HPV is changing the face of head and neck cancers

Fri, Jun 3, 2016

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Source: www.healio.com
Author: Christine Cona
 

A drastic increase in the number of HPV-associated oropharynx cancers, particularly those of the tonsil and base of tongue, has captured the attention of head and neck oncologists worldwide.

In February, at the Multidisciplinary Head and Neck Cancer Symposium in Chandler, Ariz., Maura Gillison, MD, PhD, professor and Jeg Coughlin Chair of Cancer Research at The Ohio State University in Columbus, presented data that showed that the proportion of all head and neck squamous cell cancers that were of the oropharynx — which are most commonly HPV-positive cancers — increased from 18% in 1973 to 32% in 2005.

9ea467bbf8646a69da2a432f8fcc5452Maura Gillison, MD, PhD, Jeg Coughlin Chair of Cancer Research at The Ohio State University, said screening for HPV in the head and neck is years behind cervical screening for HPV.

 

In addition, studies from the United States, Europe, Denmark and Australia indicate that HPV-positive patients have a more than twofold increased cancer survival than HPV-negative patients, according to Gillison.

With the rising incidence of HPV-related oropharynx cancers, it will soon be the predominant type of cancer in the oral or head and neck region, according to Andy Trotti, MD, director of radiation oncology clinical research, H. Lee Moffitt Cancer Center & Research Institute, in Tampa, Fla.

“We should be focusing on HPV-related oropharyngeal cancer because it will dominate the field of head and neck cancers for many years,” he said during an interview with HemOnc Today. “It is certainly an important population for which to continue to conduct research.”

Because HPV-associated oropharyngeal cancer is emerging as a distinct biological entity, the recent rise in incidence will significantly affect treatment, and prevention and screening techniques, essentially reshaping current clinical practice.

Social change driving incidence

In the analysis performed by Gillison and colleagues, trends demonstrated that change in the rates of head and neck cancers was largely due to birth cohort effects, meaning that one of the greatest determinants of risk was the year in which patients were born.

The increased incidence of HPV-related oropharyngeal squamous cell carcinoma started to occur in birth cohorts born after 1935, indicating that people who were aged in their teens and twenties in the 1960s were demonstrating increased incidence, Gillison said.

“Two important and probably related events happened in the 1960s. In 1964, the surgeon general published a report citing smoking as a risk factor for lung cancer, and public health policy began promoting smoking cessation along with encouragement not to start smoking,” she told HemOnc Today.

If you were 40 years old between 2000 and 2005, your risk for having HPV-related cancer is more than someone who was between the age of 40 and 45 years in 1970, according to Gillison. Social changes that occurred among people born after 1935, for example, a reduction in the number of smokers, is consistent with the increasing proportion of oropharyngeal cancers that were HPV-related.

“The rates for HPV-related cancers began to increase and the rates for HPV-unrelated cancers started to decline, consistent with the known decline in tobacco use in the U.S. population,” she said.

Now, most cases of head and neck squamous cell carcinoma in non-smokers are HPV-related; however, oral HPV infection is common and is a cause of oropharyngeal cancer in both smokers and non-smokers, research shows.

In addition to a decrease in tobacco use reducing HPV-unrelated oral cavity cancers, the number of sexual partners may have increased during this time and have helped to increase HPV-related oropharyngeal cancers, according to Gillison.

Determining the cause of the elevated incidence is only a small piece of the puzzle. Screening, establishing who is at risk, and weighing vaccination and treatment options are all relevant issues that must be addressed.

Screening is problematic

A critical area for examination and research is the issue of screening for oral cancers. In contrast to cervical cancer, there is no accepted screening that has been shown to reduce incidence or death from oropharyngeal cancer, according to Gillison.

Not many studies have examined the issue of screening for HPV-unrelated oral cancers, and the few that have, tend to include design flaws.

Gillison said there is a hope that dentists would examine the oral cavity and palpate the lymph nodes in the neck as a front-line screen for oral cancer; however, in her experience, and from her perspective as a scientist, this has never been shown to provide benefit for oral cancer as a whole.

Another caveat with regard to HPV detection is that head and neck HPV screening is about 20 years behind the cervical field.

“Clinicians screening for HPV in the field of gynecology were incredibly fortunate because Pap smear screening was already an accepted cervical cancer screening method before HPV was even identified,” she said. “There was already a treatment algorithm: If there were cytologic abnormalities, patients were referred to the gynecologist, who in turn did a colposcopy and biopsy.”

A similar infrastructure does not exist for oropharyngeal cancer. People with HPV16 oral infection are at a 15-fold higher risk for oropharynx cancer and a 50-fold increased risk for HPV-positive head and neck cancer, yet there is no algorithm for treatment and management of these at-risk individuals, Gillison said.

In 2007, WHO said there was sufficient evidence to conclude that HPV16 was the cause of oropharynx cancer, but with no clinical algorithm already established, progress in this area is much further behind.

Another problematic aspect of HPV-related oropharyngeal cancer screening is that the site where the cancer arises is not accessible to a brush sampling, according to Gillison.

“To try to find this incredibly small lesion in the submucosal area that you cannot see and cannot get access to with a brush, highlights that we need to develop new techniques, new technologies and new approaches,” she said.

The near future consists of establishing the actual rates of infection in the oral cavity and oropharynx, and then screening for early diagnosis, according to Erich Madison Sturgis, MD, MPH, associate professor in the department of head and neck surgery and the department of epidemiology at The University of Texas M.D. Anderson Cancer Center.

“I am not extremely hopeful because the oropharyngeal anatomy makes screening complicated, and these cancers likely begin in small areas within the tonsils and the base of the tongue,” Sturgis told HemOnc Today. “I am hopeful, however, that preventive vaccines will eventually, at a population level, start to prevent these cancers by helping people avoid initial infection by immunity through vaccination earlier in life.”

Much of the currently known information surrounding the issue of HPV-related oral cancers is new, so researchers continue to conduct research in various relevant areas. One key question to answer is who may be at higher risk for HPV-related oropharynx cancers.

Who is at risk?

As mentioned earlier, the number of oral sex partners seems to play a role in the risk for contracting the HPV virus.

In one study published in The New England Journal of Medicine in 2007, findings demonstrated that a high lifetime number of oral sex partners (at least six partners) was associated with an increased risk for oropharyngeal cancer (OR=3.4; 95% CI, 1.3-8.8).

In addition to a higher number of oral sex partners, other still unknown factors may be contributing to risk. This is an area that needs further research, according to Barbara Burtness, MD, chief of head and neck oncology, and professor of medical oncology at Fox Chase Cancer Center in Philadelphia.

The effect of smoking status is another area that needs further research. According to Burtness, smokers with HPV-associated oropharynx cancer have less favorable outcomes.

When discussing the prognosis of HPV-associated cancers, Sturgis said low risk is defined as low or no tobacco exposure and positive HPV status, and intermediate risk is defined as significant tobacco exposure but an HPV-positive tumor, and the highest risk group appears to be the HPV-negative group.

Although HPV-negative cancers are overwhelmingly tobacco-related cancers and tend to have multiple mutations, it appears that HPV-positive cancers, particularly those in patients with low tobacco and alcohol exposure, tend to lack mutations and to have a better prognosis, and this may ultimately help to guide treatment practices, according to Sturgis. Yet, there is still much to learn about HPV-related oropharyngeal cancers on various fronts.

Vaccination a hopeful ally

In HPV-related head and neck cancer, particularly oropharynx cancers, more than 90% of patients who have an HPV-type DNA identified, have type 16, according to Sturgis.

The two current HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), which are approved for cervical cancers, include HPV types 16 and 18; therefore, in theory, they should be protective against the development of infections in the oropharynx and protective at preventing these HPV-associated cancers from occurring.

The presumption is that if there was a population-wide vaccination against HPV, there would be less person-to-person transmission, and this would lead to fewer oropharynx cancers, according to Burtness, who said this theory still needs further research.

There is excitement at the possibility that therapeutic vaccines could be developed, and various groups are investigating this, Burtness added.

“There is reason to think that the vaccines may be helpful; however, when HPV infects the tonsillar tissues, it exerts control in the host cells by making two proteins: E6 and E7; so another potentially exciting therapeutic avenue would be to target those specific viral proteins,” she told HemOnc Today.

Anxiety about protection from the HPV virus is palpable, according to Sturgis. He described the worry that many patients experience about contracting and transmitting HPV infection.

“Many patients are concerned they will put their spouses and/or children at risk in ways such as kissing them; and we need to tone down those worries until we have better data,” he said.

Screening and vaccination are fundamental aspects of current ongoing research, but of equal importance is determining what clinicians should do to treat a population of patients with HPV-related oropharyngeal cancers.

HPV status may influence treatment

With rates of HPV-related cancers escalating, determining the appropriate treatment for these patients is crucial.

During the past 10 years, findings from retrospective studies have shown that patients with HPV-related cancers have a much better prognosis than patients who test negative for HPV. Findings from several retrospective analyses from clinical trials conducted during the past 2 years have come to the same conclusion, according to Gillison: HPV-positive patients have half the risk for death compared with patients negative for HPV.

Therefore, there may be several alternative treatment options, including the possibility of reducing the dose of radiation given to patients after chemotherapy, thereby reducing toxicity.

Comparing HPV-negative and HPV-positive patients may not be enough to determine proper treatment, researchers said. Data between different cohorts of HPV-positive patients also needs to be examined. Smoking, for example, may play a role in patient outcome.

In a prospective Radiation Therapy Oncology Group clinical trial (RTOG 0129), presented by Gillison at the 2009 ASCO Annual Meeting and recently published in The New England Journal of Medicine (see page 53), researchers conducted a subanalysis of the effect of smoking on outcome in uniformly staged and treated HPV-positive and HPV-negative patients while accounting for a number of potential confounders. HPV-positive patients who were never smokers had a 3-year OS of 93% compared with heavy smoking HPV-negative patients who had an OS of 46%.

The study found that smoking was independently associated with OS and PFS. Patients had a 1% increased risk for death and cancer relapse for each additional pack-year of smoking. This risk was evident in both HPV-positive and HPV-negative patients. Gillison said smoking data must be paid attention to, and she encouraged cooperative group research on the topic.

Most of the findings demonstrate improved outcomes for patients with HPV-positive oropharyngeal cancers vs. patients with HPV-negative oropharyngeal cancers, according to the experts interviewed by HemOnc Today.

Dose de-intensification for less toxicity

To date, there is no evidence that HPV-related cancers should be managed differently than HPV-unrelated cancers, but it is a hot topic among clinicians in the field, according to Burtness.

The superior outcomes for HPV-associated oropharynx cancer have suggested the possibility of treatment de-intensification. The use of effective induction chemotherapy may permit definitive treatment with a lower total radiation dose. In theory, this would reduce the severity of late toxic effects of radiation, such as swallowing dysfunction. Such a trial is being conducted by the Eastern Cooperative Oncology Group. Burtness said this is currently pure research question.

“There is still much research that needs to be done before clinicians can safely reduce the dose of radiation administered to HPV-positive patients,” Burtness said.

Currently, she and colleagues in the ECOG are conducting a study of patients with HPV-associated stage III or IV oropharynx cancers to examine the possibility of tailoring therapy to these patients. Patients are assigned to one of two groups: low-dose intensity-modulated radiotherapy 5 days per week for 5 weeks (27 fractions) plus IV cetuximab (Erbitux, ImClone) once weekly for 6 weeks, or standard-dose intensity-modulated radiotherapy 5 days per week for 6 weeks (33 fractions) plus IV cetuximab once weekly for 7 weeks.

If patients have a very good clinical response to chemotherapy, which is likely to happen with HPV-associated cancers, they are eligible to receive a reduced dose of radiation, and hopefully, they would experience less adverse effects, Burtness said.

“Patients who are treated with the full course of radiation for head and neck cancer are now getting 70 Gy, and they are often left with dry mouth, and speech and swallowing difficulty,” she said. “We are hopeful that if these particular cancers are treatment responsive to chemotherapy, we may be able to spare the patient the last 14 Gy of radiation.”

Immunotherapy a viable treatment

Another possible treatment technique that may benefit patients with HPV-related cancers is immunotherapy. One form of immunotherapy uses lymphocytes collected from the patient, and training the cells in the laboratory to recognize in this case a virus that is associated with a tumor and consequently attack it. This approach potentially may be used to treat HPV-related oropharynx cancers, according to Carlos A. Ramos, MD, assistant professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston.

“With some infections that lead to cancer, even though the virus is present in the tumor cells, the proteins shown to the immune system are limited; therefore, they do not drive a very strong immune response,” Ramos told HemOnc Today. “Training the immune system cells, T lymphocytes, may make them respond better to antigens.”

Data from ongoing trials that are taking T lymphocytes from patients and educating them to recognize antigens in patients with the Epstein-Barr virus associated tumors have shown some activity against them, according to Ramos. This adoptive transfer appears to be safe and may have the same effect on the HPV virus associated tumors. Immunotherapy does not cause the usual toxicities associated with chemotherapy, he said.

“There are currently no trials showing whether we can prevent more recurrences with this approach, but the results of trials examining viruses such as Epstein-Barr are good so far, in both patients who have no evidence of disease and in those who still have disease,” he said.

Even patients with active disease who have not responded to other therapies have responded to this therapy, Ramos said. He and colleagues are working toward compiling preclinical data to study the possibility of using immunotherapy to treat patients with HPV-related cancers.

Journey is just beginning

Much of what is known about risk, screening, prevention and treatment of HPV-related oropharynx cancers is in the early stages of discovery and much is still theoretical, according to Sturgis.

“As far as we can tell, these infections are transmitted sexually; the hope is that as we have better vaccines for prevention of cervical dysplasia, the downstream effect will help prevent other HPV-related cancers, such as anal cancers and penile cancers and oropharyngeal cancers,” he said.

Several recent studies examining new therapies that may reduce the intensity of traditional treatments while maintaining survival rates would have a major effect on the field, according to Sturgis.

Gillison said the rise in the number of cases of HPV-related cancers is changing the patient population considered to be at risk, and more research is vital.

“The most important thing for clinicians to do is be aware that trials are being developed and strongly encourage their patients to participate,” she said.  Christen Cona

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

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Frontline Cancer: vaccines for HPV near guarantee

Thu, May 26, 2016

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Source: www.lajollalight.com
Author: Dr. Scott Lippman

Dear Scott: “Our son, who is 25, went to the GP yesterday and his doc wasn’t sure about giving the Gardasil I had been bugging him to get. Didn’t you tell me about the benefits of the HPV vaccination?”

The note was from a friend. It was personal, but also a topic of wide public interest and one that remains much discussed among cancer researchers and physicians. That’s why I’m answering my friend here.

Roughly 12 percent of all human cancers worldwide — more than 1 million cases per year — are caused by viral infections (called oncoviruses) and attributed to a relatively small number of pathogens: human papilloma virus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Epstein-Barr virus (EBV). Given the emphasis upon other causal factors of cancer, such as genetic mutations or environmental sources, it’s a statistic that’s not well known nor, I would argue, fully appreciated.

Human viral oncogenesis is complex, and only a small percentage of the infected individuals develop cancer, but that 12 percent translates into more than 500,000 lives lost each year to virus-caused malignancies. Many of those deaths are preventable because effective vaccines already exist for HPV and HBV. Right now. No future discoveries required.

I want to specifically talk about the HPV vaccine. Controversy has constrained its proven effectiveness as a public health tool, but if used as prescribed, the HPV vaccine could essentially eliminate cervical and other HPV-caused cancers. Infection with HPV is very common. It’s estimated that at least 80 million Americans are affected. HPV is actually a group of more than 200 related viruses. There is no cure for HPV, but the infection typically clears on its own without lingering effect.

Forty types of HPV are easily spread through direct sexual contact. They fall into two categories: Low-risk HPVs that do not cause cancer, but can cause skin warts on or around the genitals, anus, mouth or throat. And high-risk HPVs (mostly two strains, type 16 and type 18) that cause approximately 5 percent of all human cancers worldwide. High-risk HPV strains drive the rates of cervical (the leading cause of cancer deaths in women in many developing countries), anal and a dramatically increasing subset of oropharyngeal (the tonsil and parts of the throat and tongue) cancers among men in the United States and other developed countries.

The Food and Drug Administration has approved three vaccines for preventing HPV infection: Gardasil, Garadsil-9 and Cervarix. They have strong safety records and a near-guarantee of dramatically reducing the risk of infection. But they are not widely used. The HPV vaccination rate in the U.S. is just 36 percent for girls and 14 percent for boys (and even lower for Hispanics, blacks and the poor).

The chief reason, it has been argued, relates to the recommended age of vaccination: 11-12 years. Because cancer-causing HPV viruses are transmitted through sexual contact, the idea of vaccinating a young girl or boy as a preventive measure strikes many people (i.e. parents) as premature, unsettling or enabling. My friend and colleague, Howard Bailey, M.D., director of the University of Wisconsin Carbone Cancer Center and a national leader on this topic, believes this attitude costs lives. “We need to shift focus from behavior associated with infection to preventing major cancers,” he says.

There are other factors as well. For example, full vaccination requires three doses, so persistence is required. Safety concerns continue about the vaccine (perhaps part of a larger misplaced mistrust of vaccines in general). And there remains limited public understanding of HPV or HPV-related diseases, especially in men.

The reality is that these vaccines work best if they are given at an early age before exposure to HPV. However, as Howard explained, if this window is missed, the FDA includes indications where the recommendation rises to age 26, to get vaccinated for at least some cancer-causing strains of HPV. Howard recommends every young, unvaccinated adult receive at least the 9-valent HPV vaccine, “which can provide protection against five additional HPV types that cause cancer and are less common than types 16 and 18.” There is the potential for protection against HPV types that a person hasn’t yet been exposed to and if a person hasn’t been exposed to the common HPV types (6, 11, 16 and 18), it can provide protection against them as well.

In a recently published statement paper, the American Society of Clinical Oncology called for a broad, concerted effort by health care professionals and policymakers to increase awareness of the evidence and effectiveness of HPV vaccination. It should be routine. The public health benefit is obvious and indisputable. I completely agree.

Here’s a corollary to consider: Vaccines for HBV have been available for many years and are a routine part of pediatric immunizations in the United States. In the past, countries like Taiwan and Korea suffered endemic HBV infections and high rates of hepatocellular carcinoma (HCC) or liver cancer. In the 1980s, these countries implemented universal infant HBV vaccination policies that have resulted in a dramatic 80 percent decline in HBV infections, cases of hepatitis and, more importantly, reductions in HCC incidence and mortality.

Every day, you can read headlines about research to find new treatments and cures for the many diseases called cancer. Progress is painfully slow and uneven. We’ve been fighting this war for decades. Preventing cancer altogether is a better approach and with cancers caused by HPV, we have the right weapon already at hand. We just need to use it.

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Rodeo rider raising awareness of chewing tobacco and oral cancer

Thu, May 19, 2016

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Source: www.krcrtv.com
Author: Danielle Radin

 

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REDDING, Calif. – The Redding Rodeo kicked off Wednesday night with events like barrel racing, cattle roping and mutton busting.

Professional barrel racer, Carly Twisselman said chewing tobacco is prominent at rodeos. She’s teamed up with the Oral Cancer Foundation to try to change that.

“We want to show children that you can follow your dreams, be who you want to be, pursue being a rodeo athlete and not chew tobacco,” said Twisselman.

Twisselman competes in rodeos across the country and sees chewing tobacco time and time again.

She’s teaching children chewing tobacco is not the ‘cool thing to do.’ She also wears letting on her sleeves every race that reads, “Be smart, don’t start.”

She also has a brother who chews and had a health scare from it.

“My brother’s had signs of cancer of the mouth from chewing,” said Twisselman. ”  “I just think that’s the wrong message we should be sending to this children.”

According to the oral cancer foundation, there will be about 48,000 new cases of oral cancer in 2016 in the United States. 75 percent of all oral cancer patients use tobacco.

They estimate nearly 10,000 people in the United States will die from oral cancer in 2016.

 

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In an era of rapidly proliferating, precisely targeted treatments, every cancer case has to be played by ear.

Mon, May 16, 2016

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Source: www.nytimes.com
Author: Sidhartha Mukherjee

 

15oncologist1-superJumbo-v5Illustration by Cristiana Couceiro. Photograph by Ansel Adams, via the National Archives, College Park, Md.

 

The bone-marrow biopsy took about 20 minutes. It was 10 o’clock on an unusually chilly morning in New York in April, and Donna M., a self-possessed 78-year-old woman, had flown in from Chicago to see me in my office at Columbia University Medical Center. She had treated herself to orchestra seats for “The Humans” the night before, and was now waiting in the room as no one should be asked to wait: pants down, spine curled, knees lifted to her chest — a grown woman curled like a fetus. I snapped on sterile gloves while the nurse pulled out a bar cart containing a steel needle the length of an index finger. The rim of Donna’s pelvic bone was numbed with a pulse of anesthetic, and I drove the needle, as gently as I could, into the outer furl of bone. A corkscrew of pain spiraled through her body as the marrow was pulled, and then a few milliliters of red, bone-flecked sludge filled the syringe. It was slightly viscous, halfway between liquid and gel, like the crushed pulp of an overripe strawberry.

I had been treating Donna in collaboration with my colleague Azra Raza for six years. Donna has a preleukemic syndrome called myelodysplastic syndrome, or MDS, which affects the bone marrow and blood. It is a mysterious disease with few known treatments. Human bone marrow is normally a site for the genesis of most of our blood cells — a white-walled nursery for young blood. In MDS, the bone-marrow cells acquire genetic mutations, which force them to grow uncontrollably — but the cells also fail to mature into blood, instead dying in droves. It is a dual curse. In most cancers, the main problem is cells that refuse to stop growing. In Donna’s marrow, this problem is compounded by cells that refuse to grow up.

Though there are commonalities among cancers, of course, every tumor behaves and moves — “thinks,” even — differently. Trying to find a drug that fits Donna’s cancer, Raza and I have administered a gamut of medicines. Throughout all this, Donna has been a formidable patient: perennially resourceful, optimistic and willing to try anything. (Every time I encounter her in the clinic, awaiting her biopsy with her characteristic fortitude, it is the doctor, not the patient, who feels curled and small.) She has moved nomadically from one trial to another, shuttling from city to city, and from one drug to the next, through a landscape more desolate and exhilarating than most of us can imagine; Donna calls it her “serial monogamy” with different medicines. Some of these drugs have worked for weeks, some for months — but the transient responses have given way to inevitable relapses. Donna is getting exhausted.

Her biopsy that morning was thus part routine and part experiment. Minutes after the marrow was drawn into the syringe, a technician rushed the specimen to the lab. There he extracted the cells from the mixture and pipetted them into tiny grain-size wells, 500 cells to a well. To each well — about 1,000 in total — he will add a tiny dab of an individual drug: prednisone, say, to one well, procarbazine to the next and so forth. The experiment will test about 300 medicines (many not even meant for cancer) at three different doses to assess the effects of the drugs on Donna’s cells.

Bathed in a nutrient-rich broth suffused with growth factors, the cells will double and redouble in an incubator over the course of the following two weeks, forming a lush outgrowth of malignant cells — cancer abstracted in a dish. A computer, taught to count and evaluate cells, will then determine whether any of the drugs killed the cancerous cells or forced them to mature into nearly normal blood. Far from relying on data from other trials, or patients, the experiment will test Donna’s own cancer for its reactivity against a panel of medicines. Cells, not bodies, entered this preclinical trial, and the results will guide her future treatment.

I explained all this to Donna. Still, she had a question: What would happen if the drug that appeared to be the most promising proved unsuccessful?

“Then we’ll try the next one,” I told her. “The experiment, hopefully, will yield more than one candidate, and we’ll go down the list.”

“Will the medicine be like chemotherapy?”

“It might, or it might not. The drug that we end up using might be borrowed from some other disease. It might be an anti-inflammatory pill, or an asthma drug. It might be aspirin, for all we know.”

My conversation with Donna reflected how much cancer treatment has changed in the last decade. I grew up as an oncologist in an era of standardized protocols. Cancers were lumped into categories based on their anatomical site of origin (breast cancer, lung cancer, lymphoma, leukemia), and chemotherapy treatment, often a combination of toxic drugs, was dictated by those anatomical classifications. The combinations — Adriamycin, bleomycin, vinblastine and dacarbazine, for instance, to treat Hodgkin’s disease — were rarely changed for individual patients. The prospect of personalizing therapy was frowned upon: The more you departed from the standard, the theory ran, the more likely the patient would end up being undertreated or improperly managed, risking recurrence. In hospitals and clinics, computerized systems were set up to monitor an oncologist’s compliance with standard therapy. If you chose to make an exception for a particular patient, you had to justify the choice with an adequate excuse. Big Chemo was watching you.

I memorized the abbreviated names of combination chemo — the first letter of each drug — for my board exams, and I spouted them back to my patients during my clinic hours. There was something magical and shamanic about the multiletter contractions. They were mantras imbued with promise and peril: A.B.V.D. for Hodgkin’s, C.M.F. for breast cancer, B.E.P. for testicular cancer. The lingo of chemotherapists was like a secret code or handshake; even the capacity to call such baleful poisons by name made me feel powerful. When my patients asked me for statistical data, I had numbers at my fingertips. I could summon the precise chance of survival, the probability of relapse, the chance that the chemo would make them infertile or cause them to lose their hair. I felt omniscient.

Yet as I spoke to Donna that morning, I realized how much that omniscience has begun to wane — unleashing a more experimental or even artisanal approach in oncology. Most cancer patients are still treated with those hoary standardized protocols, still governed by the anatomical lumping of cancer. But for patients like Donna, for whom the usual treatments fail to work, oncologists must use their knowledge, wit and imagination to devise individualized therapies. Increasingly, we are approaching each patient as a unique problem to solve. Toxic, indiscriminate, cell-killing drugs have given way to nimbler, finer-fingered molecules that can activate or deactivate complex pathways in cells, cut off growth factors, accelerate or decelerate the immune response or choke the supply of nutrients and oxygen. More and more, we must come up with ways to use drugs as precision tools to jam cogs and turn off selective switches in particular cancer cells. Trained to follow rules, oncologists are now being asked to reinvent them.

The thought that every individual cancer might require a specific individualized treatment can be profoundly unsettling. Michael Lerner, a writer who worked with cancer patients, once likened the experience of being diagnosed with cancer to being parachuted out of a plane without a map or compass; now it is the oncologist who feels parachuted onto a strange landscape, with no idea which way to go. There are often no previous probabilities, and even fewer certainties. The stakes feel higher, the successes more surprising and the failures more personal. Earlier, I could draw curtain upon curtain of blame around a patient. When she did not respond to chemotherapy, it was her fault: She failed. Now if I cannot find a tool in the growing kit of drugs to target a cancer’s vulnerabilities, the vector feels reversed: It is the doctor who has failed.

Yet the mapless moment that we are now in may also hold more promise for patients than any that has come before — even if we find the known world shifting under our feet. We no longer have to treat cancer only with the blunt response of standard protocols, in which the disease is imagined as a uniform, if faceless, opponent. Instead we are trying to assess the particular personality and temperament of an individual illness, so that we can tailor a response with extreme precision. It’s the idiosyncratic mind of each cancer that we are so desperately trying to capture.

Cancer — and its treatment — once seemed simpler. In December 1969, a group of cancer advocates led by the philanthropist Mary Lasker splashed their demand for a national war on cancer in a full-page ad in The New York Times: “Mr. Nixon: You Can Cure Cancer.” This epitomized the fantasy of a single solution to a single monumental illness. For a while, the centerpiece of that solution was thought to be surgery, radiation and chemotherapy, a strategy colloquially known as “slash and burn.” Using combination chemotherapy, men and women were dragged to the very brink of physiological tolerability but then pulled back just in time to send the cancer, but not its host, careering off the edge.

Throughout the 1980s and 1990s, tens of thousands of people took part in clinical trials, which compared subjects on standard chemo combinations with others administered slightly different combinations of those drugs. Some responded well, but for many others, relapses and recurrences were routine — and gains were small and incremental for most cancers. Few efforts were made to distinguish the patients; instead, when the promised cures for most advanced malignancies failed to appear, the doses were intensified and doubled. In the Margaret Edson play “Wit,” an English professor who had ovarian cancer recalled the bewildering language of those trials by making up nonsensical names for chemotherapy drugs that had been pumped into her body: “I have survived eight treatments of hexamethophosphacil and vinplatin at the full dose, ladies and gentlemen. I have broken the record.”

To be fair, important lessons were garnered from the trials. Using combinations of chemotherapy, we learned to treat particular cancers: aggressive lymphomas and some variants of breast, testicular and colon cancers. But for most men and women with cancer, the clinical achievements were abysmal disappointments. Records were not broken — but patients were.

A breakthrough came in the 2000s, soon after the Human Genome Project, when scientists learned to sequence the genomes of cancer cells. Cancer is, of course, a genetic disease at its core. In cancer cells, mutated genes corrupt the normal physiology of growth and ultimately set loose malignant proliferation. This characteristic sits at the heart of all forms of cancer: Unlike normal cells, cancer cells have forgotten how to stop dividing (or occasionally, have forgotten how to die). But once we could sequence tens of thousands of genes in individual cancer specimens, it became clear that uniqueness dominates. Say two identical-looking breast cancers arise at the same moment in identical twins; are the mutations themselves in the two cancers identical? It’s unlikely: By sequencing the mutations in one twin’s breast cancer, we might find, say, 74 mutated genes (of the roughly 22,000 total genes in humans). In her sister’s, we might find 42 mutations, and if we looked at a third, unrelated woman with breast cancer, we might find 18. Among the three cases, there might be a mere five genes that overlap. The rest are mutations particular to each woman’s cancer.

15oncologists4-master675-v2-1Dr. Azra Raza, left, speaking to Donna M., a patient who travels from Chicago for treatment for myelodysplastic syndromes, in a waiting room at NewYork-Presbyterian/Columbia. Credit Kirsten Luce for The New York Times

 

No other human disease is known to possess this degree of genetic heterogeneity. Adult-onset diabetes, for example, is a complex genetic disease, but it appears to be dominated by variations in only about a dozen genes. Cancer, by contrast, has potentially unlimited variations. Like faces, like fingerprints — like selves — every cancer is characterized by its distinctive marks: a set of individual scars stamped on an individual genome. The iconic illness of the 20th century seems to reflect our culture’s obsession with individuality.

If each individual cancer has an individual combination of gene mutations, perhaps this variability explains the extraordinary divergences in responses to treatment. Gene sequencing allows us to identify the genetic changes that are particular to a given cancer. We can use that information to guide cancer treatment — in effect, matching the treatment to an individual patient’s cancer.

Many of the remarkable successes of cancer treatments of the last decades are instances of drugs that were matched to the singular vulnerabilities of individual cancers. The drug Gleevec, for instance, can kill leukemia cells — but only if the patient’s cancer cells happen to carry a gene mutation called BCR-ABL. Tarceva, a targeted therapy for lung cancer, works powerfully if the patient’s cancer cells happen to possess a particular mutant form of a gene; for lung-cancer patients lacking that mutation, it may be no different from taking a placebo. Because the medicines target mutations or behaviors that are specific to cancer cells (but not normal cells), many of these drugs have surprisingly minimal toxicities — a far cry from combination chemotherapies of the past.

A few days after Donna’s visit to the clinic, I went to my weekly meeting with Raza on the ninth floor of the hospital. The patient that morning was K.C., a 79-year-old woman with blood cancer. Raza has been following her disease — and keeping her alive — for a decade.

“Her tumor is evolving into acute leukemia,” Raza said. This, too, is a distinctive behavior of some cancers that we can now witness using biopsies, CT scans and powerful new techniques like gene sequencing: We can see the cancers morphing from smoldering variants into more aggressive types before our eyes.

“Was the tumor sequenced?” I asked.

“Yes, there’s a sequence,” Raza said, as we leaned toward a screen to examine it. “P53, DNMT3a and Tet2,” she read from the list of mutant genes. “And a deletion in Chromosome 5.” In K.C.’s cancer, an entire segment of the genome had been lopped off and gone missing — one of the crudest mutations that a tumor can acquire.

“How about ATRA?” I asked. We had treated a few patients carrying some of K.C.’s mutations with this drug and noted a few striking responses.

“No. I’d rather try Revlimid, but at a higher dose. She’s responded to it in the past, and the mutations remain the same. I have a hunch that it might work.”

15oncologist3-superJumbo-v4

Cancer by Genes
Researchers have discovered that cancers they once assumed were quite different might be similar genetically, which means a treatment that used to work for only a small group of patients now might help a much larger group. Mutations in the gene E2F3, for example, are found in breast, lung, bladder and prostate cancers, among others. Knowing this, it’s possible to develop similar drugs that target the gene across different cancers.

 

As Raza and I returned to K.C.’s room to inform her of the plan, I couldn’t help thinking that this is what it had come down to: inklings, observations, instincts. Medicine based on premonitions. Chemo by hunch. The discussion might have sounded ad hoc to an outsider, but there was nothing cavalier about it. We parsed these possibilities with utmost seriousness. We studied sequences, considered past responses, a patient’s recent history — and then charged forward with our best guess. Our decisions were spurred by science, yes, but also a sense for the art of medicine.

Oncologists are also practicing this art in areas that rely less on genes and mutations. A week after Donna’s biopsy, I went to see Owen O’Connor, an oncologist who directs Columbia’s lymphoma center. O’Connor, in his 50s, reminds me of an amphibious all-terrain vehicle — capable of navigating across any ground. We sat in his office, with large, sunlit windows overlooking Rockefeller Plaza. For decades, he explained, oncologists had treated relapsed Hodgkin’s lymphoma in a standard manner. “There were limited options,” O’Connor said. “We gave some patients more chemotherapy, with higher doses and more toxic drugs, hoping for a response. For some, we tried to cure the disease using bone-marrow transplantation.” But the failure rate was high: About 30 percent of patients didn’t respond, and half of them died.

Then a year or two ago, he tried something new. He began to use immunological therapy to treat relapsed, refractory Hodgkin’s lymphoma. Immunological therapies come in various forms. There are antibodies: missile-like proteins, made by our own immune systems, that are designed to attack and destroy foreign microbes (antibodies can also be made artificially through genetic engineering, armed with toxins and used as “drugs” to kill cancer cells). And there are drugs that incite a patient’s own immune system to recognize and kill tumor cells, a mode of treatment that lay fallow for decades before being revived. O’Connor used both therapies and found that they worked in patients with Hodgkin’s disease. “We began to see spectacular responses,” he said.

Yet even though many men and women with relapsed Hodgkin’s lymphoma responded to immunological treatments, there were some who remained deeply resistant. “These patients were the hardest to treat,” O’Connor continued. “Their tumors seemed to be unique — a category of their own.”

15oncologists5-master675Dr. Siddhartha Mukherjee, left, speaking to K.C., who has acute myeloid leukemia, at NewYork-Presbyterian/Columbia. Credit Kirsten Luce for The New York Times

 

Lorenzo Falchi, a fellow training with O’Connor and me, was intrigued by these resistant patients. Falchi came to our hospital from Italy, where he specialized in treating leukemias and lymphomas; his particular skill, gleaned from his experience with thousands of patients, is to look for patterns behind seemingly random bits of data. Rooting about in Columbia’s medical databases, Falchi made an astonishing discovery: The men and women who responded most powerfully to the immune-boosting therapies had invariably been pretreated with another drug called azacitidine, rarely used in lymphoma patients. A 35-year-old woman from New York with relapsed lymphoma saw her bulky nodes melt away. She had received azacitidine as part of another trial before moving on to the immunotherapy. A man, with a similar stage of cancer, had not been pretreated. He had only a partial response, and his disease grew back shortly thereafter.

Falchi and O’Connor will use this small “training set” to begin a miniature trial of patients with relapsed Hodgkin’s disease. “We will try it on just two or three patients,” Falchi told me. “We’ll first use azacitidine — intentionally, this time — and then chase it with the immune activators. I suspect that we’ll reproduce the responses that we’ve seen in our retrospective studies.” In lung cancer too, doctors have noted that pretreating patients with azacitidine can make them more responsive to immunological therapy. Falchi and O’Connor are trying to figure out why patients respond if they are pretreated with a drug that seems, at face value, to have nothing to do with the immune system. Perhaps azacitidine makes the cancer cells more recognizably foreign, or perhaps it forces immune cells to become more aggressive hunters.

Falchi and O’Connor are mixing and matching unexpected combinations of medicines based on previous responses — departing from the known world of chemotherapy. Even with the new combination, Falchi suspects, there will be resistant patients, and so he will divide these into subsets, and root through their previous responses, to determine what might make these patients resistant — grinding the data into finer and finer grains until he’s down to individualized therapy for every variant of lymphoma.

Suppose every cancer is, indeed, unique, with its own permutation of genes and vulnerabilities — a sole, idiosyncratic “mind.” It’s obviously absurd to imagine that we’ll find an individual medicine to treat each one: There are 14 million new cases of cancer in the world every year, and several million of those patients will present with advanced disease, requiring more than local or surgical treatment. Trying to individualize treatment for those cases would shatter every ceiling of cost.

15oncologist2-superJumbo-v2Cancer Development
Cancer works the same way all life works, through the process of cell division and mutation. All living things grow and heal through cell division, and all living things evolve and change through the occasional mutations that occur as the cells divide. But some mutations can be deadly, leading to the unchecked growth that defines cancer. More than 14 million Americans have a history of cancer; it is expected to kill 600,000 Americans this year.

 

But while the medical costs of personalized therapy are being debated in national forums in Washington, the patients in my modest waiting room in New York are focused on its personal costs. Insurance will not pay for “off-label” uses of medicines: It isn’t easy to convince an insurance company that you intend to use Lipitor to treat a woman with pre-leukemia — not because she has high cholesterol but because the cancer cells depend on cholesterol metabolism for their growth (in one study of a leukemia subtype, the increasing cells were highly dependent on cholesterol, suggesting that high doses of Lipitor-like drugs might be an effective treatment).

In exceptional cases, doctors can requisition pharmaceutical companies to provide the medicines free — for “compassionate use,” to use the language of the pharma world — but this process is unpredictable and time-consuming. I used to fill out such requests once every few months. Now it seems I ask for such exceptions on a weekly basis. Some are approved. A majority, unfortunately, are denied.

So doctors like Falchi and O’Connor do what they can — using their wiles not just against cancer but against a system that can resist innovation. They create minuscule, original clinical trials involving just 10 or 20 patients, a far cry from the hundred-thousand-patient trials of the ’80s and ’90s. They study these patients with monastic concentration, drawing out a cosmos of precious data from just that small group. Occasionally, a patient may choose to pay for the drugs out of his or her own pockets — but it’s a rare patient who can afford the tens of thousands of dollars that the drugs cost.

But could there be some minimal number of treatments that could be deployed to treat a majority of these cancers effectively and less expensively? More than any other scientist, perhaps, Bert Vogelstein, a cancer geneticist at Johns Hopkins University, has tackled that conundrum. The combination of genetic mutations in any individual cancer is singular, Vogelstein acknowledges. But these genetic mutations can still act through common pathways. Targeting pathways, rather than individual genes, might reorganize the way we perceive and treat cancer.

15oncologists7-master675Deep freezers containing bone marrow, bone-marrow plasma and blood serum in Siddhartha Mukherjee’s research lab. Credit Kirsten Luce for The New York Times

 

Imagine, again, the cell as a complex machine, with thousands of wheels, levers and pulleys organized into systems. The machine malfunctions in the cancer: Some set of levers and pulleys gets jammed or broken, resulting in a cell that continues to divide without control. If we focus on the individual parts that are jammed and snapped, the permutations are seemingly infinite: Every instance of a broken machine seems to have a distinct fingerprint of broken cogs. But if we focus, instead, on systems that malfunction, then the seeming diversity begins to collapse into patterns of unity. Ten components function, say, in an interconnected loop to keep the machine from tipping over on its side. Snap any part of this loop, and the end result is the same: a tipped-over machine. Another 20 components control the machine’s internal thermostat. Break any of these 20 components, and the system overheats. The number of components — 10 and 20 — are deceptive in their complexity, and can have endless permutations. But viewed from afar, only two systems in this machine are affected: stability and temperature.

Cancer, Vogelstein argues, is analogous. Most of the genes that are mutated in cancer also function in loops and circuits — pathways. Superficially, the permutations of genetic flaws might be boundless, but lumped into pathways, the complexity can be organized along the archetypal, core flaws. Perhaps these cancer pathways are like Hollywood movies; at first glance, there seems to be an infinite array of plot lines in an infinite array of settings — gold-rush California, the Upper West Side, a galaxy far, far away. But closer examination yields only a handful of archetypal narratives: boy meets girl, stranger comes to town, son searches for father.

How many such pathways, or systems, operate across a subtype of cancer? Looking at one cancer, pancreatic, and mapping the variations in mutated genes across hundreds of specimens, Vogelstein’s team proposed a staggeringly simple answer: 12. (One such “core pathway,” for instance, involves genes that enable cells to invade other tissues. These genes normally allow cells to migrate through parts of the body — but in cancer, migration becomes distorted into invasion.) If we could find medicines that could target these 12 core pathways, we might be able to attack most pancreatic cancers, despite their genetic diversity. But that means inventing 12 potential ways to block these core paths — an immense creative challenge for scientists, considering that they haven’t yet figured out how to target more than, at best, one or two.

Immunological therapies provide a second solution to the impasse of unlimited diversity. One advantage of deploying a patient’s own immune system against cancer is that immunological cells are generally agnostic to the mutations that cause a particular cancer’s growth. The immune system was designed to spot differences in the superficial features of a diseased or foreign cell, thereby identifying and killing it. It cares as little about genes as an intercontinental ballistic missile cares about the email addresses, or dietary preferences, of the population that it has been sent to destroy.

A few years ago, in writing a history of cancer, I interviewed Emil Freireich. Freireich, working with Emil Frei at the National Cancer Institute in the 1960s and ’70s, stumbled on the idea of deploying multiple toxic drugs simultaneously to treat cancer — combination chemotherapy. They devised one of the first standard protocols — vincristine, Adriamycin, methotrexate and prednisone, known as VAMP — to treat pediatric leukemias. Virtually nothing about the VAMP protocol was individualized (although doses could be reduced if needed). In fact, doctors were discouraged from trying alternatives to the formula.

Yet as Freireich recalled, long before they came up with the idea for a protocol, there were small, brave experiments; before trials, there was trial and error. VAMP was brought into existence through grit, instinct and inspired lunges into the unknown. Vincent T. DeVita Jr., who worked with Freireich in the 1960s, wrote a book, “The Death of Cancer,” with his daughter, Elizabeth DeVita-Raeburn. In it, he recalled a time when the leukemic children in Freireich’s trial were dying of bacterial meningitis during treatment. The deaths threatened the entire trial: If Freireich couldn’t keep the children alive during the therapy, there would be no possibility of remission. They had an antibiotic that could kill the microbe, but the medicine wouldn’t penetrate the blood-brain barrier. So Freireich decided to try something that pushed the bounds of standard practice. He ordered DeVita, his junior, to inject it directly into the spinal cords of his patients. It was an extreme example of off-label use of the drug: The medicine was not meant for use in the cord. DeVita writes:

“The first time Freireich told me to do it, I held up the vial and showed him the label, thinking that he’d possibly missed something. ‘It says right on there, “Do not use intrathecally,” ’ I said. Freireich glowered at me and pointed a long, bony finger in my face. ‘Do it!’ he barked. I did it, though I was terrified. But it worked every time.”

When I asked Freireich about that episode and about what he would change in the current landscape of cancer therapy, he pointed to its extreme cautiousness. “We would never have achieved anything in this atmosphere,” he said. The pioneer of protocols pined for a time before there were any protocols.

Medicine needs standards, of course, otherwise it can ramble into dangerous realms, compromising safety and reliability. But cancer medicine also needs a healthy dose of Freireich: the desire to read between the (guide)lines, to reimagine the outer boundaries, to perform the experiments that become the standards of the future. In January, President Obama introduced an enormous campaign for precision medicine. Cancer is its molten centerpiece: Using huge troves of data, including gene sequences of hundreds of thousands of specimens and experiments performed in laboratories nationwide, the project’s goal is to find individualized medicines for every patient’s cancer. But as we wait for that decades-long project to be completed, oncologists still have to treat patients now. To understand the minds of individual cancers, we are learning to mix and match these two kinds of learning — the standard and the idiosyncratic — in unusual and creative ways. It’s the kind of medicine that so many of us went to medical school to learn, the kind that we’d almost forgotten how to practice.

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

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Troisi: Raising age on tobacco purchases would protect Texas children

Sat, May 14, 2016

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Source: www.mystatesman.com
Author: Catherine Troisi

Tobacco products are a known cancer-causing agent and responsible for one in three cancer deaths. Smoking kills more people than alcohol, AIDS, car crashes, illegal drugs, murders and suicides combined — and thousands more die from smoking-related causes such as fires caused by smoldering cigarettes. E-cigarettes, often touted as a safer alternative, have not been well-studied and may contain unknown poisons.

We are not protecting our children from this danger. Unlike alcohol sales, where you have to be 21 years to purchase legally, adolescents and young adults 18 and over can purchase tobacco products. While the Texas Legislature wisely raised the age to buy e-cigarettes from 14 to 18 years last year, it’s time to look at raising the legal age for all tobacco products to 21.

The problem is not just those age 18 and older smoking. This young legal age to purchase makes it easier for children under age 18 to get access to cigarettes and other products. Each year, 19,000 Texas children under the age of 18 start smoking. In Texas, almost one out of every six high school students smokes — and over their lifetime, half a million Texans who started smoking under age 18 will ultimately die of tobacco-related diseases.

Most of us have someone in our family or know someone who has been affected by a tobacco-related disease. A colleague lost both parents and his only sibling as a result of smoking that began when they were teens. Each relative suffered for over a decade before finally succumbing to the effects of tobacco. His brother was 46 when he was diagnosed with oral cancer. Cancer took his jaw, tongue, teeth and ability to speak clearly and swallow. He suffered for 13 years before it took his life.

There’s also an economic impact. Smoking by children under age 18 costs the state almost $9 billion dollars in direct costs and each Texan household’s federal tax is increased by $756 per year, according to reports from the Campaign for Tobacco-Free Kids. Imagine what we could do with that money both as a state and as individuals rather than use it for tobacco-related medical costs.

The tobacco industry knows that nine out of 10 smokers start before age 18 — and each day 3,200 children smoke their first cigarette. An estimated $636 million is spent on marketing to sell their harmful products just in Texas. Children are twice as sensitive to tobacco advertising as adults and more likely to be influenced to start smoking by these marketing tactics than they are by peer pressure. Tobacco companies have to get children smoking by age 18 — otherwise the odds that they will start are small.

Would raising the legal age to purchase actually stop children from getting these products? The tobacco company Phillip Morris thought so in a 1986 report: “Raising the legal minimum age for cigarette purchaser to 21 could gut our key young adult market (17-20)” The Institute of Medicine agreed in a 2015 report predicting that were the minimum age for the sale of tobacco products 21, over time, the adult smoking rate would decline by about 12 percent and smoking-related deaths would decline by ten percent. The report also states, “Although changes in the minimum age … will pertain to individuals who are 18 and older, the largest proportionate reduction …. will likely occur among adolescents of ages 15 to 17 years.” Research shows that kids often turn to older friends as sources of cigarettes. Raising the sale age to 21 would reduce the likelihood that a high school student will be able to legally purchase tobacco products for other students and underage friends.

The legal age for the purchase of tobacco products is set by states and in some cases counties. Hawaii became the first state to raise the tobacco sale age to 21 and just last week California joined them. At least 135 localities in nine states have also raised the tobacco age to 21.

The U.S. Federal Drug Administration recently announced a “deeming rule,” which extends its authority to cover all tobacco products. However, the rule does not restrict online e-cigarette sales and marketing, including flavors such as “cotton candy” and “gummy bears” designed to entice youth.

As Texans, we want to protect our children and make sure they grow up healthy and safe. Raising the legal age to buy tobacco products to 21 years is a proven strategy to do this. Let’s make it a priority to protect our families and communities — while saving money — by starting this discussion.

Note: Catherine Troisi is an epidemiologist at the UT Health School of Public Health in Houston.

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California Raises Smoking Age To 21

Thu, May 5, 2016

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Source: www.huffingtonpost.com
Author: Huffington Post Staff
 

The law makes it the second state to raise the minimum age to 21, following Hawaii.

 

SAN FRANCISCO, CA - MAY 31:  Isaiah Atkinson smokes a cigarette in front of the San Francisco Centre on May 31, 2011 in San Francisco, California.  Since 1987, the World Health Organization has celebrated "World No Tobacco Day" to raise awareness to the health risks associated with smoking tobacco. Smoking is the second biggest cause of death globally and is responsible for the death of one in ten adults worldwide.  (Photo by Justin Sullivan/Getty Images)

SACRAMENTO, Calif. (Reuters) – California will raise the legal age for purchasing tobacco products to 21 from 18 under a bill signed on Wednesday by Democratic Governor Jerry Brown, part of a package of anti-smoking measures that also regulates electronic cigarettes.

Under five bills signed into law on Wednesday, California will ban the sale of vaping products or tobacco to anyone under the age of 21, imposing a fine of up to $5,000 against companies that violate the law.

“It is long past due for California to update our approach to tobacco,” said Steven Larson, president of the California Medical Association. “There has been an alarming rise in the use of e-cigarettes by teens, putting them at risk for lifelong addiction.”

Under the measures, electronic cigarettes will be regulated like traditional ones. That means that wherever cigarettes are banned, such as in restaurants, workplaces and public areas, use of e-cigarettes will also be prohibited.

The state will also expand its funding for anti-smoking programs under the bills.

Brown stopped short of allowing local counties to impose their own tobacco taxes, noting in his veto message that several proposed new taxes would be placed before voters on the November ballot.

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

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Checkpoint inhibitors seen to show potential of immunotherapy in several cancer studies

Wed, May 4, 2016

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Source: immuno-oncologynews.com
Author: Magdalena Kegel

Several new checkpoint inhibitors — a class of immunotherapy drugs used in cancer — continue to show beneficial effects in numerous cancer types, according to data presented at the recent American Association for Cancer Research Annual Meeting in New Orleans.

Investigated checkpoint inhibitors confirmed earlier results showing evidence of efficacy in melanoma, and also suggested that this class of immunotherapies, which trigger a person’s immune system to attack cancer, might work in patients suffering from certain head and neck cancers.

One of the studies, CheckMate-141, exploring the checkpoint blocker nivolumab (Opdivo) in patients with squamous cell carcinoma of the head and neck, was stopped early after 36 percent of the 361 patients survived for one year — an increase of more than 100 percent compared to patients receiving other treatments.

Squamous cell carcinoma is usually treated with platinum-based chemotherapy, but the effects are often temporary as the cancer tends to return. Moreover, patients who fail to fully recover after chemotherapy are generally resistant to further treatment.

Maura Gillison from Ohio State University, who presented the CheckMate-141 data, said that no effective treatments have been approved for patients with this kind of cancer in over a decade. “I’ve treated head and neck cancers for more than twenty years, and this is the first time I’ve had a drug to go to for patients that have become resistant to first-line treatment,” she said in a press release.

Dr. Emma King, a Cancer Research UK-funded head and neck cancer expert, added that the findings are likely to have a “significant impact” for these cancer patients. “They also reinforce the important shift that we are seeing towards using immunotherapies for cancer treatment.”

“Before nivolumab can be used routinely to treat head and neck cancer in the UK, it will need to approved by the National Institute for Health and Clinical Excellence (NICE),” she added.

Nivolumab was investigated in the CheckMate-069 trial, where its efficiency in advanced melanoma was tested in combination with another checkpoint inhibitor, ipilimumab (Yervoy).

Data presented showed that 60 percent of patients on the combination therapy survived for two years. But the benefit can come with a high price, as severe side effects forced one-third of patients to stop the treatment.

“Both nivolumab and ipilimumab have changed survival expectations in advanced melanoma over the last few years, and these latest data show us that combining these two immunotherapies is an effective two-pronged attack against the cancer,” said Dr. James Larkin, a medical oncologist at the Royal Marsden Hospital.

Yet another study found nivolumab to increase five-year survival in advanced melanoma patients to one-third — again, a doubling compared to what can be achieved by conventional treatment.

Merkel cell carcinoma, a rare skin cancer linked to exposure to a common virus, was also among the cancer types showing benefits from checkpoint inhibitor treatment. Once the cancer spreads, no treatments are effective in holding it back. The checkpoint blocker pembrolizumab (Keytruda) caused tumors to shrink in about half of the 26 patients in the trial.

“The trial also suggests that patients whose Merkel cell carcinoma is linked to a virus may be more likely to benefit from this treatment, which fits with the idea that the more danger signals there are in a cancer, the easier it is for the immune system to recognise it,” said Peter Johnson, Cancer Research UK’s chief clinician.

Early data of checkpoint inhibition in liver and advanced bowel cancer, used in combination with radiofrequency ablation treatment, also showed promising results.

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HPV vaccination rates for boys in Nova Scotia climbing, province says

Wed, May 4, 2016

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Source: www.cbc.ca
Author: Jon Tattrie, CBC News

Nova Scotia has one of the best HPV vaccination rates in the country with boys getting the vaccine at the same rate as girls, the province’s chief public health officer says.

In 2008, Nova Scotia started offering the vaccine to Grade 7 girls to protect against cancer. In 2015, it expanded the program to offer it to boys, too. Strang said he has no official data yet, but frontline reports show boys and girls are getting the vaccine at equal rates.

“We have some of the best coverage rates in the country, if I may brag a little bit. We have 75 to 80 per cent coverage rate for HPV vaccine, which is substantially better than some other provinces,” Strang told Information Morning on Tuesday.

Why boys are less likely to get HPV vaccine
He said evidence shows human papillomavirus (HPV) is a cause of cervical, head and neck cancers, and that vaccination can prevent those cancers.

In Canada, girls between ages nine and 13 can receive a free HPV immunization no matter where they live. Four provinces—Alberta, Nova Scotia, British Columbia and P.E.I.—also offer the vaccine to boys.

The National Advisory Committee on Immunization (NACI), which helps to shape public policy, recommended in 2012 that the HPV vaccine should be provided to boys, just as it is to girls.

It’s a very effective vaccine, Strang said, with studies showing it produces an immune response against the virus. Detecting an impact on the cancer rate will take years, as the first class of vaccinated Nova Scotians age.

“There are some studies now showing already that we’re starting to see some direct impact and decreases in pre-cancerous lesions that can be detected [in] women in their 20s when they start to get regular pap smears,” the doctor said.

Starting a conversation
HPV is spread through sexual activity and Strang said that link has created controversy in other parts of Canada, but not in Nova Scotia.

“We haven’t had any barriers to getting information out from schools to parents. Whether parents are challenged on this at the family level? That may well be an issue for some, but I’m certainly not aware that it’s a major issue that comes out,” he said.

He added that no evidence shows getting the vaccine—or teaching students from the province’s sex guide—impacts sexual activity.

“We’re naïve to think that kids at the Grade 7 age aren’t starting to become sexually active. This is a way we can actually protect them,” he said.

“Maybe in doing that we start a conversation about other ways they need to protect themselves to be healthy while they start to understand about sexuality.”

The Department of Health and Wellness sends vaccine information to schools, which pass it on to parents. Some vaccines are one dose, others are two or three. Two clinics took place in the fall, and the third is happening now.

HPV leads to several cancers
In the absence of vaccination, about 75 per cent of sexually active Canadians will have a sexually transmitted HPV infection in their lifetime, according to NACI.

​Two types of HPV cause 70 per cent of cervical cancer in women, according to the Canadian Cancer Society. In men, the virus is responsible for a high percentage of mouth, nose and throat cancers, as well as some cancers of the penis and anus.

HPV refers to a group of more than 100 types of related viruses, according to the Canadian Cancer Society. It’s the most commonly transmitted sexually transmitted infection.

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Baidu Under Investigation After Cancer Patient’s Death

Tue, May 3, 2016

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Source: www.fortune.com
Author: Scott Cendrowski

 

Baidu, the dominant search engine in China, is being investigated by government regulators after social media users criticized the quality of medical ads appearing in its searches.

Chinese social media over the weekend gave widespread exposure to the story of Wei Zexi, a young cancer patient whose family pooled together more than $30,000 for his treatments at a government hospital he found through a Baidu search. The hospital marketed an innovative treatment for synovial sarcoma, the rare form of cancer Wei suffered from. Following an unsuccessful treatment and Wei’s death in April, reports spread that the treatment was much less effective than the hospital had advertised.

The Cyberspace Administration of China (CAC) sent investigators to Baidu today, according to China’s official Xinhua news agency

Baidu has endured criticism recently for similar instances in which dubious medical practices were promoted in paid search results. Analysts have estimated around one quarter of its revenues come from medical and health-care advertisers.

“We deeply regret the death of Zexi,” a Baidu spokeswoman said today, adding that the search engine had launched its own internal investigation of the matter.

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

 

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Researchers link hepatitis C virus to head and neck cancers

Wed, Apr 27, 2016

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Source: lymphomanewstoday.com
Author: Magdalena Kegel

A study from The University of Texas MD Anderson Cancer Center shows the hepatitis C infection, previously linked to liver cancer and non-Hodgkin’s lymphoma, is associated with cancers of the head and neck — a finding that could have immediate implications in how hepatitis-infected patients are screened, and how head and neck cancer patients are treated.

Hepatitis C affects as many as 1.5 percent of the U.S. population, making it the most common blood-borne disease in the country, with an estimated 3.9 million having the chronic infection. This number skyrockets to a whopping 130 million to 150 million when considering the global population. New antivirals with few side effects have, however, made it possible to cure up to 90 percent of all hepatitis C patients.

The study, “Association Between Hepatitis C Virus and Head and Neck Cancers,” was performed at an MD Anderson clinic focusing on the unmet medical needs of patients with hepatitis C. The clinic opened in 2009, and to date remains the only hepatitis-focused clinic among comprehensive cancer centers in the U.S.

“Obviously, a hepatitis C infection could impact how patients respond to their cancer therapy. We also realized that many of our hepatitis patients were excluded from clinical trials. Now that many with hepatitis C can be cured, it is important that we first address and potentially cure the virus, so that they can have access to necessary cancer therapy,” said senior author Harrys A. Torres, in a press release.

The viral infection has long been known to lead to liver cancer, with a risk 48 times higher in hepatitis patients compared to the general population. It has also been associated with a two to three-fold increased risk for non-Hodgkin’s lymphoma. The connection to head and neck cancers has, until now, not been investigated.

“To our surprise, we saw a number of head and neck cancer patients who tested positive for the hepatitis C virus. With this observation, we began to wonder if there was an undiscovered correlation between the two. Our findings tell us that the association between hepatitis C and oropharyngeal and non-oropharyngeal cancers is as high as its link to non-Hodgkin’s lymphoma,” said Torres, who is also an associate professor of Infectious Disease, Infection Control and Employee Health.

The study, published in the Journal of the National Cancer Institute, retrospectively analyzed data on 34,545 patients who had been tested for hepatitis C between 2004 and 2014. Among them were 409 patients with head and neck cancers – 164 with oropharyngeal and 245 with non-oropharyngeal cancer.

Since head and neck cancers are also related to smoking, the research team used another 694 patients suffering smoking-related cancers as a control group. Only 6.5 percent of patients in this group tested positive for hepatitis C.

Patients with head and neck cancers turned out to be much more likely to have a hepatitis infection – 14 percent in patients with oropharyngeal cancer and 20 percent in patients with non-oropharyngeal cancer — compared to only 6.5 percent in the control group.

Expressing it the other way around — a hepatitis C infection increased the risk of various head and neck cancers between 2 and 4.96 times.

Studies of non-Hodgkin’s lymphoma and liver cancer have shown that treating the viral infection might prevent cancer from developing, and even shrink cancers that have already appeared, as recently reported by Lymphoma News Today.

In fact, the National Comprehensive Cancer Network guidelines now recommend clinicians treat the hepatitis first, a recommendation MD Anderson plans to follow.

“What we are trying to make all understand is that this is an infection that has consequences — and it’s an infection we can cure,” Torres said.

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