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Why Oh Why Is There Phlegm?

Source: www.npr.com
Author:
Wendy Mitman Clarke

Struggling through a nasty round of bronchitis with little better to do than binge watch Netflix and feel epically sorry for myself, I pondered the ageless cold-and-flu-season question: Phlegm. Why?

It begs an answer. The human body is capable of such constant wonder, so much to awe and inspire. And then, phlegm. And not just a little phlegm. Gobs. It’s the only word that really describes the whole phlegm experience.

So I started asking around, and in so doing have learned that there’s a lot more to phlegm than meets the Kleenex.

First, some definitions. Phlegm is really just one form of mucus, which the body produces all over the place to perform useful tasks, says Murray Ramanathan Jr., medical director of otolaryngology head and neck surgery at Johns Hopkins Medicine in Bethesda, Md. And because he suffers from chronic sinusitis himself, he gets the whole mucus thing on a pretty personal level.

“The entire lining of the respiratory tract, which includes the nose all the way to the bottom of the lung, makes mucus,” he says. Phlegm, he says, is limited to mucus made in the lung and in the trachea.

Or as Mark Rosen, a pulmonologist at Mount Sinai in New York and a past president of the American College of Chest Physicians, puts it: “Phlegm is something you cough up, not something you blow out.”

When everything is running smoothly, we produce phlegm and mucus every day — about a liter, Ramanathan says. We usually swallow that daily production without even noticing.

Both mucus and phlegm act as general maintenance and cleaning mechanisms, keeping airways moist and tidy and defending against the host of pollutants, particles, viruses and other things that do not belong in your nose or lungs.

“That’s often what you see when you blow your nose,” says Ramanathan, who studies the role of pollutants and environment in respiratory issues. “In foreign countries where diesel exhaust is a major contributor to air pollution and some people use wood fires indoors for cooking, you actually see black deposition and particles from the air pollution.”

But mucus also has an immunological role in sniffing out trouble. It provides proteins that are antiviral and antibacterial. Receptors on the epithelial cells in the airway sense threats and create bug-fighting enzymes in the mucus, which moves along via the cilia—microscopic hair-like structures that can provide propulsion to help eject the foreign substance.

What we call smoker’s cough, Ramanathan says, “is when the components of cigarette smoke get into the lung and cause mucus [and phlegm] to be produced, because cigarette smoke is an irritant to the respiratory lining in both the nose and the lung.”

This primary defense system can be overwhelmed by viruses, bacteria and the resulting inflammation of the airway. That’s when mucus and phlegm production go into overdrive. And often with the increase in quantity, the quality changes too, becoming thicker to better trap and remove the offending material. Before you know it, you’ve achieved gobs status.

Sometimes phlegm can morph from its usual clear to yellow or green, a byproduct of the white blood cells that have charged in to fight infection. And then we as patients get asked that question — What color is it? — since color can sometimes, although not always, indicate the presence of infection.

As someone who tries to avoid inspection of my own snot or phlegm, I’ve always found this a rather disgusting query. But Ramanathan sees it another way. “As a sinus doctor, one of the worst nightmares you get is when people bring into the office the little Ziploc baggie of, ‘Look what I coughed out yesterday!’ In rare cases, they bring in Tupperware.”

So what to do to survive the phlegm stage, besides stock up on tissues and make sure the iPad is fully charged for the Netflix binge? Antibiotics will only help if you have a bacterial infection, and the average cold, no matter how phlegmy, usually doesn’t qualify.

“Just because your phlegm is green doesn’t mean you need antibiotics,” Rosen says. “Your cold and mine, even if you’re coughing up stuff, is usually viral, and there are no antibiotics for a virus.”

If your phlegm gets too gob-like (technical term), over-the-counter meds like Mucinex can help thin it, which makes it easier to expel, Ramanathan says. For the sinuses, using a Neti pot or decongestants can aid the mucus flow, and bending over a pot of steaming water helps some people with the symptoms, he says. I can revert straight to my childhood with the scent of Vicks VapoRub, doubling the comfort factor. And of course, chicken soup.

Eventually, as the illness subsides and the airway calms down and is no longer irritated (phlegmatic, you could say), the system goes back to producing our regular ration of mucus. Something for which we should be grateful every day.

 

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

February, 2017|Oral Cancer News|

Bill Snyder Addresses Health Situation

Source: http://www.kstatesports.com

MANHATTAN, Kan. – Kansas State head football coach Bill Snyder addressed today reports of his current health, which will not affect his duties leading the Wildcat program.

“I feel bad having to release this information about my health in this manner prior to sharing it in person with so many personal friends, distant family, players and their families, past and present, and many of the Kansas State football family so close to our program,” Snyder said. “But, with so much talk presently out there, I certainly owe it to everyone to make them aware of my condition.

“I have been diagnosed with throat cancer and have been receiving outpatient treatment at the KU Medical Center for about three weeks and am getting along very well. The doctors and staffs at both KU Med and M.D. Anderson (in Houston, Texas) have been great; working so very well together to finalize the overall treatment plan which is being conducted in Kansas City. Both ‘teams’ have projected a positive outcome and have worked out a schedule that allows me to be in Kansas City for my regular treatments and still be back in the office on a regular basis through the first week of March. Sean, along with our coaching and support staffs, remain highly productive in carrying out their responsibilities keeping us on track.

“I greatly appreciate our President, Richard Myers, and Athletic Director, John Currie, for their continued support, and I’m very grateful to those who have responded over the past 24 hours via calls, texts, emails, etc., with such kind thoughts and words. And again, my apology to each of you whom I did not have the opportunity to reach personally before this release.

“As I’ve said so often: we came to Kansas State University because of the people, we stayed because of the people and we came back because of you, the people. Nothing has changed.

“And most importantly, what an amazing personal family I have been blessed with: Sharon, our children: Sean, Shannon, Meredith, Ross and Whitney and their spouses, along with our eight grandchildren and one great grandchild, have been truly special and motivational for me and for each other during this brief setback. Sharon has made great sacrifices to help me through this and the kids are there every day with their love and encouragement. And today that same love and encouragement is coming from our Kansas State, Manhattan and community families.”

According to Snyder’s doctors, his prognosis is excellent. The hall of fame head coach fully expects to be on the field for the start of spring practice in March.

“Coach Snyder, his family, our football staff, student-athletes and athletics department administration have my full support,” said President Myers. “Coach is one of the most determined individuals I have ever met, and I know he will successfully complete this treatment program and be on the field with our student-athletes in no time.”

“Coach Snyder’s health is of the utmost importance, and he has our full support during this time,” Currie said. “We will provide all of the necessary accommodations he and his family need to ensure a smooth treatment process. He will remain our head coach during this treatment period, and we look forward to seeing him on the field this spring and in pursuit of career win No. 203 on September 2.”

K-State opens spring practice March 29 which will conclude with the Purple/White Spring Game on April 22.

 

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

 

February, 2017|Oral Cancer News|

We Have a Vaccine For Six Cancers; Why Are Less Than Half of Kids Getting It?

Author: Electra D. Paskett, Professor of Cancer Research, College of Medicine, The Ohio State University
Source: http://theconversation.com

Early in our careers, few of us imagined a vaccine could one day prevent cancer. Now there is a vaccine that keeps the risk of developing six Human Papillomavirus (HPV)-related cancers at bay, but adoption of it has been slow and surprising low.

Although it’s been available for more than a decade, as of 2014 only 40 percent of girls had received the full three doses of the vaccine, while only 22 percent of boys had received all three. That is far lower than the 87 percent vaccination rates for the Tdap vaccine, which prevents tetanus, diptheria and acellular pertussis. Rates of uptake are low in all population groups.

Some of the reasons include misinformation about the vaccine and why it’s administered to children. Because it is transmitted sexually in almost all cases, many parents assume their children do not need it until they are sexually active. Some believe that giving it will encourage early sexual behavior. Three separate doses on three separate doctor visits place a burden to many working parents. And, of course, there are those few who believe that vaccines are not good for children.

Now, however, with the approval of a two-dose regimen for children under age 15, we have an opportunity to revisit the conversation with providers and parents and reinvigorate efforts to expand HPV vaccination. If successful, we may save tens of thousands of Americans from cancer every year.

A common virus with an uncommon risk

Oncologists and cancer control researchers, including my colleagues at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, regard HPV as the leading cause of many cervical, anal, vaginal, vulvar, penile and oropharynx cancers, or head and neck cancers. In fact, studies are now revealing how HPV damages the genes in our cells and triggers the mutations of cancer.

The U.S. Centers for Disease Control and Prevention (CDC) tracks HPV infections and trends, and the numbers are daunting: 79 million Americans are currently carriers for at least one type of HPV, and about 14 million become newly infected each year. Most infections are benign, and nine of 10 fade within two years. Several strains have been directly linked to cancers, however, inflicting more than 30,000 Americans annually.

HPV is almost universally transmitted through sexual activity, but it can also be transmitted through kissing. For the vaccine to be most effective, immunity must develop well before exposure, which is why it’s important that young people get the vaccine.

The full schedule should be completed at an early age, well before engaging in these risky behaviors. Clinical trials have shown that when administered correctly, the HPV vaccine provides close to 100 percent protection against cervical precancers and genital warts, and over the last decade there has been a 64 percent reduction in the HPV infections the vaccine targets.

The first HPV vaccine, Gardasil, launched with U.S. Food and Drug Administration (FDA) approval in the summer of 2006. Almost immediately it became embroiled in dangerously incorrect assumptions – even more prevalent at that time – about vaccines, and a persistent political debate that confuses the recommended HPV vaccination age (as young as nine) with when young people become sexually active (much later).

Despite those challenges, the publicity surrounding the vaccine helped health care providers raise awareness, and vaccination rates have grown.

The current formulation, Gardasil 9, requires three doses over six months for young people aged 15 to 26. However, the CDC recently recommended Gardasil 9 as being equally effective in two doses for adolescents nine to 14 years old, with the dosages separated by as much as a year. As parents consider HPV vaccine options, the two-dose approach will likely prove more convenient and easier to provide.

Two doses, many lives

Recently, the U.S. National Cancer Institute (NCI)-designated Cancer Centers – 69 world-leading research and treatment facilities distributed across the country – called on Americans to universally endorse the vaccines and follow the CDC’s new two-dose recommendation when appropriate.

The new two-dose push is critical. Any cancer is bad, but many of the cancers caused by HPV are particularly difficult. Head and neck cancers are disfiguring and can cause tremendous problems with swallowing and with speaking. In turn, those problems can render patients unable to eat and can dramatically affect a person’s desire to socialize.

After more than a decade of use, it is clear that HPV vaccines are safe and effective. Providers must talk to parents and patients about the vaccine, understand concerns, and respond with clear information and strong recommendations. Parents and guardians, too, should talk to their health care provider to learn more about the HPV vaccine and its benefits.

There are HPV resources for both patients and physicians, such as a CDC fact sheet for patients and a series of resources for clinicians, but the most impact will come from one-on-one conversations. In trusted communication with patients, providers can emphasize the HPV vaccine’s universal safety – in both clinical trials and widespread global use – and explain why the vaccination must come well before a child is sexually active, not as an adult. Ultimately, as with MMR or the flu shot, this is about a virus, not about sex.

All parents and guardians should have their sons and daughters complete a two-dose 9-valent HPV vaccine series before age 13, or complete a catch-up vaccine series as soon as possible in older children, including three doses in those older than 15. The ideal time is when a child is receiving other childhood vaccines at age 11-12. If this bundling had been done, the HPV vaccination rate would be over 90 percent in this country.

Young men and young women up to age 26 who were not vaccinated as preteens or teens need to complete a three-dose vaccine series to protect themselves against HPV.

As a cancer control researcher, and as a parent of three boys, I have closely followed the arrival of HPV vaccines. There is no room for equivocation – these vaccines exist, they work and if they can prevent my children from developing cancer later in life, I had them vaccinated. During the last century, vaccines helped bring many diseases under control, and eradicated smallpox. There is a vaccine that may help eradicate several cancers in this century – but only if we act.

 

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

February, 2017|Oral Cancer News|

Padres Hall of Famer Randy Jones Battling Throat Cancer

Source: 10news.com
Author:
Mark Saunders
Posted: Jan 26, 2017

SAN DIEGO – Legendary San Diego Padres pitcher Randy Jones is battling throat cancer, the team’s website announced Thursday.

Jones was reportedly diagnosed in November 2016 and has been undergoing radiation and chemotherapy treatments since December at Sharp’s Hospital.

“I feel positive,” Jones said told the Padre’s Bill Center. “They caught it early. It’s all in the throat and not in the lymph nodes. I’m beating this thing.”

Jones said he used chewing tobacco as a player and has smoked cigars throughout his adult life.

“I’ve completed 90 percent of my treatment,” Jones told Center. He added that his physicians have said his cancer is linked to tobacco use. He also said his cancer is low-risk.

Since his playing days he has remained heavily involved with the team. He is a spokesperson for the team and a local radio and television personality.

The Friars drafted Jones in 1972, during the 5th round of the amateur draft.

Jones pitched for the Padres from 1973-1980. He recorded a 3.42 ERA and 735 strikeouts through his career. He was the first Padre to win the National League Cy Young Award and the first Padre to start an All-Star Game.

He was a National League all-star in 1975 and 1976, when he led the NL in ERA in 1975 and led in wins in 1976.

Jones’ number was retired by the team in 1997 and two years later, he was a member of the Padre’s first Hall of Fame class.

 

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

January, 2017|Oral Cancer News|

Cancer patients sometimes can’t get coverage at the hospitals they want

Source: Washington Post

Author: Michelle Andrews

Published: January 15

Getting cancer is scary. Discovering that your health plan doesn’t give you access to leading cancer centers may make the diagnosis even more daunting.

As insurers participating in the health marketplace shrink their provider networks and slash the number of plans that offer out-of-network coverage, some consumers with cancer are learning that their treatment options can sometimes be limited.

One reader wrote to Kaiser Health News last month saying that she was dismayed to learn that none of the plans offered on the New York marketplace provides access to Memorial Sloan Kettering Cancer Center in New York, where she is a patient.

Memorial Sloan Kettering is a well-regarded cancer center that is affiliated with the National Comprehensive Cancer Network and the National Cancer Institute.It participates in New York’s Essential Plan, which is available to lower-income people but not to people enrolling in plans with the familiar categories of bronze, silver, gold and platinum.

NCCN is an alliance of 27 cancer centers whose physicians and researchers develop clinical practice guidelines that are widely respected. The National Cancer Institute’s 69 designated cancer centers, which are recognized for their scientific leadership and research, can offer patients access to cutting-edge treatments and clinical trials.

A 2015 survey found that three-quarters of NCI-designated cancer centers said they participated in at least some exchange plans, and 13 percent said they were included in all exchange plans in their state. Among centers that didn’t participate in any exchanges, many were in states with large numbers of exchange enrollees, including Texas and New York.

Does it matter whether someone with a cancer diagnosis gets treatment at one of these centers rather than at a community hospital or some other site? Research suggests that it may.

A large study published in 2015 found that patients newly diagnosed with several types of cancer — breast, colorectal, lung, pancreatic, gastric and bile duct — were 20 to 50 percent more likely to die of it if they were initially treated somewhere other than at a NCI-designated comprehensive cancer center.

Researchers hypothesize that the cancer centers’ multidisciplinary approach to decision-making, supportive care and access to the latest treatment, among other things, contribute to the superior outcomes, said Julie Wolfson, a pediatric oncologist at the Institute for Cancer Outcomes and Survivorship at the University of Alabama at Birmingham, who co-authored the study.

Often, factors besides a hospital’s survival rates contribute to decisions about where to go for care, said Robert Carlson, NCCN’s chief executive. Those include a patient’s social and support systems and concerns about nonmedical costs such as housing and transportation.

“Most patients, if offered the option to go to a major cancer center, especially if it involves traveling, will decline it,” Carlson said.

Some cancer centers aim to give patients access to a variety of facilities. For example, City of Hope cancer center’s main academic campus is in Duarte, Calif., in Los Angeles County. That’s the best site for patients when their cancers are rare or advanced, when optimal treatment isn’t clear or when they could participate in a clinical trial, said Harlan Levine, the chief executive of the City of Hope Medical Foundation. But the cancer center also owns 14 community cancer clinics around southern California for patients who can be effectively treated in that setting.

City of Hope participates in two plans on California’s exchange, Blue Shield and Anthem, and its physicians are in network for the exchange’s Oscar health plan. But most people don’t check about cancer care when they shop for a plan.

“Cancer is an ‘infrequent purchase’ from a marketing point of view,” Levine said. In many cases, patients don’t realize their lack of access until after their diagnosis, when it may be too late.

Cancer centers may try to aid patients regardless of gaps in coverage. “We understand that each patient has a unique financial situation and we work with our patients, especially those in active treatment, to ensure they receive the care needed and that their treatment is uninterrupted,” said Ruth Landé, senior vice president for patient revenues at Memorial Sloan Kettering.

Patients who believe that it’s critical to be treated at a cancer center that’s not in their insurance network have some recourse.

When people receive a cancer diagnosis, it’s “overwhelming,” said Anna Howard, a principal for policy development at the American Cancer Society’s Cancer Action Network. “You may not be aware of the fact that if your insurance plan says you don’t have coverage at a cancer center, you can file an appeal.”

 

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

January, 2017|Oral Cancer News|

FDA Warns Against So-Called “Cancer Cure”

Source: http://www.curetoday.com/articles/fda-warns-against-socalled-cancer-cure

Published: 01/13/2017

Author: BRIELLE URCIUOLI

The US Food and Drug Administration (FDA) just added another agent, PNC-27, to the growing list of drugs that falsely claim to treat or cure cancer.

An FDA lab recently found the bacteria Variovorax paradoxus in PNC-27, a product that is claiming to treat and cure all cancers, claiming to affect lung cancer as affectively as head and neck cancer. Though no illness or serious adverse events were reported to the FDA, contact with contaminated samples can lead to life-threatening infections, especially in vulnerable populations, such as young children, elderly people, pregnant women and people who have weakened immune systems, according to a statement released by the FDA.

“In general, consumers should be cautious of products marketed and sold online claiming to treat, cure or prevent any disease. Products claiming to treat, cure or prevent disease, but are not proven safe and effective for those purposes not only defraud consumers of money, they can lead to delays in getting proper diagnosis and treatment of a potentially serious condition,” Kristofer Baumgartner, FDA spokesperson, said in an interview with CURE.

PNC-27 is being dosed in multiple ways, such as a nebulized solution, intravenous solution, vaginal suppository or rectal suppository.

The FDA is urging people not to purchase or use PNC-27, which is neither FDA evaluated or approved. Patients should consult with their licensed health care providers before deciding on a treatment plan, and if they have already taken PNC-27, they should see their doctor as soon as possible, and report any adverse events to the FDA’s MedWatch Adverse Event Reporting Program.

As a matter of policy, the FDA cannot discuss any ongoing trials in detail, Baumgartner said. – See more at: http://www.curetoday.com/articles/fda-warns-against-socalled-cancer-cure#sthash.YgMC7JgV.dpuf

 

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

January, 2017|Oral Cancer News|

NCI-Designated Cancer Centers Issue Statement in Support of New CDC Recommendations on HPV Vaccination

Source: The ASCO Post
Posted: 1/11/2017

The 69 National Cancer Institute (NCI)-designated cancer centers have issued a joint statement in support of recently revised recommendations from the Centers for Disease Control and Prevention (CDC) to improve national vaccination rates for human papillomavirus (HPV).

According to the CDC, incidence rates of HPV-associated cancers have continued to rise, with approximately 39,000 new HPV-associated cancers now diagnosed each year in the United States. Although HPV vaccines can prevent the majority of cervical, anal, oropharyngeal, and other genital cancers, vaccination rates remain low across the United States, with just 41.9% of girls and 28.1% of boys completing the recommended vaccine series.

New Recommendations

The new guidelines from the CDC recommend that children under age 15 should receive 2 doses of the 9-valent HPV vaccine at least 6 months apart. Adolescents and young adults older than 14 should continue to complete the 3-dose series.

Research shows there are a number of barriers to overcome to improve vaccination rates, including a lack of strong recommendations from physicians and parents not understanding that this vaccine protects against several types of cancer. In an effort to overcome these barriers, NCI-designated cancer centers have organized a continuing series of national summits to share new research, discuss best practices, and identify collective action toward improving vaccination rates.

The original joint statement, published in January 2016, was the major recommendation from a summit hosted at The University of Texas MD Anderson Cancer in November 2015, which brought together experts from the NCI, CDC, American Cancer Society, and more than half of the NCI-designated cancer centers.

The updated statement is the result of discussions from the most recent summit, hosted this past summer by The Ohio State University Comprehensive Cancer Center. Nearly 150 experts from across the country gathered in Columbus to present research updates and plan future collaborative actions across NCI-designated cancer centers.

 

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

January, 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|

Why the FDA Wants More Control over Some Lab Tests

The FDA finds that many so-called laboratory-derived tests may actually harm patients

By Charles Schmidt | Scientific American December 2016 Issue

Every year in the U.S., doctor’s offices and hospitals order billions of laboratory tests to measure everything from cholesterol levels in the blood to the presence of a gene thought to increase the risk of developing Alzheimer’s disease. Physicians and patients typically assume that they can trust the results of these tests. And most of the time they can. But not all lab tests are equally reliable, and faulty ones can have serious consequences. Sometimes they fail to detect life-threatening conditions. Other times they indicate a problem that does not exist, which can lead to unneeded, perhaps even dangerous treatments.

Through a quirk of regulatory history, many such tests are not subject to the same medical standards as other tools used to identify risk for disease or to definitively diagnose a condition. These are called lab-developed tests, or LDTs, defined as tests that are manufactured and interpreted by the same individual lab that designed them—in contrast to, say, a quick strep test meant to be used and understood by a wide variety of personnel in doctor’s offices everywhere. Most people first encounter an LDT during a checkup when the physician is faced with a diagnostic dilemma that cannot be resolved by widely available blood tests.

The trouble is, experts believe many of these tests are not useful, and some may even cause harm by convincing too many people that they have a rare illness when they do not, diagnosing them with a condition that has so far not been shown to be harmful or reassuring them that they are healthy when in fact there is no scientifically credible way to know if that is indeed the case. “We tend to think of lab tests as being the ultimate truth,” says Ramy Arnaout, an assistant professor of pathology at Harvard Medical School. “But no test is 100 percent accurate, and some of these LDTs aren’t medically useful at all.”

The U.S. Food and Drug Administration is now taking steps to restore confidence in the reliability of lab-developed tests. In 2014 the agency released proposed guidelines that will subject the measures, for the first time, to federal oversight—including having to submit evidence of efficacy to it before the tests may be marketed. Although the FDA would not comment for this story, several industry sources believe the final rulings may begin taking effect soon, much to the chagrin of some lab directors who say that the requirements could boost costs and hinder medical practice.

Widening Loophole

Twenty-five years ago LDTs played too small a role in medical practice for the FDA to pay them much attention. Only a few—most notably Pap smears for the detection of cervical cancer—were widely used. FDA officials adopted a policy of “enforcement discretion,” which meant they pretty much left LDTs alone while they focused on tools with an apparently greater potential for harm, such as malfunctioning pacemakers.

After researchers developed new genetic engineering techniques in the 1990s, however, the possibilities for LDTs expanded dramatically. Whereas previous generations of LDTs looked for a handful of unusual proteins, for example, some of the newly emerging genetic tests could sort through any number of the three billion base pairs, or letters, of the DNA alphabet found in the human genome, looking for abnormalities related to disease. In addition, testing became automated, making LDTs increasingly easier to design and use.

The improved technology led to an enormous rise in the number and variety of LDTs that came to market. By some estimates, about 11,000 labs now offer between 60,000 and 100,000 of them; no one knows precisely how many because, of course, these tests do not have to be registered anywhere.

Under current federal regulations, LDTs enjoy a big loophole, which means they do not have to be evaluated for their medical usefulness. Nor are they required to have research about them made public. The lab that created them does need to meet certain fundamental standards of scientific practice. But the FDA does not vet the tests either before or after doctors can start ordering them for patients, as it does for most prescription drugs or medical devices.

This loophole means that companies ranging from small start-ups offering just one or two tests to much larger diagnostic labs that offer thousands of tests can develop and charge for new LDTs much more easily than they can for most other categories of medical products. With the rise in the number of tests has come a series of reports showing that certain ones have already hurt people by delivering misleading results.

Clinical Validity

The FDA has cited 20 different types of LDTs as especially troubling, including Lyme disease and whooping cough tests that regularly give wrong answers and LDTs that purport to determine a woman’s risk for ovarian cancer such as by measuring the presence of the protein CA 125 in the blood. In September the agency concluded that screening measures for this protein offered “no proven benefit” and warned physicians against recommending or using them.

Many of the tests that have raised the FDA’s ire may indeed measure what they claim to measure. The problem is that the measured substance may not be a good indicator of a specific medical problem. In the case of the ovarian cancer tests, for instance, high levels of CA 125, which is made in the ovaries, should in theory signify the presence of extra ovarian cells—in other words, the presence of a tumor. In reality, it turns out that many women with high levels of CA 125 do not have ovarian cancer, and, conversely, many women with cancer do not have high levels of CA 125. Thus, measures of CA 125 cannot be trusted to give an accurate diagnosis of cancer—and yet a number of women who tested positive apparently feared the possibility of cancer so much that they decided to have their healthy ovaries removed anyway.

One way that investigators determine whether a medical test should be used as a guide to a patient’s condition is by applying a somewhat obscure statistical ratio called a positive predictive value, or PPV. This measure takes into account just how common a condition might be in a given group of people.

Why such a consideration would be important in determining a test’s usefulness may be best understood by analogy. If you drop a baited hook into a barrel full of fish, the chances that a tug on the line means that you have caught a fish are pretty high. On the other hand, dropping the same baited hook into a freshwater lake that has not been stocked with fish makes it much less likely that any given tug on the line represents a fish, as opposed to, say, a tree snag. Because the barrel contains many more fish for a given volume of water than the lake does, a tug in the container has a PPV close to 100 percent, whereas that of a tug in an unstocked lake is much less than 100 percent.

This crucial statistical distinction explains the problem the FDA has with one current ovarian screening test, which its developer claimed had a PPV of 99.3 percent. Closer analysis by independent biostatisticians revealed, however, that the value was calculated on the basis of a single experiment in which half the patients were already known to have ovarian cancer—a highly selected group that is the medical equivalent of a stocked pond.

When the researchers recalculated the PPV using ovarian cancer’s true frequency in the general U.S. population of one case for every 2,500 postmenopausal women, the PPV plummeted to just 6.5 percent. In other words, only one in every 15 patients who received a positive result from this malignancy test would have actually had ovarian cancer. The other 14 would, if they had relied on this test alone, very likely have undergone unnecessary operations to remove their otherwise healthy ovaries because they would have mistakenly believed they had a 99.3 percent chance of having cancer.

Changing Focus

Because the FDA does not have the resources to oversee all the LDTs that have come to market in recent years, the agency plans to divide them into three categories, based on the likelihood that a misleading or incorrect result from a particular test could cause substantial harm. Under the new guidelines, LDTs would be considered high risk if inaccurate results could lead to death or prolonged disabilities. Such tests would come under the greatest inspection, information about them would need to be entered in a national database, and manufacturers would have to prove their safety and efficacy to the FDA before they could be sold. “Basically, the FDA wants to see the supporting evidence before it allows a high-risk LDT to go out on the market,” says Joshua Sharfstein, a physician and professor at the Johns Hopkins Bloomberg School of Public Health.

Even this targeted approach worries many industry leaders and some professional medical societies, including the American Medical Association. “It really depends on how the FDA chooses to define high risk, and that currently isn’t clear,” says Curtis Hanson, chief medical officer at Mayo Medical Laboratories in Rochester, Minn., which conducts 25 million lab tests a year. “High-risk tests could amount to between 1 and 10 percent of LDTs on the market today. How is the FDA going to review and find the rare cases where you have problems and do that in an efficient way that doesn’t slow progress?”

For patients and their physicians, the question is much more basic. Why should they ever have to wonder whether a commercially available medical test does more harm than good?

This article was originally published with the title “When Medical Tests Mislead”

 

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

November, 2016|Oral Cancer News|

We Now Know Exactly How Many DNA Mutations Smoking Causes

Every 50 cigarettes you smoke gives you one extra DNA mutation per lung cell.

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Source: The Verge
Author: James Vincent

A common tactic for people trying to give up smoking is to quantify exactly how much damage — financial or physical — each cigarette or pack of cigarette does. How much does smoking cost you per month, for example, or how much shorter is your life going to be for each drag you take? Well, a new study into the dangers of smoking now lets us measure this damage right down to the number of mutations in your DNA.

A research team led by scientists from Los Alamos National Laboratory compared tissue samples from 1,063 non-smokers and 2,490 smokers, examining each individual’s DNA to look for mutations. They found that for every 50 cigarettes smoked, there is one extra DNA mutation for each cell in the lungs. Over the course of a year, this means that someone who smokes a pack a day (20 cigarettes) has 150 extra mutations per cell in the lung, 97 per larynx cell, 23 per mouth cell, 18 per bladder cell, and six per liver cell.

These changes to the cells aren’t dangerous in themselves, but each one has the potential to turn into a cancerous growth. “Smoking is like playing Russian roulette: the more you play, the higher the chance the mutations will hit the right genes and you will develop cancer,” Ludmil Alexandrov, the co-lead author of the study, told the New Scientist. “However, there will always be people who smoke a lot but the mutations do not hit the right genes.”

The reason for all these extra mutations is found in tobacco smoke — a substance that contains some 7,000 different chemicals, over 70 of which are known to cause cancer. How exactly different types of cell mutations lead to cancer is less clear, and the team from Los Alamos are hoping next to drill down further into this line of research and find out the probabilities that any individual DNA mutation will turn into cancer.

The good news for smokers, though, is that it’s never too late to quit. Although smoking causes regular DNA mutations, as soon as people give up cigarettes, the mutations stop too. One UK study from 2004 found that those who quit smoking at age 30 nearly eliminate the risk of dying prematurely, while those who quit at 50 halve it. For people trying to give up, those are certainly some more comforting odds.

 

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

November, 2016|Oral Cancer News|