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  • HPV16 Antibodies Signal Even Better Oral Cancer Outcomes

    Wed, Jun 17, 2015


    Source: www.medscape.com
    Author: Neil Osterweil

    Another prognostic tool may be in the offing for clinicians to use in evaluating patients with oropharyngeal cancers, new research suggests.

    The presence in serum of three antibodies to human papillomavirus type 16 (HPV16) was predictive of better progression-free and overall survival in these patients, according to Kristina R. Dahlstrom, PhD, from the University of Texas MD Anderson Cancer Center, in Houston, and colleagues.

    Patients whose serum was positive for the presence of three specific antibodies to “early” (E) proteins involved in replication and growth of HPV16 had dramatically better rates of overall survival (OS) and progression-free survival (PFS) compared with patients whose serum was negative for the antibodies, they reported online June 15 in Clinical Cancer Research.

    Specifically, for those patients whose serum was positive for any E antibodies, 5-year estimated OS was 87.4%, compared with 42.2% for patients whose sereum was negative for all E antibodies (P < .001). The respective 5-year PFS rates were 82.9% and 46.1% (P < .001).

    “These results hint at a prognostic stratification of patients with HPV-related oropharynx cancer reflecting humoral immune response to HPV type 16 E proteins and thus may help in choosing immunotherapy approaches for such patients in future,” said senior author Erich M. Sturgis, MD, MPH, a surgeon at MD Anderson, in comments to Medscape Medical News.

    Currently, the serology results are not strong enough to be used as clinical decision tools for choosing current therapies, she added.

    Their findings also suggest that vaccine-based immunotherapy targeted against HPV16 E-antigens combined with other immunotherapies such as checkpoint inhibitors might be effective against recurrent or metastatic HPV16-positive cancers of the oral cavity and pharynx, said Dr Sturgis.

    The findings appear to further illuminate what is going on immunologically in these patients, said an expert not involved with the research.

    “This is certainly an interesting study that builds upon our early understanding of the role of the host’s immune response in determining outcomes in HPV-associated oropharynx cancers,” commented Lori J Wirth, MD, a head and neck cancer specialist at the Massachusetts General Hospital Cancer Center, in Boston.

    “We know from responses experienced by HPV-positive oropharyngeal squamous cell carcinoma patients enrolled in early clinical trials investigating checkpoint inhibitors that the host immune system can be exploited for a therapeutic end. The more we know about the host immune response to this virally mediated cancer, the better we’ll get at taking advantage of it,” she told Medscape Medical News.

    More Cancers, Better Outcomes

    Earlier studies have shown that although the incidence of HPV-related head and neck cancers is rising, patients with oropharyngeal squamous cell carcinomas positive for HPV16 have significantly better prognoses than patients with the same cancers not related to HPV infections.

    To see whether they could identify prognostic biomarkers in patients with HPV-related oropharyngeal cancers, the investigators used enzyme-linked immunosorbent assasy to quantify immunoglobulin G antibodies to both early antigens (E1 and E4-E7) to the viral capsid proteins L1 and L2, and to the N-terminal and C-terminal fragments of E2 (NE2, CE2).

    Among serum samples taken from 209 patients with oropharyngeal cancers at diagnosis, at the end of treatment, and during follow-up, PFS was significantly better for patients testing positive for any E antigen (P < .001), but not for patients testing positive for any L antigen. Therefore, for all subsequent analyses, the investigators focused only on patients testing positive for E antigens.

    In multivariable models adjusted for age, smoking status, and treatment, the hazard ratio (HR) for death for patients with any E antibodies was 0.20 (95% confidence interval [CI], 0.1 – 0.4).

    The HR for progression for those with any E antibodies was 0.20; (95% CI, 0.1 – 0.5).

    The investigators also found that serum positivity for NE2, E1, and E6 were were all strongly associated with better OS and PFS, with respective HRs of 0.20, 0.30, and 0.30 (all significant, as shown by 95% CI).

    “Specific antibody status has the potential to be a useful prognostic indicator that may identify subsets of patients diagnosed with HPV16-positive tumors who may benefit from altered monitoring and/or treatments. In addition, the suggestion that immune response to HPV16 antigens is important to cancer outcomes suggests the potential of augmenting immune responses to improve treatment of patients with HPV-driven oropharyngeal carcinoma,” the investigators write.

    The study was supported by grants from the National Institutes of Health. Dr Sturgis and Dr Wirth have reported no relevant financial relationships.

    Clin Cancer Res. 2015:21:2861-2869. Abstract

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

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    Professional Rodeo Competitors Join Fight Against Oral Cancer

    Wed, Jun 17, 2015


    Source: www.upr.org
    Author: Melissa Allison


    The number of oral cancer deaths related to tobacco use is on the rise nationwide according to the Oral Cancer Foundation. Brian Hill is the founder of the OCF and a survivor of the disease.

    Kiser-OCFCody Kiser encourages the youth to not start using tobacco to help secure good health. Oral Cancer Foundation


    “Up until about (the year) 2000 this was primarily a disease of older men who had smoked a lot or chewed tobacco during their lifetime,” Hill said. “About that point in time we started to see a shift in the cause of the disease.”

    Hill said tobacco is still a primary cause of oral cancers and adds that the oral human papillomavirus type 16 (HPV16) is new etiology that has forced the number of cases to accelerate.

    According to an October 2014 study by Johns Hopkins researchers the HPV16 causes cancers of the mouth and throat and that any form of tobacco use increases the risk of the virus. The research suggests as few as three cigarettes a day can increase the risk of infection by almost one-third.

    Hill created the foundation in 1999 to promote change by educating the public about risk factors that contribute to the disease. Among those risks is the use of spit tobacco.

    “The world of rodeo has been the realm of sponsorship by the tobacco industry for decades,” Hill said. “With the nicotine content in a can of dip equaling approximately that of 80 cigarettes, this addiction can be one of the hardest to break. We hope to educate parents and youth about the dangers before they even get started.”

    The OCF is turning to professional rodeo competitors to serve as positive role models during a national campaign.

    Cody Kiser is a professional bareback bronc rider from Reno, Nevada.  He was in Delta, Utah recently where he competed at the Millard County Fairgrounds. Kiser told parents at the rodeo that nearly 15 percent of high school boys in the United States use smokeless tobacco.

    “My dad was a cowboy, so I know what it’s like looking up to cowboys as heroes for my whole life. Health and fitness have always been incredibly important to my family. My dad was a positive role model in my life growing up in that regard, and the idea of using spit tobacco never appealed to me,” Kiser said. “Right now, I’m pursuing rodeo as a passion of mine, and if at the same time I can do some good in the world and set the right example for young kids who might look up to me, then I’m honored and eager to do so.”

    Kiser said cowboys have a reputation that is second only to baseball players for being users of tobacco in the world of sports.  He wants to change that reputation throughout the country and in Utah, where rodeo is popular.

    “From my point of view, Utah seems to be on the front lines of health and fitness,” he said.  “I’ve been very impressed with Utah as far as a healthy lifestyle, people who don’t smoke and chew so it’s good to see in Utah that they don’t do that as much.”

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

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    Single Dose of HPV-16/18 Vaccine Looks to Be Sufficient

    Mon, Jun 15, 2015


    Source: www.medscape.com
    Author: Jenni Laidman

    A single dose of a vaccine against human papillomavirus (HPV) may prevent cervical cancer as effectively as the standard three-dose regimen, researchers concluded after analyzing the combined results of two large vaccine trials. The HPV vaccine in these studies was Cervarix (GlaxoSmithKline), which is effective against HPV strains 16/18.

    If randomized controlled trials ultimately support the result of this post hoc analysis, it could broaden protection against cervical cancer in areas of the world where vaccination programs are hardest to administer and where cervical cancer is disproportionately burdensome, the study authors say.

    “Even if you ignore the expense, the feasibility of implementing and getting back to individuals for a second and third dose is quite challenging, especially in places where there is no infrastructure,” coauthor Cosette Wheeler, PhD, Regents Professor, Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center in Albuquerque, told Medscape Medical News.

    The studies are published online June 10 in the Lancet Oncology.

    The possibility of a single-dose HPV vaccine is “a huge public health win,” coauthor Aimée R. Kreimer, PhD, Investigator, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, told Medscape Medical News. “Even if one dose protects only against HPV types included in the vaccine formulation, if we vaccinated most girls, we would have the chance to reduce cervical cancer by around 75%.”

    That’s the exciting part, Dr Wheeler added. “If we’re able to achieve success with one dose, or frankly even with two doses, that makes the possibility for worldwide prevention much greater.”

    HPV type 16 is the leading cause of cervical cancer, responsible for about 50% of all cases, and HPV 18 is the second-largest cause, at 20%.The authors note that this research was carried out with Cervarix, and it is unclear whether the results would also apply to the other HPV vaccine that is available, Gardasil (Merck & Co.), which is active against several more HPV strains and is the product that is commonly used in the United States. Whether results of this trial have any bearing on Gardasil will depend on what’s driving the strong immune response to Cervarix, the authors suggest. Cervarix carries a proprietary adjuvant, which may be responsible for the immune response.

    Surprise Over Efficacy Findings

    The idea of the current post hoc analysis arose from results in the large randomized controlled Costa Rica Vaccine Trial, in which about 20% of participants received fewer than three doses of HPV-16/18 vaccine. “We were surprised to observe that efficacy was the same regardless of the number of doses received,” Dr Kreimer told Medscape Medical News.

    That led to the post hoc analysis of the immunization results from the Costa Rica Vaccine Trial combined with results from the only other large phase 3, double-blind, randomized trial of HPV-16/18, for a total of more than 14,000 participants, ages 15 to 25 years, including about 7000 control subjects. The second trial, called PATRICIA (Papilloma Trial Against Cancer in Young Adults), took place in 14 countries. The analysis found that 4 years after vaccination, women who received the required three vaccine doses and women who received fewer than three doses — usually due to pregnancy or a colposcopy referral — were equally protected against HPV-16/18. Further, the analysis showed a potential benefit of cross-protection against closely related HPV strains 31/35/45 among women whose two doses were 6 months apart — a benefit previously seen only with three doses.

    Four-year vaccine efficacy against HPV-16/18 in the combined analysis was 77% for the 13,296 (6634 case, 6662 control) women in the three-dose group, 76% for the 549 (273 case, 276 control) women in the two-dose group, and 85.7% for the 238 (138 case, 100 control) women in the single-dose group. Efficacy against the closely related HPV-31/33/35 was 59.7% for three doses, 37.7% for two doses, and 36.6% for one dose. When data for the two doses were analyzed according to dosing regimen, the cross-protective efficacy was 10.1% for those who received their second dose 1 month after the first and 68.1% for those who received the second dose at 6 months.

    Antibody concentrations for two doses given 6 months apart were very close to concentrations for three doses, the research showed. One-dose vaccination titers at 6 to 48 months were lower than those for two or three doses, “but the titers were stable and several times higher than those identified for natural immunity,” the researchers write. “We can now infer that these lower, vaccine-induced antibody titers provide as strong HPV prevention as the titers from two or three doses, at least in the short term.”

    Just how long these vaccines will provide protection still needs to be determined. “We know with three doses we can see the protection going out toward 10 years, and we hope that maybe the protection is lifelong,” commented Dr Wheeler. “That does not mean that we know we will never need a booster. And that doesn’t mean if we give less than three doses that we know about the longevity or durability of that protection. So that’s another piece of the puzzle.”

    Although these results cannot be applied to Gardasil, Dr Wheeler notes that studies looking at Gardisil antibody titers after two doses look promising.

    In an accompanying comment, Julia M.L. Brotherton, Medical Director, National HPV Vaccination Program Register, VCS Registries, East Melbourne, Victoria, Australia, commented: “These data suggest that one dose of bivalent HPV vaccine might be adequate to protect against HPV-16 and HPV-18 persistent infections and, therefore, probably disease. HPV-16 and HPV-18 cause more than 70% of cervical cancers and the vast majority of HPV-related cancers at other anatomic sites. If this finding is confirmed, it opens up a great opportunity to extend the reach of protection using HPV vaccines to more people than we would have previously thought possible.”

    Four authors of the study are GSK employees and own shares and stock options in the company. Other researchers had financial or advisory relationships GSK, Roche Molecular Systems, Merck, and Sanofi Pasteur MSD. Dr Brotherton notes that she has been an investigator for investigator-initiated HPV epidemiology research grants partially funded by bioCSL/Merck, but this did not involve financial compensation.

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

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    Smokeless tobacco ingrained in baseball, despite bans and Gwynn’s death

    Mon, Jun 15, 2015


    Source: www.latimes.com
    Author: Gary Klein
    Utility player Mark DeRosa loads a wad of smokeless tobacco while playing for the San Francisco Giants before a game against the Dodgers on March 31, 2011. The use of smokeless tobacco is prevalent in the major leagues. (Kevork Djansezian / Getty Images)


    Rick Vanderhook played for Cal State Fullerton’s 1984 College World Series championship team and was a Titans assistant when they won two more. So he remembers the days when cans and pouches of smokeless tobacco were omnipresent in the uniform pockets of the participants.

    Not anymore. The NCAA banned tobacco use on the field in the early 1990s.

    “It’s probably cut back, I’ll say, almost 90% compared to what it was 25 years ago,” said Vanderhook, who in his fourth season as head coach has guided the Titans back to Omaha, where they will open against defending national champion Vanderbilt on Sunday at 5 p.m.

    Smokeless tobacco remains ingrained in baseball culture, however, including the college and high school levels where it is banned.

    “It sounds bad, but it’s part of the game,” said Fullerton pitcher Thomas Eshelman, echoing nearly every coach and player interviewed for this article.

    Minor league players can be fined for having tobacco products in their locker or partaking on the field. Major leaguers are prohibited from using tobacco during televised interviews and player appearances, and they cannot carry tobacco products in their uniforms. But they are otherwise not prohibited from using it on the field.

    Before he died of salivary gland cancer last year, baseball Hall of Famer Tony Gwynn said he believed his habit of using smokeless tobacco caused the disease that took his life at age 54.

    Curt Schilling, a former All-Star pitcher, said last year he had undergone treatment for cancer that resulted from smokeless tobacco use. In April, he penned an open letter to his younger self warning of the dangers.

    And last month, the mayor of San Francisco signed an ordinance that in 2016 will ban tobacco from all sporting venues in the city, including AT&T Park, home of the defending World Series champion San Francisco Giants.

    That has not stopped many college players from using smokeless tobacco.

    “No matter how many times you look a guy in the eye and say Tony Gwynn and Curt Schilling, if that guy wants to dip, he’s going to find a way,” said Andy Lopez, who guided Pepperdine and Arizona to national titles before retiring last month after 33 years as a college coach.

    The NCAA prohibits players, coaches, umpires, athletic trainers and managers from using tobacco at game sites. If umpires catch players using tobacco, the player and coach face ejection.

    “There is zero tolerance,” said Chuck Lyon, a college umpire for nearly three decades.

    According to the NCAA rule book, “umpires who use tobacco before, during or after a game in the vicinity of the site shall be reported to and punished by the proper disciplinary authority.”

    750x422-1A tin of chewing tobacco is seen tucked into the glove of Dodgers reliever Chris Hatcher when he was playing wiht the Miami Marlins last season. (Wilfredo Lee / Associated Press)


    Players and coaches interviewed for this story said they had seen umpires using tobacco. But Lyon said, “as a crew chief, I would turn that in immediately.”

    Results of the NCAA’s most recent quadrennial survey of about 21,000 college athletes from all sports showed that tobacco use by college baseball players was decreasing. The 2013 results, released last July in a report titled, “NCAA National Study of Substance Abuse Habits of College Student-Athletes,” showed a drop in “spit” tobacco use since 2009.

    In 2005, the overall percentage of acknowledged use in the previous 12 months was 42.5%. It climbed to 52.3% in 2009, but dropped to 47.2% in 2013 — though that’s still nearly half of the players in a sport in which it is banned.

    Coaches said they address tobacco with their players before every season.

    “You also bring it up throughout the season,” UCLA Coach John Savage said, “but it’s not a daily reminder.”

    Cal State Northridge Coach Greg Moore said, “We educate them constantly and talk about their choices.” But, he added, “I know that me saying smokeless tobacco is unhealthy is not going to get a guy to change his habit.”

    The California Interscholastic Federation, which governs high school sports in the state, forbids the use of tobacco products by athletes and coaches. But most players say they first experimented with tobacco in high school.

    “They get into it for the same reason 12-year-olds start smoking — they think it’s a cool thing to do,” UC Irvine Coach Mike Gillespie said.

    Chatsworth High Coach Tom Meusborn said tobacco use by players has dramatically dissipated since he began coaching at the school in 1990. “I think they understand and are becoming more health conscious with their training and diet,” he said.

    Jim Ozella, Newhall Hart’s coach since 2000, also sees fewer high school players using tobacco. “I just bring up the topic of Tony Gwynn,” said Ozella, whose son worked as an equipment manager at San Diego State when Gwynn coached there.

    College players said they were aware of the risks of using tobacco products.

    Still, Cal State Northridge infielder William Colantono began to dip as a young member of a mostly older varsity high school team. “Being around them, I picked it up,” he said. “Not that I’m proud of it.”

    Colantono said that while most of his summer league teammates used smokeless tobacco, only “a handful” of his Northridge teammates do, and they partake off the field.

    “It’s easy for me not to have to do it on the field,” he said. “I’m not crazy about it where I have to have it all the time.”

    Eshelman, Fullerton’s ace right-hander, started to dip in high school because “I thought it was cool.” Fellow Titans pitcher John Gavin began in high school on “a dare.” Both said they occasionally use tobacco, but not on the field.

    “After a game when you want to hang out and relax,” said Eshelman, a junior.

    “Just kind of a stress reliever,” said Gavin, a freshman.

    Several college baseball summer leagues, which have rosters comprised of players from across the United States, also ban the use of tobacco during games.

    Sal Colangelo, longtime manager of the Bethesda (Md.) Big Train in the Cal Ripken Collegiate League, said he attempts to educate players, but for some “it’s a way of life.”

    “You go into their trucks and there are cases and cases of tobacco and dip,” he said. “It’s like a 7-Eleven.”

    Several coaches from West Coast schools acknowledged using tobacco, though a few agreed to speak about it only if they were not identified.

    One, who said he recently quit, recalled an umpire once threatening to eject him for chewing when he went out to argue a call. Another, who has used smokeless tobacco for more than two decades, admitted he was addicted.

    “For me, personally, that would be one of my greatest accomplishments if I can stop,” he said.

    Former Pepperdine coach Steve Rodriguez played on Pepperdine’s 1992 national championship team and professionally for seven seasons, including 18 games in the major leagues. He coached the Waves for 12 seasons before being hired this week as coach of Baylor. He said he chewed leaf tobacco until about five years ago.

    “I was a hypocrite because I would say, ‘You can’t do it,’ but I would still do it,” he said, adding he is now passionate about educating his players about the risks.

    “I want to make sure,” he said, “that I give them the best opportunity to not have to deal with really, really big issues.”

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

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    Keytruda doubles efficacy of only targeted therapy for head and neck cancer

    Thu, Jun 11, 2015


    Source: www.curetoday.com
    Author: Lauren M. Green

    The immunotherapy Keytruda (pembrolizumab), in a recent study, proved twice as effective for the treatment of head and neck cancer as Erbitux (cetuximab), the only targeted therapy indicated as a therapy for the disease.

    The multisite study offers the largest experience to date of how immunotherapy can be deployed in patients with head and neck cancer, and could change the way the disease is treated. The findings were announced May 29 during the annual meeting of the American Society of Clinical Oncology, a gathering of nearly 30,000 oncology professionals taking place in Chicago.

    Keytruda is an antibody designed to disable the protein PD-1 so it cannot do its job of keeping the immune system in check; this allows T cells to become more active in recognizing and fighting cancer cells. In the study, investigators found that the drug produced broad and durable responses in patients with advanced head and neck cancer.

    Fifty-six percent of patients in the study experienced some tumor shrinkage with Keytruda, and 86 percent of those patients continued to respond to treatment at data cutoff on March 23, 2015. Keytruda produced an overall response rate (ORR) of 25 percent, and it proved active in both HPV (human papillomavirus)-positive and HPV-negative patients.

    “The efficacy was remarkable — pembrolizumab seems to be roughly twice as effective, when measured by response, as our only targeted therapy, cetuximab,” said Tanguy Seiwart, an assistant professor of medicine and associate leader of the head and neck cancer program at the University of Chicago, who presented the results in a press briefing during the ASCO meeting. “We have high hopes that immunotherapy will change the way we treat head and neck cancer.”

    Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) has a poor prognosis with a median overall survival (OS) of 13 months in patients treated in the first-line setting, and six months in previously treated patients. Previously treated patients made up the majority of the population of the study, which built on earlier findings from the KEYNOTE-012 study (NCT01848834). In that study, Keytruda — administered at 10 mg/kg every two weeks — had a 20 percent response rate in patients with advanced HNSCC whose tumors were positive for the protein PD-L1.

    The findings reported May 29 were based on results from an expansion of that first trial, which involved 132 patients with advanced HNSCC who were recruited regardless of their PD-L1 or HPV status. Importantly, said Seiwert, patients in this cohort received a fixed dose of Keytruda (200 mg every three weeks), representing “a very convenient dosing schedule.”

    Eligible patients had measureable disease based on RECIST 1.1 response evaluation criteria and an ECOG performance status of 0 or 1. The majority of enrollees were male (83 percent), and 56.8 percent had received two or more lines of therapy for disease recurrence. Radiographic imaging was used to assess tumor response every eight weeks. Patients were treated as long as they didn’t show progression of disease or as long as they demonstrated clinical improvement, Seiwert explained.

    Of 117 evaluable patients, 29 (24.8 percent; [95 percent confidence interval (CI), 17.3–33.6]) responded to treatment with Keytruda. For patients with HPV-positive HNSCC, the ORR was 20.6 percent, and in the HPV-negative cohort, ORR was 27.2 percent.

    “In addition to the 25 percent response rate,” said Seiwert, “about 25 percent also had stable disease, so when we take these together, we have a disease control rate of about 50 percent, which is remarkable in this disease, especially in a heavily pretreated population.”

    Moreover, he said, about two-thirds of patients had received two or more prior lines of therapy, which generally is an indicator of a very poor prognosis.

    For the 56 percent of patients whose tumors decreased in size, Seiwert said the responses often occurred early at eight or 16 weeks, although there were a few outliers with late responses.

    “Importantly, those patients who did respond oftentimes continued to have responses — 86 percent of patients had durable responses in this cohort,” he continued, adding that not only are responders remaining on the therapy, but so are many patients who have stable disease, with a total of 40 patients staying on the drug.

    “Overall, and in keeping with what we already know about pembrolizumab, this was a very well-tolerated agent,” said Seiwert, “certainly better tolerated than what we usually see in head and neck cancer with aggressive chemotherapy and radiotherapy.”

    Serious side effects were reported in fewer than 10 percent of patients. The most common side effects were fatigue (15.2 percent of patients), hypothyroidism (9.1 percent), and decreased appetite and rash, each occurring in 7.6 percent of patients. Four patients discontinued treatment due to immune-related side effects: two due to grade 2 interstitial lung disease and grade 3 colitis, respectively, and two patients for grade 3 pneumonitis.

    Analysis of the findings based on biomarker status is ongoing, and Seiwert is hopeful that with the emergence of new potential biomarkers, researchers will be able to pinpoint which patients with HNSCC are most likely to benefit from the immunotherapy.

    For example, another related study that Seiwert and colleagues are reporting at ASCO (abstract 6017) has shown that the expression of the gene signature interferon-gamma in head and neck tumors had a very strong negative predictive value of response to Keytruda. “In the future, these results may help us, if validated, to determine which patients should or should not [be given] pembrolizumab,” Seiwert said.

    Pembrolizumab versus standard treatment for HNSCC also is being evaluated in two phase 3 trials that are currently recruiting participants (NCT02252042 and NCT02358031).

    Seiwert TY, Haddad RI, Gupta S, et al. Antitumor activity of the anti-PD-1 antibody pembrolizumab in biomarker-unselected patients with R/M head and neck cancer: preliminary results from the KEYNOTE-012 expansion cohort. J Clin Oncol. 2015;(suppl; abstr LBA6008) – See more at: http://www.curetoday.com/articles/keytruda-doubles-efficacy-of-only-targeted-therapy-for-head-and-neck-cancer/2#sthash.44VvpPH4.dpuf

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    Canadian court orders three major tobacco companies to pay billions in damages

    Wed, Jun 3, 2015


    Source: news.vice.com
    Author: Natalie Alcoba



    Three tobacco giants have been ordered by a Canadian court to pay billions of dollars in moral and punitive damages to nearly 100,000 smokers, in what has been hailed as an “historic judgment” by the plaintiffs in Quebec.

    Imperial Tobacco Canada, Rothmans, Benson & Hedges, and JTI-Macdonald were found to have violated their general duty not to cause injury to another, their duty to inform their clients of the risks and dangers of their products, and their obligation not to mislead their clients. A Quebec Superior Court slapped the three cigarette manufacturers — which have already vowed to appeal — with damages totaling CAD $15.5 billion ($12 billion US), to be split among them.

    The ruling means that plaintiffs suffering from lung or throat cancer are entitled to receive CAD $80,000 or $100,000 ($63,000 or $80,000), while those afflicted with emphysema can receive CAD $24,000 or $30,000 ($19,000 or $24,000), plus the interest accumulated since 1998, which is when the lawsuit commenced.

    “Today marks an important day for the victims of tobacco who have waited almost 17 years for this moment”, said Mario Bujold, executive director of the Quebec Council on Tobacco and Health on Monday.

    Imperial Tobacco was held responsible for CAD $10.5 billion ($8.3 billion), while Rothmans, Benson & Hedges bear responsibility for CAD $3.1 billion ($2.4 billion), and JTI-Macdonald the remaining CAD $2 billion ($1.6 billion).

    “By choosing not to inform either the public health authorities or the public directly of what they knew, the Companies chose profits over the health of their customers,” Justice Brian Riordan wrote in his 276-page judgment. “Whatever else can be said about that choice, it is clear that it represent a fault of the most egregious nature and one that must be considered in the context of punitive damages.”

    Two class actions were heard as part of the same trial. One, spearheaded by the Council, included 99,957 Quebec smokers and ex-smokers who had developed emphysema, lung cancer, or throat cancer. A second class action was much broader, representing 918,218 people addicted to tobacco in Quebec. While the Quebec Council on Tobacco and Health said the judge sided with the plaintiffs in both cases, only those in the first group will receive compensation.

    But Rothmans, Benson & Hedges said the cases are “far from over”, a sentiment shared by the other manufacturers.

    “We will vigorously appeal this lower court’s judgment, and believe that we have very strong legal grounds to overturn the judgment in its entirety,” RBH spokeswoman Anne Edwards said in a statement.

    She noted that not a single class member, in nearly three years of trial, “showed up to say that he or she was unaware of the risks of smoking,” and said given the “prevailing law and common sense” the judgement should not stand.

    JTI-Macdonald Corp. also said it “fundamentally disagrees” with the judgment and intends to file an appeal.

    “Since the 1950s, Canadians have had a very high awareness of the health risks of smoking. That awareness has been reinforced by the health warnings printed on every legal cigarette package for more than 40 years,” it said in a statement, adding that the company complies with all Canadian and Quebec laws.

    In its statement, Imperial Tobacco Canada called it “astounding to be handed this decision when the federal government has set the standard for the conduct of Imperial Tobacco Canada with which the company has always complied.”

    Still, Andre Lesperance, one of the lawyers involved in the case for the plaintiffs, said on Monday that the companies “lied” to their customers and “hurt their right to life,” The Canadian Press reported.

    “It’s a great victory for victims as well as for society in general,” he said.

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    Pembrolizumab immunotherapy effective in recurrent, metastatic head and neck cancer

    Wed, Jun 3, 2015


    Source: www.cancertherapyadvisor.com
    Author: Debra Hughes, MS

    Pembrolizumab immunotherapy is effective for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), results of the KEYNOTE-012 trial presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting have shown.

    At a fixed dose of 200 mg intravenously every 3 weeks, pembrolizumab “was well tolerated and demonstrated a clinically meaningful overall response rate of 24.8% in patients with recurrent/metastatic SCCHN,” reported Tanguy Y. Seiwert, MD, an assistant professor of medicine, and associate HNC program leader at The University of Chicago in Chicago, IL.

    However, “it is important to note that response rate may underestimate the rate of benefit in patients, and ultimately we need to assess survival,” said Dr. Seiwert in an ASCO press release.

    “We know from other diseases where the experience with immunotherapy is larger, that patients who have disease stabilization or even initially experience disease progression upon receiving immunotherapy ultimately may derive significant benefit that can translate into longer survival.”

    Pembrolizumab (MK-3475), a humanized monoclonal antibody that blocks interaction of PD-1 with its ligands, PD-L1 and PD-L2, promotes activity of tumor-specific effector T cells.

    Previously, the KEYNOTE 012 study had demonstrated clinical activity of pembrolizumab 10 mg/kg every 2 weeks in patients with recurrent/metastatic SCCHN enriched for PD-L1–positive tumors. Response rate was 20%. Dr. Seiwert reported on the study’s larger SCCHN expansion cohort, irrespective of PD-L1 expression or HPV status, using a 3-weekly fixed dose.

    The primary end point was overall response rate per investigator assessment (RECIST 1.1). Secondary objectives included progression-free survival and overall survival.

    A total of 132 patients with recurrent/metastatic SCCHN were enrolled and evaluated every 8 weeks with radiographic imaging. Mean age was 60 years, 83.3% were male, and 37.9% had 3 or more lines of therapy for recurrent disease.

    At a median follow-up of 5.7 months (range: 0.2-8.7 months), the overall response rate was 24.8%, with 7 of the 34 patients who were HPV-positive and 22 of the 81 patients who were HPV-negative responding.

    Among all responders, there was one complete response and 26 partial responses. Median time to response was 9.0 weeks (range: 7.6-18 weeks). Median duration of response was not reached, he said. A total of 40 patients remain on therapy, and 86% of responding patients (25 of 29) remain in response.

    Drug-related adverse events (AEs) of any grade occurred in 59.8% of all enrolled patients; drug-related grade 3 or higher AEs occurred in 9.8% of patients.

    The most common drug-related AEs (≥5%) of any grade were fatigue (15.2%), hypothyroidism (9.1%), decreased appetite (7.6%), rash (7.6%), dry skin (6.8%), pyrexia (6.8%), arthralgia (5.3%), nausea (5.3%), and decrease in weight (5.3%).

    “This is yet another exciting example where PD-1 immunotherapy might work better and more reliably than existing drugs, and with fewer side effects,” said ASCO Expert Gregory A. Masters, MD, in a press release.

    “The diversity of patients who responded is greater than in any previous clinical trial. But we still need larger studies and longer follow-up to assess the impact of this treatment on patient survival.”

    Pembrolizumab is currently being evaluated in two phase 3 trials to investigate its clinical benefit compared with standard of care chemotherapy, Dr. Seiwart said.

    Seiwert TY, Haddad RI, Gupta S, et al. Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort. J Clin Oncol. 2015;33:(suppl; abstr LBA6008).

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    Marathoner Harriette Thompson, 92, runs to her own inspiring rhythm

    Wed, Jun 3, 2015


    Source: http://espn.go.com/
    Author: Lynn Olszowy

    Harriette Thompson has found a clever way to pass the time when she runs marathons. The classically trained concert pianist imagines her favorite pieces of music.

    “When I’m in a place that might be pretty boring, I run to some music in my mind,” she explained. “I hardly know I’m running when I’m thinking about that.”


    Over the weekend, musical thoughts helped Thompson run into the history books for the second year in a row. Last year, she broke the marathon record by a woman over 90 by more than two hours. On Sunday, she became the oldest woman to ever complete a marathon at the age of 92 years, 65 days.

    Two days later, she had a spring in her step.

    “I feel like a million dollars right now,” Thompson said Tuesday from her home in a Charlotte, North Carolina, retirement community. “I think it must do something to your life system or something that makes you feel up on top of the world after you’ve done a marathon.”

    Throughout her 7 hours, 24 minutes and 36 seconds of running, she had Russian composer Sergei Rachmaninoff and his Prelude in D Major keeping her company.

    “It’s fun to just think about it because I think it’s one of his most beautiful preludes,” she said over the phone Tuesday.

    But there was something else that occupied Thompson’s mind while she ran the 26.2 miles of Sunday’s San Diego Rock ‘n’ Roll Marathon.

    “I also think about all the ways I’m working to help other people,” she said.

    Thompson has run 16 marathons to raise money for the Leukemia & Lymphoma Society as part of Team in Training. In all, she’s garnered more than $100,000 in donations.

    “It makes me very grateful to all the people who have been so generous,” she said. “Every year, when I write my little letter asking my friends [to donate], they keep saying, ‘I thought last year was your last one.’”

    This year, Thompson says she had extra motivation to run. After she lost her husband of 67 years to cancer in January, her eldest son, Sydnor Thompson III, was diagnosed with colon cancer.

    “I have so much incentive because now I’m really trying to help get that research done so that maybe it will help my son get over his cancer,” she said.

    “It’s humbling,” said Sydnor, 61, a pastor in suburban Charlotte. “I don’t know of any child who has ever been loved more than I’ve been loved by my mother.”

    “I’m just praying that he’ll get better real fast,” adds Thompson. “The fact [I set] a record, that’s great, but that’s not my main reason.”

    In fact, when Thompson first took up running at age 76, she never dreamed of setting any records. She didn’t even think she’d run a marathon. She signed up for her first marathon in 1999 figuring she’d walk the length of the course.

    “But when I got out to San Diego, everybody was running, so I started to run,” she said.

    Today she credits running with keeping her going all these years, though she has overcome obstacles of her own.

    In 2010, while battling an aggressive form of oral cancer — which ate away the roof of her mouth — she was told she had only three months to live, two years at best. Thompson didn’t let that prognosis stop her from running the San Diego marathon that year or the two years that followed. She did take a break in 2013 when the cancer treatment proved too taxing.

    And for the past year, she has received radiation treatment for squamous cell carcinoma on her legs. She wore white tights during this year’s race to cover the open wounds she still has from the treatment.

    “I was really pleased my legs didn’t hurt me during the run,” she said.

    “I don’t think people realize how serious the burns are on her legs,” Sydnor said. “She just endures and pushes through.”

    The San Diego marathon is the only marathon she’s ever run because of its commitment to the Leukemia & Lymphoma Society, and the people who run the marathon are just as loyal to Thompson.

    “As people would go by, they would say, ‘C’mon Harriette,’” she said. “At least 10 people told me they signed up to run the marathon because they read about me.”

    Thompson’s biggest supporter at the race was one of her five children, Brenny, who ran alongside his mother.

    “I have to have a lot of energy [to run], so he kept feeding me,” she said. “One time someone brought me a muffin.”

    And when someone wanted a picture, Brenny, 56, was there as a safeguard.

    “My son was protecting me from having me stop,” Thompson said. “He’d say, ‘You need to take some selfies.’”

    “Even though she’s not moving that fast, she definitely has a rhythm,” said Brenny, who runs a real estate company in Charlotte.

    Keeping rhythm is something Thompson has done all her life. She actually credits her background as a pianist for her being able to endure the tedium of marathon after marathon, year after year.

    “The discipline you have to have when you’re a pianist certainly does play into doing another chore like running,” she said.

    Thompson has every intention of running for as long as she can, and knowing she’s making a difference is what’s really music to her ears.

    “I think at my age if I can do anything to help somebody, I’m amazed,” she said.

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    A Disorder That’s Hard to Swallow

    Tue, Jun 2, 2015


    Source: www.usnews.com
    Author: Anna Medaris Miller


    Ed Steger’s​ last meal was a bowl of soup in Las Vegas. “I remember it all too clearly, as if it were yesterday,” he says. But it wasn’t yesterday – it was 2006. “Life is very different” now, says Steger, a 63-year-old former program manager in Houston.

    Steger was diagnosed with head and neck cancer​ in 2005. In addition to 36 rounds of radiation and eight regimens of chemotherapy, he underwent six surgeries, including one that replaced a portion of his pharynx and removed parts of his left jawbone, tongue, epiglottis and soft palate.

    “The part that makes it odd is that I’m alive after having four recurrences,” Steger says. The part that makes it distressing is that he can’t eat solid foods.

    “There are many case studies I’ve seen where patients have said [their] swallowing disorder is the worst part of their disease – and I believe this to be true,” says Steger, who’s president of the National Foundation of Swallowing Disorders. His daily diet consists of four 8-ounce cans of the nutritional drink Boost Plus, along with two to four bottled​ Starbucks Frappuccinos, which he buys at his local supermarket. “It’s a very boring diet that allows me to maintain my weight,” says Steger, who’s 5 feet 10 inches tall and 155 pounds.

    It’s unknown how many people have dysphagia, or difficulty swallowing, but the condition can be caused by any one of 30 diverse health events, Steger says. While his dysphagia is a result of surgery, other people have difficulty swallowing due to neurological conditions such as Parkinson’s disease or stroke, digestive disorders including acid reflux or head injuries. Children with developmental disabilities like autism also often have dysphagia.

    “[Dysphagia] isn’t a disease, it’s a sign or an outcome of a disease,” says James Coyle​, an associate professor in the University of Pittsburgh’s School of Health and Rehabilitation Sciences who specializes in treating adults with swallowing disorders.

    Difficulty swallowing can also be a part of normal aging, suggests research led by Teresa Lever​, an assistant professor of otolaryngology at the University of Missouri School of Medicine. But that doesn’t mean it’s without consequence. For example, people with dysphagia are at risk for choking, dehydration, malnutrition and pneumonia, which can be triggered when food or drink enter the lungs.

    “If you can’t walk, you don’t die. If your skin looks horrible, you don’t die. But if you can’t eat and drink, you die,” Lever says. “[Swallowing] is a vital biological function that is a hugely overlooked contribution to morbidity and mortality.”

    Aiming to Eat and Drink Again

    How clinicians treat dysphagia depends on its cause. If, for example, the condition is brought on by a stroke that paralyzes one side of the throat, a swallowing specialist like a speech-language pathologist first ​might use an imaging test to identify what exactly is going wrong, and then coach the patient on ways to tilt his or her head while eating in order to better prevent food from getting into the airway.​ Such “compensatory strategies,” Coyle says, are “more or less exploiting either gravity or using the change in position to redirect the swallowed material more efficiently and with better airway protection.”

    Steger, for one, was trained to swallow by holding his breath, reclining and “letting the liquid flow” down the back of his esophagus and avoiding the airway. “When I swallow, I need to concentrate very hard,” he says.

    Mouth and throat exercises can also help patients boost their swallowing abilities. One mouthpiece-like device called SwallowSTRONG, for instance, senses how hard the patient pushes the tongue against the roof of the mouth and progressively guides him or her in resistance exercises.​ “It’s like weightlifting,” Coyle says. “You start off doing low levels of exercise, and we increase the targets every two weeks until the tongue is stronger.”

    Other exercises use a similar technique but to improve respiratory function rather than tongue strength. When patients blow against progressively increasing resistance, for example, they’ll develop a better cough reflex. That, in turn, will make it more likely that any food particles or liquids inhaled into the airways will be expelled and not enter the lungs to cause harm, Coyle says. “Dysphagia doesn’t always go away,” he says. “Sometimes we have to teach the person to swallow differently, sometimes we have to beef up other parts of the body to compensate for the fact that the swallowing isn’t going to get better.”

    If dysphagia is caused by dementia or another condition that compromises someone’s ability to learn, clinicians must defer to environmental or dietary modifications like prescribing a diet of thickened liquids. The route is a last resort, Coyle says, since “gobs of studies” show that people don’t like thickened liquids, don’t drink them and therefore, are at risk for dehydration.

    “All of our cases aren’t successful,” he says, “but when we do have a successful case, it’s so rewarding – the ability to restore a person’s ability to eat and drink.”

    Food is Secondary

    If Steger woke up tomorrow without dysphagia, he’d eat a T-bone steak grilled with Lawry’s spice, a baked potato with all the fixings and crème brulee for dessert.​ But what he’d look forward to most is going to a restaurant with friends, ordering anything he wants and keeping pace with his companions. “The food is secondary at this point,” he says.

    Living with dysphagia isn’t just a medical risk, but can also hamper one’s quality of life and mental health. People with the condition can feel isolated not only because they avoid social eating situations, but also because many of them have medical conditions that affect their voices and compromise their communication. In the support groups for people with Parkinson’s that Steger sometimes attends, the participants, many of whom have dysphagia, “are embarrassed to go out, they’re ashamed, it’s sad,” he says.

    One of his goals is to boost funding for dysphagia research, which is slow-going since major funding organizations like the National Institutes of Health are more focused on the diseases that underlie the condition, Steger says. “[Swallowing] is never top of mind when you have head and neck cancer or Parkinson’s until it happens to you,” he says .​But a focus on swallowing itself is not trivial since, for example, hospital patients with dysphagia stay in the hospital 40 percent longer than patients without it, Coyle says. “It’s very important to identify early.”

    It’s also important to dedicate resources to the disorder since it will affect more and more people as the population ages, Lever says. She’s now working to identify traits that protect mice – and hopefully, people – from developing dysphagia as they grow old. “Now that we can diagnose dysphagia, we can identify which mouse models have it, and then we can use those mouse models to try to understand what is going wrong to cause dysphagia,” she says. That, in turn, “can then give [us] some targets for treatment.”

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

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    Merck immunotherapy appears effective in head and neck cancer – study | Reuters

    Tue, Jun 2, 2015


    Source: www.firstpress.com
    Author: Bill Berkrot


    A Merck & Co drug that helps the immune system fight cancer was about twice as effective as the current standard therapy for patients with recurrent or advanced head and neck cancers, according to study data released on Friday.

    A quarter of the 132 patients who received the drug, Keytruda (pembrolizumab), saw their tumors shrink by at least 30 percent. Fifty-six percent of patients experienced at least some tumor shrinkage in the ongoing single drug Phase I study dubbed Keynote-012, researchers reported.

    “This is remarkable because we don’t usually see this level of activity with new agents. We have a track record of failure,” said Dr. Tanguy Seiwert, lead investigator of the study from the University of Chicago.

    Advanced head and neck cancer is currently treated with Eli Lilly’s Erbitux, known chemically as cetuximab, which typically has a response rate of 10 percent to 13 percent.

    “The only thing that works is cetuximab and this looks at least twice as good,” said Seiwert, who was presenting the Keytruda data at the American Society of Clinical Oncology meeting in Chicago.


    Merck shares rose more than 1 percent to $60.43 on the New York Stock Exchange.

    Keytruda and Opdivo from Bristol-Myers Squibb Co are at the forefront of a promising new class of drugs called PD-1 inhibitors that block a mechanism tumors use to evade the immune system. Keytruda is approved to treat advanced melanoma and awaits a decision for use in lung cancer. It is being tested against 30 types of cancer alone and in various combinations.

    While overall survival data was not yet available, Keytruda and Opdivo have extended survival for some patients in other cancers.

    “Response rate doesn’t do this justice,” Seiwert said. “A fraction of those patients will probably have long term survival. It can really make a difference for some patients who have incurable metastatic disease.”

    The drug appeared to work as well for patients whose cancer tested positive for human papillomavirus as those who were HPV negative. Some older treatments may be less effective in HPV positive patients, researchers said.

    Keytruda was well tolerated with few side effects, Seiwert said. Serious immune-related side effects, such as inflammation of the lungs or colon, were reported in a very small number of patients in the study.

    Head and neck cancer is the sixth most common cancer worldwide. Patients with recurrent or metastatic head and neck cancer are usually expected to live about 10 to 12 months.

    Reporting by Bill Berkrot in New York; Editing by Diane Craft.

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

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