immunotherapy

Silent no more: Woman lends voice to hope after cancer

Source: health.ucsd.edu
Author: Yadira Galindo

Singing hymns in church has always brought Cynthia Zamora joy. Today, her once sharp intonation has given way to a raspy voice. But Zamora is thankful that she has a voice at all after spending three months without the ability to utter even one syllable.

“I miss going to church and singing with people,” said Zamora. “Although, if I am in the back I’m still singing. I’m just hoping they don’t hear what sounds like a 13-year-old pubescent boy back there, because that’s how I sound. I know God thinks it’s beautiful, so I don’t worry about it. I just go on with life.”

In 2017, Zamora bit her tongue while sleeping, splitting her tongue nearly in half. She was referred to a specialist when her wound would not heal. They found a 5.4-centimeter tumor that enveloped more than half of her tongue. To save her life, her surgeon, Joseph Califano, MD, delivered grim news: Zamora would have to undergo a glossectomy — the surgical removal of all or part of the tongue.

“By the time I saw her she was really having a hard time speaking and swallowing,” said Califano, director of the Head and Neck Cancer Center at UC San Diego Health. “With Cynthia that was a difficult discussion because it was unclear how much tongue we would save and how good the function would be with the remaining tongue that would be preserved.”

A multidisciplinary team of experts that included medical oncology, surgical oncology, reconstructive surgery, radiation oncology, speech therapy, nutrition, psychiatry and a host of others came together to design a comprehensive plan to eradicate an aggressive, stage IV squamous cell carcinoma and deliver the best quality of life for a woman who was about to undergo a catastrophic surgery.

“The tongue is critical. It’s one of the strongest muscles we have in our body. In speech, our tongue is moving so rapidly within the confines of our mouth in order to generate and make certain sounds in conversation that we find it’s hard to grasp how complex that action is,” said Liza Blumenfeld, speech-language pathologist at Moores Cancer Center at UC San Diego Health. “Without a tongue you’re having to compensate for all of that movement with other structures, your lips, your cheeks and your jaw.”

During a 12-hour surgery, Califano would remove a large portion of Zamora’s tongue and place a breathing tube and feeding tube before a reconstructive microsurgeon would step in to replace the portion of tongue that was removed.

“The primary goal of surgery is to remove the cancer as best we can while sparing as much normal tissue as possible,” said Califano. “It was a challenging surgery in that we had to cut just right to save enough tongue so that she would have some function and we could still get well around the tumor. We were able to save less than half her oral tongue. That wasn’t a lot.”

Ahmed Suliman, MD, a plastic surgeon who specializes in reconstruction after cancer treatment, was tasked with reconstructing her tongue.

“When you remove the majority of the tongue you can’t really function,” said Suliman. “You can’t swallow and articulation is limited. We had to rebuild a tongue to provide bulk so that Cynthia could move food in her mouth in order to swallow and to speak.”

He used a method called anterolateral thigh perforator flap (ALT). Suliman cut a 6 by 8 centimeter tissue of skin and fat from Zamora’s leg to shape and create a new tongue. The replacement tongue does not move, but because Califano was able to spare the base of her original tongue, Suliman was able to reconstruct using the remaining tongue base to preserve some movement for Zamora. Suliman sutured the new tongue, attaching one artery and a vein from the neck using a microscope.

The reconstructive surgery and dissection of cancerous tissue in her tongue and lymph nodes left Zamora temporarily unable to walk, talk or eat. One of the advantages of performing an ALT is that minimal thigh muscle, or none at all, is cut when extracting tissue for the new tongue. This allows for a faster recovery because Zamora did not lose leg muscle function, so with physical therapy Zamora was on her feet fairly quickly.

Skin and fat tissue are more resilient to radiation therapy than muscle, said Suliman, making this tissue more ideal for someone like Zamora, who received treatment following surgery.

“The success of management of these advanced cancers rely on the coordinated efforts of a multi-disciplinary oncologic team,” said Suliman. “This leads to better planned surgery, good preoperative and post-operative care, and follow up. The success of complex cases is higher and outcomes are better, as demonstrated by Cynthia.”

While Zamora was undergoing physical therapy and speech therapy, she was also undergoing chemotherapy, radiation and was receiving an experimental immunotherapy called Pembrolizumab (Keytruda), an antibody that inhibits the abnormal interaction between the molecule PD-1 on immune cells and the molecule PD-L1 on cancer cells, allowing the immune cells to recognize and attack tumors. Pembrolizumab is FDA-approved for some cancers, such as melanoma but is still under a clinical trial for squamous cell carcinoma of the head and neck .

While Zamora continued aggressive treatment and attended physical therapy, she also met with Blumenfeld.

“Teaching somebody to regain their speaking and swallowing abilities during head and neck cancer treatment is really difficult,” said Blumenfeld. “Being able to understand what their abilities were like before, and being able to understand what their new normal looks like, helps us play on their strengths and their ability to compensate with other structures.”

Blumenfeld and Zamora worked together targeting the sounds that she had problems expressing. Zamora had to slow her speech and exaggerate each sound, compensating with her vocal chords for sounds she can no longer make with her tongue.

It is a tedious process but in three months Zamora was speaking well again.

“Previously, I was well pronounced with an expansive vocabulary. I had to be patient with myself and use more expressions in my eyes, hands and face. Sometimes I have to pick words I wouldn’t normally use because I can’t use my original vocabulary. Quality is better than quantity,” said Zamora.

“You have to want to be able to communicate in order to talk, and I wanted that more than anything, because I am a person who loves to communicate. I haven’t got singing down yet, but hopefully that will come.”

Zamora’s vocal chords are healthy and with time, patience and modifying her technique, Blumenfeld thinks that Zamora will be singing “proudly, loudly sometime soon.”

“There are people that come into your life as patients and your mind is blown by their strength of character, their humor, their wisdom, and their willingness to fight. Cynthia really embodies all of those things,” said Blumenfeld. “From the first day she was insistent that she was going to come out of this as a stronger, better person. She has really shown me, even in my own personal life, to never give up and to set your mind on a set target, and you simply do not deviate from that.”

In addition to regaining her speech, Zamora would need to relearn to eat. This was her last hurdle to recovery. It was only in early 2018 that she began to eat without a feeding tube.

“I would encourage everybody to think for a moment of what life would be like. Grab your tongue with your teeth and try to talk without a tongue. Try to think about, when you take a bite of a sandwich, everything that’s going on in your mouth,” said Blumenfeld. “In order for us to be able to chew, we have to be able to manipulate food, move it from one side of our mouth to the other side of the mouth. We have to be able to organize all that food on top of our tongue and propel that food backwards in order to swallow it. Without a tongue that becomes almost an impossible task.”

Thankfully, Zamora mastered the ability to eat again and laughs when recalling eating half a lava cake in front of her shocked family during a restaurant outing. She eats crispy fried chicken and just about anything she wants.

“With a little patience and care, and one step, baby steps, along the way, you can do anything,” said Zamora. “Look at me. I had no tongue, and I’m talking. I’m eating. I’m drinking. I’m doing great. There is life after this surgery. Don’t give up. Keep going. Be strong. Be stubborn. You can do it, you can.”

Praised West Palm attorney fought for many, but is now fighting for his life

Source: www.mypalmbeachpost.com
Author: Daphne Duret – Palm Beach Post Staff Writer

A knock on a door stopped Richard Tendler mid-sentence. His back straightened almost instinctively in his chair, just as it has at the first sign of every verdict. Two decades as a criminal defense attorney in Palm Beach County have taught the 51-year-old West Palm Beach man to never predict how things will go.

“I’ve had cases I thought I won come back guilty,” Tendler had said hours earlier. “Then there were cases I was sure I lost, and the jury would come back not guilty.”

Another certainty: Tendler knew was that he would go home a free man that night, regardless of his client’s fate. This time was different.

Tendler was seated in an examination room at Moffitt Cancer Center in Tampa, where he is one of 10 patients in an exclusive clinical trial for cancer patients whom other doctors have told to prepare to die. Knocking on the door was Dr. Christine Chung, who is treating Tendler and nine others with an immunotherapy regimen as part of a trial that includes 500 patients in the U.S. and around the world.

Chung, the chief of head and neck oncology at Moffitt, was ready to deliver her own verdict — on the results of Tendler’s third six-week cycle. She greeted Tendler’s larger-than-usual entourage that day with polite handshakes and a tight smile.

After the first two cycles, she said, the treatments have cut in half the size of one lesion on Tendler’s lung and slightly shrunk another. A pair of smaller lesions on his liver remained the same size. That much was welcome — though it’s still early in the treatments.

Regardless of whether it’s good or bad news, Tendler has been here before.

By the time he first felt a lump in his throat in December 2015, Tendler was just several months past one of his most high-profile cases. It ended with what was widely considered a great plea deal allowing Boynton Beach mother Heather Hironimus to escape criminal charges for running away with her then-4-year-old son to prevent his father from having him circumcised.

His previous cases ranged from the most tragic to the most bizarre, earning Tendler a reputation as a survivor of the grueling grind of private practice. Among his clients: People involved in deadly car wrecks, a university gunman in the wake of another college shooting, and a teenager charged with killing a goose.

Comforting his mother
Two weeks before Tendler discovered the lump in his throat, he had consoled his mother, Sonia, through a doctor’s tragic prognosis giving her just two months more to live with end-stage pancreatic cancer.

Her sister, his aunt Vera Muller, noticed the lump when he came to visit his mother at her Miami apartment.

“I said, ‘Oh, my God, Richard’ and he said ‘Shhh!’” she said before Tendler’s visit to Moffitt last month, putting her finger to her lips to mimic the gesture her nephew made back then. “He didn’t want his mother to worry.”

Doctors by then had confirmed Tendler’s suspicion. The lump was cancer, brought on by an illness Tendler didn’t know he, too, would soon be diagnosed with.

According to the Centers for Disease Control and Prevention, 79 million Americans had been infected with human papillomavirus, or HPV, as of last year. With 200 strains, most of which carry no symptoms and go away on their own, HPV is the most common sexually transmitted infection in the nation.

The strain Tendler contracted at some point in his life was the rare variety that caused his cancer, his doctors informed him. Although there now exists a vaccine for the virus that is recommended for teenage girls and boys alike, no such prevention existed when Tendler was growing up.

On Jan. 25, 2016, Tendler’s 49th birthday, he underwent a nine-hour surgery to remove the cancer from his throat. He had to be on a feeding tube for a month and recovered at his mother’s Miami apartment, with aunt Vera playing nurse to both her sister and her nephew.

Now 75, and moving to South Florida from Tendler’s native Venezuela, Vera Muller remembers her sister died six weeks into Tendler’s recovery. She was 68.

With his grief still fresh, Tendler then went through a grueling round of radiation and chemotherapy, which required him to live on the feeding tube for another four months.

“It was worse than the surgery,” Tendler remembered. “I couldn’t drink water. I couldn’t even swallow a pill.”

Three months later, Tendler returned to the courthouse much thinner and scarred from his surgery, but cancer-free according to his tests. His doctor reassured him that the worst was behind him.

“He told me ‘I’ve never had one come back,’” Tendler remembers.

His did.

In May 2017, doctors noticed a spot on his chest, and eventually discovered three cancerous lesions on his liver. The cancer had spread, or metastasized, the doctors told him.

Tendler remembers one oncologist telling him he only had months to live. The doctor suggested, matter-of-factly, that he prepare for his death.

“That oncologist talked to me like a piece of dirt,” Tendler said.

He visited several others, and although they were more gentle in their delivery, their news was largely the same. The sentence for the defense attorney was death, they told him, and it would be coming soon.

A doctor offers cautious hope
That summer, Tendler visited Chung at Moffitt. Having immigrated to the United States from Korea with her single mother and two brothers as a child, Chung went to medical school and decided she wanted to be an oncologist.

Tendler and Chung soon learned that, while in different professions, they shared similar views and experiences. Like Tendler’s clients, Chung’s patients are a varied group, including former smokers and people like Tendler, who contracted throat cancer from a rare strain of HPV. The common denominator: They all have a right to treatment.

“None of us is guaranteed good health tomorrow. It is a gift,” Chung said.

Tendler, like most criminal defense attorneys, believes every person accused of a crime, no matter how heinous, is entitled to a fair and just journey through the legal system.

Chung received grants from a pair of foundations that paid off all her medical school loans, a fact she says makes her believe her work is to serve the public. Tendler, who started his career as a public defender, understands.

And with Chung, he found not just an advocate for his life but a doctor who Tendler said was the first to really treat him like a human being. Tendler says her presence in his life tops the list of blessings he makes a habit of thanking God for daily.

Chung told him they would fight the three lesions with CT ablation, a form of targeted radiation that successfully obliterated the three spots. But soon afterward, two more lesions appeared on his liver, and another pair of cancer lesions were now in his lungs.

Chung is clear, both in her conversations with Tendler and in an interview on the day he receives his test results, that there is currently no cure for Tendler’s cancer. She calls the current clinical trial a form of palliative care, meant to reduce the cancer’s severity and alleviate Tendler’s symptoms in hopes of keeping him healthy long enough for researchers to find a cure.

The clinical trial, sponsored by Bristol-Myers Squibb, is a blind study in a treatment that involves immunotherapy, a process that stimulates parts of the patient’s own immune system to fight the cancer.

All patients in the study receive doses of the immunotherapy agent Nivolumab. Two-thirds of the patients also receive a second drug, and the others receive a placebo.

No one — not even Chung — knows which patients are receiving the second agent, a secret she says is vital to the research to see if the two agents together work better than the single Nivolumab treatment alone.

Tendler’s lesions are not as severe as some of her other patients, Chung says, and after two cycles, the results are promising.

Although he is on pain medication, his treatment has been a breeze compared to his radiation, he said. And the fight for his life has brought with it an unanticipated life lesson.

Tendler, who for 20 years poured his life into his work, is learning how to celebrate.

The rise of HPV-related cancers in men

Source: www.tmc.edu
Author: Alexandra Becker

Scott Courville admired his full beard and round belly in the mirror: He was ready for the upcoming holiday season. It was November 2015 and Courville, who plays Santa Claus in Lafayette, Louisiana, was too excited about his favorite time of year to worry much about the pain developing in his jaw.

By February, though, the ache had worsened and was accompanied by new symptoms: white spots on his right tonsil, difficulty swallowing and lumps in his throat. He finally made his way to a walk-in clinic where he was diagnosed with tonsillitis and prescribed antibiotics.

“They sent me home and said, ‘In two weeks everything should clear up,’” Courville recalled.

But his symptoms only worsened. Courville made an appointment with a local ear, nose and throat (ENT) specialist who also diagnosed Courville with tonsillitis. The doctor prescribed more antibiotics and steroids, but two weeks later there were no improvements. Courville was referred to a dentist—“In case they see something we don’t”—but that, too, was a dead end.

Courville’s dentist insisted he return to his ENT, where he ultimately had a CT scan that revealed a mass in his throat. That was June 6, 2016. Two days later, Courville underwent a biopsy. When he awoke from the surgery, his doctor was standing over him.

Courville always gets choked up retelling this part of his story.

“The hardest part for me is always remembering when the doctor said, ‘I’m sorry, but you’ve got cancer.’”

Courville was referred to The University of Texas MD Anderson Cancer Center, where doctors confirmed that he had squamous cell carcinoma of the right tonsil. But there was more: Courville learned that his cancer had been caused by the human papillomavirus—HPV.

11 million men
Courville’s story is becoming increasingly common, with the annual incidence of HPV-related cancers of the throat, tonsils and the base of the tongue in men in the United States now outnumbering cases of cervical cancer in women, according to the U.S. Centers for Disease Control and Prevention (CDC). A 2017 research paper authored by scientists at Baylor College of Medicine and The University of Texas Health Science Center at Houston School of Public Health, among others, found the overall prevalence of oral HPV in men in the U.S. to be upwards of 11 million—much higher than previously believed.

“This has implications, because pretty much everyone is exposed to HPV,” said Andrew Sikora, M.D., Ph.D., one of the authors of the paper and vice chair for research and co-director of the Head and Neck Cancer Program at Baylor College of Medicine. “When we’re talking about the prevalence of oral HPV infection, we’re talking about that infection persisting inside the tonsils or on the base of the tongue of these men, and I think that’s what sets you up for cancer later in life—it may happen decades after you were exposed to HPV.”

That lag time, coupled with an absence of symptoms, is part of the reason HPV-related oropharyngeal cancers, also referred to as head and neck cancers, are increasing.

“What makes this cancer interesting is that it’s one of the only cancers in the body that we’re actually seeing more cases of year over year,” explained Ron J. Karni, M.D., who serves as chief of the division of Head and Neck Surgical Oncology at McGovern Medical School at UTHealth and Memorial Hermann-Texas Medical Center. “In the U.S., we can expect a certain number of breast cancer cases and lung cancer cases every year, but this is actually starting to look a bit like an epidemic in that we are seeing more every year. It’s alarming.”

Holy grail
HPV is the most common sexually transmitted disease in the U.S., with an estimated 79 million individuals infected. According to the CDC, HPV is so common that most people who are sexually active will get the virus at some point in their lives if they do not get the HPV vaccine.

The virus is spread through vaginal, anal and oral sexual activity, and often exhibits no signs or symptoms. In many cases, HPV is cleared by the immune system and does not cause health problems, but it can also persist and show up decades later alongside conditions such as genital warts and cancer—including cervical cancer, anal cancer and oropharyngeal cancers. For reasons not well understood, oropharyngeal cancers predominately affect men.

Currently, there is no annual screening test for men to determine whether they have the virus. Women, on the other hand, are advised to get regular pap smears.

The Papanicolaou test, commonly known as the pap smear, involves collecting cells from inside a woman’s cervix to detect pre-cancerous changes. It is performed during a woman’s annual exam and has been widely credited for detecting early signs of HPV-related cervical cancer and saving countless lives. No such screening test has been successfully developed for oropharyngeal cancer—another reason cited for its steady rise.

“We’re at a huge disadvantage,” said Sikora, who, in addition to his research, treats patients at the Michael E. DeBakey VA Medical Center in Houston. “The pap smear, in terms of global health impact, is probably one of the best, most cost-effective things ever invented in terms of just the sheer number of women who have not had cancers because of it. We have nothing like that for men.”

Sikora explained that anatomy is, in part, to blame. Whereas the cervix is easily sampled, the tonsils are full of “nooks and crannies,” he said, and scientists have yet to develop a reliable technique for obtaining a representative sample of cells inside the throat, tonsils and back of the tongue.

“It’s sort of a holy grail for researchers in the field,” Sikora said. “It would be a game-changer in terms of prevention and early detection of cancer.”

Scientists at MD Anderson, where Courville was treated, may be closing in on some answers. Researchers, including Erich M. Sturgis, M.D., MPH, the Christopher & Susan Damico Chair in Viral Associated Malignancies, are currently conducting a clinical trial for an antibody test that could be used to screen for HPV-related throat cancer.

The HOUSTON study, an acronym for “HPV-related Oropharyngeal and Uncommon Cancers Screening Trial of Men,” is looking to recruit 5,000 men ages 50 to 64 years to provide blood and saliva samples for serologic HPV testing and oral HPV testing, respectively. If a subject is found to have a positive antibody test, he will be asked to participate in a second phase of the study, which includes an intensive screening program run through MD Anderson’s oral pre-cancer clinic.

“A researcher at Arizona State University, Dr. Karen Anderson, developed a serologic test that predicts extremely well the risk for HPV-related oropharyngeal cancer,” Sturgis explained. “We have been able to show that serum antibodies to HPV early proteins, which are rare in the general population, are markers for oropharyngeal cancer. Specifically, we found that those who had antibodies to certain HPV antigens have a greater than 450-fold higher risk of oropharyngeal cancer compared with those who do not have the antibodies.”

The hope is that this study will reveal that serological HPV antibody testing is an effective screening tool for HPV-related cancer in men: the equivalent to a pap smear.

A lump in the neck
If and when HPV-related cancer does develop, men often notice a pain in their jaw or throat, trouble swallowing, change or loss of voice that lasts more than a week or two, a sore spot on the tongue and, most often, a lump in the neck.

“There’s often a very small, primary tumor, which is the tumor that is in the tongue or in the tonsil, and it travels early to the lymph nodes,” Sikora explained. “Depending on what your neck looks like, lymph nodes can get pretty big before they become noticeable. But a lump in the neck is by far the most common symptom, and unfortunately it’s often detected much later than we would like.”

Even more troubling, many individuals who have these symptoms are commonly misdiagnosed and handed antibiotics, as in Courville’s case.

“The most important message I can convey is that if you have a lump in your neck, go see an ear, nose and throat doctor,” Karni said, emphasizing the importance of an informed diagnosis and specialized care.

Treatment for oropharyngeal cancers varies depending on the case and often involves a multidisciplinary team of clinicians, as well as some form of combined modality therapy such as radiation and chemotherapy. In the future, Sturgis sees novel therapies, including immunotherapy options, changing the landscape of treatment protocols.

Karni hopes UTHealth’s dedicated HPV-related throat cancer program will carry patients through the entire arc of treatment by offering minimally invasive robotic surgery for qualifying cases, as well as annual community-wide screening clinics, rehabilitation therapists, and numerous other specialists.

“We want to think about cancer the way Target thinks about shopping or the way the best airlines think about flying,” Karni said. “We designed a program that is patient-centered. We asked, ‘What does the patient need on their fourth week of radiation? What do they need on their third month post-radiation? How can we get that into one clinic space?’ It’s a large team and it’s all centered around this one disease.”

47th in the nation
In 2006, an HPV vaccine named Gardasil hit the market. It was originally intended to prevent HPV in females and, ultimately, HPV-related cervical cancer. But as scientists learned more about HPV—first that males could be carriers and later that it causes cancer in men, as well—public health professionals and clinicians unanimously recommended the vaccine to everyone. The CDC recommends all young women through the age of 26 and all young men through age 21 receive two doses for the vaccine to be effective.

And it is. A recent report published in May by Cochrane, a global independent network of clinical researchers and health care professionals, concluded that the HPV vaccine protects against cervical cancer in young women, especially when they are vaccinated between the ages of 15 and 26.

Which begs the question: Will the vaccine protect young men against the development of oropharyngeal cancers?

“There is a lot more data on cervical cancer in women and the vaccine than there is on head and neck cancer in men and the vaccine, but what data exists suggests that it is going to be a very effective intervention,” Sikora said.

Yet despite scientific evidence that prophylactic HPV vaccination of children and young adults will drastically reduce HPV-related cancers, vaccination rates in the U.S. remain alarmingly low—and Texas ranks 47th. Even more, several generations did not have the vaccine available to them and are currently at risk for HPV-related cancer.

As Karni said, it is alarming.

“Because the median age of oropharynx cancer related to HPV is about 55 and, in some studies, 60, and because the vaccine does not seem to work in individuals who have already been exposed, the benefits of vaccination on HPV-related cancer will not be realized for several decades,” Sturgis said. “Even if we vaccinate 100 percent of our boys and girls tomorrow, we have a whole generation or two who are at risk for this cancer and cannot do anything about it.”

Courville endured six rounds of chemotherapy and 33 daily rounds of radiation to treat his cancer. He lost a year of his life, 100 pounds, his taste buds and salivary glands, and can no longer grow his full beard— but his therapy was successful. He has now made it his life’s mission to inform the public about the importance of the vaccine as well as ongoing advocacy and research surrounding HPV-related cancers.

“If you can educate the public and educate the parents, they will vaccinate their kids,” Courville said. “And if we can vaccinate this generation, we could eliminate these types of cancers.”

The Society for Immunotherapy of Cancer highlights immunotherapy during Oral, Head and Neck Cancer Awareness Week

Source: www.prweb.com
Author: press release

The Society for Immunotherapy of Cancer (SITC) recognizes Oral, Head and Neck Cancer Awareness Week, April 8-15, 2018, in an effort to highlight targeted immunotherapy to treat patients with these types of cancer.

To educate and guide patients, SITC provides informative and engaging online education dedicated to cancer immunotherapy through SITC Cancer Immunotherapy connectED. Two head and neck cancer-specific resources are available on SITC connectED:

Beyond Chemotherapy for Treatment of Head and Neck Cancer: Developed for patients with head and neck cancers and their care partners, the goal of this online class is to learn about treatment options for the newly diagnosed, treatment after chemotherapy, and questions to ask the patient’s healthcare team.

Understanding Cancer Immunotherapy Patient Resource Guide: This guide provides current, medically accurate information on cancer (including head and neck cancers) – intended for patients and caregivers to outline available cancer immunotherapy options, the role of the immune system in this type of cancer treatment and what to expect while undergoing treatment. (free registration required)

Aiming to make cancer immunotherapy a standard of care for cancer patients everywhere, these SITC connectED resources educate and guide patients on immunotherapy treatment options for head and neck cancer. For more information, visit the SITC website at sitcancer.org.

About SITC
Established in 1984, the Society for Immunotherapy of Cancer (SITC) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC aims to one day make the word “cure” a reality for cancer patients everywhere. Learn more about SITC, our educational offerings and other resources at sitcancer.org and follow us on Twitter, LinkedIn, Facebook and YouTube.

April, 2018|Oral Cancer News|

Evolving role of surgery in multidisciplinary care for head and neck cancer

Source: www.onclive.com
Author: Danielle Bucco

Even with the advent of systemic therapeutic advancements to the armamentarium of head and neck cancer, surgery and novel techniques continue to rapidly evolve to effectively treat patients and leave less opportunity for adverse events (AEs).

Additionally, the role of the surgeon has changed to be a more integrative role in patient care.

“We are more precise and more integrated with other therapeutic modalities,” said Joseph A. Califano, MD. “Together, we work as a team and that is the best way that patients can receive their optimal outcomes. We do not just want to cure their cancer but to get back to function and wellness.”

In an interview during the 2017 OncLive State of the Science SummitTM on Head and Neck Squamous Cell Carcinoma, Califano, a professor of surgery at the University of California, San Diego, discussed how surgery factors into modern multidisciplinary care for patients with head and neck cancer.

OncLive: Please provide an overview of your presentation on surgery for patients with head and neck cancer.
Califano: I discussed the fact that the surgery that we do now for head and neck cancers is very different from what used to be done 15 to 20 years ago. Our ability to do effective surgery is good, but now we can do it in a way that leaves patients with excellent function and cosmetic results.

When you see someone walking down the street who has had major head and neck surgery, you wouldn’t know it because we are doing new techniques that are going through natural orifices to do major significant surgeries.

Can you discuss robotic surgery in this space?
Robotic surgery is part of what we do as head and neck surgeons. It is effective in terms of taking care of tumors—particularly in the throat, the tonsils, the back of the tongue, and perhaps even in the nasopharynx. Ordinarily, we cannot get to them unless we have robotic instrumentation. The beauty of robotic surgery in this setting is that we can have patients with excellent function, good swallowing, good voice, and rapid recovery from a significant procedure that was not available 10 years ago.

How do you believe surgeons fit into multidisciplinary care in head
and neck cancer?
Multidisciplinary care is one of the most important things that we practice when we take care of patients with head and neck cancer. It is not just medical professionals who do chemotherapy or radiation surgery; it is a whole host of other people, such as speech pathologists, dentists, dieticians, social workers, nurses, occupational therapists, and physical therapists.

The reason this is so important is that the effects of our therapy combined are good in terms of curing cancers. The AEs need to be treated. We need to get people back to not just curative cancer, but functioning and happy, as well.

What is your message to community oncologists who do not understand the importance of surgery when systemic therapies are available?
Together as a team, we can do much more effective therapy and leave people with much better functions than we could in isolation. The second message is that surgery has rapidly evolved in the past 5 to 10 years. If you are a community oncologist or a community radiation oncologist, you do not realize that we can treat diseases that 10 years ago were treated with radiotherapy alone. We can very effectively treat with surgery alone or in combination with radiation therapy to reduce the AEs. Those AEs are what our patients are going to feel 10 or 15 years down the road.

For example, the risk of stroke after radiotherapy long term is as high as 6% at 12 years. If we can treat people effectively with surgery alone, then we can eliminate that risk of stroke and eliminate some of the long-term effects of other therapies.

What are some big concerns in head and neck cancer and what would you like to see addressed in the next 5 to 10 years?
Some of the newer targeted therapy and immunotherapy approaches are going to blend in well with surgery; it will be one way we can tell whether someone responds to a systemic agent. For example, if a patient receives immunotherapy alone and has a complete response, we can do a minimally invasive surgery to not only make sure that we clear the disease but even to document that there is no disease and spare the patient additional therapy.

The second thing I would say is that we are going to have a host of imaging technologies available. They are just starting to become clinically applicable. We are going to know exactly where the tumor is so that when we do surgery, we can make sure that we get all the cancer [out] most of the time and reduce the need for additional therapy, such as debilitating combination therapy. We can choose who is good for surgery, who is not, and who is better treated with other therapeutic approaches, such as radiation, chemotherapy, immunotherapy, and targeted therapy.

How is surgery an integrated part of the team?
Historically, we are unlike a lot of other surgeries. We follow our patients throughout the rest of their lifetimes and we are an integrated part of the care team. There are other things we can do as surgeons, for example. We can move salivary glands out of the way of radiation for patients with good saliva function to swallow better and have a better quality of life.

We do not think of ourselves as an isolated [group] to take out the cancer, but we are also there to reconstruct, rehabilitate, and help people get on their way to being well.

The head and neck is all about who we are, how we interact socially, and how we feel about ourselves. Social things that we do with other people are eating, talking, and communicating. There are many who now have these functions after head and neck cancer.

December, 2017|Oral Cancer News|

What’s next after creating a cancer-prevention vaccine?

Source: www.scientificamerican.com
Author: Dina Fine Maron

A winner of this year’s Lasker Awards talks about his work with HPV

Imagine a vaccine that protects against more than a half-dozen types of cancer—and has a decade of data and experience behind it.

We have one. It’s the human papillomavirus (HPV) vaccine, and it was approved for the U.S. market back in June 2006. It can prevent almost all cervical cancers and protect against cancers of the mouth, throat and anus. It also combats the sexually transmitted genital warts that some forms of the virus can cause.

On Wednesday, two researchers who completed fundamental work on these vaccines received one of this year’s prestigious Lasker Awards, a group of medical prizes sometimes called the “American Nobels.” Douglas Lowy and John Schiller, whose research provided the basis for the HPV vaccine, were selected alongside a researcher who separately unraveled key aspects of metabolic control of cell growth. Planned Parenthood was also given an award, for its public service. Lowy and Schiller, who both work at the U.S. National Cancer Institute (NCI), received the Lasker for their research on animal and human papillomaviruses—work that enabled the development of a vaccine against HPV-16 type, a form of the virus that fuels many HPV malignancies. The duo’s experiments proved that the vaccine is effective in animals, and they also conducted the first clinical trial of an HPV-16 vaccine in humans. That gave pharmaceutical companies the evidence they needed to invest in their own vaccines designed to protect against multiple kinds of HPV, and ultimately led to the versions administered around the world today.

Yet HPV shots have had a difficult run. Despite overwhelming evidence of their safety and effectiveness, in some developed countries—including the U.S.—HPV inoculations face opposition from individuals and groups that fear the shots are still too new and unproved to use on their children. The HPV vaccine also faces another hurdle beyond other routine pediatric shots: the virus is transmitted via sexual contact—which some parents and communities believe teens should not or will not have, and thus that the shots should not be mandatory. (The U.S. Centers for Disease Control and Prevention [CDC] currently recommends administering two doses of the vaccines to children 11 to 12 years old, administered at least six months apart.)

Scientific American spoke with Schiller, a virologist, about his and Lowy’s award-winning HPV research, their future plans and how to combat anti-vaccine attitudes.

[An edited transcript of the interview follows.]

What’s the biggest hurdle to getting more coverage with the HPV vaccine?
The biggest problem is actually not in the West or most developed countries; it is in the lower- and middle-income countries because of availability there and vaccine prices that limit availability. In those settings vaccine acceptance is actually very high. But those settings present the biggest problem, since some 85 percent of cervical cancers occur in low-resource settings. In the more developed countries there are many different factors involved [in vaccine hesitancy], and they differ by country. In the U.S. it is more about fear of vaccines in general. And there are some issues with HPV vaccines specifically related to this being about a sexually transmitted disease.

So far, more than 270 million doses of HPV vaccines have been distributed worldwide. But in the United States, by 2015 only 28 percent of teen males and 42 percent of teen girls had received the full course of three shots then recommended by the CDC. How can the science community help combat HPV vaccine hesitancy?
There are quite a few studies that show one of the biggest issues is that the vaccine is not being promoted sufficiently by pediatricians and general practitioners. If you look at other vaccines like for meningitis and hepatitis B—which are also administered to adolescents and could be given in the same visit as HPV—they are given at greater rates than HPV. So, there is some disconnect in communication between pediatricians and parents there. Part of the problem here is that the HPV vaccine is a prophylactic vaccine to prevent a disease—cervical cancer—that those providers never see. Obstetrician-gynecologists see it, but pediatricians don’t, which is the opposite of most other childhood or pediatric vaccines. Right now it’s being singled out as something special instead of treated as a routine childhood or adolescent vaccine. But we’ve had this vaccine for 10 years now and it’s not the new kid on the block anymore.

Mounting evidence suggests that among people who feel vaccines are unsafe, any new data showing that they arereally safe does not move the needle to convince them. So, what can be done?
My feeling is that there is a certain percentage of people who, no matter what facts you present to them, they are just not going to be convinced. Quite frankly it doesn’t pay to spend a lot of resources trying to convince that relatively small fraction. What we need to focus on is a much larger fraction of the population who aren’t having their kids vaccinated for reasons like convenience—like it’s a hassle—or they just need a bit more information to make them comfortable. People against all vaccines, those people would not be convinced to get an HPV vaccine so it’s not worth spending a lot of resources on them. I think one of the things that would increase HPV vaccine coverage would be allowing people to get them at their local CVS. I’m not an expert on this, but I have a daughter who as a teen spent much more time at the local CVS than at her local Kaiser clinic. Different states have different laws about which vaccines can and can’t be delivered at pharmacies—but if someone could go get an HPV vaccine at the same place they get their flu vaccine, presumably it would lead to an uptick.

I see you studied molecular biology as an undergrad at the University of Wisconsin–Madison. Did you always want to work on vaccines?
No, absolutely not. When I first started out I was an academic purist and thought you should study knowledge for its own sake. I was fascinated by molecular biology. When I first heard about the way metabolism works in bacteria, plants and humans, that just wowed me because that was a common feature of all life. I just wanted to study that. I thought people who did translational work were sort of selling out to the man—this was in the 1970s. I didn’t get interested in vaccines until much later. Now, I’m very fascinated with translational research.

So, what changed?
It was a very gradual thing. To this day we still do basic research, and it’s still intrinsically valuable to do basic research because you don’t know when it will lead to a transformational breakthrough.

What led you to work on HPV?
When I had just joined the field, suddenly there was this discovery that made papilloma viruses important for human health as opposed to just an understanding of how cells become cancerous. I had joined Doug Lowy’s lab at the National Cancer Institute as a postdoc back in 1983, and the second lecture I went to there was by Harald zur Hausen—who later won the Nobel Prize—and his lecture was saying “eureka! We found a virus that seems to cause 50 percent of cervical cancers”—and that virus turned out to be a human papilloma virus strain, HPV-16. So basically we went from looking at a model about how a normal cell transforms to become carcinogenic to something probably involved in causing human cancer. It was somewhat serendipitous.

What are you working on now?
One thing we are doing at the NCI, and cosponsored by the Bill & Melinda Gates Foundation, is testing if one dose of HPV vaccine is enough to provide long-term protection. It would be transformative, especially in the developing country setting, if you could just have one dose at a younger age. This new trial is going to be done in Costa Rica in collaboration with the Costa Rican government. That’s the site where we had done a prior pilot trial that suggested one dose may be enough.

We are also looking into cancer immunotherapy work. It turns out that these virus-like particles that we work with for the HPV vaccine—these are typically the outer shell of a virus, like from the HPV-16 strain or other animal, or human papilloma virus particles—have a unique ability to infect tumor cells and bind to them specifically. So we are using that knowledge to develop cancer therapies that are broad-spectrum. It turns out these cancers, like melanoma, do bind these particles, specifically.

One other thing we are doing is trying to develop vaccines that would treat herpes simplex infections and HPV infections in the female genital tract. Again, this would take advantage of these virus-like particles’ structures.

Last year I interviewed Michael Sofia, who won a Lasker Award for his hepatitis C vaccine work. The name of that vaccine, sofosbuvir—brand name Sovaldi—is a nod to his last name. But the National Institutes of Health (NIH) do a lot of early-stage research, and then it’s passed off to private companies that develop it further. Your name isn’t part of the HPV vaccines Gardasil or Cervarix, for example. Is it frustrating doing a lot of that behind-the-scenes work?
It’s funny because I would never have thought of that. It would have never entered my mind to name a vaccine after ourselves. We are so used to doing this translational work. My job is to move a project along so it’s interesting enough for a company to invest hundreds of millions of dollars for the benefit of large numbers of people. NIH doesn’t have the money to do phase III trials for lots of drugs, and even if they did it wouldn’t lead to all the drugs we need—because NIH wouldn’t have the money to develop them. This translational and basic research is what NIH does best. That work is way too fraught with failure for companies to do it all. It has to be done in the public sector, and then when things look more promising companies can take it over.

What advice would you offer someone considering becoming a scientist now?

It’s got to be a passion because being a scientist—especially early in your career—is more a lifestyle than occupation. You have to really want to do it, because there is a lot of uncertainty—especially about running your own lab and getting funding. Success and failure can be on a knife’s edge sometimes. The other thing is that you need to be strategic about thinking of what you want to go into, and that’s hard for young people because they don’t have the perspective: There are some fields just opening up ripe for discoveries. And there are some areas that are very mature, that we have been working on for a long time, where there are a lot of scientists working already—so the chances of making a big impact are lower. From my own life, this is like when we started with human papilloma viruses. When I went into this field, we had just been given the tools to study them and so it seemed like a great opportunity to get involved. In some ways it’s best if you can pick an emerging field with new tools to answer big questions. But you have to pick something you are really interested in and go with it.

The other thing I’d say is read a lot. Now with PubMed and access to all these journals there is no excuse for not knowing the background in something that basically has already been done. Young people tend to want to get out and do experiments, but a few days searching PubMed may save someone years of work trying to reinvent the wheel.

Right now, what would you say is the biggest challenge—or one of the biggest challenges—that needs to be solved?
That’s a really tough one. I think as scientists we are all sort of locked into the things we study. I could say cancer, obviously. But Alzheimer’s is something we obviously need to solve. HIV infection. All these different things. One of the things that really needs to be solved in terms of the whole scientific enterprise now is stable funding. Right now we are in a situation where there are too many good scientists—especially young scientists—competing for a limited pot of money. So you lose some good people because there’s not enough money to go around. Also, people are forced to do relatively mundane things that are really a methodological extension of something they’ve done before instead of something truly transformative that would have a large chance of failure. Grant reviewers are looking at something likely to succeed and move the field incrementally, or something transformative that may have a high chance of failure, and have to make those decisions. This is an issue across the sciences. The obvious solution would be to have more funding, but then that raises the question about how to do that. And I’m not a politician.

What, if anything, does this Lasker Award do for your work?
Quite honestly, probably nothing, because one of the nice things about being part of intramural research [at NIH] is that I have stable funding. I’ve had six people in my lab for the last 25 years, so this won’t lead to more grants or me doubling the size of my lab, or anything like that. I’m happy with my moderate-sized lab and collaborations with a lot of great people. That’s why I’m here. Every four years we have a site visit, which is a retrospective review of “what have you done for us lately,” and if it’s reasonable I will continue to get funding. So the award won’t affect my research career much at all.

Right now, some in the scientific community fear amid this political climate that facts matter less than they once did and thus science matters less. What’s your take on that?
Obviously, my perspective is science matters a lot. I really can’t comment on what’s happening in the country overall—and whether this is something that is pervasive where science is really held in less esteem, or it’s that there is a vocal minority being heard a lot now. I would hope it’s the latter.

September, 2017|Oral Cancer News|

Health Beat: Hunting head and neck cancer cells

Source: www.wfmz.com
Author: Melanie Falcon

Leonard Monteith led a healthy lifestyle. That’s why sudden problems with his mouth caught his attention.

“I noticed that when I would stick my tongue out, it would deviate to one side, and I thought that’s not right,” said Monteith, 66.

Doctors found an inch-wide tumor at the base of Monteith’s tongue. He was diagnosed with HPV positive cancer.

“The traditional treatment for head and neck cancer is really toxic and exhaustive and leads to side-effects that are very significant,” said Dr. Nabil Saba, a medical oncologist at Emory University Winship Cancer Institute in Atlanta.

After treatment, Monteith’s cancer went away for six months, but then it came back in his lungs.

Saba is a nationally-known expert in the treatment of head and neck cancers. He thought Monteith would be a good candidate for a new therapy.

“Immunotherapy is really, I think, a complete game changer,” said Saba.

Saba said two separate immunotherapy drugs are showing real promise. A drug called Nivolumab blocks the cancer receptors, allowing the body’s immune system to fight the cancer. Another drug, Pembrolizumab, also works in a similar way.

Because the trials are ongoing, Saba can’t say which specific drug Monteith was on.

“He had very good response to the treatment, to the point where we could not see any more lung lesions on the scan,” Saba said.

Monteith has been improving for three years, but he knows his condition could change without warning.

“I just live my life as I think I would have anyway,” said Monteith.

Doctors say the survival rates for patients who continued on Nivolumab were twice of those who did not take the immunotherapy drug. Twenty percent of the patients on the drug had their tumors shrink.

Research Summary: Hunting head and neck cancer cells (pdf format)

Magnolia man joins exclusive trial in battle against cancer

Source: www.cantonrep.com
Author: Denise Sautters

Rich Bartlett is looking forward to getting back to his hobbies — woodworking and nature watching — and enjoying a good steak and potato dinner. Until then, though, he is in a fight for his life, one he plans to win.

Bartlett is a cancer patient and the first participant in a clinical trial at University Hospitals Seidman Cancer Center in Cleveland to test the safety of an immunotherapy drug — Pembrolizumab — when added to a regimen of surgery, chemotherapy and radiation therapy.

Back to the beginning
Bartlett went to the dentist in October for a checkup.

“He had a sore in his mouth he thought was an abscess,” explained his wife, Nancy Bartlett, who pointed out that, because radiation and chemo treatments cause the inside of the mouth to burn and blister, it is hard for Bartlett to talk.

“When the dentist looked at his sore, he sent Richard to a specialist in Canton, and in early November, he had a biopsy done. It came back positive for cancer.”

From there, he was referred to Dr. Pierre Lavertu, director of head and neck surgery and oncology at University Hospitals, and Dr. Chad Zender from the otolaryngology department, who did Bartlett’s surgery.

“They let us know it was serious,” said Nancy. “It had gone into the bone and the roof of the mouth, but they were not sure if it had gone into the lymph nodes. By the time we got through that appointment, it was the first part of December and (they) scheduled him for surgery on Dec. 22.”

The cancer tripled in size by then and the surgery lasted 10 hours. Doctors had to remove the tumor, all of the lymph nodes and parts of the jaw and the roof of Bartlett’s mouth.

“They harvested skin from his hand to rebuild the inside of his mouth, and took the veins and arteries and reattached everything through his (right) cheek,” she said. “He could not even have water until February because of the patch. He uses a feeding tube to eat now.”

The tube is temporary until Bartlett heals.

Clinical trial
Just before he started chemo and radiation therapies, the hospital called him about the clinical trial.

The trial is the first to use quadra-modality therapy — or four different types of therapy — against the cancer, according to Dr. Min Yao, the principal investigator.

Yao said Bartlett has squamous cell carcinoma of the oral cavity, with only a 50 percent chance of survival.

“Patients have surgery, then followed by six weeks of radiation and chemotherapy and immunotherapy,” Yao said in an email interview. “That is followed by six more months of immunotherapy, one dose every three weeks.”

Bartlett currently is in the radiation, chemotherapy and immunotherapy part of the study.

“It is too early to tell how he is responding,” said Yao. “His tumor has been resected. After the treatment, we will see them periodically with scans. Cancer often recurs in the first two years after treatment.”

Pembrolizumab originally was developed to activate the body’s immune system in the fight against melanoma. Former president Jimmy Carter was treated with the drug for his brain metastases from melanoma in 2015.

A truck driver by trade, Bartlett will undergo daily fluoride treatments for the rest of his life to protect his teeth.

“We did not realize until we got to Cleveland just how bad this was,” said Nancy. “When you have oral cancer, and they are getting ready to do radiation and chemo, you have to go have your teeth cleaned and examined and get anything done that needs to be done because radiation tends to compromise your blood flow in your mouth. That was a step we didn’t know.”

Although he was shocked to hear the outcome of that sore in his mouth, Bartlett is grateful to be a part of the trial.

“Who wouldn’t feel good about something like this? I mean, you got something that was used on Jimmy Carter, who is recovered and is now making public appearances again,” said Bartlett, who is looking forward to June when hopefully he can start eating again and enjoying his hobbies.

“I am very hopeful about this. The whole thing has been a trial. I have a dentist in Cleveland who said I was going to be in the fight of my life, and I am. I am in a huge fight. The chemotherapy is what has knocked me down the most, but I am very positive about the outcome of this.”

March, 2017|Oral Cancer News|

Immunotherapies Form New Frontier in Treating Head and Neck Cancers

Source: OncLive.com

Date: January 2nd, 2017

In August 2016, the FDA approved pembrolizumab (Keytruda) for patients with platinum-refractory squamous cell carcinoma of the head and neck (SCCHN).1 Not only was it the first immunotherapy approved for head and neck cancer (HNC), but it marked the first new drug approval for HNC in the United States in 20 years.

“Now we have an agent that really changes the paradigm—a new class of treatment—and we are seeing amazing benefit in some patients,” said Tanguy Seiwert, MD, during an OncLive Peer Exchange® panel held during the 2016 European Society for Medical Oncology (ESMO) Annual Meeting.

Less than a month later, the menu of immunotherapy options expanded as the FDA approved nivolumab (Opdivo) for the treatment of patients with recurrent or metastatic SCCHN with disease progression on or after a platinum-based therapy.

During the Peer Exchange, the panelists provided an overview of the immunotherapy terrain in HNC, a discussion that was filled with considerable hope and excitement. “When we try immunotherapies in the second-line setting, we see objective responses—sometimes deep, clinically meaningful, extremely durable responses—and we’re beginning to think that maybe, on some occasions, we may be able to cure patients with relapsed metastatic head and neck cancer,” said Kevin Harrington, MD, PhD. This is especially remarkable since such patients have generally had a survival of ≤1 year.

The panelists concurred that the care of patients with HNC will evolve significantly over the next 5 to 10 years, as the tip of the immunotherapy iceberg is just starting to be scratched. During the Peer Exchange, they provided a rationale for using immunotherapies in HNC, including human papillomavirus (HPV)-positive and HPV-negative disease; outlined key immunotherapy studies; and offered their thoughts on the future of immunotherapies in HNC, including use of biomarkers to guide therapy and the opportunity to improve response by using combination treatments.

“Next-generation sequencing efforts are beginning to shed light on the hidden complexities of these tumors, leading to the identification of multiple molecular subtypes,” said Ezra Cohen, MD, who served as moderator for the session. “As key differences between tumors, with and without HPV infection, are beginning to emerge, the challenge is to find ways to use this information to personalize treatment for individual patients.”

Rationale for Immunotherapy in HNC

In patients with locally advanced HNC, HPV status has generally determined outcomes, with HPV-positive patients having a good prognosis and higher likelihood of cure, and HPV-negative patients having a poorer prognosis and a lower likelihood of cure.

However, outcomes with conventional therapy in recurrent metastatic disease have been poor across the board, especially in the setting of platinum- refractory disease, indicating a tremendous unmet need. Before pembrolizumab was approved in this setting, the recommendation was to use a taxane, such as methotrexate or cetuximab (Erbitux), as a single agent, but the outcomes have been unsatisfactory. In contrast, immunotherapy studies have shown promising results in these patients, with HPV-negative patients also benefiting.

“The rationale for [using immunotherapies] for HPV-positive tumors may be the virus, as well as mutations, and for HPV-negative tumors, it’s likely the mutation load,” said Seiwert. He explained that HPV-negative tumors are often smoking-associated tumors and, therefore, have high mutation loads, a factor that has been associated with good response to immunotherapy, whereas HPV-positive tumors resemble melanoma, with significant inflammation, another factor associated with good response.

Although efficacy was found to be the same for HPV-positive and HPV-negative tumors in KEYNOTE-012, which was the study that led to pembrolizumab’s approval for HNC, some CheckMate-141 subanalyses suggest there might be slightly more activity in HPV-positive patients, noted Seiwert.

Despite such findings, he said, “HPV status should not actually dissuade us one way or the other from using immunotherapy—it’s clearly active in both HPV-negative and HPV-positive tumors.” And, as Harrington pointed out earlier in the discussion, since nothing else works well in the second-line setting, “why not try it?”

Key Pembrolizumab Studies

The panelists proceeded to provide an overview of several instrumental pembrolizumab studies, including the KEYNOTE-012 expansion study and KEYNOTE-055 studies, and of the phase III CheckMate-141 study, which paved the way for nivolumab’s approval.2-4 They also discussed a subanalysis of CheckMate-141 presented at ESMO that demonstrated good patient-reported outcomes following nivolumab therapy, lending further support to its use in SCCHN.5

KEYNOTE-012 Expansion Study

The phase Ib KEYNOTE-012 expansion study administered 200 mg of pembrolizumab intravenously once every 3 weeks to 132 patients with recurrent or metastatic SCCHN, irrespective of their programmed death-ligand 1 (PD-L1) or HPV status.2 Primary endpoints included overall response rate (ORR), and safety and secondary endpoints included progression-free survival (PFS), overall survival (OS), and PD-L1 expression’s impact on response.

Pembrolizumab was well tolerated, and yielded a clinically meaningful ORR with evidence of durable responses; median duration of response was not reached. The ORR was 18% by central imaging vendor review and 20% by investigator analysis. A statistically significant increase in ORR was observed for PD-L1–positive versus PD- L1–negative patients (22% vs 4%, respectively; P = .021).

At 6 months, PFS and OS rates were 23% and 59%, respectively. “And we have patients living far beyond what we usually expect for metastatic disease…we now have patients who have completed 2 years of treatment in a setting with a median life expectancy of about 6 months,” revealed Seiwert, who is involved with the study.

Pembrolizumab was also well tolerated. Grade ≥3 events occurred in 9% of patients. “[This is] within the range of toxicities that we have seen in other studies,” said Viktor Grünwald, MD. “Because we’re approaching a very sick and morbid patient population, we might expect different toxicity outcomes, so I think it’s very reassuring that we’re seeing the same amount of toxicity as in other studies,” he explained.

While checkpoint inhibitors are generally well tolerated and have favorable toxicity profiles, the panelists warned that severe side effects can occur and careful patient monitoring is required. A key concern they discussed is pneumonitis.

“Although it only occurs in about 1% to 2% of patients, you must screen for it because it’s life threatening,” said Seiwert. “If somebody says, ‘I am short of breath’ or ‘I have a little bit of a cough,’ I scan them right away to look for it,” he said, explaining that immediate treatment with high-dose steroids is warranted.

KEYNOTE-055 Preliminary Results

KEYNOTE-055 enrolled 172 patients with recurrent or metastatic SCCHN to receive pembrolizumab 200 mg every 3 weeks after progression on platinum plus cetuximab. The preliminary analysis, which reported on 92 evaluable patients, was initially presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.3 Primary endpoints include ORR and safety.

As with KEYNOTE-012, pembrolizumab was found to be well tolerated and to have significant antitumor activity, with 17% to 18% response rates. Evaluation of the full study cohort will include analyses of HPV status and response by anatomic site. “I think that’s the story we’re seeing for pembrolizumab in head and neck cancer—patients are already being treated in single-arm clinical studies, which is somewhat unusual, but reflects the speed of knowledge that we’re gaining that is leading to approvals,” said Grünwald.

Nivolumab also had a lower incidence of treatment-related adverse events (TRAEs) than IC. Any grade TRAEs occurred in 59.3% and 77.5% of patients on nivolumab or IC, respectively. Grade 3/4 TRAEs occurred in 13.6% and 35.1% of patients, respectively, indicating the treatment is well tolerated, which also translated to improvements in quality of life in the patient-reported outcomes study.5

“A very detailed analysis of patient-reported outcomes using 3 well-validated questionnaires showed nivolumab was able to maintain good patient-re- ported outcomes in terms of their quality of life, their functioning, and their symptom scores, whereas IC showed serious detriment in those scores,” said Harrington.

In the study,5 patients treated with nivolumab had delayed worsening of functioning and symptoms compared with IC at approximately 4 months of follow-up, with patients receiving nivolumab reporting longer maintenance of function and less pain, fatigue, and dyspnea on treatment, as compared with those receiving IC.

“So not only do we have clear evidence that these drugs can work in terms of improving survival and delivering meaningful responses, but they do so with fewer episodes of treatment-related toxicity and disease-associated morbidity,” said Harrington.

Future of Immunotherapy in HNC

The panelists noted that use of biomarkers and combination therapies are key areas of future development for HNC. Both areas are already being examined in clinical trials and have relevance across the vast HNC spectrum, from those with minimal disease to those with previously treated advanced disease, potentially offering a curative pathway to more patients.

“It’s fantastic to have drugs that work in second-line relapsed metastatic or first-line metastatic setting, but what I want and what patients want is to be cured at the time they first present with their disease so they never have treatment in relapsed metastatic setting,” said Harrington.

Biomarkers

Although biomarkers such as PD-L1 expression are already being used and can help identify patients who are more likely to respond, high PD-L1 expression does not guarantee response, nor does no or low PD-L1 expression ensure lack of response or lack of durable response.

Subsequently, use of pembrolizumab and nivolumab is without use of this biomarker for patient selection. “While [a PD-L1 assay] can help inform patients of their likelihood to respond, it is not an assay that can select patients,” said Seiwert, who is working to identify novel biomarkers.

“I’ve been involved in looking at a novel biomarker called interferon gamma signature, which can be assayed quite easily with a rapid turn-around, and seems to perform somewhat better than PD-L1 expression,” said Seiwert. “It seems to have a high negative predictive value, and it may eventually allow us to exclude some patients who have no chance of having benefit, but it needs further validation.” He said that other biomarkers are also under investigation, including mutational load, immunogenic mutations, and dynamic biomarkers, but all are still experimental.

“What we really need is a biomarker that would predict progressive disease,” said Grünwald. “To me, that would be much more usable than an assay that just allows us to say to patients ‘your chance of response is 30%.’ I see biomarkers as having the potential to guide development of treatment algorithms,” he said.

Combinations

Currently, PD-L1–targeted agents have seen the greatest development, and studies are starting to suggest that response with these agents can be enhanced when they are combined with other treatments, including chemotherapy, CTLA-4 blockade, and radiotherapy. “About 70% of HNCs have some level of PD-L1 expression—some level of inflammation—but we only see responses in 15% to 18% of patients, so the pool of patients who might benefit from combinations is huge,” said Seiwert.

He noted that the melanoma and lung cancer settings have already shown combining PD-1 inhibitors with chemotherapy or a second checkpoint inhibitor to be particularly promising in the front line, and he suspects one or both combinations will eventually receive approval in these settings and warrant serious investigation for patients with SCCHN.

“Some of our patients do not benefit from a checkpoint inhibitor, and we can’t identify these patients in advance, but giving them chemotherapy might buy us time,” he said. “It’s almost like a pharmacodynamic effect, where we have more time for the immunotherapy to work, and maybe, also make the immune system stronger and expose antigens.”

In the locally advanced setting, animal studies have shown promise combining chemoradiotherapy with immunotherapy, but results of a small study presented at ESMO revealed some dosing challenges in humans.6

In the study, 18 patients with various forms of intermediate- or high-risk SCCHN received ipilimumab, an anti–CTLA-4 antibody, in addition to standard intensity-modulated radiotherapy with cetuximab. Dermatologic immune-related adverse events limited dosing. “There are some safety hints that it may not be a piece of cake getting through radiotherapy, and maybe cetuximab might not be the optimal part now, but I think there is still a lot of promise combining radiochemotherapy with immunotherapy,” said Grünwald. “It could be a future way in how we successfully treat early forms of localized SCCHN.”

Combining checkpoint inhibition with radiation is another intriguing combination, and one that has the potential to act like an in situ vaccination that can lead to abscopal responses (ie, responses at distant sites), noted Harrington, something he has, thus far, only observed rarely with radiation.

“The idea behind combining checkpoint inhibition and radiation is that we could use the confluence of the two different mechanisms to make abscopal responses more predictable and more effective at a distant site, while engendering an immunologically relevant response that allows us to treat macroscopic metastatic disease while also getting rid of micrometastatic disease that could lead to metastatic failure,” he said.

Although immunotherapy combinations are showing promise in SCCHN and other cancers, the panelists warned that they should only be attempted as part of clinical trials. “There are still a lot of question marks about combinations, so they must be done as part of a clinical trial,” said Seiwert. Not only are toxicities and immunosuppressive effects best managed in clinical trials, but trials are essential in advancing these therapies and identifying the next breakthroughs in the field, he said.

 

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

January, 2017|Oral Cancer News|

Blood-borne HPV antibodies indicate head, neck cancer prognosis

Source: medicalxpress.com
Author: provided by Brown University

People with head and neck cancers with evidence of human papillomavirus (HPV) infection generally have a better prognosis than people without evidence of infection. A new study in JAMA Oncology suggests that to produce a strong, reliable prognostic signal, all that’s needed is a blood serum test for two specific HPV antibodies, rather than lab work on a biopsy. Further, the researchers said, the study shows that this blood-based biomarker is predictive of outcome for all types of head and neck cancer.

bloodbornehp

The human papillomavirus causes not only cervical cancer but also cancers of the head and neck. Credit: National Cancer Institute

“What this adds is that it helps us know how best to measure clinically the HPV contribution to this disease,” said study senior author Karl Kelsey, a professor of epidemiology and of pathology and laboratory medicine at Brown University. Kelsey collaborated with lead author Heather Nelson of the University of Minnesota Masonic Cancer Center in making the findings.

Moreover, Nelson, Kelsey and their colleagues wrote, referring to the common HPV16 strain of the virus: “These data are among the first to demonstrate a convincing relationship between HPV16 and improved patient survival for tumors of the larynx and oral cavity.”

Appraising antibodies
The study examined blood serum samples and five-year survival rates among more than 1,000 Boston-area head and neck cancer patients diagnosed between 1999 and 2011. Overall, those who tested positive for antibodies to the oncogenic HPV proteins E6 or E7 were less likely to die during the five year follow-up period after diagnosis compared to those who tested negative for the antibodies. Based on the analysis, the researchers estimated that those with evidence of an immune response to HPV were 25% less likely to die during the course of follow-up compared to those with no immune response to HPV.

The study’s purpose was to determine whether the antibodies provide a reliable indication of prognosis. In ongoing trials, doctors are testing whether patients with HPV-associated cancers can be treated less aggressively—and hopefully with fewer negative side effects—than people with non-HPV-associated cancers, Kelsey said. If trials prove successful, then it will be particularly important to determine whether cancers are HPV-associated.

“The assessment of a patient’s HPV status likely will affect treatment,” he said. “That’s why there’s real interest in getting it right; for instance, how do you test?”

Better prognosis across the board
Prior studies have focused primarily on the role of HPV in the oropharynx—the area of the throat right behind the mouth. An important contribution of the current study, Nelson said, is demonstration that an immune response to HPV is important for all forms of head and neck cancer, although the benefit does show some variance based on the exact cancer location. Those patients with an HPV immune response with tumors located in the oropharynx and larynx had a similar risk of dying during the follow-up period, though the reduced risk was slightly attenuated for those patients with tumors located in the oral cavity.

The results didn’t depend significantly on whether people had high or low levels of the antibodies, so long as they had some, the researchers found, though testing positive for both E6 and E7 was better than for just one.

The reduced chance of dying by five years carried through for people who tested positive for the antibodies even if they consumed tobacco and alcohol. But the worst prognoses in the study were among smokers whose cancers could not be traced to HPV.

In all, the findings controlled for the statistical influences not only of tobacco and alcohol exposure, but also of age, race, gender, education and how far advanced the cancer was.

Relates to broader advances
Kelsey said the findings could help bring head and neck cancer treatment closer into line with two emerging practices of fighting the disease: personalized medicine and immunotherapy.

“To me, personalized medicine really reflects using all the information you can glean about an individual tumor to treat it appropriately,” Kelsey said. “Here HPV is an example of a causal factor that delineates the mechanism of the tumor suppressor genes that drive the tumor and that gives you insight into the differences in the tumor.”

Meanwhile, the study might help shed light on why immunotherapy—in which the body’s immune system is marshaled to attack cancer—appears to help for some head and neck cancers, Kelsey said. It may not be coincidence, for instance, that the prognosis is better among people whose cancers are associated with a virus that promotes a robust immune response, in the form of antibodies, than among people without a viral cause for their cancer.

If HPV-related cancers can indeed be treated differently, Kelsey said, then serum-based testing to determine the role of the virus could soon be available, too.

December, 2016|Oral Cancer News|