Michigan, were co-authors of the study.

Additional co-authors were Kalika P. Sarma of the Carle Illinois College of Medicine, M. Yanina Pepino of the U. of I., and Zonggui Li and Yi Tang Chen, both then-graduate students at the U. of I.

In addition to the C-STAR program, an Academy of Nutrition and Dietetics Colgate Palmolive Fellowship in Nutrition and Oral Health, and the U.S. Department of Agriculture National Institute of Food and Agriculture supported the research.

December, 2019|Oral Cancer News|

Acupuncture prevents radiation induced dry mouth

Source: www.healthcmi.com/
Author: staff

Acupuncture reduces the frequency and severity of xerostomia (dry mouth). University of Texas MD Anderson Cancer Center (Houston) and Fudan University Cancer Center (Shanghai) researchers conducted a randomized controlled clinical trial. The phase-three patient and assessor blinded investigation of acupuncture’s effects on head and neck cancer patients receiving radiation therapy demonstrated groundbreaking results. The researchers concluded that acupuncture “resulted in significantly fewer and less severe RIX [radiation-induced xerostomia] symptoms 1 year after treatment vs SCC [standard care control].” [1]

Salivary glands may be temporarily or permanently damaged by radiation therapy. There is a high-incidence of RIX, which may lead to complications including difficult or painful swallowing, impairment of the sense of taste (dysgeusia), and dental problems. Other RIX complications may include insomnia and difficulty speaking.

The study compared true acupuncture, sham acupuncture, and standard care control groups. True acupuncture produced significantly greater positive patient outcomes than the other groups. Outcome measures were based on a questionnaire, salivary flow, incidence of xerostomia, salivary contents, and quality of life scores. One year after completion of all acupuncture treatments, the true acupuncture group maintained significantly higher patient outcome rates over the standard care and sham groups.

All acupuncture treatments were provided by credentialed acupuncturists. The researchers note that their findings are consistent with several prior investigations. True acupuncture patients that received acupuncture three times per week during their six to seven week course of radiation therapy had significantly less dry mouth a year after completion of treatments than standard care control patients. No adverse effects occurred at University of Texas MD Anderson. One adverse effect was reported at the Fudan study location.

The researchers find that acupuncture is superior to standard care for the relief of radiation induced xerostomia. They comment that acupuncture is “minimally invasive” and “has a very low incidence of adverse effects.” [2] Based on the evidence, further research is warranted.

All participants in the study were at least 18 years of age, provided informed consent, had a diagnosis of head and neck carcinoma, and were scheduled for radiation therapy at a mean dose of 24 Gy to a minimum of one parotid gland. An extensive list of exclusion criteria was used to prevent variables created by comorbidity.

All acupuncturists providing treatment during the course of the study were licensed and were prepared and trained at the University of Texas MD Anderson Cancer Center. The acupuncture point prescription chosen for the study was the following:

  • CV24
  • LU7
  • KD6
  • Auricular: Shenmen, Point Zero, Salivary Gland 2 Prime, Larynx

Standard needle depths were used and the elicitation of deqi at the acupoints was at the discretion of treating acupuncturists. Notably, once deqi was elicited, needles were no longer manually stimulated (with the exception of displaced needles). Electroacupuncture was not used at any point.

Body-style acupuncture needles were of 0.25 mm diameter and 40 mm length. Auricular acupuncture needles were of 0.16 diameter and 15 mm length. Acupuncture treatments were provided a total of three times per week for the duration of the 6-7 week radiation treatment period.

The researchers chose to avoid the use of local points other than CV24 with the intent of preventing disturbance of tissues damaged by radiation. All patients were treated on the day of radiation therapy in a semisupine or supine position. Acupuncture was applied either before or after radiation therapy. Based on the data, the researchers note that acupuncture “should be considered for the prevention of radiation-induced xerostomia.” [3]

The investigators note that prior research indicates that acupuncture regulates blood flow at the parotid glands. In addition, a variety of other studies find acupuncture effective for the treatment of xerostomia. One of the studies cited in the investigation finds acupuncture effective for up to three years after treatment. Two pilot studies by the research group prior to this phase three clinical trial find acupuncture effective for the prevention of RIX if provided with radiation therapy.

The study employed strict controls and researchers monitored treatment facilities and licensed acupuncturists during the investigation. Further research will help to support standardization of acupuncture protocols for the prevention and treatment of RIX for inpatient and outpatient settings.

References:
1. Garcia, M.K., Meng, Z., Rosenthal, D.I., Shen, Y., Chambers, M., Yang, P., Wei, Q., Hu, C., Wu, C., Bei, W. and Prinsloo, S., 2019. Effect of True and Sham Acupuncture on Radiation-Induced Xerostomia Among Patients With Head and Neck Cancer: A Randomized Clinical Trial. JAMA Network Open, 2(12), pp.e1916910-e1916910.
2. Ibid.
3. Ibid.

December, 2019|Oral Cancer News|

Survivorship clinic helps patients with what comes after head and neck cancer

Source: www.pittwire.pitt.edu/
Author: Gavin Jenkins, excerpted from the fall 2019 issue of Pitt Med magazine

Jonas Johnson presses his hand on Edward Christopher’s neck. The examination room at the UPMC Head and Neck Cancer Survivorship Clinic is chilly on this June morning as Johnson, chair of the University of Pittsburgh Department of Otolaryngology, glides his fingers along the left side of Christopher’s throat.

“Your skin is stiff,” Johnson says. “Scar tissue doesn’t go away.”

Five years ago, Christopher was diagnosed with human papillomavirus (HPV) positive cancer on the base of his tongue, left tonsil and the lymph nodes on the left side of his neck. After undergoing surgery to remove the tumors, he received radiation treatment and chemotherapy, followed by another procedure to remove his lymph nodes.

When he completed the treatment, he posted a picture on Facebook holding a sign that read “cancer free!” That night, he and his family celebrated with dinner at an Italian restaurant. Christopher felt lucky to be alive and grateful to Pitt doctors. He had no idea how difficult the years to come would be. He credits Marci Lee Nilsen, a nurse who is an assistant professor in Pitt’s School of Nursing, with opening his eyes.

In 2016, Johnson and Nilsen created the Survivorship Clinic to help patients like Christopher improve their quality of life after beating head and neck cancer. Most patients grapple with dysphagia—difficulty swallowing—and trismus, commonly known as lockjaw. They might experience a loss of taste, tooth decay, dry mouth and mouth sores. The side effects from radiation and chemotherapy can often cause patients to struggle to talk, hear and sleep, as well. The combination of these treatments with surgery can also lead to mobility issues; many patients end up on disability. Insomnia and sleep apnea can exacerbate anxiety and depression, which also are common issues.

Getting care for these conditions can place a financial strain on patients who have already spent tens of thousands of dollars to overcome cancer.

Survivorship clinics for head and neck cancer are sprouting up across the country. Some of those clinics have more than a few specialists. UPMC’s clinic patients see an otolaryngologist, audiologist, dentist, speech pathologist and physical therapist in one day. And unlike any other survivorship clinic in the United States, they are charged just one co-pay.

The Survivorship Clinic also sets itself apart by how it monitors patients from the start. Nilsen and Johnson meet with patients before they receive radiation and chemotherapy, and then again a month after treatment is completed. After that, patients visit the clinic at least once a year, and depending on their needs, Johnson and Nilsen will coordinate with the appropriate primary care physician, dentist or physical therapist.

Historically, the struggles of head and neck cancer survivors have been approached as an afterthought by many hospitals and primary care physicians. That’s changing as providers recognize the fallout from treatments, which can be lifesaving but also life hobbling. Johnson and Nilsen have seen more than a thousand patients in their three years at UPMC’s Survivorship Clinic. Their work has highlighted the importance of long-term care.

For Johnson, a renowned head and neck cancer surgeon who has been with Pitt since 1977, the Survivorship Clinic represents a new chapter in his career.

“I’ve reinvented myself,” he says. “I say to my residents: Don’t think I’ve repudiated the last 40 years of my career. I still believe in surgery. But I’ve embraced the notion that we must recognize the trouble we cause (treating cancer), and we have to help people with it.”

There’s more to this story. Continue reading about Johnson and Nilsen’s partnership and more patients benefiting from their work.

November, 2019|Oral Cancer News|

Oral mucositis: preventing the side effect before undergoing cancer treatment

Source: www.curetoday.com/
Author: Katie Kosko

Oral mucositis can be painful and, in some cases, require hospitalization of patients being treated for cancer with chemotherapy and other radiation therapies. However, along with your care team, you can take steps to prevent this uncomfortable side effect.

In an interview CURE®, Dr. Alessandro Villa, assistant professor in oral medicine and dentistry at the Harvard School of Dental Medicine, Brigham and Women’s Hospital in Boston, spotlighted the number of patients with cancer who are affected by oral mucositis, explained the benefits of two agents approved by the Federal Drug Administration (FDA) for intervention and explored how patients can control the side effect from the comfort of their homes.

CURE®: Can you explain what types of cancer treatment cause oral mucositis?
Villa: Oral mucositis is an iconic toxicity of cancer therapy and remains one of the most painful and disrupting side effects of radiation therapy and chemotherapy. When I talk about radiation therapy, I talk about patients with head and neck cancer. In these patients, usually 100% receiving radiation therapy develop oral mucositis. We also see mucositis in approximately 60% to 80% of patients who undergo bone marrow transplants. And finally, we see it in 20% to 40% of patients who receive conventional chemotherapy for any cancer.

What are the consequences of oral mucositis?
Oral mucositis is one of the most painful toxicities in patients receiving radiation therapy to the head and neck. It’s the number one cause of hospitalization in these patients. It can sometimes be so severe and painful that patients can’t speak, swallow or eat. It’s a very debilitating toxicity. If they are not able to eat, they may end up receiving a feeding tube. The cost associated with oral mucositis is higher than $17,000 per patient. There is still a huge unmet need out there for patients.

What questions should patients and/or caregivers ask their health care team about oral mucositis?
The first question I would have them ask is, what can I expect? Because it can be different between radiation and chemotherapy. And as we have discussed, they can also ask: What can I do at home to minimize this risk? And what are the preventative measures?

How can oral mucositis be prevented?
The FDA has approved two agents for mucositis intervention. One is called palifermin, which is approved for the prevention of severe oral mucositis in patients who receive certain treatment in preparation for bone marrow transplant. The second agent, which is for mitigation of mucositis in patients treated with radiation for head and neck cancer, is a rinse called benzydamine hydrochloride.

Cryotherapy is recommended by the American Society of Clinical Oncology in patients who receive a specific chemotherapy, 5-fluorouracil or more commonly 5FU. Patients can swish on ice chips for about 30 minutes starting about five minutes before the drug is administered. And to control mucositis pain, morphine may be used in patients who undergo stem cell transplantation.

What can patients do at home to help avoid the side effect or reduce its severity?
There are specific recommendations that patients should follow to minimize oral mucositis. One of them is maintaining good oral hygiene using a soft toothbrush. Patients can also use a saline solution 3-4 times a day, then rinse and spit. Cleansing of the mouth and good lubrication of the inside of the cheeks and lips can help with the pain and inflammation. The reason behind it is that, from a scientific standpoint, the microbiome (the bacteria and all the bugs that we have in the mouth) can contribute in the development and worsening of the mucositis. The cleaner the mouth, the better it is. Of course, patients may be sensitive to certain toothpastes, so it’s important to use mild-flavored fluoridated toothpaste when brushing. In some cases, patients should avoid spicy, acidic or hot foods because these may trigger symptoms for the patient.

How is the side effect monitored?
This depends on the type of treatment they are receiving. If they are receiving radiation, they come in the hospital Monday through Friday, so they are monitored daily.

For those with chemotherapy, most of these drugs are administered through IV in the hospital. However, there are some new chemotherapies given by mouth and patients take these at home, but they can give different side effects.

Is there anything else that you would like to add about oral mucositis?
Right now, this is a huge unmet clinical problem for patients and a devastating toxicity, but the development for oral mucositis is pretty robust with a wide range of new agents. This is promising, and there are some good results in current clinical trials with some of these new agents in progress. If I’m being optimistic, I think that there should be new options ready for approval in the next 5-10 years. There is a lot in the pipeline.

November, 2019|Oral Cancer News|

Radiation for head and neck cancer may cause problems years later

Source: www.usnews.com
Author: Steven Reinberg

Ten years after radiation treatment for head and neck cancer, some patients may develop problems speaking and swallowing, a new study finds.

These problems are related to radiation damage to the cranial nerves, the researchers explained. The condition is called radiation-induced cranial neuropathy.

“We had always thought that radiation did not damage cranial nerves because they get treated in every patient with head and neck cancer, and we do not see cranial neuropathy that commonly,” said Dr. Thomas Galloway, of the department of radiation oncology at the Fox Chase Cancer Center in Philadelphia.

“What our data is suggesting is that a small percentage of people do get cranial nerve damage from treatment, but it occurs after a long latency period,” Galloway said.

For the study, the researchers collected data on 1,100 patients who had radiation for head and neck cancer between 1990 and 2005. Among these patients, 112 were followed for at least 10 years.

Of the 112 patients, 14% developed at least one cranial neuropathy. The median time until the condition was seen was more than seven years. It took some patients more than 10 years to develop the problem, the findings showed.

Curing the initial cancer is the most important concern, Galloway said. But these patients need to be followed for the rest of their lives, if possible, he added.

The report was published recently in the journal Oral Oncology.

October, 2019|Oral Cancer News|

Researchers: Favorable survival, fewer side effects after reduced therapy for HPV-linked head and neck cancer

Source: medicalxpress.com
Author: University of North Carolina at Chapel Hill School of Medicine

University of North Carolina Lineberger Comprehensive Cancer Center researchers reported that reducing the intensity of radiation treatment for patients with human papillomavirus-associated head and neck cancer produced a promising two-year progression-free survival rate and resulted in fewer side effects.

The findings, published in the Journal of Clinical Oncology, were drawn from a phase II clinical trial that included 114 patients with HPV-linked head and neck cancer and a limited smoking history. The researchers reported that they saw a similar progression free survival rate, and that patients experienced fewer long-term side effects in the study compared with patients who received standard intensity treatment in previous studies.

“A simple de-intensification strategy of reducing radiation and chemotherapy appears to be as effective at cancer control as the standard seven-week regimen,” said UNC Lineberger’s Bhishamjit S. Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology. “Furthermore, there were fewer toxicities.”

For the trial, patients received six weeks of treatment, including a reduced intensity of radiation therapy of 60 Gray with weekly low-dose chemotherapy of cisplatin. The standard of care regimen is seven weeks of treatment 70 Gray and high-dose chemotherapy.

The main outcome that the researchers were studying was two-year progression-free survival. On the reduced regimen, researchers found that the two-year progression free survival was 86 percent, compared to a two-year progression free survival reported from other studies using standard treatment doses of 87 percent.

Chera said the major long-term side effects of radiation treatment are related to swallowing and dry mouth. Previous studies have shown the majority of patients treated with standard intensity chemoradiotherapy require a temporary feeding tube and some have significant long-term swallowing dysfunction.

Notably, in this study, patients reported that their swallowing returned to baseline after de-intensified treatment, and only 34 percent required a temporary feeding tube.

The results need to be validated in larger, randomized clinical trials, Chera said, and studies are ongoing to investigate this.

He added that while this study included patients with a limited smoking history, other current studies include patients with more extensive smoking histories.

Chera said that researchers want to continue to improve two-year progression free response rates while achieving better side effect results. They want to do that by identifying additional biomarkers to drive precision medicine strategies.

Although traditional clinical risk help clinicians predict outcomes and select patients for clinical trials of de-intensified treatments, Chera said that these risk factors are imprecise. He and his colleagues are currently evaluating additional novel biomarkers that they believe could be used to better predict a patient’s prognosis and outline a course of treatment.

Specifically, they have shown in a previous study how levels of circulating HPV DNA in the blood, and how quickly patients clear this from the blood, were linked to outcomes.

September, 2019|Oral Cancer News|

Oral rinse could improve mouth pain associated with radiation therapy

Source: www.specialtypharmacytimes.com
Author: staff

An oral rinse containing diphenhydramine, lidocaine, and antacids, was found to significantly decrease pain caused by oral mucositis in patients undergoing radiation therapy for head and neck cancer compared with placebo, according to a study published in JAMA.

The multi-institution, randomized, double-blind, placebo-controlled phase 3 clinical trial was led by Robert Miller, MD, an emeritus Mayo Clinic radiation oncologist.

“Our group published a study in 2012 showing that an oral rinse of doxepin reduced oral mucositis-related pain compared to placebo,” Miller said in a press release. “However, there were no large randomized controlled trials studying the potential benefits of magic mouthwash.”

The researchers evaluated 275 patients between November 2014 and May 2016. The study revealed that treatment with both doxepin and the mouthwash combination significantly reduced pain associated with oral mucositis compared with placebo.

The doxepin and mouthwash combination treatment was also well-tolerated by patients, according to the study.

“Radiation therapy may cause mouth sores because it is designed to kill rapidly growing cells, such as cancer cells,” co-author, Terence Sio, MD, a Mayo Clinic radiation oncologist, said in a press release. “Unfortunately, healthy cells in your mouth also divide and grow rapidly, and may be damaged during radiation therapy, which can cause discomfort. We’re glad to have identified a proven method to help treat the discomfort of this side effect.”

How do speech-language pathologists support cancer patients?

Source: syvnews.com
Author: Aundie Werner

Question: What are speech-language pathologists and how do they support cancer patients?

It is estimated that about 100,000 people will be diagnosed with a head, neck or thyroid cancer this year.

Although this does not grab headlines as often as many other cancers, for those affected the disease and treatment can have a significant impact on their lives. In general, most people survive head and neck cancer; however, side effects of treatment can sometimes be a long-term problem.

The support and guidance of a speech-language pathologist (SLP) can do much to help promote recovery and cope with the difficult symptoms of treatment. Ideally, the SLP becomes involved when the patient has been identified as having head and neck cancer before their surgery or before their chemotherapy/radiation protocol. Counseling and education are provided as to the functions of voice, speech and swallowing. Assessment is made to determine the patient’s baseline and to provide guidance as to the patient’s role in their rehabilitation.

Frequently, the SLP works with patients who have difficulty eating and drinking. Treatment is based on the cause of the problem: anatomical changes from surgery, decreased saliva, changes in taste, difficulty opening the mouth due to trismus, and problems protecting the airway, which can result in coughing and choking during meals.

Maintaining nutrition after surgery and during treatment is necessary to help the body heal. At times, the patient may need to have a feeding tube to help with nutrition when it becomes too difficult to swallow. The SLP assesses the patient’s current needs, instructs the patient in specific swallowing exercises, compensatory swallowing strategies or diet modification recommendations. The goal is for patients to continue to eat and drink during and after treatment.

Following radiation therapy, patients may experience lymphedema and/or fibrosis of the radiated tissue. These effects can persist long after the treatment concludes. Difficulties can include problems opening the mouth to eat from a spoon or fork, or decreased ability of the throat muscles to protect the airway while eating or drinking. In these cases, specific testing and exercises are instructed by the SLP.

Voice changes may also occur after surgery or radiation. The SLP instructs patients how to use their voice efficiently so as not to strain the muscles. Patients who have had their voice box removed are instructed in alternative methods to produce voicing to communicate.

Additionally, articulation and resonance changes can occur from surgery and/or radiation. Patients who have had sinus, palatal, jaw or tongue cancer are instructed how to articulate more clearly through customized treatment or prosthetic devices, if needed.

Each patient’s cancer is unique, as is the plan of care developed by the SLP. The Central Coast has excellent speech-language pathologists who are trained to provide their expertise to facilitate your road to recovery.

March, 2019|Oral Cancer News|

Israeli company set to begin testing new radiation cancer therapy

Source: www.forbes.com
Author: Robin Seaton Jefferson

An Israeli medical technology company is set to begin testing its new radiation cancer therapy in leading medical centers in Italy. The Alpha DaRT (Dіffusіng Alpha-emіtters Radіatіon Therapy) device delivers high-precision alpha radiation that is released when radioactive substances decay inside the tumor and kills cancer cells while sparing the surrounding healthy tissue, the company says.

The company hopes to get approval from the European Commission by next year for the therapy.

Early results from an ongoing pre-clinical trial on patients with squamous cell carcinoma (SCC) tumors at the Rabin Medical Center in Israel and the IRST (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori) in Italy showed a reduction in all tumor sizes and more than 70 percent of the tumors completely disappearing within a few weeks after treatment, NoCamels reported.

The therapy has already been tested on more than 6,000 animals and has been found “to be effective and safe for various indications, including tumors considered to be resistant to standard radiotherapy.” according to the breakthrough innovation news site NoCamels.

Alpha Tau Medical was founded in 2016 to focus on research and development as well as commercialization of its Alpha DaRT cancer treatment. The therapy was initially developed in 2003 by Professors Itzhak Kelson and Yona Keisari at Tel Aviv University.

According to the National Cancer Institute (NCI), cancers that are known collectively as head and neck cancers, or squamous cell carcinomas of the head and neck, usually begin in the squamous cells that line the moist, mucosal surfaces inside the head and neck (for example, inside the mouth, the nose, and the throat).

Head and neck cancers account for about 4% of all cancers in the United States, are more than twice as common among men as they are among women, and are more often diagnosed among people over age 50.

Cancers of the head and neck are further categorized by the area of the head or neck in which they begin including the oral cavity, pharynx (throat), larynx, paranasal sinuses and nasal cavity, and salivary glands. They can include hypopharyngeal cancer, laryngeal cancer, lip and oral, cavity cancer, metastatic squamous neck cancer with occult primary, nasopharyngeal cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, salivary gland cancer.

The Alpha DaRT treatment can be applied under local anesthesia in a short single session and can be combined with chemotherapy and immunotherapy to increase effectiveness, according to Alpha Tau Medical. The company reports Alpha DaRT can even trigger anti-tumor immunity for the elimination of distant metastases, NoCamels reported.

Clinical trials for Alpha DaRT will be conducted at the Sapienza University of Rome, which is initiating Alpha Tau’s clinical trial protocol for squamous cell carcinomas of the skin and oral cavity, and the IFO (Istituti Fisioterapici Ospitalieri), which is conducting its first study of Alpha DaRT for the treatment of cutaneous and mucosal malignant neoplasia (CMN).

Alpha Tau is also collaborating with key cancer physicians worldwide to investigate the Alpha DaRT as a treatment for other cancers, including pancreatic, breast and prostate, NoCamels reported.

November, 2018|Oral Cancer News|

A Look at Therapy Toxicities & Biology in Head & Neck Cancers

Source: journals.lww.com
Author: Valerie Neff Newitt

A measure of intrigue and discovery pertaining to head and neck cancer, spiked with compassion for patients struggling against treatment toxicities, helps quench the intellectual thirst of Yvonne Mowery, MD, PhD, Butler Harris Assistant Professor of Radiation Oncology at Duke University Medical Center, Durham, N.C.

Splitting time between the clinic and laboratory, Mowery is actively engaged in patient care as well as preclinical, translational, and clinical research. “I hope to get a better understanding of the biology of head and neck cancer and determine pathways that we can target to reduce metastatic spread of the disease and improve responsiveness to available treatments,” she told Oncology Times.

Long before reaching her current status as an award-winning investigator, Mowery grew up in Richmond, Va., in the midst of a “completely non-scientific” family. “I was an oddball,” she joked, while recalling her parents’ patience with her backyard composting experiments that became so foul-smelling that the health department was contacted. As a kid, her idea of a great present was an encyclopedia of science, and the thing that caught her eye at the toy store was a junior chemistry set.

Science was clearly her path when she headed to the University of Virginia. In her sophomore year, Mowery began working in a genetics lab. That’s where the lure of fruit flies took hold. “I looked at the development of their reproductive system and found that very interesting,” she recalled.

Nearing the completion of her undergraduate education, Mowery debated between attending medical school or graduate school. The eventual winner? Both. “I investigated physician-scientist training programs and arrived at Duke in 2004 to do a combined MD/PhD.” Today, Mowery spends 1 day a week in clinic where she sees patients, then moves to the lab for the remainder of the week to find strategies to improve patient care and develop therapies to deliver better outcomes for patients, both present and future.

Clinical Challenges
“I treat cancers primarily of the head and neck—such as oral cavity, larynx, tonsils, base of tongue, sinuses—with radiation therapy. I think of head and neck cancers as being in a ‘very high-stakes real estate’ area,” she said, “because they are often close to saliva glands, vocal cords, etc. This requires intricate planning for radiation treatment. Visualization of the tumor through fiberoptic laryngoscopy allows me to see a tumor responding to radiation and chemotherapy during the weeks of treatment; it is gratifying to watch it happen with your own eyes.”

Mowery said toxicity associated with treatment of this area of the body can be severe, partially due to the fact that it is typically “…one of the longer courses of radiation that we do—about 7 weeks, 5 days a week,” she explained. “Patients typically require pain medicine to eat and drink a soft diet, lose their sense of taste, and experience very dry mouth, sometimes requiring a feeding tube for nutrition. In addition, the skin on their neck often falls off.” Comparing it to severe sunburn, Mowery said skin typically blisters and peels off, leaving behind a neck that is “red, angry, and very uncomfortable. It just comes with the territory.”

In addition to these side effects, Mowery said there is also an unusual biological aspect to head and neck cancers which figures largely in her work. “Something very interesting scientifically drew me to these cancers,” she informed. “There are two main causes of cancer in this area: tobacco use and human papillomavirus (HPV). Outcomes for patients with HPV-positive oropharynx cancers are excellent; even when the cancer is locally advanced about 80-90 percent of patients are cured. But the tobacco-induced cancers, by contrast, do much worse (about 60% or less survival rate for locally advanced disease). Even if the tumor size is the same and the number of involved lymph nodes are the same, the biology is completely different for the HPV-related and the HPV-unrelated disease.”

In fact, the staging system was changed at the beginning of this year so that HPV-related cancers and HPV-negative cancers are staged differently. “HPV-positive cancers that used to be staged at IVA may now be staged at I or II, but they remain at stage IVA if the cancer is HPV-negative,” Mowery detailed.

Asked why tobacco-related cancer behaves so badly, Mowery answered, “We do not have a good understanding of that; it is something I am studying. We do know, however, that HPV-negative tumors exhibit a loss of function of the p53 gene, [which] is really the king of all tumor suppressors. In HPV-related tumors, p53 is usually genetically still intact but its activity is affected by HPV.”

She also commented that people still actively smoking during treatment tend to do much worse, likely due in part to having lower oxygen levels in the tumor, which in turn causes the radiation to work less effectively. “If we can figure out ways to make HPV-negative tumors behave more like HPV-positive tumors, outcomes would improve.”

From Clinic to Research
These realities on the clinical side have informed and inspired some of Mowery’s research efforts. One of her projects aims at reducing the toxicity of treatment while maintaining good outcomes in patients.

“A clinical trial that I am about to start will use PET/CT, a type of metabolic imaging, as an early litmus test to evaluate how patients are responding during treatment. If we find they are responding well, we will de-intensify and back off on the chemotherapy and radiation dose while still trying to achieve good outcomes,” Mowery explained.

She noted that because HPV-positive and HPV-negative cancers are still treated exactly the same way when not on a clinical trial, investigators also hope to find out if treatment can be de-intensified for the HPV-positive patients who tend to have more successful outcomes by virtue of their cancer type, thus allowing them to avoid some of the severe side effects.

“Of course, even in HPV-positive cancers, not every patient is cured,” cautioned Mowery, “so we want to see if we can identify, early on, who is going to do well and who, in contrast, still needs that full 7-week intensive course of radiation therapy and chemotherapy.”

Another clinical trial ongoing at Duke in which Mowery is involved is testing a drug called BMX-001 given to patients through a subcutaneous injection during radiation. “We hope the drug will reduce the—the inflammation and irritation of the lining of the mouth and throat during radiation—and dry mouth,” she said.

Mowery is also busy in lab with intensive work in developing new mouse models of both HPV-related and HPV-unrelated squamous cell carcinoma of the head and neck. “My objective is to develop a platform in which I can develop radiation with immunotherapy, as well as with chemotherapy and various novel systemic agents, to try to improve outcomes particularly for HPV-negative disease,” noted Mowery, also the winner of a 2017 Conquer Cancer Young Investigator Award. “I want to discover if there are ways that we can make our bodies and our immune system realize that these cells are not ‘self’ and activate the immune system to attack and eliminate them.”

Tobacco-related cancer is induced in mice by giving them a carcinogen present in tobacco, “… causing them to become like a tobacco chewer or smoker,” Mowery explained. “Having that exposure causes mutations in cells in the lining of their mouth.”

Mowery further said her research is taking advantage of large sequencing projects in which various head and neck tumors have been sequenced. These data are publicly available and published primarily by The Cancer Genome Atlas organization. “I have been able to see which genes are most commonly mutated and then can genetically engineer mice to have those mutations. In other words, I can specifically knock out certain genes in the head and neck to model the cancer in mice.”

This is extremely important because it allows Mowery and team to interrogate the biology of the mutations, and determine which genetic changes and pathways lead to the cancer spreading from its site of origin to the lymph nodes or the lungs. “It helps us to develop therapies to block the cancer and keep it at bay, and to determine if there are better ways to sensitize the cancer to radiation and chemotherapy,” she detailed. “And we have an opportunity to test drugs that we hope will help with side effects of radiation. We must make sure that drugs protecting normal tissue are not also protecting the tumor. Having great animal models of human cancer is really important to making progress.”

As if her work in head and neck cancer were not enough, Mowery is continuing an earlier effort begun in the lab of her research mentor David G. Kirsch, MD, PhD, by acting as radiation oncology principal investigator for a multi-site, international prospective randomized clinical trial investigating the combination of the immune checkpoint inhibitor pembrolizumab (anti-PD-1 antibody) and radiation therapy for patients with high-risk soft tissue sarcoma of the extremities. The researchers are also examining the biology behind the effects of radiation combined with pembrolizumab in a co-clinical trial using primary mouse models of sarcoma.

“We saw promising results combining them in this model. Our hope is by using this combination during the early stage of disease we may be able to eliminate those cells that have escaped the primary tumor before they cause a problem.”

Who Has Time for Hobbies?
Asked about her life outside of the clinic and lab, Mowery admitted that little time is left for hobbies. “I used to play tennis, but now I just enjoy watching it,” she said through a chuckle. “I splurged on a Labor Day vacation to the U.S. Open in New York. In my off time, I mostly read and spend time with my family. I am married; my wife is a nurse at Duke working in bone marrow transplant. We have no children.”

But the couple does have the patter of little feet in their midst. “We have two small dogs, Heidi and Cassie, a Maltese and a Maltese Shih Tzu mix—both less than 10 lbs.,” Mowery offered. “We live in downtown Durham, N.C., which is a burgeoning area. It’s kind of cool, and a little bit grungy—but in a good way. I love going for walks and checking out new restaurants. And I love food,” she added brightly.

After a brief pause, Mowery turned her thoughts again to patients. “There is one other clinical trial we’ve recently opened in the head and neck space. We are looking at financial toxicity of patients,” she said. “We are very concerned about the bills patients incur for cancer care and how that affects their quality of life.

“Unfortunately, some people just can’t afford to fill their whole prescription. Some take their drugs every other day because they are worried about cost. Some patients just do not follow through on therapy. We need to get a better sense of how much of that is going on and if there are early warning signs we can detect allowing us to intervene.”

Mowery added that better communications between health care providers and patients are needed to help patients better understand costs they face and identify resources that can help them.

“We just opened this survey-based pilot trial in June. We hope to have data next year and be able to develop a follow-up plan to employ the strategies that we find,” said Mowery. “There are a lot of ways we can try to help our patients.”

November, 2018|Oral Cancer News|