radiation

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.

Heading back to the office following head and neck cancer

Source: blogs.biomedcentral.com
Author: Daniel Caley

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

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

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

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

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

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

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

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

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

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

Source: www.eurekalert.org
Author: press release

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

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

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

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

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

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

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

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

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

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

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

Chemotherapy + radiation may improve survival for some elderly

Source: journals.lww.com
Author: Carlson, Robert H., Oncology Times

Because the toxicity of concurrent chemoradiation is greater than radiation therapy alone for definitive head and neck cancer treatment, many clinicians have reservations about offering chemoradiotherapy for elderly head and neck cancer patients.

But a new study shows that combining chemotherapy with radiation therapy improves survival rates for those head and neck cancer patients ages 71 to 79 years who have low comorbidity scores and advanced disease stage, with survival rates similar to that of younger patients.

The study, which used data from the National Cancer Data Base (NCDB), suggests elderly patients are being underrepresented in prospective clinical trials that have defined standards of care for head and neck cancer.

“In the era of improved radiation techniques, improved systemic therapy, and better supportive care, we found that chemoradiotherapy does, in fact, improve survival for a large segment of this population,” said Sana Karam, MD, PhD, Assistant Professor of Radiation Oncology at the University of Colorado School of Medicine in Aurora, and senior author on the study.“

“These findings challenge historical data demonstrating no benefit of chemoradiotherapy for patients older than 70 years,” Karam said.

The study was presented at the 2016 Multidisciplinary Head & Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology (ASTRO) and the American Society of Clinical Oncology (ASCO). First author is Arya Amini, MD, a fourth-year resident in the Department of Radiation Oncology at the University of Colorado School of Medicine.

Before the meeting, Karam discussed the study in an online audio preview for the press.

She said current guidelines for treatment of elderly head and neck cancer are based on trials that are included in the MACH-NC meta-analysis of 16,485 patients in 87 randomized trials (Radiotherapy and Oncology 2009;92:4-14).

While the meta-analysis confirmed a benefit of concomitant chemotherapy in locally-advanced head and neck cancer greater than the benefit with induction chemotherapy, it showed those benefits decreasing with age with no overall survival benefit for patients age 71 and above.

“But only 4 percent of the patients in this meta-analysis were age 71 and above, compared with 9 percent of the 2010 U.S. Census,” Karam pointed out. “The meta-analysis was underpowered, yet it has set our clinical practice guidelines.”

The researchers examined records from the NCDB for patients older than between 1998 and 2011. From 1998-2011, 23 percent of patients in the database were over age 70. Cases for these elderly patients were stratified by whether or not they received chemotherapy concurrent with radiotherapy.

All patients received definitive radiotherapy (66.0-81.6 Gy in 1.2-2.0 Gy fractions). Concurrent chemoradiation was defined as beginning a course of chemotherapy 14 days before or after the start of radiotherapy.

Karam said 68 percent of the patients received radiotherapy alone, and 32 percent received chemoradiotherapy.

Five-Year Survival Improved If Comorbidity Low
The study showed that five-year survival in head and neck cancer patients ages 71 to 79 years was 30.3 percent with concomitant chemotherapy and radiotherapy, versus 15.2 percent for radiotherapy alone.

“Our results showed clearly a significant overall survival benefit with the addition of chemotherapy to radiation therapy,” Karam said.

Chemoradiotherapy was associated with improved survival when patients had comorbidity scores of zero or one, and advanced disease stage.

The researchers also found an overall survival benefit of chemoradiotherapy for patients treated with intensity modulated radiotherapy.

But patients who did not see an overall survival benefit from chemoradiotherapy tended to be ages 79 or older, had a comorbidity score of two or greater, or presented with T-I or T-II disease.

The trend toward worse overall survival for patients with multiple comorbidities was only marginally significant, Karam added.

“These findings may aid clinicians in discussing treatment options with their elderly head and neck cancer patients, and they could guide future prospective trials to confirm the benefit of multimodality treatment in elderly patients, not only for head and neck cancer, but for other cancer sites as well,” Karam said.

Comorbidity, Not Age
In an online audio preview of the meeting for the press, moderator Christine G. Gourin, MD, Associate Professor of Narratology-Head and Neck Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, said, “These data show us that the key factor is not age, but comorbidity. As we age, we collect comorbidities, and that’s what is probably more significant.”

Gourin commented on the MACH-NC meta-analysis, “that we all know is used by our colleagues in Europe to support not using chemotherapy in elderly patients.

She said her own research using the SEER (Surveillance, Epidemiology and End Results) Medicare database found survival results can differ by tumor site—chemoradiation is superior to radiation in oropharyngeal cancer in terms of survival, she said; but in larynx cancer, overall survival is actually worse for chemoradiation.

Those differences were due to late toxicity of treatment, aspiration pneumonia, and dyspepsia.

Karam said her research also found differences between those two tumor sites, but that chemoradiotherapy improved overall survival for both subsets nonetheless.

“There are many differences in the data sets between the NCDB and SEER Medicare databases, including the historic staging analysis. The patient populations are a little different; our reviewers picked up on that when we were submitting the manuscript.”

“Unfortunately, we don’t have a clear cut variable for toxicity, but we did look at time to completion of radiotherapy. We found that patients who got concurrent chemoradiation had a longer time to completion of radiotherapy, suggesting perhaps more treatment breaks.”

“But even after controlling for treatment breaks, we still saw an overall survival advantage regardless of the subset, except for the very elderly and those with multiple comorbidities,” Karam said.

Source:
Oncology Times: 25 April 2016 – Volume 38 – Issue 8 – p 27
doi: 10.1097/01.COT.0000482924.27883.03

April, 2016|Oral Cancer News|